bluuebunny/crossref_metadata_2025_split huggingface dataset:
The nucleocytoplasmic translocation of HINT1 regulates the maturation of cell density
Authors: Zhang Xiaofang , Nakamura Fumihiko 
Published: January 2025

AbstractCell contact inhibition progresses through three stages: (i) increasing cell density leads to reduced movement while mitosis continues; (ii) a rapid shift to epithelial morphology; and (iii) ongoing division with decreased cell size. This transition involves reorganizing the actin cytoskeleton from stress fibers to a cortical network, stabilizing cell shape, and strengthening cell-cell connections. However, the signaling pathways regulating the final stage remain unclear. We identified histidine triad nucleotide-binding protein 1 (HINT1), also known as protein kinase C inhibitor 1 (PKCI-1), as essential for monolayer maturation. At low density, HINT1 is located in the nucleus, binding to open chromatin. As density increases, exportin-1 relocates HINT1 to the cytoplasm, where it inhibits PKC and remodels the actin cytoskeleton. While monolayer formation can occur without HINT1, its presence is necessary for fully confining cells and achieving a mature monolayer. Additionally, MARCKS phosphorylation decreases in high-density cells, and loss of HINT1 leads to increased cell area, similar to hypertrophic conditions in patients with low HINT1 levels.Summary blurbHistidine triad nucleotide-binding protein 1 shuttles between the nucleus and cytoplasm based on cell density, regulating gene expression in the nucleus and inhibiting protein kinase C in the cytoplasm to remodel actin.
Large-scale audiometric phenotyping identifies distinct genes and pathways involved in hearing loss subtypes
Authors: Ahmed Samah , Vaden Kenneth I. , Leitao Darren , Dubno Judy R. , Drögemöller Britt I. 
Published: January 2025

SummaryAge-related hearing loss affects one-third of the population over 65 years. However, the diverse pathologies underlying these heterogenous phenotypes complicate genetic studies. To overcome challenges associated with accurate phenotyping for older adults with hearing loss, we applied computational phenotyping approaches based on audiometrically measured hearing loss. This novel phenotyping strategy uncovered distinct genetic variants associated with sensory and metabolic hearing loss. Sex-stratified analyses of these sexually dimorphic hearing loss phenotypes revealed a novel locus of relevance to sensory hearing loss in males, but not females. Enrichment analyses revealed that genes involved in frontotemporal dementia were implicated in metabolic hearing loss, while genes relating to sensory processing of sound by hair cells were implicated in sensory hearing loss. Our study has enhanced our understanding of these two distinct hearing loss phenotypes, representing the first step in the development of more precise treatments for these pathologically distinct hearing loss phenotypes.
Describing variability of intensively collected longitudinal ordinal data with latent spline models
Authors: Lunt Mark , Selby David A. , Dixon William G. 
Published: January 2025

AbstractPopulation health studies increasingly collect longitudinal, patient-reported symptom data via mobile devices, offering unique insights into experiences outside clinical settings, such as pain, fatigue or mood. However, such data present challenges due to ordinal measurement scales, irregular sampling and temporal autocorrelation.This paper introduces two novel summary measures for analysing ordinal outcomes: (1)the mean absolute deviation from the median(Madm) for cross-sectional analyses and (2) themean absolute deviation from expectation(Made) for longitudinal data. The latter is based on a latent cumulative model with penalized splines, enabling smooth transitions between irregular time points while accounting for the ordinal nature of the data. Unlike black-box machine learning approaches, this method is interpretable, computationally efficient and easy to implement in standard statistical software.Through simulations, we demonstrate that the proposed measures outperform standard methods when the assumptions of normality or stationarity are violated. Application to real-world data from a national smartphone study,Cloudy with a Chance of Pain, highlights the utility of these measures in characterising symptom variability and trends over time.The methods developed here provide intuitive tools for analysing patient-reported outcomes in longitudinal studies, with potential applications in prediction modelling, causal discovery and evaluation of interventions.
Adaptive Transfer Learning for Time-to-Event Modeling with Applications in Disease Risk Assessment
Authors: Lu Yuying , Gu Tian , Duan Rui 
Published: January 2025

