bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Common Longitudinal Intensive Care Unit data Format (CLIF) to enable multi-institutional federated critical illness research
Authors: Rojas Juan C. , Lyons Patrick G. , Chhikara Kaveri , Chaudhari Vaishvik , Bhavani Sivasubramanium V. , Nour Muna , Buell Kevin G. , Smith Kevin D. , Gao Catherine A. , Amagai Saki , Mao Chengsheng , Luo Yuan , Barker Anna K , Nuppnau Mark , Beck Haley , Baccile Rachel , Hermsen Michael , Liao Zewei , Park-Egan Brenna , Carey Kyle A , XuanHan  , Hochberg Chad H , Ingraham Nicholas E , Parker William F 
Published: September 2024

ABSTRACTBackgroundCritical illness, or acute organ failure requiring life support, threatens over five million American lives annually. Electronic health record (EHR) data are a source of granular information that could generate crucial insights into the nature and optimal treatment of critical illness. However, data management, security, and standardization are barriers to large-scale critical illness EHR studies.MethodsA consortium of critical care physicians and data scientists from eight US healthcare systems developed the Common Longitudinal Intensive Care Unit (ICU) data Format (CLIF), an open-source database format that harmonizes a minimum set of ICU Data Elements for use in critical illness research. We created a pipeline to process adult ICU EHR data at each site. After development and iteration, we conducted two proof-of-concept studies with a federated research architecture: 1) an external validation of an in-hospital mortality prediction model for critically ill patients and 2) an assessment of 72-hour temperature trajectories and their association with mechanical ventilation and in-hospital mortality using group-based trajectory models.ResultsWe converted longitudinal data from 94,356 critically ill patients treated in 2020-2021 (mean age 60.6 years [standard deviation 17.2], 30% Black, 7% Hispanic, 45% female) across 8 health systems and 33 hospitals into the CLIF format, The in-hospital mortality prediction model performed well in the health system where it was derived (0.81 AUC, 0.06 Brier score). Performance across CLIF consortium sites varied (AUCs: 0.74-0.83, Brier scores: 0.06-0.01), and demonstrated some degradation in predictive capability. Temperature trajectories were similar across health systems. Hypothermic and hyperthermic-slow-resolver patients consistently had the highest mortality.ConclusionsCLIF facilitates efficient, rigorous, and reproducible critical care research. Our federated case studies showcase CLIF’s potential for disease sub-phenotyping and clinical decision-support evaluation. Future applications include pragmatic EHR-based trials, target trial emulations, foundational multi-modal AI models of critical illness, and real-time critical care quality dashboards.
The differential effects of common and rare genetic variants on cognitive performance across development
Authors: Malawsky Daniel S. , Koko Mahmoud , Danacek Petr , Huang Wei , Wootton Olivia , Huang Qin Qin , Wade Emma E. , Lindsay Sarah J. , Arden Rosalind , Hurles Matthew E. , Martin Hilary C. 
Published: September 2024

AbstractCommon and rare genetic variants that impact adult cognitive performance also predispose to rare neurodevelopmental conditions involving cognitive deficits in children. However, their influence on cognition across early life remains poorly understood. Here, we investigate the contribution of common genome-wide and rare exonic variation to cognitive performance across childhood and adolescence primarily using the Avon Longitudinal Study of Parents and Children (n=6,495 unrelated children). We show that the effect of common variants associated with educational attainment and adult cognitive performance increases as children age. Conversely, the negative effect of deleterious rare variants attenuates with age. Using trio analyses, we show that these age-related trends are driven by direct genetic effects on the individual who carries these variants rather than indirect genetic effects mediated via the family environment. We further find that the increasing effects of common variants are stronger in individuals at the upper end of the phenotype distribution, whereas the attenuating effects of rare variants are stronger in those at the lower end. Concordant results were observed in the Millenium Cohort Study (5,920 children) and UK Biobank (101,232 adults). The effects of common and rare genetic variation on childhood cognitive performance are broadly comparable in magnitude to those of other factors such as parental educational attainment, maternal illness and preterm birth. The effects of maternal illness and preterm birth on childhood cognitive performance also attenuate with age, whereas the effect of parental educational attainment does not. We show that the relative contribution of these various factors differs depending on whether one considers their contribution to phenotypic variance across the entire population or to the risk of poor outcomes. Our findings may help explain the apparent incomplete penetrance of rare damaging variants associated with neurodevelopmental conditions. More generally, they also show the importance of studying dynamic genetic influences across the life course and their differential effects across the phenotype distribution.
Assessing Cerebral Microvascular Volumetric Pulsatility with High-Resolution 4D CBV MRI at 7T
Authors: Guo Fanhua , Zhao Chenyang , Shou Qinyang , Jin Ning , Jann Kay , Shao Xingfeng , Wang Danny JJ 
Published: September 2024

