Javtor/biomedical-topic-categorization-cased

The innate immune system in diabetic retinopathy. The prevalence of diabetes has been rising steadily in the past half-century, along with the burden of its associated complications, including diabetic retinopathy (DR). DR is currently the most common cause of vision loss in working-age adults in the United States. Historically, DR has been diagnosed and classified clinically based on what is visible by fundoscopy; that is vasculature alterations. However, recent technological advances have confirmed pathology of the neuroretina prior to any detectable vascular changes. These, coupled with molecular studies, and the positive impact of anti-inflammatory therapeutics in DR patients have highlighted the central involvement of the innate immune system. Reminiscent of the systemic impact of diabetes, immune dysregulation has become increasingly identified as a key element of the pathophysiology of DR by interfering with normal homeostatic systems. This review uses the growing body of literature across various model systems to demonstrate the clear involvement of all three pillars of the immune system: immune-competent cells, mediators, and the complement system. It also demonstrates how the relative contribution of each of these requires more extensive analysis, including in human tissues over the continuum of disease progression. Finally, although this review demonstrates how the complex interactions of the immune system pose many more questions than answers, the intimately connected nature of the three pillars of the immune system may also point to possible new targets to reverse or even halt reverse retinopathy.

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Microwave hydrothermal renovating and reassembling spent lithium cobalt oxide for lithium-ion battery. With the growing number of lithium-ion batteries (LIBs) that are consumed by worldwide people, recycling is necessary for addressing environmental problems and alleviating energy crisis. Especially, it is meaningful to regenerate LIBs from spent batteries. In this paper, the microwave hydrothermal method is used to replenish lithium, assemble particles and optimize the crystal structure of the spent lithium cobalt oxide. The microwave hydrothermal process can shorten the reaction time, improve the internal structure, and uniformize the particle size distribution of lithium cobalt oxide. It helps to construct a regenerated lithium cobalt oxide (LiCoO 2 ) battery with high-capacity and high-rate properties (141.7 mAh g -1 at 5C). The cycle retention rate is 94.5% after 100 cycles, which is far exceeding the original lithium cobalt oxide (89.7%) and LiCoO 2 regenerated by normal hydrothermal method (88.3%). This work demonstrates the feasibility to get lithium cobalt oxide batteries with good structural stability from spent lithium cobalt oxide batteries.

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Altered hepatic lipid metabolism in mice lacking both the melanocortin type 4 receptor and low density lipoprotein receptor. Obesity is often associated with dyslipidemia and hepatosteatosis. A number of animal models of non-alcoholic fatty liver disease (NAFLD) are established but they significantly differ in the molecular and biochemical changes depending on the genetic modification and diet used. Mice deficient for melanocortin type 4 receptor (Mc4rmut) develop hyperphagia, obesity, and subsequently NAFLD already under regular chow and resemble more closely the energy supply-driven obesity found in humans. This animal model was used to assess the molecular and biochemical consequences of hyperphagia-induced obesity on hepatic lipid metabolism. We analyzed transcriptome changes in Mc4rmut mice by RNA sequencing and used high resolution 1H magic angle spinning NMR spectroscopy and MALDI-TOF mass spectrometry to assess changes in the lipid composition. On the transcriptomic level we found significant changes in components of the triacylglycerol metabolism, unsaturated fatty acids biosynthesis, peroxisome proliferator-activated receptor signaling pathways, and lipid transport and storage compared to the wild-type. These findings were supported by increases in triacylglycerol, monounsaturated fatty acid, and arachidonic acid levels. The transcriptome signatures significantly differ from those of other NAFLD mouse models supporting the concept of hepatic subphenotypes depending on the genetic background and diet. Comparative analyses of our data with previous studies allowed for the identification of common changes and genotype-specific components and pathways involved in obesity-associated NAFLD.

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Education can reduce health differences related to genetic risk of obesity. This work investigates whether genetic makeup moderates the effects of education on health. Low statistical power and endogenous measures of environment have been obstacles to the credible estimation of such gene-by-environment interactions. We overcome these obstacles by combining a natural experiment that generated variation in secondary education with polygenic scores for a quarter-million individuals. The additional schooling affected body size, lung function, and blood pressure in middle age. The improvements in body size and lung function were larger for individuals with high genetic predisposition to obesity. As a result, education reduced the gap in unhealthy body size between those in the top and bottom terciles of genetic risk of obesity from 20 to 6 percentage points.

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Risk of venous and arterial thromboembolism in patients with giant cell arteritis and/or polymyalgia rheumatica: A Veterans Health Administration population-based study in the United States. Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are systemic inflammatory diseases that primarily affect elderly women.

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[Relationship between frailty and depression in elderly patients]. Objective: To investigate the relationship between frailty and depression by analyzing the clinical data, frailty and depression in the elderly outpatients. Methods: This study included outpatients who visited the Geriatric Section of West China Hospital from July 1, 2016 to December 31, 2016.Clinical characteristics and complications in patients were evaluated comprehensively.The debilitating condition of patient was assessed by the international society for elderly nutrition simple weakness questionnaire (Fatigue, Resistance, Ambulation, Illnesses, Loss of Weight.FRAIL). The depression was assessed by the 30-Item Geriatric Depression. Results: Regression analysis showed that pre-frail ( OR 3.286, 95% CI 1.59-3.98) and frail ( OR 4.139, 95% CI 1.52-14.40) elder adults had a higher risk of depression than other elders. Conclusion: Pre-frail and frail elders are at high risk of depression.

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Randomized controlled study of a diagnosis and treatment plan for moderate coronavirus disease 2019 that integrates Traditional Chinese and Western Medicine. To investigate the clinical efficacy and safety of a diagnosis and treatment plan for moderate coronavirus disease 2019 (COVID-19) that integrates traditional Chinese (TCM) and western medicine.

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Peripheral blood immunological parameters of children with adenoid hypertrophy with otitis media with effusion: propensity score matching. To evaluate peripheral blood immunological parameters and the possible correlation with age, gender and adenoid size in children with adenoid hypertrophy with OME.

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School meals' centesimal and mineral composition and their nutritional value for Brazilian children. The assessment of meals served under the Brazilian National School Meal Program (PNAE) is an important tool to verify its adequacy to the proposed parameters and the nutritional needs of school-aged children. The aim of this study was to evaluate the centesimal and mineral composition of the meals offered by the program and adequacy to the nutritional recommendations in three municipalities of the state of Bahia, Brazil. Centesimal composition of meals was determined according to the reference guidelines and mineral composition was analyzed by atomic absorption spectrometry. Non-parametric analysis of variance was used to test the differences of the medians among the municipalities and Student-t test to compare the means between the two sampling periods. There were inadequacies in the carbohydrate, lipid and protein contents, and none of the municipalities reached the recommendation of 20%. Mineral concentration, especially Fe, Se, Cu and K were much lower than expected. Sodium levels were three-folds higher than the recommended, being worrisome due to higher risk of elevated blood pressure. There were inadequacies with regard to the PNAE guidelines, and there is a need to reevaluate the meals that are being offered to better meet childreńs needs and to form healthy habits from childhood.

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Cooking and Meal Planning as Predictors of Fruit and Vegetable Intake and BMI in First-Year College Students. The objective was to determine if cooking skills and meal planning behaviors are associated with greater fruit and vegetable intake and lower body mass index (BMI) in first-year college students who are at risk for excessive weight gain. A cross-sectional analysis was conducted using baseline data from a multi-state research project aimed at preventing weight gain in first-year college students. Cooking type, frequency and confidence, self-instruction for healthful mealtime behavior intention, self-regulation of healthful mealtime behavior, and cup equivalents of fruits and vegetables (FV) were measured using validated surveys. BMI was calculated from measured height and weight. First-year students ( n = 1108) considered at risk for weight gain from eight universities completed baseline assessments within the first month of entering college. Multiple linear regression was used to determine associations among independent variables of cooking patterns, meal planning behaviors, and dependent variables of fruit and vegetable intake and BMI, after controlling for the influence of sex. Cooking more frequently, cooking with greater skills, and practicing meal planning behaviors are associated with greater fruit and vegetable intake and lower BMI in first-year college students. Interventions aimed at improving health in college students may be enhanced by incorporating cooking and meal planning components.

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Does antenatal and post-natal program reduce infant mortality? A meta-analytical review on 24 developing countries based on Demographic and Health Survey data. This study intended to reveal the effectiveness of Antenatal Care (ANC) and Postnatal care (PNC) services on infant mortality in 24 developing countries by utilizing the recent Demographic and Health Survey (DHS) data.

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Almond as a nutraceutical and therapeutic agent in Persian medicine and modern phytotherapy: A narrative review. Sweet almond (Prunus dulcis (Mill.) D.A.Webb) is a known nut, which has long been used in several ethnomedical systems, especially in Persian medicine (PM) for its nutritional and therapeutic activities. In this study, we aimed to provide a summary on traditional uses, phytochemistry, and pharmacological activities of sweet almond. Thus, we reviewed textbooks of PM and electronic literature on traditional medicine. Moreover, the available data on the usage of sweet almond were searched in electronic databases to find articles on its pharmacological properties and phytochemistry. According to phytochemical investigations, this plant contains macronutrients, micronutrients, essential oils, various phenolic compounds, and phytosterols. Current pharmacological studies represent that Prunus dulcis has several biological activities including prebiotic, antimicrobial, antioxidant, antiinflammatory, anticancer, hepatoprotective, cardiometabolic protection, nootropic, anxiolytic, sedative-hypnotic, and nervous-improving effects. Further clinical trials and meta-analysis are required to draw a definitive conclusion on the efficacy and therapeutic activities of almond.

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svist4get: a simple visualization tool for genomic tracks from sequencing experiments. High-throughput sequencing often provides a foundation for experimental analyses in the life sciences. For many such methods, an intermediate layer of bioinformatics data analysis is the genomic signal track constructed by short read mapping to a particular genome assembly. There are many software tools to visualize genomic tracks in a web browser or with a stand-alone graphical user interface. However, there are only few command-line applications suitable for automated usage or production of publication-ready visualizations.

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Predicting hospital length of stay and short-term function after hip or knee arthroplasty: are both performance and comorbidity measures useful? Variations in hospital length of stay (LOS) and function are present after hip or knee arthroplasty. Comorbidity and performance measures have been associated with post-operative outcomes. It is however not known if both independently contribute to outcome prediction. The objective of this study was to evaluate the combined predictive ability of comorbidity scores (American Society of Anesthesiologists classification system (ASA), Charlson comorbidity index (CCI), 2008 version of the CCI (CCI08)) and a performance measure (Timed-Up-and-Go (TUG)) on LOS and short-term function in patients undergoing knee or hip arthroplasty.

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Chronic wound healing: A specific antibiofilm protein-asymmetric release system. Chronic infection is a major cause of delayed wound-healing. It is recognized to be associated with infectious bacterial communities called biofilms. Currently used conventional antibiotics alone often reveal themselves ineffective, since they do not specifically target the wound biofilm. Here, we report a new conceptual tool aimed at overcoming this drawback: an antibiofilm drug delivery system targeting the bacterial biofilm as a whole, by inhibiting its formation and/or disrupting it once it is formed. The system consists of a micro/nanostructured poly(butylene-succinate-co-adipate) (PBSA)-based asymmetric membrane (AM) with controlled porosity. By the incorporation of hydrophilic porogen agents, polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG), we were able to obtain AMs with high levels of porosity, exhibiting interconnections between pores. The PBSA-PEG membrane presented a dense upper layer with pores small enough to block bacteria penetration. Upon using such porogen agents, under dry and wet conditions, membrane's integrity and mechanical properties were maintained. Using bovine serum albumin (BSA) as a model protein, we demonstrated that protein loading and release from PBSA membranes were affected by the membrane structure (porosity) and the presence of residual porogen. Furthermore, the release curve profile consisted of a fast initial slope followed by a second slow phase approaching a plateau within 24 h. This can be highly beneficial for the promotion of wound healing. Cross-sectional confocal laser scanning microscopy (CLSM) images revealed a heterogeneous distribution of fluorescein isothiocyanate (FITC) labeled BSA throughout the entire membrane. PBSA membranes were loaded with dispersin B (DB), a specific antibiofilm matrix enzyme. Studies using a Staphylococcus epidermidis model, indicate significant efficiency in both inhibiting or dispersing preformed biofilm (up to 80 % eradication). The asymmetric PBSA membrane prepared with the PVP porogen (PBSA-PVP) displayed highest antibiofilm activity. Moreover, in vitro cytotoxicity assays using HaCaT and reconstructed human epidermis (RHE) models revealed that unloaded and DB-loaded PBSA-PVP membranes had excellent biocompatibility suitable for wound dressing applications.

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Effects of FSHR polymorphisms on premature ovarian insufficiency in human beings: a meta-analysis. Whether follicle-stimulating hormone receptor (FSHR) polymorphisms are implicated in premature ovarian insufficiency (POI) remains controversial. Thus, we performed this study to explore correlation between FSHR polymorphisms and POI in human beings.

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Cairo consensus on the IVF laboratory environment and air quality: report of an expert meeting. This proceedings report presents the outcomes from an international Expert Meeting to establish a consensus on the recommended technical and operational requirements for air quality within modern assisted reproduction technology (ART) laboratories. Topics considered included design and construction of the facility, as well as its heating, ventilation and air conditioning system; control of particulates, micro-organisms (bacteria, fungi and viruses) and volatile organic compounds (VOCs) within critical areas; safe cleaning practices; operational practices to optimize air quality while minimizing physicochemical risks to gametes and embryos (temperature control versus air flow); and appropriate infection-control practices that minimize exposure to VOC. More than 50 consensus points were established under the general headings of assessing site suitability, basic design criteria for new construction, and laboratory commissioning and ongoing VOC management. These consensus points should be considered as aspirational benchmarks for existing ART laboratories, and as guidelines for the construction of new ART laboratories.

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Chemodiversity of Brevetoxins and Other Potentially Toxic Metabolites Produced by Karenia spp. and Their Metabolic Products in Marine Organisms. In recent decades, more than 130 potentially toxic metabolites originating from dinoflagellate species belonging to the genus Karenia or metabolized by marine organisms have been described. These metabolites include the well-known and large group of brevetoxins (BTXs), responsible for foodborne neurotoxic shellfish poisoning (NSP) and airborne respiratory symptoms in humans. Karenia spp. also produce brevenal, brevisamide and metabolites belonging to the hemi-brevetoxin, brevisin, tamulamide, gymnocin, gymnodimine, brevisulcenal and brevisulcatic acid groups. In this review, we summarize the available knowledge in the literature since 1977 on these various identified metabolites, whether they are produced directly by the producer organisms or biotransformed in marine organisms. Their structures and physicochemical properties are presented and discussed. Among future avenues of research, we highlight the need for more toxin occurrence data with analytical techniques, which can specifically determine the analogs present in samples. New metabolites have yet to be fully described, especially the groups of metabolites discovered in the last two decades (e.g tamulamides). Lastly, this work clarifies the different nomenclatures used in the literature and should help to harmonize practices in the future.

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Upconversion Nanoprobes for the Ratiometric Luminescent Sensing of Nitric Oxide. By taking advantage of the optical properties of upconversion nanoparticles (UCNPs), we have designed a luminescence ratiometric nanosensor for measuring nitric oxide (NO) in biological fluids, live cells, and tissues. This nanoconjugate consists of a UCNP core with two strong fluorescence emission peaks at 540 and 656 nm as the upconversion fluorophore, NO-reactive rhodamine B-derived molecules (RdMs) encapsulated within the mesopores of the mSiO 2 shell, and a β-cyclodextrin (βCD) layer on the exterior of the particle. Reaction of the analyte with the O-phenylenediamine of the RdM induces opening of the spiro-ring and is accompanied by an appearance of a strong rhodamine B (RdB) absorption band between 500 and 600 nm, which has spectral overlap with the green emission (540 nm) of the UCNPs. This results in an increase in the I 656 /I 540 ratio and quantitatively correlates with [NO]. The assay is validated under clean buffer conditions as well as inserum and liver tissue slices obtained from mouse models.

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Stability, dissolution, and cytotoxicity of NaYF 4 -upconversion nanoparticles with different coatings. Upconversion nanoparticles (UCNPs) have attracted considerable attention owing to their unique photophysical properties. Their utilization in biomedical applications depends on the understanding of their transformations under physiological conditions and their potential toxicity. In this study, NaYF 4 :Yb,Er UCNPs, widely used for luminescence and photophysical studies, were modified with a set of four different coordinatively bound surface ligands, i.e., citrate, alendronate (AA), ethylendiamine tetra(methylene phosphonate) (EDTMP), and poly(maleic anhydride-alt-1-octadecene) (PMAO), as well as silica coatings with two different thicknesses. Subsequently, the aging-induced release of fluoride ions in water and cell culture media and their cytotoxic profile to human keratinocytes were assessed in parallel to the cytotoxic evaluation of the ligands, sodium fluoride and the lanthanide ions. The cytotoxicity studies of UCNPs with different surface modifications demonstrated the good biocompatibility of EDTMP-UCNPs and PMAO-UCNPs, which is in line with the low amount of fluoride ions released from these samples. An efficient prevention of UCNP dissolution and release of cytotoxic ions, as well as low cytotoxicity was also observed for UCNPs with a sufficiently thick silica shell. Overall, our results provide new insights into the understanding of the contribution of surface chemistry to the stability, dissolution behavior, and cytotoxicity of UCNPs. Altogether, the results obtained are highly important for future applications of UCNPs in the life sciences and bioimaging studies.

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Hydraulic separation of plastic wastes: Analysis of liquid-solid interaction. The separation of plastic wastes in mechanical recycling plants is the process that ensures high-quality secondary raw materials. An innovative device employing a wet technology for particle separation is presented in this work. Due to the combination of the characteristic flow pattern developing within the apparatus and density, shape and size differences among two or more polymers, it allows their separation into two products, one collected within the instrument and the other one expelled through its outlet ducts. The kinematic investigation of the fluid flowing within the apparatus seeded with a passive tracer was conducted via image analysis for different hydraulic configurations. The two-dimensional turbulent kinetic energy results strictly connected to the apparatus separation efficacy. Image analysis was also employed to study the behaviour of mixtures of passive tracer and plastic particles with different physical characteristics in order to understand the coupling regime between fluid and solid phases. The two-dimensional turbulent kinetic energy analysis turned out to be fundamental to this aim. For the tested operating conditions, two-way coupling takes place, i.e., the fluid exerts an influence on the plastic particle and the opposite occurs too. Image analysis confirms the outcomes from the investigation of the two-phase flow via non-dimensional numbers (particle Reynolds number, Stokes number and solid phase volume fraction).

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[Clinical value of herbal terpenes after extracorporeal shock-wave therapy]. Rowatinex is a combined drug based on plant terpenes which provides diuretic, anti-inflammatory and antispasmodic effect. A use of herbal preparation Rowatinex in patients with urinary stone disease after extracorporeal shock-wave therapy (ESWL) is analyzed in the article.

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Nonlinear Extensional Rheology of Poly( n -alkyl methacrylate) Melts with a Fixed Number of Kuhn Segments and Entanglements per Chain. Molecular theories for dynamics of entangled polymers are based on both the number of Kuhn segments per entanglement N e and the number of entanglements per chain N / N e . Extensive studies have shown that, for polymer chains in the solutions or melts, linear viscoelasticity can be properly normalized, whereas the nonlinear extensional rheological properties cannot be normalized when N / N e is kept the same. The failure of the latter normalization has been attributed to a difference in N e . Nevertheless, nonlinear rheological studies are lacking for a suitable model system with fixed N e and N / N e . In this study, we identify poly( n -alkyl methacrylate)s with the number of carbons per alkyl group below seven as a model system. We find that the degree of the transient strain hardening during extensional flow strengthens with increasing the size of the alkyl group even when N e and N / N e are kept the same, which is attributable to the weaker friction reduction when the main backbones are more separated.

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Application of spectral induced polarization for characterizing surfactant-enhanced DNAPL remediation in laboratory column experiments. The widespread presence of entrapped dense non-aqueous phase liquid (DNAPL) in the subsurface poses a continuing challenge to groundwater remediation. Cost-effective and high-resolution subsurface characterization is a critical issue for further DNAPL recovery due to the complexity of DNAPL source zone architecture (SZA). Geophysical techniques provide a noninvasive, spatially continuous and cost-effective way for monitoring the DNAPL remediation process. In particular, the spectral induced polarization (SIP) method has shown great potential in environmental problems. In this study, we performed real-time SIP measurements on DNAPL contaminated soil in columns to quantitatively assess the ability of SIP method for monitoring surfactant-enhanced DNAPL remediation process. Chemical data was simultaneously collected during the remediation process to verify the results obtained by SIP method. Taking account into the variations of subsurface environment, we conducted a series of column flushing experiments under different flow rate, surfactant concentrations and fluid salinities. The results highlight that SIP method is able to effectively monitor the DNAPL remediation process, as well as to evaluate the remediation efficiency under different conditions. The variations in the flow rate, the concentration of surfactant and the salinity of pore water not only affect remediation effectiveness, but also have an impact on the SIP signatures. This study shows that SIP performs better for monitoring DNAPL remediation at a relatively low flow rate of ~ 0.4 m/d, low surfactant concentration of 5000 mg/L and high salinity of 1.0 S/m, with an error of saturation estimation (RMSE S ) <0.1.

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REL-1017 (Esmethadone) as Adjunctive Treatment in Patients With Major Depressive Disorder: A Phase 2a Randomized Double-Blind Trial. Objective: The purpose of this study was to examine the effects of REL-1017 (esmethadone), a novel N -methyl-d-aspartate receptor (NMDAR) channel blocker, in patients with major depressive disorder who failed to benefit from one to three standard antidepressant treatments in their current major depressive episode. Methods: A 7-day phase 2 multicenter randomized double-blind placebo-controlled trial, comprising three arms, was conducted to assess the safety, tolerability, pharmacokinetics, and efficacy of two dosages of REL-1017 (25 mg or 50 mg orally once a day). Patients were randomly assigned in a 1:1:1 ratio to placebo (N=22), REL-1017 25 mg/day (N=19), or REL-1017 50 mg/day (N=21). Safety scales included the 4-item Positive Symptom Rating Scale for psychotomimetic symptoms, the Clinician-Administered Dissociative States Scale for dissociative symptoms, the Clinical Opiate Withdrawal Scale for withdrawal signs and symptoms, and the Columbia-Suicide Severity Rating Scale for suicidality. The primary efficacy endpoint was the Montgomery-Åsberg Depression Scale (MADRS) score. All 62 randomly assigned patients were included in the full analysis set population analysis. Results: Patients experienced mild or moderate transient adverse events and no evidence of dissociative or psychotomimetic effects, opioid effects, or withdrawal signs and symptoms. The improvement in MADRS score shown on day 4 in both of the REL-1017 dosage groups was sustained through day 7 (last dose) and day 14 (7 days after the last dose), with effect sizes from 0.7 to 1.0. Conclusions: This trial showed favorable safety, tolerability, and pharmacokinetic profiles and suggests that REL-1017 may have rapid and sustained antidepressant effects compared with placebo in patients with inadequate responses to antidepressant treatments. These results will need confirmation in larger and longer trials.

