bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying Optimal Parameters for Neuroscience-Informed Interventions for Misophonia
Authors: Neacsiu Andrada D. , Beynel Lysianne , Gerlus Nimesha , Szymkiewicz Victoria , LaBar Kevin S. , Bukhari-Parlakturk Noreen , Rosenthal M. Zachary 
Published: June 2023

AbstractBackgroundMisophonia is the inability to tolerate certain aversive, repetitive common sounds.MethodsUsing a within-subjects experimental design, twenty-nine participants with misophonia and thirty clinical controls with high emotion dysregulation received inhibitory neurostimulation (1Hz) over a personalized medial prefrontal cortex (mPFC) target functionally connected to the left insula; excitatory neurostimulation (10Hz) over a personalized dorsolateral PFC (dlPFC) target; and sham stimulation over either target. Stimulations were applied while participants were either listening or cognitively downregulating emotions associated with personalized aversive, misophonic, or neutral sounds. Subjective units of distress (SUDS) and psychophysiological measurements (skin conductance response[SCR] and level [SCL], and high-frequency heart rate variability [HF-HRV]) were collected.ResultsCompared to controls, participants with misophonia reported higher distress (ΔSUDS= 1.91-1.93,ps<.001) when listening to and when downregulating misophonic distress, although no psychophysiological differences were found. Both types of neurostimulation reduced distress significantly more than sham, with excitatory rTMS providing the most benefit (Cohen’sdSUDS=0.53;dSCL= 0.14). Excitatory rTMS also enhanced the regulation of emotions associated with misophonic sounds in both groups when measured by SUDS (dcontrol= 1.28;dMisophonia=0.94), and in the misophonia group alone when measured with SCL (d= 0.20). Both types of neurostimulation were well tolerated and feasible to administer.DiscussionClinical controls and misophonic participants were different in their self-report but not in psychophysiological measures of distress and regulations. Participants reported the lowest misophonic distress when engaging in cognitive restructuring enhanced with high-frequency neurostimulation, a finding that offers insight into the best path forward for misophonia interventions.
Real-World Effectiveness and Safety of Evolocumab in Very High-risk Atherosclerotic Cardiovascular Disease Patients with Acute Ischemic Stroke
Authors: Zhang Ting , Zhang Yajing , Yang Yun , Liao Haibing , Li Xun , Liu Ran , Liu Xueqing , Yang Liqin , Yue Wei 
Published: June 2023

AbstractBackgroundWe investigated evolocumab’s real-world effectiveness and safety on a background of statin therapy in the acute phase of ischemic stroke (IS) patients with a very high-risk of atherosclerotic cardiovascular disease (ASCVD).MethodsA real-world, single-center, retrospective study was conducted in the neurology department at Tianjin Huanhu Hospital in China. Patients were divided into two groups: evolocumab treatment (140 mg every two weeks) or the standard of care (SOC) group. The primary efficacy outcome of the study was the achievement of a targeted lipid control rate and the incidence of major adverse cardiovascular events (MACE) by the end of the follow-up. Propensity score matching (PSM) analysis was utilized to account for confounding factors between groups. Survival analysises were performed using the Kaplan-Meier method.Results1080 AIS patients with very high-risk ASCVD were recruited. After PSM, there were 528 individuals, with 206 in the evolocumab group and 322 in the standard of care (SOC) group. At 12 months of follow-up, the proportion of LDL-C < 1.4mmol/L and ≥50% reduction was 44.9% in the evolocumab group, compared with only 3.1% of SOC-treated patients (p= 0.000). The median follow-up time for clinical events was 15 months. The evolocumab group was associated with a lower risk of cerebrovascular events compared to the SOC group (HR, 0.45; 95% CI, 0.23-0.89;p= 0.022) but did not significantly reduce the incidence of cardiovascular events (HR, 0.51; 95% CI, 0.17-1.51;p= 0.224), event-related deaths (HR, 0.71; 95% CI, 0.34-1.46;p= 0.349), or MACE (HR, 0.71; 95% CI, 0.44-1.06;p= 0.089).ConclusionsThis real-world study suggested that evolocumab on a background of statin reduced the LDL-C levels significantly with a well-tolerated profile and lowered the incidence of recurrent cerebrovascular events in the very high-risk ASCVD patients with AIS in China.
Targeting hepatitis B vaccine escape using immunogenetics in Bangladeshi infants
Authors: Butler-Laporte Guillaume , Auckland Kathryn , Noor Zannatun , Kabir Mamun , Alam Masud , Carstensen Tommy , Wojcik Genevieve L , Chong Amanda Y , Pomilla Cristina , Noble Janelle A , McDevitt Shana L. , Smits Gaby , Wareing Susan , van der Klis Fiona RM , Jeffery Katie , Kirkpatrick Beth D , Sirima Sodiomon , Madhi Shabir , Elliott Alison , Richards J Brent , Hill Adrian VS , Duggal Priya ,   PROVIDE authors,   Cryptosporidiosis Birth Cohort authors, Sandhu Manjinder S , Haque Rashidul , Petri William A , Mentzer Alexander J 
Published: June 2023