AbstractArterial pulsation is crucial for promoting fluid circulation and for influencing neuronal activity. Previous studies assessed the pulsatility index based on blood flow velocity pulsatility in relatively large cerebral arteries of human. Here, we introduce a novel method to quantify the volumetric pulsatility of cerebral microvasculature across cortical layers and in white matter (WM), using high-resolution 4D vascular space occupancy (VASO) MRI with simultaneous recording of pulse signals at 7T. Microvascular volumetric pulsatility index (mvPI) and cerebral blood volume (CBV) changes across cardiac cycles are assessed through retrospective sorting of VASO signals into cardiac phases and estimating mean CBV in resting state (CBV0) by arterial spin labeling (ASL) MRI at 7T. Using data from 11 young (28.4±5.8 years) and 7 older (61.3±6.2 years) healthy participants, we investigated the aging effect on mvPI and compared microvascular pulsatility with large arterial pulsatility assessed by 4D-flow MRI. We observed the highest mvPI in the cerebrospinal fluid (CSF) on the cortical surface (0.19±0.06), which decreased towards the cortical layers as well as in larger arteries. In the deep WM, a significantly increased mvPI (p = 0.029) was observed in the older participants compared to younger ones. Additionally, mvPI in deep WM is significantly associated with the velocity pulsatility index (vePI) of large arteries (r = 0.5997, p = 0.0181). We further performed test-retest scans, non-parametric reliability test and simulations to demonstrate the reproducibility and accuracy of our method. To the best of our knowledge, our method offers the first in vivo measurement of microvascular volumetric pulsatility in human brain which has implications for cerebral microvascular health and its relationship research with glymphatic system, aging and neurodegenerative diseases.
Single-session intervention with and without video support to prevent the worsening of emotional distress among healthcare workers during the SARS-CoV-2 pandemic: a randomized clinical trial
Authors: Salum Giovanni Abrahão , Spanemberg Lucas , Costa Marianna de Abreu , Simioni André Rafael , Gosmann Natan Pereira , de Souza Lívia Hartmann , Cuijpers Pim , Pine Daniel Samuel , Brunoni André Russowsky , Katz Natan , Umpierre Roberto Nunes , Kristensen Christian Haag , Manfro Gisele Gus , Fleck Marcelo Pio de Almeida , Dreher Carolina Blaya 
Published: September 2024