AbstractObjectiveTo address the challenges in for modeling time-to-event outcomes in small-sample settings by leveraging transfer learning techniques while accounting for potential covariate and concept shifts between source and target datasets.MethodsWe propose a novel transfer learning approach, termed CoxTL, for modeling time-to-event data based on the widely used Cox proportional hazards model. CoxTL utilizes a combination of density ratio weighting and importance weighting techniques to address multi-level data heterogeneity, including covariate and coefficient shifts between source and target datasets. Additionally, it accounts for potential model misspecification, ensuring robustness across a wide range of settings. We assess the performance of CoxTL through extensive simulation studies, considering data under various types of distributional shifts. Additionally, we apply CoxTL to predict End-Stage Renal Disease (ESRD) in the Hispanic population using electronic health record-derived features from the All of Us Research Program. Data from non-Hispanic White and non-Hispanic Black populations are leveraged as source cohorts. Model performance is evaluated using the C-index and Integrated Brier Score (IBS).ResultsIn simulation studies, CoxTL demonstrates higher predictive accuracy, particularly in scenarios involving multi-level heterogeneity between target and source datasets. In other scenarios, CoxTL performs comparably to alternative methods specifically designed to address only a single type of distributional shift. For predicting the 2-year risk of ESRD in the Hispanic population, CoxTL achieves increase in C-index up to 6.76% compared to the model trained exclusively on target data. Furthermore, itdemonstrates up to 17.94% increase in the C-index compared to the state-of-the-art transfer learning method based on Cox model.ConclusionThe proposed method effectively utilizes source data to enhance time-to-event predictions in target populations with limited samples. Its ability to handle various sources and levels of data heterogeneity ensures robustness, making it particularly well-suited for real-world applications involving target populations with small sample sizes, where traditional Cox models often struggle.
Extreme high-diversity barcoded HIV library enables single cell multi-omics analysis of viral expression and fate determination
Authors: Zhang Tian-hao , Sheng Li , Meng Xiangzhi , Lai Wenjin , Du Yushen , Shi Yuan , Wen Jing , Kamata Masakazu , Chanda Sumit K. , Chen Irvin SY. , Sun Ren 
Published: January 2025

ABSTRACTHIV-1 persists as a global health challenge due to its ability to establish latent reservoirs that evade eradication by antiretroviral therapy (ART). This study introduces a high-diversity barcoded HIV-1 library combined with a novel peptide barcode system to enable single-cell multi-dimensional analysis of viral integration, transcription, splicing, and translation of distinct viral mRNA isoform. Our method revealed over 80 distinct HIV-1 splicing isoforms and uncovered significant temporal variation in mRNA diversity, driven by integration site and chromatin context. By linking HIV-1 5’UTR with peptide barcoding, we quantified the translation efficiency of alternative 5′ UTRs and demonstrated correlations with abundance of each viral mRNA isoform. Additionally, we showed that latency reversal agents, such as SAHA and Bryostatin, selectively reactivate proviruses depending on their genomic and chromatin context and leads to distinct viral RNA splicing program. This platform revealed the diversity of HIV-infected cells at levels of transcripts as well as at proteins, and subsequently the fate determination. The detailed understanding of the stochastic diversity and dynamic nature of HIV-1 latency, inform the development of targeted therapies to eliminate latent reservoirs.
Pseudomonassuperinfection drives Pf phage transmission within airway infections in patients with cystic fibrosis
Authors: Pourtois Julie D. , Haddock Naomi L. , Gupta Aditi , Khosravi Arya , Martinez Hunter , Schmidt Amelia K. , Prakash Prema S. , Jain Ronit , Fleming Piper , Chang Tony H. , Milla Carlos , Secor Patrick R. , De Leo Giulio A. , Bollyky Paul L. , Burgener Elizabeth B. 
Published: January 2025

