bluuebunny/crossref_metadata_2025_split huggingface dataset:
Country-Wide Agent-Based Epidemiological Modeling Using 17 Million Individual-Level Microdata
Authors: Hesam Ahmad , Pijpers Frank P , Breitwieser Lukas , Hofstee Peter , Al-Ars Zaid 
Published: May 2024

AbstractCalibration is a crucial step in developing agent-based models. Agent-based models are notorious for being difficult to calibrate as they can express various degrees of freedom when model parameters are unknown. Models that appear correctly calibrated to match macro-level observed data perform poorly when micro-level insights need to be inferred. As a result, policymakers cannot be certain that an agent-based model can accurately describe the dynamics of the real-world phenomena that the model tries to mimic. To begin tackling this challenge, we developed a methodology for an epidemiological use case at a full population scale of 17 million agents to observe the effects of using microlevel data for the calibration on the accuracy of the microlevel model outcomes. We show that by calibrating a model on national statistics, but using individual-level microdata, we can on average get 36% more accurate model outcomes on a subnational level. Our model implementation performs two orders of magnitude faster than prior work and allows efficient calibration on HPC computer systems.
Guidelines and Standard Frameworks for Artificial Intelligence in Medicine: A Systematic Review
Authors: Shiferaw Kirubel Biruk , Roloff Moritz , Balaur Irina , Welter Danielle , Waltemath Dagmar , Zeleke Atinkut Alamirrew 
Published: May 2024

AbstractA growing volume of evidence marks the potential of Artificial Intelligence (AI) in medicine, in improving diagnostic accuracy, clinical decision support, risk/event prediction, drug discovery, and patient management. However, the continuous integration of AI into clinical settings requires the development of up-to-date and robust guidelines and standard frameworks that consider the evolving challenges of AI implementation in medicine. This review evaluates these guidelines’ quality and summarizes ethical frameworks, best practices, and recommendations.The Appraisal of Guidelines, Research, and Evaluation (AGREE II) tool was used to assess the quality of guidelines based on six domains: scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, and editorial independence. The protocol of this review including the eligibility criteria, the search strategy data extraction sheet and methods, was published prior to the actual review with International Registered Report Identifier (IRRID) of(DERR1-10.2196/47105).The initial search resulted in 4,975 studies from two databases and five studies from manual search. Nine articles were selected for data extraction based on the eligibility criteria. We found that while guidelines generally excel in scope, purpose, and editorial independence, there is significant variability in applicability and the rigour of guideline development. Well-established initiatives such as DECIDE-AI, SPIRIT-AI, and CONSORT-AI have shown high quality, particularly in terms of stakeholder involvement. However, applicability remains a prominent challenge among the guidelines. We conclude that the reproducibility, ethical and environmental aspects of AI in medicine still need attention from both medical and AI communities. This review emphasizes the crucial need for high-quality guidelines and opens a new avenue in evaluating guidelines themselves. Our work highlights the need for working toward the development of integrated and comprehensive reporting guidelines that adhere to the principles of Findability, Accessibility, Interoperability and Reusability (FAIR). This alignment is essential for fostering a cultural shift towards transparency and open science, which are pivotal milestone for sustainable digital health research.
PITPβ promotes COPI vesicle fission through lipid transfer and membrane contact formation
Authors: Park Kunyou , Ju Sungeun , Choi Hyewon , Gao Peng , Bang Geul , Choi Jung Hoon , Jang Jiwon , Morris Andrew J. , Kang Byung-Ho , Hsu Victor W. , Park Seung-Yeol 
Published: May 2024

