bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and disease risks for male and female sex chromosome trisomies: a registry-based phenome-wide association study in 1.5 million participants of MVP, FinnGen, and UK Biobank
Authors: Davis Shanlee M. , Liu Aoxing , Teerlink Craig C. , Lapato Dana M. , Gorman Bryan , Genovese Giulio , Singh Madhurbain , Reeve Mary P. , Gentry Amanda Elswick , Donner Kati M. , Sipilä Timo P. , Ghazal Awaisa , Pagadala Meghana S. , Panizzon Matthew S. , Lancaster Eva E. ,   FinnGen banner authorship,   UKB working group authorship, Chatzinakos Chris , Ganna Andrea , Bigdeli Tim B. , Daly Mark J , Lynch Julie A. , Ross Judith , Peterson Roseann E. , Hauger Richard L. 
Published: February 2025

ABSTRACTSex chromosome trisomies (SCT) are the most common whole chromosome aneuploidy in humans. Yet, our understanding of the prevalence and associated health outcomes is largely driven by observational studies of clinically diagnosed cases, resulting in a disproportionate focus on 47,XXY and associated hypogonadism. We analyzed microarray intensity data of sex chromosomes for 1.5 million individuals enrolled in three large cohorts—Million Veteran Program, FinnGen, and UK Biobank—to identify individuals with 47,XXY, 47,XYY, and 47,XXX. We examined disease conditions associated with SCTs by performing phenome-wide association studies (PheWAS) using electronic health records (EHR) data for each cohort, followed by meta-analysis across cohorts. Association results are presented for each SCT and also stratified by presence or absence of a documented clinical diagnosis for 47,XXY. We identified 2,769 individuals with (47,XXY: 1,319; 47,XYY: 1,108; 47,XXX: 342), most of whom had no documented clinical diagnosis (47,XXY: 73.8%; 47,XYY: 98.6%; 47,XXX: 93.6%). The identified phenotypic associations with SCT spanned all PheWAS disease categories except neoplasms. Many associations are shared among three SCT subtypes, particularly for vascular diseases (e.g., chronic venous insufficiency (OR [95% CI] for 47,XXY 4.7 [3.9,5.8]; 47,XYY 5.6 [4.5,7.0]; 4 7,XXX 4.6 [2.7,7.6], venous thromboembolism (47,XXY 4.6 [3.7-5.6]; 47,XYY 4.1 [3.3-5.0]; 47,XXX 8.1 [4.2-15.4]), and glaucoma (47,XXY 2.5 [2.1-2.9]; 47,XYY 2.4 [2.0-2.8]; 47,XXX 2.3 [1.4-3.5]). A third sex chromosome confers an increased risk for systemic comorbidities, even if the SCT is not documented. SCT phenotypes largely overlap, suggesting one or more X/Y homolog genes may underlie pathophysiology and comorbidities across SCTs.
Assessing Algorithm Fairness Requires Adjustment for Risk Distribution Differences: Re-considering the Equal Opportunity Criterion
Authors: Hegarty Sarah E. , Linn Kristin A. , Zhang Hong , Teeple Stephanie , Albert Paul S. , Parikh Ravi B. , Courtright Katherine , Kent David M. , Chen Jinbo 
Published: February 2025

AbstractThe proliferation of algorithm-assisted decision making has prompted calls for careful assessment of algorithm fairness. One popular fairness metric, equal opportunity, demands parity in true positive rates (TPRs) across different population subgroups. However, we highlight a critical but overlooked weakness in this measure: at a given decision threshold, TPRs vary when the underlying risk distribution varies across subgroups, even if the model equally captures the underlying risks. Failure to account for variations in risk distributions may lead to misleading conclusions on performance disparity. To address this issue, we introduce a novel metric called adjusted TPR (aTPR), which modifies subgroup-specific TPRs to reflect performance relative to the risk distribution in a common reference subgroup. Evaluating fairness using aTPRs promotes equal treatment for equal risk by reflecting whether individuals with similar underlying risks have similar opportunities of being identified as high risk by the model, regardless of subgroup membership. We demonstrate our method through numerical experiments that explore a range of differential calibration relationships and in a real-world data set that predicts 6-month mortality risk in an in-patient sample in order to increase timely referrals for palliative care consultations.
Contrasting patterns of subtelomeric satellite superfamily in theCannabaceaefamily
Authors: Horáková Lucie , Bačovský Václav , Janoušek Bohuslav , Patzak Josef , Hobza Roman 
Published: February 2025