SUMMARYBACKGROUNDThe SARS-CoV-2 pandemic was a major stressful event that significantly affected healthcare providers. This study aimed to compare the efficacy of a single-session intervention (SSI) with and without weekly personalized pre-recorded videos to prevent the worsening of emotional distress.METHODSNationwide randomized clinical trial conducted in Brazil from May 19, 2020 to December 31, 2021. We included healthcare professionals with levels of anxiety, depression, or irritability below a T-score of 70, defined by the Patient-Reported Outcomes Measurement Information System. The exclusion criterion was suicide risk. Participants were randomized to SSI or SSI plus weekly personalized pre-recorded videos for four weeks (SSI-ET). The primary outcome was the proportion of participants with a significant escalation of symptoms (i.e., T-score above 70). The trial was registered withClinicalTrials.gov(NCT04632082).FINDINGSOf the 3328 volunteers assessed for eligibility, 1112 participants were allocated to either SSI (n=549) or SSI-ET (n=563). The cumulative proportion of incident cases at six months was 17.5% (95% CI 13.1% to 21.6%) for SSI and 15% (95% CI 10.9% to 18.8%) for SSI-ET, with no difference between groups (HR=0.81, 95% CI 0.83 to 1.79). Both groups presented significant symptom reduction in the one-month assessment and maintained over three and six-month follow-ups (Cohen’s d range = 0.68 - 1.08).CONCLUSIONSWe found no benefit of adding asynchronous videos to SSIs; however, we found strong effects for the synchronous component for preventing symptom worsening. This component emphasizes core elements of mental health support, such as active listening, validation, and empathic care. Due to its simplicity and scalability, this intervention shows promise as a public health measure to be widely implemented.FUNDINGMinistry of Health of Brazil, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and Fundo de Incentivo à Pesquisa/Hospital de Clínicas de Porto Alegre.
Properties of Alzheimer’s disease brain-derived tau aggregates define tau processing by human astrocytes
Authors: Reid Matthew J. , Salazar Melissa Leija , Troakes Claire , Lynham Steven , Srivastava Deepak P. , Perez-Nievas Beatriz Gomez , Noble Wendy 
Published: September 2024

SummaryThe templated misfolding of tau proteins accounts for tau pathology spread in Alzheimer’s disease (AD). Post-translational modifications, including phosphorylation at specific residues, are closely linked with tau seeding ability and clinical disease progression. Increasing evidence supports a contributing role for astrocytes in tau spread. This study demonstrates that tau aggregates from postmortem AD brain are internalized and processed by human astrocytes. Differences in the efficiency of tau internalization, clearance and/or seeding were noted, which may reflect molecular properties of tau. Notably, we observed a direct relationship between alterations in tau handling by astrocytes and astrocyte responses, which were evident in transcriptomic data. Dysregulated genes include several previously identified as upregulated in reactive astrocytes in AD brain, as well as being implicated in pathological tau clearance by autophagy and other pathways. The study provides new insights into the complex interplay between tau molecular diversity and astrocyte responses in AD.
Genotype inference from aggregated chromatin accessibility data reveals genetic regulatory mechanisms
Authors: Wenz Brandon M. , He Yuan , Chen Nae-Chyun , Pickrell Joseph K. , Li Jeremiah H. , Dudek Max F. , Li Taibo , Keener Rebecca , Voight Benjamin F. , Brown Christopher D. , Battle Alexis 
Published: September 2024

AbstractBackgroundUnderstanding the genetic causes for variability in chromatin accessibility can shed light on the molecular mechanisms through which genetic variants may affect complex traits. Thousands of ATAC-seq samples have been collected that hold information about chromatin accessibility across diverse cell types and contexts, but most of these are not paired with genetic information and come from diverse distinct projects and laboratories.ResultsWe report here joint genotyping, chromatin accessibility peak calling, and discovery of quantitative trait loci which influence chromatin accessibility (caQTLs), demonstrating the capability of performing caQTL analysis on a large scale in a diverse sample set without pre-existing genotype information. Using 10,293 profiling samples representing 1,454 unique donor individuals across 653 studies from public databases, we catalog 23,381 caQTLs in total. After joint discovery analysis, we cluster samples based on accessible chromatin profiles to identify context-specific caQTLs. We find that caQTLs are strongly enriched for annotations of gene regulatory elements across diverse cell types and tissues and are often strongly linked with genetic variation associated with changes in expression (eQTLs), indicating that caQTLs can mediate genetic effects on gene expression. We demonstrate sharing of causal variants for chromatin accessibility and diverse complex human traits, enabling a more complete picture of the genetic mechanisms underlying complex human phenotypes.ConclusionsOur work provides a proof of principle for caQTL calling from previously ungenotyped samples, and represents one of the largest, most diverse caQTL resources currently available, informing mechanisms of genetic regulation of gene expression and contribution to disease.
RTN4IP1 is essential for the final stages of mitochondrial complex I assembly and coenzyme Q biosynthesis
Authors: Oláhová Monika , Guerra Rachel M. , Collier Jack J. , Heidler Juliana , Thompson Kyle , White Chelsea R. , Castañeda-Tamez Paulina , Cabrera-Orefice Alfredo , Lightowlers Robert N. , Chrzanowska-Lightowlers Zofia M. A. , Wittig Ilka , Pagliarini David J. , Taylor Robert W. 
Published: September 2024