AbstractIntracellular transport among organellar compartments occurs in two general ways, by membrane-bound carriers or membrane contacts. Specific circumstances that involve the coordination of these two modes of transport remain to be defined. Studying Coat Protein I (COPI) transport, we find that phosphatidylcholine with short acyl chains (sPC) is delivered through membrane contact from the endoplasmic reticulum (ER) to sites of COPI vesicle formation at the Golgi to support the fission stage. Phosphatidylinositol transfer protein beta (PITPβ) plays a key role in this process, with the elucidation of this role advancing a new understanding of how PITPβ acts, providing a mechanistic understanding of a specific circumstance when vesicular transport requires membrane contact, and contributing to a basic understanding of how transport carriers in a model intracellular pathway are formed.SummarySpecific circumstances that membrane contact is needed for vesicular transport remain to be defined. We find that a critical lipid is delivered through membrane contact to support the fission stage of a model intracellular transport pathway.
An orphan viral genome with controversial evolutionary status sheds light on a distinct lineage of flavi-like virus infecting plants
Authors: Xu Zhongtian , Zheng Luping , Gao Fangluan , Li Yiyuan , Sun Zongtao , Chen Jianping , Zhang Chuanxi , Li Junmin , Wang Xifeng 
Published: May 2024

AbstractAdvancements in high-throughput sequencing and associated bioinformatics methods have significantly expanded the RNA virus repertoire, including novel viruses with highly divergent genomes encoding ‘orphan’ proteins that apparently lack homologous sequences. This absence of homologs in routine sequence similarity search complicates their taxonomic classification and raises a fundamental question: Do these orphan viral genomes representbona fideviruses? In 2022, an orphan viral genome encoding a large polyprotein was identified in alfalfa (Medicago sativa) and named Snake River alfalfa virus (SRAV). Initially, SRAV was proposed to be within the flavi-like lineage of the familyFlaviviridae. Subsequently, another research group showed its common occurrence in alfalfa but challenged its taxonomic position, suggesting it belongs to the familyEndornaviridaerather thanFlaviviridae. In this study, a large-scale analysis of 77 publicly available small RNA datasets indicated that SRAV could be detected across various tissues and cultivars of alfalfa, and has a broad geographical distribution. Moreover, profiles of the SRAV-derived small interfering RNAs (vsiRNAs) exhibited typical characteristics of virus in plant hosts. Through comprehensive evolutionary analysis, we demonstrated that SRAV should be a positive single-stranded RNA (ssRNA) flavi-like virus that infects alfalfa, rather than a member of the double-stranded RNA (dsRNA) of the familyEndornaviridae. Our findings suggest that SRAV represents a unique class of plant-hosted flavi-like viruses with unusual genome organization and evolutionary status, differing from previously identified flavi-like viruses documented to infect plants. The latter shows a close evolutionary relationship to flavi-like viruses primarily found in plant-feeding invertebrates and lacks evidence of triggering host RNA interference (RNAi) responses so far. In summary, our study resolves the taxonomic controversy surrounding SRAV and suggests the potential existence of two distinct clades of plant-hosted flavi-like viruses with independent evolutionary origins. Furthermore, our research provides the first evidence of plant-hosted flavi-like viruses triggering the host’s RNAi antiviral response. The widespread occurrence of SRAV underscores its potential ecological significance in alfalfa, a crop of substantial economic importance.
Cardiorenal effects of dual blockade with Angiotensin-converting enzyme inhibitors and Angiotensin receptor blockers in people with CKD: analysis of routinely collected data with emulation of a reference trial (ONTARGET)
Authors: Baptiste Paris J , Wong Angel YS , Schultze Anna , Clase Catherine M , Leyrat Clémence , Williamson Elizabeth , Powell Emma , Mann Johannes FE , Cunnington Marianne , Teo Koon , Bangdiwala Shrikant I , Gao Peggy , Wing Kevin , Tomlinson Laurie 
Published: May 2024

