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36196476 | Events at the Interface: How Do Interfaces Modulate the Dynamics and Functionalities of Guest Molecules? | Chemical and biological interfaces are of various types, which could be between two materials of the same and/or different states, two phases of the same material, biological substrates and the outer environment, surfactant or polymeric membranes and the bulk, and so forth. Small-molecule guests frequently interact with such interfaces that decide their functionalities. The structural and behavioral properties undergo considerable characteristic changes, which control their final course of action in the targeted application. This Perspective will discuss mainly the chemical interfaces constituted by the surfactants, polymers, lipids, and nucleic acids and their impacts on the dynamics of small-molecule guests. Some specific and interesting phenomena and future prospects will be elucidated in this Perspective. |
36196477 | The emperor has no clothes: a synthesis of findings from the Transformative Research on the Alcohol industry, Policy and Science research programme. | The Transformative Research on the Alcohol industry, Policy and Science (TRAPS) programme investigates the alcohol industry, with an innovative focus on public health sciences. TRAPS adds to an under-developed literature on the study of alcohol industry influence on alcohol science and policymaking. This paper provides a synthesis of TRAPS findings to inform future research. |
36196478 | Isolating the impact of antipsychotic medication on metabolic health: Secondary analysis of a randomized controlled trial of antipsychotic medication versus placebo in antipsychotic medication naïve first-episode psychosis (the STAGES study). | Cardiovascular and metabolic diseases are the leading contributors to the early mortality associated with psychotic disorders. To date, it has not been possible to disentangle the effect of medication and non-medication factors on the physical health of people with a first episode of psychosis (FEP). This study aimed to isolate the effects of antipsychotic medication on anthropometric measurements, fasting glucose and lipids. |
36196479 | Stimulation of naïve B cells with a fusion protein consisting of FlaA and Bet v 1 induces regulatory B cells ex vivo. | The experimental fusion protein rFlaA:Betv1 was shown to efficiently suppress allergen-specific sensitization in mice. However, the detailed mechanism of rFlaA:Betv1-mediated immune modulation is not fully understood. In this study, we investigated the effect of rFlaA:Betv1 on naïve murine B cells. |
36196480 | Silver Nanoparticle-Decorated Multiwalled Carbon Nanotube Ink for Advanced Wearable Devices. | Silver nanoparticles of average size 12-13 nm were successfully decorated on the surface of multiwalled carbon nanotubes (MWCNTs) through a scalable wet chemical method without altering the structure of the MWCNTs. Employing this Ag@MWCNT, a multifunctional room-temperature curable conductive ink was developed, with PEDOT:PSS as the conductive binder. Screen printing of the ink could yield conductive planar traces with a 9.5 μm thickness and a conductivity of 28.99 S/cm, minimal surface roughness, and good adhesion on Mylar and Kapton. The versatility of the ink for developing functional elements for printed electronics was demonstrated by fabricating prototypes of a wearable strain sensor, a smart glove, a wearable heater, and a wearable breath sensor. The printed strain sensor exhibited a massive sensing range for wearable applications, including an impressive 1332% normalized resistance change under a maximum stretchability of 23% with superior cyclic stability up to 10 000 cycles. The sensor also exhibited an impeccable gauge factor of 142 for a 5% strain (59 for 23%). Furthermore, the sensor was integrated into a smart glove that could flawlessly replicate a human finger's gestures with a minimal response time of 225-370 ms. Piezoresistive vibration sensors were also fabricated by printing the ink on Mylar, which was employed to fabricate a smart mask and a smart wearable patch to monitor variations in human respiratory and pulmonary cycles. Finally, an energy-efficient flexible heater was fabricated using the developed ink. The heater could generate a uniform temperature distribution of 130 °C at the expense of only 393 mW/cm |
36196481 | Analysis of the association between MICA gene polymorphisms and schizophrenia. | The major plex (MHC) has been implicated in schizophrenia. This study aimed to explore the correlation between the major plex class I polypeptide-related sequence A (MICA) polymorphisms and schizophrenia. |
36196483 | Trabectedin use in soft-tissue sarcoma patients in a real-world setting: Data from an Italian national drug-access registry. | Trabectedin is a marine-derived anticancer drug approved for the treatment of patients with advanced soft-tissue as (STS). Here, we aimed to analyze its use in a large cohort of STS patients treated in Italy in a real-world setting. Data on STS patients treated with trabectedin in Italy were prospectively collected from January 2013 to December 2019 by the national drug regulator, the Italian Medicines Agency (AIFA). Time-to-off-treatment (TToT) was defined as the time between the initial prescription of trabectedin and the date of treatment discontinuation for any cause. The impact of the different baseline covariates, including the initial prescribed dose of trabectedin, on TToT was evaluated using an accelerated failure time (AFT) models with log-logistic distribution. In total, we analyzed data from 2633 a patients and 14 950 individual cycles of trabectedin. The median number of cycles of trabectedin received per patient was 3 (interquartile range 2-7). The labeled 1.5 mg/sqm dose was used in 27.3% of all first prescriptions. Overall, the median TToT was 93 days. In the final AFT model, the variables significantly associated to longer TToT were female gender (+13% increase in TToT); ECOG performance status 0 (+50%); histological diagnosis of a (+22%), well-differentiated/dedifferentiated a (+72%) or myxoid a (+61%); receiving treatment in a high-volume center (+23%). In this large real-world cohort of STS patients treated with trabectedin, our findings support the use of trabectedin in STS patients, in particular in a and a patients, and highlight the role of treatment center volume in their management. |
36196484 | Biodegradable Smart Face Masks for Machine Learning-Assisted Chronic Respiratory Disease Diagnosis. | Utilizing smart face masks to monitor and analyze respiratory signals is a convenient and effective method to give an early warning for chronic respiratory diseases. In this work, a smart face mask is proposed with an air-permeable and biodegradable self-powered breath sensor as the ponent. This smart face mask is easily fortable to use, eco-friendly, and has sensitive and stable output performances in real wearable conditions. To verify the practicability, we use smart face masks to record respiratory signals of patients with chronic respiratory diseases when the patients do not have obvious symptoms. With the assistance of the machine learning algorithm of the bagged decision tree, the accuracy for distinguishing the healthy group and three groups of chronic respiratory diseases (asthma, bronchitis, and chronic obstructive pulmonary disease) is up to 95.5%. These results indicate that the strategy of this work is feasible and may promote the development of wearable health monitoring systems. |
36196485 | Incidence of cancer among Nordic police officers. | Police work may expose officers to various circumstances that have potential for increasing their risk of cancer, including traffic-related air pollution, night shift work and radiation from radars. In this study, we examined the incidence of cancer among Nordic male and female police officers. We utilize data from the Nordic Occupational Cancer (NOCCA) project, which linked census data on occupations from Finland, Iceland, Norway and Sweden to national cancer registries for the period 1961 to 2005. We report standardized incidence ratios (SIR) and 95% confidence intervals (CI) of selected cancers for each country by sex, age and calendar period. The cohort included 38 523 male and 1998 female police officers. pared with the general population, male police officers had a 7% (95% CI: 4-9%) excess cancer risk, with elevated SIRs for various cancer sites, including prostate (SIR 1.19, 1.14-1.25), breast (SIR 1.77, 1.05-2.80), colon (SIR 1.22, 1.12-1.32) and skin melanoma (SIR 1.44, 1.28-1.60). Conversely, male police officers had a lower risk of lung cancer than the general population (SIR 0.72, 0.66-0.77). In female police officers, the SIR for cancer overall was 1.15 (0.98-1.34), and there was a slight excess of cancers of the breast (SIR 1.25, 0.97-1.59) and colon (SIR 1.21, 0.55-2.30). In conclusion, cancer incidence among the police officers was slightly higher than in the general population. Notably, SIRs were elevated for cancer sites potentially related to night shift work, namely colon, breast and prostate cancer. |
