bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conserved untranslated regions of multipartite viruses: Natural markers of novel viral genomic components and tags of viral evolution
Authors: Zhang Song , Yang Caixia , Qiu Yuanjian , Liao Ruiling , Xuan Zhiyou , Ren Fang , Dong Yafeng , Xie Xiaoying , Han Yanhong , Wu Di , Ramos-González Pedro Luis , Freitas-Astúa Juliana , Yang Huadong , Zhou Changyong , Cao Mengji 
Published: January 2024

Abstract
Viruses with split genomes are classified as being either segmented or multipartite based on whether their genomic segments occur within a single virion or across different virions. Despite variations in number and sequence during evolution, the genomic segments of many viruses are conserved within the untranslated regions (UTRs). In this study, we present a methodology that combines RNA sequencing with iterative BLASTn of UTRs (https://github.com/qq371260/Iterative-blast-v.1.0) to identify new viral genomic segments. Some novel multipartite-like viruses related to the phylum Kitrinoviricota were annotated using sequencing data from field plant samples and public databases. We identified potentially plant-infecting jingmen-related viruses (order Amarillovirales) and jivi-related viruses (order Martellivirales) with at least six genomic components. The number of RNA molecules associated with a genome of the novel viruses in the families Closteroviridae, Kitaviridae, and Virgaviridae within the order Martellivirales reached five. Several of these viruses seem to represent new taxa at the subgenus, genus, and family levels. The diversity of novel genomic components and the multiple duplication of proteins or protein domains within single or multiple genomic components emphasize the evolutionary roles of genetic recombination (horizontal gene transfer), reassortment, and deletion. The relatively conserved UTRs at the genome level might explain the relationships between monopartite and multipartite viruses, as well as how subviral agents such as defective RNAs and satellite viruses can coexist with their helper viruses.
LoopSage: An Energy-Based Monte Carlo approach for the Loop Extrusion Modelling of Chromatin
Authors: Korsak Sevastianos , Plewczynski Dariusz 
Published: January 2024

AbstractThe connection between the patterns observed in 3C-type experiments and the modeling of polymers remains unresolved. This paper presents a simulation pipeline that generates thermodynamic ensembles of 3D structures for topologically associated domain (TAD) regions by loop extrusion model (LEM). The simulations consist of two main components: a stochastic simulation phase, employing a Monte Carlo approach to simulate the binding positions of cohesins, and a dynamical simulation phase, utilizing these cohesins’ positions to create 3D structures. In this approach, the system’s total energy is the combined result of the Monte Carlo energy and the molecular simulation energy, which are iteratively updated. The structural maintenance of chromosomes (SMC) protein complexes are represented as loop extruders, while the CCCTC-binding factor (CTCF) locations on DNA sequence are modeled as energy minima on the Monte Carlo energy landscape. Finally, the spatial distances between DNA segments from ChIA-PET experiments are compared with the computer simulations, and we observe significant Pearson correlations between predictions and the real data. LoopSage model offers a fresh perspective on chromatin loop dynamics, allowing us to observe phase transition between sparse and condensed states in chromatin.
Time dependent changes in feeding behavior and energy balance associated with weight gain in mice fed obesogenic diets
Authors: Fathi Payam A. , Bales Michelle B. , Ayala Julio E. 
Published: January 2024