AbstractHepatitis B virus (HBV) vaccine escape mutants (VEM) are increasingly described, threatening progress in control of this virus worldwide. Here we studied the relationship between host genetic variation, vaccine immunogenicity and viral sequences implicating VEM emergence. In a cohort of 1,096 Bangladeshi children, we identified human leukocyte antigen (HLA) variants associated with response vaccine antigens. Using an HLA imputation panel with 9,448 south Asian individualsDPB1*04:01was associated with higher HBV antibody responses (p=4.5×10−30). The underlying mechanism is a result of higher affinity binding of HBV surface antigen epitopes to DPB1*04:01 dimers. This is likely a result of evolutionary pressure at the HBV surface antigen ‘a-determinant’ segment incurring VEM specific to HBV. Prioritizing pre-S isoform HBV vaccines may tackle the rise of HBV vaccine evasion.One-Sentence SummaryHost genetics underlying hepatitis B vaccine response in Bangladeshi infants identifies mechanisms of viral vaccine escape, and how to prevent it.
Scalable Integration of Multiomic Single Cell Data Using Generative Adversarial Networks
Authors: Giansanti Valentina , Giannese Francesca , Botrugno Oronza A. , Gandolfi Giorgia , Balestrieri Chiara , Antoniotti Marco , Tonon Giovanni , Cittaro Davide 
Published: June 2023

AbstractSingle cell profiling has become a common practice to investigate the complexity of tissues, organs and organisms. Recent technological advances are expanding our capabilities to profile various molecular layers beyond the transcriptome such as, but not limited to, the genome, the epigenome and the proteome. Depending on the experimental procedure, these data can be obtained from separate assays or from the very same cells. Despite development of computational methods for data integration is an active research field, most of the available strategies have been devised for the joint analysis of two modalities and cannot accommodate a high number of them.To solve this problem, we here propose a multiomic data integration framework based on Wasserstein Generative Adversarial Networks (MOWGAN) suitable for the analysis of paired or unpaired data with high number of modalities (>2). At the core of our strategy is a single network trained on all modalities together, limiting the computational burden when many molecular layers are evaluated. Source code of our framework is available athttps://github.com/vgiansanti/MOWGAN.
GEMspa: a Napari plugin for analysis of single particle tracking data
Authors: Keegan Sarah , Fenyö David , Holt Liam J. 
Published: June 2023

ABSTRACTThe cellular environment is crowded with macromolecules and far from thermodynamic equilibrium. This active, crowded environment influences biochemical reactions and the formation of cellular structures such as membraneless organelles. These physical properties can change during normal physiology and in disease states such as neurodegenerative diseases and cancer, impacting cell behavior and function. Therefore, it is crucial to develop methods to characterize these properties. Microrheology is the inference of physical properties from the motion of tracer particles embedded within a material. This technique requires single particle tracking (SPT) and analysis of these tracks through the framework of soft-condensed matter physics. Analysis of SPT data can be challenging due to the lack of comprehensive user-friendly software tools. To address this, we introduce GEMspa, a software package implemented as a plugin for the open source image analysis platform, napari. GEMspa provides a GUI for a commonly used localization/tracking algorithm (via Trackpy), and a suite of methods to extract basic parameters describing particle motion. This platform aims to streamline the workflow of data analysis steps and allow researchers to visualize and optimize parameters for high-quality results, thereby making microrheology accessible to non-expert scientists.
The circadian molecular clock in the suprachiasmatic nucleus is necessary but not sufficient for fear entrainment in the mouse
Authors: Bussi Ivana L. , Ben-Hamo Miriam , Leon Luis E. Salazar , Casiraghi Leandro P. , Zhang Victor Y. , Neitz Alexandra F. , Lee Jeffrey , Takahashi Joseph S. , Kim Jeansok J. , de la Iglesia Horacio O. 
Published: June 2023

