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The Natural Products Magnetic Resonance Database (NP-MRD; https://np-mrd.org) is a comprehensive, freely accessible, web-based resource for the deposition, distribution, extraction, and retrieval of nuclear magnetic resonance (NMR) data on natural products (NPs). The NP-MRD was initially established to support compound de-replication and data dissemination for the NP community. However, that community has now grown to include many users from the metabolomics, microbiomics, foodomics, and nutrition science fields. Indeed, since its launch in 2022, the NP-MRD has expanded enormously in size, scope, and popularity. The current version of NP-MRD now contains nearly 7× more compounds (281 859 versus 40 908) and 7× more NMR spectra (5.5 million versus 817 278) than the first release. More specifically, an additional 4.6 million predicted spectra and another 11 000 spectra simulated from experimental chemical shifts were deposited into the database. Likewise, the number of NMR raw spectral data depositions has grown from 165 spectra per year to >10 000 per year. As a result of this expansion, the number of monthly webpage views has grown from 55 to 20 000 and the number of monthly visitors has increased from 7 to 2500. To address this growth and to better support the expanding needs of its diverse community of users, many additional improvements to the NP-MRD have been made. These include significant enhancements to the data submission process, notable updates to the database's spectral search utilities and useful additions to support better NMR spectral analysis/prediction. Significant efforts have also been undertaken to remediate and update many of NP-MRD's database entries. This manuscript describes these database improvements and expansion efforts, along with how they have been implemented and what future upgrades to the NP-MRD are planned., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Social skills (e.g., assertiveness, empathy, ability to accept criticism) are essential for the medical profession and therefore also for the selection and development of medical students. However, the term "social skills" is understood differently in different contexts. There is no agreed upon taxonomy for classifying physicians' social skills, and skills with the same meaning often have different names. This conceptual ambiguity presents a hurdle to cross-context communication and to the development of methods to assess social skills. Drawing from behavioral psychology, we aim to contribute to a better understanding of social skills in the medical context. To this end, we introduce a theoretically and empirically informed taxonomy that can be used to integrate the large number of different social skills. We consider how skills manifest at the behavioral level to ensure that we focus only on skills that are actually observable, distinguishable, and measurable. Here, behavioral research has shown that three overarching skill dimensions can be seen in interpersonal situations and are clearly distinguishable from each other: agency skill (i.e., getting ahead in social situations), communion skill (i.e., getting along in social situations), and interpersonal resilience (i.e., staying calm in social situations). We show that almost all social skills relevant for physicians fit into this structure. The approach presented allows redundant descriptions to be combined under three clearly distinguishable and behavior-based dimensions of social skills. This approach has implications for the assessment of social skills in both the selection and development of students., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

There is increasing awareness that marine invertebrates such as abalones are at risk from the combined stressors of fishing and climate change. Abalones are an important marine fishery resource and of cultural importance to Indigenous and non-Indigenous people. A highly priced marine delicacy, they are inherently vulnerable: individuals are slow-growing and long-lived and successful reproduction requires dense assemblages. However, their global conservation status is poorly understood. Using IUCN Red List methodology, we assessed the extinction risk to all 54 species of abalone (genus Haliotis). Of the 21 fished commercially for human consumption either now and/or in the past, 15 (71.43%) are classified as threatened, i.e., those identified as Critically Endangered, Endangered or Vulnerable. Of the 33 unexploited species, only five (15.15%) are so classified, making exploited species over four times more likely to face extinction, underscoring the impact of fishing on abalones already confronting a changing climate. The highest concentration of threatened species occurs along the North American Pacific coast. Here six of the seven species have been exploited, yet despite years of fishery closures with exemptions only in Alaska and Mexico, all are categorised as threatened. Climate driven stressors have led to mass mortalities, with competition from sea urchins and disease, aggravated by harmful algal blooms. In Australia the picture is mixed despite robust stock management, with some regions experiencing mass mortalities from marine heatwaves and viral spread. Poaching has reached its apogee in South Africa, where organised criminal gangs have reduced the legal fishery of Haliotis midae, 'perlemoen' almost to a footnote, accompanied by widespread recruitment failure. In response, the authorities have focused on abalone ranching and stock enhancement. In Japan, with a long history of abalone fishing, wild stocks are routinely supplemented with hatchery-bred juveniles. Collaboration between restoration aquaculture and fisheries, including sea urchin control and kelp restoration, offers hope for rebuilding stocks against a backdrop of escalating environmental stressors., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Peters et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The COVID-19 pandemic has significantly impacted global health, especially in vulnerable populations like kidney transplant recipients (KTRs). Recently, mass spectrometry-based proteomics has emerged as a powerful tool to shed light on a broad spectrum of dysregulated biological processes in KTRs with COVID-19. In this study, we prospectively collected blood samples from 17 COVID-19-positive KTRs and 10 non-infected KTRs between May and September 2020. Using tandem mass tag-based quantitative proteomics, we analyzed peripheral blood mononuclear cells (PBMCs), plasma protein biomarkers, and lymphocyte counts, followed by bioinformatics analysis. Our results revealed significant proteomic alterations in COVID-19-infected KTRs, particularly in pathways related to glycolysis, glucose metabolism, and neutrophil degranulation. Additionally, we observed an altered immune response characterized by elevated cytokines and decreased lymphocyte counts. Notably, KTRs with AKI exhibited worse clinical outcomes, including higher rates of ICU admission and mechanical ventilation. Comparative analysis of PBMC proteomic profiles between AKI and non-AKI patients identified distinct immune-related pathways, with AKI patients showing marked changes in innate immune responses, particularly neutrophil degranulation. Furthermore, we observed a negative correlation between T cell counts and neutrophil degranulation, suggesting a role for immune dysregulation in COVID-19. Our findings provide critical insights into the immune and metabolic responses in COVID-19-infected KTRs, especially those with AKI, highlighting the need for focused research and therapeutic strategies targeting immune dysregulation in this high-risk population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Leite, Sousa, Rodrigues, Brunialti, Medina-Pestana, Butler, Peters-Sengers, Requião-Moura and Salomão.)

Background: Hepatic glycogen storage diseases (GSDs) are characterised by enzyme defects affecting liver glycogen metabolism, where carbohydrate supplementation to prevent overnight hypoglycaemia is common. Concerns around sleep quality in hepatic GSDs relate to emerging evidence that overnight dysglycaemia impacts sleep quality., Methods: This prospective observational study reported sleep quality and duration in children with hepatic GSDs over 7 days utilising: actigraphy (Actiwatch 2 by Phillips Respironics), sleep diaries, proxy reported age-appropriate sleep and quality-of-life (QoL) questionnaires, in the context of nocturnal glycaemic profiles continuous glucose monitor (CGM, Dexcom G6) and nocturnal dietary management strategies. Significant hypo- and hyperglycaemia were defined as ≥1% of sleep diary documented nocturnal period, recording <3.5 and >10.0 mmol/L, respectively., Results: Seven children with hepatic GSD (aged 1-17 years) participated. Objective sleep quality was poor, with actigraphy demonstrating that no child achieved the minimum sleep duration recommended for age. Subjective sleep quality was also poor, with 4/5 documenting significant daytime sleepiness and 6/6 reporting poor sleep hygiene. Children prescribed overnight bolus feeds (OBF) ( n  = 2) recorded shorter sleep duration compared to other nocturnal management strategies. Parent-reported QoL suggested poor disease-related QoL outcomes for this cohort., Conclusion: Objective and subjective sleep disturbances and reduced QoL are common within our sample of children with hepatic GSD. From our observations these outcomes may be linked to nutritional overnight interventions, especially OBFs, rather than overnight glucose levels. Consideration of the impacts of overnight feeding strategies on sleep quality and QoL in children with hepatic GSD should inform future management strategies., Competing Interests: Lucas Agnoletto, Moya Vandeleur, Mary White, Anne‐Marie Adams, Rebecca Halligan and Heidi Peters all declare they have no conflicts of interest., (© 2024 The Author(s). JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.)