36196486 | Detection of circulating tumour DNA after neoadjuvant chemoradiotherapy in patients with locally advanced oesophageal cancer. | Active surveillance instead of standard surgery after neoadjuvant chemoradiotherapy (nCRT) has been proposed for patients with oesophageal cancer. Circulating tumour DNA (ctDNA) may be used to facilitate selection of patients for surgery. We show that detection of ctDNA after nCRT seems highly suggestive of major residual disease. Tumour biopsies and blood samples were taken before, and 6 and 12 weeks after, nCRT. Biopsies were analysed with regular targeted next-generation sequencing (NGS). Circulating cell-free DNA (cfDNA) was analysed using targeted NGS with unique molecular identifiers and digital polymerase chain reaction. cfDNA mutations matching pre-treatment biopsy mutations confirmed the presence of ctDNA. In total, 31 patients were included, of whom 24 had a biopsy mutation that was potentially detectable in cfDNA (77%). Pre-treatment ctDNA was detected in nine of 24 patients (38%), four of whom had incurable disease progression before surgery. Pre-treatment ctDNA detection had a sensitivity of 47% (95% CI 24-71) (8/17), specificity of 85% (95% CI 42-99) (6/7), positive predictive value (PPV) of 89% (95% CI 51-99) (8/9), and negative predictive value (NPV) of 40% (95% CI 17-67) (6/15) for detecting major residual disease (>10% residue in the resection specimen or progression before surgery). After nCRT, ctDNA was detected in three patients, two of whom had disease progression. Post-nCRT ctDNA detection had a sensitivity of 21% (95% CI 6-51) (3/14), specificity of 100% (95% CI 56-100) (7/7), PPV of 100% (95% CI 31-100) (3/3), and NPV of 39% (95% CI 18-64) (7/18) for detecting major residual disease. The addition of ctDNA to the current set of diagnostics did not lead to more patients being clinically identified with residual disease. These results indicate that pre-treatment and post-nCRT ctDNA detection may be useful in identifying patients at high risk of disease progression. The addition of ctDNA analysis to the current set of diagnostic modalities may not improve detection of residual disease after nCRT. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. |
36196487 | Controversial role of mast cells in NSCLC tumor progression and angiogenesis. | Mast cells (MCs) are multifunctional immune cells implicated in both physiological and pathological processes. Among the latter, MCs play a crucial role in cancer. Many studies have shown a correlation between MCs and tumor progression in several solid and hematological malignancies. In particular, MCs can directly promote tumor growth via c-kit/stem cell factor-dependent signaling and via the release of histamine, which modulate tumor growth through H1 and H2 receptors. At the same time, MCs can increase tumor progression by stimulating angiogenesis via both proangiogenic cytokines stored in their cytoplasm, and by acting on the tumor microenvironment and extracellular matrix. With regard to NSCLC, the role of MCs has not yet been established, with studies showing a correlation with a poor prognosis on the one hand and suggesting a protective effect of MCs on the other hand. These controversial evidences are at least, in part, due to the heterogeneity of the studies exploring the role of MCs in NSCLC, with some studies describing only the MC count without specification of the activation and degranulation state, and without reporting the intratumoral localization and the proximity to other immune and cancer cells. A better knowledge of the role of MCs in NSCLC is mandatory, not only to define their prognostic and predictive proprieties but also because targeting them could be a possible therapeutic strategy. |
36196488 | Cumulative consumption of tea is associated with lower risk of liver cancer: Updated results from the Shanghai Women's Health Study. | Prospective epidemiological studies have provided limited evidence for an association between tea consumption and liver cancer risk. Based on a population-based prospective cohort study in middle-aged Chinese women, we investigated the association between tea consumption and the risk of primary liver cancer. Detailed information on tea drinking habits and other potential confounders was obtained at the baseline interview. Incident liver cancer cases were identified through record linkage with the population-based cancer registry and verified through home visits and review of medical charts by medical experts. Multiple aspects of tea drinking habits including starting age, duration, intensity and cumulative consumption of any type of tea and green tea were considered. Multivariable-adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs) were derived from the Cox regression models. After a median follow-up time of 18.12 (interquartile range = 1.59) years, 253 incident liver cancer cases were identified from 71 841 cohort members. Compared with never tea drinkers, the risk of liver cancer for participants who have consumed over 30 kg of dried tea leaves cumulatively was 0.56 (95% CI: 0.32-0.97). For those who drank green tea only, the aHR was 0.54 (95% CI: 0.30-0.98). This updated study suggested an inverse association between cumulative consumption of tea, especially green tea and the risk of primary liver cancer. |
36196489 | Personal comorbidities and their subsequent risks for liver, gallbladder and bile duct cancers. | Many environmental risk factors for hepatobiliary cancers are known but whether they are associated with specific cancer types is unclear. We present here a novel approach of assessing standardized incidence ratios (SIRs) of previously orbidities for hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cholangiocarcinoma (CCA) and ampullary cancer. The orbidities included alcohol and nonalcohol related liver disease, chronic obstructive pulmonary disease, gallstone disease, viral and other kinds of hepatitis, infection of bile ducts, hepatic and other autoimmune diseases, obesity and diabetes. Patients were identified from the Swedish Inpatient Register from 1987 to 2018, and their cancers were followed from 1997 onwards. SIRs for HCC were 80 to 100 in men and women diagnosed with hepatitis C virus and they were also >10 in patients diagnosed with hepatitis B virus, other kind of hepatitis, hepatic autoimmune disease and nonalcohol related liver disease. Many of these risks, as well as alcohol related liver disease, were either specific to HCC or were shared with intrahepatic CCA. For GBC, CCA and ampullary cancer infection of bile ducts was the main risk factor. Gallstone disease, nonhepatic autoimmune diseases and diabetes were associated with all hepatobiliary cancers. The limitations of the study include inability to cover some rare risk factors and limited follow-up time. Many of the orbidities are characterized by chronic inflammation and/or overt immune disturbance in autoimmune diseases. The results suggest that local chronic inflammation and a related immune disturbance is the carcinogenic trigger for all these cancers. |
36196490 | Performance comparison of two nucleic acid amplification systems for SARS-CoV-2 detection: A multi-center study. | Many rapid nucleic acid testing systems have emerged to halt the development and spread of COVID-19. However, so far relatively few studies pared the diagnostic performance between these testing systems and conventional detection systems. Here, we performed a retrospective analysis to evaluate the clinical detection performance between SARS-CoV-2 rapid and conventional nucleic acid detection system. |
36196498 | Genetic diversity and thermotolerance in Holstein cows: Pathway analysis and marker development using whole-genome sequencing. | Heat stress causes extensive losses in the dairy sector, due to negative effects on milk production and reproduction. Cows have evolved a series of protective mechanisms, (physiological, biochemical, behavioural) to cope with the thermostressing environments, which have allowed the preservation of productive and reproductive potential of specific animals during summer; these animals are considered thermotolerant and could be used to design programs of selective breeding. These programs, targeting the generations of a population of heat-resistant animals, would increase the frequency of the desired phenotypes, tackling the financial losses on one hand and reducing the carbon footprints of the dairy sector on the other. The development of genomics techniques has enabled genome wide variant calling, to detect SNPs associated with the desired phenotypes. In this study, we used parative genomics approach to detect genetic variation associated with thermotolerance and to design molecular markers for characterizing the animals as tolerant/sensitive. A total of 40 cows from each group were split in four sequencing pools and a whole-genome sequencing approach was used. Results and conclusion: Genome-wide genetic variation between groups was characterized and enrichment analysis revealed specific pathways which participate in the adaptive mechanisms of thermotolerance, implicated into systemic and cellular responses, including the immune system functionality, Heat Stress and Unfolded Protein Response. The markers made a promising set of results, as specific SNPs in five genes encoding for Heat Shock Proteins were significantly associated with thermotolerance. |
36196499 | Understanding pain related to adjuvant endocrine therapy after breast cancer: A qualitative report. | Most patients report pain while taking adjuvant endocrine therapy (AET) for the treatment of breast cancer. While studies have examined patients' experiences with side effects, none solely capture patients' experiences with AET-related pain, a troubling symptom that reduces quality of life and impairs treatment adherence. This study explored themes of AET-related pain to inform future intervention development. |
36196501 | Resilience, and positive parenting in parents of children with syndromic autism and intellectual disability. Evidence from the impact of the COVID-19 pandemic on family's quality of life and parent-child relationships. | Family quality of life (FQoL) es collected during the first year of COVID-19 has bined with 2018 data to estimate the outbreak's impact on parental es on a sample of 230 families with syndromic autistic children and those with intellectual disabilities (IDs). Despite challenges imposed by the COVID-19 outbreak, our study found that FQoL es reported by participating parents during the first year of COVID-19 appears to be similar to ratings from a prepandemic study of families with the same conditions. Parents of children in our sample generally displayed a stable functioning trajectory as measured by the validated FQoL instrument. Across syndromic autistic groups considered, families reported that their relationships with their children were positive. Our findings provide evidence of families' resilience which might explain the presence of positive parent-child interactions during COVID-19. Exploring mechanisms which would explain how families with autistic and ID children confront, manage disruptive experiences, and buffer COVID-19 induced stress is a fruitful direction for future research. |