AbstractNocturnal aversive stimuli presented to mice during eating and drinking outside of their safe nest can entrain circadian behaviors, leading to a shift toward daytime activity. We show that the canonical molecular circadian clock is necessary for fear entrainment and that an intact molecular clockwork in the suprachiasmatic nucleus (SCN), the site of the central circadian pacemaker, is necessary but not sufficient to sustain fear entrainment of circadian rhythms. Our results demonstrate that entrainment of a circadian clock by cyclic fearful stimuli can lead to severely mistimed circadian behavior that persists even after the aversive stimulus is removed. Together, our results support the interpretation that circadian and sleep symptoms associated with fear and anxiety disorders may represent the output of a fear-entrained clock.One-Sentence SummaryCyclic fearful stimuli can entrain circadian rhythms in mice, and the molecular clock within the central circadian pacemaker is necessary but not sufficient for fear-entrainment.
Porous membrane electrical cell-substrate impedance spectroscopy for versatile assessment of biological barriers in vitro
Authors: Chebotarev Oleg , Ugodnikov Alisa , Simmons Craig A. 
Published: June 2023

AbstractCell culture models of endothelial and epithelial barriers typically use porous membrane inserts (e.g., Transwell inserts) as a permeable substrate on which barrier cells are grown, often in co-culture with other cell types on the opposite side of the membrane. Current methods to characterize barrier function in porous membrane inserts can disrupt the barrier or provide bulk measurements that cannot isolate barrier cell resistance alone. Electrical cell-substrate impedance sensing (ECIS) addresses these limitations but its implementation on porous membrane inserts has been limited by costly manufacturing and low sensitivity. Here we present porous membrane ECIS (PM-ECIS), a cost-effective method to adapt ECIS technology to porous substrate-basedin vitromodels. We demonstrate high fidelity patterning of electrodes on porous membranes that can be incorporated into well plates of a variety of sizes with excellent cell biocompatibility with mono- and co-culture set ups. PM-ECIS provided sensitive, real-time measurement of isolated changes in endothelial cell barrier impedance with cell growth and barrier disruption. Barrier function characterized by PM-ECIS resistance correlated well with permeability coefficients obtained from molecular tracer permeability assays performed on the same cultures, validating the device. Integration of ECIS into conventional porous cell culture inserts provides a versatile, sensitive, and automated alternative to current methods to measure barrier function in vitro, including molecular tracer assays and transepithelial/endothelial electrical resistance (TEER).
Rural Public Health Landscape: Funding, Personnel, Expertise, Community Resources, and Barriers in Rural Settings
Authors: Ellison Olivia , Silenzio Vincent 
Published: June 2023

AbstractObjectivesTo describe and understand the funding, personnel, expertise, community resources, and issues in rural settings by local public health departments post COVID-19.MethodsRural county health departments in ten states were sent a survey via web link in the Spring of 2021. 552 responses were collected with a 63% completion rate for all counties surveyed.ResultsMost counties utilized public health nurses, administrators, or community health professionals. Of these, 25% had formal education in public health and 10% had public health experience. 65% of respondents disagreed with having adequate funding, staff, and resources. 83% of counties reported working with nonprofits and 43% utilized volunteers. The top two issues in rural public health identified were mental health and substance use.ConclusionsRural county public health departments do not have the support needed to sustain or advance public health in their specific population.Policy implicationsThis report gives insight into the needs of rural health in 2021 that can be used to guide policy and funding to support rural health’s specific needs.
PharmGScore scores of compound genetic variant burden for psychiatric treatment optimization
Authors: Borczyk Malgorzata , Hajto Jacek , Piechota Marcin , Korostynski Michal 
Published: June 2023

