bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coordinated changes in a cortical circuit sculpt effects of novelty on neural dynamics
Authors: Ito Shinya , Piet Alex , Bennett Corbett , Durand Séverine , Belski Hannah , Garrett Marina , Olsen Shawn R. , Arkhipov Anton 
Published: October 2023

AbstractRecent studies have found dramatic cell-type specific responses to stimulus novelty, highlighting the importance of analyzing the cortical circuitry at the cell-type specific level of granularity to understand brain function. Although initial work classified and characterized activity for each cell type, the specific alterations in cortical circuitry—particularly when multiple novelty effects interact—remain unclear. To address this gap, we employed a large-scale public dataset of electrophysiological recordings in the visual cortex of awake, behaving mice using Neuropixels probes and designed population network models to investigate the observed changes in neural dynamics in response to a combination of distinct forms of novelty. The model parameters were rigorously constrained by publicly available structural datasets, including multi-patch synaptic physiology and electron microscopy data. Our systematic optimization approach identified tens of thousands of model parameter sets that replicate the observed neural activity. Analysis of these solutions revealed generally weaker connections under novel stimuli, as well as a shift in the balance e between SST and VIP populations. Along with this, PV and SST populations experienced overall more excitatory influences compared to excitatory and VIP populations. Our results also highlight the role of VIP neurons in multiple aspects of visual stimulus processing and altering gain and saturation dynamics under novel conditions. In sum, our findings provide a systematic characterization of how the cortical circuit adapts to stimulus novelty by combining multiple rich public datasets.
Whole brain mapping of orexin receptor mRNA expression visualized by branchedin situhybridization chain reaction
Authors: Tsuneoka Yousuke , Funato Hiromasa 
Published: October 2023

AbstractOrexins, which are produced within neurons of the lateral hypothalamic area, play a pivotal role in the regulation of various behaviors, including sleep/wakefulness, reward behavior, and energy metabolism, via orexin receptor type 1 (OX1R) and type 2 (OX2R). Despite the advanced understanding of orexinergic regulation of behavior at the circuit level, the precise distribution of orexin receptors in the brain remains unknown. Here, we develop a new branchedin situhybridization chain reaction (bHCR) technique to visualize multiple target mRNAs in a semiquantitative manner, combined with immunohistochemistry, which provided comprehensive distribution of orexin receptor mRNA and neuron subtypes expressing orexin receptors in mouse brains. Only a limited number of cells expressing bothOx1randOx2rwere observed in specific brain regions, such as the dorsal raphe nucleus and ventromedial hypothalamic nucleus. In many brain regions,Ox1r-expressing cells andOx2r-expressing cells belong to different cell types, such as glutamatergic and GABAergic neurons. Moreover, our findings demonstrated considerable heterogeneity inOx1r- orOx2r-expressing populations of serotonergic, dopaminergic, noradrenergic, cholinergic, and histaminergic neurons. The majority of orexin neurons did not express orexin receptors. This study provides valuable insights into the mechanism underlying the physiological and behavioral regulation mediated by the orexin system, as well as the development of therapeutic agents targeting orexin receptors.Significance statementThe neuropeptide orexin regulates sleep and other behaviors through its receptors, OX1R and OX2R, which are targets for the development of therapeutic agents for sleep and related disorders. However, the cellular distribution of orexin receptors in the brain is only partially known. We applied a newly developed branchedin situhybridization chain reaction (bHCR) technique and conducted a whole-brain mapping of orexin receptor mRNA expression in the brain with neuron subtype markers. Few cells expressed both OX1R and OX2R, and OX1R and OX2R were expressed in the different neuronal subtypes in many brain regions. This study fills an important gap in understanding and modulating the orexin system.
The biological role of local and global fMRI BOLD signal variability in human brain organization
Authors: Baracchini Giulia , Zhou Yigu , Castanheira Jason da Silva , Hansen Justine Y. , Rieck Jenny , Turner Gary R. , Grady Cheryl L. , Misic Bratislav , Nomi Jason , Uddin Lucina Q. , Spreng R. Nathan 
Published: October 2023