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Effects of walking exercise training on learning and memory and hippocampal neuroimaging outcomes in MS: A targeted, pilot randomized controlled trial. The current pilot study involved a single-blind, randomized controlled trial (RCT) on the effects of treadmill walking exercise training compared with an active control condition on learning and memory (L/M) and hippocampal neuroimaging outcomes in 11 fully-ambulatory persons with multiple sclerosis (MS) who demonstrated impairments in new learning.

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Neonatal diabetes mellitus due to a new KCNJ11 mutation - 10 years of the patient`s follow-up. Mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the ATP-sensitive potassium channel, often result in neonatal diabetes.

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Low-intensity pulsed ultrasound regulates proliferation and differentiation of neural stem cells through notch signaling pathway. Low-intensity pulsed ultrasound (LIPUS) is widely used to regulate stem cell proliferation and differentiation. However, the effect of LIPUS stimulation on neural stem cells (NSCs) is not well documented. In this study, we have identified the optimal parameters, and investigated the cellular mechanisms of LIPUS to regulate the proliferation and differentiation of NSCs in vitro. NSCs were obtained and identified by nestin immunostaining. The proliferation of NSCs were measured by using Cell Counting Kit-8 (CCK-8). The expressions of nutritional factors (NTFs) were detected with immunoassay (ELISA). NSCs differentiation were detected by immunofluorescence and immunoblotting analysis. The expression level of proteins involved in the Notch signaling pathway was also measured by immunoblotting assay. Our results showed the intensity of 69.3 mW/cm 2 (1 MHz, 8 V) was applicable for LIPUS stimulation. ELISA analysis demonstrated that LIPUS treatment promoted the expression of nutritional factors of NSCs in vitro. Immunofluorescence and immunoblotting analyses suggested that the LIPUS not only reduced the astrocyte differentiation, but also stimulated the differentiation to neurons. Additionally, LIPUS stimulation significantly upregulated expression level of Notch1 and Hes1. Results from our study suggest that LIPUS triggers NSCs proliferation and differentiation by modulating the Notch signaling pathway. This study implies LIPUS as a potential and promising therapeutic platform for the optimization of stem cells and enable noninvasive neuromodulation for central nervous system diseases.

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Cardiac resynchronization therapy in the ageing population - With or without an implantable defibrillator? Cardiac resynchronization therapy (CRT) is an effective treatment option for systolic heart failure, but the benefit of an additional implantable cardioverter-defibrillator (ICD) in elderly patients is not well established. The aim of our study was to evaluate the impact of an additional ICD on survival in elderly CRT recipients.

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Epigenetics and pulmonary diseases in the horizon of precision medicine: a review. Epigenetic mechanisms represent potential molecular routes which could bridge the gap between genetic background and environmental risk factors contributing to the pathogenesis of pulmonary diseases. In patients with COPD, asthma and pulmonary arterial hypertension (PAH), there is emerging evidence of aberrant epigenetic marks, mainly including DNA methylation and histone modifications which directly mediate reversible modifications to the DNA without affecting the genomic sequence. Post-translational events and microRNAs can be also regulated epigenetically and potentially participate in disease pathogenesis. Thus, novel pathogenic mechanisms and putative biomarkers may be detectable in peripheral blood, sputum, nasal and buccal swabs or lung tissue. Besides, DNA methylation plays an important role during the early phases of fetal development and may be impacted by environmental exposures, ultimately influencing an individual's susceptibility to COPD, asthma and PAH later in life. With the advances in omics platforms and the application of computational biology tools, modelling the epigenetic variability in a network framework, rather than as single molecular defects, provides insights into the possible molecular pathways underlying the pathogenesis of COPD, asthma and PAH. Epigenetic modifications may have clinical applications as noninvasive biomarkers of pulmonary diseases. Moreover, combining molecular assays with network analysis of epigenomic data may aid in clarifying the multistage transition from a "pre-disease" to "disease" state, with the goal of improving primary prevention of lung diseases and its subsequent clinical management.We describe epigenetic mechanisms known to be associated with pulmonary diseases and discuss how network analysis could improve our understanding of lung diseases.

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Prognostic value of reduction in left atrial size during a follow-up of heart failure: an observational study. The association between sequential changes in left atrial diameter (LAD) and prognosis in heart failure (HF) remains to be elucidated. The present study aimed to investigate the link between reduction in LAD and clinical outcomes in patients with HF.

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Does competition affect the clinical decision-making of dentists? A geospatial analysis. To investigate the association between dentists' geographic density and perceptions of market competition with clinical decision-making among a representative sample of dentists in Ontario, Canada's most populated province.

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Structural and organizational factors shaping access to medication treatment for opioid use disorder in community supervision. Four million individuals in the U.S. criminal-legal system are supervised in the community under probation or parole. Sentences to community supervision often mandate participation in substance use treatment. Yet evidence-based treatment with medication (i.e., methadone, buprenorphine, or naltrexone) is rarely offered to people under community supervision with opioid use disorder (OUD). This qualitative study explores the structural and organizational factors shaping OUD medication treatment use in community supervision.

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Oral transfer of chemical cues, growth proteins and hormones in social insects. Social insects frequently engage in oral fluid exchange - trophallaxis - between adults, and between adults and larvae. Although trophallaxis is widely considered a food-sharing mechanism, we hypothesized that endogenous components of this fluid might underlie a novel means of chemical communication between colony members. Through protein and small-molecule mass spectrometry and RNA sequencing, we found that trophallactic fluid in the ant Camponotus floridanus contains a set of specific digestion- and non-digestion related proteins, as well as hydrocarbons, microRNAs, and a key developmental regulator, juvenile hormone. When C. floridanus workers' food was supplemented with this hormone, the larvae they reared via trophallaxis were twice as likely to complete metamorphosis and became larger workers. Comparison of trophallactic fluid proteins across social insect species revealed that many are regulators of growth, development and behavioral maturation. These results suggest that trophallaxis plays previously unsuspected roles in communication and enables communal control of colony phenotypes.

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Assessing a novel way to measure step count while walking using a custom mobile phone application. Walking speed has been associated with many clinical outcomes (e.g., frailty, mortality, joint replacement need, etc.). Accurately measuring walking speed (stride length x step count/time) typically requires significant clinician/staff time or a gait lab with specialized equipment (i.e., electronic timers or motion capture). In the present study, our goal was to measure "step count" via smartphones through novel software and to compare with step tracking software that come standard with iOS and Android smartphones as a first step in walking speed measurement.

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Current Treatment Options for HCC: From Pharmacokinetics to Efficacy and Adverse Events in Liver Cirrhosis. Hepatocellular carcinoma (HCC) is among the world's most common cancers. For over ten years, the only medical treatment for it has been the multikinase inhibitor Sorafenib. Currently, however, other first or second-line therapeutic options have also shown efficacy against HCC, such as multikinase inhibitors (Regorafenib, Lenvatinib, and Cabozantinib), a monoclonal antibody against the vascular endothelial growth factor receptor 2 (Ramucirumab), and immune-checkpoint inhibitors (Nivolumab, Pembrolizumab, Ipilimumab).

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Surgical technique and outcomes following coronal-sparing glans resurfacing for benign and malignant penile lesions. The aim of this study is to describe the outcomes for a modified glans-resurfacing technique for benign and malignant penile conditions in which the uninvolved glans corona is preserved in order to maintain glans erogenous sensation. A total of 13 patients underwent coronal-sparing glans resurfacing (CSGR), with follow-up every 3 months for ≥2 years. Positive surgical margin and local recurrence (LR) rates were evaluated. Surgical complications and cosmetic outcomes were also recorded. Patients were asked to complete the International Index of Erectile Function-5 (IIEF-5) questionnaire starting 12 months after the surgery. The median (interquartile range [IQR]) age and follow-up periods were 63 (53-68) years and 29 (14-38) months, respectively. Eight patients were diagnosed with primary penile squamous cell carcinoma (SCC), three had refractory lichen sclerosus, and two had penile intraepithelial neoplasia (PeIN). No surgical complications were recorded. All patients had a complete graft take and reported satisfactory cosmetic results with preserved erogenous sensation. Two cancer patients developed LR which was managed with further penile preserving surgery. The median (IQR) postoperative IIEF-5 value was 20 (17-23). This modified coronal-sparing technique was suitable for glans lesions that spare the coronal ridge and coronal sulcus. Preservation of the coronal ridge helps maintain sexual function and provides excellent cosmetic outcomes.

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Stachydrine hydrochloride alleviates pressure overload-induced heart failure and calcium mishandling on mice. Traditional Chinese medicine Leonurus japonicus Houtt. has a long history in the treatment of cardiovascular diseases. Stachydrine hydrochloride, the main bioactive ingredient extracted from Leonurus japonicus Houtt., has been shown to have cardioprotective effects. However, the underlying mechanisms of stachydrine hydrochloride haven't been comprehensively studied so far.

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Clinical assessment of the impact of pelvic pain on women. We aimed to develop a questionnaire that assesses the impact of pelvic pain on women, regardless of diagnosis, that has high utility, sound psychometric performance, easy scoring, and high reliability. Two studies, with 3 separate cohorts, were undertaken. Both studies were completed online. Studies included women with self-reported pelvic pain. Women were eligible to participate regardless of whether their pelvic pain was undiagnosed, self-diagnosed, or diagnosed by a clinician. Study 1 used a 3-round "patient-as-expert" Delphi technique. These rounds defined the 10 aspects of life with the self-reported greatest impact on the lives of women with pelvic pain, which formed the questionnaire. Study 2 used Rasch analysis to assess the psychometric properties of the resultant 10-item questionnaire. To assess its reliability, a subgroup completed the questionnaire 3 times over a 3-week period. In study 1, 443 women with pelvic pain participated. The resultant 10-item questionnaire consisted of 8 Likert questions and 2 supplemental, nonscored questions. In study 2, 1203 women with pelvic pain completed the questionnaire. Rasch analysis showed that the questionnaire targeted the pelvic pain population well, had appropriate Likert categories, constituted a unidimensional scale, and showed internal consistency. Twenty-seven women with pelvic pain completed the reliability trial. Test-retest reliability was high (intraclass correlation coefficient 0.91, P < 0.001). The resultant Pelvic Pain Impact Questionnaire assesses the life impact of pelvic pain. It uses patient-generated language, is easily administered and scored, has very strong psychometric properties, and it is suitable for research and clinical settings across primary, secondary, and tertiary care.

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Patterns and predictors of private and public health care utilization among residents of an informal settlement in Nairobi, Kenya: a cross-sectional study. Knowledge of health care utilization is important in low-and middle-income countries where inequalities in the burden of diseases and access to primary health care exist. Limited evidence exists on health seeking and utilization in the informal settlements in Kenya. This study assessed the patterns and predictors of private and public health care utilization in an urban informal settlement in Kenya.

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A new species of Bent-toed Gecko (Squamata, Gekkonidae, Cyrtodactylus) from the Shan Plateau in eastern Myanmar (Burma). An integrative taxonomic analysis of the Cyrtodactylus linnwayensis group of the Shan Plateau recovered two new populations from isolated karst habitats near Pinlaung Town, Shan State as a new species, C. pinlaungensis sp. nov. Cyrtodactylus pinlaungensis sp. nov. is most closely related to a clade comprising C. linnwayensis and C. ywanganensis from the western edge of the Shan Plateau approximately 90 km to the northwest. Cyrtodactylus pinlaungensis sp. nov. can be distinguished from all members of the C. linnwayensis group by a number of statistically different morphological characters, discrete color pattern differences, and its heavy tuberculation. It also bears an uncorrected pairwise sequence divergence of 5.0-7.6% from all other species combined based on the mitochondrial gene ND2 and its flanking tRNAs. The discovery of this new species on the Shan Plateau continues to underscore the fact that this region is rapidly emerging as a herpetological diversity hot-spot for Myanmar.

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Cell-Nanoparticle Interactions at (Sub)-Nanometer Resolution Analyzed by Electron Microscopy and Correlative Coherent Anti-Stokes Raman Scattering. A wide variety of nanoparticles are playing an increasingly important role in drug delivery. Label-free imaging techniques are especially desirable to follow the cellular uptake and intracellular fate of nanoparticles. The combined correlative use of different techniques, each with unique advantages, facilitates more detailed investigation about such interactions. The synergistic use of correlative coherent anti-Stokes Raman scattering and electron microscopy (C-CARS-EM) imaging offers label-free, chemically-specific, and (sub)-nanometer spatial resolution for studying nanoparticle uptake into cells as demonstrated in the current study. Coherent anti-Stokes Raman scattering (CARS) microscopy offers chemically-specific (sub)micron spatial resolution imaging without fluorescent labels while transmission electron microscopy (TEM) offers (sub)-nanometer scale spatial resolution and thus visualization of precise nanoparticle localization at the sub-cellular level. This proof-of-concept imaging platform with unlabeled drug nanocrystals and macrophage cells revealed good colocalization between the CARS signal and electron dense nanocrystals in TEM images. The correlative TEM images revealed subcellular localization of nanocrystals inside membrane bound vesicles, showing multivesicular body (MVB)-like morphology typical for late endosomes (LEs), endolysosomes, and phagolysosomes. C-CARS-EM imaging has much potential to study the interactions between a wide range of nanoparticles and cells with high precision and confidence.

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Dexamethasone delivery to the ocular posterior segment by sustained-release Laponite formulation. This paper presents a novel nanoformulation for sustained-release delivery of dexamethasone (DEX) to the ocular posterior segment using a Laponite (LAP) carrier-DEX/LAP 1:10 w w -1 formulation; 10 mg ml -1 . In vivo ocular feasibility and pharmacokinetics after intravitreal (IV) and suprachoroidal (SC) administration in rabbit eyes are compared against IV administration of a DEX solution (1 mg ml -1 ). Thirty rabbit eyes were injected with the DEX/LAP formulation (15 suprachoroid/15 intravitreous). Ophthalmological signs were monitored at day 1 and at weeks 1-4-12-24 post-administration. Three eyes per sample time point were used to quantify DEX concentration using high-performance liquid chromatography-mass spectrometry. The ocular tissues' pharmacokinetic parameters (lens, vitreous humour, choroid-retina unit and sclera) were studied. DEX/LAP was well tolerated under both administration methods. Peak intraocular DEX levels from the DEX/LAP were detected in the vitreous humour after both deliveries soon after administration. The vitreous area under the curve was significantly greater after both DEX/LAP deliveries (IV: 205 968.47; SC: 11 442.22 ng g -1 d -1 ) than after IV administration of the DEX solution (317.17 ng g -1 d -1 ). Intravitreal DEX/LAP delivery extended higher vitreous DEX levels up to week 24 (466.32 ± 311.15 ng g -1 ). With SC delivery, DEX levels were detectable in the choroid-retina unit (12.04 ± 20.85 ng g -1 ) and sclera (25.46 ± 44.09 ng g -1 ) up to week 24. This study demonstrated the intraocular feasibility of both SC and IV administration of the DEX/LAP formulation. The LAP increased the intraocular retention time of DEX when compared with conventional solutions. DEX/LAP could be considered a biocompatible and useful sustained-release formulation for treating posterior-pole eye diseases.

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Genetic analysis of surgical margins in oral cavity cancer. A histological, tumour-free surgical margin does not guarantee recurrence-free survival in patients with cancer. This study investigated the association between microsatellite alteration in tumour-free surgical margins and local recurrence in patients with oral cavity squamous cell carcinoma.

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Unraveling neuroHIV in the Presence of Substance Use Disorders. This special issue contains 10 invited review papers that highlighted and extended the presentations at the NIDA-sponsored workshop "Unraveling NeuroAIDS in the Presence of Substance Use Disorders" at the 25th Society on NeuroImmune Pharmacology conference in 2019. The topics covered by these papers focused on the interactive, additive or synergistic effects of substance use disorders (SUD) with HIV infection on the immune system and on neuropathogenesis. These papers reviewed four categories of substances of abuse (opioids, tobacco, stimulants, and cannabis) and how comorbid HIV infection (including models with HIV proteins, HIV transgenic rodent models and SIV) might further impact the dysregulated dopaminergic and immune systems, and the subsequent neuropathogenesis and behavioral disorders known as HIV-associated neurological disorders (HAND). These reviews provided detailed background knowledge regarding how each of these addictive substances and HIV individually or collectively affected the immune system at the cellular, molecular and system levels, and the subsequent clinical and behavioral outcomes. The authors also identified gaps, confounds or constraints in the current disease models and approaches, and proposed future research directions.

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Sex differences in the acute pharmacological and subjective effects of smoked cannabis combined with alcohol in young adults. Objective: The prevalence of co-use of alcohol and cannabis is increasing, particularly among young adults. Sex differences in the effects of alcohol alone and cannabis alone have been observed in animals and humans. However, sex differences in the acute pharmacological effects of cannabis combined with alcohol have not yet been studied. In young adults, aged 19-29 years, we aimed to examine sex differences following an intoxicating dose of alcohol (target 0.08% breath alcohol content) combined with a moderate dose of cannabis (12.5% Δ⁹-tetrahydrocannabinol; THC) using an ad libitum smoking procedure. Method: Using a within-subjects design, 28 regular cannabis users (16 males; 12 females) received in random order: (a) placebo alcohol and placebo cannabis, (b) active alcohol and placebo cannabis, (c) placebo alcohol and active cannabis, and (d) active alcohol and active cannabis. Blood samples for THC were collected and measures of vital signs, subjective drug effects, and cognition were collected. Results: In the alcohol-cannabis combined condition, females smoked significantly less of the cannabis cigarette compared to males ( p < .001), although both sexes smoked similar amounts in the other conditions. There was minimal evidence that females and males differed in THC blood concentrations, vitals, subjective effects, or cognitive measures. Conclusions: In the alcohol-cannabis combined condition, females experienced the same acute pharmacological and subjective effects of alcohol and cannabis as males, after smoking less cannabis, which has potential implications for informing education and policy. Further research is warranted on sex differences in cannabis pharmacology, as well as the combined effects of alcohol and cannabis. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

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Microbial electrohydrogenesis linked to dark fermentation as integrated application for enhanced biohydrogen production: A review on process characteristics, experiences and lessons. Microbial electrohydrogenesis cells (MECs) are devices that have attracted significant attention from the scientific community to generate hydrogen gas electrochemically with the aid of exoelectrogen microorganisms. It has been demonstrated that MECs are capable to deal with the residual organic materials present in effluents generated along with dark fermentative hydrogen bioproduction (DF). Consequently, MECs stand as attractive post-treatment units to enhance the global H 2 yield as a part of a two-stage, integrated application (DF-MEC). In this review article, it is aimed (i) to assess results communicated in the relevant literature on cascade DF-MEC systems, (ii) describe the characteristics of each steps involved and (iii) discuss the experiences as well as the lessons in order to facilitate knowledge transfer and help the interested readers with the construction of more efficient coupled set-ups, leading eventually to the improvement of overall biohydrogen evolution performances.

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Prevalence of temporomandibular disorder in adult patients with chronic pain. Chronic pain patients often suffer in multiple locations. In health care, examinations of bodily pain usually do not include questions about temporomandibular disorders (TMD); hence TMD symptoms and potential comorbidities are not regularly assessed. Therefore, the primary aim was to evaluate the prevalence of TMD in patients referred to a pain rehabilitation clinic, and the secondary aim was to evaluate possible factors associated with TMD symptoms.

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Kin selection promotes female productivity and cooperation between the sexes. Hamilton's theory of kin selection explains the evolution of costly traits that benefit other individuals by highlighting the fact that passing genes to offspring is not the only way of increasing the representation of those genes in subsequent generations: Genes are also shared with other classes of relatives. Consequently, any heritable trait that affects fitness of relatives should respond to kin selection. We tested this core prediction of kin selection theory by letting bulb mites ( Rhizoglyphus robini ) evolve in populations structured into groups of relatives or nonrelatives during the reproductive phase of the life cycle. In accordance with predictions derived from kin selection theory, we found that evolution in groups of relatives resulted in increased female reproductive output. This increase at least partly results from the evolution of male traits that elevate their partners' fecundity. Our results highlight the power and universality of kin selection.

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Do Season and Environment Have a Role in the Incidence of Anterior Uveitis Attacks? To investigate the seasonal influence on the incidence of uveitis attacks.

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Establishing the Prevalence of Intimate Partner Violence Among Hair Salon Clients. This study determined prevalence of intimate partner violence (IPV) victimization among female clients at three hair salons in Connecticut using an anonymous tablet based screening tool. While many may assume that women receive services at hair salons, victims of IPV are often isolated by their partners and unable to access help. Of the 203 clients who participated, 40 (20%) had experienced IPV in her lifetime. In identifying the prevalence of IPV within the salon setting, this study provides support for community-based programs and supports their legitimacy as an important locus for identifying women experiencing IPV and connecting them to resources.

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Endometriosis shows no impact on the euploid blastocyst rate per cohort of inseminated metaphase-II oocytes: A case-control study. To evaluate the true impact of endometriosis on oocytes' competence defined as blastulation, euploidy and implantation rates.

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Radiomics in PET/CT: Current Status and Future AI-Based Evolutions. This short review aims at providing the readers with an update on the current status, as well as future perspectives in the quickly evolving field of radiomics applied to the field of PET/CT imaging. Numerous pitfalls have been identified in study design, data acquisition, segmentation, features calculation and modeling by the radiomics community, and these are often the same issues across all image modalities and clinical applications, however some of these are specific to PET/CT (and SPECT/CT) imaging and therefore the present paper focuses on those. In most cases, recommendations and potential methodological solutions do exist and should therefore be followed to improve the overall quality and reproducibility of published studies. In terms of future evolutions, the techniques from the larger field of artificial intelligence (AI), including those relying on deep neural networks (also known as deep learning) have already shown impressive potential to provide solutions, especially in terms of automation, but also to maybe fully replace the tools the radiomics community has been using until now in order to build the usual radiomics workflow. Some important challenges remain to be addressed before the full impact of AI may be realized but overall the field has made striking advances over the last few years and it is expected advances will continue at a rapid pace.

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Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study. Achondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported.

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How is orthodontic treatment need associated with perceived esthetic impact of malocclusion in adolescents? The purpose of this research was to evaluate the esthetic impact of orthodontic treatment need in adolescents.