AbstractThe acceptability of antidepressant drugs partly depends on genetic factors. The list of genes involved in antidepressant response, including Adverse Drug Reactions (ADRs) is broad and contains both drug-metabolizing enzymes (pharmacogenes) and genes involved in pharmacodynamics. Variants in pharmacogenes are traditionally reported in the form of star alleles and are partially annotated with known phenotypic consequences. As it is unfeasible to analyze all genotype-phenotype pairs, computational approaches remain the practical solution. A pharmacogenetic framework to predict responses to antidepressant drug treatment would provide great benefit to patients. In this study, we present a scoring system (PharmGScore) to assess both rare and common genetic variant burden across multiple genes. The PharmGScore is constructed by normalizing and aggregating existing, well-established computational variant predictors (CADD, Fathmm-xf, PROVEAN, Mutation Assessor). We show that this score effectively distinguishes no and decreased function from normal and increased function pharmacogenetic variants reported in PharmVar (PharmGScore AUC = 0.86). PharmGScore has improved performance when compared to its component scores (AUCs: CADD = 0.79; FATHMM-XF = 0.81; PROVEAN = 0.81; Mutation Assessor = 0.75). We then apply the PharmGScore to the 200k exome sequences of the UK Biobank (UKB). We report the overrepresentation of UKB participants with high (>50) gene PharmGScore forCYP2C19andCYP2C9and with high (>100) compound PharmGScore from nine pharmacogenes within a group with an antidepressant toxicity diagnostic code (T43.2). We then analyze all UKB participants that received any antidepressant toxicity or ADR diagnosis (n = 602). We indicate genes for which a higher burden may be associated with antidepressant toxicity or ADRs and confirm the known roles ofCYP2C19andCYP2D6in this process. Finally, we show that patients who experienced ADRs to antidepressants in the therapeutic process or accidental poisoning with antidepressants have a higher PharmGScore composed of nine cytochrome P450 genes. Our study proposes a novel paradigm to assess the compound genetic variant burden associated with antidepressant response from exome sequencing data. This approach can be further applied to a user-defined set of genes to investigate other pharmacological traits.
Epidemiology of Atrial Fibrillation in Colombia 2010-2015
Authors: Miranda-Machado Pablo Andrés , Guzman-Saenz Roberto Carlos 
Published: June 2023

AbstractAtrial Fibrillation (AF) is a common cardiac arrhythmia. Its prevalence worldwide has doubled in the last decade due to increased capacity for diagnosis and management of heart disease and chronic non-cardiac. The purpose of this study was to estimate the prevalence, incidence and demand for treatment of AF in Colombia during the period 2010 to 2015.
EPIDEMIOLOGY OF ANAPHYLAXIS IN COLOMBIA 2010-2015
Authors: Miranda-Machado Pablo Andrés 
Published: June 2023

ABSTRACTBackgroundThe lifetime prevalence of anaphylaxis from all triggers is estimated to range from 0.05 % to 2.6 %. Data on anaphylaxis in the Latin American region and Colombia are scant.ObjectiveEstimate the prevalence, incidence and mortality for anaphylaxis in Colombia.MethodsRecords with diagnosis of anaphylaxis (ICD-10 code T78.0-T78.2) of Information System of Social Protection (SISPRO) between 2010 and 2015 were included. To determine the prevalence, incidence and mortality for anaphylaxis, population estimates from the National Statistics Department of Colombia (DANE) were used.ResultsThe average estimated annual prevalence of anaphylaxis were 25.1 cases per million. The average estimated annual incidence of anaphylaxis were 3.2 cases per million. Most cases range between 45 and 49 years age. On average 8.4 cases of anaphylaxis deaths per year were estimated. The average estimated annual mortality of anaphylaxis were 0.16 cases per million.ConclusionsBoth under-diagnosis and under-report of anaphylaxis are common in the world. Population studies in Colombia, with diagnoses of based primarily on clinical history and clinical criteria for accurate and early identification of anaphylaxis recently established are required.
Understanding consumers to inform market interventions for Singapore’s shark fin trade
Authors: Choy Christina , Booth Hollie , Veríssimo Diogo 
Published: June 2023