36196502 | Primary Anal Cancer Screening Results From 381 Women With Human Immunodeficiency Virus. | Women with human immunodeficiency virus (WWH) have an elevated risk for human papillomavirus (HPV)-associated anal cancer. Primary anal cancer screening results from this population could inform practice guidelines. |
36196503 | The use of subchondral bone topography to approximate the center of rotation of the elbow joint in dogs. | The aim of this study was pare the approximate center of rotation in normal and diseased elbows in dogs. |
36196504 | Synthesis of Vinylene-Linked Thiopyrylium-, Pyrylium-, and Pyridinium-Based Covalent Organic Frameworks by Acid-Catalyzed Aldol Condensation. | The development of new vinylene-linked covalent organic frameworks (COFs) with special ionic structure and high stability is challenging. Herein, we report a facile, general method for constructing ionic vinylene-linked thiopyrylium-based COFs from 2,4,6-trimethylpyrylium tetrafluoroborate and mon reagents by means of acid-catalyzed Aldol condensation. Besides, pyrylium-, and pyridinium-based COFs also can be prepared from the same monomer under slightly different reaction conditions. The COFs exhibited uniform nanofibrous morphologies with excellent crystallinities, special ionic structures, well-defined nanochannels, and high specific surface areas. |
36196505 | Can immune gene silencing via dsRNA feeding promote pathogenic viruses to control the globally invasive Argentine ant? | Pest control methods that can target pest species with limited environmental impacts are a conservation and economic priority. Species-specific pest control using RNA interference is a challenging but promising avenue in developing the next generation of pest management. We investigate the feasibility of manipulating a biological invader's immune system using double-stranded RNA (dsRNA) in order to increase susceptibility to naturally occurring pathogens. We used the invasive Argentine ant as a model, targeting the immunity-associated genes Spaetzle and Dicer-1 with dsRNA. We show that feeding with Spaetzle dsRNA can result in partial target gene silencing for up to 28 days in the laboratory and 5 days in the field. Dicer-1 dsRNA only resulted in partial gene knockdown after 2 days in the laboratory. Double-stranded RNA treatments were associated with significant gene expression disruptions across immune pathways in the laboratory and to a lower extent in the field. In total, 12 viruses and four bacteria were found in these ant populations. Some changes in viral loads in dsRNA-treated groups were observed. For example, Linepithema humile Polycipivirus 2 (LhuPCV2) loads increased after 2 days of treatment with Spaetzle and Dicer-1 dsRNA treatments in the laboratory. After treatment with the dsRNA in the field, after 5 days the virus Linepithema humile toti-like virus 1 (LhuTLV1) was significantly more abundant. However, immune pathway disruption did not result in a consistent increase in microbial infections, nor did it alter ant abundance in the field. Some viruses even declined in abundance after dsRNA treatment. Our study explored the feasibility of lowering a pest's immunity as a control tool. We demonstrate that it is possible to alter immune gene expression of pest species and pathogen loads, although in our specific system the affected pathogens did not appear to influence pest abundance. We provide suggestions on future directions for dsRNA-mediated immune disruption in pest species, including potential avenues to improve dsRNA delivery as well as the importance of pest and pathogen biology. Double-stranded RNA targeting immune function might be especially useful for pest control in systems in which viruses or other microorganisms are prevalent and have the potential to be pathogenic. |
36196507 | Five-year surveillance study of clinical and environmental Triazole-Resistant Aspergillus fumigatus isolates in Iran. | Invasive aspergillosis is one of the mon fungal infections and azole resistance in Aspergillus fumigatus (ARAf) is a growing medical concern in high-risk patients. To our knowledge, there is prehensive epidemiological surveillance study on the prevalence and incidence of ARAf isolates available in Iran. |
36196508 | Hepatoprotective effects of a chemically-characterized extract from artichoke ( | This study was conducted to investigate the protective potential of a pharmaceutically formulated capsule of artichoke leaf powder (ArLP) against aflatoxin B |
36196509 | Clinical and laboratory responses to tigecycline in children. | The frequency of multidrug-resistant bacterial infections is increasing worldwide. Tigecycline may be an important option for children with life-threatening ial infections due to multidrug-resistant bacteria. However, there are few published data on the use of tigecycline in paediatric patients. By examining the results of tigecycline use in children, we aimed to draw attention to the fact that tigecycline may be an alternative in the treatment of resistant infections in children. |
36196510 | Validation of a rapid potency assay for cord blood stem cells using phospho flow cytometry: The IL-3-pSTAT5 assay. | Public cord blood banks (CBBs) are required to measure cord blood units (CBUs) potency before their release, allowing for the identification of units that may be unsuitable for haematopoietic transplantation. We have developed a rapid flow cytometry assay based on the measurement of STAT-5 phosphorylation of CD34+ stem cells in response to IL-3 stimulation. |
36196511 | Sodium and quantitative hydrogen parameter changes in muscle tissue after eccentric exercise and in delayed-onset muscle soreness assessed with magnetic resonance imaging. | The objective of the current study was to assess sodium ( |
36196512 | Effect of the application of software on the volumetric and cross-sectional assessment of the oropharyngeal airway of patients with and without an open bite: A CBCT study. | Using different software to evaluate the airways, with different thresholds, but within the range for airway recognition, could yield different measurements in the same patient with or without craniofacial disharmony. |
36196513 | Anatomical localization of posterior superior alveolar artery: A retrospective study by cone-beam computed tomography. | Familiarity with the anatomy of the arteries in the sinus wall is essential to prevent the perforation of the sinus membrane and bleeding during dental implant surgery. |
36196514 | Questionable accuracy of CBCT in determining bone density: A comparative CBCT-CT in vitro study. | The accuracy of the estimation of radiological bone density with the use of the puted tomography (CBCT) grayscale is still questionable. Standardization and correlation with the gold puted tomography (CT) Hounsfield units (HU) is required prior to clinical application. |
36196516 | Drug Value of Drynariae Rhizoma Root-Derived Extracellular Vesicles for Neurodegenerative Diseases Based on Proteomics and Bioinformatics. | Extracellular vesicles (EVs) are nano-sized membrane vesicles released by various cell types. Mammalian EVs have been studied in-depth, but the role of plant EVs has rarely been explored. For the first time, EVs from |
36196517 | Clonal functional traits favor the invasive success of alien plants into native communities. | Functional traits are frequently proposed to determine the invasiveness of alien species. However, few empirical studies have directly manipulated functional traits and tested their importance in the invasion success of alien species into native munities, particularly under global change. We manipulated clonal integration (a key clonal functional trait) of four alien clonal plants by severing inter-ramet connections or keeping them intact and simulated their invasion into native munities with two levels of species diversity, population density and nutrient availability. munity diversity and density impeded the invasion success of the alien clonal plants. Clonal integration of the alien plants promoted their invasion success, particularly in the munities associated with low species diversity or nutrient addition, which resulted in a negative correlation between the performance of alien plants and munities, as expected under global change. Thus, clonal integration can favor the invasion success of alien clonal plants into degraded munities with a high degree of disturbance and eutrophication. Our findings confirm the role of clonal functional traits in facilitating alien plant invasions into native munities and suggest that clonal functional traits should be considered to efficiently restore munities heavily invaded by alien clonal plants. |
36196518 | Employability and employment outcomes of nutrition science graduates: A qualitative exploration. | This study aimed to explore experiences of employability and employment for graduates of a three-year nutrition science degree. |
36196520 | Influence of genetic variants on remifentanil sensitivity in Chinese women. | Significant individual differences have been observed in pain sensitivity and analgesic effect of opioids. Previous studies have shown that genetic factors contributed to analgesics requirement obviously. Therefore, we investigated the role of genetic polymorphisms in the sensitivity to the analgesic effect of remifentanil in this study. |
36196515 | Evaluation of the effect of the photobiomodulation therapy on the pain related to dental injections: A preliminary clinical trial. | Pain from dental injections is mon reason why people fear dentistry and avoid dental treatment. Thus, researchers have attempted to find methods to decrease dental injection pain. |
36196521 | K | Patients with kidney failure are at risk for plications from hyperkalemia. Resuscitation, medications, and hemodialysis are used to mitigate increased potassium (K |
36196523 | MLC performance prognosis using a degradation model based on trajectory log data from a daily test. | This paper investigates the feasibility of implementing a predictive maintenance program for a multileaf collimator (MLC) based on data collected in trajectory logs (TLs) obtained by conducting a simple daily test, with the aim of minimizing unscheduled downtime. |