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Proteomics insights into the effects of MSTN on muscle glucose and lipid metabolism in genetically edited cattle. The molecular mechanism underlying myostatin (MSTN)-regulated metabolic cross-talk remains poorly understood. In this study, we performed comparative proteomic and phosphoproteomic analyses of gluteus muscle tissues from MSTN -/- transgenic cattle using a shotgun-based tandem mass tag (TMT) 6-plex labeling method to explore the signaling pathway of MSTN in metabolic cross-talk and cellular metabolism during muscle development. A total of 72 differentially expressed proteins (DEPs) and 36 differentially expressed phosphoproteins (DEPPs) were identified in MSTN -/- cattle compared to wild-type cattle. Bioinformatics analyses showed that MSTN knockout increased the activity of many key enzymes involved in fatty acid β-oxidation and glycolysis processes in cattle. Furthermore, comprehensive pathway analyses and hypothesis-driven AMP-activated protein kinase (AMPK) activity assays suggested that MSTN knockout triggers the activation of AMPK signaling pathways to regulate glucose and lipid metabolism by increasing the AMP/ATP ratio. Our results shed new light on the potential regulatory mechanism of MSTN associated with metabolic cross-talk in muscle development, which can be used in animal breeding to improve meat production in livestock animals, and can also provide valuable insight into treatments for obesity and diabetes mellitus in humans.

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Prevalence of malnutrition among older people in medical and surgical wards in hospital and quality of nutritional care: A multicenter, cross-sectional study. To determine and compare the prevalence of malnutrition in medical and surgical hospital units; to assess quality of nutritional care and patients' perception about quality of food and nutritional care.

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Anatomical Risk Factors for Anterior Cruciate Ligament Injury Are Not Important As Patellar Instability Risk Factors in Patients with Acute Knee Injury. To compare in magnetic resonance imaging the anatomical risk factors for anterior cruciate ligament (ACL) injury and patellar dislocation among patients who suffered acute knee injury, 105 patients with acute knee injury resulting in 38 patellar dislocations (patella group), 35 ACL injuries (ACL group), and 32 meniscus or medial collateral ligament injuries (control group) were included. These groups were compared for risk factors for patellar dislocation (patellar height, trochlear dysplasia, and quadriceps angle of action) and for ACL injury (intercondylar width, posterior inclination of tibial plateaus, and depth of the medial plateau). Univariate analysis found statistically significant differences ( p < 0.05) between the patella and ACL groups in patellar height (Caton-Deschamps [CD] 1.23 vs. 1.07), trochlear facet asymmetry (55 vs. 68%), PTTG (13.08 vs. 8.01 mm), and the patellar tip and trochlear groove (PTTG) angle (29.5 vs. 13.71 degrees). The patella group also differed from control in medial plateau inclination (4.8 vs. 1.87 degrees), patellar height (CD 1.23 vs 1.08), trochlear facet asymmetry (55 vs. 69%), lateral trochlear inclination (17.11 vs. 20.65 degrees), trochlear depth (4.1 vs. 6.05 mm), PTTG (13.08 vs. 9.85 mm), and the PTTG angle (29.5 vs. 17.88 degrees). The ACL and control groups were similar in all measures. Multivariate analysis found the following significant determinants between the Patella and Control groups: patellar height (CD index, odds ratio [OR]: 80.13, p = 0.015), trochlear anatomy (asymmetry of facets M/L, OR: 1.06, p = 0.031) and quadriceps action angle (PTTG angle, OR: 1.09, p = 0.016); between the ACL and control groups: PTTG angle (OR: 0.936, p = 0.04) and female gender (OR: 3.876, p = 0.032); and between the patella and ACL groups, the CD index (OR: 67.62, p = 0.026), asymmetry of the M/L facets (OR: 1.07, p = 0.011) and PTTG angle (OR: 1.16, p < 0.001). In conclusion, in patients with acute knee injury, the anatomical factors patellar height, trochlear dysplasia, and quadriceps angle of action were related to the occurrence of patellar dislocation. None of the anatomical factors studied was related to the occurrence of anterior cruciate ligament injury.

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Research of Distorted Vehicle Magnetic Signatures Recognitions, for Length Estimation in Real Traffic Conditions. Reliable cost-effective traffic monitoring stations are a key component of intelligent transportation systems (ITS). While modern surveillance camera systems provide a high amount of data, due to high installation price or invasion of drivers' personal privacy, they are not the right technology. Therefore, in this paper we introduce a traffic flow parameterization system, using a built-in pavement sensing hub of a pair of AMR (anisotropic magneto resistance) magnetic field and MEMS (micro-electromechanical system) accelerometer sensors. In comparison with inductive loops, AMR magnetic sensors are significantly cheaper, have lower installation price and cause less intrusion to the road. The developed system uses magnetic signature to estimate vehicle speed and length. While speed is obtained from the cross-correlation method, a novel vehicle length estimation algorithm based on characterization of the derivative of magnetic signature is presented. The influence of signature filtering, derivative step and threshold parameter on estimated length is investigated. Further, accelerometer sensors are employed to detect when the wheel of vehicle passes directly over the sensor, which cause distorted magnetic signatures. Results show that even distorted signatures can be used for speed estimation, but it must be treated with a more robust method. The database during the real-word traffic and hazard environmental condition was collected over a 0.5-year period and used for method validation.

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Is urban living good for mental health? The questions of urban living, mental health and well-being are complex issues correlated to many interacting factors. The purpose of this review is to provide data on mental health challenges of urban life and perspectives to address these challenges.

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Testing depth of suppression in childhood intermittent exotropia. A test of suppression was developed to provide a standardized approach to detecting and grading density of suppression in children with intermittent exotropia when manifestly exotropic. This new Office Suppression Test is a three-step procedure to grade suppression on a 4-point scale (from 0 for "negligible suppression" to 3 for "dense suppression"). The test was performed in 57 children 3-13 years of age with intermittent exotropia (distance angle of 16 Δ -35 Δ , with spontaneous tropia) during enrollment in a randomized trial. Of the 57 children, 51 could complete testing: 28 (55%) had dense suppression, 12 (24%) had moderate suppression, 5 (10%) had mild suppression, and 6 (12%) had negligible suppression. In a subgroup of 20 untreated children, suppression was evaluated again at 8 weeks. There was moderate agreement between suppression scores at baseline and at 8 weeks (weighted κ = 0.65 [95% CI, 0.45-0.84]).

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Association Between Parental Marital Status and Types of Suicidal Behavior Among Korean Adolescents: A Cross-sectional Study. Adolescent suicide is a global problem. This study aimed to identify associations between parental marital status and suicidal behavior.

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Genome-Wide Identification of the LAC Gene Family and Its Expression Analysis Under Stress in Brassica napus . Lignin is an important biological polymer in plants that is necessary for plant secondary cell wall ontogenesis. The laccase ( LAC ) gene family catalyzes lignification and has been suggested to play a vital role in the plant kingdom. In this study, we identified 45 LAC genes from the Brassica napus genome ( BnLACs ), 25 LAC genes from the Brassica rapa genome ( BrLACs ) and 8 LAC genes from the Brassica oleracea genome ( BoLACs ). These LAC genes could be divided into five groups in a cladogram and members in same group had similar structures and conserved motifs. All BnLACs contained hormone- and stress- related elements determined by cis-element analysis. The expression of BnLACs was relatively higher in the root, seed coat and stem than in other tissues. Furthermore, BnLAC4 and its predicted downstream genes showed earlier expression in the silique pericarps of short silique lines than long silique lines. Three miRNAs (miR397a, miR397b and miR6034) target 11 BnLACs were also predicted. The expression changes of BnLACs under series of stresses were further investigated by RNA sequencing (RNA-seq) and quantitative real-time polymerase chain reaction (qRT-PCR). The study will give a deeper understanding of the LAC gene family evolution and functions in B. napus.

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Network structures and temporal stability of self- and informant-rated affective symptoms in Alzheimer's disease. Affective symptoms in Alzheimer's disease (AD) can be rated with both informant- and self-ratings. Information from these two modalities may not converge. We estimated network structures of affective symptoms in AD with both rating modalities and assessed the longitudinal stability of the networks.

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Analytic autoethnography of familial and institutional social identity construction of My Dad with Alzheimer's: In the emergency room with Erving Goffman and Oliver Sacks. This paper analyzes variable social identity construction for my Dad over his last two years, within his family, and then within several institutions, before he died of Alzheimer's Disease (AD). This article makes epistemic and methodological contributions to research on persons with AD by using analytic autoethnography and long-term ethnographic case development to trace processes by which my Dad's evolving social identity was constructed -- and increasingly socially constructed -- as his memory became more impaired and he moved from home into several institutions. It analyzes how our family resisted his conversion into an "AD patient" - the stigmatized sum of his symptoms - but engaged in what felt like Goffmanian betrayals to care for him. The paper recognizes the value and need to fight the image of AD as social death in research, the medical system, and popular understanding, but proposes a family Memory-Relationship self to conceptually capture the trauma many families feel as AD increasingly impairs the loved one with AD and leads to their death (unless they die of something else first). My Dad's placement in five institutions in six months created awful natural experiment-like leverage, because he was alternatively constructed in institutions as a legally competent adult, a dangerous patient, and an AD patient, and often responded correspondingly.

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[Antiangiogenic therapy in high-risk keratoplasty]. To analyze the effectiveness and safety of VEGF inhibitor used to improve keratoconus transplant survival in patients with corneal neovascularization as stand-alone and in combination with laser coagulation of ingrowing vessels before keratoplasty.

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Supplemental Oxygen and Surgical Site Infection in Colorectal Surgery: A Systematic Review and Meta-analysis. Surgical site infection (SSI) is a common preventable iatrogenic infection following surgery with an approximated overall occurrence of 2-4%. Despite numerous studies, controversies still exist regarding the efficacy, safety, and cost effectiveness of strategies to decrease SSI. The World Health Organization issued recommendations for the prevention of SSIs including oxygenation with 80% fraction of inspired oxygen (FiO 2 ). The primary outcome of our systematic review and metaanalysis was the effect of high inspired FiO 2 related to SSI in the colorectal surgery population. Secondary outcomes included incidence of anastomotic leaks and length of hospital stay. Eleven trials consisting of 8245 were included in the analysis. We found moderate quality of evidence that 80% FiO2 was not effective in reducing SSI (RR, 0.91; 95% CI, 0.74 to 1.13; P = .41) anastomotic leaks (RR, 0.75; 95% CI, 0.53 to 1.06; P = 0.10). Conversely, we found low quality evidence of no effect on length of stay measured in days (MD, 0.39; 95% CI -0.59 to 1.36; P = 0.44). Although additional studies are required to decrease heterogeneity of the studies, the current review showed high FiO 2 does not decrease the incidence of SSI in the colorectal surgery population.

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A mixed-methods examination of autonomous sensory meridian response: Comparison to frisson. Autonomous Sensory Meridian Response (ASMR) is a pleasurable, head-oriented tingling sensation, typically induced by exposure to audiovisual triggers, producing feelings of relaxation and euphoria. This article explores the induction of ASMR experiences in a laboratory setting amongst non-specialised participants, as well as the relationship between ASMR and frisson, or 'musical chills'. In previous work, the ASMR-15 was found to be a reliable measure of ASMR propensity, however, the predictive validity of the measure has yet to be determined. The aim of this study was to assess whether ASMR-15 scores predict greater ASMR induction in an experimental setting. To address this, N = 100 undergraduate psychology students completed the ASMR-15 and a measure of frisson, before viewing ASMR stimuli under controlled conditions. Mixed-methods analyses indicated the successful induction of ASMR amongst some participants, convergence between ASMR-15 scores and video ratings, as well as divergence between ASMR and frisson scores.

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Prevalence of myocardial bridging associated with coronary endothelial dysfunction in patients with chest pain and non-obstructive coronary artery disease. Myocardial bridging (MB), characterised by the epicardial coronary vessel diving into the myocardium, is present in up to one third of adults and is associated with angina and acute coronary syndromes. MB is accompanied by altered blood flow mechanics and regional changes in wall sheer stress. The purpose of this study was to determine the association between myocardial bridging and coronary endothelial dysfunction.

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Shortened G1 phase of cell cycle and decreased histone H3K27 methylation are associated with AKT-induced enhancement of primordial germ cell reprogramming. Primordial germ cells (PGCs) are reprogrammed into pluripotent embryonic germ cells (EGCs) under specific culture conditions, but the detailed mechanisms of PGC reprogramming have not yet been fully clarified. Previous studies have demonstrated that AKT, an important intracellular signaling molecule, promotes reprogramming of PGCs into EGCs. Because AKT likely inhibits p53 functions to enhance PGC reprogramming, and p53 negatively regulates cell cycle progression, we analyzed cell cycle changes in PGCs following AKT activation and found that the ratio of PGCs in the G1/G0 phase was decreased while that of PGCs in the G2/M phase was increased after AKT activation. We also showed that the expression of the CDK inhibitor p27kip1, which prevents the G1‐S transition and is transcriptionally activated by p53, was significantly downregulated by AKT activation. The results suggested that the characteristic cell cycle changes of PGCs by AKT activation are, at least in part, due to decreased expression of p27 kip1 . We also investigated changes in histone H3K27 tri-methylation (H3K27me3) by AKT activation in PGCs, because we previously found that decreased H3K27me3 was involved in PGC reprogramming via upregulation of cyclin D1. We observed that AKT activation in PGCs resulted in H3K27 hypomethylation. In addition, DZNeP, an inhibitor of the H3K27 trimethyl transferase Ezh2, stimulated EGC formation. These results together suggested that AKT activation promotes G1-S transition and downregulates H3K27me3 to enhance PGC reprogramming.

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Mortality After Paclitaxel Coated Balloon Angioplasty and Stenting of Superficial Femoral and Popliteal Artery in the Vascular Quality Initiative. To compare mortality after treatment of superficial femoral-popliteal artery disease with paclitaxel and nonpaclitaxel devices using a multicenter vascular registry.

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Shining light on spindle positioning. Optogenetic approaches are leading to a better understanding of the forces that determine the plane of cell division.

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Public policy on the prevention of subsequent adolescent pregnancy: what type of policy prevails? This study aims to conduct a search of public-policy instruments seeking explicit references to subsequent adolescent pregnancy, as well as to discern what kinds of actions have been proposed as part of the international and national agendas to facilitate subsequent adolescent pregnancy prevention and care. During June 2021, we used an integrative review to search and to analyze national and international public policy instruments along with other documents related to subsequent adolescent pregnancy. We observed, for each, the presence of statements on subsequent adolescent pregnancy. The research team was then divided into triads to discuss and to classify each reference under one of the following categories: (a) a symbolic statement, that is, an intention not implying a specific action but rather presenting a vision for the future; (b) a substantive-material statement concerning an action intended to solve a problem; and (c) a procedural-material statement indicating specific actions, processes, budgets, and actors. We analyzed a total of 135 public-policy documents: 102 in Mexico and 33 internationally. Only four national and six international documents contained either symbolic or substantive-material references to the subject of interest and only one specified a procedural-material statement. The prevention and care of subsequent adolescent pregnancy are addressed only secondarily on the public agendas. Only a minimal number of actions comprise specific and standardized measures to prevent subsequent adolescent pregnancy according to the different actors involved. Designing a greater number of procedural-material policies will help to reduce morbidity and mortality in the mother-child binomial and promote a comprehensive development of this population.

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Generation of Hepatic Stellate Cells from Human Pluripotent Stem Cells Enables In Vitro Modeling of Liver Fibrosis. The development of complex in vitro hepatic systems and artificial liver devices has been hampered by the lack of reliable sources for relevant cell types, such as hepatic stellate cells (HSCs). Here we report efficient differentiation of human pluripotent stem cells into HSC-like cells (iPSC-HSCs). iPSC-HSCs closely resemble primary human HSCs at the transcriptional, cellular, and functional levels and possess a gene expression profile intermediate between that of quiescent and activated HSCs. Functional analyses revealed that iPSC-HSCs accumulate retinyl esters in lipid droplets and are activated in response to mediators of wound healing, similar to their in vivo counterparts. When maintained as 3D spheroids with HepaRG hepatocytes, iPSC-HSCs exhibit a quiescent phenotype but mount a fibrogenic response and secrete pro-collagen in response to known stimuli and hepatocyte toxicity. Thus, this protocol provides a robust in vitro system for studying HSC development, modeling liver fibrosis, and drug toxicity screening.

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The influence of the interaction of sous-vide cooking time and papain concentration on tenderness and technological characteristics of meat products. The food industry has been slow in harnessing technological developments to expand opportunities and benefit the community. One such opportunity is in the application of proteolytic enzymes to the development of softer-textured meat products that require reduced mastication force, for those with impaired dentition, and reduced strength including older adults. Proteolytic enzymes haven't been fully explored for their potential in this area. Here a response surface methodology (RSM) was applied to model the interactive effects of sous-vide and papain application on texture, color, and cooking loss of meat. An innovative meat product formulation with a reduced toughness (120 min cooking sous-vide and 0.01 mg papain/100 g) was optimized and the technological performance of the formulation was validated. Bias values of the optimized model were in the range of 0.97 to 1.06, while accuracy factors for shear force values, chewiness, TPA hardness, cooking loss, color parameters ranged from 1.00 and 1.06, both of which metrics indicated the reliability of the resultant models.

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Safety and Outcome of Carotid Dissection Stenting During the Treatment of Tandem Occlusions: A Pooled Analysis of TITAN and ETIS. The efficacy of endovascular therapy in patients with acute ischemic stroke due to tandem occlusion is comparable to that for isolated intracranial occlusion in the anterior circulation. However, the optimal management of acute cervical internal carotid artery lesions is unknown, especially in the setting of carotid dissection, but emergency carotid artery stenting (CAS) is frequently considered. We investigated the safety and efficacy of emergency CAS for carotid dissection in patients with acute stroke with tandem occlusion in current clinical practice.

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[The use of Gliathiline in patients with sensorineural hearing loss]. The results of treatment of 38 patients suffering from sensorineural hearing loss with the Gliatilin (solution 3 ml intravenously for 10 days, capsules 400 mg 3 times a day or solution for ingestion 600 mg 2 times a day for 3 months) are presented. All patients in dynamics were given a comprehensive audiological, neurological examination, as well as an assessment of psycho-emotional status and cognitive function. Subjective improvement of ear noise tolerance by patients by 40 days of observation and continuation of this trend during the whole period (100 days) outside of the form of the medicinal preparation is noted. A reliable improvement in the 50% speech intelligibility threshold by day 100 of observation was established in patients of both groups, with a tendency towards earlier (on day 70 of the study) onset of this effect when taking the drug inside as a solution. The Gliatilin has been proven to reduce anxiety and depression, as well as reliably improve cognitive function. Thus, Gliatilin (injection solution, ingestion solution, capsules) can be used to improve the subjective tolerance of ear noise, speech intelligibility and quality of life of patients in chronic sensorineural hearing loss.

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Using town watching technique to raise disaster awareness for different audiences. Communities need to be aware of all the risks and consequences of disasters, which have increased both in numbers, economic and human losses in the recent decades. This study aims to show how town watching technique has a positive effect in raising disaster awareness in different types of learning experiences for different target groups so that individuals understand the disaster risks and make plans to decrease their vulnerabilities. Application of town watching for two different target audiences are explained; undergraduate engineering major students, local government officials, and volunteer community members. Results of surveys conducted for an elective humanities course for engineering major undergraduates named disaster awareness are presented. Interviews with volunteers from other target groups who participated in community-based disaster capacity building projects are also included in this study. It can be clearly seen that town watching creates synergy while disaster awareness is internalized, and the participants learn about disasters, risks, and resources at hand that may also help toward the countries' resilience to disasters.

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Seven-year study of monsoonal rainwater chemistry over the mid-Brahmaputra plain, India: assessment of trends and source regions of soluble ions. This work is a 7-year study of monsoonal rainwater chemistry (n = 302), over mid-Brahmaputra plain during 2012 to 2018. The samples were analyzed for major chemical parameters viz. pH, electrical conductivity (EC), and ions (SO 4 2- , NO 3 - , Br - , Cl - , F - , Mg 2+ , Ca 2+ , K + , NH 4 + , Na + , and Li + ) to assess the chemistry. The mean pH of rainwater varied among the years, which was maximum in 2018 (6.18 ± 0.72) and minimum in the year 2014 (5.39 ± 0.54), and the variations were significant at p < 0.0001. Ridgeline plots were drawn to visualize interannual variations, which revealed that Ca 2+ was the dominant cation in the early years, whereas NH 4 + prevailed in the latter years. Mann-Kendall analysis and Sen's slope statistical tests were employed, and it was found that all the ions showed positive S values indicating increasing trends. Enrichment factors (EF) of K + , SO 4 2- , and NO 3 - were found to be high with respect to both soil and seawater suggesting the influence of emissions from fossil fuel and biomass burning in the chemistry of rainwater. Principal component analysis (PCA) was applied to identify the sources of rain constituents, and five factors were obtained explaining crustal dust, biomass burning, fossil fuel combustion, agricultural emissions, and coal burning as possible sources. Airmass back trajectory clusters and Potential Source Contribution Function (PSCF) were computed by application of HYbrid Single-Particle Lagrangian Integrated Trajectory model to appreciate the terrestrial influence on the chemistry. The results indicated inputs from both local and regional dust and anthropogenic constituents that influenced the monsoonal rainwater chemistry over Brahmaputra Valley.

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The Role of DNA Looping in the Search for Specific Targets on DNA by Multisite Proteins. Many cellular processes involve simultaneous interactions between DNA and protein molecules at several locations. They are regulated and controlled by special protein-DNA complexes, which are known as synaptic complexes or synaptosomes. Because of the multisite nature of involved proteins, it was suggested that during the formation of synaptic complexes DNA loops might appear, but their role is unclear. We developed a theoretical model that allowed us to evaluate the effect of transient DNA loop formation. It is based on a discrete-state stochastic method that explicitly takes into account the free-energy contributions due to the appearance of DNA loops. The formation of the synaptic complexes is viewed as a search for a specific binding site on DNA by the protein molecule already bound to DNA at another location. It was found that the search might be optimized by varying the position of the target and the total length of DNA. Furthermore, the formation of transient DNA loops leads to faster dynamics if it is associated with favorable enthalpic contributions to nonspecific protein-DNA interactions. It is also shown that DNA looping might reduce stochastic noise in the system.

