bluuebunny/crossref_metadata_2025_split huggingface dataset:
The TRIPOD-LLM Statement: A Targeted Guideline For Reporting Large Language Models Use
Authors: Gallifant Jack , Afshar Majid , Ameen Saleem , Aphinyanaphongs Yindalon , Chen Shan , Cacciamani Giovanni , Demner-Fushman Dina , Dligach Dmitriy , Daneshjou Roxana , Fernandes Chrystinne , Hansen Lasse Hyldig , Landman Adam , Lehmann Lisa , McCoy Liam G. , Miller Timothy , Moreno Amy , Munch Nikolaj , Restrepo David , Savova Guergana , Umeton Renato , Gichoya Judy Wawira , Collins Gary S. , Moons Karel G. M. , Celi Leo A. , Bitterman Danielle S. 
Published: July 2024

AbstractLarge Language Models (LLMs) are rapidly being adopted in healthcare, necessitating standardized reporting guidelines. We present TRIPOD-LLM, an extension of the TRIPOD+AI statement, addressing the unique challenges of LLMs in biomedical applications. TRIPOD-LLM provides a comprehensive checklist of 19 main items and 50 subitems, covering key aspects from title to discussion. The guidelines introduce a modular format accommodating various LLM research designs and tasks, with 14 main items and 32 subitems applicable across all categories. Developed through an expedited Delphi process and expert consensus, TRIPOD-LLM emphasizes transparency, human oversight, and task-specific performance reporting. We also introduce an interactive website (https://tripod-llm.vercel.app/) facilitating easy guideline completion and PDF generation for submission. As a living document, TRIPOD-LLM will evolve with the field, aiming to enhance the quality, reproducibility, and clinical applicability of LLM research in healthcare through comprehensive reporting.COIDSB: Editorial, unrelated to this work: Associate Editor of Radiation Oncology,HemOnc.org(no financial compensation); Research funding, unrelated to this work: American Association for Cancer Research; Advisory and consulting, unrelated to this work: MercurialAI. DDF: Editorial, unrelated to this work: Associate Editor of JAMIA, Editorial Board of Scientific Data, Nature; Funding, unrelated to this work: the intramural research program at the U.S. National Library of Medicine, National Institutes of Health. JWG: Editorial, unrelated to this work: Editorial Board of Radiology: Artificial Intelligence, British Journal of Radiology AI journal and NEJM AI. All other authors declare no conflicts of interest.
Evaluating genetically-predicted causal effects of lipoprotein(a) in human diseases: a phenome-wide Mendelian randomization study
Authors: Shi Jingchunzi , Shringarpure Suyash S. , Hinds David ,   23andMe Research Team, Auton Adam , Holmes Michael V 
Published: July 2024

AbstractBackgroundLipoprotein(a) (Lp[a]) is a circulating plasma lipoprotein that is emerging as an important independent risk factor for vascular disease. Lp(a) levels are 75-90% heritable, predominantly determined by copy number variation and single nucleotide polymorphisms (SNPs) at theLPAgene.MethodsUsing ∼370K individuals with serum measurements of Lp(a) in the UK Biobank European cohort, we constructed a genetic risk score (GRS) consisting of 29 SNPs in the vicinity ofLPAwhich explained 68.18% of variation in Lp(a). Using theLPAGRS to instrument Lp(a), we conducted phenome-wide Mendelian randomization analysis (MR-PheWAS) across a spectrum of 489 medically-relevant phenotypes in ∼7.3M individuals from the 23andMe, Inc. database, and compared effects to those derived from a GRS for low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB). Through multivariable MR, we sought to assess the direct causal effect of Lp(a) on cardiovascular disease risks while keeping LDL-C or apoB constant.ResultsMR-PheWAS confirmed previously reported Lp(a) causal effects on coronary artery disease (CAD: OR = 1.199, 95% CI = [1.193, 1.205], p-value < 2.23×10-308, for every 59.632 nmol/L higher Lp(a) instrumented by theLPAGRS), and revealed additional genetically-predicted effects largely confined to cardiovascular endpoints, including a novel effect for restrictive cardiomyopathy (OR = 1.101, 95% CI = [1.068, 1.134], p-value = 3×10-10). We scaled theLPA, LDL-C and apoB GRS such that they each had the same OR for MACE (major adverse cardiovascular events). Using the scaling rubric, similar magnitudes of effect were seen for the three lipid traits for most vascular diseases, with the exception of peripheral artery disease, aortic stenosis and dilated cardiomyopathy, where Lp(a) had larger genetically–predicted effect sizes compared to LDL-C and apoB. Multivariable MR identified Lp(a) to retain a causal effect on MACE while accounting for LDL-C or apoB. To achieve the 25% relative risk reduction in major vascular events, as seen with a 1 mmol/L reduction in LDL-C from statin trials, we anticipate that Lp(a) ought to be reduced by ∼ 90 mg/dL (200 nmol/L), highlighting the importance of not only using therapies that have a profound impact on Lp(a) lowering, but also selecting individuals that have high Lp(a) concentrations at baseline.ConclusionLp(a) has genetically-predicted causal effects on a broad range of cardiovascular diseases beyond CAD, with minimal effects seen for non-vascular disease.
Phrenic Neuropathy Etiologies and Recovery Trajectories in Outpatient Rehabilitation and Neuromuscular Medicine Clinics: A Retrospective Analysis
Authors: Demetriou Nicholas , Jensen Alexandra S. , Farr Ellen , Coleman John M. , Ajroud-Driss Senda , Adewuyi Adenike A. , Wolfe Lisa F. , Franz Colin K. 
Published: July 2024