AbstractObesity is characterized by dysregulated homeostatic mechanisms resulting in positive energy balance, yet when this dysregulation occurs is unknown. We assessed the time course of alterations to behaviors promoting weight gain in male and female mice switched to obesogenic 60% or 45% high fat diet (HFD). Switching mice to obesogenic diets promotes transient bouts of hyperphagia during the first 2 weeks followed by persistent caloric hyperphagia. Energy expenditure increases but not sufficiently to offset increased caloric intake, resulting in a sustained net positive energy balance. Hyperphagia is associated with consumption of calorically larger meals (impaired satiation) more frequently (impaired satiety) particularly during the light-cycle. Running wheel exercise delays weight gain in 60% HFD-fed male mice by enhancing satiation and increasing energy expenditure. However, exercise effects on satiation are no longer apparent after 2 weeks, coinciding with weight gain. Thus, exposure to obesogenic diets engages homeostatic regulatory mechanisms for ∼2 weeks that ultimately fail, and consequent weight gain is characterized by impaired satiation and satiety. Insights into the etiology of obesity can be obtained by investigating changes to satiation and satiety mechanisms during the initial ∼2 weeks of HFD exposure.What is already known about this subject?Obesity is associated with dysregulated homeostatic mechanisms.Increased caloric consumption contributes to obesity.Obese rodents tend to eat larger, more frequent meals.What are the new findings in your manuscript?Exposure to obesogenic diets promotes transient attempts to maintain weight homeostasis.After ∼2 weeks, caloric hyperphagia exceeds increased energy expenditure, promoting weight gain.This is associated with consumption of larger, more frequent meals.How might your results change the direction of research or the focus of clinical practice?Our findings suggest that molecular studies focusing on mechanisms that regulate meal size and frequency, particularly those engaged during the first ∼2 weeks of obesogenic diet feeding that eventually fail, can provide unique insight into the etiology of obesity.
Influence of social and semantic contexts on phonetic encoding in naturalistic conversations
Authors: Abassi Etienne , Zatorre Robert J. 
Published: January 2024

ABSTRACTSocial interactions occupy a significant part of life, and understanding others’ conversations is key to navigating our social world. While the role of semantics in speech comprehension is well-established at the word or sentence level, its influence on larger conversational scales, alongside social context, is less understood. This study examined how semantic and social contexts modulate phonetic encoding during natural conversations using a speech-in-noise paradigm. Participants listened to AI-generated dialogues (two speakers) or monologues (one speaker) in intact or sentence-scrambled order. Each trial contained five sentences, with the fifth embedded in multi-talker babble noise. The same sentence was then repeated without noise, with one word either altered or unchanged. Healthy adults identified whether the sentence matched the in-noise version. Across several online experiments (N=195), both social and semantic contexts showed influences on speech-in-noise processing with improved performance for dialogues over monologues and for intact over sentence-scrambled conversations. These results suggest that both semantic and social factors shape speech comprehension, emphasizing their role in auditory cognition. This raises important questions about predictive and other mechanisms involved in processing complex, multi-sentence conversations, further underscoring the critical role of social interaction in communication.
Synaptotagmin 7 C2 domains induce membrane curvature stress via electrostatic interactions and the wedge mechanism
Authors: Beaven Andrew H. , Bikkumalla Vrishank , Chon Nara L. , Matthews Ariel E. , Lin Hai , Knight Jefferson D. , Sodt Alexander J. 
Published: January 2024

0.ABSTRACTSynaptotagmin 7 (Syt-7) is part of the synaptotagmin protein family that regulates exocytotic lipid membrane fusion. Among the family, Syt-7 stands out by its membrane binding strength and stabilization of long-lived membrane fusion pores. Given that Syt-7 vesicles form long-lived fusion pores, we hypothesize that its interactions with the membrane stabilize the specific curvatures, thicknesses, and lipid compositions that support a metastable fusion pore. Using all-atom molecular dynamics simulations and FRET-based assays of Syt-7’s membrane-binding C2 domains (C2A and C2B), we found that Syt-7 C2 domains sequester anionic lipids, are sensitive to cholesterol, thin membranes, and generate lipid membrane curvature by two competing, but related mechanisms. First, Syt-7 forms strong electrostatic contacts with the membrane, generating negative curvature stress. Second, Syt-7’s calcium binding loops embed in the membrane surface, acting as a wedge to thin the membrane and induce positive curvature stress. These curvature mechanisms are linked by the protein insertion depth as well as the resulting protein tilt. Simplified quantitative models of the curvature-generating mechanisms link simulation observables to their membrane-reshaping effectiveness.
CutaneousLeishmania mexicanaInfections in the United States: Defining Strains Through Endemic Human Pediatric Cases in Northern Texas
Authors: Nepal Binita , McCormick-Baw Clare , Patel Karisma , Firmani Sarah , Wetzel Dawn M. 
Published: January 2024

