bluuebunny/crossref_metadata_2025_split huggingface dataset:
A rare case of Aerococcus urinae native valve endocarditis
Authors: Goes Sofie Eva , Callebaut Kim , Pierard Denis , Wybo Ingrid , De Geyter Deborah , Muyldermans Astrid , Geers Jolien , Kerselaers Laura , Demuyser Thomas 
Published: February 2025

Background

Aerococcus urinae, was initially considered a commensal of the urinary tract, but there is now increasing evidence for its involvement in urinary tract and systemic infections. A. urinae endocarditis has a non-negligible mortality rate and occurs mainly in patients with underlying conditions or presence of extraneous material.

Case presentation

This report handles the case of a 65 year old male with cardiac antecedents, who was admitted to the cardiology department after a syncope of unknown origin and diagnosed with severe mixed aortic valve disease and mitral valve sclerosis through the means of a transesophageal echocardiography (TEE). During hospitalisation, the patient progressively deteriorated with the development of shortness of breath and an inflammatory syndrome. Both the urine and blood cultures showed growth of A. urinae. Treatment with piperacillin/tazobactam was started empirically. Repeated TEE showed evidence for endocarditis with vegetation and perforation of the mitral valve that required an emergency surgery with mitral valve repair. After surgery, gentamicin and penicillin G were administered for 48 hours, followed by combined ceftriaxone/penicillin G treatment for 6 weeks. At first, flucloxacillin was also associated as the culture of the valve was negative. Finally, 16S rRNA polymerase chain reaction (PCR) on the valve tissue, confirmed the A. urinae endocarditis.

Conclusion

A. urinae is an underestimated cause of serious infections such as endocarditis. Urinary tract infections mainly in older men can be an entry point for this type of invasive infection.
Bridging mental health, cognition and the brain in mild traumatic brain injury: A multilayer network analysis of the TRACK-TBI study
Authors: Domínguez D. Juan F. , Singh Mervyn , Firman-Sadler Lyndon , Guarnera Jade , Simpson-Kent Ivan L. , Imms Phoebe , Irimia Andrei , Caeyenberghs Karen ,   TRACK-TBI Investigators
Published: February 2025

ABSTRACTBackgroundMild traumatic brain injury (mTBI) patients suffer from several mental health symptoms (e.g., anxiety, depressive symptoms) and cognitive deficits (e.g., attentional deficits, slowed processing speed). However, symptoms in TBI are largely investigated in isolation, using univariate approaches, ignoring the interactions between symptoms and the underlying large-scale brain networks. We constructed the first multilayer network in mTBI to examine the relationships between networks of cognition, mental health and structural brain measures and to identify key variables bridging relationships across these networks.MethodsChronic phase cross-sectional data (6-month follow-up) from 457 mTBI patients was extracted from the TRACK-TBI Longitudinal study. We selected four variables from self-report mental health questionnaires (affective layer), eight cognitive test scores from the NIH toolbox (cognitive layer), and grey matter volumes from eight brain regions of the central executive and salience networks from anatomical MRI scans (brain layer). We used a multilayer network approach to examine the relationships (edges) between all variables (nodes) across layers. We then used the bridge strength centrality metric to identify nodes that ‘bridge’ the affective, cognitive, and brain layers.ResultsInsomnia severity, immediate verbal memory, somatisation and processing speed nodes exceeded ana priori80th percentile threshold on the bridge strength scores and can therefore be regarded as key nodes bridging relationships across affective, cognitive and brain layers.ConclusionsThe bridging nodes identified in our multilayer network analyses suggest targets for future studies to develop more customized, efficient, and efficacious treatments to alleviate mental health symptoms and cognitive deficits in mTBI patients.
Deep Learning based deconvolution methods: a systematic review
Authors: Redondo Alba Lomas , Sánchez Velázquez Jose M. , García Tejedor Álvaro J. , Sánchez–Arévalo Víctor Javier 
Published: February 2025

AbstractWithin this systematic review we examine the role of Artificial Intelligence (AI) and Deep Learning (DL) in the development of cellular deconvolution tools, with an special focus on their application to the analysis of transcriptomics data from RNA sequencing. We emphasize the critical importance of high–quality reference profiles for enhancing the accuracy of the discussed deconvolution methods, which is essential to determine cellular compositions in complex biological samples. To ensure the robustness of our work, we have applied a rigorous selection process following the Preferred Reporting Items for Systematic Reviews and Meta–Analysis (PRISMA) guidelines. Through the review process, we have identified several key research gaps, highlighting the necessity for standardized methodologies and the improvement of the interpretability of the models. Overall, we present a comprehensive, up to date overview of the different methodologies, datasets, and findings associated with DL–driven deconvolution tools, paving the way for future research and emphasizing the value of collaboration between computational and biological sciences.
Insights into the structure and modulation of human TWIK-2
Authors: Ma Qianqian , Hernandez Ciria C. , Navratna Vikas , Kumar Arvind , Lee Abraham , Mosalaganti Shyamal 
Published: February 2025