AbstractPf bacteriophages, lysogenic viruses that infectPseudomonas aeruginosa (Pa),are implicated in the pathogenesis of chronicPainfections; phage-infected (Pf+) strains are known to predominate in people with cystic fibrosis (pwCF) who are older and have more severe disease. However, the transmission patterns of Pf underlying the progressive dominance of Pf+ strains are unclear. In particular, it is unknown whether phage transmission commonly occurs horizontally between bacteria within the airway via viral particles or if Pf+ bacteria are mostly acquired via newPseudomonasinfections. Here, we have studiedPagenomic sequences from 3 patient cohorts totaling 663 clinical isolates from 105 pwCF. We identify Pf+ isolates and analyze transmission patterns of Pf within patients between genetically similar groups of bacteria called “clone types”. We find that Pf is predominantly passed down vertically withinPalineages and rarely via horizontal transfer between clone types within the airway. Conversely, we find extensive evidence ofPasuperinfection by a new, genetically distinctPathat is Pf+. Finally, we find that clinical isolates show reduced activity of the type IV pilus and reduced susceptibility to Pfin vitro.These results cast new light on the transmission of virulence-associated phages in the clinical setting.
Small or absent Visual Word Form Area is a trait of dyslexia
Authors: Mitchell Jamie L. , Yablonski Maya , Stone Hannah L. , Fuentes-Jimenez Mia , Takada Megumi E. , Tang Kenny A. , Tran Jasmine E. , Chou Clementine , Yeatman Jason D. 
Published: January 2025

AbstractUnderstanding the balance between plastic and persistent traits in the dyslexic brain is critical for developing effective interventions. This longitudinal intervention study examines the Visual Word Form Area (VWFA) in dyslexic and typical readers, exploring how this key component of the brain’s reading circuitry changes with learning. We found that dyslexic readers show significant differences in VWFA presence, size, and tuning properties compared to typical readers. While reading intervention improved reading skills and increased VWFA size, disparities persisted, suggesting that VWFA abnormalities are an enduring trait of dyslexia. Notably, we found that even with sufficient intervention to close the reading skill gap, dyslexic readers are still expected to have smaller VWFAs. Our results reveal intervention-driven long-term neural and behavioral changes, while also elucidating stable differences in the functional architecture of the dyslexic brain. This provides new insights into the potential and limitations of learning-induced plasticity in the human visual cortex.
Integrated model of the protein molecular clock across mammalian species
Authors: Saini Anshul , Usmanova Dinara R. , Vitkup Dennis 
Published: January 2025

AbstractOne of the foundational concepts in molecular evolution is the protein molecular clock [1-3], encapsulating the observation that proteins tend to accumulate amino acid substitutions at approximately constant and protein-specific rates over long evolutionary timescales. According to the neutral theory of molecular evolution, the majority of protein substitutions have neutral or nearly neutral effects on species fitness. The neutral theory suggests the existence of a strong generation time effect, positing that species with shorter generation times should accumulate protein substitutions faster per unit time compared to species with longer generation times. However, earlier studies failed to detect a significant generation time effect for amino acid substitutions in vertebrates, raising questions about core tenets of the neutral theory. In this study, we take advantage of the recently accumulated evolutionary and genomics data to investigate the scaling of substitution rates with generation time among many dozens of mammalian species and thousands of proteins. Our findings reveal a strong generation time effect both for synonymous and non-synonymous substitutions. We demonstrate that the empirically observed generation time effect is fully consistent with several mechanisms, such as functional and mutation rate selection. Building on these results, we develop an integrated model of protein evolution that incorporates changes in substitution rates due to variation in species generation times throughout their evolutionary history. Overall, our analysis shows that protein evolution is consistent with neutral or nearly neutral theories and explains time-like behavior of the protein molecular clock across deep phylogenetic lineages.
Unintended bias in the pursuit of collinearity solutions in fMRI analysis
Authors: Mumford Jeanette A. , Demidenko Michael I. , Bjork James M. , Chaarani Bader , Feczko Eric J. , Garavan Hugh P. , Hagler Donald J. , Nelson Steven M. , Wager Tor D. , Poldrack Russell A. 
Published: January 2025