Background: The immunological determinants of delayed viral clearance and intrahost viral evolution that drive the development of new pathogenic virus strains in immunocompromised individuals are unknown. Therefore, we longitudinally studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immune responses in relation to viral clearance and evolution in immunocompromised individuals., Methods: Among Omicron-infected immunocompromised individuals, we determined SARS-CoV-2-specific T- and B-cell responses, anti-spike immunoglobulin G (IgG) and IgG3 titers, neutralization titers, and monoclonal antibody (mAb) resistance-associated mutations. The 28-day post-enrollment nasopharyngeal specimen defined early (reverse-transcription polymerase chain reaction [RT-PCR] negative ≤28 days) or late (RT-PCR positive >28 days) viral clearance., Results: Of 30 patients included (median age, 61.9 [interquartile range, 47.4-72.3] years; 50% females), 20 (66.7%) received mAb therapy. Thirteen (43.3%) demonstrated early and 17 (56.7%) late viral clearance. Patients with early viral clearance and patients without resistance-associated mutations had significantly higher baseline interferon-γ release, and patients with early viral clearance had a higher frequency of SARS-CoV-2-specific B cells at baseline. In non-mAb-treated patients, day 7 IgG and neutralization titers were significantly higher in those with early versus late viral clearance., Conclusions: An early robust adaptive immune response is vital for efficient viral clearance and associated with less emergence of mAb resistance-associated mutations in Omicron-infected immunocompromised patients. This emphasizes the importance of early SARS-CoV-2-specific T- and B-cell responses and thereby provides a rationale for development of novel therapeutic approaches., Competing Interests: Potential conflicts of interest. W. J. W. reported receiving grant support from the NWO, grant from the Amsterdam UMC Graduate School outside the submitted work, and personal fees (paid to his institution) from AstraZeneca and Shionogi. E. B. reported receiving grant support from the NWO, outside the submitted work. H. P.-S. reported receiving a Kolff postdoc grant, outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: In this study, we employ a multiomic approach to identify major cell types and subsets, and their transcriptomic profiles within the infrapatellar fat pad (IFP), and to determine differences in the IFP based on knee osteoarthritis (KOA), sex and obesity status., Methods: Single-nucleus RNA sequencing of 82 924 nuclei from 21 IFPs (n=6 healthy control and n=15 KOA donors), spatial transcriptomics and bioinformatic analyses were used to identify contributions of the IFP to KOA. We mapped cell subclusters from other white adipose tissues using publicly available literature. The diversity of fibroblasts within the IFP was investigated by bioinformatic analyses, comparing by KOA, sex and obesity status. Metabolomics was used to further explore differences in fibroblasts by obesity status., Results: We identified multiple subclusters of fibroblasts, macrophages, adipocytes and endothelial cells with unique transcriptomic profiles. Using spatial transcriptomics, we resolved distributions of cell types and their transcriptomic profiles and computationally identified putative cell-cell communication networks. Furthermore, we identified transcriptomic differences in fibroblasts from KOA versus healthy control donor IFPs, female versus male KOA-IFPs and obese versus normal body mass index (BMI) KOA-IFPs. Finally, using metabolomics, we defined differences in metabolite levels in supernatants of naïve, profibrotic stimuli-treated and proinflammatory stimuli-treated fibroblasts from obese compared to normal BMI KOA-IFPs., Conclusions: Overall, by employing a multiomic approach, this study provides the first comprehensive map of the cellular and transcriptomic diversity of human IFP and identifies IFP fibroblasts as key cells contributing to transcriptomic and metabolic differences related to KOA disease, sex or obesity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Background: Hospital mergers remain common, but their influence on healthcare quality varies. Data on effects of European hospital mergers are ill defined, and academic hospitals in particular. This case study assesses early quality of care changes in two formerly competing Dutch academic hospitals that merged on June 6, 2018., Methods: Statistical process control and interrupted time series analysis were performed. All adult, non-psychiatric patients, admitted between 01-03-2016 and 01-10-2022 were eligible for analysis. Primary outcome measure was all cause in-hospital mortality (or hospice), secondary outcomes were unplanned 30-day readmissions to same hospital, length of stay, and patients' hospital rating. Data were obtained from electronic health records, and patient experience surveys., Findings: The mean (SD) age of the 573 813 included patients was 54·3 (18·9) years. The minority was female (277 817, 48·4 %), and most admissions were acute (308 597, 53·8 %). No merger related change in mortality was found in the first 20 months post-merger (limited to the pre-Covid-19 era). For this same period, the 30-day readmission incidence changed to a downward slope post-merger, and the length of stay shortened (immediate level-change -3·796 % (95 % CI, -5·776 % to -1·816 %) and trend-change -0·150 % per month (95 % CI, -0·307 % to 0·007 %)). Patients' hospital ratings seemed to improve post-merger., Interpretation: In this quality improvement study, a full- and gradual post-merger integration strategy for a Dutch academic hospital merger was not associated with changes in in-hospital mortality, and yielded slight improved results for secondary quality of care outcomes., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:IJA Wissink reports a relationship with Amsterdam University Medical Centres that includes: employment. APJ Vlaar reports a relationship with Amsterdam University Medical Centres that includes: employment. M Schinkel reports a relationship with Amsterdam University Medical Centres that includes: employment. K Kruijthof reports a relationship with Amsterdam University Medical Centres that includes: board membership. H Peters-Sengers reports a relationship with Amsterdam University Medical Centres that includes: employment. WJ Wiersinga reports a relationship with Amsterdam University Medical Centres that includes: employment. S. A. Jones has no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Kidneys donated after circulatory death (DCD) perform similarly to kidneys donated after brain death (DBD). However, the respective incidences of delayed graft function (DGF) differ. This questions the donor type-specific impact of early graft function on long-term outcomes. Using competing risk and Cox-regression analysis, we compared death-censored graft loss between types of early graft function: DGF (temporary dialysis dependency started within 7 days after transplantation), slow graft function (3-day plasma creatinine decline less than 10% per day), and immediate graft function. In 1061 DBD and 1605 DCD graft recipients (January 2014 until January 2023), graft survival was similar. DGF was associated with death-censored graft loss in DBD and DCD (adjusted hazard ratios: DGF in DBD: 1.79 [1.04-2.91], P = .027, DGF in DCD: 1.84 [1.18-2.87], P = .008; Reference: no DGF). Slow graft function was associated with death-censored graft loss in DBD, but not significantly in DCD (adjusted hazard ratios DBD: 2.82 (1.34-5.93), P = .007, and DCD: 1.54 (0.72-3.35), P = .262; Reference: immediate graft function). Early graft dysfunction has a differential impact on graft outcome in DBD and DCD. The differences between DBD and DCD should be accounted for in research and the clinic., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Microbiota alterations are common in patients hospitalised for severe infections, and preclinical models have shown that anaerobic butyrate-producing gut bacteria protect against systemic infections. However, the relationship between microbiota disruptions and increased susceptibility to severe infections in humans remains unclear. We investigated the relationship between gut microbiota and the risk of future infection-related hospitalisation in two large population-based cohorts., Methods: In this observational microbiome study, gut microbiota were characterised using 16S rRNA gene sequencing in independent population-based cohorts from the Netherlands (HELIUS study; derivation cohort) and Finland (FINRISK 2002 study; validation cohort). HELIUS was conducted in Amsterdam, Netherlands, and included adults (aged 18-70 years at inclusion) who were randomly sampled from the municipality register of Amsterdam. FINRISK 2002 was conducted in six regions in Finland and is a population survey that included a random sample of adults (aged 25-74 years). In both cohorts, participants completed questionnaires, underwent a physical examination, and provided a faecal sample at inclusion (Jan 3, 2013, to Nov 27, 2015, for HELIUS participants and Jan 21 to April 19, 2002, for FINRISK participants. For inclusion in our study, a faecal sample needed to be provided and successfully sequenced, and national registry data needed to be available. Primary predictor variables were microbiota composition, diversity, and relative abundance of butyrate-producing bacteria. Our primary outcome was hospitalisation or mortality due to any infectious disease during 5-7-year follow-up after faecal sample collection, based on national registry data. We examined associations between microbiota and infection risk using microbial ecology and Cox proportional hazards., Findings: We profiled gut microbiota from 10 699 participants (4248 [39·7%] from the derivation cohort and 6451 [60·3%] from the validation cohort). 602 (5·6%) participants (152 [3·6%] from the derivation cohort; 450 [7·0%] from the validation cohort) were hospitalised or died due to infections during follow-up. Gut microbiota composition of these participants differed from those without hospitalisation for infections (derivation p=0·041; validation p=0·0002). Specifically, higher relative abundance of butyrate-producing bacteria was associated with a reduced risk of hospitalisation for infections (derivation cohort cause-specific hazard ratio 0·75 [95% CI 0·60-0·94] per 10% increase in butyrate producers, p=0·013; validation cohort 0·86 [0·77-0·96] per 10% increase, p=0·0077). These associations remained unchanged following adjustment for demographics, lifestyle, antibiotic exposure, and comorbidities., Interpretation: Gut microbiota composition, specifically colonisation with butyrate-producing bacteria, was associated with protection against hospitalisation for infectious diseases in the general population across two independent European cohorts. Further studies should investigate whether modulation of the microbiome can reduce the risk of severe infections., Funding: Amsterdam UMC, Porticus, National Institutes of Health, Netherlands Organisation for Health Research and Development (ZonMw), and Leducq Foundation., Competing Interests: Declaration of interests DM owns stock in and is a consultant for Biomesense. AHMvdZ reports grants from Health Hjolland, GSK, Boehringer Ingelheim, and Vertx; consulting fees from Boehringer Ingelheim and AstraZeneca; and honoraria from GSK, all outside the submitted work; and is a chair of the data safety monitoring board of a study on bronchopulmonary dysplasia in neonates. B-JvdB is the chair of the cardiovasular theme of HELIUS, the Netherlands Society of Hypertension, and Amsterdam Cardiovascular Sciences; and participates on the committee of the Dutch Cardiovascular Alliance. RK is on the Scientific Advisory Board of Gencirq, Cybele, DayTwo, Biomesense, and Micronoma; owns stock in Gencirq, Cybele, Biomesense, Micronoma, and Biota; is a consultant for DayTwo and Biomesense; and is a cofounder of Micronoma and Biota. MN is on the Scientific Advisory Board of Caelus Pharmaceuticals. TN reports grants from the Finnish Research Council, Emil Aaltonen Foundation, Sigrid Jusélius Foundation, and Finnish Foundation for Cardiovascular Research; and honoraria from Servier Finland and AstraZeneca. WJW reports grants from ZonMw/NWO and EU (Eurostars); and ad hoc consultancy for AstraZeneca and Shionogi, outside the submitted work. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective and Background: Epilepsy patients rank memory problems as their most significant cognitive comorbidity. Current clinical assessments are laborious to administer and score and may not always detect subtle memory decline. The Famous Faces Task (FF) has robustly demonstrated that left temporal lobe epilepsy (LTLE) patients remember fewer names and biographical details compared to right TLE (RTLE) patients and healthy controls (HCs). We adapted the FF task to capture subjects' entire spontaneous spoken recall, then scored responses using manual and natural language processing (NLP) methods. We expected to replicate previous group level differences using spontaneous speech and semi-automated analysis., Methods: Seventy-three (N=73) adults (28 LTLE, 18 RTLE, and 27 HCs) were included in a case-control prospective study design. Twenty FF in politics, sports, and entertainment (active 2008-2017) were shown to subjects, who were asked if they could recognize and spontaneously recall as much biographical detail as possible. We created human-generated and automatically-generated keyword dictionaries for each celebrity, based on a randomly selected training set of half of the HC transcripts. To control for speech output, we measured the speech duration, total word count and content word count for the FF task and a Cookie Theft Control Task (CTT), in which subjects were merely asked to describe a visual scene. Subjects' responses to FF and CTT tasks were recorded, transcribed, and analyzed in a blinded manner with a combination of manual and automated NLP approaches., Results: Famous face recognition accuracy was similar between groups. LTLE patients recalled fewer biographical details compared to HCs and RTLEs using both the gold-standard human-generated dictionary (24%±12% vs. 31%±12% and 30%±12%, p=0.007) and the automated dictionary (24%±12% vs. 31%±12% and 32%±13%, p=0.007). There were no group level differences in speech duration, total word count, or content word count for either the FF and CTT to explain difference in recall performance. There was a positive, statistically significant relationship between MOCA score and FF recall performance as scored by the human-generated (ρ= .327, p= .029) and automatically-generated dictionaries (ρ= .422, p= .004) for TLE subjects, but not HCs, an effect that was driven by LTLE subjects., Discussion: LTLE patients remember fewer details of famous people than HCs or RTLE patients, as discovered by NLP analysis of spontaneous recall. Decreased biographical memory was not due to decreased speech output and correlated with lower MOCA scores. NLP analysis of spontaneous recall can detect memory dysfunction in clinical populations in a semi-automated, objective, and sensitive manner.