AbstractTheTandem of pore domain in aWeak InwardRectifyingK+channel 2(TWIK-2; KCNK6) is a member of the Two-Pore Domain K+(K2P) channel family, which is associated with pulmonary hypertension, lung injury, and inflammation. The structure and regulatory mechanisms of TWIK-2 remain largely unknown. Here, we present the cryo-electron microscopy (cryo-EM) structure of human TWIK-2 at ∼3.7 Å and highlight its conserved and unique features. Using automated whole-cell patch clamp recordings, we demonstrate that gating in TWIK-2 is voltage-dependent and insensitive to changes in the extracellular pH. We identify key residues that influence TWIK-2 activity by employing structure and sequence-guided site-directed mutagenesis and provide insights into the possible mechanism of TWIK-2 regulation. Additionally, we demonstrate the application of high-throughput automated whole-cell patch clamp platforms to screen small molecule modulators of TWIK-2. Our work serves as a foundation for designing high-throughput small molecule screening campaigns to identify specific high-affinity TWIK-2 modulators, including promising new anti-inflammatory therapeutics.
Time-series RNA metabarcoding of the activePopulus tremuloidesroot microbiome reveals hidden temporal dynamics and dormant core members
Authors: Nash Jake , Tremble Keaton , Schadt Christopher , Cregger Melissa A. , Bryan Corbin , Vilgalys Rytas 
Published: February 2025

AbstractDormancy is a key life history stage of many microbes that involves existence in a metabolically inactive state. Although dormant taxa may contribute little to community function, most microbial metabarcoding community surveys of microbial systems target DNA which captures dormant and dead taxa in addition to the active and living fraction of the community. RNA metabarcoding offers the potential to delineate the active fraction of microbial communities. Transitions between dormancy and activity may also serve as a rapid response mechanism for communities for communities to alter their function faster than turnover in community composition. Additionally, a focus on active microbiomes may provide further insight into which taxa should be prioritized as part of the core microbiome. We used DNA and RNA metabarcoding in samples collected as a time-series of the quaking aspen (Populus tremuloides) root microbiome across a natural environmental gradient to identify the degree of spatiotemporal dynamism in active and total microbial communities and to document the extent of dormancy in the core microbiome. We found that active bacterial and fungal communities were more temporally dynamic than total communities, while total communities exhibited a stronger response to spatial variability in site conditions. Additionally, we found that core microbiome members are frequently inactive, resulting in a reduced active core microbiome. This study stresses the need to focus on turnover in the active microbial community to detect variation in microbial communities in time-series and to use microbial activity levels as a key determinant of core microbiome membership.
Missense mutations in intrinsically disordered protein regions link pathogenicity and phase separation
Authors: Kipp Oliver L. , Lewis Karen A. , Hough Loren E. , Whitten Steven T. 
Published: February 2025

AbstractThe impact of missense genetic variations on protein function is often enigmatic, especially for mutations that map to intrinsically disordered regions (IDRs). Given the functional importance of phase separation of IDRs, it has been proposed that mutations that modulate phase separation might preferentially lead to disease. To examine this idea, we used the robust predictability of phase-separating (PS) IDRs and annotation of disease-associated proteins and mutations to map the correlation between disease and phase separation. Consistent with previous work linking phase separation to cancer and autism spectrum disorder, we find a higher prevalence of predicted phase separation behavior in disease-associated proteins than typical for human proteins. We map the prevalence of phase separation across a wide range of diseases, finding that most, but not all, show an enrichment of phase separation in the proteins associated with them. Strikingly, the frequency of pathogenic mutations in predicted PS IDRs was elevated three-fold relative to IDRs not predicted to phase separate. Substitutions involving arginine and the aromatic types were among the most pathogenic for PS IDRs, while substitutions involving serine, threonine, and alanine the most benign. We applied these trends to mutations of uncertain clinical significance and predict that half found in PS IDRs are likely pathogenic. We find that phosphorylation sites were enriched in PS IDRs when compared to other protein regions, though mutations at such sites were mostly benign. Pathogenicity was highest for mutations in predicted PS IDRs when also found in a short linear motif, known mediators of protein-protein interactions.
Data retention in awake infant fMRI: Lessons from more than 750 scanning sessions
Authors: Behm Lillian , Yates Tristan S. , Trach Juliana E. , Choi Dawoon , Du Haoyu , Osumah Camille , Deen Ben , Kosakowski Heather L. , Chen Emily M. , Kamps Frederik S. , Olson Halie A. , Ellis Cameron T. , Saxe Rebecca , Turk-Browne Nicholas B. 
Published: February 2025