36196524 | The inexorable increase of biologic exposure in paediatric inflammatory bowel disease: a Scottish, population-based, longitudinal study. | The use of biologics in paediatric-onset inflammatory bowel disease (PIBD) is rapidly changing. |
36196525 | Novel machine learning algorithm can identify patients at risk of poor overall survival following curative resection for colorectal liver metastases. | The primary cause of mortality in colorectal cancer is metastatic disease. We investigated the ability of a machine learning (ML) algorithm to stratify overall survival (OS) of patients undergoing curative resection for colorectal liver metastases (CRLM). |
36196526 | Prospective registration study of diagnostic yield and sample size in forceps biopsy using a novel device under digital cholangioscopy guidance with macroscopic on-site evaluation. | Although the SpyGlass Direct Visualization System can be clinically useful for diagnosing indeterminate biliary stricture, it employs SpyBite forceps, which typically obtain only a small amount of tissue and have a low sampling rate. An improved forceps biopsy device for SpyGlass DS has recently been released (SpyBite MAX). The aim of this prospective registration study was to assess the diagnostic yield and efficacy of histological biopsy tissue obtained with SpyBite MAX pared with SpyBite forceps in patients with indeterminate biliary stricture. |
36196527 | The modified inframammary fold suture method and its clinical significance in primary augmentation mammoplasty. | The inframammary approach is one of the monly used incisions in breast augmentation. There are many suture methods for inframammary incisions; however, no one method has proven optimal. We modified the traditional three-layer suture method according to the inframammary fold (IMF) cadaver dissection results. This study aims to investigate whether using a modified suture method can improve postoperative es. |
36196530 | The Impact of a Continuity-of-Care Model From Hospitalization to Outpatient Clinic for Patients With Severe Mental Illness. | The authors sought to assess the impact of a continuity-of-care model on quality-of-care measures among hospitalized patients with severe mental illness in Israel. A "continuity-of-care physician" provided psychiatric care to patients during hospitalization and outpatient care after discharge. In the year after the model's implementation, emergency department visits significantly decreased by 32% and rehospitalization rates of patients discharged within 30 and 90 days decreased by 40% and 29%, respectively. The yearly rate pulsory admissions decreased from 35% to 25%, and the proportion of patients who entered rehabilitation significantly increased (from 9% to 13%). This model shows promise for improving quality of care of patients with severe mental illness admitted to acute psychiatric wards. |
36196533 | Enhancing Use of Medications for Opioid Use Disorder Through External Coaching. | This randomized controlled trial tested whether external coaching influences addiction treatment providers' utilization of medications to treat opioid use disorder (MOUDs). |
36196534 | Polo-like kinase and Aurora B kinase phosphorylate and cooperate with the CIF1-CIF2 complex to promote cytokinesis initiation in | Cytokinesis in eukaryotes is regulated by a Polo-like kinase-mediated and Aurora B kinase-mediated signalling pathway that promotes the assembly of the actomyosin contractile ring, a cytokinesis machinery conserved across evolution from yeast to humans. |
36196536 | AMPK phosphorylates NAMPT to regulate NAD | Radiation-induced oral mucositis is the plication for patients who receive head/neck radiotherapy. Nicotinamide adenine dinucleotide (NAD |
36196537 | Higher phage virulence accelerates the evolution of host resistance. | Pathogens vary strikingly in their virulence and the selection they impose on their hosts. While the evolution of different virulence levels is well studied, the evolution of host resistance in response to different virulence levels is less understood and, at present, mainly based on observations and theoretical predictions with few experimental tests. Increased virulence can increase selection for host resistance evolution if the benefits of avoiding infection outweigh resistance costs. To test this, we experimentally evolved the bacterium |
36196535 | Lipopolysaccharide detection by the innate immune system may be an uncommon defence strategy used in nature. | Since the publication of the Janeway's Pattern Recognition hypothesis in 1989, study of pathogen-associated molecular patterns (PAMPs) and their immuno-stimulatory activities has accelerated. Most studies in this area have been conducted in model organisms, which leaves many open questions about the universality of PAMP biology across living systems. Mammals have evolved multiple proteins that operate as receptors for the PAMP lipopolysaccharide (LPS) from Gram-negative bacteria, but LPS is not immuno-stimulatory in all eukaryotes. In this review, we examine the history of LPS as a PAMP in mammals, recent data on LPS structure and its ability to activate mammalian innate immune receptors, and how these pare monly studied eukaryotes. We discuss why LPS may have evolved to be immuno-stimulatory in some eukaryotes but not others and propose two hypotheses about the evolution of PAMP structure based on the ecology and environmental context of the organism in question. Understanding PAMP structures and stimulatory mechanisms across multi-cellular life will provide insights into the evolutionary origins of innate immunity and may lead to the discovery of new PAMP variations of scientific and therapeutic interest. |
36196538 | The power of vision: calibration of auditory space after sight restoration from congenital cataracts. | Early visual deprivation typically results in spatial impairments in other sensory modalities. It has been suggested that, since vision provides the most accurate spatial information, it is used for calibrating space in the other senses. Here we investigated whether sight restoration after prolonged early onset visual impairment can lead to the development of more accurate auditory space perception. We tested participants who were surgically treated for congenital dense bilateral cataracts several years after birth. In Experiment 1 we assessed participants' ability to understand spatial relationships among sounds, by asking them to spatially bisect three consecutive, laterally separated sounds. Participants performed better after surgery than participants tested before. However, they still performed worse than sighted controls. In Experiment 2, we demonstrated that single sound localization in the two-dimensional frontal plane improves quickly after surgery, approaching performance levels of sighted controls. Such recovery seems to be mediated by visual acuity, as participants gaining higher post-surgical visual acuity performed better in both experiments. These findings provide strong support for the hypothesis that vision calibrates auditory space perception. Importantly, this also demonstrates that this process can occur even when vision is restored after years of visual deprivation. |
36196539 | The dinosaurian femoral head experienced a morphogenetic shift from torsion to growth along the avian stem. | Significant evolutionary shifts in otor behaviour often paratively subtle anatomical transitions. For dinosaurian and avian evolution, medial overhang of the proximal femur has been central to discussions. However, there is an apparent conflict with regard to the evolutionary origin of the dinosaurian femoral head, with neontological and palaeontological data suggesting seemingly incongruent hypotheses. To reconcile this, we reconstructed the evolutionary history of morphogenesis of the proximal end of the femur from early archosaurs to crown birds. parison of living archosaurs (crocodylians and birds) suggests the acquisition of the greater overhang of the femoral head in dinosaurs results from additional growth of the proximal end in the medial-ward direction. On the other hand, the fossil record suggests that this overhang was acquired by torsion of the proximal end, which projected in a more rostral direction ancestrally. We reconcile this apparent conflict by inferring that the medial overhang of the dinosaur femoral head was initially acquired by torsion, which was then superseded by mediad growth. Details of anatomical shifts in fossil forms support this hypothesis, and their biomechanical implications are congruent with the general consensus regarding broader morpho-functional evolution on the avian stem. |
36196540 | Natural variation in developmental condition has limited effect on spatial cognition in a wild food-caching bird. | Laboratory studies show that increased physiological burden during development results in cognitive impairment. In the wild, animals experience a wide range of developmental conditions, and it is critical to understand how variation in such conditions affects cognitive abilities later in life, especially in species that strongly depend on such abilities for survival. We tested whether variation in developmental condition is associated with differences in spatial cognitive abilities in wild food-caching mountain chickadees. Using tail feathers grown during development in juvenile birds, we measured feather corticosterone (Cort |
36196541 | Colour patterns influence symbiosis and competition in the anemonefish-host anemone symbiosis system. | Colour patterns in fish are often used as an important medium munication. Anemonefish, characterized by specific patterns of white bars, inhabit host anemones and defend the area around an anemone as their territory. The host anemone is used not only by the anemonefish, but also by other fish species that use anemones as temporary shelters. Anemonefish may be able to identify petitors by their colour patterns. We first examined the colour patterns of fish using host anemones inhabited by |
