bluuebunny/crossref_metadata_2025_split huggingface dataset:
A vasopressin circuit that modulates sex-specific social interest and anxiety-like behavior in mice
Authors: Rigney Nicole , Campos-Lira Elba , Kirchner Matthew K. , Wei Wei , Belkasim Selma , Beaumont Rachael , Singh Sumeet , de Vries Geert J. , Petrulis Aras 
Published: November 2023

AbstractOne of the largest sex differences in brain neurochemistry is the male-biased expression of the neuropeptide arginine vasopressin (AVP) within the vertebrate social brain. Despite the long-standing implication of AVP in social and anxiety-like behavior, the precise circuitry and anatomical substrate underlying its control are still poorly understood. By employing optogenetic manipulation of AVP cells within the bed nucleus of the stria terminalis (BNST), we have unveiled a central role for these cells in promoting social investigation, with a more pronounced role in males relative to females. These cells facilitate male social investigation and anxiety-like behavior through their projections to the lateral septum (LS), an area with the highest density of sexually-dimorphic AVP fibers. Blocking the vasopressin 1a receptor (V1aR) in the LS eliminated stimulation-mediated increases in these behaviors. Together, these findings establish a distinct BNST AVP → LS V1aR circuit that modulates sex-specific social interest and anxiety-like behavior.Significance StatementThe function of sex differences in the brain is poorly understood. Here we test the function of one of the most consistently found sex differences in vertebrate brains, the male-biased vasopressin projections from the bed nucleus of the stria terminalis. Using optogenetic techniques, we demonstrate that these cells and their projection to the lateral septum are much more important in driving male than female social investigation. These studies make a strong contribution to understanding how sexually dimorphic circuitry controls social behavior.
Dynamics of the viral community on the surface of a French smear-ripened cheese during maturation and persistence across production years
Authors: Paillet Thomas , Lamy-Besnier Quentin , Figueroa Clarisse , Petit Marie-Agnès , Dugat-Bony Eric 
Published: November 2023

ABSTRACTThe surface of smear-ripened cheeses constitutes a dynamic microbial ecosystem resulting from the successive development of different microbial groups such as lactic acid bacteria, fungi and ripening bacteria. Recent studies indicate that a viral community, mainly composed of bacteriophages, also represents a common and substantial part of the cheese microbiome. However, the composition of this community, its temporal variations and associations between bacteriophages and their hosts remain poorly characterized. Here, we studied a French smear-ripened cheese by both viral metagenomics and 16S metabarcoding approaches to assess both the succession of phages and bacterial communities on the cheese surface during cheese ripening, and their temporal variations in ready-to-eat cheeses over the years of production. We observed a clear transition of the phage community structure during ripening with a decreased relative abundance of viral species (vOTUs) associated withLactococcusphages, which were replaced by vOTUs associated with phages infecting ripening bacteria such asBrevibacterium, Glutamicibacter, PseudoalteromonasandVibrio. The dynamics of the phage community was strongly associated with bacterial successions observed on the cheese surface. Finally, while some variations in the distribution of phages were observed in ready-to-eat cheeses produced at different dates spanning more than 4 years of production, the most abundant phages were detected throughout. This result revealed the long-term persistence of the dominant phages in the cheese production environment. Together, these findings offer novel perspectives on the ecology of bacteriophages in smear-ripened cheese and emphasize the significance of incorporating bacteriophages in the microbial ecology studies of fermented foods.IMPORTANCEThe succession of diverse microbial populations is critical for ensuring the production of high-quality cheese. We observed a temporal succession of phages on the surface of a smear-ripened cheese, with new phage communities showing up at the time when ripening bacteria start covering this surface. Interestingly, the final phage community of this cheese is also consistent over large periods of time, as the same bacteriophages were found in cheese products from the same manufacturer made over 4-years. This research highlights the importance of considering these bacteriophages when studying the microbial life of fermented foods like cheese.
Gibberellin Perception Sensors 1 and 2 reveal cellular GA dynamics articulated by COP1 and GA20ox1 that are necessary but not sufficient to pattern hypocotyl cell elongation
Authors: Griffiths Jayne , Rizza Annalisa , Tang Bijun , Frommer Wolf B. , Jones Alexander M. 
Published: November 2023