AbstractFunctional magnetic resonance imaging (fMRI) in awake infants has the potential to reveal how the early developing brain gives rise to cognition and behavior. However, awake infant fMRI poses significant methodological challenges that have hampered wider adoption. The present work takes stock after the collection of a substantial amount of awake infant fMRI data across multiple studies from two labs at different institutions. We leveraged these data to glean insights on participant recruitment, experimental design, and data acquisition that could be useful to consider for future studies. Across 766 awake infant fMRI sessions, we explored the factors that influenced how much usable data were obtained per session (average of 9 minutes). The age of an infant predicted whether they would successfully enter the scanner (younger was more likely) and, if they did enter, the number of minutes of functional data retained after preprocessing. The amount of functional data retained was also influenced by assigned sex (female more), experimental paradigm (movies better than blocks and events), and stimulus content (social better than abstract). In addition, we assessed the value of attempting to collect multiple experiments per session, an approach that yielded more than one usable experiment averaging across all sessions (including those with no data). Although any given scan is unpredictable, these findings support the feasibility of awake infant fMRI and suggest practices to optimize future research.
Early onset memory deficit of WMI rats compared to their nearly isogenic WLIs is reversed by enriched environment in females
Authors: Ji Michelle T. , Przybyl Katherine J. , Harter Aspen M. , Nemesh Mariya , Jenz Sophia , Yamazaki Anna , Kim Chris , Mulligan Megan K. , Chen Hao , Redei Eva E. 
Published: February 2025

AbstractWe tested the hypothesis that environmental enrichment (EE) can attenuate early-onset cognitive decline in a stress-hyperresponsive rat strain. The novel genetic model, the Wistar Kyoto More Immobile (WMI) inbred rat strain demonstrates increased stress reactivity and enhanced depression-like behavior compared to its nearly isogenic control, the Wistar Kyoto Less Immobile strain (WLI). Middle-aged (12 months) WMI females exhibited diminished fear, and spatial memory in the contextual fear conditioning and Morris Water Maze paradigms, respectively, compared to young animals (6 months) of both strains and to middle-aged WLIs. Middle-aged WMI males showed a lesser age-induced deficit. EE from six to 12 months of age reversed these memory deficits in middle-aged WMI females and attenuated them in WMI males. Plasma levels of estradiol followed the same pattern as memory in WMI females following EE. RNA sequencing from female hippocampi revealed significant strain, age, and enrichment-induced differentially expressed genes. Among these, solute carrier family 35, member A4 (Slc35a4) and potassium inwardly rectifying channel, subfamily J, member 2 (Kcnj2) were confirmed to show hippocampal expression changes parallel to that of memory in the WMI. These genes have critical roles in the integrated stress response, cellular metabolism, and the effects of stress on neurovascular coupling, respectively. Pathway analyses revealed the involvement of oxidative phosphorylation and mitochondrial dysfunction in the hippocampal processes of aging and EE-induced reversal. These findings underscore the critical involvement of molecular stress responses in early-onset memory decline and suggest potential therapeutic targets for age-related cognitive impairment.HighlightsHeightened innate stress response and depression leads to early onset memory declineEnriched environment reverses memory decline of middle-aged femalesEnriched environment also reverses declining estrogen levels of middle-aged femalesMitochondrial dysfunction may underly mid-life cognitive and molecular changes
Mathematical modelling predicts novel mechanisms of stream confinement from Trail/Colec12/Dan in the collective migration of cranial neural crest cells
Authors: Johnson Samuel W.S. , Kulesa Paul M. , Baker Ruth E. , Maini Philip K. 
Published: February 2025

BackgroundIn vertebrate embryogenesis, cranial neural crest cells (CNCCs) migrate along discrete pathways. Analyses in the chick have identified key molecular candidates for the confinement of CNCC migration to stereotypical pathways as Colec12, Trail, and Dan. The effects of these factors on CNCCsin vitroare known, but how they confine migration to discrete streamsin vivoremains poorly-understood. Here, we propose and test several hypothetical mechanisms by which these factors confine cell streams and maintain coherent migration, simulating an expanded agent-based model for collective CNCC migration.ResultsModel simulations suggest that Trail enhances adhesion between CNCCs, facilitating movement towards stereotypical migratory pathways, whereas Colec12 confines CNCCs by inducing longer, branched filopodia that facilitate movement down Colec12 gradients and re-connections with streams. Moreover, we find that Trail and Colec12 facilitate the exchange of CNCCs and formation of CNCC-bridges between adjacent streams that are observedin vivobut poorly-understood mechanistically. Finally, we predict that Dan increases the coherence of streams by preferentially modulating the speed of CNCCs at the leading edge of collectives to prevent escape.ConclusionsOur work highlights the importance of Trail, Colec12, and Dan in CNCC migration and predicts novel mechanisms for the confinement of CNCCs to stereotypical pathwaysin vivo.
Episodic pain in Fabry disease is mediated by a heat shock protein-TRPA1 axis
Authors: Enders Jonathan D , Prodoehl Eve K , Penn Signe M , Sriram Anvitha , Stucky Cheryl L 
Published: February 2025