36196542 | Metatarsal fusion resisted bending as jerboas (Dipodidae) transitioned from quadrupedal to bipedal. | Hind limbs undergo dramatic changes in loading conditions during the transition from quadrupedal to bipedal otion. For example, the most early diverging bipedal jerboas (Rodentia: Dipodidae) are some of the smallest mammals in the world, with body masses that range between 2-4 g. The larger jerboa species exhibit developmental and evolutionary fusion of the central three metatarsals into a single cannon bone. We hypothesize that small body size and metatarsal fusion are mechanisms to maintain the safety factor of the hind limb bones despite the higher ground reaction forces associated with bipedal otion. Using finite-element analysis to model collisions between the substrate and the metatarsals, we found that body size reduction was insufficient to reduce bone stress on unfused metatarsals, based on the scaled dynamics of larger jerboas, and that fused bones developed lower stresses than unfused bones when all metatarsals are scaled to the same size and loading conditions. Based on these results, we conclude that fusion reinforces larger jerboa metatarsals against high ground reaction forces. Because smaller jerboas with unfused metatarsals develop higher peak stresses in response to loading conditions scaled from larger jerboas, we hypothesize that smaller jerboas use alternative dynamics of bipedal otion to reduce the impact of collisions between the foot and substrate. |
36196543 | Combined effects of warming and drought on plant biomass depend on plant woodiness and community type: a meta-analysis. | Global warming and precipitation extremes (drought or increased precipitation) strongly affect plant primary production and thereby terrestrial ecosystem functioning. Recent syntheses show bined effects of warming and precipitation extremes on plant biomass are generally additive, while individual experiments often show interactive effects, indicating bined effects are more negative or positive than expected based on the effects of single factors. Here, we examined whether variation in biomass responses to single bined effects of warming and precipitation extremes can be explained by plant growth form munity type. We performed a meta-analysis of 37 studies, which experimentally crossed warming and precipitation treatments, to test whether biomass responses bined effects of warming and precipitation extremes depended on plant woodiness munity type (monocultures versus mixtures). Our results confirmed that the effects of warming and precipitation extremes were overall additive. bined effects of warming and drought on above- and belowground biomass were less negative in woody- than in herbaceous plant systems and more negative in plant mixtures than in monocultures. We further show that drought effects on plant biomass were more negative in greenhouse, than in field studies, suggesting that greenhouse experiments may overstate drought effects in the field. Our results highlight the importance of plant system characteristics to better understand plant responses to climate change. |
36196544 | Sensory biases in response to novel complex acoustic signals in male and female grey treefrogs, | The sensory bias hypothesis proposes that female preferences for male sexual signalling traits evolved in contexts other than mating. Individuals of both sexes may experience similar selection pressures in these contexts; thus males may have similar biases to females for variation in signal traits. We tested this prediction in the grey treefrog, |
36196545 | Temperature-associated selection linked to putative chromosomal inversions in king scallop ( | The genomic landscape of divergence-the distribution of differences among populations or species across the genome-is increasingly characterized to understand the role that microevolutionary forces such as natural selection and bination play in causing and maintaining genetic divergence. This line of inquiry has also revealed chromosome structure variation to be an important factor shaping the landscape of adaptive genetic variation. Owing to a high prevalence of chromosome structure variation and the strong pressure for local adaptation necessitated by their sessile nature, bivalve molluscs are an ideal taxon for exploring the relationship between chromosome structure variation and local adaptation. Here, we report a population genomic survey of king scallop ( |
36196546 | Large genetic divergence underpins cryptic local adaptation across ecological and evolutionary gradients. | Environmentally covarying local adaptation is a form of cryptic local adaptation in which the covariance of the genetic and environmental effects on a phenotype obscures the divergence between locally adapted genotypes. Here, we systematically document the magnitude and drivers of the genetic effect (V |
36196547 | Epidemiological dynamics of bacteriocin competition and antibiotic resistance. | Bacteriocins, toxic peptides involved in petition between bacterial strains, are extremely diverse. Previous work on bacteriocin dynamics has highlighted the role of non-transitive petition in maintaining the coexistence of different bacteriocin profiles. The focus to date has primarily been on bacteriocin interactions at the within-host scale (i.e. within a single bacterial population). Yet in species such as |
36196548 | Rising floor and dropping ceiling: organ heterogeneity in response to cold acclimation of the largest extant amphibian. | Low temperature imposes strong selective pressure on ectotherms. To maximize their overall fitness under cold conditions, the ectotherms may either try to maintain their physiological activities through pensation or enter into metabolic depression; however, some species adopt both strategies to cope with different degrees of cold. Nevertheless, how these two seemingly opposite strategies are coordinated has rarely been elucidated. Here, we investigated the molecular strategy underlying the cold acclimation of |
36196551 | Group augmentation on trial: helpers in small groups enhance antipredator defence of eggs. | Mechanisms selecting for the evolution of cooperative breeding are hotly debated. While kin selection theory has been the central paradigm to explain the seemingly altruistic behaviour of non-reproducing helpers, it is increasingly recognized that direct fitness benefits may be highly relevant. The group augmentation hypothesis proposes that alloparental care may evolve to enhance group size when larger groups yield increased survival and/or reproductive success. However, there is a lack of empirical tests. Here we use the cooperatively breeding cichlid fish |
36196552 | Migratory hoverflies orientate north during spring migration. | Migratory hoverflies are long-range migrants that, in the Northern Hemisphere, move seasonally to higher latitudes in the spring and lower latitudes in the autumn. The preferred migratory direction of hoverflies in the autumn has been the subject of radar and flight simulator studies, while spring migration has proved to be more difficult to characterize owing to a lack of ground observations. Consequently, the preferred migratory direction during spring has only been inferred from entomological radar studies and patterns of local abundance, and currently lacks ground confirmation. Here, during a springtime arrival of migratory insects onto the Isles of Scilly and mainland Cornwall, UK, we provide ground proof that spring hoverfly migrants have an innate northward preference. Captured migratory hoverflies displayed northward vanishing bearings when released under sunny conditions under both favourable wind and zero-wind conditions. In addition, and unlike autumn migrants, spring individuals were also able to orientate when the sun was obscured. Analysis of winds suggests an origin for insects arriving on the Isles of Scilly as being in western France. These findings of spring migration routes and preferred migration directions are likely to extend to the diverse set of insects found within the western European migratory assemblage. |
36196553 | Confirmation of the first intronic sequence in the bivalvian mitochondrial genome of | In 2020, the first male-type mitochondrial genome from the clam |
36196554 | Increased superfetation precedes the evolution of advanced degrees of placentotrophy in viviparous fishes of the family Poeciliidae. | The causes and consequences of the evolution of placentotrophy (post-fertilization nutrition of developing embryos of viviparous organisms by means of a maternal placenta) in non-mammalian vertebrates are still not fully understood. In particular, in the fish family Poeciliidae there is an evolutionary link between placentotrophy and superfetation (ability of females to simultaneously bear embryos at distinct developmental stages), with no conclusive evidence for which of these two traits facilitates the evolution of more advanced degrees of the other. Using a robust parative method based on Ornstein-Uhlenbeck models of adaptive evolution and data from 36 poeciliid species, we detected a clear causality pattern. The evolution of extensive placentotrophy has been facilitated by the preceding evolution of more simultaneous broods. Therefore, placentas became plex as an adaptive response to evolutionary increases in the degree of superfetation. This finding represents a substantial contribution to our knowledge of the factors that have shaped placental evolution in poeciliid fishes. |