AbstractThe phytohormone gibberellin (GA) is critical for environmentally sensitive plant development including germination, skotomorphogenesis and flowering. The FRET biosensor GIBBERELLIN PERCEPTION SENSOR1, which permits single-cell GA measurementsin vivo, was previously used to observe a GA gradient correlated with cell length in dark-grown but not light-grown hypocotyls. We sought to understand how light signalling integrates into cellular GA regulation. Here we show how the E3 ligase COP1 and transcription factor HY5 play central roles in directing cellular GA distribution in skoto- and photomorphogenic hypocotyls, respectively. We demonstrate that the expression pattern of biosynthetic enzymeGA20ox1is the key determinant of the GA gradient in dark-grown hypocotyls and is a target of COP1 signalling. We engineered a second generation GPS2 biosensor with improved orthogonality and reversibility to show the cellular pattern of GA depletion during the transition to growth in the light. This GA depletion partly explains the resetting of hypocotyl growth dynamics during photomorphogenesis. Achieving cell-level resolution has revealed how GA distributions link environmental conditions with morphology and morphological plasticity and the GPS2 biosensor is an ideal tool for GA studies in further conditions, organs and plant species.
The Temporal Profile of Dual-task Interference in the Human Brain
Authors: Hashemirad Seyed-Reza , Vaziri-Pashkam Maryam , Abbaszadeh Mojtaba 
Published: November 2023

AbstractDue to the brain’s limited cognitive capacity, simultaneous execution of multiple tasks can lead to performance impairments, mainly when the tasks occur closely in time. This limitation is known as dual-task interference. We aimed to investigate the time course of this phenomenon in the brain, utilizing a combination of EEG, multivariate pattern analysis (MVPA), and drift-diffusion modeling (DDM). Here, participants first performed a tone discrimination task, followed by a lane-change task with either short or long onset time differences (Stimulus Onset Asynchrony, SOA), in a simulated driving environment. As expected, the dual-task interference increased the second task’s (lane-change) reaction time. The DDM analysis indicated that this increase was attributable to changes in both the decision time and the post-decision time. Our MVPA findings revealed a decrease in decoding accuracy for the lane-change task in short SOA compared to both long SOA and single-task conditions throughout the trial, highlighting the presence of interference. Moreover, the temporal generalization analysis identified a significant interference effect in short SOA compared to long SOA and single-task conditions after ∼250 ms relative to stimulus onset. Additionally, the conditional generalization analysis showed a delayed response after ∼450 ms. Searchlight analysis illustrated the progression of this information reduction, starting in occipital, parietal, and parieto-occipital leads responsible for perceptual and central processing and then transferring to the frontal leads for mapping decisions onto motor actions. Consistent with the hybrid dual-task interference theory, our results suggest that the processing of the two tasks occurs in a partial parallel manner for the first few hundred milliseconds and primarily in the perceptual and decision-processing stages. Subsequently, another competition arises between the two tasks to route information to motor areas for execution, resulting in the second task’s serial processing and delay or lengthening.
Diet-induced obesity results in endothelial cell desensitization to VEGF-A and permanent islet vascular dysfunction
Authors: Xiong Yan , Dicker Andrea , Visa Montse , Ilegems Erwin , Berggren Per-Olof 
Published: November 2023