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Functional characterization of partial recombinant goat conglutinin: Its role as innate immunity marker and use as antigen in sandwich ELISA. Conglutinin, a liver synthesized versatile innate immune marker consisting C-type lectin domain belongs to collectin superfamily of proteins. The protein, first detected in bovine serum as soluble pattern recognition receptor (PRR) has wide range of antimicrobial activities. In the present study, open reading frame (ORF) encoding neck and carbohydrate recognition domain (NCRD) of goat conglutinin gene ligated to the vector pRSET-A was expressed in E. coli BL-21(pLys) cells. The 27 kDa recombinant protein (rGCGN) purified by single step Ni +2 -NTA affinity chromatography was found to cross-react with recombinant anti-buffalo conglutinin antibody raised in poultry. Further, it displayed calcium-dependant sugar binding activity towards yeast mannan and calcium-independent binding activity towards LPS. The mannan binding activity of rGCGN was inhibited in the presence of N-acetyl-glucosamine because of higher affinity towards this sugar. The recombinant protein was found to stimulate production of superoxide ions and hydrogen peroxide in goat neutrophils, which are instrumental in stimulating phagocytic activity of cells. When used as antigen in Sandwich ELISA, straight line (Y = 0.299x + 0.067, R 2 = 0.997) was observed within the concentration range of 200-1000 ng/100 μl of rGCGN. Using this equation, the native conglutinin concentration in goat sera was estimated to be 0.5-7.5 μg/ml. The results indicated that prokaryotically expressed functionally active rGCGN can be used as antigen to assess native serum conglutinin levels in Sandwich ELISA and as immunomodulator in therapeutic applications to sequester unwanted immune complexes from the circulation.

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mcIRBP-19 of Bitter Melon Peptide Effectively Regulates Diabetes Mellitus (DM) Patients' Blood Sugar Levels. This study was conducted to test the effectiveness of a particular bitter melon peptide (BMP), with a specific sequence of 19 amino acids (mcIRBP-19), in regulating diabetic patients' blood glucose. In order to test the product with the specially processed BMP, a total of 142 diabetic patients were solicited as study subjects, of which 64 were assigned to an experiment group and 78 to a control group. Biochemical data were compared with a paired t- test to verify the significance of changes over different time periods. The clinical results showed that BMP started to improve the subjects' glycated hemoglobin (HbA1c) levels at the end of the second month (T2), with mean values being significantly lowered from 7.8 ± 1.4% (T0) to 7.5 ± 1.4% (T2) ( p = 0.004). The values reduced continuously, eventually reaching 7.4 ± 1.1% ( p = 0.000) at the end of the experiment (T3). HbA1c levels for the control group were 7.5 ± 1.2% in T0 and 7.5 ± 1.1% (T3), and not significantly different ( p = 0.852) over the same period. This study provides clinical evidence that helps to verify the effectiveness of the new BMP product in regulating diabetic patients' blood sugar levels.

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Vγ4 γδ T Cells Provide an Early Source of IL-17A and Accelerate Skin Graft Rejection. Activated γδ T cells have been shown to accelerate allograft rejection. However, the precise role of skin-resident γδ T cells and their subsets-Vγ5 (epidermis), Vγ1, and Vγ4 (dermis)-in skin graft rejection have not been identified. Here, using a male to female skin transplantation model, we demonstrated that Vγ4 T cells, rather than Vγ1 or Vγ5 T cells, accelerated skin graft rejection and that IL-17A was essential for Vγ4 T-cell-mediated skin graft rejection. Moreover, we found that Vγ4 T cells were required for early IL-17A production in the transplanted area, both in skin grafts and in the host epidermis around grafts. Additionally, the chemokine (C-C motif) ligand 20-chemokine receptor 6 pathway was essential for recruitment of Vγ4 T cells to the transplantation area, whereas both IL-1β and IL-23 induced IL-17A production from infiltrating cells. Lastly, Vγ4 T-cell-derived IL-17A promoted the accumulation of mature dendritic cells in draining lymph nodes to subsequently regulate αβ T-cell function after skin graft transplantation. Taken together, our data reveal that Vγ4 T cells accelerate skin graft rejection by providing an early source of IL-17A.

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Association between Gut Microbial Diversity and Carotid Intima-Media Thickness. Background and Objectives: There is an increasing focus on the effect of the gut microbiome on developing atherosclerosis, but there is still no unified standpoint. We aimed to find associations between intestinal microbiome diversity and a marker of subclinical atherosclerosis, the carotid intima-media thickness (IMT). Materials and Methods: Recruited from the Hungarian Twin Registry, 108 monozygotic (MZ) twins (mean age 52.4 ± 14.1 years, 58% female) underwent a comprehensive carotid ultrasound examination (Samsung RS85). Of the 108 MZ twins, 14 pairs (mean age 65 ± 6.4 years, 71% female) discordant for carotid IMT were selected to undergo a stool sample collection. A special stool sampling container was mailed and received from each participant. After DNA extraction, library construction was performed specifically for the V3-V4 hypervariable region of microbial 16S rRNA. Next, the microbiome composition of the samples was determined using Kraken software. Two hypotheses were tested with the exact permutation test: (1) in the group with normal IMT, the Shannon index of the phyla is higher; and (2) the Firmicutes/Bacteroidetes ratio is greater in the group with high IMT values. Furthermore, the abundance of different bacterial strains present at higher and normal IMT was also explored. Statistical analysis was carried out using R software. Results: Increased Firmicutes/Bacteroidetes ratio was associated with increased IMT (mean Firmicutes/Bacteroidetes ratio of IMT > 0.9 and IMT < 0.9 groups: 2.299 and 1.436, respectively; p = 0.031). In the group with normal IMT values, a substantially higher fraction of Prevotellaceae was observed in contrast with subjects having subclinical atherosclerosis. However, there was no significant difference in the alpha diversity between the two groups. Conclusions: The determining role of individual genera and their proportions in the development and progression of atherosclerosis can be assumed. Further studies are needed to clarify if these findings can be used as potential therapeutic targets.

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Removal of Migrating Lumbar Spine Bullet: Case Report and Surgical Video. Gunshot wounds to the spine are devastating injuries. Rarely, the bullet has been reported to migrate. Migration is associated with progressive neurologic deficits that often improve with bullet removal. The authors report a case of removal of a migrating lumbar spine bullet. This is supplemented by an operative video and a review of the literature.

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Sorafenib in patients with progressed and refractory bone tumors. Patients with metastatic, progressive, or recurrent bone tumors have a dismal outcome. Sorafenib has been proposed as an effective salvage regimen for some malignancies. Thus, we sought to evaluate this approach for young patients with relapsed or refractory bone tumors. Twelve patients with refractory bone tumors (two with Ewing sarcoma, two with chondrosarcoma, and eight with osteosarcoma) received salvage treatment with sorafenib. All patients had standard tumor imaging and laboratory evaluation. All toxicities were documented. At the time of the beginning of sorafenib treatment median age among 12 patients was 18 years (range 4.1-27.9 years), eight were male, and eight had osteosarcoma. All received sorafenib because of relapse. Seven patients were treated parallel to other standard chemotherapy. Overall response rate was 75%. Median time to sorafenib time to progression for patients with osteosarcoma was 4 months (range 1.8-7.9 months). Four patients (33%) are alive, in that two with no evidence of disease with a median follow-up of 41 months (range 26.5-60.9 months). The estimated 5 year overall survival (OS) for the whole group was 64.49%. There were no serious toxicities. Sorafenib is well-tolerated in young patients with bone tumors, and particularly could be an option for patients with metastatic disease and refractory osteosarcoma. Sorafenib only allows to extend OS and different procedures are needed to achieve permanent remission. This regimen deserves further investigation in the upfront management of patients with high-risk bone tumors.

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Engineering immunity via skin-directed drug delivery devices. Extensive research is underway to discover a safe and effective vehicle to deliver the vaccines at the desired cutaneous site. These efforts majorly comprise the development of a fit-to-purpose vehicle for in-situ intracutaneous vaccine delivery for achieving the systemic cellular and humoral response to combat infectious diseases. Advancements in nanoscience, bioengineering, and skin science provided much support to vaccine adjuvant development. However, the bench-to-bed side translation of vaccines is still unsatisfactory. A skilfully designed vaccine delivery program aiming to translate the product into market use must address safety, efficacy, scaleup, reproducibility, cost of production, self-administrative potential, and regulatory concerns. This review provides deep insights into skin immunization approaches like mucosal vaccines, cellular/molecular immunological responses, and antigen-adjuvant combinations in modulating immunity. Further, the manuscript discusses distinct vaccine delivery systems used to date for engineering skin immunization, including microparticles, nanoparticles, spherical nucleic acids, STAR particles, niosomes, dendrimers, ethosomes, liposomes, and microneedles. The manuscript will interest researchers working towards developing a next-generation fit-to-purpose vehicle for intracutaneous vaccine delivery.

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A Complementary Intervention to Promote Wellbeing and Stress Management for Early Career Teachers. The educational climate and culture in our schools present a variety of environmental (contextual) factors that influence teacher wellbeing, job satisfaction, and work-related stress. The magnitude of contextual factors cannot be ignored, and directing attention towards the environment teachers face daily is essential. Primary (organisational)-level interventions are documented in organisational health and wellbeing literature; however, to provide teachers with stress management strategies for promoting wellbeing, attention must also be directed towards secondary (individual)-level interventions. The present study addressed the issue of stress management techniques for early career teachers ( n = 24) and aimed to contribute to the research surrounding complementary interventions (CIs) for educators. The intervention was designed to include strategies that operated through cognitive and physiological mechanisms that regulated the stress response and increased awareness of behaviours, emotions, and reactivity. The self-report measures included perceived stress, attention awareness, subjective wellbeing, burnout, and job-related affective wellbeing. The results indicated a statistically significant decrease in perceived stress and increases in attention awareness and subjective wellbeing. The salivary cortisol levels (waking and resting) decreased from baseline to week 6, and the pre- and post-session salivary cortisol levels indicated an immediate decrease in cortisol for weeks 4 to 6.

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[Screening of periodontal and salivary parameters in patients with frequent acute exacerbation of chronic obstructive pulmonary disease]. Objective: To screen the risk factors of patients with frequent acute exacerbation of chronic obstructive pulmonary disease (COPD) by detecting the clinical indicators of periodontitis and the level of bacterial and inflammatory markers in saliva. Methods: Thirty-eight COPD patients in their stable period were recruited and detected from Beijing Chao-Yang Hospital,Capital Medical University during December 2016 to May 2017. The periodontal index were recorded. The levels of inflammatory factors in saliva samples were examined by using enzyme linked immunosorbent assay (ELISA). The bacteria composition in the saliva samples were identified by using 16SrRNA gene pyrosequencing. All patients were followed up and monitored for acute exacerbation of COPD for 12 months. The patients were divided into frequent acute exacerbation group (≥2 times/year, n= 10) and non frequent acute exacerbation group (<2 times/year, n= 28). Results: In univariate analysis, the patients' average age of frequent acute exacerbation group (69.0±7.3) was significantly older than that of non-frequent acute exacerbation group (61.8±8.3) ( P= 0.02). The numbers of remaining teeth ≤26 [100% (10/10)] was significantly higher and plaque index ≤2.5 (2/10) in frequent acute exacerbation group was significantly lower compared with the remaining teeth ≤26 [43% (12/28)] and the plaque index ≤2.5 [71% (21/28)] in non-frequent acute exacerbation group ( P =0.02, P= 0.01). The proportions of salivary inflammatory factors interleukin-6 (IL-6) level ≤60 ng/L (10%),C-reactive protein (CRP) level ≤1 550 μg/L (30%), matrix metalloproteinase-8 (MMP-8) level ≤140 μg/L (30%) and fibrinogen level ≤90 mg/L (30%) in frequent acute exacerbation group were significantly lower compared with salivary inflammatory factors IL-6 level ≤60 ng/L (71%),CRP level ≤1 550 μg/L (71%), MMP-8 level ≤140 μg/L (86%) and fibrinogen level ≤90 mg/L (71%) in non-frequent acute exacerbation group ( P< 0.05). The differences of relative abundances of salivary bacteria,such as species of Chloroflexi, Anaerolineae, Anaeroales, Corynebacteriales, Anaerolineaceae, Tissierellaceae, Leptotrichiaceae, Corynebacteriaceae, Leptotrichia, Moryella, Lachnoanaerobaculum and Corynebacterium between frequent acute exacerbation group and non-frequent acute exacerbation group were significantly different ( P< 0.05). In multivariate logistics regression analysis,the level of IL-6 >60 ng/L and the relative abundance of Corynebacteriales >0.2 had significant difference ( P< 0.05). Conclusions: The level of IL-6 and the relative abundance of Corynebacteriales might be the markers of frequent acute exacerbation in COPD patients.

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The stringent response of marine bacteria - assessment of (p)ppGpp accumulation upon stress conditions. Microorganisms are particularly adapted to alterations in their environment. One of the global regulatory mechanisms involved in these adaptations is the stringent response. The unusual nucleotides, guanosine penta and tetraphosphates, (p)ppGpp act as alarmones of this response, heralding nutrient limitation and stressors. Marine bacteria encounter numerous stresses of sparse nutrient supplies and changes in physicochemical conditions. The aim of this work was to assess whether the stress conditions common in marine environment can induce the stringent response and what is a kinetic of this process. The representative bacterial species, Shewanella baltica, Acinetobacter johnsonii, Vibrio harveyi, and Escherichia coli were subjected to a variety of stressors. We analyzed the kinetics of (p)ppGpp synthesis by labeling in vivo nucleotides and analysis by thin layer chromatography. The (p)ppGpp accumulation followed the elevated temperature and amino acid starvation for all bacteria tested. The carbon and nitrogen limitation resulted in the response limited to V. harveyi and S. baltica. The DNA damaging agents induced the (p)ppGpp production in all strains, while osmotic stress did not result in significant alarmone synthesis. The representative marine bacteria species were shown to induce with varying extent the stringent response upon the onset of stress and limitation conditions. Importantly, the in vivo labeling and subsequent separation of the nucleotides by thin layer chromatography serves as a valid method for the analysis of the stringent response and (p)ppGpp accumulation in environmental bacteria.

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PEGylation-Dependent Metabolic Rewiring of Macrophages with Silk Fibroin Nanoparticles. Silk fibroin nanoparticles are emerging as promising nanomedicines, but their full therapeutic potential is yet to be realized. These nanoparticles can be readily PEGylated to improve colloidal stability and to tune degradation and drug release profiles; however, the relationship between silk fibroin nanoparticle PEGylation and macrophage activation still requires elucidation. Here, we used in vitro assays and nuclear magnetic resonance based metabolomics to examine the inflammatory phenotype and metabolic profiles of macrophages following their exposure to unmodified or PEGylated silk fibroin nanoparticles. The macrophages internalized both types of nanoparticles, but they showed different phenotypic and metabolic responses to each nanoparticle type. Unmodified silk fibroin nanoparticles induced the upregulation of several processes, including production of proinflammatory mediators (e.g., cytokines), release of nitric oxide, and promotion of antioxidant activity. These responses were accompanied by changes in the macrophage metabolomic profiles that were consistent with a proinflammatory state and that indicated an increase in glycolysis and reprogramming of the tricarboxylic acid cycle and the creatine kinase/phosphocreatine pathway. By contrast, PEGylated silk fibroin nanoparticles induced milder changes to both inflammatory and metabolic profiles, suggesting that immunomodulation of macrophages with silk fibroin nanoparticles is PEGylation-dependent. Overall, PEGylation of silk fibroin nanoparticles reduced the inflammatory and metabolic responses initiated by macrophages, and this observation could be used to guide the therapeutic applications of these nanoparticles.

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Health-care resource use and current treatment of adult atopic dermatitis patients in Japan: A retrospective claims database analysis. The real-world evidence on the profiles of patients suffering from atopic dermatitis (AD) in Japan is sparse. A retrospective claim database analysis was conducted to estimate the health-care resource use (HCRU) and current AD treatment. Data from October 2013 to September 2016 were extracted from the JMDC (Tokyo, Japan) claims database. HCRU was assessed by a comparison of AD patients and matched non-AD controls. A multivariate analysis was performed to estimate HCRU attributable to AD. AD patients (n = 39 893) have more claims of certain diagnoses such as rhinitis, viral and fungal infections, sleep disorders and conjunctivitis as well as higher HCRU (outpatient visits, prescriptions of AD-related and non-AD-related medications, phototherapy, laboratory tests) than matched non-AD controls (n = 39 893). Treatment pattern analysis included treatment-naive patients (n = 8478) and previously treated AD patients (n = 30 109). Approximately 20% of previously treated patients were on the continuous systemic treatment during 18-month follow up. Systemic corticosteroids were the most frequently used systemic treatments. Oral cyclosporin was less frequently used in both groups, but for the longest duration. Almost half of previously treated patients with oral cyclosporin continued treatment for more than 3 months. In conclusion, HCRU was higher in AD patients than non-AD controls, indicating a high burden of the disease imposed on AD patients. Continuous administration of systemic treatment, such as oral cyclosporin, systemic corticosteroids and phototherapy, observed in AD patients sheds light on the difficulties of managing AD in Japanese clinical practise.

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Microenvironment remodeled by tumor and stromal cells elevates fibroblast-derived COL1A1 and facilitates ovarian cancer metastasis. Wide peritoneal metastasis is the cause of the highest lethality of ovarian cancer in gynecologic malignancies. Ascites play a key role in ovarian cancer metastasis, but involved mechanism is uncertain. Here, we performed a quantitative proteomics of ascites, and found that collagen type I alpha 1 (COL1A1) was notably elevated in ascites from epithelial ovarian cancer patients compared to normal peritoneal fluids, and verified that elevated COL1A1 was mainly originated from fibroblasts. COL1A1 promoted migration and invasion of ovarian cancer cells, but such effects were partially eliminated by COL1A1 antibodies. Intraperitoneally injected COL1A1 accelerated intraperitoneal metastasis of ovarian cancer xenograft in NOD/SCID mice. Further, COL1A1 activated downstream AKT phosphorylation by binding to membrane surface receptor integrin β1 (ITGB1). Knockdown or blockage of ITGB1 reversed COL1A1 enhanced migration and invasion in ovarian cancer cells. Conversely, ovarian cancer ascites and fibrinogen promoted fibroblasts to secrete COL1A1. Elevated fibrinogen in ascites might be associated with increased vascular permeability induced by ovarian cancer. Our findings suggest that microenvironment remodeled by tumor cells and stromal cells promotes fibroblasts to secrete COL1A1 and facilitates the metastasis of ovarian cancer, which may provide a new approach for ovarian cancer therapeutics.

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Acute myeloid leukaemia presenting as proptosis in an infant. Paediatric patients with acute myeloid leukaemia (AML) often present with symptoms associated with the disruption of normal haematopoiesis and subsequent cellular deficiencies. Periosteal reactions are common in paediatric leukaemia, but typically manifest as a thin, laminated pattern along long bones. Aggressive periosteal reactions are much less frequently seen. Here, we report a case of paediatric AML initially presenting with proptosis and periorbital swelling caused by aggressive, sunburst periosteal reactions surrounding the sphenoid and zygomatic bones. This unique presentation emphasises the importance of considering leukaemic infiltration in the differential for sunburst periosteal reaction in paediatric patients.

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Improved Whole-Genome Sequence of Phytophthora capsici Generated by Long-Read Sequencing. The soilborne oomycete Phytophthora capsici is the most destructive pathogen of vegetable crops and is responsible for substantial economic losses worldwide. Here, we present an improved genome assembly of P. capsici generated by Oxford Nanopore long-read sequencing (for de novo assembly) and Illumina short-read sequencing (for polishing). The genome of P. capsici is 100.5 Mb in length (GC content = 50.8%) and contains 26,069 predicted protein-coding genes. The whole genome of P. capsici is assembled into 194 scaffolds, 90% of which are larger than 300 kb. The N 50 scaffold length and maximum scaffold length are 1.0 and 4.1 Mb, respectively. The whole-genome sequence of P. capsici will broaden our knowledge of this pathogen and enhance our understanding of the molecular basis of its pathogenicity, which will facilitate the development of effective management strategies.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

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A survey on patients medication reconciliation process in an oncological hospital. The purpose of this study was to assess the impact of medication reconciliation in the clinical practice from a hospital pharmacist point of view.

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Phi class glutathione transferases as molecular targets towards multiple-herbicide resistance: Inhibition analysis and pharmacophore design. Multiple-herbicide resistance (MHR) is a global threat to weed control in cereal crops. MHR weeds express a specific phi class glutathione transferase (MHR-GSTF) that confers resistance against multiple herbicides and therefore represents a promising target against MHR weeds. Kinetics inhibition analysis of MHR-GSTFs from grass weeds Lolium rigidum (LrGSTF) Alopecurus myosuroides (AmGSTF) and crops Hordeum vulgare (HvGSTF) and Triticum aestivum (TaGSTF) allowed the identification of the acetanilide herbicide butachlor as a potent and selective inhibitor towards MHR-GSTFs. Also, butachlor is a stronger inhibitor for LrGSTF and AmGSTF compared to HvGSTF and TaGSTF from crops. The crystal structure of LrGSTF was determined at 1.90 Å resolution in complex with the inhibitor S-(4-nitrobenzyl)glutathione. A specific 3D pharmacophore targeting the MHR-GSTFs was designed and used to identify structural elements important for potent and selective inhibition. Structural analysis of GSTFs revealed a decisive role of conserved Tyr118 in ligand binding and pharmacophore design. Its positioning is dependent on an outer patch of adjacent residues that span from position 132 to 134 which are similar for both LrGSTF and AmGSTF but different in HvGSTF and TaGSTF. The results presented here provide new knowledge that may be adopted to cope with MHR weeds.

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Biometry data and prevalence of corneal astigmatism in caucasian spanish candidates for cataract surgery. To describe ocular biometric parameters and the prevalence of corneal astigmatism as well as age and gender correlations in a population of cataract surgery candidates and to estimate the number of eyes that would be candidates for a toric intraocular lens (IOL).

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High-Performance Liquid Chromatography Method for Rich Pharmacokinetic Sampling Schemes in Translational Rat Toxicity Models With Vancomycin. A translational need exists to understand and predict vancomycin-induced kidney toxicity. We describe: (i) a vancomycin high-performance liquid chromatography (HPLC) method for rat plasma and kidney tissue homogenate; (ii) a rat pharmacokinetic (PK) study to demonstrate utility; and (iii) a catheter retention study to enable future preclinical studies. Rat plasma and pup kidney tissue homogenate were analyzed via HPLC for vancomycin concentrations ranging from 3-75 and 15.1-75.5 μg/mL, respectively, using a Kinetex Biphenyl column and gradient elution of water with 0.1% formic acid: acetonitrile (70:30 v/v). Sprague-Dawley rats (n = 10) receiving 150 mg/kg of vancomycin intraperitoneally had plasma sampled for PK. Finally, a catheter retention study was performed on polyurethane catheters to assess adsorption. Precision was <6.1% for all intra-assay and interassay HPLC measurements, with >96.3% analyte recovery. A two-compartment model fit the data well, facilitating PK exposure estimates. Finally, vancomycin was heterogeneously retained by polyurethane catheters.

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Development and internal validation of PI-RADs v2-based model for clinically significant prostate cancer. Our objective is to build a model based on Prostate Imaging Reporting and Data System version 2 (PI-RADs v2) and assess its accuracy by internal validation.