Purpose: Patients who use substances (PWUS) report experiencing stigmatizing encounters and undertreatment of pain and withdrawal symptoms that increase the likelihood of patient-directed discharge (PDD). This scoping review examines North American literature to gain insights about how institutional factors intersect with patient experiences and contribute to PDD., Methods: A scoping review was conducted using MEDLINE, CINAHL, Scopus, and EMBASE databases. Screening was completed by two reviewers. A data extraction tool developed by the research team was used to collect demographic information and explore patients' experiences and reasons for PDD., Results: We present four themes related to PDD: i) effective management of pain and withdrawal symptoms, ii) therapeutic alliance with healthcare providers, iii) hospital policies, protocols, and procedures, and iv) recommendations. Notably, all patients in all qualitative studies reported predominant experiences of uncaring, stigmatizing interactions with healthcare providers., Discussion: Findings suggest that transformations are required at individual and institutional levels. At an individual level, to provide equitable care to all patients, healthcare providers in all practice settings should be competent to effectively and compassionately care for PWUS. At an institutional level, policies need to be re-envisioned to support the implementation of effective practices., Conclusion: Hospitals are faced with the challenges to ensure respectful care environments guided by harm reduction policies that will improve engagement of PWUS in services.

Introduction: The extent to which individuals living with HIV experience residential and healthcare mobility during pregnancy in the UK is unknown. We aimed to determine a minimum estimate of residential and healthcare mobility during pregnancy in people living with HIV in the UK in 2009-2019 to explore patterns of and factors associated with mobility and to assess whether mobility was associated with specific HIV outcomes., Methods: We analyzed data from the Integrated Screening Outcomes Surveillance Service to assess pregnancies with HIV in the UK and included livebirths and stillbirths with estimated delivery in 2009-2019. Residential mobility was defined as changing residential postcode between notification and delivery, and healthcare mobility was defined as changing NHS Trust or Strategic Health Authority (SHA) in that same timeframe. We used logistic regression to determine factors associated with residential and healthcare mobility and with detectable delivery viral load., Results: Among 10 305 pregnancies, 19.6% experienced residential mobility, 8.1% changed NHS Trust, and 4.5% changed SHA during pregnancy. Mobility was more likely to be experienced by younger women, migrants, and those with new antenatal diagnosis; residential but not healthcare mobility declined over time. In a fully adjusted model, mobility was not associated with having a detectable viral load at delivery. Higher proportions of infants were lost to follow-up after mobile pregnancies than after non-mobile pregnancies., Conclusions: This analysis provides new knowledge on mobility during pregnancy in the context of HIV, but further research is needed to understand its broader impacts and its utility as a marker to help identify families requiring additional follow-up and support., (© 2024 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Purpose: The purpose of this study is to report on the design, implementation, use and evaluation of TELLme, an online platform with annotated multiple-choice questions (MCQs) for formative assessment of knowledge acquisition covering an entire undergraduate medical curriculum., Materials and Methods: We used the Educational Design Research (EDR) framework to develop TELLme as an online platform with 24/7 access for students in a co-creation process between educators, faculty and students. EDR cycle 1 focused on prototyping, while EDR cycle 2 focused on upscaling, usage analysis and evaluation. Database entries were analysed for TELLme usage. Online surveys evaluated platform usability and support for student learning., Results: At the end of EDR cycle 2, TELLme contained 6,713 fully annotated MCQs aligned with the cognitive learning objectives of the curriculum. Up to 600 students per day used TELLme to self-assess their knowledge, answering 3,168,622 MCQs in two semesters. Surveys indicated good usability of TELLme, 75% of students indicated that TELLme helped them to identify knowledge gaps, and 72% agreed that TELLme supported their learning., Conclusions: Medical students use TELLme extensively to formatively assess their learning in a self-directed manner across the entire curriculum. TELLme aligns with the existing summative and formative system of assessment of the study programme.