AbstractBackgroundPancreatic islet microvasculature is essential for optimal islet function and glucose homeostasis. However, islet vessel pathogenesis and its role in the manifestation of metabolic disorders remain understudied. Here we depict a time-resolved decline of intra-islet endothelial cell sensitivity to vascular endothelial cell growth factor A (VEGF-A) in a mouse model of diet-induced obesity.MethodsMice were transplanted with reporter islets in their eyes and put on different diet schemes for 48 weeks. Islet vascular morphology, VEGF-A signaling activity in islet endothelial cells and vessel function were longitudinally monitored by in vivo imaging, while the metabolic implication of islet vessel alterations was measured by glucose tolerance tests and insulin secretion assays.ResultsIn parallel with substantial islet vasculature remodeling, diminished VEGF-A response in islet endothelial cells emerged after 12 weeks of western diet feeding. This led to vessel barrier dysfunction and hemodynamic dysregulation, which delayed transportation of secreted insulin into the blood. Islet vessels also exhibited a remarkable metabolic memory long after the removal of western diet. Neither islet endothelial cell VEGF-A sensitivity nor the vascular damage elicited by 24 weeks of western diet feeding was restored by switching to control diet for another 24 weeks. As a result, these refed mice still exhibited mild but significant impairment in glucose clearance, despite a complete normalization of body weight and insulin sensitivity. While plasma levels of soluble VEGF receptor 1 – the natural VEGF-A trap – were similar in all diet groups, increased activity of atypical protein kinase C (aPKC) was observed under both western diet and recovery conditions, which inhibited VEGF receptor 2 (VEGFR2) internalization and dampened VEGF-A triggered signal transduction in vivo and in human endothelial cells cultured under diet-mimicking conditions.ConclusionsLong-term western diet feeding causes irreversible VEGF-A desensitization in islet endothelial cells and islet vessel dysfunction which undermines glucose homeostasis.
Prevalence and factors associated with advanced HIV disease among young people aged 15 - 24 years in a national referral hospital in Sierra Leone: A cross-sectional study
Authors: Baldeh Mamadu , Kizito Samuel , Lakoh Sulaiman , Sesay Daniel , Dennis Frida , Barrie Umu , Williams Samuel Adeyemi , Robinson Dimbintsoa Rakotomalala , Lamontagne Franck , Amahowe Franck , Turay Patrick , Sensory-Bahar Ozge , Geng Elvin , Ssewamala Fred M. 
Published: November 2023

AbstractBackgroundAdvanced HIV in young people living with HIV is an increasingly pressing public health issue in sub-Saharan Africa. Despite global progress in early HIV testing and reducing HIV-related deaths, many young people with HIV continue to experience HIV disease progression in sub-Saharan Africa. This study provides an overview of the prevalence, clinical manifestations, and factors associated with advanced HIV in young people seeking medical services in a major hospital in Sierra Leone.MethodsWe used a cross-sectional design to collect data from HIV patients aged 15 to 24 years at a major hospital in Sierra Leone between September 2022 and March 2023. Advanced HIV was defined as (i) CD4+ below 200 cells/mm3 or (ii) WHO clinical stage 3 or 4. Logistic regression models determined the association between observable independent characteristics and advanced HIV. The statistical significance level was set at 0.05 for all statistical tests.ResultsAbout 40% (231/574) of patients were recruited; 70.6% (163/231) were inpatients, and 29.4% (68/231) were outpatients. The mean age was approximately 21.6 years (SD ±2.43). The overall prevalence of advanced HIV was 42.9% (99/231), 51.5% (35/68) of outpatients, and 39.3% (64/163) of inpatients. Age of inpatients (OR, 1.23; 95% CI, 1.00-1.52; p= 0.047) was associated with a higher risk. Female sex (OR, 0.51; 95% CI, 0.28-0.94; p= 0.030), higher education (OR, 0.27; 95% CI, 0.10 – 0.78; p= 0.015), and Body Mass (OR, 0.10; 95% CI, 0.01-0.77; p= 0.028) were at lower risk of advance HIV. Common conditions diagnosed in this population are tuberculosis (13.58%), hepatitis B (6.13%), Kaposi sarcoma (3.07%), and esophageal candidiasis (2.45%).ConclusionWe reported a high prevalence of advanced HIV among young patients in a referral Hospital in Sierra Leone. This emphasises the need to strengthen public health measures and policies that address challenges of access to HIV services.Strengths and limitations of this studyThis is the first study in Sierra Leone and the sub-region to examine the burden of advanced HIV and its predictors in young people living with HIV.Calls for a more targeted approach to addressing gaps in health service delivery for young people living with HIV in Sierra Leone.The study is limited by the unavailability of several laboratory investigations to monitor patient progress.
Capability of GPT-4V(ision) in Japanese National Medical Licensing Examination
Authors: Nakao Takahiro , Miki Soichiro , Nakamura Yuta , Kikuchi Tomohiro , Nomura Yukihiro , Hanaoka Shouhei , Yoshikawa Takeharu , Abe Osamu 
Published: November 2023