AbstractSatellite DNA (satDNA) is a rapidly evolving component of plant genomes, often found in centromeric, telomeric, and heterochromatic regions. Due to their variability and species- or population-specific distribution, satDNA serves as valuable cytogenetic markers for studying chromosomal rearrangements and karyotype evolution in closely related species. In dioecious speciesCannabis sativa, Humulus lupulus, andHumulus japonicus, previous studies have identified species-specific subtelomeric repeats CS-1, HSR1, and HJSR. While these satellites have been used to differentiate sex chromosomes from autosomes, their evolutionary origins, sequence variation and pattern of conservation among related species remain largely unexplored. In this study, we combine bioinformatics analysis with molecular cloning to analyze sequence similarity among these shared satellites and determine their inter-specific chromosomal localization using fluorescencein situhybridization (FISH). Our results reveal that HSR1 and HJSR satellites are shared among all studied species suggested oaring from a common ancestor. In contrast, CS-1 satellite exhibit higher sequence divergence. Although all satellites are predominantly localized in subtelomeric regions, CS-1 inH. lupulusand HSR inC. sativaare localized in pericentromeric regions. These findings provide new insight into the evolutionary dynamics of satDNA inCannabaceaefamily and its role in genome organization.
Analysis of The Senescence Secretome During Zebrafish Retina Regeneration
Authors: Konar Gregory J. , Vallone Kyle T. , Nguyen Tu D. , Patton James G. 
Published: February 2025

AbstractZebrafish possess the innate ability to regenerate any lost or damaged retinal cell type with Müller glia serving as resident stem cells. Recently, we discovered that this process is aided by a population of damage-induced senescent immune cells. As part of the Senescence Associated Secretory Phenotype (SASP), senescent cells secrete numerous factors that can play a role in the modulation of inflammation and remodeling of the retinal microenvironment during regeneration. However, the identity of specific SASP factors that drive initiation and progression of retina regeneration remains unclear. Here, we mined the SASP Atlas and RNAseq datasets to identify differentially expressed SASP factors after retina injury, including two distinct acute damage regimens, as well as a chronic, genetic model of retina degeneration. We discovered a 31-factor “Regeneration-associated Senescence Signature” (RASS) that represents SASP factors and senescence markers that are conserved across all data sets and are upregulated after damage. Among these, we show that depletion of Nucleophosmin 1 (npm1a)inhibits retina regeneration. Our data support the model that differential expression of SASP factors promotes regeneration after both acute and chronic retinal damage.
Financial barriers to accessing mental healthcare services among visually impaired people
Authors: Pan Annabelle A. , Aguirre Bani A. , Betzler Bjorn K. , Singh Mandeep S. 
Published: February 2025

AbstractAimsVisual impairment (VI) is associated with heightened levels of loneliness, anxiety, and depression – yet few people with VI use mental healthcare services (MHS). The reasons for this are incompletely understood. Here, we aimed to understand possible financial barriers by analyzing the association of VI with delaying or foregoing MHS due to cost in a population database.MethodsWe conducted a cross-sectional study using the National Health Interview Survey (NHIS) of the U.S. Centers for Disease Control and Prevention (2019 to 2022). The primary outcome measure was the rate of delaying and foregoing obtaining MHS due to cost among participants with VI. Secondary outcomes included associations between sociodemographic characteristics and delaying or foregoing MHS due to cost. Logistic regressions were adjusted for demographic characteristics including household income.ResultsAmong 18,475 participants, 27% reported VI. Participants with VI were more likely to be older, female, have lower income, and had lower educational attainment than those without VI. VI was associated with greater odds of delaying (adjusted odds ratio (aOR): 1.5, 95% confidence interval (CI) 1.3-1.6) and foregoing (aOR: 1.5, 95% CI 1.3-1.6) MHS due to cost. Among individuals with VI, those who were female and younger had higher odds of delaying and foregoing MHS due to cost.ConclusionsIndividuals with VI and depression or anxiety may be at higher risk of delaying or foregoing MHS due to cost. These findings underscore the importance of addressing financial barriers to ensure equitable access to MHS for individuals with VI.
ROR2 drives right ventricular heart failure via disruption of proteostasis
Authors: Hartman Hali , Uy Genevieve , Uchida Keita , Scarborough Emily A. , Yang Yifan , Barr Eric , Williams Spencer , Kavar Sanam L. , Brandimarto Jeff , Li Li , Lai Ling , Griffin Joanna , Yucel Nora , Shewale Swapnil , Rajagopal Hari , Eaton Deborah M. , Dorwart Tanis , Bedi Kenneth C. , Conn Crystal S. , Margulies Kenneth , Prosser Benjamin , Arany Zoltan , Edwards Jonathan J. 
Published: February 2025