SummaryA biochemical deficiency of mitochondrial complex I (CI) underlies ∼30% of cases of primary mitochondrial disease, yet the inventory of molecular machinery required for CI assembly remains incomplete. We previously characterised patients with isolated CI deficiency caused by segregating variants inRTN4IP1,encoding a mitochondrial NAD(P)H oxidoreductase. Here, we demonstrate that RTN4IP1 deficiency causes a CI assembly defect in both patient fibroblasts and knockout cells, and report that RTN4IP1 is abona fideCI assembly factor. Complexome profiling revealed accumulation of unincorporated ND5-module and impaired N-module production. RTN4IP1 patient fibroblasts also exhibited defective coenzyme Q biosynthesis, substantiating this emerging function of RTN4IP1. Thus, our data reveal RTN4IP1 plays an essential role in both the terminal stages of CI assembly and in coenzyme Q metabolism, and that pathogenicRTN4IP1variants impair both functions in patients with mitochondrial disease.
Right Caudate Volume and Executive Functions in Children with Attention-Deficit/Hyperactivity Disorder (ADHD)
Authors: Hai Tasmia , Swansburg Rose , Kahl Cynthia K. , Mrazik Martin , Lemay Jean-François , MacMaster Frank P. 
Published: September 2024

AbstractBackgroundThe caudate and putamen have previously been implicated in Attention-Deficit/Hyperactivity Disorder (ADHD). However, previous studies have not investigated the relationship between the caudate and putamen with executive function (EF). The current study investigated the clinical relevance of the caudate and putamen with respect to EF.MethodWe studied 49 children (24 ADHD/25 typically developing children (TDC)). All participants in the ADHD group had to undergo a 48-hour stimulant medication washout period. Participants completed cognitive tasks related to working memory/inhibition and underwent a T1-weighted MRI sequence. All parents completed behaviour rating scales using the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2). Data were analyzed using multivariate analysis of covariance, Pearson correlations, and linear regressions.ResultsChildren with ADHD demonstrated a higher frequency of perseverative errors compared to TDC (p <.05), and their parents reported significantly more EF challenges(p<.001). No difference was observed in the working memory tasks. No significant volumetric differences were seen in the caudate or the putamen. A linear regression model suggested that the right caudate volume accounted for 10.3% of the variance in emotion regulation as reported by parents on the BRIEF-2 in the overall sample.DiscussionWe observed significant EF challenges without volumetric differences. However, the right caudate was correlated to parent ratings of emotional regulation, highlighting the need to consider emotional regulation difficulties in ADHD.
Brain-wide circuitry underlying altered auditory habituation in zebrafish models of autism
Authors: Wilde Maya , Ghanbari Anahita , Mancienne Tessa , Moran Ailís , Poulsen Rebecca E. , Constantin Lena , Lee Conrad , Scholz Leandro Aluisio , Arnold Joshua , Qin Wei , Karle Timothy J. , Petrou Steven , Favre-Bulle Itia , Hoffman Ellen J. , Scott Ethan K. 
Published: September 2024