AbstractWe aimed to explore whether the ONTARGET trial results, which led to an end of recommendations of dual angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) use, extended to patients with chronic kidney disease (CKD) who were underrepresented in the trial.We selected people prescribed an ACEi and/or an ARB in the UK Clinical Practice Research Datalink Aurum during 1/1/2001-31/7/2019. We specified an operational definition of dual users and applied ONTARGET eligibility criteria. We used propensity-score—weighted Cox-proportional hazards models to compare dual therapy to ACEi for the primary composite trial outcome (cardiovascular death, myocardial infarction, stroke, or hospitalisation for heart failure), as well as a primary composite renal outcome (≥50% reduction in GFR or end-stage kidney disease), and other secondary outcomes, including hyperkalaemia. Conditional on successfully benchmarking results against the ONTARGET trial, we explored treatment effect heterogeneity by CKD at baseline.In the propensity-score—weighted trial-eligible analysis cohort (n=412 406), for dual therapy vs ACEi we observed hazard ratio (HR) 0.98 (95% CI: 0.93, 1.03), for the primary composite outcome, consistent with the trial results (ONTARGET HR 0.99, 95% CI: 0.92, 1.07). Dual therapy use was associated with an increased risk of the primary renal composite outcome, HR 1.25 (95% CI: 1.15, 1.36) vs ONTARGET HR 1.24 (1.01, 1.51) and hyperkalaemia, HR 1.15 (95% CI: 1.09, 1.22) in the trial eligible cohort, consistent with ONTARGET. The presence of CKD at baseline had minimal impact on results.Translational statementWe extended ONTARGET trial findings of the comparative effectiveness of dual ARB and ACEi therapy use compared to ACEi alone for a composite cardiovascular outcome to UK patients at high-risk of cardiovascular disease, including those with CKD. As in ONTARGET, we found an increased risk of a composite renal outcome (≥50% reduction in GFR or end-stage kidney disease) and an increased risk of hyperkalaemia among dual users compared to ACEi alone. Consistent results were observed among patients with CKD at baseline. This is evidence against the hypothesis that dual blockade provides cardiorenal benefits among high-risk cardiovascular patients with CKD.
HYDINvariants cause primary ciliary dyskinesia in the Finnish population
Authors: Burgoyne Thomas , Fassad Mahmoud R , Schultz Rüdiger , Elenius Varpu , Lim Jacqueline S Y , Freke Grace , Rai Ranjit , Mohammed Mai A , Mitchison Hannah M , Sironen Anu I 
Published: May 2024

AbstractPrimary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by chronic respiratory tract infections and in some cases laterality defects and infertility. The symptoms of PCD are caused by malfunction of motile cilia, hair-like organelles protruding out of the cell that are responsible for removal of mucus from the airways, organizing internal organ positioning during embryonic development and gamete transport. PCD is caused by mutations in genes coding for structural or assembly proteins of motile cilia. Thus far, mutations in over 50 genes have been identified and these variants explain around 70% of all known cases. Population specific genetics underlying PCD has been reported underlining the importance of characterizing gene variants in different populations for development of gene-based diagnostics and management. In this study, we identified disease causing genetic variants in the axonemal central pair component HYDIN. Three Finnish PCD patients carried homozygous loss-of-function variants and one patient had compound heterozygous variants within theHYDINgene. The functional effect of theHYDINvariants was confirmed by immunofluorescence and electron tomography, which demonstrated defects in the axonemal central pair complex. All patients had clinical PCD symptoms including chronic wet cough and recurrent airway infections due to almost static airway cilia. Our results are consistent with the previously identified important role of HYDIN in the axonemal central pair complex and improve specific diagnostics of PCD in different ethnical backgrounds.
MRI-based cortical gray/white matter contrast in young adults who endorse psychotic experiences or are at genetic risk for psychosis
Authors: Naseri Nasimeh , Beck Dani , Ferschmann Lia , Aksnes Eira R. , Havdahl Alexandra , Jalbrzikowski Maria , Norbom Linn B. , Tamnes Christian K. 
Published: May 2024