AbstractBackgroundNo therapies exist to reverse right ventricular failure (RVF), and the molecular mechanisms that drive RVF remain poorly studied. We recently reported that the developmentally restricted noncanonical WNT receptor ROR2 is upregulated in human RVF in proportion to severity of disease. Here we test mechanistic role of ROR2 in RVF pathogenesis.MethodsROR2 was overexpressed or knocked down in neonatal rat ventricular myocytes (NRVMs). ROR2-modified NRVMs were characterized using confocal microscopy, RNAseq, proteomics, proteostatic functional assays, and contractile properties with pacing. The impact of cardiac ROR2 expression was evaluated in mice by AAV9-mediated overexpression and by AAV9-mediated delivery of shRNA to knockdown ROR2 in a pulmonary artery banded pressure overload RVF model. ROR2-modified mice were evaluated by echocardiography, RV protein synthetic rates and proteasome activity.ResultsIn NRVMs, we find that ROR2 profoundly dysregulates the coordination between protein translation and folding. This imbalance leads to excess protein clearance by the ubiquitin proteasome system (UPS) with dramatic impacts on sarcomere and cytoskeletal structure and function. In mice, forced cardiac ROR2 expression is sufficient to disrupt proteostasis and drive RVF, while conversely ROR2 knockdown partially rescues proteostasis and cardiac function in a pressure overload model of RVF.ConclusionsIn sum, ROR2 is a key driver of RVF pathogenesis through proteostatic disruption and, thus, provides a promising target to treat RVF.
Quorum sensing regulation by the nitrogen phosphotransferase system inPseudomonas aeruginosa
Authors: Banerjee Samalee , Smalley Nicole E. , Saenjamsai Pradtahna , Fehr Anthony , Dandekar Ajai A. , Cabeen Matthew T. , Chandler Josephine R. 
Published: February 2025

ABSTRACTIn the opportunistic pathogenPseudomonas aeruginosa, the nitrogen-related phosphotransferase system (PTSNtr) influences multiple virulence behaviors. The PTSNtris comprised of three enzymes: first PtsP, then the PtsO phosphocarrier, and the final PtsN phosphoacceptor. We previously showed thatptsPinactivation increases LasI-LasR quorum sensing, a system by whichP. aeruginosaregulates genes in response to population density. LasI synthesizes a diffusible autoinducer that binds and activates the LasR receptor, which activates a feedback loop by increasinglasIexpression. In this study, we examined the impact of the PTSNtron quorum sensing. Disruption ofptsPincreased the expression of some, but not all, tested quorum-controlled genes, includinglasI, phzM(pyocyanin biosynthesis),hcnA(hydrogen cyanide biosynthesis), and, to a lesser extent,rsaL(quorum sensing regulator). Expression of these genes remained dependent on LasR and the autoinducer, whether provided endogenously or exogenously. IncreasedlasIexpression in ΔptsP(or ΔptsO) cells was partly due to the presence of unphosphorylated PtsN, which alone was sufficient to elevatelasIexpression. However, we observed residual increases in ΔptsPor ΔptsOcells even in the absence of PtsN, suggesting that PtsP and PtsO can regulate gene expression independent of PtsN. Indeed, genetically disrupting the PtsO phosphorylation site impacted gene expression in the absence of PtsN, and transcriptomic evidence suggested that PtsO and PtsN have distinct regulons. Our results expand our view of how the PTSNtrcomponents function both within and apart from the classic phosphorylation cascade to regulate key virulence behaviors inP. aeruginosa.IMPORTANCEPseudomonas aeruginosaoften causes severe and difficult-to-treat infections.P. aeruginosavirulence requires the nitrogen-related phosphotransferase system (PTSNtr), which comprises the phosphocarrier proteins PtsP and PtsO and the final phosphoacceptor, PtsN. The PTSNtris known to modulate quorum sensing, but little is known about the mechanism of regulation. Here, we examined quorum sensing regulation by the PTSNtr. We showed that the PTSNtrincreases quorum sensing-mediated activation of certain genes through the additive effects of both PtsO and PtsN. We also used transcriptomics to determine the regulons of PtsO and PtsN and found that they are largely nonoverlapping. The results position PtsO and PtsN as independent effectors in the Nitro-PTS and shed new light on virulence regulation in this important pathogen.
Glutamate methylation, a novel histone mark in diatoms: Mass spectrometry identification and structural characterization
Authors: Téletchéa Stéphane , Lombard Bérangère , Hendrickx Johann , Loew Damarys , Tirichine Leïla 
Published: February 2025