AbstractSharks, rays and their cartilaginous relatives (Class Chondricthyes, herein ‘sharks’) are amongst the world’s most threatened species groups, primarily due to overfishing, which in turn is driven by complex market forces including demand for fins. Understanding the high-value shark fin market is a global priority for conserving shark and rays, yet the preferences of shark fin consumers are not well understood. This gap hinders the design of evidence-based consumer-focused conservation interventions.Using an online discrete choice experiment, we explored preferences for price, quality, size, menu types (as a proxy for exclusivity) and source of fins (with varying degrees of sustainability) among 300 shark fin consumers in Singapore: a global entrepot for shark fin trade.Overall, consumers preferred lower-priced fins sourced from responsible fisheries or produced using novel lab-cultured techniques. We also identified four consumer segments, each with distinct psychographic characteristics and consumption behaviors.These preferences and profiles could be leveraged to inform new regulatory and market-based interventions regarding the sale and consumption of shark fins, and incentivize responsible fisheries and lab-cultured innovation for delivering conservation and sustainability goals.In addition, message framing around health benefits, shark endangerment and counterfeiting could reinforce existing beliefs amongst consumers in Singapore and drive behavioral shifts to ensure that market demand remains within the limits of sustainable supply.
Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptors
Authors: Enriquez-Traba Juan , Yarur-Castillo Hector E , Flores Rodolfo J , Weil Tenley , Roy Snehashis , Usdin Ted B , LaGamma Christina T , Arenivar Miguel , Wang Huikun , Tsai Valerie S , Moritz Amy E , Sibley David R , Moratalla Rosario , Freyberg Zachary Z , Tejeda Hugo A 
Published: June 2023

AbstractDopamine release in striatal circuits, including the nucleus accumbens (NAc), tracks separable features of reward such as motivation and reinforcement. However, the cellular and circuit mechanisms by which dopamine receptors transform dopamine release into distinct constructs of reward remain unclear. Here, we show that dopamine D3 receptor (D3R) signaling in the NAc drives motivated behavior by regulating local NAc microcircuits. Furthermore, D3Rs co-express with dopamine D1 receptors (D1Rs), which regulate reinforcement, but not motivation. Paralleling dissociable roles in reward function, we report non-overlapping physiological actions of D3R and D1R signaling in NAc neurons. Our results establish a novel cellular framework wherein dopamine signaling within the same NAc cell type is physiologically compartmentalized via actions on distinct dopamine receptors. This structural and functional organization provides neurons in a limbic circuit with the unique ability to orchestrate dissociable aspects of reward-related behaviors that are relevant to the etiology of neuropsychiatric disorders.
Unidirectional expression of enhancers with cell type-dependent direction of transcription
Authors: Agrawal Saumya , Kanamaru Emi , Saito Yoriko , Ishikawa Fumihiko , de Hoon Michiel 
Published: June 2023

AbstractEnhancers are genomic regulatory elements that can affect expression of genes over megabases of genomic distances. As previous evidence suggested that transcription initiation at enhancers occurs in a bidirectional pattern, balanced expression of divergently transcribed capped RNAs has been used as a hallmark for enhancer detection from transcriptome data.By analyzing deep Cap Analysis Gene Expression (CAGE) data from FANTOM5, FANTOM6, and other studies, we show that enhancers are usually unidirectionally transcribed in a given cell type. However, since the preferred direction of transcription of an enhancer may switch between cell types, enhancers may appear to be bidirectionally expressed when using CAGE data aggregated over many cell types. By analyzing expression directionality of enhancers across cell types, we classified enhancers into bidirectionally expressed, unidirectionally expressed with a consistent direction of transcription, and unidirectionally expressed with a switching direction, which was the largest category.We conclude that requiring bidirectional expression during enhancer prediction from transcriptome data may lead to false negatives. Also, the preference of a given cell type for a specific direction of transcription at an enhancer suggests that enhancer RNAs are not transcriptional noise, but may be functional.