36196555 | Multidisciplinary management of mammary Paget's disease: recommendations to optimize oncological and aesthetic outcomes. | We read with interest the article of Francesca Maria Plutino entitled "A peculiar case of Paget's disease of the breast" and would like to make some considerations about this particular topic 1. Mammary Paget's Disease (MPD) or Paget's disease of the breast is an mon pathology which accounts for less than 5% of breast cancers 1-3. MPD occurs with alterations of the plex (NAC) such as redness, eczema, bleeding ulceration and usually itching 1-3. In the era of personalized care, a careful multidisciplinary management is mandatory to optimize the results and minimize the risk of overtreatment 4; an adequate knowledge of the MPD, surgical skills and use of appropriate adjuvant therapies allow to reduce the risk of local recurrence and improve the aesthetic es and patient's quality of life; however, a successful work can be more easily achieved thanks to the repetitive performance of some standardized tasks, such as 5: - an accurate radiological preoperative assessment with mammography and ultrasonography is important to identify associated glandular lesions; an underlying breast carcinoma (in situ and/or invasive) may be present up to about 80% to 90% of MPD although often without an evident breast mass or mammographic abnormality (2,5); therefore, all patients with MPD should also perform a magnetic resonance imaging to detect possible underlying occult breast carcinoma and define the true extent of disease 5,6; - a pathological diagnosis should be early established by nipple scrape cytology when a MPD is clinically suspected; full-thickness punch or wedge biopsy of the NAC may be necessary to accurately diagnose MPD; the histological examination must detect malignant intraepithelial carcinoma cells, also known as "Paget cells", in the epidermis of the NAC 2,3; a needle biopsy is also required for any suspicious glandular lesion identified by imaging and associated with MPD 5; - a multidisciplinary "Surgery Board" is mandatory to select the more adequate local treatment for the patient: breast-conserving surgery (BCS) followed by radiotherapy (RT) is the optimal local treatment when a NAC resection and wide local excision of any underlying cancer allows to achieve tumour-free margins and appropriate aesthetic es 4,5,7; the oncoplastic techniques with the remodelling of breast tissue and placement of clips within the excision cavity as a landmark to guide adjuvant RT should always be used in BCS in order to optimize oncological and cosmetic results 5,8,9,10. Instead, skin-sparing mastectomy with immediate breast reconstruction is indicated for MPD associated to multicentric or extensive carcinoma, inadequate margins after BCS, contraindications to adjuvant RT and patient preference 5,8. Staging and surgical treatment of the axilla in MPD is based on the possible presence of underlying cancer; sentinel lymph node biopsy (SLB) is not necessary when BCS is used to treat pure MPD or MPD associate with ductal carcinoma in situ; SLB must be performed when MPD is associated with underlying invasive cancer and treated with breast-conserving surgery; SLB is always mended when a mastectomy is performed in order to plete axillary lymph node dissection in case an ponent is revealed at final pathology of the gland (mastectomy precludes subsequent use of SLB) 5,7,8; - a multidisciplinary "Tumor Board" is crucial to choose the adjuvant treatment; whole breast radiation should be always performed after BCS and a radiation boost should be considered for the site of the resected NAC and any associated resected cancer site 2,4,5; adjuvant systemic therapies in patients with MPD should be based on biological features and the stage of the underlying cancer; no data are available to support the use of endocrine therapy in the MPD without an associated DCIS or invasive carcinoma 5. In conclusion, a dedicated multidisciplinary pathway with meticulous repetitive performance of some specific tasks could help to perform a successful work while optimizing oncological and aesthetic es in patients with MPD. |
36196556 | New Targeted Therapy for Non-Small Cell Lung Cancer. | Lung cancer ranks first in cancer mortality in Korea and cancer incidence in Korean men. More than half of Korean lung cancer patients undergo chemotherapy, including adjuvant therapy. Cytotoxic agents, targeted therapy, and immune checkpoint inhibitors are used in chemotherapy according to the biopsy and genetic test results. Among chemotherapy, the one that has developed rapidly is targeted therapy. The National Comprehensive Cancer Network (NCCN) guidelines have been updated recently for targeted therapy of multiple gene mutations, and targeted therapy is used not only for chemotherapy but also for adjuvant therapy. While previously targeted therapies have been developed mon genetic mutations, recently targeted therapies have been developed to e mon mutations or drug resistance that have occurred since previous targeted therapy. Therefore, this study describes recent, rapidly developing targeted therapies. |
36196557 | Characteristics of gastroesophageal reflux disease in children with interstitial lung disease. | Childhood interstitial lung disease (chILD) is a rare group of respiratory tract disorders. One of the factors suggested to be associated with its etiopathogenesis is microaspiration related to gastroesophageal reflux disease (GERD). The aim of the present study was to determine the frequency and characteristics of GERD in children with chILD, with a particular focus on proximal GER episodes. |
36196559 | [Non-inferiority studies efficacy and safety: review of methodological and statistical aspects in clinical trials and non-interventional studies with medicinal products.] | Non-inferiority studies are increasingly mon for introducing new medicines in the market. Despite being situations where the use of this study design is justified, there is not mon analytical approach on how to conduct them. Pursuing a rigorous methodology, both in the study conduction and in its disseminations, is critical to ensure robust results to enable regulatory agencies and clinicians to reach valid conclusions and decisions which ultimately will benefit clinical practice. Most of the published reviews focus on the efficacy es of non-inferiority clinical trials. We are unaware of other reviews that goes beyond and includes specific aspects for non-interventional designs and for studies focused on safety. Moreover, this review provides a simple and practical perspective with a minimum mathematical content on plex type of studies. |
36196560 | [Risk of sarcopenia and malnutrition related to COVID-19 in an institutionalized population of Castilla-La Mancha (Spain): determined by R-MAPP.] | Knowing the risk status of malnutrition and sarcopenia in institutionalized patients is essential to understand the current context after the impact of the coronavirus (COVID-19) pandemic. |
36196562 | Healthcare burden and outcomes of hepatorenal syndrome among cirrhosis-related hospitalisations in the US. | Hepatorenal syndrome (HRS) contributes to significant morbidity and mortality in hospitalised patients with cirrhosis. |
36196563 | The impact of anemia on treatment management and clinical outcomes of women hospitalized for uterine leiomyomas. | Uterine leiomyomas are the mon benign gynecological tumors. Symptomatic leiomyomas represent a major cause of hospitalization, particularly those associated with abnormal uterine bleeding (AUB) and anemia. The aim of this study was to identify predictors of anemia in women hospitalized due to uterine leiomyomas and evaluate its impact on treatment management and clinical es. |
36196564 | Quality of life in patients with overactive bladder following botulinum toxin treatment: a preliminary report. | The aim of the present study was pare the subjective quality of life in patients with overactive bladder (OAB) prior to intravesical botulinum toxin injection and three and six months thereafter. |
36196565 | Epidural anesthesia during childbirth - retrospective analysis of maternal and neonatal results. | In Poland, in accordance with applicable regulations, every woman should have access to epidural anesthesia. The advantage of this type of analgesia is primarily analgesic effectiveness. The aim of the study is to identify variables related to epidural anesthesia and to verify the relationship between them and the occurrence of plications in the mother and the child. |
36196566 | Endometrial regeneration in Asherman's syndrome and endometrial atrophy using Wharton's jelly-derived mesenchymal stem cells. | Reconstruction of the endometrium in patients with endometrial atrophy and Asherman's syndrome using Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs). |
36196567 | [Reliability and Validity of the Perceived Physical Fitness Scale questionnaire in Spanish students.] | Self-perception questionnaires are considered a useful alternative to assess the level of physical fitness (PF) of a specific population. However, very few questionnaires of this type have been validated in the Spanish population. The aim of this study was to identify the reliability and validity of the Perceived Physical Fitness Scale (PPFS) in Spanish students. |
36196568 | Population Pharmacokinetics of Tacrolimus in Pediatric Patients With Umbilical Cord Blood Transplant. | Tacrolimus was frequently used in pediatric patients with umbilical cord blood transplant for the prevention of graft-versus-host disease. The aim of the present study was to evaluate the population pharmacokinetics of tacrolimus among pediatric patients with umbilical cord blood transplant and find potential influenced factors. A total of 275 concentrations from 13 pediatric patients were used to build a polulation pharmacokinetic model using a nonlinear mixed-effects modeling approach. The impact of demographic features, biological characteristics, and itant medications, including sex, age, body weight, postoperative day, white blood cell count, red blood cell count, hemoglobin, platelets, hematocrit, blood urea nitrogen, creatinine, aspartate transaminase, alanine transaminase, total bilirubin, albumin, and total protein were investigated. The pharmacokinetics of tacrolimus were best described by a partment model with first- and zero-order mixed absorption and first-order elimination. The clearance and volume of distribution of tacrolimus were 1.93 L/h and 75.1 L, respectively. A covariate analysis identified that postoperative day and co-administration with trimethoprim-sulfamethoxazole were significant covariates influencing clearance of tacrolimus. Frequent blood monitoring and dose adjustment might be needed with the prolongation of postoperative day and coadministration with trimethoprim-sulfamethoxazole. |