AbstractBackgroundPrevious research applying large language models (LLMs) to medicine was focused on text-based information. Recently, multimodal variants of LLMs acquired the capability of recognizing images.ObjectiveTo evaluate the capability of GPT-4V, a recent multimodal LLM developed by OpenAI, in recognizing images in the medical field by testing its capability to answer questions in the 117th Japanese National Medical Licensing Examination.MethodsWe focused on 108 questions that had one or more images as part of a question and presented GPT-4V with the same questions under two conditions: 1) with both the question text and associated image(s), and 2) with the question text only. We then compared the difference in accuracy between the two conditions using the exact McNemar’s test.ResultsAmong the 108 questions with images, GPT-4V’s accuracy was 68% when presented with images and 72% when presented without images (P= .36).ConclusionsThe additional information from the images did not significantly improve the performance of GPT-4V in the Japanese Medical Licensing Examination.
Combining genomic data and infection estimates to characterize the complex dynamics of SARS-CoV-2 Omicron variants in the United States
Authors: Lopes Rafael , Pham Kien , Klaassen Fayette , Chitwood Melanie H. , Hahn Anne M. , Redmond Seth , Swartwood Nicole A. , Salomon Joshua A. , Menzies Nicolas A. , Cohen Ted , Grubaugh Nathan D. 
Published: November 2023

AbstractSARS-CoV-2 Omicron surged as a variant of concern in late 2021. Subsequently, several distinct Omicron variants have appeared and overtaken each other. We combined variant frequencies and infection estimates from a nowcasting model for each US state to estimate variant-specific infections, attack rates, and effective reproduction numbers (Rt). BA.1 rapidly emerged, and we estimate that it infected 47.7% of the US population between late 2021 and early 2022 before it was replaced by BA.2. We estimate that BA.5, despite a slower takeoff than BA.1, infected 35.7% of the US population, persisting in circulation for nearly 6 months. Other Omicron variants - BA.2, BA.4, and XBB - together infected 30.7% of the US population. We found a positive correlation between the state-level BA.1 attack rate and social vulnerability and a negative correlation between the BA.1 and BA.2 attack rates. Our findings illustrate the complex interplay between viral evolution, population susceptibility, and social factors during the Omicron emergence in the US.
Comprehensive Analysis of Cell-Free DNA Fragmentation Across Cancer Stages
Authors: Guo Xin , Nie Lijuan , Yan Junjun , Ling Tinsheng , Zhang Fei , Chen Yi , Li Mengyu , Zeng Wenqi , Chen Yugen , Chu Wen-Ming , Ge Olivia , Guo Qing , Ge Dongliang , Zhou Xiqiao 
Published: November 2023

AbstractCirculating cell-free DNA (cfDNA) in the bloodstream displays cancer-derived fragmentation patterns, offering a non-invasive diagnostic avenue for cancer patients. However, the association between cfDNA fragmentation patterns and cancer progression remains largely unexplored. In this study, we analyzed this relationship using 214 whole-genome cfDNA samples across seven solid cancer types and revealed that the relation between cfDNA fragmentation patterns and cancer stages vary across cancer types. Among them, cfDNA fragmentation patterns in colorectal cancer (CRC) showed a strong correlation with cancer stages. This finding is further validated with an independent targeted cfDNA dataset from 29 CRC samples. Inspired by these findings, we designed “frag2stage”, a machine learning model that exploits cfDNA fragmentation data to differentiate cancer stages of CRC. Evaluated on two independent cfDNA datasets, our model can distinguish cancer stages of CRC with the area under the curve (AUC) values ranging from 0.68 to 0.99. The results suggest that cfDNA fragmentation patterns might carry yet undiscovered genetic and epigenetic signals, highlighting their promising potential for broader diagnostic applications in oncology.
Single locus theory of admixture is insufficient for the study of complex traits in admixed populations
Authors: Lee Hanbin , Lee Moo-Hyuk , Hou Kangcheng , Pasaniuc Bogdan , Han Buhm 
Published: November 2023