AbstractTwo-thirds of patients with Fabry disease suffer debilitating pain attacks triggered by exercise, fever, and exposure to environmental heat. These patients face endure even greater risk of heat-related episodic pain in the face of global climate change. Almost nothing is known about the biological mechanisms underlying heat-induced pain crises in Fabry disease, and there is no preclinical model available for to study Fabry crises. Here, we established the first model of heat-induced pain attacks in Fabry disease by exposing transgenic Fabry rats to environmental heat. Heat exposure precipitated robust mechanical hypersensitivity, closely matching temporal features reported by patients with Fabry disease. At the cellular level, heat exposure sensitized Fabry dorsal root ganglia (DRG) neurons to agonists for transient receptor potential cation channel A1 (TRPA1), but not TRPV1. The heat shock response, which normally confers heat-resilience, was impaired in Fabry disease, and we demonstrated that heat shock proteins (HSP70 and HSP90) regulate TRPA1. Strikingly, pharmacologically inhibiting HSP90 completely prevented cellular and behavioral sensitization by environmental heat in Fabry disease. Together, this work establishes the first model of episodic pain in Fabry disease, implicates the heat shock response in heat-evoked pain episodes, and identifies a novel heat shock protein-TRPA1 regulatory axis.Abstract Figure
Proteomic profiling of plasma extracellular vesicles identifies signatures of innate immunity, coagulation, and endothelial activation in septic patients
Authors: Park Chanhee , Ryu Taekyung , Mohamed-Hinds Rashida , Kim Kyungdo , Kim Jin Hyeok , Zou Lin , Williams Brittney , Na Chan Hyun , Chao Wei 
Published: February 2025

AbstractPlasma extracellular vesicles (EVs) are cell-derived lipid particles and reportedly play a role in sepsis pathogenesis. This study aimed to identify EV cargo proteins in septic patients and explore their association with key sepsis pathophysiology. Plasma EVs were subjected to Tandem Mass Tag (TMT)-based quantitative proteomic analysis. We identified 522 differentially expressed (DE) EV proteins in septic patients (n=15) compared to the healthy controls (n=10). The KEGG analysis of the DE proteins revealed multiple functional pathways linked to sepsis,e.g.,complement/coagulation, platelet activation, phagosome, inflammation, and neutrophil extracellular trap formation. Weighted Gene Coexpression Network Analysis of 1,642 EV proteins identified nine unique protein modules, some of which were highly correlated with the sepsis diagnosis and diverse plasma markers, including organ injury, inflammation, coagulopathy, and endothelial activation. Cell type-specific enrichment analysis revealed the cellular origins of EVs, including immune and epithelial cells, neurons, and glial cells. Thus, the current study discovered complex proteomic signatures in plasma EVs that are closely associated with key pathophysiological responses in sepsis. These findings support the importance of EV cargo proteins in the patients’ immune responses, coagulation, and endothelial activation and lay the foundation for future mechanistic study of plasma EVs in sepsis pathogenesis.
Trajectories of Heart Failure with Reduced Ejection Fraction: Insights from EHR Data on Recovery and Transitions
Authors: Do Duy , Murugiah Karthik , Sawano Mitsuaki , Cartwright Brianna M. Goodwin , Rodriguez Patricia J. , Gratzl Samuel , Baker Charlotte , Curtis Lesley H. , Stucky Nicholas L 
Published: February 2025

What is the clinical question being addressed?Heart failure with reduced ejection fraction (HFrEF) is a leading cause of morbidity and mortality, with guideline-directed medical therapy (GDMT) shown to improve left ventricular ejection fraction (LVEF) and clinical outcomes. However, contemporary real-world trajectories of LVEF changes following an initial transthoracic echocardiography (TTE) diagnosis of HFrEF and how these changes relate to patient characteristics, GDMT use, and outcomes are not well described.What is the main finding?Repeat LVEF assessment occurred in only one-third of patients with HFrEF within one year of the initial TTE. Among those with repeat imaging, 23.9% remained in HFrEF, 18.6% improved to heart failure with mid-range ejection fraction (HFmrEF), and 57.5% improved to heart failure with recovered ejection fraction (HFrecEF). Patients transitioning to HFmrEF or HFrecEF were more likely to be female, White, have a higher baseline LVEF, and fewer cardiovascular comorbidities. GDMT use was low across all LVEF transition categories, highlighting significant opportunities to improve heart failure outcomes.