AbstractIntroduction/AimsPhrenic Neuropathy (PhN) impairs diaphragm muscle function, causing a spectrum of breathing disability. PhN etiologies and their natural history are ill defined. This knowledge gap hinders informed prognosis and management decisions. This study aims to help fill this knowledge gap on PhN etiologies, outcomes, and recovery patterns, especially in the context of non-surgical clinical practice.MethodsThis is a retrospective study from two interdisciplinary clinics, physiatry and neurology based. Patients were included if PhN was identified, and other causes of hemi-diaphragm muscle dysfunction excluded. Patients were followed serially per the discretion of the neuromuscular trained neurologist or physiatrist. Recovery was assessed using pulmonary function tests (PFTs), diaphragm muscle US thickening ratio, and patient-reported outcomes in patients presenting within two years of PhN onset.ResultsWe identified 151 patients with PhN. The most common etiologies included idiopathic (27%), associated with cardiothoracic procedure (24%), and intensive care unit (17%). Of these patients, 117 (77%) were evaluated within two years of PhN onset. Of patients included in outcome analyses, 69% saw improvement on serial US, 50% on serial PFTs and 79% reported symptomatic improvement at an average of 13, 16, and 17 months respectively.ConclusionThis study maps PhN etiologies and recovery. A clear majority of PhN patients show improvement in diaphragm muscle function, but on average improvements took 13-17 months depending on the assessment type. These insights are vital for developing tailored treatments and can guide physicians in prognosis and decision-making, especially if more invasive interventions are being considered.
The smallest worthwhile effect on pain and function for rotator cuff repair surgery: a benefit-harm trade-off study
Authors: Hansford Harrison J , Buchbinder Rachelle , Zadro Joshua R , McAuley James H , Ferreira Manuela L , Lewin Adriane , Page Richard S , Harris Ian A 
Published: July 2024