ABSTRACTOver a six-month span, three patients under five years old with cutaneous leishmaniasis presented to the Pediatric Infectious Diseases Clinic at the University of Texas Southwestern Medical Center/Children’s Health Dallas. None had traveled outside of the United States (US); all had confirmedL. mexicanainfections by PCR. We provide case descriptions and images to increase the awareness of this disease among US physicians and scientists. Two patients responded to fluconazole, but one required topical paromomycin. Combining these cases with guidelines and our literature review, we suggest that: 1) higher doses (ten-twelve mg/kg/day) of fluconazole should be considered in young children to maximize likelihood and rapidity of response and 2) patients should transition to alternate agents if they do not respond to high-dose fluconazole within six weeks. Furthermore, and of particular interest to the broad microbiology community, we used samples from these cases as a proof-of-concept to propose a mechanism to strain-type US-endemicL. mexicana.For our analysis, we sequenced three housekeeping genes and the internal transcribed sequence 2 of the ribosomal RNA gene. We identified genetic changes that not only allow us to distinguish US-basedL. mexicanastrains from strains found in other areas of the Americas, but also establish polymorphisms that differ between US isolates. These techniques will allow documentation of genetic changes in this parasite as its range expands. Hence, our cases of cutaneous leishmaniasis provide significant evolutionary, treatment and public health implications as climate change increases exposure to formerly tropical diseases in previously non-endemic areas.IMPORTANCELeishmaniasis is a parasitic disease that typically affects tropical regions worldwide. However, the vector that carriesLeishmaniais spreading northward into the United States (US). Within a six-month period, three young cutaneous leishmaniasis patients were seen at the Pediatric Infectious Diseases Clinic at The University of Texas Southwestern/Children’s Health Dallas. None had traveled outside of north Texas. We document their presentations, treatments, and outcomes and compare their management to clinical practice guidelines for leishmaniasis. We also analyzed the sequences of three critical genes inLeishmania mexicanaisolated from these patients. We found changes that not only distinguish US-based strains from strains found elsewhere, but also differ between US isolates. Monitoring these sequences will allow tracking of genetic changes in parasites over time. Our findings have significant US public health implications as people are increasingly likely to be exposed to what were once tropical diseases.
Epidemiology and burden of respiratory syncytial virus in Italian adults: A systematic review and meta-analysis
Authors: Domnich Alexander , Calabrò Giovanna Elisa 
Published: January 2024

AbstractObjectiveRespiratory syncytial virus (RSV) is a common respiratory pathogen not only in children, but also in adults. Country-specific data on the epidemiology and burden of disease are essential for policy decisions. In view of a recent authorization of adult RSV vaccines, we aimed to comprehensively collect and assess evidence on the epidemiology and burden of RSV in Italian adults.MethodsA systematic literature review was conducted according to the available guidelines. Random-effects proportional meta-analysis was performed to obtain pooled estimates and the observed heterogeneity was investigated by using both subgroup and meta-regression analyses.ResultsA total of 35 studies were identified. RSV seasonal attack rates ranged from 0.8 ‰ in community-dwelling older adults to 10.9% in hematological outpatients. On average, 4.5% (95% CI: 3.2–5.9%) of respiratory samples tested positive for RSV. This positivity prevalence was higher in older adults (4.4%; 95% CI: 2.8– 6.3%) than in working-age adults (3.5%; 95% CI: 2.5–4.6%) and in outpatient (4.9%; 95% CI: 3.1–7.0%) than inpatient (2.9%; 95% CI: 1.5–4.8%) settings. Study location and sample size were also significant predictors of RSV detection frequency. The pooled estimate of in-hospital mortality was as high as 7.2% (95% CI: 4.7– 10.3%). However, other important indicators of the diseases burden, such as complication and hospitalization rates, are missing.ConclusionRSV poses a measurable burden on Italian adults, especially those of older age and with some co-morbidities. Policy makers should give priority to health technology assessment of the novel RSV vaccines.
Alzheimer’s Disease biological PET staging using plasma p217+tau
Authors: Feizpour Azadeh , Doré Vincent , Krishnadas Natasha , Bourgeat Pierrick , Doecke James D. , Saad Ziad S. , Triana-Baltzer Gallen , Laws Simon M. , Shishegar Rosita , Huang Kun , Fowler Christopher , Ward Larry , Masters Colin L. , Fripp Jurgen , Kolb Hartmuth C. , Villemagne Victor L. , Rowe Christopher C. 
Published: January 2024