Large language models (LLMs) demonstrate increasingly human-like abilities across a wide variety of tasks. In this paper, we investigate whether LLMs like ChatGPT can accurately infer the psychological dispositions of social media users and whether their ability to do so varies across socio-demographic groups. Specifically, we test whether GPT-3.5 and GPT-4 can derive the Big Five personality traits from users' Facebook status updates in a zero-shot learning scenario. Our results show an average correlation of r = 0.29 ( range = [ 0.22 , 0.33 ] ) between LLM-inferred and self-reported trait scores-a level of accuracy that is similar to that of supervised machine learning models specifically trained to infer personality. Our findings also highlight heterogeneity in the accuracy of personality inferences across different age groups and gender categories: predictions were found to be more accurate for women and younger individuals on several traits, suggesting a potential bias stemming from the underlying training data or differences in online self-expression. The ability of LLMs to infer psychological dispositions from user-generated text has the potential to democratize access to cheap and scalable psychometric assessments for both researchers and practitioners. On the one hand, this democratization might facilitate large-scale research of high ecological validity and spark innovation in personalized services. On the other hand, it also raises ethical concerns regarding user privacy and self-determination, highlighting the need for stringent ethical frameworks and regulation., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Background: Current continuous kidney replacement therapy (CKRT) protocols ignore physiological renal compensation for hypercapnia. This study aimed to explore feasibility, safety, and clinical benefits of pCO2-adapted CKRT for hypercapnic acute respiratory distress syndrome (ARDS) patients with indication for CKRT., Methods: We enrolled mechanically ventilated hypercapnic ARDS patients (pCO2 > 7.33 kPa) receiving regional citrate anticoagulation (RCA) based CKRT in a prospective, randomized-controlled pilot-study across five intensive care units at the Charité-Universitätsmedizin Berlin, Germany. Patients were randomly assigned 1:1 to the control group with bicarbonate targeted to 24 mmol/l or pCO 2 -adapted-CKRT with target bicarbonate corresponding to physiological renal compensation. Study duration was six days. Primary outcome was bicarbonate after 72 h. Secondary endpoints included safety and clinical endpoints. Endpoints were assessed in all patients receiving treatment., Results: From September 2021 to May 2023 40 patients (80% male) were enrolled. 19 patients were randomized to the control group, 21 patients were randomized to pCO 2 -adapted-CKRT. Five patients were excluded before receiving treatment: three in the control group (consent withdrawal, lack of inclusion criteria fulfillment (n = 2)) and two in the intervention group (lack of inclusion criteria fulfillment, sudden unexpected death) and were therefore not included in the analysis. Median plasma bicarbonate 72 h after randomization was significantly higher in the intervention group (30.70 mmol/l (IQR 29.48; 31.93)) than in the control group (26.40 mmol/l (IQR 25.63; 26.88); p < 0.0001). More patients in the intervention group received lung protective ventilation defined as tidal volume < 8 ml/kg predicted body weight. Thirty-day mortality was 10/16 (63%) in the control group vs. 8/19 (42%) in the intervention group (p = 0.26)., Conclusion: Tailoring CKRT to physiological renal compensation of respiratory acidosis appears feasible and safe with the potential to improve patient care in hypercapnic ARDS., Trial Registration: The trial was registered in the German Clinical Trials Register (DRKS00026177) on September 9, 2021 and is now closed., (© 2024. The Author(s).)

Background: The concept of entrustable professional activities (EPAs) has recently been extended to operationalize professional tasks in teacher training and faculty development in health professions education. The aim of this study is to report on the process and results of defining a set of teaching EPAs (t-EPAs) tailored to the local characteristics of a particular undergraduate medical program., Methods: The undergraduate medical program at the Charité - Universitätsmedizin Berlin is competency-based, integrates thematic modules and spans 6 years. A writing team identified teaching EPAs based on the program's study regulations and drafted content descriptions with titles, specifications and knowledge, skills and attitudes. Content validation involved a modified Delphi procedure with a systematic, iterative interaction between a panel of content experts consisting of purposively selected educators and physicians from our faculty (n = 11) and the writing team. The threshold for a consensus was an agreement of 80% of the participants., Results: After two Delphi rounds, a consensus was reached regarding the teaching activities to be included and their content descriptions. The response rate was 100% in both Delphi rounds. The Delphi results include the content descriptions of a total of 13 teaching EPAs, organized into the two overarching EPA domains of classroom-based (n = 10) and workplace-based (n = 3) activities. Tailoring the classroom EPAs to small group teaching and the workplace EPAs to supervising medical students led to several distinct EPAs. Another feature was the development of 2 teaching EPAs for interdisciplinary teaching., Conclusions: In systematic, Delphi-based process, we defined a set of 13 distinct teaching EPAs tailored to a specific undergraduate medical program that cover the core teaching tasks for faculty in this program. Our report on the principles of the process and the results may guide other medical schools and educators in defining and tailoring teaching EPAs according to their contexts., (© 2024. The Author(s).)

Purpose: The concept of Entrustable Professional Activities (EPA) is increasingly used to operationalize learning in the clinical workplace, yet little is known about the emotions of learners feeling the responsibility when carrying out professional tasks., Methods: We explored the emotional experiences of medical students in their final clerkship year when performing clinical tasks. We used an online reflective diary. Text entries were analysed using inductive-deductive content analysis with reference to the EPA framework and the control-value theory of achievement emotions., Results: Students described a wide range of emotions related to carrying out various clinical tasks. They reported positive-activating emotions, ranging from enjoyment to relaxation, and negative-deactivating emotions, ranging from anxiety to boredom. Emotions varied across individual students and were related to the characteristics of a task, an increasing level of autonomy, the students' perceived ability to perform a task and the level of supervision provided., Discussion: Emotions are widely present and impact on the workplace learning of medical students which is related to key elements of the EPA framework. Supervisors play a key role in eliciting positive-activating emotions and the motivation to learn by providing a level of supervision and guidance appropriate to the students' perceived ability to perform the task.

While a large proportion of the population in Papua New Guinea (PNG) maintain a subsistence lifestyle, exposure to modernisation and industrialisation since European contact has influenced a transition towards Western diets. This review aimed to scope and summarise the published research on dietary intake among Pacific Islander adults in PNG. Four electronic databases and grey literature were searched. Two reviewers completed the screening and data extraction. Fourteen studies were included from the Highlands ( n = 7), Southern ( n = 5), Momase ( n = 1) and both the Highlands/Southern region ( n = 1). No studies were from the Islands region. The majority of the studies were published prior to the year 2000 ( n = 9). Geographical region and degree of urbanisation had an impact on dietary intake. Urban areas reported higher intakes of energy, protein and fat compared to rural areas. In the Southern region, a variety of foods, including sago, taro, kaukau, cooked banana, coconut and cassava contributed to energy intake, while kaukau was the main energy and protein source in the Highlands. The main foods contributing to protein in the Southern region were fresh fish, land animals and purchased animals. This review highlights an evidence gap regarding dietary intake research. Within the context of international initiatives, there is an urgent call for research aimed at understanding the social and cultural contextualisation of dietary behaviours in PNG.

Background & Aims: Clostridioides difficile is a toxin-secreting bacteria that is an urgent antimicrobial resistance threat, with approximately 25% of patients developing recurrent infections. Inflammatory bowel disease (IBD) patients are at increased risk of severe, recurrent C. difficile infection., Methods: To investigate a role for C. difficile infection in IBD pathogenesis, we collected peripheral blood and stool from 20 each of ulcerative colitis patients, Crohn's disease patients, and healthy control subjects. We used a flow cytometric activation induced marker assay to quantify C. difficile toxin-specific CD4+ T cells and 16S ribosomal RNA sequencing to study microbiome diversity., Results: We found IBD patients had significantly increased levels of C. difficile toxin B-specific CD4+ T cells, but not immunoglobulin G or immunoglobulin A, compared with healthy control subjects. Within antigen-specific CD4+ T cells, T helper type 17 cells and cells expressing the gut homing receptor integrin β7 were reduced compared with healthy control subjects, similar to our previous study of non-IBD patients with recurrent C. difficile infection. Stool microbiome analysis revealed that gut homing, toxin-specific CD4+ T cells negatively associated with microbial diversity and, along with T helper type 17 cells, positively associated with bacteria enriched in healthy control subjects., Conclusions: These data suggest that IBD patients, potentially due to underlying intestinal dysbiosis, experience undiagnosed C. difficile infections that result in impaired toxin-specific immunity. This may contribute to the development of inflammatory T cell responses toward commensal bacteria and provide a rationale for C. difficile testing in IBD patients., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background: The study objective was to develop and validate a questionnaire to capture facilitation activities in PBL by the tutor and the group with reference to a theoretical model of teaching quality., Methods: We developed 19 items assigned to six factors to evaluate collaborative learning processes in relation to facilitation by the tutor and the student PBL group. We analysed construct and criterion validity in 419 undergraduate medical students in 152 online PBL groups., Results: Construct validity was confirmed based on factor dimensionality in line with the theoretical assumptions as well as satisfactory internal reliabilities and intraclass correlation coefficients. Criterion validity was supported by the correlation of a) tutor facilitation activities with the success of group self-facilitation and b) facilitation activities with learning gain and satisfaction in the PBL sessions., Discussion: The questionnaire provides a more comprehensive understanding of collaborative learning processes in PBL and the interplay between facilitation activities by the tutor and the group.