AbstractBackgroundThe smallest worthwhile effect (SWE) is the minimum benefit required in addition to that from a comparator, for an intervention to be considered worthwhile by patients. We aimed to estimate the SWE for rotator cuff repair (with decompression and debridement) compared to either decompression and debridement alone or to non-surgical treatment for people with atraumatic shoulder pain.MethodsBenefit-harm trade-off study. We recruited English speaking adults aged 45-75 years with shoulder pain of intensity ≥4 (on a 0-10 scale) for ≥6 months to our online survey through paid advertising on Facebook. Participants must have sought care in the past 6-months and could not have had recent shoulder surgery or significant recent shoulder trauma. Participants were explained three treatments: rotator cuff repair (with subacromial decompression and debridement), subacromial decompression and debridement alone and non-surgical treatment. Participants completed the benefit-harm trade-off survey to determine the SWE of improvements in pain and function for rotator cuff repair compared to the other treatments and again after one week to assess reliability. We used univariable linear regression to estimate associations between baseline characteristics and SWE.ResultsWe recruited 56 participants. The mean ± standard deviation age was 58.4±6.7 years and 39 (70%) were female. For rotator cuff repair to be worthwhile compared to decompression and debridement alone participants needed to see at least a median 40% (interquartile range (IQR) 20-62.5) between-group improvement in pain and function.Compared to non-surgical treatment, the SWE was a median 40% (IQR 30-60). On the Western Ontario Rotator Cuff (WORC) Index the SWE values equate to a between-group improvement of 28/100 points (533/2100 on the raw WORC score). Female sex was associated with larger SWEs for both comparisons. Reliability analyses were underpowered, 25/56(45%) provided follow-up data; the intraclass correlation coefficient estimates ranged from 0.60-0.77.ConclusionsThis SWE indicates the benefit required by people with shoulder pain to consider the costs and risks of surgical rotator cuff repair worthwhile is larger than previously estimated minimum clinically important differences (13.5-28/100 on the WORC Index). This SWE may be used to inform the design or interpret the findings of trials of these comparisons.
Outcomes from the Victorian Healthy Homes Program: a randomised control trial of home energy upgrades
Authors: Page Katie , Hossain Lutfun , Liu Dan , Kim Yohan , Wilmot Kerryn , Kenny Patricia , Campbell Margaret , Cumming Toby , Kelly Scott , Longden Thomas , van Gool Kees , Viney Rosalie ,   VHHP team
Published: July 2024

ABSTRACTIntroductionThe Victorian Healthy Homes Program (VHHP) is the first randomised control trial (RCT) in Australia that investigates the impact of thermal home upgrades on energy and health outcomes in vulnerable individuals over winter in Victoria Australia.MethodsA staggered parallel-group RCT design of 984 vulnerable households. The intervention group received their upgrade prior to their winter of recruitment and the control group received their upgrade after the winter of their recruitment.ResultsA relatively low-cost and simple home upgrade (average cost AU$2,809) resulted in reduced gas consumption (−25.5 MJ/day) and increased indoor winter temperatures (average daily increase of 0.33°C), and a reduction of exposure to cold conditions (<18°C) by an average of 0.71 hours (43 minutes) per day. The intervention group experienced improved mental health as measured by the SF-36 mental component summary and social care related quality of life measured by adult social care outcomes toolkit (ASCOT), and lower healthcare costs overall (an average of AU$887 per person) over the winter period.ConclusionsThe home upgrades significantly increased average winter indoor temperature, improved mental health and social care-related quality of life, and made householders more comfortable while bringing about reductions in overall healthcare use and costs.STRENGTHS AND LIMITATIONS OF THIS STUDYFirst randomised control trial of its kind in Australia to study the impact of thermal home upgrades on energy and health outcomes.The use of RCTs for such interventions is uncommon but provides a powerful approach to evaluation that can minimise the effects of confounding.The program was specifically designed to target vulnerable populations. These are groups with the most potential to benefit from home upgrades, either because of their socio-economic status or because of their chronic health conditions, or both.The retrofitted upgrade was tailored to each home based on need and delivered for a modest budget (up to AU$3,500)COVID-19 impacted the power of the study because not all upgrades were able to be delivered prior to winter. This was particularly relevant for the secondary health outcome measures.
MultiOmicsAgent: Guided extreme gradient-boosted decision trees-based approaches for biomarker-candidate discovery in multi-omics data
Authors: Settelmeier Jens , Goetze Sandra , Boshart Julia , Fu Jianbo , Steiner Sebastian N. , Gesell Martin , Schüffler Peter J. , Salimova Diyora , Pedrioli Patrick G. A. , Wollscheid Bernd 
Published: July 2024