36196570 | Genomic full-length confirmatory sequence of HLA-DQB1*04:59N allele in three Colombian individuals. | The extended genomic sequence of HLA-DQB1*04:59N allele. |
36196573 | When Cancer Cells Become the Enablers of an Antitumor Immune Response. | Tumor-specific cytotoxic T cells unleashed by the blockade of immune checkpoints have to e a hostile tumor microenvironment (TME). They start from very small numbers of T cells with tumor antigen specificity and, despite expansion, likely remain at a numerical disadvantage to the tumor cells they target. To e these obstacles, we propose that T cells need to change the TME to make it permissive for their antitumor effects by altering the phenotype of cells beyond the cancer cells they are in physical contact with. In this process, IFNγ secreted by tumor-specific T cells plays a critical role, as it changes the expression of hundreds of genes in cancer cells and other immune cells in the TME up to 40 layers of cells away from their location, effectively turning these cells into enablers of the antitumor immune response. In this perspective, we postulate that the clinical activity of cancer immunotherapy with immune-checkpoint blocking antibodies and adoptively transferred T cells requires that cancer cells facilitate the antitumor immune response. IFNγ effectively changes the balance of power in the TME to enable the antitumor activity of tumor antigen-specific cytotoxic T cells. |
36196569 | Treatment adaptations and outcomes of patients experiencing inflammatory bowel disease flares during the early COVID-19 pandemic: the PREPARE-IBD multicentre cohort study. | The COVID-19 pandemic offered a unique opportunity to understand inflammatory bowel disease (IBD) management during unexpected disruption. This could help to guide practice overall. |
36196574 | GOT2: An Unexpected Mediator of Immunosuppression in Pancreatic Cancer. | In this issue, Abrego and colleagues describe an unexpected role for the mitochondrial enzyme glutamic-oxaloacetic transaminase (GOT2) in pancreatic cancer, whereby it acts as a nuclear fatty acid transporter binding to and activating the PPARδ nuclear receptor. In turn, the GOT2-PPARδaxis drives immunosuppression by suppressing T cell-mediated antitumor immunity. See related article by Abrego et al., p. 2414 (3). |
36196575 | The Boring Schwann Cells: Tumor Me-TAST-asis along Nerves. | Perineural spread is an ominous feature of cancer. Here, Deborde and colleagues describe for the first time the biophysical coupling driving this route of tumor spread and the role of Schwann cell activation in the mobilization of cancer cells within and along the tumor-associated nerves. See related article by Deborde et al., p. 2454 (8). |
36196576 | Dangerous Liaisons between Tet2 Mutation, Inflammatory Monocytes, and Leukemogenesis. | Transgenic knockin mice expressing mon loss-of-function mutation in human TET2 exhibit aging-related accelerated myeloid leukemia development and skewing of myelopoiesis toward the production of proinflammatory MHC-IIhi monocytes that may contribute to disease. See related article by Yeaton et al., p. 2392 (2). |
36196577 | Impact of Respiratory Infection and Chronic Comorbidities on Early Pediatric Antibiotic Dispensing in the United States. | In the United States, children aged <5 years receive high volumes of antibiotics, which may contribute to antibiotic resistance. It has been unclear what role preventable illnesses and orbidities play in prompting antibiotic prescriptions. |
36196581 | WITHDRAWN: Comment on "Comparison of the clinical performance of the i-gelTM, LMA SupremeTM, and Ambu AuraGainTM in adult patients during general anesthesia: a prospective and randomized study" | Ahead of Print article withdrawn by publisher. |
36196582 | Coxa valga and antetorta increases differences among different femoral version measurements : potential implications for derotational femoral osteotomy planning. | To evaluate how abnormal proximal femoral anatomy affects different femoral version measurements in young patients with hip pain. |
36196583 | Risk of death associated with incident heart failure in patients with known or suspected chronic coronary syndrome. | Traditional adverse events in chronic coronary syndrome (CCS) include atherothrombotic events but usually exclude heart failure (HF). Data are scarce about how new-onset HF modifies mortality risk. We aimed to determine the incidence of HF pare its long-term mortality risk with myocardial infarction (MI) and stroke in patients with known or suspected CCS. |
36196584 | Association between functional recovery and medication adherence in schizophrenia. | Medication adherence is important for achieving functional recovery from schizophrenia and monly assessed using the Drug Attitude Inventory-30 (DAI-30). Subscales of the DAI-30, including "awareness of the need for medication," "awareness of the effects of psychiatric drugs," and "impression of medication," have been used to assess medication adherence. To determine which of these subscales are associated with the prognosis of schizophrenia, this study followed patients with schizophrenia to identify the prognosis and examine the subscales related to "recovery." |
36196585 | Dentate gyrus morphogenesis is regulated by β-catenin function in hem-derived fimbrial glia. | The dentate gyrus, a gateway for input to the hippocampal formation, arises from progenitors in the medial telencephalic neuroepithelium adjacent to the cortical hem. Dentate progenitors navigate plex migratory path guided by two cell populations that arise from the hem, the fimbrial glia and Cajal-Retzius (CR) cells. As the hem expresses multiple Wnt genes, we examined whether β-catenin, which mediates canonical Wnt signaling and also participates in cell adhesion, is necessary for the development of hem-derived lineages. We report that, in mice, the fimbrial glial scaffold is disorganized and CR cells are mispositioned upon hem-specific disruption of β-catenin. Consequently, the dentate migratory stream is severely affected, and the dentate gyrus fails to form. Using selective Cre drivers, we further determined that β-catenin function is required in the fimbrial glial scaffold, but not in the CR cells, for guiding the dentate migration. Our findings highlight a primary requirement for β-catenin for the organization of the fimbrial scaffold and a secondary role for this factor in dentate gyrus morphogenesis. |
36196586 | Leveraging Serosurveillance and Postmortem Surveillance to Quantify the Impact of Coronavirus Disease 2019 in Africa. | The coronavirus disease 2019 (COVID-19) pandemic has had a devastating impact on global health, the magnitude of which appears to differ intercontinentally: For example, reports suggest that 271 900 per million people have been infected in Europe versus 8800 per million people in Africa. While Africa is the second-largest continent by population, its reported COVID-19 prise <3% of global cases. Although social and environmental explanations have been proposed to clarify this discrepancy, systematic underascertainment of infections may be equally responsible. |
36196587 | Arterial stiffness nomogram identification by cluster analysis: A new approach of vascular phenotype modeling. | Arterial stiffness, measured by arterial stiffness index (ASI), can be considered as a major denominator in cardiovascular diseases. Thus, it remains essential to highlight patient phenotyping profiles with high ASI values. A nomogram of arterial stiffness was evaluated by calculation of ASI nomogram. Theoretical ASI can be performed according to age, sex, mean blood pressure, and heart rate, allowing to form an individual ASI nomogram [(measured ASI - theoretical ASI)/theoretical ASI]. An ASI nomogram > 0 defined AS. This study investigates among UK Biobank participants without cardiovascular diseases, the hypothesis that K-means cluster analysis can be used to identify homogeneous phenotyping subgroups of participants according to ASI levels and then, the phenotype differences observed between these clusters. ASI nomogram was applied on 132 851 participants. K-means clustering was implemented with 10 clusters (optimal CCC value of 105.246). One cluster showed 100% rate of AS, corresponding to 25 393 participants (41.6% of the AS participants) with ASI nomogram = .26 (.22), ASI = 11.6 (2.3)m/s. A second cluster showed a 100% of non-AS, corresponding to 27 844 participants (38.8% of the participants with no arterial stiffness) with ASI nomogram = -.22 (.13), ASI = 7.1 (1.44)m/s. Threshold values of independent factors for differencing these two clusters were total cholesterol > 5.409 mmol/L (P < .001), triglycerides > 1.286 mmol/L (P < .001), smoking pack years > 11.8 pack/years, CRP > .99 (P < .001), daily alcohol consumption > 1.794 units/days and BMI > 26.641 kg/m |
36196590 | Modified micromarsupialization technique as an alternative primary treatment for ranulas: A case series in a resource-challenged economy. | Ranula is one of monest salivary gland cysts that mostly occur due to mucus extravasation from the sublingual salivary gland. Treatment of this lesion is still somewhat shrouded in controversy and varies from conservative treatment to surgical excision of the causative gland. |
36196591 | UEG and EAES rapid guideline: Update systematic review, network meta-analysis, CINeMA and GRADE assessment, and evidence-informed European recommendations on surgical management of GERD. | There are several options for the surgical management of GERD in adults. Previous guidelines and systematic reviews pared the effects of total fundoplication versus pooled effects of different techniques of partial fundoplication. |
36196592 | Evaluation of urinary neutrophil gelatinase-associated lipocalin to detect renal tubular damage in dogs with stable myxomatous mitral valve disease. | Dogs with myxomatous mitral valve disease (MMVD) can experience progressive renal tubular damage and dysfunction. The prevalence of renal tubular damage is not known in dogs with stable MMVD. |