AbstractIn task functional magnetic resonance imaging (fMRI), collinearity between task regressors in a design matrix may impact power. Researchers often optimize task designs by assessing collinearity between task regressors to minimize downstream effects. However, some methods intended to reduce collinearity during optimization and data analysis may fail, in some cases introducing unintended bias into the parameter estimates. Although relevant to all task-based fMRI studies, we describe these issues and illustrate them using the Monetary Incentive Delay (MID) task fMRI data from the Adolescent Brain Cognitive Development (ABCD®) study. Specifically, we show that omitting regressors for certain task components, using impulse regressors for extended activations, and ignoring response time adjustments can bias common contrast estimates. We present a “Saturated” model that models all stimuli and response times, which minimizes bias in MID task simulations and validly estimates task-relevant whole brain activity, offering greater flexibility in studying contrasts that might otherwise be avoided due to potential biases.
HIV prevalence, risk factors for infection, use of prevention methods, and interventions among taxi drivers and commercial motorcyclists in sub-Saharan Africa: A scoping review
Authors: Asiimwe John Baptist , Betunga Benjamin , Birungi Lilian , Kabasindi Joy , Wankiiri Moses , Nuwabaine Lilian , Kawuki Joseph , Kumakech Edward 
Published: January 2025

AbstractBackgroundTransport workers, particularly taxi drivers and commercial motorcyclists, comprise a population at high risk for HIV and account for nearly one-third of new HIV infections in sub-Saharan Africa (SSA). Furthermore, transport workers bridge HIV infections from high-risk populations to the general population. This scoping review aimed to map the available evidence around HIV prevalence, risk factors for HIV infection, use of HIV prevention methods, and HIV interventions among taxi drivers and commercial motorcyclists in SSA.MethodThis scoping review used the Arksey and O’Malley framework. Published articles were retrieved from MEDLINE (via PubMed), CINAHL, African Index Medicus, Web of Science, Scopus, EMBASE, HINARI, and Google Scholar from inception to August 2024. Two authors screened the titles and abstracts of retrieved studies and examined the references of relevant articles for additional literature. Three authors independently extracted data from the included studies using a standard data extraction form. Data were analyzed using descriptive statistics and content analysis techniques. The themes were collated, and a descriptive summary of the findings was reported.ResultsThis review included 24 studies. The HIV prevalence was 2.02%–9.9% among commercial motorcyclists, and reached 33.4% in samples comprising both motorcyclists and taxi drivers. The high HIV infection rate was attributable to numerous behavioral (e.g., multiple sex partners), psychosocial (e.g., stigma), and sociodemographic (e.g., age, income) risk factors. However, there was suboptimal use of HIV prevention methods such as safe male circumcision (20.7%–64.9%) and condoms (26%–45.7%). The two HIV interventional studies were conducted among commercial motorcyclists. Despite HIV testing being an entry point for chronic care, we found no study reporting the HIV cascade for commercial motorcyclists or taxi drivers who were diagnosed with HIV, including the use of antiretroviral therapy, pre-exposure prophylaxis (PREP), and post- exposure prophylaxis.ConclusionsThe numerous research gaps highlight the need for longitudinal research on HIV incidence and predictors in this key population, especially the structural determinants of HIV infection. There is also a need for interventional and observational research on new models of HIV testing (e.g., HIV oral testing), antiretroviral-based HIV prevention methods (e.g., PREP), and the role of peer-to- peer educator or group support/counseling models in reducing HIV infection and mitigating risky HIV-related sexual behavior. Such studies may provide evidence to inform better HIV prevention and control policies and programs among taxi drivers and commercial motorcyclists in SSA.
Genetic changes linked to two different syndromic forms of autism enhance reinforcement learning in adolescent male but not female mice
Authors: Chase Juliana , Li Jing-Jing , Lin Wan Chen , Tai Lung-Hao , Castro Fernanda , Collins Anne GE , Wilbrecht Linda 
Published: January 2025