AbstractVariability drives the organization and behavior of complex systems, including the human brain. Understanding the variability of brain signals is thus necessary to broaden our window into brain function and behavior. Few empirical investigations of macroscale brain signal variability have yet been undertaken, given the difficulty in separating biological sources of variance from artefactual noise. Here, we characterize the temporal variability of the most predominant macroscale brain signal, the fMRI BOLD signal, and systematically investigate its statistical, topographical and neurobiological properties. We contrast fMRI acquisition protocols, and integrate across histology, microstructure, transcriptomics, neurotransmitter receptor and metabolic data, fMRI static connectivity, and empirical and simulated magnetoencephalography data. We show that BOLD signal variability represents a spatially heterogeneous, central property of multi-scale multi-modal brain organization, distinct from noise. Our work establishes the biological relevance of BOLD signal variability and provides a lens on brain stochasticity across spatial and temporal scales.
Screening Peptide Drug Candidates to Neutralize Whole Viral Agents : A Case study with SARS-CoV-2 Virus
Authors: Özçelik Cemile Elif , Araz Cemre Zekiye , Yılmaz Özgür , Gülyüz Sevgi , Özkul Aykut , Şeker Urartu Özgür Şafak 
Published: October 2023

AbstractCovid19 pandemic revealed the reality for the need of therapeutic and pharmaceutical molecule development in a short time with different approaches. Although the enhancement of immunological memory by vaccination was the quicker and robust strategy, still medication is required for immediate treatment for a patient. For this purpose, one of the approaches is developing new therapeutic molecule development like peptide-based drugs. Also, peptides can be used developing other molecules like nanobodies. Here, M13 phage display library was used for selecting SARS-CoV-2 interacting peptides for developing a neutralizing molecule for further use. Biopanning was applied with four iterative cycles to select phages displaying different 12-amino acid-long peptides. Then, the M13 phage genomic region where peptide sequences expressed were analyzed and sequences were obtained. Randomly selected peptide sequences were synthesized by solid-state peptide synthesis method. These peptides were analyzed by quartz crystal microbalance method in terms or peptide interaction capacity with specifically wild-type S protein. Next, QCM data was further validated by enzyme-linked immunosorbent assay (ELISA) in order to check peptides according to their neutralizing capacity rather than binding to S1 protein. The results showed that, phage display served an opportunity for selecting peptides which can be used and developed further as pharmaceutical molecules. More specifically, scpep3, scpep8 and scpep10 had both binding and neutralizing capacity for S1 protein as a candidate for therapeutic molecule.
Comparing ancestry calibration approaches for a trans-ancestry colorectal cancer polygenic risk score
Authors: Rosenthal Elisabeth A. , Hsu Li , Thomas Minta , Peters Ulrike , Kachulis Christopher , Patterson Karynne , Jarvik Gail P. 
Published: October 2023

AbstractBackgroundColorectal cancer (CRC) is a complex disease with monogenic, polygenic and environmental risk factors. Polygenic risk scores (PRS) are being developed to identify high polygenic risk individuals. Due to differences in genetic background, PRS distributions vary by ancestry, necessitating calibration.MethodsWe compared four calibration methods using the All of Us Research Program Whole Genome Sequence data for a CRC PRS previously developed in participants of European and East Asian ancestry. The methods contrasted results from linear models with A) the entire data set or an ancestrally diverse training set AND B) covariates including principal components of ancestry or admixture. Calibration with the training set adjusted the variance in addition to the mean.ResultsAll methods performed similarly within ancestry with OR (95% C.I.) per s.d. change in PRS: African 1.5 (1.02, 2.08), Admixed American 2.2 (1.27, 3.85), European 1.6 (1.43, 1.89), and Middle Eastern 1.1 (0.71, 1.63). Using admixture and an ancestrally diverse training set provided distributions closest to standard Normal with accurate upper tail frequencies.ConclusionAlthough the PRS is predictive of CRC risk for most ancestries, its performance varies by ancestry.Post-hoccalibration preserves the risk prediction within ancestries. Training a calibration model on ancestrally diverse participants to adjust both the mean and variance of the PRS, using admixture as covariates, created standard Normal z-scores. These z-scores can be used to identify patients at high polygenic risk, and can be incorporated into comprehensive risk scores including other known risk factors, allowing for more precise risk estimates.
READi-Dem: ML-powered, web-interface tool for Robust, Efficient, Affordable Diagnosis of Dementia
Authors: Klar Verena , Thompson Elinor , Atay Melvin Selim , Owoade Peter , Toniolo Sofia , Dehsarvi Amir , Rathee Sanjay 
Published: October 2023