36196593 | Heterologous expression of a lycophyte protein enhances angiosperm seedling vigor. | Seedling vigor is a key agronomic trait that determines juvenile plant performance. Angiosperm seeds develop inside fruits and are connected to the mother plant through vascular tissues. Their formation requires plant-specific genes, such as BREVIS RADIX (BRX) in Arabidopsis thaliana roots. BRX family proteins are found throughout the euphyllophytes but also occur in non-vascular bryophytes and non-seed lycophytes. They consist of four conserved domains, including the tandem BRX domains. We found that bryophyte or lycophyte BRX homologs can only partially substitute for Arabidopsis BRX (AtBRX) because they miss key features in the linker between the BRX domains. Intriguingly, however, expression of a BRX homolog from the lycophyte Selaginella moellendorffii (SmBRX) in an A. thaliana wild-type background confers robustly enhanced root growth vigor that persists throughout the life cycle. This effect can be traced to a substantial increase in seed and embryo size, is associated with enhanced vascular tissue proliferation, and can be reproduced with a modified, SmBRX-like variant of AtBRX. Our results thus suggest that BRX variants can boost seedling vigor and shed light on the activity of ancient, non-angiosperm BRX family proteins. |
36196594 | Glycine-β-muricholic acid antagonizes the intestinal farnesoid X receptor-ceramide axis and ameliorates NASH in mice. | Nonalcoholic steatohepatitis (NASH) is a rapidly developing pathology around the world, with limited treatment options available. Some farnesoid X receptor (FXR) agonists have been applied in clinical trials for NASH, but side effects such as pruritus and low-density lipoprotein elevation have been reported. Intestinal FXR is recognized as a promising therapeutic target for metabolic diseases. Glycine-β-muricholic acid (Gly-MCA) is an intestine-specific FXR antagonist previously shown to have favorable metabolic effects on obesity and insulin resistance. Herein, we identify a role for Gly-MCA in the pathogenesis of NASH, and explore the underlying molecular mechanism. Gly-MCA improved lipid accumulation, inflammatory response, and collagen deposition in two different NASH models. Mechanistically, Gly-MCA decreased intestine-derived ceramides by suppressing ceramide synthesis-related genes via decreasing intestinal FXR signaling, leading to lower liver endoplasmic reticulum (ER) stress and proinflammatory cytokine production. The role of bile acid metabolism and adiposity was excluded in the suppression of NASH by Gly-MCA, and a correlation was found between intestine-derived ceramides and NASH severity. This study revealed that Gly-MCA, an intestine-specific FXR antagonist, has beneficial effects on NASH by reducing ceramide levels circulating to liver via lowering intestinal FXR signaling, and ceramide production, followed by decreased liver ER stress and NASH progression. Intestinal FXR is a promising drug target and Gly-MCA a novel agent for the prevention and treatment of NASH. |
36196595 | The Impact of Surgical versus Transcatheter Aortic Valve Replacement on Postprocedural Acute Kidney Injury in Patients with Chronic Kidney Disease. | This study aimed to evaluate the impact of the treatment modality on post-procedural acute kidney injury (AKI) and other clinical es in patients with advanced chronic kidney disease who underwent surgical or transcatheter aortic valve replacement (AVR). |
36196596 | Comparison of tibial alignment parameters based on clinically relevant anatomical landmarks : a deep learning radiological analysis. | Accurate identification of the ankle joint centre is critical for estimating tibial coronal alignment in total knee arthroplasty (TKA). The purpose of the current study was to leverage artificial intelligence (AI) to determine the accuracy and effect of using different radiological anatomical landmarks to quantify mechanical alignment in relation to a traditionally defined radiological ankle centre. |
36196597 | Association of cardiorespiratory fitness with the risk factors of cardiovascular disease: Evaluation using the Japan step test from the National Institute of Occupational Safety and Health. | Cardiorespiratory fitness (CRF) is an important factor for evaluating cardiovascular disease (CVD) risk. We recently developed a novel method (National Institute of Occupational Safety and Health, Japan step test [JST]) for evaluating CRF in workers; its criterion validity has been investigated. However, its association with health risk must be confirmed before its application in the workplace. Therefore, we aimed to determine the association of JST-evaluated CRF with the prevalence of CVD risk among Japanese workers. |
36196598 | Cathelicidin as a marker for subclinical cardiac changes and microvascular complications in children and adolescents with type 1 diabetes. | To detect cathelicidin levels in pediatric patients with type 1 diabetes (T1D) as a potential marker for diabetic plications and to assess its relation to diastolic dysfunction as an index for subclinical macrovasculopathy. |
36196601 | An evaluation of a supratherapeutic dose of inclisiran on cardiac repolarization in healthy volunteers: A phase I, randomized study. | Inclisiran is a small interfering RNA molecule that has been shown to provide an effective and sustained reduction in low-density lipoprotein cholesterol levels. This study aimed to determine whether a supratherapeutic dose of inclisiran affects cardiac repolarization and conduction in healthy volunteers. A phase I, randomized, double-blind, double-dummy, placebo- and positive-controlled, three-way crossover study was performed in 48 healthy volunteers. Volunteers were assigned to three treatments in a randomized sequence: a supratherapeutic dose of inclisiran sodium (900 mg), placebo, or moxifloxacin 400 mg as a positive control, with a minimum 7-day washout period between treatments. Continuous electrocardiogram monitoring was performed from >60 min before dosing until 48 h after dosing. Pharmacokinetics, pharmacodynamics, and safety were also assessed. Inclisiran, at a supratherapeutic dose, did not show a clinically significant effect on the QT interval (Fridericia correction formula [QTcF]; maximal placebo- and baseline-corrected change: 2.5 ms [90% confidence interval: 0.6, 4.5]) near the maximal plasma concentrations at 4 h. In addition, inclisiran did not show any effects on other electrocardiogram intervals or ST- and T-wave morphology. The positive control, moxifloxacin, demonstrated the expected changes in QTcF interval, validating the adequate sensitivity of the study. A supratherapeutic dose of inclisiran sodium (900 mg) had no effect on the QTcF interval or other electrocardiogram parameters, providing additional insight and reassurance regarding the safety profile of inclisiran. |
36196604 | Current street tree communities reflect race-based housing policy and modern attempts to remedy environmental injustice. | Humans promote and inhibit other species on the urban landscape, shaping biodiversity patterns. Institutional racism may underlie the distribution of urban species by creating disproportionate resources in space and time. Here, we examine whether present-day street tree occupancy, diversity, position in Baltimore, MD, USA, neighborhoods reflect their 1937 classification into grades of loan risk-from most desirable (A = green) to least desirable (D = "redlined")-using racially discriminatory criteria. We find that neighborhoods that were redlined have consistently lower street tree α-diversity and are nine times less likely to have large (old) trees occupying a viable planting site. Simultaneously, redlined neighborhoods were locations of recent tree planting activities, with a high occupancy rate of small (young) trees. However, position of these young trees exhibited lower species turnover and reordering across pared to those in higher grades, due to heavy reliance on a single tree species. Overall, while the negative effects of redlining remain detectable in present-day street munities, there are clear signs of recent investment. A strategy of planting diverse tree cohorts paired with investments in site rehabilitation and maintenance may be necessary if cities wish to e ecological feedbacks associated with legacies of environmental injustice. |
36196602 | Specialized germline P-bodies are required to specify germ cell fate in Caenorhabditis elegans embryos. | In animals with germ plasm, specification of the germline involves 'germ granules', cytoplasmic condensates that enrich maternal transcripts in the germline founder cells. In Caenorhabditis elegans embryos, P granules enrich maternal transcripts, but surprisingly P granules are not essential for germ cell fate specification. Here, we describe a second condensate in the C. elegans germ plasm. Like canonical P-bodies found in somatic cells, 'germline P-bodies' contain regulators of mRNA decapping and deadenylation and, in addition, the intrinsically-disordered proteins MEG-1 and MEG-2 and the TIS11-family RNA-binding protein POS-1. Embryos lacking meg-1 and meg-2 do not stabilize ponents, misregulate POS-1 targets, mis-specify the germline founder cell and do not develop a germline. Our findings suggest that specification of the germ line involves at least two distinct condensates that independently enrich and regulate maternal mRNAs in the germline founder cells. This article has an associated 'The people behind the papers' interview. |
36196606 | The Evaluation of Surrogate Laboratory Parameters for Predicting the Trend of Viral Loads in Patients with Severe Fever with Thrombocytopenia Syndrome: Cross-Correlation Analysis of Time Series. | There is a correlation between the severe fever with thrombocytopenia syndrome (SFTS) viral load and disease severity; however, measurement of viral load is difficult in general laboratory and it takes time to obtain a viral load value. Here, the laboratory parameters for predicting the dynamic changes in SFTS viral load were identified. In addition, we tried to evaluate a specific time point for the early determination of clinical deterioration using dynamic change of laboratory parameters. |