AbstractGroup-level differences in brain macrostructure between individuals at risk for psychosis and healthy controls have been well documented. However, while differences in cortical grey/white matter contrast (GWC), likely reflecting differences in myelin content, have been reported in clinical populations with psychotic disorders, no studies have explored GWC in individuals at elevated risk for psychosis. In this study, we explored whether brain microstructure, as measured with GWC, differs between young adults who endorsed psychotic experiences or genetic high risk for psychosis and healthy controls, and whether individual differences in GWC in at-risk individuals are associated with the number and psychotic experiences. The sample included individuals from two magnetic resonance imaging (MRI) substudies of the Avon Longitudinal Study of Parents and Children (ALSPAC): the psychotic experiences study and the schizophrenia recall-by-genotype study. The final sample included four groups of young adults 19-24 years old: individuals endorsing psychotic experiences (n=119) and health controls (n=117) and individuals with high (n=95) and low genetic risk for psychosis (n=95). Statistical analyses were performed using FSL’s Permutation Analysis of Linear Models (PALM), controlling for age and sex. The results showed no statistically significant differences in GWC between any of the groups and no significant associations between GWC and the number and experiences of psychotic experiences. In conclusion, the results indicate that GWC is not a sensitive neuroimaging marker for psychosis risk in young adults.
Linear regression reporting practices for health researchers, a cross-sectional meta-research study
Authors: Jones Lee , Barnett Adrian , Vagenas Dimitrios 
Published: May 2024

AbstractBackgroundDecisions about health care, such as the effectiveness of new treatments for disease, are regularly made based on evidence from published work. However, poor reporting of statistical methods and results is endemic across health research and risks ineffective or harmful treatments being used in clinical practice. Statistical modelling choices often greatly influence the results. Authors do not always provide enough information to evaluate and repeat their methods, making interpreting results difficult. Our research is designed to understand current reporting practices and inform efforts to educate researchers.MethodsReporting practices for linear regression were assessed in 95 randomly sampled published papers in the health field from PLOS ONE in 2019, which were randomly allocated to statisticians for post-publication review. The prevalence of reporting practices is described using frequencies, percentages, and Wilson 95% confidence intervals.ResultsWhile 92% of authors reported p-values and 81% reported regression coefficients, only 58% of papers reported a measure of uncertainty, such as confidence intervals or standard errors. Sixty-nine percent of authors did not discuss the scientific importance of estimates, and only 23% directly interpreted the size of coefficients.ConclusionOur results indicate that statistical methods and results were often poorly reported without sufficient detail to reproduce them. To improve statistical quality and direct health funding to effective treatments, we recommend that statisticians be involved in the research cycle, from study design to post-peer review. The research environment is an ecosystem, and future interventions addressing poor statistical quality should consider the interactions between the individuals, organisations and policy environments. Practical recommendations include journals producing templates with standardised reporting and using interactive checklists to improve reporting practices. Investments in research maintenance and quality control are required to assess and implement these recommendations to improve the quality of health research.
A CROSS-SECTIONAL STUDY OF THE PSYCHOLOGICAL IMPACT OF COVID-19 ON MEDICAL STUDENTS DURING & AFTER RECOVERY FROM COVID-19
Authors: Misra Anushka , Rane Damini , Arun Bhat P. 
Published: May 2024

ABSTRACTIntroductionMental health of medical students has been an utmost topic of discussion. It is important to know whether the upcoming doctors are mentally equipped to handle the pressure that comes with the profession. There is substantial literature indicating negative impact on the mental health during COVID-19 pandemic. Studies regarding the same on frontline workers seems scarce. Therefore, it is essential to assess the prevalence of symptoms anxiety and depression among medical students during and after the recovery from COVID-19 infection.Materials and methodsIt is a cross-sectional time bound study on 32 medical undergraduate students with active COVID-19 infection. They were screened using Self-reporting Questionnaire 20 (SRQ). Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HAM-D) were administered on those who screened positive on SRQ-20 to assess the severity of anxiety and depressive symptoms. These were administered during and after COVID-19 infection on virtual platform.ResultsIn our study, 59.37% population was screened positive for mental health disorder during COVID-19 infection. 89.5% of the positively screened respondents had mild anxiety symptoms and 10.5% had moderate anxiety symptoms. 47.4% of screened respondents had mild depressive symptoms, 31.6% reported moderate depressive symptoms and 21.1% had severe depressive symptoms. Following recovery, there was a reduction in severity of anxiety and depressive symptoms which was statistically significant (p<0.001).ConclusionMedical students have a propensity to develop anxiety and depressive symptoms while suffering from COVID-19 infection. Some may continue to have residual anxiety and depressive symptoms after recovery but the severity significantly reduces.
IL-2-mediated CD4 T-cell activation correlates highly with effective serological and T-cell responses to SARS-CoV-2 vaccination in people living with HIV (PLWH)
Authors: Gupta Akshita , Righi Elda , Konnova Angelina , Sciammarella Concetta , Spiteri Gianluca , Averbeke Vincent Van , Berkell Matilda , Hotterbeekx An , Sartor Assunta , Mirandola Massimo , Malhotra-Kumar Surbhi , Azzini Anna Maria , Pezzani Diletta , Monaco Maria Grazia Lourdes , Vanham Guido , Porru Stefano , Tacconelli Evelina , Kumar-Singh Samir 
Published: May 2024