AbstractBackgroundDementia screening tools typically involve face-to-face cognitive testing. Indeed, this introduces an increasing burden on the clinical staff, particularly in low-resource settings. The objective of our study is to develop an integrated online platform for efficient dementia screening, using a brief and cost-effective assessment.MethodsWe used the Longitudinal Ageing Study in India dataset (LASI-DAD, n=2528) to predict dementia diagnosis based on the Clinical Dementia Rating (CDR). Using feature selection algorithms and principal component analysis (PCA), we identified key predictive features. We compared the performance of six machine learning (ML) classifiers that were trained on the 42 selected features (full model) and the two components identified by PCA (minimal model). The best-performing model was selected for our web platform.ResultsSelected features mapped onto two distinct, interpretable domains: a cognitive domain and an informant domain. The first two principal components cumulatively explained 90.2% of the variance and included questions from the Mini-Mental State Exam (MMSE) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Classifiers trained on the minimal model performed on par with the full model, with Support Vector Machine performing best (93.4%). The model did not reliably predict Parkinson’s disease (67% accuracy) or stroke (53.1% accuracy), suggesting dementia specificity. The respective questions from MMSE and IQCODE (27 items) were incorporated into our online platform.ConclusionWe built an online platform enabling end-to-end screening for dementia from assessment to prediction, based on patient and caregiver reports. Web App code is available at GitHub:https://github.com/sanjaysinghrathi/READi-Dem& Web App link is available at Web Page:https://researchmind.co.uk/readi-dem. For the convenience of researchers, a video summarizing our work is also accessible on theWeb App PageandYouTube Link.
Clostridioides difficileMreE (PBP2) variants facilitate clinical disease during cephalosporin exposures
Authors: Worley Jay Noboru , Benedetto Nicholas D. , Delaney Mary , Paiva Ana Oliveira , Chapot-Chartier Marie-Pierre , Peltier Johann , Bry Lynn 
Published: October 2023

AbstractCephalosporins are the most common triggers of healthcare-associatedClostridioides difficileinfections (CDI). Here, we confirm gene-level drivers of cephalosporin resistance and their roles in promoting disease. Genomic-epidemiologic analyses of 306C. difficileisolates from a hospital surveillance program monitoring asymptomatic carriers and CDI patients identified prevalent third-generation cephalosporin resistance to ceftriaxone at >256 ug/mL in 26% of isolates. Resistance was associated with patient cephalosporin exposures 8-10 days beforeC. difficiledetection. Genomic analyses identified variants in themreEpenicillin binding protein 2 (PBP2) associated with resistance to multiple beta-lactam classes. Transfer of variants into susceptible strain CD630 elevated resistance to first and third-generation cephalosporins. Transfer into the mouse-infective strain ATCC 43255 enabled disease when mice were exposed to 500ug/mL cefoperazone, a dose that inhibited the isogenic susceptible strain. Our findings establish roles of cephalosporins andmreE-cephalosporin-resistant variants in CDI and provide testable genetic loci for detecting resistance in patient strains.
Device-measured vigorous intermittent lifestyle physical activity and major cardiovascular events
Authors: Stamatakis Emmanuel , Ahmadi Matthew N. , Biswas Raaj Kishore , del Pozo Cruz Borja , Thøgersen-Ntoumani Cecilie , Murphy Marie H , Sabag Angelo , Lear Scott A. , Gill Jason MR , Chow Clara K , Hamer Mark 
Published: October 2023