AbstractBackgroundPlasma phospho-tau biomarkers, such as p217+tau, excel at identifying Alzheimer’s Disease (AD) neuropathology. However, questions remain regarding their capacity to inform AD biological PET stages at group level and maintain the same precision at individual patient level.MethodParticipants included 248 cognitively unimpaired (CU) and 227 cognitively impaired (CI) individuals, with Janssen plasma p217+tau Simoa® assay,18F-NAV4694 Aβ PET (A) and18F-MK6240 tau PET (T) data. Biological PET stages were defined based on the draft NIA-AA Revised Criteria (July 2023): Initial (A+T-), Early (A+TMTL+), Intermediate (A+TMOD+), and Advanced (A+THIGH+). We used thresholds for A+ of 25 Centiloid and for THIGHof 80 Centaur (2.68 SUVRtemporo-parietal). Adding an A-T- stage for comparison, we assessed the performance of p217+tau in discriminating between these stages at the group level using Receiver Operating Characteristic (ROC) analysis and at the individual level using logistic regression.ResultsPlasma p217+tau concentrations increased across the stages, with significant differences between them, except for the Initial and Early stages. Screening for Advanced (vs. lower stages), combined Intermediate/Advanced (vs. lower stages), or all stages (vs. A-T-), p217+tau showed good group-level discriminations (AUC 0.91, 0.92 and 0.92; CI only: AUC 0.83, 0.89, 0.93, respectively). At the individual level, the likelihood of PET stagevs. p217+tau level showed good discrimination of A-T- vs any A+ stage and of combined Intermediate/Advanced disease stage vs lower stages in the CI.ConclusionIn addition to accurately screening for A+ individuals, plasma p217+tau shows promise for separating persons with either Intermediate or Advanced stage AD from those at a lower stage, providing prognostic information and informing better selection for trials and disease modifying therapies.
Psychosocial distress and health status as risk factors for ten-year major adverse cardiac events and mortality in patients with non-obstructive coronary artery disease
Authors: Mommersteeg Paula M.C. , Lodder Paul , Aarnoudse Wilbert , Magro Michael , Widdershoven Jos W. 
Published: January 2024

AbstractBackgroundPatients with non-obstructive coronary artery disease (NOCAD) experience psychological distress and are at risk for major adverse cardiac events with mortality (MACE). We examined the risk of psychosocial distress, including Type D personality, depressive symptoms, anxiety, positive mood, hostility, and health status fatigue and disease specific and generic quality of life for MACE in patients with NOCAD.MethodsIn the Tweesteden mild stenosis (TWIST) study, 546 patients with NOCAD were followed for 10 years to examine the occurrence of cardiac mortality, a major cardiac event, or non-cardiac mortality in the absence of a cardiac event. Cox proportional hazard models were used to examine the impact of psychosocial distress and health status on the occurrence of MACE while adjusting for age, sex, disease severity, and lifestyle covariates. Sex differences and interactions were explored.ResultsIn total 19% of the patients (mean age baseline = 61, SD 9 years; 52% women) experienced MACE, with an annualized event rate (AER) of 20 events per 1,000 person-years, and a lower risk for women compared to men. Positive mood (HR 0.97, 95%CI 0.95-1.00), fatigue (HR 1.03, 95%CI 1.00-1.06), and physical limitation (HR 0.99, 95%CI 0.98-1.00) were associated with MACE in adjusted models. No significant interactions between sex and psychosocial factors were present. Depressive symptoms were predictive of MACE, but no longer after adjustment. Neither Type D personality, anxiety, hostility, mental health status, or angina frequency and stability were significantly associated with MACE.ConclusionsIn patients with NOCAD fatigue, low positive mood, and a lower physical limitation score were associated with MACE, without marked sex differences. Type D personality, psychosocial factors, and health status were not predictive of adverse outcomes. Reducing psychosocial distress is a valid intervention goal by itself, though it is less likely to affect MACE in patients with NOCAD.
Characteristics, temporal trends, and outcomes of intravenous thrombolysis in stroke patients aged > 80 years in China
Authors: Li Chang-sheng , Jiang Ying-yu , Gu Hong-Qiu , Wang Meng , Chen Zi-mo , Yang Xin , Zhou Qi , Meng Xia , Wang Chun-juan , Li Zi-xiao 
Published: January 2024