Background: The qualities of trainees play a key role in entrustment decisions by clinical supervisors for the assignments of professional tasks and levels of supervision. A recent body of qualitative research has shown that in addition to knowledge and skills, a number of personality traits are relevant in the workplace; however, the relevance of these traits has not been investigated empirically. The aim of this study was to analyse the workplace performance of final-year medical students using an Entrustable Professional Activity (EPA) framework in relation to their personality traits., Methods: Medical students at the end of their final clerkship year were invited to participate in an online survey-based, cross-sectional field study. In the survey, the workplace performance was captured using a framework consisting of levels of experienced supervision and a defined set of 12 end-of-undergraduate medical training EPAs. The Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism, and openness) of the participating medical students were measured using the Big Five Inventory-SOEP (BFI-S), which consists of 15 items that are rated on a seven-point Likert scale. The data were analysed using descriptive and inferential statistics., Results: The study included 880 final-year medical students (mean age: 27.2 years, SD = 3.0; 65% female). The levels of supervision under which the final-year clerkship students carried out the EPAs varied considerably. Significant correlations were found between the levels of experienced supervision and all Big Five dimensions The correlations with the dimensions of extraversion, agreeableness, conscientiousness and openness were positive, and that for the neuroticism dimension was negative (range r = 0.17 to r = - 0.23). Multiple regression analyses showed that the combination of the Big Five personality traits accounted for 0.8-7.5% of the variance in supervision levels on individual EPAs., Conclusions: Using the BFI-S, we found that the levels of supervision on a set of end-of-undergraduate medical training EPAs were related to the personality traits of final-year medical students. The results of this study confirm the existing body of research on the role of conscientiousness and extraversion in entrustment decision-making and, in particular, add the personality trait of neuroticism as a new and relevant trainee quality to be considered., (© 2024. The Author(s).)

Rationale: The plasma lipidome has the potential to reflect many facets of the host status during severe infection. Previous work is limited to specific lipid groups or was focused on lipids as prognosticators. Objectives: To map the plasma lipidome during sepsis due to community-acquired pneumonia (CAP) and determine the disease specificity and associations with clinical features. Methods: We analyzed 1,833 lipid species across 33 classes in 169 patients admitted to the ICU with sepsis due to CAP, 51 noninfected ICU patients, and 48 outpatient controls. In a paired analysis, we reanalyzed patients still in the ICU 4 days after admission ( n  = 82). Measurements and Main Results: A total of 58% of plasma lipids were significantly lower in patients with CAP-attributable sepsis compared with outpatient controls (6% higher, 36% not different). We found strong lipid class-specific associations with disease severity, validated across two external cohorts, and inflammatory biomarkers, in which triacylglycerols, cholesterol esters, and lysophospholipids exhibited the strongest associations. A total of 36% of lipids increased over time, and stratification by survival revealed diverging lipid recovery, which was confirmed in an external cohort; specifically, a 10% increase in cholesterol ester levels was related to a lower odds ratio (0.84; P  = 0.006) for 30-day mortality (absolute mortality, 18 of 82). Comparison with noninfected ICU patients delineated a substantial common illness response (57.5%) and a distinct lipidomic signal for patients with CAP-attributable sepsis (37%). Conclusions: Patients with sepsis due to CAP exhibit a time-dependent and partially disease-specific shift in their plasma lipidome that correlates with disease severity and systemic inflammation and is associated with higher mortality.

In 2005, Olle ten Cate introduced the concept of Entrustable Professional Activities (EPAs) in the assessment of medical trainees in competency-based postgraduate training (ten Cate, 2005). Over the past two decades, EPAs have found their way into mainstream competency-based education and training for almost all health care professions, from medicine to pharmacy, nursing, dentistry, veterinary dietetics, and the physician assistant field (ten Cate, 2020). Although the terms 'entrustable' and later, 'entrustability', were defined as neologisms at the time, the concept of trust was not unfamiliar to clinicians who are continually required to manage risks in the inherently complex health care business and education (Damodaran et al. 2017). Patient trust in the doctor, the health care system and medical profession, and supervisor trust in the trainee are examples of interpersonal, social, and organizational levels of trust. Therefore, the language of trust and entrustability has offered a more authentic and practical vocabulary than that of competency (Damodaran et al. 2017).

Background: Sepsis is a life-threatening condition arising from an aberrant host response to infection. Recent single-cell RNA sequencing investigations identified an immature bone-marrow-derived CD14 + monocyte phenotype with immune suppressive properties termed "monocyte state 1" (MS1) in patients with sepsis. Our objective was to determine the association of MS1 cell profiles with disease presentation, outcomes, and host response characteristics., Methods: We used the transcriptome deconvolution method (CIBERSORTx) to estimate the percentage of MS1 cells from blood RNA profiles of patients with sepsis admitted to the intensive care unit (ICU). We compared these profiles to ICU patients without infection and to healthy controls. Host response dysregulation was further studied by gene co-expression network and gene set enrichment analyses of blood leukocytes, and measurement of 15 plasma biomarkers indicative of pathways implicated in sepsis pathogenesis., Results: Sepsis patients (n = 332) were divided into three equally-sized groups based on their MS1 cell levels (low, intermediate, and high). MS1 groups did not differ in demographics or comorbidities. The intermediate and high MS1 groups presented with higher disease severity and more often had shock. MS1 cell abundance did not differ between survivors and non-survivors, or between patients who did or did not acquire a secondary infection. Higher MS1 cell percentages were associated with downregulation of lymphocyte-related and interferon response genes in blood leukocytes, with concurrent upregulation of inflammatory response pathways, including tumor necrosis factor signaling via nuclear factor-κB. Previously described sepsis host response transcriptomic subtypes showed different MS1 cell abundances, and MS1 cell percentages positively correlated with the "quantitative sepsis response signature" and "molecular degree of perturbation" scores. Plasma biomarker levels, indicative of inflammation, endothelial cell activation, and coagulation activation, were largely similar between MS1 groups. In ICU patients without infection (n = 215), MS1 cell percentages and their relation with disease severity, shock, and host response dysregulation were highly similar to those in sepsis patients., Conclusions: High MS1 cell percentages are associated with increased disease severity and shock in critically ill patients with sepsis or a non-infectious condition. High MS1 cell abundance likely indicates broad immune dysregulation, entailing not only immunosuppression but also anomalies reflecting exaggerated inflammatory responses., (© 2024. The Author(s).)

Matching the language or content of a message to the psychological profile of its recipient (known as "personalized persuasion") is widely considered to be one of the most effective messaging strategies. We demonstrate that the rapid advances in large language models (LLMs), like ChatGPT, could accelerate this influence by making personalized persuasion scalable. Across four studies (consisting of seven sub-studies; total N = 1788), we show that personalized messages crafted by ChatGPT exhibit significantly more influence than non-personalized messages. This was true across different domains of persuasion (e.g., marketing of consumer products, political appeals for climate action), psychological profiles (e.g., personality traits, political ideology, moral foundations), and when only providing the LLM with a single, short prompt naming or describing the targeted psychological dimension. Thus, our findings are among the first to demonstrate the potential for LLMs to automate, and thereby scale, the use of personalized persuasion in ways that enhance its effectiveness and efficiency. We discuss the implications for researchers, practitioners, and the general public., (© 2024. The Author(s).)