AbstractAuditory processing is widely understood to occur differently in autism, though the patterns of brain activity underlying these differences are not well understood. The diversity of autism also means brain-wide networks may change in various ways to produce similar behavioral outputs. We used larval zebrafish to investigate auditory habituation in four genetic lines relevant to autism:fmr1,mecp2,scn1labandcntnap2. In free-swimming behavioral tests, we found each line had a unique profile of auditory hypersensitivity and/or delayed habituation. Combining the optical transparency of larval zebrafish with genetically encoded calcium indicators and light-sheet microscopy, we then observed brain-wide activity at cellular resolution during auditory habituation. As with behavior, each line showed unique alterations in brain-wide spontaneous activity, auditory processing, and adaptation in response to repetitive acoustic stimuli. We also observed commonalities in activity across our genetic lines that indicate shared circuit changes underlying certain aspects of their behavioral phenotypes. These were predominantly in regions involved in sensory integration and sensorimotor gating rather than primary auditory areas. Overlapping phenotypes include differences in the activity and functional connectivity of the telencephalon, thalamus, dopaminergic regions, and the locus coeruleus, and excitatory/inhibitory imbalance in the cerebellum. Unique phenotypes include loss of activity in the habenula inscn1lab, increased activity in auditory regions infmr1,and differences in network activity over time inmecp2andcntnap2. Comparing these distinct but overlapping brain-wide auditory networks furthers our understanding of how diverse genetic factors can produce similar behavioral effects through a range of circuit- and network-scale mechanisms.
E. coliassociated with Crohn’s disease exhibit distinct strategies to colonize macrophages
Authors: Bruder Emma , Nedjar Hosni , Quenech’Du Nicole , Chevarin Caroline , Vazeille Emilie , Granotier Marie , Singh Parul , Buisson Anthony , Barnich Nicolas , Espéli Olivier 
Published: September 2024

AbstractPatients with Crohn’s disease exhibit abnormal colonization of the intestine by Proteobacteria, particularly the adherent-invasiveEscherichia coli(AIEC) group. These bacteria are predominant in the mucus, adhere to epithelial cells, colonize them, and survive inside macrophages. We recently demonstrated that the acclimation of strain LF82 to phagolysosomal stress occurs in two distinct steps: first, a replication halt producing stress- tolerant persisters, and second, a replication phase that leads to the formation of Intracellular Bacterial Communities (IBC) organized with a biofilm-like matrix. Given the significant genomic diversity among strains with the AIEC phenotype, we conducted a comparative analysis of the genomes and macrophage colonization characteristics of 13 AIEC strains collected from patients during a clinical study conducts by the CHU of Clermont-Ferrand. Our results demonstrate that IBCs serve as replicative niches for all AIEC strains within macrophages. However, these strains form IBCs using different strategies, including varying levels of phagosome detoxification, distinct biofilm characteristics, and diverse macrophage responses. Our study reveals a strong positive correlation between vacuole acidification and persister induction that explains intracellular survival of the different strains. In addition, we revealed distinct AIEC dissemination strategies outside macrophages, which may contribute to the propagation of inflammation in the human host. These findings highlight that research on pathogens and pathobionts with plastic genomes should not rely solely on a few laboratory models.
The Hox Gene,abdominal Acontrols timely mitotic entry of neural stem cell and their growth during CNS development inDrosophila
Authors: Das Papri , Murthy Smrithi , Abbas Eshan , White Kristin , Arya Richa 
Published: September 2024

AbstractThe size of a cell is important for its function and physiology. Interestingly, size variation can be easily observed in clonally derived embryonic and hematopoietic stem cells. Here, we investigated the regulation of stem cell growth and its association with cell fate. We observed heterogeneous sizes of neuroblasts or neural stem cells (NSCs) in theDrosophilaventral nerve cord (VNC). Specifically, thoracic NSCs were larger than those in the abdominal region of the VNC. Our research uncovered a significant role of the Hox geneabdominal A(abdA) in the regulation of abdominal NSC growth. Developmental expression of AbdA retards their growth and delays mitotic entry compared to thoracic NSCs. The targeted loss ofabdAenhanced their growth and caused an earlier entry into mitosis with a faster cycling rate. Furthermore, ectopic expression ofabdAreduced the size of thoracic NSCs and delayed their entry into mitosis. We suggest thatabdAplays an instructive role in regulating NSC size and exit from quiescence. This study demonstrates for the first time the involvement ofabdAin NSC fate determination by regulating their growth, entry into mitosis and proliferation rate, and thus their potential to make appropriate number of progeny for CNS patterning.Significance statementUnderstanding the upstream regulation of various aspects of the cell cycle is very important, how cell growth influences the process is largely unknown.We found an instructive role of the Hox geneabdominal Ain maintaining the small size of neural stem cells (NSCs) and limiting their ability to undergo mitosis.This mechanism is crucial, as it helps NSCs generate the necessary number of neurons at the appropriate developmental stage, thereby contributing to proper central nervous system patterning.