AbstractMultiOmicsAgent (MOAgent) is an innovative, Python based open-source tool for biomarker discovery, utilizing machine learning techniques specifically extreme gradient-boosted decision trees to process multi-omics data. With its cross-platform compatibility, user-oriented graphical interface and a well-documented API, MOAgent not only meets the needs of both coding professionals and those new to machine learning but also addresses common data analysis challenges like data incompleteness, class imbalances and data leakage between disjoint data splits. MOAgent’s guided data analysis strategy opens up data-driven insights from digitized clinical biospecimen cohorts and makes advanced data analysis accessible and reliable for a wide audience.Biographical NoteJens Settelmeier, Julia Boshart, Martin Gesell are Ph.D. candidates, Jianbo Fu, Sebastian N. Steiner are Post Doc candidates and Sandra Goetze, Patrick Pedrioli senior scientists at the Institute of Translational Medicine at Health Sciences and Technology department at ETH Zürich, Switzerland, within Professor Bernd Wollscheid’s research group who has been working in the fields of bioinformatics, clinical multi-omics with a focus on spatial cell surface proteomics.Peter J. Schüffler is professor at the institute of Pathology at the TU Munich, Germany and has been working in the field of digital pathology and clinical multi-modal studies.Diyora Salimova is junior professor at the department of Applied Mathematics at the Albert-Ludwigs-University of Freibug, Germany and has been working in the field of stochastic processes, approximation theory and machine learning related topics.Key PointsMOAgent enables a guided biomarker-candidate discovery in multi-omics studies, providing a graphical interface and well-documented API.A user can run MOAgent on a personal computer without the requirement of coding a single line.MOAgent is a Python-based solution for biomarker-candidate discovery, using machine learning to analyze multi-omics data.MOAgent can address challenges like data incompleteness and class imbalances, ensuring reliable analysis.MOAgent makes advanced data analysis accessible, enhancing insights from clinical data.
Somatic hypermutation-mediated paratope flexibility improves the cross-reactivity of human malaria antibodies
Authors: Murugan Rajagopal , Hanke Anton , Oludada Opeyemi Ernest , Costa Giulia , Flores-Garcia Yevel , Mustafa Ghulam , Li Kan , Huntwork Richard H. C. , Horn Gillian Q. , Dennison S. Moses , Tomaras Georgia D , Zavala Fidel , Levashina Elena A. , Ketchem Randal R. , Wade Rebecca C. , Wardemann Hedda 
Published: July 2024

ABSTRACTThe protective capacity of antibodies targeting circumsporozoite protein on sporozoites of the malaria parasitePlasmodium falciparum(PfCSP) is linked to high affinity and cross-reactivity with the PfCSP central repeat domain and N-terminal junction. However, the role of somatic hypermutation (SHM) in the development of such antibodies remains unclear. Here we define the contributions of SHM to the high affinity and strong repeat and N-junction cross-reactivity of the potent anti-PfCSP monoclonal antibody (mAb) 4493 and of similar antibodies with shared SHM and affinity maturation trajectories. Molecular dynamics simulations reveal that SHM reduces the flexibility of the unbound mAb 4493 but increases the flexibility of the antigen-bound complex, thereby lowering the entropic cost for antigen binding. Furthermore, we identify an inverse relation between antibody affinity and serum stability, which limits the protective capacity of these antibodies. Our study provides molecular level evidence for the different roles that the SHM process plays in increasing VH3-49+Vκ3-20 antibody affinity and cross-reactivity and demonstrates how antibody affinity maturation can negatively impact antibody stability and thereby function.
Drug-induced cis-regulatory elements in human hepatocytes affect molecular phenotypes associated with adverse reactions
Authors: Gotoh-Saito Saki , Wada Ryoko , Kawaji Hideya 
Published: July 2024

AbstractBackgroundGenomic variations contribute to the phenotypic diversity of individuals. A number of polymorphisms in protein-coding regions that alter drug efficacy or lead to adverse reactions have been characterized; however, noncoding regions that affect drug responses are largely overlooked, except for a limited number of well-studied enhancers.ResultsWe conducted a quantitative assessment ofcis-regulatory elements (CREs) based on transcription initiation profiling of mRNAs and noncoding RNAs, including enhancer RNAs, by using CAGE (Cap Analysis of Gene Expression). Candidate CREs identified in a hepatocellular carcinoma HepG2 cell line with stable expression of drug-responsive transcription factor pregnane X receptor (PXR) were further narrowed down by integrating data of PXR-binding sites in human primary hepatocytes and genome-wide association studies. We found more than 100-fold enrichments of the candidates to genetically associated loci with circulating levels of bilirubin and vitamin D, which implicated a link to adverse reactions of PXR ligands. We uncovered novel enhancers ofUGT1A1andTSKUthrough CRISPR/Cas9 knockout experiments. We identified alleles altering regulatory activities ofUGT1A1andCYP24A1enhancers by using luciferase reporter assay. Furthermore, our siRNA experiments revealed an unexpected impact of TSKU on the expression of vitamin D-metabolizing enzymes.ConclusionsOur transcriptome-based assessment of CREs expanded the list of drug-inducible and PXR-mediated enhancers and super-enhancers. We identified regulatory alleles that alter drug-induced gene expressions, and discovered a novel molecular cascade associated with an adverse reaction. Our results contribute a precise understanding of the noncoding elements of the human genome underlying drug responses.
Epigenetic control of metabolic identity across cell types
Authors: Pacheco Maria Pires , Gerard Déborah , Mangan Riley J. , Chapman Alec R. , Hecker Dennis , Kellis Manolis , Schulz Marcel H. , Sinkkonen Lasse , Sauter Thomas 
Published: July 2024