ABSTRACTImportanceVigorous physical activity is a time-efficient and potent preventive intervention for major adverse cardiovascular events (MACE), although longer traditional exercise sessions are unappealing or inaccessible to most adults.ObjectiveWe examined the dose-response associations of device-measured vigorous intermittent lifestyle physical activity (VILPA, brief sporadic bouts of higher intensity occurring during daily living) with MACE and its sub-types in women and men. We also undertook analogous analyses in a sample of exercisers.Design, Setting, and ParticipantsProspective cohort analysis of 13,018 women and 9,350 men non-exercisers from the UK Biobank accelerometry sub-study; the contextual analyses involved 34,364 female/24,284 male exercisers from the same sub-study.ExposuresWrist accelerometer assessed daily VILPA duration of bouts lasting up to 1 and up to 2 minutes.Outcomes and MeasuresOverall and sex-specific dose-response associations of daily VILPA with MACE and its subtypes (incident myocardial infarction, heart failure and stroke).ResultsAmong female/male non-exercisers there were 331/488 all-MACE events (129/250 myocardial infarction, 96/119 heart failure,106/119 stroke events) over a mean 7.9-year follow-up. Daily VILPA duration exhibited a near-linear dose-response association with all MACE, myocardial infarction, and heart failure in women but not in men. Compared to women with no VILPA, the median daily VILPA duration of 3.4 minutes per day was associated with HRs of 0.55 (0.41, 0.75) for all MACE; and 0.33 (0.18, 0.59) for heart failure. Women’s minimum doses (the dose associated with 50% of the optimal risk reduction) of 1.2-1.6 minutes of VILPA per day were associated with HRs of 0.70 (0.58, 0.86) for all-MACE, 0.67 (0.50, 0.91) for myocardial infarction and 0.60 (0.45, 0.81) for heart failure, respectively. The equivalent analyses in exercisers in the UK Biobank showed comparable beneficial associations of vigorous intensity activity with all MACE, myocardial infarction and heart failure in both sex groups.Conclusions and RelevanceAmongst non-exercisers, small amounts of VILPA were associated with substantially lower risk of myocardial infarction and heart failure in women but not in men. No such sex differences were evident among exercisers. VILPA may be a promising physical activity target for CVD prevention in women not willing or able to exercise.
Comparison of metabolic syndrome prevalence using three different definitions: A population-based study in Peru
Authors: Vera-Ponce Víctor Juan , Zuzunaga-Montoya Fiorella E. , Romero Luisa Erika Milagros Vásquez , Loayza-Castro Joan A. , Valladares-Garrido Mario J. 
Published: October 2023

AbstractIntroductionMetabolic syndrome (MetS) is important for public health; however, there are different ways to define it.Objectives1) to estimate the prevalence of MetS using three different definitions: the criteria of the International Diabetes Federation (IDF), the World Health Organization (WHO), and the National Cholesterol Education Program’s Adult Treatment Panel III (ATPIII), 2) to identify the factors associated with the presence of MetS according to each criterion, and 3) to evaluate the agreement between these three.Materials and MethodsA secondary and cross-sectional analysis of the database from the Life Stages Food and Nutrition Surveillance Survey (VIANEV) was conducted. For the definition of MetS, the aforementioned definitions were used. A multivariable Poisson regression analysis with robust variance and agreement was evaluated through the Kappa index.ResultsAccording to ATPIII, IDF, and WHO, the prevalence of MetS was 42.60%, 46.78%, and 49.49%, respectively. The agreement between IDF with WHO and ATPIII criteria was 0.42 and 0.45, while for ATPIII and WHO it was 0.44. In general, the associated factors were identified as sex, marital status, age, region of residence, level of physical activity, smoking habit, and body mass index (BMI). However, the association of these varied according to the definition used.ConclusionThe prevalence of MetS varies significantly according to the criteria used. This was higher when the WHO definition was used compared to the others. Additionally, the associated factors varied according to the definition used, although a consistency was observed across all definitions with BMI.
Interaction Between the Prefrontal and Visual Cortices Supports Subjective Fear
Authors: Taschereau-Dumouchel Vincent , Côté Marjorie , Manuel Shawn , Valevicius Darius , Cushing Cody A. , Cortese Aurelio , Kawato Mitsuo , Lau Hakwan 
Published: October 2023