AbstractAutism Spectrum Disorder (ASD) is characterized by restricted and repetitive behaviors and social differences, both of which may manifest, in part, from underlying differences in corticostriatal circuits and reinforcement learning. Here, we investigated reinforcement learning in mice with mutations in eitherTsc2orShank3, both high-confidence ASD risk genes associated with major syndromic forms of ASD. Using an odor-based two-alternative forced choice (2AFC) task, we tested adolescent mice of both sexes and found maleTsc2andShank3Bheterozygote (Het) mice showed enhanced learning performance compared to their wild type (WT) siblings. No gain of function was observed in females. Using a novel reinforcement learning (RL) based computational model to infer learning rate as well as policy-level task engagement and disengagement, we found that the gain of function in males was driven by an enhanced positive learning rate in bothTsc2andShank3BHet mice. The gain of function in Het males was absent when mice were trained with a probabilistic reward schedule. These findings in two ASD mouse models reveal a convergent learning phenotype that shows similar sensitivity to sex and environmental uncertainty. These data can inform our understanding of both strengths and challenges associated with autism, while providing further evidence that sex and experience of uncertainty modulate autism-related phenotypes.Significance StatementReinforcement learning is a foundational form of learning that is widely used in behavioral interventions for autism. Here, we measured reinforcement learning in adolescent mice carrying genetic mutations linked to two different syndromic forms of autism. We found that males showed strengths in reinforcement learning compared to their wild type siblings, while females showed no differences. This gain of function in males was no longer observed when uncertainty was introduced into the reward schedule for correct choices. These findings support a model in which diverse genetic changes interact with sex to generate common phenotypes underlying autism. Our data further support the idea that autism risk genes may produce strengths as well as challenges in behavioral function.
Political ideology drives the integration of country-of-origin and offshoring sustainability impact information toward globally prosocial product decisions
Authors: Maxwell-Smith Matthew , Rotman Jeff D. , Johnson Allison R. 
Published: January 2025

Purpose
We investigate how white Western consumers make prosocial decisions on domestically branded products manufactured in countries with a developing economy (CDEs). Citizens in these countries manufacture products routinely sold in Western markets under Western companies and brands as part of an offshore supply chain.

Design/methodology/approach
We propose that prosocial decision-making about these products can be traced to an interactive effect between consumers’ perceptions of the social sustainability impact of offshoring on CDE nations and social dominance orientation (SDO)-Dominance (SDO-D), an ideological preference for higher-status groups to forcefully oppress lower-status groups. In three studies with white Western consumers, this paper measured SDO-D, measured or experimentally manipulated the harmful versus beneficial impact of offshoring on CDEs, and presented assessed participants’ willingness to purchase domestically branded and CDE-manufactured products across a series of decision trials.

Findings
White Western consumers with low SDO-D prosocially displayed weaker purchase intentions toward products with a domestic brand manufactured in a CDE (“DCDE products”) when offshoring was perceived as harming those countries, and stronger intentions when offshoring was perceived as beneficial. This effect was mediated by consumers’ trust in domestic firms to treat workforce issues appropriately. Conversely, high SDO-Ds’ intentions were unaffected by the perceived harmful or beneficial impact of offshoring.

Research limitations/implications
Future work in this area will ideally use field purchasing situations while testing for brand familiarity – as a covariate or moderator.

Practical implications
Firms that market or sell these products are advised to understand if their target segments have lower or higher levels of SDO-D, and how they evaluate the impact of the offshored supply chain on CDE citizens. Our research also suggests Western low SDO-Ds attributed the responsibility of foreign worker treatment to their own domestic companies, rather than foreign governments or offshoring agencies, when CDE workers were harmed by offshoring.

Originality/value
These findings have broad implications for the various markets and policies behind the sale and positioning of DCDE products and help identify the consumers who demand socially sustainable supply chains and offshore operations.