AbstractBackground/PurposeNo large cohort study has examined intravenous thrombolysis (IVT) in Chinese patients aged > 80 years.We aim to evaluate temporal trends in alteplase use, clinical characteristics, and outcomes in acute ischemic stroke (AIS) patients over 80 years of age in China.MethodsData were collected from The China Stroke Center Alliance program, which is a nationwide, multicenter, prospective registry at 1751 hospitals in 31 provinces, between January 1, 2018, and December 14, 2022.The primary outcome was a modified Rankin scale score (mRS) of 0-2 at discharge, and the secondary study outcomes were an mRS score 0-1 and independent ambulation at discharge. The safety outcomes included in-hospital mortality and symptomatic intracranial hemorrhage(sICH).ResultsOf 212,814 patients eligible for thrombolysis, 30,902 patients were aged > 80 years; among them, 8,673 patients (median [IQR] age, 84 [82-87] years) were treated with alteplase, 52.7% of whom were female (n=4570). The usage rate of alteplase in elderly patients increased from 22.1% in 2018 to 35.7% in 2022, while the rate among younger patients increased from 30.5% in 2018 to 43.3% in 2022. Patients treated with alteplase had better short-term functional outcomes, including mRS scores 0-2 (adjusted OR [aOR] 1.13, 95% CI 1.08-1.19, p<0.001), mRS scores 0-1 (aOR 1.14, 95% CI 1.09-1.20, p<0.001), and independent ambulation at discharge (aOR 1.27, 95% CI 1.19-1.39, p<0.001). Furthermore, there was no increased risk of in-hospital mortality (aOR 0.92, 95% CI 0.79-1.08, p=0.31). However, alteplase was associated with a higher risk of sICH (aOR 2.85, 95% CI 2.48-3.27, p<0.001).ConclusionsElderly patients receiving IVT with alteplase had better short-term functional outcomes without an increased risk of in-hospital mortality; however, elderly patients are at higher risk of developing symptomatic intracranial hemorrhage.
Functional trajectory following pediatric stroke: a cohort study of acute inpatient rehabilitation outcomes
Authors: Wu Jennifer , Godfrey Deena S. , Orme Patricia , Wishart Brian D. 
Published: January 2024

ABSTRACTBackgroundStroke in childhood is a significant cause of morbidity and mortality. Neurologic impairments due to childhood stroke are associated with long-term disability and decreased quality of life. However, there are limited studies examining functional outcomes of childhood stroke. The goal of this study was to characterize functional outcomes of children and adolescents admitted to acute inpatient rehabilitation following stroke.MethodsA retrospective cross-sectional study of 100 patients aged 0 to 21 years admitted to a pediatric acute inpatient rehabilitation program following new diagnosis of stroke in childhood. The primary outcome measures were Functional Independence Measure in Children (WeeFIM) score at admission and discharge. Secondary outcome measures included change in WeeFIM score and IRF Efficiency score.ResultsThe 56 male/43female/1 transgender patients were 10.4±6.1 years old with ischemic (n=53), hemorrhagic (n=41), and hemorrhagic converted ischemic (n=6) strokes. At admission, the group demonstrated moderate-to-severe functional impairments (WeeFIM total score=47.9±26.3 points). Inpatient rehabilitation length of stay was 34.1±28.6 days and at inpatient rehabilitation discharge, WeeFIM total score improved to 73.2±31.5 points, representing a group IRF Efficiency score of 1.42±1.5 points/day. Group effects were also found for medical management of agitation, stroke prophylaxis, and stimulant therapy.ConclusionsAcute inpatient rehabilitation demonstrates statistically and clinically significant functional improvements following pediatric stroke as measured on the WeeFIM scale. Additional studies are needed to examine group effects found from medical management in the inpatient rehabilitation setting.