AbstractIt has been reported that threatening and non-threatening visual stimuli can be distinguished based on the multi-voxel patterns of hemodynamic activity in the human ventral visual stream. Do these findings mean that there may be evolutionarily hardwired mechanisms within early perception, for the fast and automatic detection of threat, and maybe even for the generation of the subjective experience of fear? In this human neuroimaging study, we presented participants (Fear group: N=30; No Fear group: N = 30) with 2700 images of animals that could trigger subjective fear or not as a function of individual’s idiosyncratic “fear profiles” (i.e., fear ratings of animals reported by a given participant). We provide evidence that the ventral visual stream may represent affectively neutral visual features that are statistically associated with fear ratings of participants, without representing the subjective experience of fear itself. More specifically, we show that patterns of hemodynamic activity predictive of a specific “fear profile” can be observed in the ventral visual stream whether a participant reports being afraid of the stimuli or not. Further, we found that the multivariate information synchronization between ventral visual areas and prefrontal regions distinguished participants who reported being subjectively afraid of the stimuli from those who did not. Together, these findings support the view that the subjective experience of fear may depend on the relevant visual information triggering implicit metacognitive mechanisms in the prefrontal cortex.
Distinct eLPBChATprojections for methamphetamine anxiety and relapse
Authors: Chen Wenwen , Guo Hao , Zhou Ning , Xu Xing , Mai Yuning , He Teng , Wen Jun , Ge Feifei , Qin Shan , Liu Chengyong , Wu Wenzhong , Kim Hee Young , Fan Yu , Guan Xiaowei 
Published: October 2023

AbstractCholine acetyltransferase-positive neurons in the external lateral parabrachial nucleus (eLPBChAT) send projections to PKCδ-positive (PKCδ+) neurons in lateral portion of central nucleus of amygdala (lCeAPKCδ) and oval portion of bed nucleus of the stria terminalis (ovBNSTPKCδ), forming eLPBChAT–lCeAPKCδand eLPBChAT–ovBNSTPKCδpathways. At least in part, the eLPBChATneurons positively innervate lCeAPKCδand ovBNSTPKCδthrough regulating synaptic elements of presynaptic acetylcholine (Ach) release and postsynaptic nicotinic acetylcholine receptors (nAChRs). Methamphetamine (METH) withdrawal anxiety and METH-primed reinstatement of conditioned place preference (CPP) recruit eLPBChAT–lCeAPKCδpathway and eLPBChAT–ovBNSTPKCδpathway in male METH-exposed mice, respectively.
Imaginary scenes are represented in cortical alpha activity
Authors: Stecher Rico , Kaiser Daniel 
Published: October 2023

AbstractImagining natural scenes enables us to engage with a myriad of simulated environments. How do our brains generate such complex mental images? Recent research suggests that cortical alpha activity carries information about individual objects during visual imagery. However, it remains unclear if more complex imagined contents such as natural scenes are similarly represented in alpha activity. Here, we answer this question by decoding the contents of imagined scenes from rhythmic cortical activity patterns. In an EEG experiment, participants imagined natural scenes based on detailed written descriptions, which conveyed four complementary scene properties: openness, naturalness, clutter level and brightness. By conducting classification analyses on EEG power patterns across neural frequencies, we were able to decode both individual imagined scenes as well as their properties from the alpha band, showing that also the contents of complex visual images are represented in alpha rhythms. An additional cross-classification analysis between alpha power patterns during the imagery task and during a perception task, in which participants were presented images of the described scenes, showed that scene representations in the alpha band are shared between imagery and late stages of perception. This suggests that alpha activity mediates the top-down re-activation of scene-related visual contents during imagery.