AbstractBackgroundConstraint-based network modeling is a powerful genomic-scale approach for analyzing cellular metabolism, capturing metabolic variations across tissues and cell types, and defining the metabolic identity essential for identifying disease-associated transcriptional states.ResultsUsing RNA-seq and epigenomic data from the EpiATLAS resource of the International Human Epigenome Consortium (IHEC), we reconstructed metabolic networks for 1,555 samples spanning 58 tissues and cell types. Analysis of these networks revealed the distribution of metabolic functionalities across human cell types and provides a compendium of human metabolic activity. This integrative approach allowed us to define, across tissues and cell types, i) reactions that fulfil the basic metabolic processes (core metabolism), and ii) cell type-specific functions (unique metabolism), that shape the metabolic identity of a cell or a tissue. Integration with EpiATLAS-derived cell-type-specific gene-level chromatin states and enhancer-gene interactions identified enhancers, transcription factors, and key nodes controlling core and unique metabolism. Transport and first reactions of pathways were enriched for high expression, active chromatin state, and Polycomb-mediated repression in cell types where pathways are inactive, suggesting that key nodes are targets of repression.DiscussionThis integrative analysis forms the basis for identifying regulation points that control metabolic identity in human cells.
Improved accuracy of the whole body Center of Mass position through Kalman filtering
Authors: Charlotte Le Mouel 
Published: July 2024

AbstractThe trajectory of the body center of mass (CoM) is critical for evaluating balance. The position of the CoM can be calculated using either kinematic or kinetic methods. Each of these methods has its limitations, and it is difficult to evaluate their accuracy as there is no ground truth to which the CoM trajectory can be compared. In this paper, we use as ground truth the fact that, during the flight phase of running, the acceleration of the CoM is equal to gravity. We evaluate the accuracy of kinematic models of different complexity and find that the error ranges from 14 % to 36 % of gravity. We propose a novel method for optimally combining kinematic and force plate information. When using this proposed method, the error drops to 1.1 to 3.1 % for all kinematic models. Moreover, the proposed method provides a more reliable evaluation of foot placement control, which is commonly used as an indicator of balance during locomotion.The code for calculating this optimal combination is available in both Python and Matlab at:https://github.com/charlotte-lemouel/center_of_massThe documentation is available at:https://center-of-mass.readthedocs.io
Stable centromere association of the yeast histone variant Cse4 requires its essential N-terminal domain
Authors: Popchock Andrew R. , Hedouin Sabrine , Mao Yizi , Asbury Charles L. , Stergachis Andrew B , Biggins Sue 
Published: July 2024

ABSTRACTChromosome segregation relies on kinetochores that assemble on specialized centromeric chromatin containing a histone H3 variant. In budding yeast, a single centromeric nucleosome containing Cse4 assembles at a sequence-defined 125 bp centromere. Yeast centromeric sequences are poor templates for nucleosome formationin vitro, suggesting the existence of mechanisms that specifically stabilize Cse4 nucleosomesin vivo. The extended Cse4 N-terminal tail binds to the chaperone Scm3, and a short essential region called END within the N-terminal tail binds the inner kinetochore complex OA. To address the roles of these interactions, we utilized single molecule fluorescence assays to monitor Cse4 during kinetochore assembly. We found that OA and Scm3 independently stabilize Cse4 at centromeres via their END interaction. Scm3 binding to the Cse4 END is enhanced by Ipl1/Aurora B phosphorylation, identifying a previously unknown role for Ipl1 in ensuring Cse4 stability. Strikingly, an Ipl1 phosphomimetic mutation in the Cse4 END enhances Scm3 binding and can restore Cse4 recruitment in mutants defective in OA binding. Together, these data suggest that a key function of the essential Cse4 N-terminus is to ensure Cse4 localization at centromeres.