AbstractPeople living with HIV (PLWH) despite having appreciable depletion of CD4+T-cell show a good SARS- CoV-2 vaccination response. The underlying mechanism(s) are currently not understood. We studied serological and polyfunctional T-cell responses in PLWH receiving anti-retroviral therapy stratified on CD4+counts as PLWH-high (CD4 ≥500 cells/μL) and PLWH-low (<500 cells/μL). Responses were assessed longitudinally before the first vaccination (T0), 1-month after the first dose (T1), and 3- months (T2), and 6-months (T3) after the second dose. Expectedly, both PLWH-high and -low groups developed similar serological responses after T2, which were also non-significantly different to age and vaccination-matched HIV-negative controls at T3. The IgG titers were also protective showing a good correlation with ACE2-neutralizations (R=0.628, P=0.005). While no difference at T3 was observed between PLWH and controls in activated CD4+CD154+and CD4+memory T-cells, spike- specific CD4+polyfunctional cytokine expression analysis showed that PLWH preferentially express IL-2 (P<0.001) and controls, IFN-γ (P=0.017). CD4+T-cell counts negatively correlated with IL-2- expressing CD4+T-cells including CD4+memory T-cells (Spearman ρ: -0.85 and -0.80, respectively; P<0.001). Our results suggest that the durable serological and CD4+T-cell responses developing in vaccinated PLWH are associated with IL-2-mediated CD4+T-cell activation that likely compensates for CD4+T-cell depletion in PLWH.
Weight Loss-Independent Changes in Human Growth Hormone During Water-Only Fasting: A Secondary Evaluation of a Randomized Controlled Trial
Authors: Horne Benjamin D. , Anderson Jeffrey L. , May Heidi T. , Bair Tami L. , Le Viet T. , Iverson Leslie , Knowlton Kirk U. , Muhlestein Joseph B. 
Published: May 2024

AbstractIntroductionWater-only fasting for one day or more may provide health benefits independent of weight loss. Human growth hormone (HGH) may play a key role in multiple fasting-triggered mechanisms. Whether HGH changes during fasting are independent of weight loss and how basal HGH and HGH change relate to other fasting-induced changes are unknown.MethodsApparently healthy individuals (N=30) were randomized by Latin square to begin two days with either 24-hour water-only fasting or a control of 24-hourad libitumeating. On day 2, subjects were crossed over to control (if day 1 was fasting) or fasting (if they ate on day 1). HGH, weight, and other parameters were measured at baseline and at the end of the first and second days.ResultsBaseline HGH had median 0.50 ng/mL for females (n=20) and 0.04 ng/mL for males (n=10), and correlated inversely with weight, glucose, insulin, and triglycerides and positively with changes in insulin and HOMA-IR. The 24-hour fasting-induced HGH change was uncorrelated with weight loss (r= 0.01, p=0.98), but correlated with changes in glucose, HGB, and IGF-1. The percent increase in HGH was greater (p<0.001) for lower (females ≤0.15 ng/mL, males ≤0.05 ng/mL) vs. higher baseline HGH (median: 1,225% vs. 50.3%, respectively). Subjects with lower baseline HGH had a trend to greater reduction of HOMA-IR (median: −6.15 vs. −1.35 for lower vs. higher HGH, respectively, p=0.08).ConclusionsFasting increased HGH and the HGH changes were independent of weight loss. Basal HGH and fasting-induced HGH changes correlated inversely with cardiometabolic risk factors.