The lipidome of immune cells during infection has remained unexplored, although evidence of the importance of lipids in the context of immunity is mounting. In this study, we performed untargeted lipidomic analysis of blood monocytes and neutrophils from patients hospitalized for pneumonia and age- and sex-matched noninfectious control volunteers. We annotated 521 and 706 lipids in monocytes and neutrophils, respectively, which were normalized to an extensive set of internal standards per lipid class. The cellular lipidomes were profoundly altered in patients, with both common and distinct changes between the cell types. Changes involved every level of the cellular lipidome: differential lipid species, class-wide shifts, and altered saturation patterns. Overall, differential lipids were mainly less abundant in monocytes and more abundant in neutrophils from patients. One month after hospital admission, lipidomic changes were fully resolved in monocytes and partially in neutrophils. Integration of lipidomic and concurrently collected transcriptomic data highlighted altered sphingolipid metabolism in both cell types. Inhibition of ceramide and sphingosine-1-phosphate synthesis in healthy monocytes and neutrophils resulted in blunted cytokine responses upon stimulation with lipopolysaccharide. These data reveal major lipidomic remodeling in immune cells during infection, and link the cellular lipidome to immune functionality.

Rationale: Lymphopenia in coronavirus disease (COVID-19) is associated with increased mortality. Objectives: To explore the association between lymphopenia, host response aberrations, and mortality in patients with lymphopenic COVID-19. Methods: We determined 43 plasma biomarkers reflective of four pathophysiological domains: endothelial cell and coagulation activation, inflammation and organ damage, cytokine release, and chemokine release. We explored if decreased concentrations of lymphocyte-derived proteins in patients with lymphopenia were associated with an increase in mortality. We sought to identify host response phenotypes in patients with lymphopenia by cluster analysis of plasma biomarkers. Measurements and Main Results: A total of 439 general ward patients with COVID-19 were stratified by baseline lymphocyte counts: normal (>1.0 × 10 9 /L; n  = 167), mild lymphopenia (>0.5 to ⩽1.0 × 10 9 /L; n  = 194), and severe lymphopenia (⩽0.5 × 10 9 /L; n  = 78). Lymphopenia was associated with alterations in each host response domain. Lymphopenia was associated with increased mortality. Moreover, in patients with lymphopenia ( n  = 272), decreased concentrations of several lymphocyte-derived proteins (e.g., CCL5, IL-4, IL-13, IL-17A) were associated with an increase in mortality (at P  < 0.01 or stronger significance levels). A cluster analysis revealed three host response phenotypes in patients with lymphopenia: "hyporesponsive" (23.2%), "hypercytokinemic" (36.4%), and "inflammatory-injurious" (40.4%), with substantially differing mortality rates of 9.5%, 5.1%, and 26.4%, respectively. A 10-biomarker model accurately predicted these host response phenotypes in an external cohort with similar mortality distribution. The inflammatory-injurious phenotype showed a remarkable combination of relatively high inflammation and organ damage markers with high antiinflammatory cytokine levels yet low proinflammatory cytokine levels. Conclusions: Lymphopenia in COVID-19 signifies a heterogenous group of patients with distinct host response features. Specific host responses contribute to lymphopenia-associated mortality in COVID-19, including reduced CCL5 levels.

First released in 2006, DrugBank (https://go.drugbank.com) has grown to become the 'gold standard' knowledge resource for drug, drug-target and related pharmaceutical information. DrugBank is widely used across many diverse biomedical research and clinical applications, and averages more than 30 million views/year. Since its last update in 2018, we have been actively enhancing the quantity and quality of the drug data in this knowledgebase. In this latest release (DrugBank 6.0), the number of FDA approved drugs has grown from 2646 to 4563 (a 72% increase), the number of investigational drugs has grown from 3394 to 6231 (a 38% increase), the number of drug-drug interactions increased from 365 984 to 1 413 413 (a 300% increase), and the number of drug-food interactions expanded from 1195 to 2475 (a 200% increase). In addition to this notable expansion in database size, we have added thousands of new, colorful, richly annotated pathways depicting drug mechanisms and drug metabolism. Likewise, existing datasets have been significantly improved and expanded, by adding more information on drug indications, drug-drug interactions, drug-food interactions and many other relevant data types for 11 891 drugs. We have also added experimental and predicted MS/MS spectra, 1D/2D-NMR spectra, CCS (collision cross section), RT (retention time) and RI (retention index) data for 9464 of DrugBank's 11 710 small molecule drugs. These and other improvements should make DrugBank 6.0 even more useful to a much wider research audience ranging from medicinal chemists to metabolomics specialists to pharmacologists., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Pneumonia caused by multi-drug-resistant Klebsiella pneumoniae (MDR- Kpneu ) poses a major public health threat, especially to immunocompromised or hospitalized patients. This study aimed to determine the immunostimulatory effect of the Toll-like receptor 5 ligand flagellin on primary human lung epithelial cells during infection with MDR- Kpneu . Human bronchial epithelial (HBE) cells, grown on an air-liquid interface, were inoculated with MDR- Kpneu on the apical side and treated during ongoing infection with antibiotics (meropenem) and/or flagellin on the basolateral and apical side, respectively; the antimicrobial and inflammatory effects of flagellin were determined in the presence or absence of meropenem. In the absence of meropenem, flagellin treatment of MDR- Kpneu -infected HBE cells increased the expression of antibacterial defense genes and the secretion of chemokines; moreover, supernatants of flagellin-exposed HBE cells activated blood neutrophils and monocytes. However, in the presence of meropenem, flagellin did not augment these responses compared to meropenem alone. Flagellin did not impact the outgrowth of MDR- Kpneu . Flagellin enhances antimicrobial gene expression and chemokine release by the MDR- Kpneu -infected primary human bronchial epithelium, which is associated with the release of mediators that activate neutrophils and monocytes. Topical flagellin therapy may have potential to boost immune responses in the lung during pneumonia.

Nuclear magnetic resonance (NMR) spectral analysis of biofluids can be a time-consuming process, requiring the expertise of a trained operator. With NMR becoming increasingly popular in the field of metabolomics, there is a growing need to change this paradigm and to automate the process. Here we introduce MagMet, an online web server, that automates the processing and quantification of 1D 1 H NMR spectra from biofluids-specifically, human serum/plasma metabolites, including those associated with inborn errors of metabolism (IEM). MagMet uses a highly efficient data processing procedure that performs automatic Fourier Transformation, phase correction, baseline optimization, chemical shift referencing, water signal removal, and peak picking/peak alignment. MagMet then uses the peak positions, linewidth information, and J-couplings from its own specially prepared standard metabolite reference spectral NMR library of 85 serum/plasma compounds to identify and quantify compounds from experimentally acquired NMR spectra of serum/plasma. MagMet employs linewidth adjustment for more consistent quantification of metabolites from higher field instruments and incorporates a highly efficient data processing procedure for more rapid and accurate detection and quantification of metabolites. This optimized algorithm allows the MagMet webserver to quickly detect and quantify 58 serum/plasma metabolites in 2.6 min per spectrum (when processing a dataset of 50-100 spectra). MagMet's performance was also assessed using spectra collected from defined mixtures (simulating other biofluids), with >100 previously measured plasma spectra, and from spiked serum/plasma samples simulating known IEMs. In all cases, MagMet performed with precision and accuracy matching the performance of human spectral profiling experts. MagMet is available at http://magmet.ca., (© 2023 The Authors. Magnetic Resonance in Chemistry published by John Wiley & Sons Ltd.)

Aims: Ischemia-reperfusion injury (IRI) during kidney transplant procedures is associated with adverse outcome. Alkaline phosphatase (AP) is an enzyme that has the potential to dampen IRI. Prior to this study, it had not been tested in the setting of kidney transplantation. This study aimed to evaluate the safety and feasibility of peri-procedural AP administration in living donor kidney transplantation., Methods: In this double blind, randomized, placebo-controlled, single-center pilot study, all eligible recipients of living donor kidneys were asked to give informed consent. AP (bRESCAP) or a placebo was administered intravenously over 24 hours after the transplantation procedure. The primary outcome-graft function at 1 year-was represented by iohexol measured glomerular filtration rate (mGFR). Serum and urine biomarkers within seven days after surgery were used as surrogate markers of kidney function and injury., Results: Eleven patients were enrolled of whom five were treated with bRESCAP and six with placebo. After 1 year, mGFR was not different between groups. No specific adverse events were observed in the bRESCAP group. Urine expression of injury biomarkers CCL14, NGAL and Cystatin C was lower in the bRESCAP group at day seven. This was statistically significant., Conclusion: This study illustrates that bRESCAP treatment is feasible in kidney transplantation, might have a dampening effect on IRI induced renal inflammation, and raises no safety concerns. Future research will evaluate the effects of bRESCAP treatment in donation after circulatory death kidney transplantation where IRI is more pronounced., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