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The innate immune system in diabetic retinopathy. The prevalence of diabetes has been rising steadily in the past half-century, along with the burden of its associated complications, including diabetic retinopathy (DR). DR is currently the most common cause of vision loss in working-age adults in the United States. Historically, DR has been diagnosed and classified clinically based on what is visible by fundoscopy; that is vasculature alterations. However, recent technological advances have confirmed pathology of the neuroretina prior to any detectable vascular changes. These, coupled with molecular studies, and the positive impact of anti-inflammatory therapeutics in DR patients have highlighted the central involvement of the innate immune system. Reminiscent of the systemic impact of diabetes, immune dysregulation has become increasingly identified as a key element of the pathophysiology of DR by interfering with normal homeostatic systems. This review uses the growing body of literature across various model systems to demonstrate the clear involvement of all three pillars of the immune system: immune-competent cells, mediators, and the complement system. It also demonstrates how the relative contribution of each of these requires more extensive analysis, including in human tissues over the continuum of disease progression. Finally, although this review demonstrates how the complex interactions of the immune system pose many more questions than answers, the intimately connected nature of the three pillars of the immune system may also point to possible new targets to reverse or even halt reverse retinopathy.	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Microwave hydrothermal renovating and reassembling spent lithium cobalt oxide for lithium-ion battery. With the growing number of lithium-ion batteries (LIBs) that are consumed by worldwide people, recycling is necessary for addressing environmental problems and alleviating energy crisis. Especially, it is meaningful to regenerate LIBs from spent batteries. In this paper, the microwave hydrothermal method is used to replenish lithium, assemble particles and optimize the crystal structure of the spent lithium cobalt oxide. The microwave hydrothermal process can shorten the reaction time, improve the internal structure, and uniformize the particle size distribution of lithium cobalt oxide. It helps to construct a regenerated lithium cobalt oxide (LiCoO 2 ) battery with high-capacity and high-rate properties (141.7 mAh g -1 at 5C). The cycle retention rate is 94.5% after 100 cycles, which is far exceeding the original lithium cobalt oxide (89.7%) and LiCoO 2 regenerated by normal hydrothermal method (88.3%). This work demonstrates the feasibility to get lithium cobalt oxide batteries with good structural stability from spent lithium cobalt oxide batteries.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Altered hepatic lipid metabolism in mice lacking both the melanocortin type 4 receptor and low density lipoprotein receptor. Obesity is often associated with dyslipidemia and hepatosteatosis. A number of animal models of non-alcoholic fatty liver disease (NAFLD) are established but they significantly differ in the molecular and biochemical changes depending on the genetic modification and diet used. Mice deficient for melanocortin type 4 receptor (Mc4rmut) develop hyperphagia, obesity, and subsequently NAFLD already under regular chow and resemble more closely the energy supply-driven obesity found in humans. This animal model was used to assess the molecular and biochemical consequences of hyperphagia-induced obesity on hepatic lipid metabolism. We analyzed transcriptome changes in Mc4rmut mice by RNA sequencing and used high resolution 1H magic angle spinning NMR spectroscopy and MALDI-TOF mass spectrometry to assess changes in the lipid composition. On the transcriptomic level we found significant changes in components of the triacylglycerol metabolism, unsaturated fatty acids biosynthesis, peroxisome proliferator-activated receptor signaling pathways, and lipid transport and storage compared to the wild-type. These findings were supported by increases in triacylglycerol, monounsaturated fatty acid, and arachidonic acid levels. The transcriptome signatures significantly differ from those of other NAFLD mouse models supporting the concept of hepatic subphenotypes depending on the genetic background and diet. Comparative analyses of our data with previous studies allowed for the identification of common changes and genotype-specific components and pathways involved in obesity-associated NAFLD.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Education can reduce health differences related to genetic risk of obesity. This work investigates whether genetic makeup moderates the effects of education on health. Low statistical power and endogenous measures of environment have been obstacles to the credible estimation of such gene-by-environment interactions. We overcome these obstacles by combining a natural experiment that generated variation in secondary education with polygenic scores for a quarter-million individuals. The additional schooling affected body size, lung function, and blood pressure in middle age. The improvements in body size and lung function were larger for individuals with high genetic predisposition to obesity. As a result, education reduced the gap in unhealthy body size between those in the top and bottom terciles of genetic risk of obesity from 20 to 6 percentage points.	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Risk of venous and arterial thromboembolism in patients with giant cell arteritis and/or polymyalgia rheumatica: A Veterans Health Administration population-based study in the United States. Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are systemic inflammatory diseases that primarily affect elderly women.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
[Relationship between frailty and depression in elderly patients]. Objective: To investigate the relationship between frailty and depression by analyzing the clinical data, frailty and depression in the elderly outpatients. Methods: This study included outpatients who visited the Geriatric Section of West China Hospital from July 1, 2016 to December 31, 2016.Clinical characteristics and complications in patients were evaluated comprehensively.The debilitating condition of patient was assessed by the international society for elderly nutrition simple weakness questionnaire (Fatigue, Resistance, Ambulation, Illnesses, Loss of Weight.FRAIL). The depression was assessed by the 30-Item Geriatric Depression. Results: Regression analysis showed that pre-frail ( OR 3.286, 95% CI 1.59-3.98) and frail ( OR 4.139, 95% CI 1.52-14.40) elder adults had a higher risk of depression than other elders. Conclusion: Pre-frail and frail elders are at high risk of depression.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Randomized controlled study of a diagnosis and treatment plan for moderate coronavirus disease 2019 that integrates Traditional Chinese and Western Medicine. To investigate the clinical efficacy and safety of a diagnosis and treatment plan for moderate coronavirus disease 2019 (COVID-19) that integrates traditional Chinese (TCM) and western medicine.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Peripheral blood immunological parameters of children with adenoid hypertrophy with otitis media with effusion: propensity score matching. To evaluate peripheral blood immunological parameters and the possible correlation with age, gender and adenoid size in children with adenoid hypertrophy with OME.	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
School meals' centesimal and mineral composition and their nutritional value for Brazilian children. The assessment of meals served under the Brazilian National School Meal Program (PNAE) is an important tool to verify its adequacy to the proposed parameters and the nutritional needs of school-aged children. The aim of this study was to evaluate the centesimal and mineral composition of the meals offered by the program and adequacy to the nutritional recommendations in three municipalities of the state of Bahia, Brazil. Centesimal composition of meals was determined according to the reference guidelines and mineral composition was analyzed by atomic absorption spectrometry. Non-parametric analysis of variance was used to test the differences of the medians among the municipalities and Student-t test to compare the means between the two sampling periods. There were inadequacies in the carbohydrate, lipid and protein contents, and none of the municipalities reached the recommendation of 20%. Mineral concentration, especially Fe, Se, Cu and K were much lower than expected. Sodium levels were three-folds higher than the recommended, being worrisome due to higher risk of elevated blood pressure. There were inadequacies with regard to the PNAE guidelines, and there is a need to reevaluate the meals that are being offered to better meet childreńs needs and to form healthy habits from childhood.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cooking and Meal Planning as Predictors of Fruit and Vegetable Intake and BMI in First-Year College Students. The objective was to determine if cooking skills and meal planning behaviors are associated with greater fruit and vegetable intake and lower body mass index (BMI) in first-year college students who are at risk for excessive weight gain. A cross-sectional analysis was conducted using baseline data from a multi-state research project aimed at preventing weight gain in first-year college students. Cooking type, frequency and confidence, self-instruction for healthful mealtime behavior intention, self-regulation of healthful mealtime behavior, and cup equivalents of fruits and vegetables (FV) were measured using validated surveys. BMI was calculated from measured height and weight. First-year students ( n = 1108) considered at risk for weight gain from eight universities completed baseline assessments within the first month of entering college. Multiple linear regression was used to determine associations among independent variables of cooking patterns, meal planning behaviors, and dependent variables of fruit and vegetable intake and BMI, after controlling for the influence of sex. Cooking more frequently, cooking with greater skills, and practicing meal planning behaviors are associated with greater fruit and vegetable intake and lower BMI in first-year college students. Interventions aimed at improving health in college students may be enhanced by incorporating cooking and meal planning components.	0	1	0	0	0	0	0	0	0	0	1	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Does antenatal and post-natal program reduce infant mortality? A meta-analytical review on 24 developing countries based on Demographic and Health Survey data. This study intended to reveal the effectiveness of Antenatal Care (ANC) and Postnatal care (PNC) services on infant mortality in 24 developing countries by utilizing the recent Demographic and Health Survey (DHS) data.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Almond as a nutraceutical and therapeutic agent in Persian medicine and modern phytotherapy: A narrative review. Sweet almond (Prunus dulcis (Mill.) D.A.Webb) is a known nut, which has long been used in several ethnomedical systems, especially in Persian medicine (PM) for its nutritional and therapeutic activities. In this study, we aimed to provide a summary on traditional uses, phytochemistry, and pharmacological activities of sweet almond. Thus, we reviewed textbooks of PM and electronic literature on traditional medicine. Moreover, the available data on the usage of sweet almond were searched in electronic databases to find articles on its pharmacological properties and phytochemistry. According to phytochemical investigations, this plant contains macronutrients, micronutrients, essential oils, various phenolic compounds, and phytosterols. Current pharmacological studies represent that Prunus dulcis has several biological activities including prebiotic, antimicrobial, antioxidant, antiinflammatory, anticancer, hepatoprotective, cardiometabolic protection, nootropic, anxiolytic, sedative-hypnotic, and nervous-improving effects. Further clinical trials and meta-analysis are required to draw a definitive conclusion on the efficacy and therapeutic activities of almond.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
svist4get: a simple visualization tool for genomic tracks from sequencing experiments. High-throughput sequencing often provides a foundation for experimental analyses in the life sciences. For many such methods, an intermediate layer of bioinformatics data analysis is the genomic signal track constructed by short read mapping to a particular genome assembly. There are many software tools to visualize genomic tracks in a web browser or with a stand-alone graphical user interface. However, there are only few command-line applications suitable for automated usage or production of publication-ready visualizations.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Predicting hospital length of stay and short-term function after hip or knee arthroplasty: are both performance and comorbidity measures useful? Variations in hospital length of stay (LOS) and function are present after hip or knee arthroplasty. Comorbidity and performance measures have been associated with post-operative outcomes. It is however not known if both independently contribute to outcome prediction. The objective of this study was to evaluate the combined predictive ability of comorbidity scores (American Society of Anesthesiologists classification system (ASA), Charlson comorbidity index (CCI), 2008 version of the CCI (CCI08)) and a performance measure (Timed-Up-and-Go (TUG)) on LOS and short-term function in patients undergoing knee or hip arthroplasty.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Chronic wound healing: A specific antibiofilm protein-asymmetric release system. Chronic infection is a major cause of delayed wound-healing. It is recognized to be associated with infectious bacterial communities called biofilms. Currently used conventional antibiotics alone often reveal themselves ineffective, since they do not specifically target the wound biofilm. Here, we report a new conceptual tool aimed at overcoming this drawback: an antibiofilm drug delivery system targeting the bacterial biofilm as a whole, by inhibiting its formation and/or disrupting it once it is formed. The system consists of a micro/nanostructured poly(butylene-succinate-co-adipate) (PBSA)-based asymmetric membrane (AM) with controlled porosity. By the incorporation of hydrophilic porogen agents, polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG), we were able to obtain AMs with high levels of porosity, exhibiting interconnections between pores. The PBSA-PEG membrane presented a dense upper layer with pores small enough to block bacteria penetration. Upon using such porogen agents, under dry and wet conditions, membrane's integrity and mechanical properties were maintained. Using bovine serum albumin (BSA) as a model protein, we demonstrated that protein loading and release from PBSA membranes were affected by the membrane structure (porosity) and the presence of residual porogen. Furthermore, the release curve profile consisted of a fast initial slope followed by a second slow phase approaching a plateau within 24 h. This can be highly beneficial for the promotion of wound healing. Cross-sectional confocal laser scanning microscopy (CLSM) images revealed a heterogeneous distribution of fluorescein isothiocyanate (FITC) labeled BSA throughout the entire membrane. PBSA membranes were loaded with dispersin B (DB), a specific antibiofilm matrix enzyme. Studies using a Staphylococcus epidermidis model, indicate significant efficiency in both inhibiting or dispersing preformed biofilm (up to 80 % eradication). The asymmetric PBSA membrane prepared with the PVP porogen (PBSA-PVP) displayed highest antibiofilm activity. Moreover, in vitro cytotoxicity assays using HaCaT and reconstructed human epidermis (RHE) models revealed that unloaded and DB-loaded PBSA-PVP membranes had excellent biocompatibility suitable for wound dressing applications.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Effects of FSHR polymorphisms on premature ovarian insufficiency in human beings: a meta-analysis. Whether follicle-stimulating hormone receptor (FSHR) polymorphisms are implicated in premature ovarian insufficiency (POI) remains controversial. Thus, we performed this study to explore correlation between FSHR polymorphisms and POI in human beings.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cairo consensus on the IVF laboratory environment and air quality: report of an expert meeting. This proceedings report presents the outcomes from an international Expert Meeting to establish a consensus on the recommended technical and operational requirements for air quality within modern assisted reproduction technology (ART) laboratories. Topics considered included design and construction of the facility, as well as its heating, ventilation and air conditioning system; control of particulates, micro-organisms (bacteria, fungi and viruses) and volatile organic compounds (VOCs) within critical areas; safe cleaning practices; operational practices to optimize air quality while minimizing physicochemical risks to gametes and embryos (temperature control versus air flow); and appropriate infection-control practices that minimize exposure to VOC. More than 50 consensus points were established under the general headings of assessing site suitability, basic design criteria for new construction, and laboratory commissioning and ongoing VOC management. These consensus points should be considered as aspirational benchmarks for existing ART laboratories, and as guidelines for the construction of new ART laboratories.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Chemodiversity of Brevetoxins and Other Potentially Toxic Metabolites Produced by Karenia spp. and Their Metabolic Products in Marine Organisms. In recent decades, more than 130 potentially toxic metabolites originating from dinoflagellate species belonging to the genus Karenia or metabolized by marine organisms have been described. These metabolites include the well-known and large group of brevetoxins (BTXs), responsible for foodborne neurotoxic shellfish poisoning (NSP) and airborne respiratory symptoms in humans. Karenia spp. also produce brevenal, brevisamide and metabolites belonging to the hemi-brevetoxin, brevisin, tamulamide, gymnocin, gymnodimine, brevisulcenal and brevisulcatic acid groups. In this review, we summarize the available knowledge in the literature since 1977 on these various identified metabolites, whether they are produced directly by the producer organisms or biotransformed in marine organisms. Their structures and physicochemical properties are presented and discussed. Among future avenues of research, we highlight the need for more toxin occurrence data with analytical techniques, which can specifically determine the analogs present in samples. New metabolites have yet to be fully described, especially the groups of metabolites discovered in the last two decades (e.g tamulamides). Lastly, this work clarifies the different nomenclatures used in the literature and should help to harmonize practices in the future.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Upconversion Nanoprobes for the Ratiometric Luminescent Sensing of Nitric Oxide. By taking advantage of the optical properties of upconversion nanoparticles (UCNPs), we have designed a luminescence ratiometric nanosensor for measuring nitric oxide (NO) in biological fluids, live cells, and tissues. This nanoconjugate consists of a UCNP core with two strong fluorescence emission peaks at 540 and 656 nm as the upconversion fluorophore, NO-reactive rhodamine B-derived molecules (RdMs) encapsulated within the mesopores of the mSiO 2 shell, and a β-cyclodextrin (βCD) layer on the exterior of the particle. Reaction of the analyte with the O-phenylenediamine of the RdM induces opening of the spiro-ring and is accompanied by an appearance of a strong rhodamine B (RdB) absorption band between 500 and 600 nm, which has spectral overlap with the green emission (540 nm) of the UCNPs. This results in an increase in the I 656 /I 540 ratio and quantitatively correlates with [NO]. The assay is validated under clean buffer conditions as well as inserum and liver tissue slices obtained from mouse models.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Stability, dissolution, and cytotoxicity of NaYF 4 -upconversion nanoparticles with different coatings. Upconversion nanoparticles (UCNPs) have attracted considerable attention owing to their unique photophysical properties. Their utilization in biomedical applications depends on the understanding of their transformations under physiological conditions and their potential toxicity. In this study, NaYF 4 :Yb,Er UCNPs, widely used for luminescence and photophysical studies, were modified with a set of four different coordinatively bound surface ligands, i.e., citrate, alendronate (AA), ethylendiamine tetra(methylene phosphonate) (EDTMP), and poly(maleic anhydride-alt-1-octadecene) (PMAO), as well as silica coatings with two different thicknesses. Subsequently, the aging-induced release of fluoride ions in water and cell culture media and their cytotoxic profile to human keratinocytes were assessed in parallel to the cytotoxic evaluation of the ligands, sodium fluoride and the lanthanide ions. The cytotoxicity studies of UCNPs with different surface modifications demonstrated the good biocompatibility of EDTMP-UCNPs and PMAO-UCNPs, which is in line with the low amount of fluoride ions released from these samples. An efficient prevention of UCNP dissolution and release of cytotoxic ions, as well as low cytotoxicity was also observed for UCNPs with a sufficiently thick silica shell. Overall, our results provide new insights into the understanding of the contribution of surface chemistry to the stability, dissolution behavior, and cytotoxicity of UCNPs. Altogether, the results obtained are highly important for future applications of UCNPs in the life sciences and bioimaging studies.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Hydraulic separation of plastic wastes: Analysis of liquid-solid interaction. The separation of plastic wastes in mechanical recycling plants is the process that ensures high-quality secondary raw materials. An innovative device employing a wet technology for particle separation is presented in this work. Due to the combination of the characteristic flow pattern developing within the apparatus and density, shape and size differences among two or more polymers, it allows their separation into two products, one collected within the instrument and the other one expelled through its outlet ducts. The kinematic investigation of the fluid flowing within the apparatus seeded with a passive tracer was conducted via image analysis for different hydraulic configurations. The two-dimensional turbulent kinetic energy results strictly connected to the apparatus separation efficacy. Image analysis was also employed to study the behaviour of mixtures of passive tracer and plastic particles with different physical characteristics in order to understand the coupling regime between fluid and solid phases. The two-dimensional turbulent kinetic energy analysis turned out to be fundamental to this aim. For the tested operating conditions, two-way coupling takes place, i.e., the fluid exerts an influence on the plastic particle and the opposite occurs too. Image analysis confirms the outcomes from the investigation of the two-phase flow via non-dimensional numbers (particle Reynolds number, Stokes number and solid phase volume fraction).	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
[Clinical value of herbal terpenes after extracorporeal shock-wave therapy]. Rowatinex is a combined drug based on plant terpenes which provides diuretic, anti-inflammatory and antispasmodic effect. A use of herbal preparation Rowatinex in patients with urinary stone disease after extracorporeal shock-wave therapy (ESWL) is analyzed in the article.	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Nonlinear Extensional Rheology of Poly( n -alkyl methacrylate) Melts with a Fixed Number of Kuhn Segments and Entanglements per Chain. Molecular theories for dynamics of entangled polymers are based on both the number of Kuhn segments per entanglement N e and the number of entanglements per chain N / N e . Extensive studies have shown that, for polymer chains in the solutions or melts, linear viscoelasticity can be properly normalized, whereas the nonlinear extensional rheological properties cannot be normalized when N / N e is kept the same. The failure of the latter normalization has been attributed to a difference in N e . Nevertheless, nonlinear rheological studies are lacking for a suitable model system with fixed N e and N / N e . In this study, we identify poly( n -alkyl methacrylate)s with the number of carbons per alkyl group below seven as a model system. We find that the degree of the transient strain hardening during extensional flow strengthens with increasing the size of the alkyl group even when N e and N / N e are kept the same, which is attributable to the weaker friction reduction when the main backbones are more separated.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Application of spectral induced polarization for characterizing surfactant-enhanced DNAPL remediation in laboratory column experiments. The widespread presence of entrapped dense non-aqueous phase liquid (DNAPL) in the subsurface poses a continuing challenge to groundwater remediation. Cost-effective and high-resolution subsurface characterization is a critical issue for further DNAPL recovery due to the complexity of DNAPL source zone architecture (SZA). Geophysical techniques provide a noninvasive, spatially continuous and cost-effective way for monitoring the DNAPL remediation process. In particular, the spectral induced polarization (SIP) method has shown great potential in environmental problems. In this study, we performed real-time SIP measurements on DNAPL contaminated soil in columns to quantitatively assess the ability of SIP method for monitoring surfactant-enhanced DNAPL remediation process. Chemical data was simultaneously collected during the remediation process to verify the results obtained by SIP method. Taking account into the variations of subsurface environment, we conducted a series of column flushing experiments under different flow rate, surfactant concentrations and fluid salinities. The results highlight that SIP method is able to effectively monitor the DNAPL remediation process, as well as to evaluate the remediation efficiency under different conditions. The variations in the flow rate, the concentration of surfactant and the salinity of pore water not only affect remediation effectiveness, but also have an impact on the SIP signatures. This study shows that SIP performs better for monitoring DNAPL remediation at a relatively low flow rate of ~ 0.4 m/d, low surfactant concentration of 5000 mg/L and high salinity of 1.0 S/m, with an error of saturation estimation (RMSE S ) <0.1.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