AbstractAdmixed populations offer valuable insights into the genetic architecture of complex traits. Such an investigation demands a delicate theory that can handle the linkage disequilibrium structure of admixed genomes. With additional assumptions, we show that Pritchard-Stephens-Donnelly (PSD) can predict empirical GWAS findings. We call this the extended PSD (ePSD) model and evaluate the predictions using real data. When applied to real data of admixed genomes, the prediction of the ePSD model is very successful in explaining single-locus behaviors while falling short in predicting two-loci phenomena involving linkage disequilibrium. Our results show that a mosaic of independent single-continental segments is an insufficient approximation of contemporary admixed populations. A more advanced theory that better models linkage disequilibrium of admixed populations will be crucial to better understanding the genetic architecture of complex traits.
QRS detection in single-lead, telehealth electrocardiogram signals: benchmarking open-source algorithms
Authors: Kristof Florian , Kapsecker Maximilian , Nissen Leon , Brimicombe James , Cowie Martin R. , Ding Zixuan , Dymond Andrew , Jonas Stephan M. , Lindén Hannah Clair , Lip Gregory Y. H. , Williams Kate , Mant Jonathan , Charlton Peter H. ,   the SAFER Investigators
Published: November 2023

ABSTRACTBackground and ObjectivesA key step in electrocardiogram (ECG) analysis is the detection of QRS complexes, particularly for arrhythmia detection. Telehealth ECGs present a new challenge for automated analysis as they are noisier than traditional clinical ECGs. The aim of this study was to identify the best-performing open-source QRS detector for use with telehealth ECGs.MethodsThe performance of 18 open-source QRS detectors was assessed on six datasets. These included four datasets of ECGs collected under supervision, and two datasets of telehealth ECGs collected without clinical supervision. The telehealth ECGs, consisting of single-lead ECGs recorded between the hands, included a novel dataset of 479 ECGs collected in the SAFER study of screening for atrial fibrillation (AF). Performance was assessed against manual annotations.ResultsA total of 12 QRS detectors performed well on ECGs collected under clinical supervision (F1score ≥ 0.96). However, fewer performed well on telehealth ECGs: five performed well on the TELE ECG Database; six performed well on high-quality SAFER data; and performance was poorer on low-quality SAFER data (three QRS detectors achievedF1of 0.78-0.84). The presence of AF had little impact on performance.ConclusionsThe Neurokit and University of New South Wales QRS detectors performed best in this study. These performed sufficiently well on high-quality telehealth ECGs, but not on low-quality ECGs. This demonstrates the need to handle low-quality ECGs appropriately to ensure only ECGs which can be accurately analysed are used for clinical decision making.
A Randomized, Double-Blind, Placebo Controlled Trial to Assess the Effectiveness and Safety of Melatonin and Three Formulations of Floraworks Proprietary TruCBN™ for Improving Sleep
Authors: Kolobaric Antonija , Saleska Jessica , Hewlings Susan J , Bryant Corey , Colwell Christopher S. , D’Adamo Christopher R. , Chen Jeff , Pauli Emily K 
Published: November 2023

AbstractIntroduction: Prescription sleep aids often have side effects, making alternative solutions necessary. Melatonin is an efficacious sleep aid and is often the comparator for alternatives. The phytocannabinoid cannabinol (CBN), has a potential mechanism of action but minimal evidence to support its effectiveness. Methods: TruCBN™ is a hemp-derived cannabinol (CBN) sleep aid. The primary aim of this randomized, double-blind, placebo-controlled study was to assess the safety and effects of three formulations of TruCBN™ [25 mg (n=206), 50 mg (n=205), 100 mg (n=203)], on sleep quality measured by PROMIS Sleep Disturbance 8A scale, relative to placebo (n=204). As a secondary aim, the effectiveness and safety of these formulations relative to a 4 mg melatonin (n=202) were assessed. Exploratory measures were stress (PROMIS Stress 4A), anxiety (Anxiety 4A), pain (PROMIS™ PEG) and well-being (WHO 5). Results: All treatment groups (25, 50 and 100 mg TruCBN™) and the 4 mg melatonin group experienced significant improvement in sleep quality relative to placebo. There were no significant differences between any of the TruCBN™ groups and melatonin for improving sleep. Participants taking 100 mg TruCBN™ showed a larger decrease in stress compared to the placebo group. There were no significant differences in anxiety, pain, well-being or frequency of side effects between any TruCBN™ group and placebo. There was no significant difference in improvements in sleep quality between any of the treatment groups and 4mg melatonin. Discussion: Orally ingested TruCBN™, 25 mg, 50 mg and 100 mg, is a safe and effective alternative for the improvement of sleep.Sterling Institutional Review Board (SIRB) approved the study [10147-EKPauli]. The study was registered onClinicalTrials.gov[NCT05511818] on August 21, 2023.