The use of magnesium stearate along with lactose in Dry Powder Inhaler (DPI) formulations is increasing. The impact of different conditions of high shear blending on the distribution of magnesium stearate on lactose particles was investigated in this study. The formulated blends were manufactured using high shear blending of pre-blended coarse and fine lactose particles with 1.0% (w/w) magnesium stearate under different blending conditions, specifically blending speed and time. The effects of blending conditions on the distribution of magnesium stearate on lactose particles were clearly identifiable by characterizing the formulated blends by means of rheological evaluations, scanning electron microscopy, and chemical surface analysis using time-of-flight secondary ion mass spectrometry (ToF-SIMS). Rheological properties were significantly affected in blends with magnesium stearate compared to blends without magnesium stearate. Blending speed exhibited a strong influence on the distribution of magnesium stearate on lactose surface, while blending time had relatively minor effect., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Nuclear magnetic resonance (NMR) data are rarely deposited in open databases, leading to loss of critical scientific knowledge. Existing data reporting methods (images, tables, lists of values) contain less information than raw data and are poorly standardized. Together, these issues limit FAIR (findable, accessible, interoperable, reusable) access to these data, which in turn creates barriers for compound dereplication and the development of new data-driven discovery tools. Existing NMR databases either are not designed for natural products data or employ complex deposition interfaces that disincentivize deposition. Journals, including the Journal of Natural Products (JNP), are now requiring data submission as part of the publication process, creating the need for a streamlined, user-friendly mechanism to deposit and distribute NMR data.

Objectives: To determine the perspective of final-year medical students on the use of computed tomography (CT) in patients with sepsis., Methods: A total of 207 questionnaires were distributed to final-year medical students at a large university medical center, and 113 returned questionnaires met the criteria for inclusion in the analysis. Questions referred to sepsis guidelines, CT indications, and the use of contrast agents. Control variables included a level of practical experience as a final-year student (trimester of student's practical year) and previous radiological experience. Statistical hypothesis tests such as the Mann-Whitney U test and chi-square test were performed., Results: The majority of participating students, 85% (n = 91/107), considered a Systemic Organ Failure Assessment (SOFA) score ≥ 2 as a diagnostic criterion for sepsis. The presence of ≥ 2 positive systemic inflammatory response syndrome (SIRS) criteria was considered relevant for diagnosing sepsis by 34% (n = 34/100). Ninety-nine percent (n = 64/65) of the participants who fully agreed with a SOFA score ≥ 2 being relevant for diagnosing sepsis would also use it as an indication for a CT scan. Seventy-six percent (n = 78/103) of the students rated a known severe allergic reaction to contrast agents as an absolute contraindication for its administration. Ninety-five percent (n = 78/82) considered radiation exposure as problematic in CT examinations, especially in repeat CTs., Conclusion: Most final-year medical students were familiar with the sepsis criteria. Still, some referred to outdated diagnostic criteria. Participants saw the ability to plan further patient management based on CT as a major benefit. Most participants were aware of radiation as a risk of CT., Critical Relevance Statement: More detailed knowledge of CT in septic patients should be implemented in the medical curriculum. Retraining of medical students could help increase student confidence potentially improving patient care., Key Points: 1. Whereas the majority of final-year medical students were familiar with sepsis criteria, some referred to outdated diagnostic criteria. 2. Participants saw the ability to plan further patient management based on CT as a major benefit. 3. Most participants were aware of radiation as a risk of CT., (© 2023. The Author(s).)

Purpose: The heterogeneity in sepsis is held responsible, in part, for the lack of precision treatment. Many attempts to identify subtypes of sepsis patients identify those with shared underlying biology or outcomes. To date, though, there has been limited effort to determine overlap across these previously identified subtypes. We aimed to determine the concordance of critically ill patients with sepsis classified by four previously described subtype strategies., Methods: This secondary analysis of a multicenter prospective observational study included 522 critically ill patients with sepsis assigned to four previously established subtype strategies, primarily based on: (i) clinical data in the electronic health record (α, β, γ, and δ), (ii) biomarker data (hyper- and hypoinflammatory), and (iii-iv) transcriptomic data (Mars1-Mars4 and SRS1-SRS2). Concordance was studied between different subtype labels, clinical characteristics, biological host response aberrations, as well as combinations of subtypes by sepsis ensembles., Results: All four subtype labels could be adjudicated in this cohort, with the distribution of the clinical subtype varying most from the original cohort. The most common subtypes in each of the four strategies were γ (61%), which is higher compared to the original classification, hypoinflammatory (60%), Mars2 (35%), and SRS2 (54%). There was no clear relationship between any of the subtyping approaches (Cramer's V = 0.086-0.456). Mars2 and SRS1 were most alike in terms of host response biomarkers (p = 0.079-0.424), while other subtype strategies showed no clear relationship. Patients enriched for multiple subtypes revealed that characteristics and outcomes differ dependent on the combination of subtypes made., Conclusion: Among critically ill patients with sepsis, subtype strategies using clinical, biomarker, and transcriptomic data do not identify comparable patient populations and are likely to reflect disparate clinical characteristics and underlying biology., (© 2023. The Author(s).)

Background: The aetiology of idiopathic nephrotic syndrome (INS) remains partially unknown. Viral infections have been associated with INS onset. Since we observed fewer first onset INS cases during the Covid-19 pandemic, we hypothesised that lower INS incidence was the result of lockdown measures. Therefore, the aim of this study was to evaluate the incidence of childhood INS before and during the COVID-19 pandemic in two independent European INS cohorts., Methods: Children with new INS in the Netherlands (2018-2021) and Paris area (2018-2021) were included. We estimated incidences using census data for each region. Incidences were compared using two proportion Z-tests., Results: A total of 128 and 324 cases of first onset INS were reported in the Netherlands and Paris area, respectively, corresponding to an annual incidence of 1.21 and 2.58 per 100,000 children/year. Boys and young children (< 7 years) were more frequently affected. Incidence before and during the pandemic did not differ. When schools were closed, incidence was lower in both regions: 0.53 vs. 1.31 (p = 0.017) in the Netherlands and 0.94 vs. 2.63 (p = 0.049) in the Paris area. During peaks of hospital admissions for Covid-19, no cases were reported in the Netherlands or Paris area., Conclusions: Incidence of INS before and during the Covid-19 pandemic was not different, but when schools were closed during lockdown, incidence was significantly lower. Interestingly, incidences of other respiratory viral infections were also reduced as was air pollution. Together, these results argue for a link between INS onset and viral infections and/or environmental factors. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s).)

Background: The availability and correct use of personal protective equipment (PPE) to prevent and control infections plays a critical role in the safety of medical students in clinical placements. This study explored their experiences and perspectives in their final clerkship year with PPE during the COVID-19 pandemic., Methods: This qualitative study was based on social constructivism and was conducted in 2021 at the Charité - Universitätsmedizin Berlin. In three online focus group discussions, 15 medical students in their final clerkship year reported their experiences with PPE training and use during the COVID-19 pandemic. Data were recorded, transcribed and analysed based on Kuckartz's approach to content analysis. We drew upon the a priori dimensions of the capability, opportunity, motivation - behaviour (COM-B) model as main categories as well as emergent issues raised by the study participants (subcategories)., Results: In addition to the three main categories of the COM-B model, eleven subcategories were identified through inductive analysis. The study participants reported several factors that hindered the correct use of PPE. In the area of capabilities, these factors were related to learning experience with PPE in terms of both theoretical and practical learning together with later supervision in practice. In the area of opportunities, these factors included the limited availability of some PPE components, a lack of time for PPE instruction and supervision and inappropriate role modelling due to the inconsistent use of PPE by physicians and nursing staff. The area of motivation to use PPE was characterized by an ambivalent fear of infection by the SARS-CoV-2 virus and the prioritization of patient safety, i.e., the need to prevent the transmission of the virus to patients., Conclusions: Our study revealed several limitations pertaining to the enabling factors associated with the trainable behaviour "correct use of PPE". The concept of shared responsibility for student safety was used to derive recommendations for future improvement specifically for the medical school as an organization, the teachers and supervisors, and students themselves. This study may guide and stimulate other medical schools and faculties to explore and analyse components of student safety in clinical settings in times of infectious pandemics., (© 2023. The Author(s).)