REL-1017 (Esmethadone) as Adjunctive Treatment in Patients With Major Depressive Disorder: A Phase 2a Randomized Double-Blind Trial. Objective: The purpose of this study was to examine the effects of REL-1017 (esmethadone), a novel N -methyl-d-aspartate receptor (NMDAR) channel blocker, in patients with major depressive disorder who failed to benefit from one to three standard antidepressant treatments in their current major depressive episode. Methods: A 7-day phase 2 multicenter randomized double-blind placebo-controlled trial, comprising three arms, was conducted to assess the safety, tolerability, pharmacokinetics, and efficacy of two dosages of REL-1017 (25 mg or 50 mg orally once a day). Patients were randomly assigned in a 1:1:1 ratio to placebo (N=22), REL-1017 25 mg/day (N=19), or REL-1017 50 mg/day (N=21). Safety scales included the 4-item Positive Symptom Rating Scale for psychotomimetic symptoms, the Clinician-Administered Dissociative States Scale for dissociative symptoms, the Clinical Opiate Withdrawal Scale for withdrawal signs and symptoms, and the Columbia-Suicide Severity Rating Scale for suicidality. The primary efficacy endpoint was the Montgomery-Åsberg Depression Scale (MADRS) score. All 62 randomly assigned patients were included in the full analysis set population analysis. Results: Patients experienced mild or moderate transient adverse events and no evidence of dissociative or psychotomimetic effects, opioid effects, or withdrawal signs and symptoms. The improvement in MADRS score shown on day 4 in both of the REL-1017 dosage groups was sustained through day 7 (last dose) and day 14 (7 days after the last dose), with effect sizes from 0.7 to 1.0. Conclusions: This trial showed favorable safety, tolerability, and pharmacokinetic profiles and suggests that REL-1017 may have rapid and sustained antidepressant effects compared with placebo in patients with inadequate responses to antidepressant treatments. These results will need confirmation in larger and longer trials.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Effects of walking exercise training on learning and memory and hippocampal neuroimaging outcomes in MS: A targeted, pilot randomized controlled trial. The current pilot study involved a single-blind, randomized controlled trial (RCT) on the effects of treadmill walking exercise training compared with an active control condition on learning and memory (L/M) and hippocampal neuroimaging outcomes in 11 fully-ambulatory persons with multiple sclerosis (MS) who demonstrated impairments in new learning.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Neonatal diabetes mellitus due to a new KCNJ11 mutation - 10 years of the patient`s follow-up. Mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the ATP-sensitive potassium channel, often result in neonatal diabetes.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Low-intensity pulsed ultrasound regulates proliferation and differentiation of neural stem cells through notch signaling pathway. Low-intensity pulsed ultrasound (LIPUS) is widely used to regulate stem cell proliferation and differentiation. However, the effect of LIPUS stimulation on neural stem cells (NSCs) is not well documented. In this study, we have identified the optimal parameters, and investigated the cellular mechanisms of LIPUS to regulate the proliferation and differentiation of NSCs in vitro. NSCs were obtained and identified by nestin immunostaining. The proliferation of NSCs were measured by using Cell Counting Kit-8 (CCK-8). The expressions of nutritional factors (NTFs) were detected with immunoassay (ELISA). NSCs differentiation were detected by immunofluorescence and immunoblotting analysis. The expression level of proteins involved in the Notch signaling pathway was also measured by immunoblotting assay. Our results showed the intensity of 69.3 mW/cm 2 (1 MHz, 8 V) was applicable for LIPUS stimulation. ELISA analysis demonstrated that LIPUS treatment promoted the expression of nutritional factors of NSCs in vitro. Immunofluorescence and immunoblotting analyses suggested that the LIPUS not only reduced the astrocyte differentiation, but also stimulated the differentiation to neurons. Additionally, LIPUS stimulation significantly upregulated expression level of Notch1 and Hes1. Results from our study suggest that LIPUS triggers NSCs proliferation and differentiation by modulating the Notch signaling pathway. This study implies LIPUS as a potential and promising therapeutic platform for the optimization of stem cells and enable noninvasive neuromodulation for central nervous system diseases.	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cardiac resynchronization therapy in the ageing population - With or without an implantable defibrillator? Cardiac resynchronization therapy (CRT) is an effective treatment option for systolic heart failure, but the benefit of an additional implantable cardioverter-defibrillator (ICD) in elderly patients is not well established. The aim of our study was to evaluate the impact of an additional ICD on survival in elderly CRT recipients.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Epigenetics and pulmonary diseases in the horizon of precision medicine: a review. Epigenetic mechanisms represent potential molecular routes which could bridge the gap between genetic background and environmental risk factors contributing to the pathogenesis of pulmonary diseases. In patients with COPD, asthma and pulmonary arterial hypertension (PAH), there is emerging evidence of aberrant epigenetic marks, mainly including DNA methylation and histone modifications which directly mediate reversible modifications to the DNA without affecting the genomic sequence. Post-translational events and microRNAs can be also regulated epigenetically and potentially participate in disease pathogenesis. Thus, novel pathogenic mechanisms and putative biomarkers may be detectable in peripheral blood, sputum, nasal and buccal swabs or lung tissue. Besides, DNA methylation plays an important role during the early phases of fetal development and may be impacted by environmental exposures, ultimately influencing an individual's susceptibility to COPD, asthma and PAH later in life. With the advances in omics platforms and the application of computational biology tools, modelling the epigenetic variability in a network framework, rather than as single molecular defects, provides insights into the possible molecular pathways underlying the pathogenesis of COPD, asthma and PAH. Epigenetic modifications may have clinical applications as noninvasive biomarkers of pulmonary diseases. Moreover, combining molecular assays with network analysis of epigenomic data may aid in clarifying the multistage transition from a "pre-disease" to "disease" state, with the goal of improving primary prevention of lung diseases and its subsequent clinical management.We describe epigenetic mechanisms known to be associated with pulmonary diseases and discuss how network analysis could improve our understanding of lung diseases.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Prognostic value of reduction in left atrial size during a follow-up of heart failure: an observational study. The association between sequential changes in left atrial diameter (LAD) and prognosis in heart failure (HF) remains to be elucidated. The present study aimed to investigate the link between reduction in LAD and clinical outcomes in patients with HF.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Does competition affect the clinical decision-making of dentists? A geospatial analysis. To investigate the association between dentists' geographic density and perceptions of market competition with clinical decision-making among a representative sample of dentists in Ontario, Canada's most populated province.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Structural and organizational factors shaping access to medication treatment for opioid use disorder in community supervision. Four million individuals in the U.S. criminal-legal system are supervised in the community under probation or parole. Sentences to community supervision often mandate participation in substance use treatment. Yet evidence-based treatment with medication (i.e., methadone, buprenorphine, or naltrexone) is rarely offered to people under community supervision with opioid use disorder (OUD). This qualitative study explores the structural and organizational factors shaping OUD medication treatment use in community supervision.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Oral transfer of chemical cues, growth proteins and hormones in social insects. Social insects frequently engage in oral fluid exchange - trophallaxis - between adults, and between adults and larvae. Although trophallaxis is widely considered a food-sharing mechanism, we hypothesized that endogenous components of this fluid might underlie a novel means of chemical communication between colony members. Through protein and small-molecule mass spectrometry and RNA sequencing, we found that trophallactic fluid in the ant Camponotus floridanus contains a set of specific digestion- and non-digestion related proteins, as well as hydrocarbons, microRNAs, and a key developmental regulator, juvenile hormone. When C. floridanus workers' food was supplemented with this hormone, the larvae they reared via trophallaxis were twice as likely to complete metamorphosis and became larger workers. Comparison of trophallactic fluid proteins across social insect species revealed that many are regulators of growth, development and behavioral maturation. These results suggest that trophallaxis plays previously unsuspected roles in communication and enables communal control of colony phenotypes.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Assessing a novel way to measure step count while walking using a custom mobile phone application. Walking speed has been associated with many clinical outcomes (e.g., frailty, mortality, joint replacement need, etc.). Accurately measuring walking speed (stride length x step count/time) typically requires significant clinician/staff time or a gait lab with specialized equipment (i.e., electronic timers or motion capture). In the present study, our goal was to measure "step count" via smartphones through novel software and to compare with step tracking software that come standard with iOS and Android smartphones as a first step in walking speed measurement.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Current Treatment Options for HCC: From Pharmacokinetics to Efficacy and Adverse Events in Liver Cirrhosis. Hepatocellular carcinoma (HCC) is among the world's most common cancers. For over ten years, the only medical treatment for it has been the multikinase inhibitor Sorafenib. Currently, however, other first or second-line therapeutic options have also shown efficacy against HCC, such as multikinase inhibitors (Regorafenib, Lenvatinib, and Cabozantinib), a monoclonal antibody against the vascular endothelial growth factor receptor 2 (Ramucirumab), and immune-checkpoint inhibitors (Nivolumab, Pembrolizumab, Ipilimumab).	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	1	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0
Surgical technique and outcomes following coronal-sparing glans resurfacing for benign and malignant penile lesions. The aim of this study is to describe the outcomes for a modified glans-resurfacing technique for benign and malignant penile conditions in which the uninvolved glans corona is preserved in order to maintain glans erogenous sensation. A total of 13 patients underwent coronal-sparing glans resurfacing (CSGR), with follow-up every 3 months for ≥2 years. Positive surgical margin and local recurrence (LR) rates were evaluated. Surgical complications and cosmetic outcomes were also recorded. Patients were asked to complete the International Index of Erectile Function-5 (IIEF-5) questionnaire starting 12 months after the surgery. The median (interquartile range [IQR]) age and follow-up periods were 63 (53-68) years and 29 (14-38) months, respectively. Eight patients were diagnosed with primary penile squamous cell carcinoma (SCC), three had refractory lichen sclerosus, and two had penile intraepithelial neoplasia (PeIN). No surgical complications were recorded. All patients had a complete graft take and reported satisfactory cosmetic results with preserved erogenous sensation. Two cancer patients developed LR which was managed with further penile preserving surgery. The median (IQR) postoperative IIEF-5 value was 20 (17-23). This modified coronal-sparing technique was suitable for glans lesions that spare the coronal ridge and coronal sulcus. Preservation of the coronal ridge helps maintain sexual function and provides excellent cosmetic outcomes.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Stachydrine hydrochloride alleviates pressure overload-induced heart failure and calcium mishandling on mice. Traditional Chinese medicine Leonurus japonicus Houtt. has a long history in the treatment of cardiovascular diseases. Stachydrine hydrochloride, the main bioactive ingredient extracted from Leonurus japonicus Houtt., has been shown to have cardioprotective effects. However, the underlying mechanisms of stachydrine hydrochloride haven't been comprehensively studied so far.	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Clinical assessment of the impact of pelvic pain on women. We aimed to develop a questionnaire that assesses the impact of pelvic pain on women, regardless of diagnosis, that has high utility, sound psychometric performance, easy scoring, and high reliability. Two studies, with 3 separate cohorts, were undertaken. Both studies were completed online. Studies included women with self-reported pelvic pain. Women were eligible to participate regardless of whether their pelvic pain was undiagnosed, self-diagnosed, or diagnosed by a clinician. Study 1 used a 3-round "patient-as-expert" Delphi technique. These rounds defined the 10 aspects of life with the self-reported greatest impact on the lives of women with pelvic pain, which formed the questionnaire. Study 2 used Rasch analysis to assess the psychometric properties of the resultant 10-item questionnaire. To assess its reliability, a subgroup completed the questionnaire 3 times over a 3-week period. In study 1, 443 women with pelvic pain participated. The resultant 10-item questionnaire consisted of 8 Likert questions and 2 supplemental, nonscored questions. In study 2, 1203 women with pelvic pain completed the questionnaire. Rasch analysis showed that the questionnaire targeted the pelvic pain population well, had appropriate Likert categories, constituted a unidimensional scale, and showed internal consistency. Twenty-seven women with pelvic pain completed the reliability trial. Test-retest reliability was high (intraclass correlation coefficient 0.91, P < 0.001). The resultant Pelvic Pain Impact Questionnaire assesses the life impact of pelvic pain. It uses patient-generated language, is easily administered and scored, has very strong psychometric properties, and it is suitable for research and clinical settings across primary, secondary, and tertiary care.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0
Patterns and predictors of private and public health care utilization among residents of an informal settlement in Nairobi, Kenya: a cross-sectional study. Knowledge of health care utilization is important in low-and middle-income countries where inequalities in the burden of diseases and access to primary health care exist. Limited evidence exists on health seeking and utilization in the informal settlements in Kenya. This study assessed the patterns and predictors of private and public health care utilization in an urban informal settlement in Kenya.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
A new species of Bent-toed Gecko (Squamata, Gekkonidae, Cyrtodactylus) from the Shan Plateau in eastern Myanmar (Burma). An integrative taxonomic analysis of the Cyrtodactylus linnwayensis group of the Shan Plateau recovered two new populations from isolated karst habitats near Pinlaung Town, Shan State as a new species, C. pinlaungensis sp. nov. Cyrtodactylus pinlaungensis sp. nov. is most closely related to a clade comprising C. linnwayensis and C. ywanganensis from the western edge of the Shan Plateau approximately 90 km to the northwest. Cyrtodactylus pinlaungensis sp. nov. can be distinguished from all members of the C. linnwayensis group by a number of statistically different morphological characters, discrete color pattern differences, and its heavy tuberculation. It also bears an uncorrected pairwise sequence divergence of 5.0-7.6% from all other species combined based on the mitochondrial gene ND2 and its flanking tRNAs. The discovery of this new species on the Shan Plateau continues to underscore the fact that this region is rapidly emerging as a herpetological diversity hot-spot for Myanmar.	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cell-Nanoparticle Interactions at (Sub)-Nanometer Resolution Analyzed by Electron Microscopy and Correlative Coherent Anti-Stokes Raman Scattering. A wide variety of nanoparticles are playing an increasingly important role in drug delivery. Label-free imaging techniques are especially desirable to follow the cellular uptake and intracellular fate of nanoparticles. The combined correlative use of different techniques, each with unique advantages, facilitates more detailed investigation about such interactions. The synergistic use of correlative coherent anti-Stokes Raman scattering and electron microscopy (C-CARS-EM) imaging offers label-free, chemically-specific, and (sub)-nanometer spatial resolution for studying nanoparticle uptake into cells as demonstrated in the current study. Coherent anti-Stokes Raman scattering (CARS) microscopy offers chemically-specific (sub)micron spatial resolution imaging without fluorescent labels while transmission electron microscopy (TEM) offers (sub)-nanometer scale spatial resolution and thus visualization of precise nanoparticle localization at the sub-cellular level. This proof-of-concept imaging platform with unlabeled drug nanocrystals and macrophage cells revealed good colocalization between the CARS signal and electron dense nanocrystals in TEM images. The correlative TEM images revealed subcellular localization of nanocrystals inside membrane bound vesicles, showing multivesicular body (MVB)-like morphology typical for late endosomes (LEs), endolysosomes, and phagolysosomes. C-CARS-EM imaging has much potential to study the interactions between a wide range of nanoparticles and cells with high precision and confidence.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dexamethasone delivery to the ocular posterior segment by sustained-release Laponite formulation. This paper presents a novel nanoformulation for sustained-release delivery of dexamethasone (DEX) to the ocular posterior segment using a Laponite (LAP) carrier-DEX/LAP 1:10 w w -1 formulation; 10 mg ml -1 . In vivo ocular feasibility and pharmacokinetics after intravitreal (IV) and suprachoroidal (SC) administration in rabbit eyes are compared against IV administration of a DEX solution (1 mg ml -1 ). Thirty rabbit eyes were injected with the DEX/LAP formulation (15 suprachoroid/15 intravitreous). Ophthalmological signs were monitored at day 1 and at weeks 1-4-12-24 post-administration. Three eyes per sample time point were used to quantify DEX concentration using high-performance liquid chromatography-mass spectrometry. The ocular tissues' pharmacokinetic parameters (lens, vitreous humour, choroid-retina unit and sclera) were studied. DEX/LAP was well tolerated under both administration methods. Peak intraocular DEX levels from the DEX/LAP were detected in the vitreous humour after both deliveries soon after administration. The vitreous area under the curve was significantly greater after both DEX/LAP deliveries (IV: 205 968.47; SC: 11 442.22 ng g -1 d -1 ) than after IV administration of the DEX solution (317.17 ng g -1 d -1 ). Intravitreal DEX/LAP delivery extended higher vitreous DEX levels up to week 24 (466.32 ± 311.15 ng g -1 ). With SC delivery, DEX levels were detectable in the choroid-retina unit (12.04 ± 20.85 ng g -1 ) and sclera (25.46 ± 44.09 ng g -1 ) up to week 24. This study demonstrated the intraocular feasibility of both SC and IV administration of the DEX/LAP formulation. The LAP increased the intraocular retention time of DEX when compared with conventional solutions. DEX/LAP could be considered a biocompatible and useful sustained-release formulation for treating posterior-pole eye diseases.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Genetic analysis of surgical margins in oral cavity cancer. A histological, tumour-free surgical margin does not guarantee recurrence-free survival in patients with cancer. This study investigated the association between microsatellite alteration in tumour-free surgical margins and local recurrence in patients with oral cavity squamous cell carcinoma.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Unraveling neuroHIV in the Presence of Substance Use Disorders. This special issue contains 10 invited review papers that highlighted and extended the presentations at the NIDA-sponsored workshop "Unraveling NeuroAIDS in the Presence of Substance Use Disorders" at the 25th Society on NeuroImmune Pharmacology conference in 2019. The topics covered by these papers focused on the interactive, additive or synergistic effects of substance use disorders (SUD) with HIV infection on the immune system and on neuropathogenesis. These papers reviewed four categories of substances of abuse (opioids, tobacco, stimulants, and cannabis) and how comorbid HIV infection (including models with HIV proteins, HIV transgenic rodent models and SIV) might further impact the dysregulated dopaminergic and immune systems, and the subsequent neuropathogenesis and behavioral disorders known as HIV-associated neurological disorders (HAND). These reviews provided detailed background knowledge regarding how each of these addictive substances and HIV individually or collectively affected the immune system at the cellular, molecular and system levels, and the subsequent clinical and behavioral outcomes. The authors also identified gaps, confounds or constraints in the current disease models and approaches, and proposed future research directions.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Sex differences in the acute pharmacological and subjective effects of smoked cannabis combined with alcohol in young adults. Objective: The prevalence of co-use of alcohol and cannabis is increasing, particularly among young adults. Sex differences in the effects of alcohol alone and cannabis alone have been observed in animals and humans. However, sex differences in the acute pharmacological effects of cannabis combined with alcohol have not yet been studied. In young adults, aged 19-29 years, we aimed to examine sex differences following an intoxicating dose of alcohol (target 0.08% breath alcohol content) combined with a moderate dose of cannabis (12.5% Δ⁹-tetrahydrocannabinol; THC) using an ad libitum smoking procedure. Method: Using a within-subjects design, 28 regular cannabis users (16 males; 12 females) received in random order: (a) placebo alcohol and placebo cannabis, (b) active alcohol and placebo cannabis, (c) placebo alcohol and active cannabis, and (d) active alcohol and active cannabis. Blood samples for THC were collected and measures of vital signs, subjective drug effects, and cognition were collected. Results: In the alcohol-cannabis combined condition, females smoked significantly less of the cannabis cigarette compared to males ( p < .001), although both sexes smoked similar amounts in the other conditions. There was minimal evidence that females and males differed in THC blood concentrations, vitals, subjective effects, or cognitive measures. Conclusions: In the alcohol-cannabis combined condition, females experienced the same acute pharmacological and subjective effects of alcohol and cannabis as males, after smoking less cannabis, which has potential implications for informing education and policy. Further research is warranted on sex differences in cannabis pharmacology, as well as the combined effects of alcohol and cannabis. (PsycInfo Database Record (c) 2021 APA, all rights reserved).	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Microbial electrohydrogenesis linked to dark fermentation as integrated application for enhanced biohydrogen production: A review on process characteristics, experiences and lessons. Microbial electrohydrogenesis cells (MECs) are devices that have attracted significant attention from the scientific community to generate hydrogen gas electrochemically with the aid of exoelectrogen microorganisms. It has been demonstrated that MECs are capable to deal with the residual organic materials present in effluents generated along with dark fermentative hydrogen bioproduction (DF). Consequently, MECs stand as attractive post-treatment units to enhance the global H 2 yield as a part of a two-stage, integrated application (DF-MEC). In this review article, it is aimed (i) to assess results communicated in the relevant literature on cascade DF-MEC systems, (ii) describe the characteristics of each steps involved and (iii) discuss the experiences as well as the lessons in order to facilitate knowledge transfer and help the interested readers with the construction of more efficient coupled set-ups, leading eventually to the improvement of overall biohydrogen evolution performances.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Prevalence of temporomandibular disorder in adult patients with chronic pain. Chronic pain patients often suffer in multiple locations. In health care, examinations of bodily pain usually do not include questions about temporomandibular disorders (TMD); hence TMD symptoms and potential comorbidities are not regularly assessed. Therefore, the primary aim was to evaluate the prevalence of TMD in patients referred to a pain rehabilitation clinic, and the secondary aim was to evaluate possible factors associated with TMD symptoms.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Kin selection promotes female productivity and cooperation between the sexes. Hamilton's theory of kin selection explains the evolution of costly traits that benefit other individuals by highlighting the fact that passing genes to offspring is not the only way of increasing the representation of those genes in subsequent generations: Genes are also shared with other classes of relatives. Consequently, any heritable trait that affects fitness of relatives should respond to kin selection. We tested this core prediction of kin selection theory by letting bulb mites ( Rhizoglyphus robini ) evolve in populations structured into groups of relatives or nonrelatives during the reproductive phase of the life cycle. In accordance with predictions derived from kin selection theory, we found that evolution in groups of relatives resulted in increased female reproductive output. This increase at least partly results from the evolution of male traits that elevate their partners' fecundity. Our results highlight the power and universality of kin selection.	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Do Season and Environment Have a Role in the Incidence of Anterior Uveitis Attacks? To investigate the seasonal influence on the incidence of uveitis attacks.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Establishing the Prevalence of Intimate Partner Violence Among Hair Salon Clients. This study determined prevalence of intimate partner violence (IPV) victimization among female clients at three hair salons in Connecticut using an anonymous tablet based screening tool. While many may assume that women receive services at hair salons, victims of IPV are often isolated by their partners and unable to access help. Of the 203 clients who participated, 40 (20%) had experienced IPV in her lifetime. In identifying the prevalence of IPV within the salon setting, this study provides support for community-based programs and supports their legitimacy as an important locus for identifying women experiencing IPV and connecting them to resources.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Endometriosis shows no impact on the euploid blastocyst rate per cohort of inseminated metaphase-II oocytes: A case-control study. To evaluate the true impact of endometriosis on oocytes' competence defined as blastulation, euploidy and implantation rates.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Radiomics in PET/CT: Current Status and Future AI-Based Evolutions. This short review aims at providing the readers with an update on the current status, as well as future perspectives in the quickly evolving field of radiomics applied to the field of PET/CT imaging. Numerous pitfalls have been identified in study design, data acquisition, segmentation, features calculation and modeling by the radiomics community, and these are often the same issues across all image modalities and clinical applications, however some of these are specific to PET/CT (and SPECT/CT) imaging and therefore the present paper focuses on those. In most cases, recommendations and potential methodological solutions do exist and should therefore be followed to improve the overall quality and reproducibility of published studies. In terms of future evolutions, the techniques from the larger field of artificial intelligence (AI), including those relying on deep neural networks (also known as deep learning) have already shown impressive potential to provide solutions, especially in terms of automation, but also to maybe fully replace the tools the radiomics community has been using until now in order to build the usual radiomics workflow. Some important challenges remain to be addressed before the full impact of AI may be realized but overall the field has made striking advances over the last few years and it is expected advances will continue at a rapid pace.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study. Achondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported.	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