AbstractPost-translational modifications of histones (PTMs) play a crucial role in regulating chromatin function. These modifications are integral to numerous biological processes, including transcription, DNA repair, replication, and chromatin remodeling. While several PTMs have been identified, enhancing our understanding of their roles in these processes, there is still much to discover given the potential for virtually any histone residue to be modified. In this study, we report the discovery of a novel PTM in the model diatomPhaeodactylum tricornutum, glutamate methylation identified by mass spectrometry at multiple positions on histone H4 and at position 96 on histone H2B. This modification was also detected in other model organisms, includingDrosophila melanogaster,Caenorhabditis elegans, and humans, but not inArabidopsis. Structural bioinformatics analyses, including molecular dynamics simulations, revealed that methylation of glutamate residues on histones induces displacement of these residues, exposing them to solvent and disrupting interactions with neighboring residues in associated histones. This disruption may interfere with histone complexes promoting histone eviction or facilitating interactions with regulatory proteins or complexes, which may compromise the overall nucleosome stability.
ShigellaOspF blocks rapid p38-dependent priming of the NAIP–NLRC4 inflammasome
Authors: Turcotte Elizabeth A. , Kim Kyungsub , Eislmayr Kevin D. , Goers Lisa , Mitchell Patrick S. , Lesser Cammie F. , Vance Russell E. 
Published: February 2025

AbstractThe NAIP–NLRC4 inflammasome senses pathogenic bacteria by recognizing the cytosolic presence of bacterial proteins such as flagellin and type III secretion system (T3SS) subunits. In mice, the NAIP–NLRC4 inflammasome provides robust protection against bacterial pathogens that infect intestinal epithelial cells, including the gastrointestinal pathogenShigella flexneri. By contrast, humans are highly susceptible toShigella, despite the ability of human NAIP–NLRC4 to robustly detectShigellaT3SS proteins. Why the NAIP–NLRC4 inflammasome protects mice but not humans againstShigellainfection remains unclear. We previously found that human THP-1 cells infected withShigellalose responsiveness to NAIP–NLRC4 stimuli, while retaining sensitivity to other inflammasome agonists. Using mT3Sf, a “minimalShigella” system, to express individual secretedShigellaeffector proteins, we found that the OspF effector specifically suppresses NAIP–NLRC4-dependent cell death during infection. OspF was previously characterized as a phosphothreonine lyase that inactivates p38 and ERK MAP kinases. We found that p38 was critical for rapid priming of NAIP–NLRC4 activity, particularly in cells with low NAIP–NLRC4 expression. Overall, our results provide a mechanism by whichShigellaevades inflammasome activation in humans, and describe a new mechanism for rapid priming of the NAIP–NLRC4 inflammasome.
Bacterial IF2’s N-terminal IDR drives cold-induced phase separation and promotes fitness during cold stress
Authors: Ghosh Aishwarya , Mallikaarachchi Kaveendya S. , Dzurik Kathryn G. , Nandana Vidhyadhar , Nunez Nathaniel R. , Childers W. Seth , Schrader Jared M. 
Published: February 2025

SummaryTranslation initiation factor 2 (IF2) plays an essential role in bacterial cells by delivering the fMet-tRNAfMetto the ribosome pre-initiation complex. IF2 is known to have an N-terminal disordered region which is present across bacterial species, yet its function is not fully understood. Deletion of the IDR inE. colishowed no phenotypes at normal growth temperature (37°C); however, this IDR was found to be required for growth at cold temperatures (15°C). Since large IDRs can drive phase separation of various RNA binding proteins into biomolecular condensates, we investigated whetherE. coliIF2 could phase separate. We discovered that IF2’s N-terminal IDR drives phase separation inE. coliandC. crescentus, suggesting that IF2 condensation is a conserved property. Finally, usingE. coli, we found that the IDR strongly drives phase separation in the cold, suggesting IF2 condensates promote fitness during cold stress.HighlightsIF2’s IDR promotes phase separation with RNA.Cold temperature promotes IF2 condensation with RNA.IF2’s IDR promotes fitness during cold shock.
HIF1α gates tendon response to overload and drives tendinopathy independently of vascular recruitment
Authors: Moschini Greta , Mohanan Archana G. , Niewczas Izabella S. , Taylor Diane E. , Jaeger Patrick K. , Hussien Amro A. , Wunderli Stefania L. , Baumberger Olivia , Wolleb Maja , Niederoest Barbara , Bollhalder Maja , Ardicoglu Raphaela , Turiel Guillermo , Masschelein Evi , Morice Sarah , Ardiles Santiago , Mous Lieke , Aronoff Matthew R. , Hilbe Monika , Selman Farah , Wieser Karl , Fucentese Sandro F. , Passini Fabian S. , Blache Ulrich , Surdez Didier , Wennemers Helma , Elewaut Dirk , Clark Jonathan , De Bock Katrien , Snedeker Jess G. 
Published: February 2025