Background: While acknowledgement of emotions' importance in simulation-based education is emerging, there are concerns regarding how education researchers understand the concept of emotions for them to deliberately incorporate emotionally charged scenarios into simulation-based education. This concern is highlighted especially in the context of medical education often lacking strong theoretical integration. To map out how current simulation-based education literature conceptualises emotion, we conducted a scoping review on how emotions and closely related constructs (e.g. stress, and emotional intelligence) are conceptualised in simulation-based education articles that feature medical students, residents, and fellows., Methods: The scoping review was based on articles published in the last decade identified through database searches (EMBASE and Medline) and hand-searched articles. Data extraction included the constructs featured in the articles, their definitions, instruments used, and the types of emotions captured. Only empirical articles were included (e.g. no review or opinion articles). Data were charted via descriptive analyses., Results: A total of 141 articles were reviewed. Stress was featured in 88 of the articles, while emotions and emotional intelligence were highlighted in 45 and 34 articles respectively. Conceptualisations of emotions lacked integration of theory. Measurements of emotions mostly relied on self-reports while stress was often measured via physiological and self-report measurements. Negative emotions such as anxiety were sometimes seen as interchangeable with the term stress. No inferences were made about specific emotions of participants from their emotional intelligence., Conclusions: Our scoping review illustrates that learners in simulation-based education are most often anxious and fearful. However, this is partially due to medical education prioritising measuring negative emotions. Further theoretical integration when examining emotions and stress may help broaden the scope towards other kinds of emotions and better conceptualisations of their impact. We call for simulation education researchers to reflect on how they understand emotions, and whether their understanding may neglect any specific aspect of affective experiences their simulation participants may have., (© 2023. Society in Europe for Simulation Applied to Medicine (SESAM) and BioMed Central Ltd.)

Objectives: This study aims to develop and pilot a hospital care coordination team intervention for patients with multimorbidity and identify key uncertainties., Methods: Practice-based, participatory pilot study with mixed methods in a middle-large teaching hospital. We included adult patients who had visited seven or more outpatient specialist clinics in 2018. The intervention consisted of an intake, a comprehensive review by a dedicated care coordination team, a consultation to discuss results and two follow-up appointments. We collected both quantitative and qualitative data., Results: Out of 131 invited patients, 28 participants received the intake and comprehensive review. The intervention resulted in mixed outputs and short-term outcomes. Among the 28 participants, 21 received recommendations for at least two out of three categories (medication, involved medical specialists, other). Patients' experienced effects ranged from no to very large effects. Key uncertainties were how to identify patients with a need for care coordination and the minimum of required data that can be collected during regular clinical care with feasible effort., Discussion: Recruitment and selection for hospital care coordination should be refined to include patients with multimorbidity who might benefit most. Outcomes of research and clinical care should align and first focus on evaluating the results of care coordination before evaluating health-related outcomes.

Background: Thrombocytopenia is associated with increased mortality in COVID-19 patients., Objective: To determine the association between thrombocytopenia and alterations in host response pathways implicated in disease pathogenesis in patients with severe COVID-19., Patients/methods: We studied COVID-19 patients admitted to a general hospital ward included in a national (CovidPredict) cohort derived from 13 hospitals in the Netherlands. In a subgroup, 43 host response biomarkers providing insight in aberrations in distinct pathophysiological domains (coagulation and endothelial cell function; inflammation and damage; cytokines and chemokines) were determined in plasma obtained at a single time point within 48 h after admission. Patients were stratified in those with normal platelet counts (150-400 × 10 9 /L) and those with thrombocytopenia (<150 × 10 9 /L)., Results: 6.864 patients were enrolled in the national cohort, of whom 1.348 had thrombocytopenia and 5.516 had normal platelets counts; the biomarker cohort consisted of 429 patients, of whom 85 with thrombocytopenia and 344 with normal platelet counts. Plasma D-dimer levels were not different in thrombocytopenia, although patients with moderate-severe thrombocytopenia (<100 × 10 9 /L) showed higher D-dimer levels, indicating enhanced coagulation activation. Patients with thrombocytopenia had lower plasma levels of many proinflammatory cytokines and chemokines, and antiviral mediators, suggesting involvement of platelets in inflammation and antiviral immunity. Thrombocytopenia was associated with alterations in endothelial cell biomarkers indicative of enhanced activation and a relatively preserved glycocalyx integrity., Conclusion: Thrombocytopenia in hospitalized patients with severe COVID-19 is associated with broad host response changes across several pathophysiological domains. These results suggest a role of platelets in the immune response during severe COVID-19., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Primary hyperoxaluria type 1 (PH1) has a highly heterogeneous disease course. Apart from the c.508G>A (p.Gly170Arg) AGXT variant, which imparts a relatively favorable outcome, little is known about determinants of kidney failure. Identifying these is crucial for disease management, especially in this era of new therapies., Methods: In this retrospective study of 932 patients with PH1 included in the OxalEurope registry, we analyzed genotype-phenotype correlations as well as the impact of nephrocalcinosis, urolithiasis, and urinary oxalate and glycolate excretion on the development of kidney failure, using survival and mixed model analyses., Results: The risk of developing kidney failure was the highest for 175 vitamin-B6 unresponsive ("null") homozygotes and lowest for 155 patients with c.508G>A and c.454T>A (p.Phe152Ile) variants, with a median age of onset of kidney failure of 7.8 and 31.8 years, respectively. Fifty patients with c.731T>C (p.Ile244Thr) homozygote variants had better kidney survival than null homozygotes ( P  = 0.003). Poor outcomes were found in patients with other potentially vitamin B6-responsive variants. Nephrocalcinosis increased the risk of kidney failure significantly (hazard ratio [HR] 3.17 [2.03-4.94], P  < 0.001). Urinary oxalate and glycolate measurements were available in 620 and 579 twenty-four-hour urine collections from 117 and 87 patients, respectively. Urinary oxalate excretion, unlike glycolate, was higher in patients who subsequently developed kidney failure ( P  = 0.034). However, the 41% intraindividual variation of urinary oxalate resulted in wide confidence intervals., Conclusion: In conclusion, homozygosity for AGXT null variants and nephrocalcinosis were the strongest determinants for kidney failure in PH1., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Dogs have repeatedly been shown to give their paw to an experimenter more times for no reward when a rewarded conspecific partner is absent than when a rewarded conspecific is present, thereby showing inequity aversion. However, rather than being inequity averse, dogs might give their paw more when a partner is absent due to the experimenter's procedure in which they move food in front of the subject to mimic feeding a partner. This action could increase subjects' perception of reward attainability. We tested this hypothesis by introducing an improved type of control condition in which subjects were unrewarded for giving the paw in the presence of a rewarded box, a condition that more closely resembles the inequity condition. Inequity averse subjects' performance did not differ based on whether the partner was another dog or a box. Moreover, these subjects gave the paw more times when no partner was present and the experimenter mimicked the feeding of a partner than when rewards were placed in the box. These results suggest that responses in the previous studies were inflated by subjects' increased perception of reward attainability when no partner was present and, therefore, over-exaggerated dogs' propensity to give up due to inequity aversion., (© 2023. The Author(s).)

Background: Coronavirus disease 2019 (COVID-19)-induced mortality occurs predominantly in older patients. Several immunomodulating therapies seem less beneficial in these patients. The biological substrate behind these observations is unknown. The aim of this study was to obtain insight into the association between ageing, the host response and mortality in patients with COVID-19., Methods: We determined 43 biomarkers reflective of alterations in four pathophysiological domains: endothelial cell and coagulation activation, inflammation and organ damage, and cytokine and chemokine release. We used mediation analysis to associate ageing-driven alterations in the host response with 30-day mortality. Biomarkers associated with both ageing and mortality were validated in an intensive care unit and external cohort., Results: 464 general ward patients with COVID-19 were stratified according to age decades. Increasing age was an independent risk factor for 30-day mortality. Ageing was associated with alterations in each of the host response domains, characterised by greater activation of the endothelium and coagulation system and stronger elevation of inflammation and organ damage markers, which was independent of an increase in age-related comorbidities. Soluble tumour necrosis factor receptor 1, soluble triggering receptor expressed on myeloid cells 1 and soluble thrombomodulin showed the strongest correlation with ageing and explained part of the ageing-driven increase in 30-day mortality (proportion mediated: 13.0%, 12.9% and 12.6%, respectively)., Conclusions: Ageing is associated with a strong and broad modification of the host response to COVID-19, and specific immune changes likely contribute to increased mortality in older patients. These results may provide insight into potential age-specific immunomodulatory targets in COVID-19., Competing Interests: Conflicts of interest: The authors declare no potential conflicts of interest., (Copyright ©The authors 2023.)