How is orthodontic treatment need associated with perceived esthetic impact of malocclusion in adolescents? The purpose of this research was to evaluate the esthetic impact of orthodontic treatment need in adolescents.	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Proteomics insights into the effects of MSTN on muscle glucose and lipid metabolism in genetically edited cattle. The molecular mechanism underlying myostatin (MSTN)-regulated metabolic cross-talk remains poorly understood. In this study, we performed comparative proteomic and phosphoproteomic analyses of gluteus muscle tissues from MSTN -/- transgenic cattle using a shotgun-based tandem mass tag (TMT) 6-plex labeling method to explore the signaling pathway of MSTN in metabolic cross-talk and cellular metabolism during muscle development. A total of 72 differentially expressed proteins (DEPs) and 36 differentially expressed phosphoproteins (DEPPs) were identified in MSTN -/- cattle compared to wild-type cattle. Bioinformatics analyses showed that MSTN knockout increased the activity of many key enzymes involved in fatty acid β-oxidation and glycolysis processes in cattle. Furthermore, comprehensive pathway analyses and hypothesis-driven AMP-activated protein kinase (AMPK) activity assays suggested that MSTN knockout triggers the activation of AMPK signaling pathways to regulate glucose and lipid metabolism by increasing the AMP/ATP ratio. Our results shed new light on the potential regulatory mechanism of MSTN associated with metabolic cross-talk in muscle development, which can be used in animal breeding to improve meat production in livestock animals, and can also provide valuable insight into treatments for obesity and diabetes mellitus in humans.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Prevalence of malnutrition among older people in medical and surgical wards in hospital and quality of nutritional care: A multicenter, cross-sectional study. To determine and compare the prevalence of malnutrition in medical and surgical hospital units; to assess quality of nutritional care and patients' perception about quality of food and nutritional care.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Anatomical Risk Factors for Anterior Cruciate Ligament Injury Are Not Important As Patellar Instability Risk Factors in Patients with Acute Knee Injury. To compare in magnetic resonance imaging the anatomical risk factors for anterior cruciate ligament (ACL) injury and patellar dislocation among patients who suffered acute knee injury, 105 patients with acute knee injury resulting in 38 patellar dislocations (patella group), 35 ACL injuries (ACL group), and 32 meniscus or medial collateral ligament injuries (control group) were included. These groups were compared for risk factors for patellar dislocation (patellar height, trochlear dysplasia, and quadriceps angle of action) and for ACL injury (intercondylar width, posterior inclination of tibial plateaus, and depth of the medial plateau). Univariate analysis found statistically significant differences ( p < 0.05) between the patella and ACL groups in patellar height (Caton-Deschamps [CD] 1.23 vs. 1.07), trochlear facet asymmetry (55 vs. 68%), PTTG (13.08 vs. 8.01 mm), and the patellar tip and trochlear groove (PTTG) angle (29.5 vs. 13.71 degrees). The patella group also differed from control in medial plateau inclination (4.8 vs. 1.87 degrees), patellar height (CD 1.23 vs 1.08), trochlear facet asymmetry (55 vs. 69%), lateral trochlear inclination (17.11 vs. 20.65 degrees), trochlear depth (4.1 vs. 6.05 mm), PTTG (13.08 vs. 9.85 mm), and the PTTG angle (29.5 vs. 17.88 degrees). The ACL and control groups were similar in all measures. Multivariate analysis found the following significant determinants between the Patella and Control groups: patellar height (CD index, odds ratio [OR]: 80.13, p = 0.015), trochlear anatomy (asymmetry of facets M/L, OR: 1.06, p = 0.031) and quadriceps action angle (PTTG angle, OR: 1.09, p = 0.016); between the ACL and control groups: PTTG angle (OR: 0.936, p = 0.04) and female gender (OR: 3.876, p = 0.032); and between the patella and ACL groups, the CD index (OR: 67.62, p = 0.026), asymmetry of the M/L facets (OR: 1.07, p = 0.011) and PTTG angle (OR: 1.16, p < 0.001). In conclusion, in patients with acute knee injury, the anatomical factors patellar height, trochlear dysplasia, and quadriceps angle of action were related to the occurrence of patellar dislocation. None of the anatomical factors studied was related to the occurrence of anterior cruciate ligament injury.	0	0	0	0	0	1	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Research of Distorted Vehicle Magnetic Signatures Recognitions, for Length Estimation in Real Traffic Conditions. Reliable cost-effective traffic monitoring stations are a key component of intelligent transportation systems (ITS). While modern surveillance camera systems provide a high amount of data, due to high installation price or invasion of drivers' personal privacy, they are not the right technology. Therefore, in this paper we introduce a traffic flow parameterization system, using a built-in pavement sensing hub of a pair of AMR (anisotropic magneto resistance) magnetic field and MEMS (micro-electromechanical system) accelerometer sensors. In comparison with inductive loops, AMR magnetic sensors are significantly cheaper, have lower installation price and cause less intrusion to the road. The developed system uses magnetic signature to estimate vehicle speed and length. While speed is obtained from the cross-correlation method, a novel vehicle length estimation algorithm based on characterization of the derivative of magnetic signature is presented. The influence of signature filtering, derivative step and threshold parameter on estimated length is investigated. Further, accelerometer sensors are employed to detect when the wheel of vehicle passes directly over the sensor, which cause distorted magnetic signatures. Results show that even distorted signatures can be used for speed estimation, but it must be treated with a more robust method. The database during the real-word traffic and hazard environmental condition was collected over a 0.5-year period and used for method validation.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Is urban living good for mental health? The questions of urban living, mental health and well-being are complex issues correlated to many interacting factors. The purpose of this review is to provide data on mental health challenges of urban life and perspectives to address these challenges.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Testing depth of suppression in childhood intermittent exotropia. A test of suppression was developed to provide a standardized approach to detecting and grading density of suppression in children with intermittent exotropia when manifestly exotropic. This new Office Suppression Test is a three-step procedure to grade suppression on a 4-point scale (from 0 for "negligible suppression" to 3 for "dense suppression"). The test was performed in 57 children 3-13 years of age with intermittent exotropia (distance angle of 16 Δ -35 Δ , with spontaneous tropia) during enrollment in a randomized trial. Of the 57 children, 51 could complete testing: 28 (55%) had dense suppression, 12 (24%) had moderate suppression, 5 (10%) had mild suppression, and 6 (12%) had negligible suppression. In a subgroup of 20 untreated children, suppression was evaluated again at 8 weeks. There was moderate agreement between suppression scores at baseline and at 8 weeks (weighted κ = 0.65 [95% CI, 0.45-0.84]).	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Association Between Parental Marital Status and Types of Suicidal Behavior Among Korean Adolescents: A Cross-sectional Study. Adolescent suicide is a global problem. This study aimed to identify associations between parental marital status and suicidal behavior.	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Genome-Wide Identification of the LAC Gene Family and Its Expression Analysis Under Stress in Brassica napus . Lignin is an important biological polymer in plants that is necessary for plant secondary cell wall ontogenesis. The laccase ( LAC ) gene family catalyzes lignification and has been suggested to play a vital role in the plant kingdom. In this study, we identified 45 LAC genes from the Brassica napus genome ( BnLACs ), 25 LAC genes from the Brassica rapa genome ( BrLACs ) and 8 LAC genes from the Brassica oleracea genome ( BoLACs ). These LAC genes could be divided into five groups in a cladogram and members in same group had similar structures and conserved motifs. All BnLACs contained hormone- and stress- related elements determined by cis-element analysis. The expression of BnLACs was relatively higher in the root, seed coat and stem than in other tissues. Furthermore, BnLAC4 and its predicted downstream genes showed earlier expression in the silique pericarps of short silique lines than long silique lines. Three miRNAs (miR397a, miR397b and miR6034) target 11 BnLACs were also predicted. The expression changes of BnLACs under series of stresses were further investigated by RNA sequencing (RNA-seq) and quantitative real-time polymerase chain reaction (qRT-PCR). The study will give a deeper understanding of the LAC gene family evolution and functions in B. napus.	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Network structures and temporal stability of self- and informant-rated affective symptoms in Alzheimer's disease. Affective symptoms in Alzheimer's disease (AD) can be rated with both informant- and self-ratings. Information from these two modalities may not converge. We estimated network structures of affective symptoms in AD with both rating modalities and assessed the longitudinal stability of the networks.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Analytic autoethnography of familial and institutional social identity construction of My Dad with Alzheimer's: In the emergency room with Erving Goffman and Oliver Sacks. This paper analyzes variable social identity construction for my Dad over his last two years, within his family, and then within several institutions, before he died of Alzheimer's Disease (AD). This article makes epistemic and methodological contributions to research on persons with AD by using analytic autoethnography and long-term ethnographic case development to trace processes by which my Dad's evolving social identity was constructed -- and increasingly socially constructed -- as his memory became more impaired and he moved from home into several institutions. It analyzes how our family resisted his conversion into an "AD patient" - the stigmatized sum of his symptoms - but engaged in what felt like Goffmanian betrayals to care for him. The paper recognizes the value and need to fight the image of AD as social death in research, the medical system, and popular understanding, but proposes a family Memory-Relationship self to conceptually capture the trauma many families feel as AD increasingly impairs the loved one with AD and leads to their death (unless they die of something else first). My Dad's placement in five institutions in six months created awful natural experiment-like leverage, because he was alternatively constructed in institutions as a legally competent adult, a dangerous patient, and an AD patient, and often responded correspondingly.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
[Antiangiogenic therapy in high-risk keratoplasty]. To analyze the effectiveness and safety of VEGF inhibitor used to improve keratoconus transplant survival in patients with corneal neovascularization as stand-alone and in combination with laser coagulation of ingrowing vessels before keratoplasty.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Supplemental Oxygen and Surgical Site Infection in Colorectal Surgery: A Systematic Review and Meta-analysis. Surgical site infection (SSI) is a common preventable iatrogenic infection following surgery with an approximated overall occurrence of 2-4%. Despite numerous studies, controversies still exist regarding the efficacy, safety, and cost effectiveness of strategies to decrease SSI. The World Health Organization issued recommendations for the prevention of SSIs including oxygenation with 80% fraction of inspired oxygen (FiO 2 ). The primary outcome of our systematic review and metaanalysis was the effect of high inspired FiO 2 related to SSI in the colorectal surgery population. Secondary outcomes included incidence of anastomotic leaks and length of hospital stay. Eleven trials consisting of 8245 were included in the analysis. We found moderate quality of evidence that 80% FiO2 was not effective in reducing SSI (RR, 0.91; 95% CI, 0.74 to 1.13; P = .41) anastomotic leaks (RR, 0.75; 95% CI, 0.53 to 1.06; P = 0.10). Conversely, we found low quality evidence of no effect on length of stay measured in days (MD, 0.39; 95% CI -0.59 to 1.36; P = 0.44). Although additional studies are required to decrease heterogeneity of the studies, the current review showed high FiO 2 does not decrease the incidence of SSI in the colorectal surgery population.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
A mixed-methods examination of autonomous sensory meridian response: Comparison to frisson. Autonomous Sensory Meridian Response (ASMR) is a pleasurable, head-oriented tingling sensation, typically induced by exposure to audiovisual triggers, producing feelings of relaxation and euphoria. This article explores the induction of ASMR experiences in a laboratory setting amongst non-specialised participants, as well as the relationship between ASMR and frisson, or 'musical chills'. In previous work, the ASMR-15 was found to be a reliable measure of ASMR propensity, however, the predictive validity of the measure has yet to be determined. The aim of this study was to assess whether ASMR-15 scores predict greater ASMR induction in an experimental setting. To address this, N = 100 undergraduate psychology students completed the ASMR-15 and a measure of frisson, before viewing ASMR stimuli under controlled conditions. Mixed-methods analyses indicated the successful induction of ASMR amongst some participants, convergence between ASMR-15 scores and video ratings, as well as divergence between ASMR and frisson scores.	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Prevalence of myocardial bridging associated with coronary endothelial dysfunction in patients with chest pain and non-obstructive coronary artery disease. Myocardial bridging (MB), characterised by the epicardial coronary vessel diving into the myocardium, is present in up to one third of adults and is associated with angina and acute coronary syndromes. MB is accompanied by altered blood flow mechanics and regional changes in wall sheer stress. The purpose of this study was to determine the association between myocardial bridging and coronary endothelial dysfunction.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Shortened G1 phase of cell cycle and decreased histone H3K27 methylation are associated with AKT-induced enhancement of primordial germ cell reprogramming. Primordial germ cells (PGCs) are reprogrammed into pluripotent embryonic germ cells (EGCs) under specific culture conditions, but the detailed mechanisms of PGC reprogramming have not yet been fully clarified. Previous studies have demonstrated that AKT, an important intracellular signaling molecule, promotes reprogramming of PGCs into EGCs. Because AKT likely inhibits p53 functions to enhance PGC reprogramming, and p53 negatively regulates cell cycle progression, we analyzed cell cycle changes in PGCs following AKT activation and found that the ratio of PGCs in the G1/G0 phase was decreased while that of PGCs in the G2/M phase was increased after AKT activation. We also showed that the expression of the CDK inhibitor p27kip1, which prevents the G1‐S transition and is transcriptionally activated by p53, was significantly downregulated by AKT activation. The results suggested that the characteristic cell cycle changes of PGCs by AKT activation are, at least in part, due to decreased expression of p27 kip1 . We also investigated changes in histone H3K27 tri-methylation (H3K27me3) by AKT activation in PGCs, because we previously found that decreased H3K27me3 was involved in PGC reprogramming via upregulation of cyclin D1. We observed that AKT activation in PGCs resulted in H3K27 hypomethylation. In addition, DZNeP, an inhibitor of the H3K27 trimethyl transferase Ezh2, stimulated EGC formation. These results together suggested that AKT activation promotes G1-S transition and downregulates H3K27me3 to enhance PGC reprogramming.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Mortality After Paclitaxel Coated Balloon Angioplasty and Stenting of Superficial Femoral and Popliteal Artery in the Vascular Quality Initiative. To compare mortality after treatment of superficial femoral-popliteal artery disease with paclitaxel and nonpaclitaxel devices using a multicenter vascular registry.	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Shining light on spindle positioning. Optogenetic approaches are leading to a better understanding of the forces that determine the plane of cell division.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Public policy on the prevention of subsequent adolescent pregnancy: what type of policy prevails? This study aims to conduct a search of public-policy instruments seeking explicit references to subsequent adolescent pregnancy, as well as to discern what kinds of actions have been proposed as part of the international and national agendas to facilitate subsequent adolescent pregnancy prevention and care. During June 2021, we used an integrative review to search and to analyze national and international public policy instruments along with other documents related to subsequent adolescent pregnancy. We observed, for each, the presence of statements on subsequent adolescent pregnancy. The research team was then divided into triads to discuss and to classify each reference under one of the following categories: (a) a symbolic statement, that is, an intention not implying a specific action but rather presenting a vision for the future; (b) a substantive-material statement concerning an action intended to solve a problem; and (c) a procedural-material statement indicating specific actions, processes, budgets, and actors. We analyzed a total of 135 public-policy documents: 102 in Mexico and 33 internationally. Only four national and six international documents contained either symbolic or substantive-material references to the subject of interest and only one specified a procedural-material statement. The prevention and care of subsequent adolescent pregnancy are addressed only secondarily on the public agendas. Only a minimal number of actions comprise specific and standardized measures to prevent subsequent adolescent pregnancy according to the different actors involved. Designing a greater number of procedural-material policies will help to reduce morbidity and mortality in the mother-child binomial and promote a comprehensive development of this population.	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Generation of Hepatic Stellate Cells from Human Pluripotent Stem Cells Enables In Vitro Modeling of Liver Fibrosis. The development of complex in vitro hepatic systems and artificial liver devices has been hampered by the lack of reliable sources for relevant cell types, such as hepatic stellate cells (HSCs). Here we report efficient differentiation of human pluripotent stem cells into HSC-like cells (iPSC-HSCs). iPSC-HSCs closely resemble primary human HSCs at the transcriptional, cellular, and functional levels and possess a gene expression profile intermediate between that of quiescent and activated HSCs. Functional analyses revealed that iPSC-HSCs accumulate retinyl esters in lipid droplets and are activated in response to mediators of wound healing, similar to their in vivo counterparts. When maintained as 3D spheroids with HepaRG hepatocytes, iPSC-HSCs exhibit a quiescent phenotype but mount a fibrogenic response and secrete pro-collagen in response to known stimuli and hepatocyte toxicity. Thus, this protocol provides a robust in vitro system for studying HSC development, modeling liver fibrosis, and drug toxicity screening.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
The influence of the interaction of sous-vide cooking time and papain concentration on tenderness and technological characteristics of meat products. The food industry has been slow in harnessing technological developments to expand opportunities and benefit the community. One such opportunity is in the application of proteolytic enzymes to the development of softer-textured meat products that require reduced mastication force, for those with impaired dentition, and reduced strength including older adults. Proteolytic enzymes haven't been fully explored for their potential in this area. Here a response surface methodology (RSM) was applied to model the interactive effects of sous-vide and papain application on texture, color, and cooking loss of meat. An innovative meat product formulation with a reduced toughness (120 min cooking sous-vide and 0.01 mg papain/100 g) was optimized and the technological performance of the formulation was validated. Bias values of the optimized model were in the range of 0.97 to 1.06, while accuracy factors for shear force values, chewiness, TPA hardness, cooking loss, color parameters ranged from 1.00 and 1.06, both of which metrics indicated the reliability of the resultant models.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Safety and Outcome of Carotid Dissection Stenting During the Treatment of Tandem Occlusions: A Pooled Analysis of TITAN and ETIS. The efficacy of endovascular therapy in patients with acute ischemic stroke due to tandem occlusion is comparable to that for isolated intracranial occlusion in the anterior circulation. However, the optimal management of acute cervical internal carotid artery lesions is unknown, especially in the setting of carotid dissection, but emergency carotid artery stenting (CAS) is frequently considered. We investigated the safety and efficacy of emergency CAS for carotid dissection in patients with acute stroke with tandem occlusion in current clinical practice.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
[The use of Gliathiline in patients with sensorineural hearing loss]. The results of treatment of 38 patients suffering from sensorineural hearing loss with the Gliatilin (solution 3 ml intravenously for 10 days, capsules 400 mg 3 times a day or solution for ingestion 600 mg 2 times a day for 3 months) are presented. All patients in dynamics were given a comprehensive audiological, neurological examination, as well as an assessment of psycho-emotional status and cognitive function. Subjective improvement of ear noise tolerance by patients by 40 days of observation and continuation of this trend during the whole period (100 days) outside of the form of the medicinal preparation is noted. A reliable improvement in the 50% speech intelligibility threshold by day 100 of observation was established in patients of both groups, with a tendency towards earlier (on day 70 of the study) onset of this effect when taking the drug inside as a solution. The Gliatilin has been proven to reduce anxiety and depression, as well as reliably improve cognitive function. Thus, Gliatilin (injection solution, ingestion solution, capsules) can be used to improve the subjective tolerance of ear noise, speech intelligibility and quality of life of patients in chronic sensorineural hearing loss.	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Using town watching technique to raise disaster awareness for different audiences. Communities need to be aware of all the risks and consequences of disasters, which have increased both in numbers, economic and human losses in the recent decades. This study aims to show how town watching technique has a positive effect in raising disaster awareness in different types of learning experiences for different target groups so that individuals understand the disaster risks and make plans to decrease their vulnerabilities. Application of town watching for two different target audiences are explained; undergraduate engineering major students, local government officials, and volunteer community members. Results of surveys conducted for an elective humanities course for engineering major undergraduates named disaster awareness are presented. Interviews with volunteers from other target groups who participated in community-based disaster capacity building projects are also included in this study. It can be clearly seen that town watching creates synergy while disaster awareness is internalized, and the participants learn about disasters, risks, and resources at hand that may also help toward the countries' resilience to disasters.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Seven-year study of monsoonal rainwater chemistry over the mid-Brahmaputra plain, India: assessment of trends and source regions of soluble ions. This work is a 7-year study of monsoonal rainwater chemistry (n = 302), over mid-Brahmaputra plain during 2012 to 2018. The samples were analyzed for major chemical parameters viz. pH, electrical conductivity (EC), and ions (SO 4 2- , NO 3 - , Br - , Cl - , F - , Mg 2+ , Ca 2+ , K + , NH 4 + , Na + , and Li + ) to assess the chemistry. The mean pH of rainwater varied among the years, which was maximum in 2018 (6.18 ± 0.72) and minimum in the year 2014 (5.39 ± 0.54), and the variations were significant at p < 0.0001. Ridgeline plots were drawn to visualize interannual variations, which revealed that Ca 2+ was the dominant cation in the early years, whereas NH 4 + prevailed in the latter years. Mann-Kendall analysis and Sen's slope statistical tests were employed, and it was found that all the ions showed positive S values indicating increasing trends. Enrichment factors (EF) of K + , SO 4 2- , and NO 3 - were found to be high with respect to both soil and seawater suggesting the influence of emissions from fossil fuel and biomass burning in the chemistry of rainwater. Principal component analysis (PCA) was applied to identify the sources of rain constituents, and five factors were obtained explaining crustal dust, biomass burning, fossil fuel combustion, agricultural emissions, and coal burning as possible sources. Airmass back trajectory clusters and Potential Source Contribution Function (PSCF) were computed by application of HYbrid Single-Particle Lagrangian Integrated Trajectory model to appreciate the terrestrial influence on the chemistry. The results indicated inputs from both local and regional dust and anthropogenic constituents that influenced the monsoonal rainwater chemistry over Brahmaputra Valley.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