AbstractTendons are mostly avascular dense connective tissues that link muscles to bones, withstanding some of the highest mechanical stresses in the body. Mechanical overload and tissue hypervascularity are implicated in tendinopathy, a common musculoskeletal disorder, but mechanistic understanding of their roles is largely lacking. Here, we identify HIF1α not only as a marker but as a driver of tendinopathy. Initial histological and multi-omics evaluation of human tendinopathic samples revealed extensive extracellular matrix remodeling, including pathological collagen crosslinking coinciding with active hypoxic signaling. Hypothesizing a causal contribution of hypoxia signaling, we generated mice with tenocyte-targeted deletions of the Von Hippel-Lindau (VHL) gene, which controls hypoxia signaling by regulating HIFα degradation. We demonstrated that VHL inactivation suffices to induce pathological hallmarks of tendinopathy, such as collagen matrix disorganization, crosslinking, altered mechanics and neuro-vascular ingrowth. This phenotype was HIF1α-dependent, since co-deleting HIF1α rescued tendon morphology and mechanics. Moreover, deleting vascular endothelial growth factor A (VEGFA) alongside VHL effectively decoupled the effects of vascular ingrowth from persistently aberrant extracellular matrix remodeling and mechanical dysfunction, emphasizing a direct role of HIF1α in driving tendon disease that is independent of angiogenesis. Mechanistically, we linked tendon mechanical overload to the onset of HIF1α signaling in primary cultured human tendon cells. Furthermore, genetically removing HIF1α from tenocytes prevented aberrant tendon remodeling in response to chronic overload. These findings position HIF1α signaling as a central driver of tendinopathy that acts through a maladaptive tissue response to chronic overload, providing mechanistic insights that could be leveraged for improved therapeutic approaches.One Sentence SummaryHIF1α activation promotes tendinopathy and its inhibition prevents overload-induced maladaptation, suggesting therapeutic potential.
Multi-output computation by single neuron biophysics in a visual system
Authors: Seung H. Sebastian 
Published: February 2025

AbstractAs long anticipated (Sandberg and Bostrom 2008; Seung 2012; Szigeti et al. 2014), connectomics is providing a new foundation for brain simulation by replacing theoretical assumptions about network connectivity with solid empirical facts. Connectomics also yields detailed information about neuronal morphology, which is useful for simulating the biophysics of single neurons (Yang et al. 2016; Meier and Borst 2019; T. X. Liu et al. 2022). Here I introduce a formalism for simulating a brain as a network of synapses interacting via an effective resistance matrix. By computing this matrix for fly visual interneurons, I find evidence that some neurons may be true multi-output devices, neither well approximated as “point neurons” (Lappalainen et al. 2024; Shiu et al. 2024), nor as collections of functionally independent compartments (Meier and Borst 2019). Within a linear approximation, such a neuron is instead equivalent to a hierarchy of virtual neurons that spatially pool over multiple length scales. The computational powers of multi-output neurons may support highly sophisticated normalizations in the fly visual system (Seung 2024a).
Meeting market and student expectations: the synergy of sustainability and educational transformation
Authors: Kotula Nina , Małagocka Karolina Agnieszka 
Published: February 2025

Purpose
The purpose of this paper is to investigate the relationship between digital transformation and sustainable development within the context of higher education institutions.

Design/methodology/approach
This paper uses a systematic review methodology to analyze the intersection of digital transformation and sustainability in higher education institutions, drawing on academic sources and institutional reports.

Findings
Universities face a dual challenge of advancing digital transformation while integrating and enhancing sustainable development, necessitating a balance between inclusivity and innovation to meet the evolving demands of a digital-centric world and global sustainability goals. Digital transformation of higher education institutions is not only influenced by socioeconomic changes and market demands but also offers practical pathways to enhance sustainability efforts across campus operations and curriculum delivery.

Originality/value
This paper provides an overview of the concepts of digital transformation and sustainable development in the higher education environment.