The Role of DNA Looping in the Search for Specific Targets on DNA by Multisite Proteins. Many cellular processes involve simultaneous interactions between DNA and protein molecules at several locations. They are regulated and controlled by special protein-DNA complexes, which are known as synaptic complexes or synaptosomes. Because of the multisite nature of involved proteins, it was suggested that during the formation of synaptic complexes DNA loops might appear, but their role is unclear. We developed a theoretical model that allowed us to evaluate the effect of transient DNA loop formation. It is based on a discrete-state stochastic method that explicitly takes into account the free-energy contributions due to the appearance of DNA loops. The formation of the synaptic complexes is viewed as a search for a specific binding site on DNA by the protein molecule already bound to DNA at another location. It was found that the search might be optimized by varying the position of the target and the total length of DNA. Furthermore, the formation of transient DNA loops leads to faster dynamics if it is associated with favorable enthalpic contributions to nonspecific protein-DNA interactions. It is also shown that DNA looping might reduce stochastic noise in the system.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Functional characterization of partial recombinant goat conglutinin: Its role as innate immunity marker and use as antigen in sandwich ELISA. Conglutinin, a liver synthesized versatile innate immune marker consisting C-type lectin domain belongs to collectin superfamily of proteins. The protein, first detected in bovine serum as soluble pattern recognition receptor (PRR) has wide range of antimicrobial activities. In the present study, open reading frame (ORF) encoding neck and carbohydrate recognition domain (NCRD) of goat conglutinin gene ligated to the vector pRSET-A was expressed in E. coli BL-21(pLys) cells. The 27 kDa recombinant protein (rGCGN) purified by single step Ni +2 -NTA affinity chromatography was found to cross-react with recombinant anti-buffalo conglutinin antibody raised in poultry. Further, it displayed calcium-dependant sugar binding activity towards yeast mannan and calcium-independent binding activity towards LPS. The mannan binding activity of rGCGN was inhibited in the presence of N-acetyl-glucosamine because of higher affinity towards this sugar. The recombinant protein was found to stimulate production of superoxide ions and hydrogen peroxide in goat neutrophils, which are instrumental in stimulating phagocytic activity of cells. When used as antigen in Sandwich ELISA, straight line (Y = 0.299x + 0.067, R 2 = 0.997) was observed within the concentration range of 200-1000 ng/100 μl of rGCGN. Using this equation, the native conglutinin concentration in goat sera was estimated to be 0.5-7.5 μg/ml. The results indicated that prokaryotically expressed functionally active rGCGN can be used as antigen to assess native serum conglutinin levels in Sandwich ELISA and as immunomodulator in therapeutic applications to sequester unwanted immune complexes from the circulation.	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
mcIRBP-19 of Bitter Melon Peptide Effectively Regulates Diabetes Mellitus (DM) Patients' Blood Sugar Levels. This study was conducted to test the effectiveness of a particular bitter melon peptide (BMP), with a specific sequence of 19 amino acids (mcIRBP-19), in regulating diabetic patients' blood glucose. In order to test the product with the specially processed BMP, a total of 142 diabetic patients were solicited as study subjects, of which 64 were assigned to an experiment group and 78 to a control group. Biochemical data were compared with a paired t- test to verify the significance of changes over different time periods. The clinical results showed that BMP started to improve the subjects' glycated hemoglobin (HbA1c) levels at the end of the second month (T2), with mean values being significantly lowered from 7.8 ± 1.4% (T0) to 7.5 ± 1.4% (T2) ( p = 0.004). The values reduced continuously, eventually reaching 7.4 ± 1.1% ( p = 0.000) at the end of the experiment (T3). HbA1c levels for the control group were 7.5 ± 1.2% in T0 and 7.5 ± 1.1% (T3), and not significantly different ( p = 0.852) over the same period. This study provides clinical evidence that helps to verify the effectiveness of the new BMP product in regulating diabetic patients' blood sugar levels.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vγ4 γδ T Cells Provide an Early Source of IL-17A and Accelerate Skin Graft Rejection. Activated γδ T cells have been shown to accelerate allograft rejection. However, the precise role of skin-resident γδ T cells and their subsets-Vγ5 (epidermis), Vγ1, and Vγ4 (dermis)-in skin graft rejection have not been identified. Here, using a male to female skin transplantation model, we demonstrated that Vγ4 T cells, rather than Vγ1 or Vγ5 T cells, accelerated skin graft rejection and that IL-17A was essential for Vγ4 T-cell-mediated skin graft rejection. Moreover, we found that Vγ4 T cells were required for early IL-17A production in the transplanted area, both in skin grafts and in the host epidermis around grafts. Additionally, the chemokine (C-C motif) ligand 20-chemokine receptor 6 pathway was essential for recruitment of Vγ4 T cells to the transplantation area, whereas both IL-1β and IL-23 induced IL-17A production from infiltrating cells. Lastly, Vγ4 T-cell-derived IL-17A promoted the accumulation of mature dendritic cells in draining lymph nodes to subsequently regulate αβ T-cell function after skin graft transplantation. Taken together, our data reveal that Vγ4 T cells accelerate skin graft rejection by providing an early source of IL-17A.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Association between Gut Microbial Diversity and Carotid Intima-Media Thickness. Background and Objectives: There is an increasing focus on the effect of the gut microbiome on developing atherosclerosis, but there is still no unified standpoint. We aimed to find associations between intestinal microbiome diversity and a marker of subclinical atherosclerosis, the carotid intima-media thickness (IMT). Materials and Methods: Recruited from the Hungarian Twin Registry, 108 monozygotic (MZ) twins (mean age 52.4 ± 14.1 years, 58% female) underwent a comprehensive carotid ultrasound examination (Samsung RS85). Of the 108 MZ twins, 14 pairs (mean age 65 ± 6.4 years, 71% female) discordant for carotid IMT were selected to undergo a stool sample collection. A special stool sampling container was mailed and received from each participant. After DNA extraction, library construction was performed specifically for the V3-V4 hypervariable region of microbial 16S rRNA. Next, the microbiome composition of the samples was determined using Kraken software. Two hypotheses were tested with the exact permutation test: (1) in the group with normal IMT, the Shannon index of the phyla is higher; and (2) the Firmicutes/Bacteroidetes ratio is greater in the group with high IMT values. Furthermore, the abundance of different bacterial strains present at higher and normal IMT was also explored. Statistical analysis was carried out using R software. Results: Increased Firmicutes/Bacteroidetes ratio was associated with increased IMT (mean Firmicutes/Bacteroidetes ratio of IMT > 0.9 and IMT < 0.9 groups: 2.299 and 1.436, respectively; p = 0.031). In the group with normal IMT values, a substantially higher fraction of Prevotellaceae was observed in contrast with subjects having subclinical atherosclerosis. However, there was no significant difference in the alpha diversity between the two groups. Conclusions: The determining role of individual genera and their proportions in the development and progression of atherosclerosis can be assumed. Further studies are needed to clarify if these findings can be used as potential therapeutic targets.	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Removal of Migrating Lumbar Spine Bullet: Case Report and Surgical Video. Gunshot wounds to the spine are devastating injuries. Rarely, the bullet has been reported to migrate. Migration is associated with progressive neurologic deficits that often improve with bullet removal. The authors report a case of removal of a migrating lumbar spine bullet. This is supplemented by an operative video and a review of the literature.	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Sorafenib in patients with progressed and refractory bone tumors. Patients with metastatic, progressive, or recurrent bone tumors have a dismal outcome. Sorafenib has been proposed as an effective salvage regimen for some malignancies. Thus, we sought to evaluate this approach for young patients with relapsed or refractory bone tumors. Twelve patients with refractory bone tumors (two with Ewing sarcoma, two with chondrosarcoma, and eight with osteosarcoma) received salvage treatment with sorafenib. All patients had standard tumor imaging and laboratory evaluation. All toxicities were documented. At the time of the beginning of sorafenib treatment median age among 12 patients was 18 years (range 4.1-27.9 years), eight were male, and eight had osteosarcoma. All received sorafenib because of relapse. Seven patients were treated parallel to other standard chemotherapy. Overall response rate was 75%. Median time to sorafenib time to progression for patients with osteosarcoma was 4 months (range 1.8-7.9 months). Four patients (33%) are alive, in that two with no evidence of disease with a median follow-up of 41 months (range 26.5-60.9 months). The estimated 5 year overall survival (OS) for the whole group was 64.49%. There were no serious toxicities. Sorafenib is well-tolerated in young patients with bone tumors, and particularly could be an option for patients with metastatic disease and refractory osteosarcoma. Sorafenib only allows to extend OS and different procedures are needed to achieve permanent remission. This regimen deserves further investigation in the upfront management of patients with high-risk bone tumors.	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Engineering immunity via skin-directed drug delivery devices. Extensive research is underway to discover a safe and effective vehicle to deliver the vaccines at the desired cutaneous site. These efforts majorly comprise the development of a fit-to-purpose vehicle for in-situ intracutaneous vaccine delivery for achieving the systemic cellular and humoral response to combat infectious diseases. Advancements in nanoscience, bioengineering, and skin science provided much support to vaccine adjuvant development. However, the bench-to-bed side translation of vaccines is still unsatisfactory. A skilfully designed vaccine delivery program aiming to translate the product into market use must address safety, efficacy, scaleup, reproducibility, cost of production, self-administrative potential, and regulatory concerns. This review provides deep insights into skin immunization approaches like mucosal vaccines, cellular/molecular immunological responses, and antigen-adjuvant combinations in modulating immunity. Further, the manuscript discusses distinct vaccine delivery systems used to date for engineering skin immunization, including microparticles, nanoparticles, spherical nucleic acids, STAR particles, niosomes, dendrimers, ethosomes, liposomes, and microneedles. The manuscript will interest researchers working towards developing a next-generation fit-to-purpose vehicle for intracutaneous vaccine delivery.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
A Complementary Intervention to Promote Wellbeing and Stress Management for Early Career Teachers. The educational climate and culture in our schools present a variety of environmental (contextual) factors that influence teacher wellbeing, job satisfaction, and work-related stress. The magnitude of contextual factors cannot be ignored, and directing attention towards the environment teachers face daily is essential. Primary (organisational)-level interventions are documented in organisational health and wellbeing literature; however, to provide teachers with stress management strategies for promoting wellbeing, attention must also be directed towards secondary (individual)-level interventions. The present study addressed the issue of stress management techniques for early career teachers ( n = 24) and aimed to contribute to the research surrounding complementary interventions (CIs) for educators. The intervention was designed to include strategies that operated through cognitive and physiological mechanisms that regulated the stress response and increased awareness of behaviours, emotions, and reactivity. The self-report measures included perceived stress, attention awareness, subjective wellbeing, burnout, and job-related affective wellbeing. The results indicated a statistically significant decrease in perceived stress and increases in attention awareness and subjective wellbeing. The salivary cortisol levels (waking and resting) decreased from baseline to week 6, and the pre- and post-session salivary cortisol levels indicated an immediate decrease in cortisol for weeks 4 to 6.	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
[Screening of periodontal and salivary parameters in patients with frequent acute exacerbation of chronic obstructive pulmonary disease]. Objective: To screen the risk factors of patients with frequent acute exacerbation of chronic obstructive pulmonary disease (COPD) by detecting the clinical indicators of periodontitis and the level of bacterial and inflammatory markers in saliva. Methods: Thirty-eight COPD patients in their stable period were recruited and detected from Beijing Chao-Yang Hospital,Capital Medical University during December 2016 to May 2017. The periodontal index were recorded. The levels of inflammatory factors in saliva samples were examined by using enzyme linked immunosorbent assay (ELISA). The bacteria composition in the saliva samples were identified by using 16SrRNA gene pyrosequencing. All patients were followed up and monitored for acute exacerbation of COPD for 12 months. The patients were divided into frequent acute exacerbation group (≥2 times/year, n= 10) and non frequent acute exacerbation group (<2 times/year, n= 28). Results: In univariate analysis, the patients' average age of frequent acute exacerbation group (69.0±7.3) was significantly older than that of non-frequent acute exacerbation group (61.8±8.3) ( P= 0.02). The numbers of remaining teeth ≤26 [100% (10/10)] was significantly higher and plaque index ≤2.5 (2/10) in frequent acute exacerbation group was significantly lower compared with the remaining teeth ≤26 [43% (12/28)] and the plaque index ≤2.5 [71% (21/28)] in non-frequent acute exacerbation group ( P =0.02, P= 0.01). The proportions of salivary inflammatory factors interleukin-6 (IL-6) level ≤60 ng/L (10%),C-reactive protein (CRP) level ≤1 550 μg/L (30%), matrix metalloproteinase-8 (MMP-8) level ≤140 μg/L (30%) and fibrinogen level ≤90 mg/L (30%) in frequent acute exacerbation group were significantly lower compared with salivary inflammatory factors IL-6 level ≤60 ng/L (71%),CRP level ≤1 550 μg/L (71%), MMP-8 level ≤140 μg/L (86%) and fibrinogen level ≤90 mg/L (71%) in non-frequent acute exacerbation group ( P< 0.05). The differences of relative abundances of salivary bacteria,such as species of Chloroflexi, Anaerolineae, Anaeroales, Corynebacteriales, Anaerolineaceae, Tissierellaceae, Leptotrichiaceae, Corynebacteriaceae, Leptotrichia, Moryella, Lachnoanaerobaculum and Corynebacterium between frequent acute exacerbation group and non-frequent acute exacerbation group were significantly different ( P< 0.05). In multivariate logistics regression analysis,the level of IL-6 >60 ng/L and the relative abundance of Corynebacteriales >0.2 had significant difference ( P< 0.05). Conclusions: The level of IL-6 and the relative abundance of Corynebacteriales might be the markers of frequent acute exacerbation in COPD patients.	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
The stringent response of marine bacteria - assessment of (p)ppGpp accumulation upon stress conditions. Microorganisms are particularly adapted to alterations in their environment. One of the global regulatory mechanisms involved in these adaptations is the stringent response. The unusual nucleotides, guanosine penta and tetraphosphates, (p)ppGpp act as alarmones of this response, heralding nutrient limitation and stressors. Marine bacteria encounter numerous stresses of sparse nutrient supplies and changes in physicochemical conditions. The aim of this work was to assess whether the stress conditions common in marine environment can induce the stringent response and what is a kinetic of this process. The representative bacterial species, Shewanella baltica, Acinetobacter johnsonii, Vibrio harveyi, and Escherichia coli were subjected to a variety of stressors. We analyzed the kinetics of (p)ppGpp synthesis by labeling in vivo nucleotides and analysis by thin layer chromatography. The (p)ppGpp accumulation followed the elevated temperature and amino acid starvation for all bacteria tested. The carbon and nitrogen limitation resulted in the response limited to V. harveyi and S. baltica. The DNA damaging agents induced the (p)ppGpp production in all strains, while osmotic stress did not result in significant alarmone synthesis. The representative marine bacteria species were shown to induce with varying extent the stringent response upon the onset of stress and limitation conditions. Importantly, the in vivo labeling and subsequent separation of the nucleotides by thin layer chromatography serves as a valid method for the analysis of the stringent response and (p)ppGpp accumulation in environmental bacteria.	1	0	1	0	0	0	0	0	0	1	0	0	0	0	1	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
PEGylation-Dependent Metabolic Rewiring of Macrophages with Silk Fibroin Nanoparticles. Silk fibroin nanoparticles are emerging as promising nanomedicines, but their full therapeutic potential is yet to be realized. These nanoparticles can be readily PEGylated to improve colloidal stability and to tune degradation and drug release profiles; however, the relationship between silk fibroin nanoparticle PEGylation and macrophage activation still requires elucidation. Here, we used in vitro assays and nuclear magnetic resonance based metabolomics to examine the inflammatory phenotype and metabolic profiles of macrophages following their exposure to unmodified or PEGylated silk fibroin nanoparticles. The macrophages internalized both types of nanoparticles, but they showed different phenotypic and metabolic responses to each nanoparticle type. Unmodified silk fibroin nanoparticles induced the upregulation of several processes, including production of proinflammatory mediators (e.g., cytokines), release of nitric oxide, and promotion of antioxidant activity. These responses were accompanied by changes in the macrophage metabolomic profiles that were consistent with a proinflammatory state and that indicated an increase in glycolysis and reprogramming of the tricarboxylic acid cycle and the creatine kinase/phosphocreatine pathway. By contrast, PEGylated silk fibroin nanoparticles induced milder changes to both inflammatory and metabolic profiles, suggesting that immunomodulation of macrophages with silk fibroin nanoparticles is PEGylation-dependent. Overall, PEGylation of silk fibroin nanoparticles reduced the inflammatory and metabolic responses initiated by macrophages, and this observation could be used to guide the therapeutic applications of these nanoparticles.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Health-care resource use and current treatment of adult atopic dermatitis patients in Japan: A retrospective claims database analysis. The real-world evidence on the profiles of patients suffering from atopic dermatitis (AD) in Japan is sparse. A retrospective claim database analysis was conducted to estimate the health-care resource use (HCRU) and current AD treatment. Data from October 2013 to September 2016 were extracted from the JMDC (Tokyo, Japan) claims database. HCRU was assessed by a comparison of AD patients and matched non-AD controls. A multivariate analysis was performed to estimate HCRU attributable to AD. AD patients (n = 39 893) have more claims of certain diagnoses such as rhinitis, viral and fungal infections, sleep disorders and conjunctivitis as well as higher HCRU (outpatient visits, prescriptions of AD-related and non-AD-related medications, phototherapy, laboratory tests) than matched non-AD controls (n = 39 893). Treatment pattern analysis included treatment-naive patients (n = 8478) and previously treated AD patients (n = 30 109). Approximately 20% of previously treated patients were on the continuous systemic treatment during 18-month follow up. Systemic corticosteroids were the most frequently used systemic treatments. Oral cyclosporin was less frequently used in both groups, but for the longest duration. Almost half of previously treated patients with oral cyclosporin continued treatment for more than 3 months. In conclusion, HCRU was higher in AD patients than non-AD controls, indicating a high burden of the disease imposed on AD patients. Continuous administration of systemic treatment, such as oral cyclosporin, systemic corticosteroids and phototherapy, observed in AD patients sheds light on the difficulties of managing AD in Japanese clinical practise.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Microenvironment remodeled by tumor and stromal cells elevates fibroblast-derived COL1A1 and facilitates ovarian cancer metastasis. Wide peritoneal metastasis is the cause of the highest lethality of ovarian cancer in gynecologic malignancies. Ascites play a key role in ovarian cancer metastasis, but involved mechanism is uncertain. Here, we performed a quantitative proteomics of ascites, and found that collagen type I alpha 1 (COL1A1) was notably elevated in ascites from epithelial ovarian cancer patients compared to normal peritoneal fluids, and verified that elevated COL1A1 was mainly originated from fibroblasts. COL1A1 promoted migration and invasion of ovarian cancer cells, but such effects were partially eliminated by COL1A1 antibodies. Intraperitoneally injected COL1A1 accelerated intraperitoneal metastasis of ovarian cancer xenograft in NOD/SCID mice. Further, COL1A1 activated downstream AKT phosphorylation by binding to membrane surface receptor integrin β1 (ITGB1). Knockdown or blockage of ITGB1 reversed COL1A1 enhanced migration and invasion in ovarian cancer cells. Conversely, ovarian cancer ascites and fibrinogen promoted fibroblasts to secrete COL1A1. Elevated fibrinogen in ascites might be associated with increased vascular permeability induced by ovarian cancer. Our findings suggest that microenvironment remodeled by tumor cells and stromal cells promotes fibroblasts to secrete COL1A1 and facilitates the metastasis of ovarian cancer, which may provide a new approach for ovarian cancer therapeutics.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Acute myeloid leukaemia presenting as proptosis in an infant. Paediatric patients with acute myeloid leukaemia (AML) often present with symptoms associated with the disruption of normal haematopoiesis and subsequent cellular deficiencies. Periosteal reactions are common in paediatric leukaemia, but typically manifest as a thin, laminated pattern along long bones. Aggressive periosteal reactions are much less frequently seen. Here, we report a case of paediatric AML initially presenting with proptosis and periorbital swelling caused by aggressive, sunburst periosteal reactions surrounding the sphenoid and zygomatic bones. This unique presentation emphasises the importance of considering leukaemic infiltration in the differential for sunburst periosteal reaction in paediatric patients.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Improved Whole-Genome Sequence of Phytophthora capsici Generated by Long-Read Sequencing. The soilborne oomycete Phytophthora capsici is the most destructive pathogen of vegetable crops and is responsible for substantial economic losses worldwide. Here, we present an improved genome assembly of P. capsici generated by Oxford Nanopore long-read sequencing (for de novo assembly) and Illumina short-read sequencing (for polishing). The genome of P. capsici is 100.5 Mb in length (GC content = 50.8%) and contains 26,069 predicted protein-coding genes. The whole genome of P. capsici is assembled into 194 scaffolds, 90% of which are larger than 300 kb. The N 50 scaffold length and maximum scaffold length are 1.0 and 4.1 Mb, respectively. The whole-genome sequence of P. capsici will broaden our knowledge of this pathogen and enhance our understanding of the molecular basis of its pathogenicity, which will facilitate the development of effective management strategies.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
A survey on patients medication reconciliation process in an oncological hospital. The purpose of this study was to assess the impact of medication reconciliation in the clinical practice from a hospital pharmacist point of view.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Phi class glutathione transferases as molecular targets towards multiple-herbicide resistance: Inhibition analysis and pharmacophore design. Multiple-herbicide resistance (MHR) is a global threat to weed control in cereal crops. MHR weeds express a specific phi class glutathione transferase (MHR-GSTF) that confers resistance against multiple herbicides and therefore represents a promising target against MHR weeds. Kinetics inhibition analysis of MHR-GSTFs from grass weeds Lolium rigidum (LrGSTF) Alopecurus myosuroides (AmGSTF) and crops Hordeum vulgare (HvGSTF) and Triticum aestivum (TaGSTF) allowed the identification of the acetanilide herbicide butachlor as a potent and selective inhibitor towards MHR-GSTFs. Also, butachlor is a stronger inhibitor for LrGSTF and AmGSTF compared to HvGSTF and TaGSTF from crops. The crystal structure of LrGSTF was determined at 1.90 Å resolution in complex with the inhibitor S-(4-nitrobenzyl)glutathione. A specific 3D pharmacophore targeting the MHR-GSTFs was designed and used to identify structural elements important for potent and selective inhibition. Structural analysis of GSTFs revealed a decisive role of conserved Tyr118 in ligand binding and pharmacophore design. Its positioning is dependent on an outer patch of adjacent residues that span from position 132 to 134 which are similar for both LrGSTF and AmGSTF but different in HvGSTF and TaGSTF. The results presented here provide new knowledge that may be adopted to cope with MHR weeds.	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Biometry data and prevalence of corneal astigmatism in caucasian spanish candidates for cataract surgery. To describe ocular biometric parameters and the prevalence of corneal astigmatism as well as age and gender correlations in a population of cataract surgery candidates and to estimate the number of eyes that would be candidates for a toric intraocular lens (IOL).	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
High-Performance Liquid Chromatography Method for Rich Pharmacokinetic Sampling Schemes in Translational Rat Toxicity Models With Vancomycin. A translational need exists to understand and predict vancomycin-induced kidney toxicity. We describe: (i) a vancomycin high-performance liquid chromatography (HPLC) method for rat plasma and kidney tissue homogenate; (ii) a rat pharmacokinetic (PK) study to demonstrate utility; and (iii) a catheter retention study to enable future preclinical studies. Rat plasma and pup kidney tissue homogenate were analyzed via HPLC for vancomycin concentrations ranging from 3-75 and 15.1-75.5 μg/mL, respectively, using a Kinetex Biphenyl column and gradient elution of water with 0.1% formic acid: acetonitrile (70:30 v/v). Sprague-Dawley rats (n = 10) receiving 150 mg/kg of vancomycin intraperitoneally had plasma sampled for PK. Finally, a catheter retention study was performed on polyurethane catheters to assess adsorption. Precision was <6.1% for all intra-assay and interassay HPLC measurements, with >96.3% analyte recovery. A two-compartment model fit the data well, facilitating PK exposure estimates. Finally, vancomycin was heterogeneously retained by polyurethane catheters.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Development and internal validation of PI-RADs v2-based model for clinically significant prostate cancer. Our objective is to build a model based on Prostate Imaging Reporting and Data System version 2 (PI-RADs v2) and assess its accuracy by internal validation.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0