bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review and meta-analysis ofHyalomma marginatumvertebrate hosts in the EU
Authors: Bah Madiou Thierno , Vial Laurence , Busani Lucas , Souq Léa , Grosbois Vladimir , Bernard Celia , Jori Ferran 
Published: September 2024

AbstractHost choice is a determining component of tick population and pathogen transmission dynamics. In Europe, ticks of the genusHyalomma, which are involved in the transmission of several pathogens such as the Crimean Congo Haemorrhagic fever (CCHF) virus, are suspected to be spreading into new territories where they were previously unreported. Therefore, we performed a systematic review of the tick-host relationship ofHyalomma sppin Europe with a focus onHyalomma marginatum, combined with a meta-analysis and meta-regression to describe its host preference pattern using three outcome values. Our initial qualitative analysis highlighted an increase in tick-host interaction rate in the last decades mostly in South-eastern and Central Europe.H. marginatumalso appeared as the species holding the highest citation rate in terms of its association with hosts, and for which the largest number of host species were reported. The meta-analysis onHyalomma marginatumhost choice revealed preferential interactions for horses in the adult stage and birds of theEmberizidaeandStrigidaefamilies, in immature stages. Nevertheless, most of the heterogeneity of tick-host interactions remained unexplained suggesting the involvement of multiple drivers such as environmental or climatic conditions. Our results suggest thatH. marginatumis a generalist tick whose distribution depends primarily on environmental conditions such as climate and habitat. Current limitations of our meta-analysis approach to identify hosts preference forH. marginatumand suggestions ways for improvement are further discussed.
Cleavage site heterogeneity at the pre-mRNA 3′-untranslated region regulates gene expression in oxidative stress response
Authors: Shaji Feba , Ali Jamshaid , Laishram Rakesh S. 
Published: September 2024

ABSTRACTEndonucleolytic cleavage step of the eukaryotic mRNA 3′-end processing is considered imprecise that leads to heterogeneity of cleavage site (CS) with hitherto unknown function. Contrary to the popular belief, we show that this imprecision in cleavage is tightly regulated resulting in CS heterogeneity (CSH) that controls gene expression in antioxidant response. CSH centres at a primary CS followed by a number of subsidiary cleavages that is determined by the position of the CS. Globally and by using reporter antioxidant NQO1 mRNA, we discovered an inverse relationship between the number of CS and the gene expression with the primary CS exhibiting highest cleavage efficiency. Strikingly, reducing CSH and increasing primary CS usage induces gene expression. Under oxidative stress condition (tBHQ, H2O2or NaAsO2), there is a decrease in the CSH and an increase in the primary CS usage to induce antioxidant gene expression. Concomitantly, ectopic NQO1 expression from the primary CS or reduction in CSH imparts cellular oxidative stress tolerance. Genome-wide CS analysis of stress response genes also shows a concomitant result. We show that oxidative stress induces affinity/strength of cleavage complex assembly increasing the fidelity of cleavage at the primary CS thereby reducing CSH inducing antioxidant response.
Inhibition mediated by group III mGluRs regulates habenula activity and defensive behaviors
Authors: Ostenrath Anna Maria , Faturos Nicholas , Çiftci Çobanoğlu Yağnur Işık , Serneels Bram , Jeong Inyoung , Enz Anja , Hinrichsen Francisca , Mutlu Aytac Kadir , Bardenhewer Ricarda , Jetti Suresh Kumar , Neuhauss Stephan C. F. , Jurisch-Yaksi Nathalie , Yaksi Emre 
Published: September 2024

ABSTRACTInhibition contributes to various brain computations from sensory motor transformations to cognitive operations. While most studies on inhibition focus on GABA, the main excitatory neurotransmitter of the brain, glutamate, can also elicit inhibition via metabotropic glutamate receptors (mGluRs). The function of mGluR-mediated inhibition remains largely elusive. Here, we investigated the role of group III mGluR-dependent inhibition in the habenula. This primarily glutamatergic and conserved forebrain region acts as a hub between multiple forebrain inputs and neuromodulatory mid- and hindbrain targets that regulate adaptive behaviors. We showed that both zebrafish and mice habenula express group III mGluRs. We identified that group III mGluRs regulate the membrane potential and calcium activity of zebrafish dorsal habenula. Pharmacological and genetic perturbation of group III mGluRs increased sensory-evoked excitation and reduced selectivity of habenular neurons to different sensory modalities. We also observed that inhibition is the main channel of communication between primarily glutamatergic habenula neurons. Blocking group III mGluRs reduced inhibition within habenula and increased correlations during spontaneous activity. In line with such inhibition within habenula, we identified that multi-sensory information is integrated mainly through competition and suppression across habenular neurons, which in part relies on group III mGluRs. Finally, genetic perturbation of a habenula-specific group III mGluR, mGluR6a, amplified neural responses and defensive behaviors evoked by sensory stimulation and environmental changes. Altogether, our results revealed that mGluR driven inhibition is essential in encoding, integration, and communication of information between Hb neurons, ultimately playing a critical role in regulating defensive and adaptive behaviors.
Adrenergic C1 neurons enhance anxiety via projections to PAG
Authors: Fernández-Peña Carlos , Pace Rachel L. , Fernando Lourds M. , Pittman Brittany G. , Schwarz Lindsay A. 
Published: September 2024

AbstractAnxiety is an emotional state precipitated by the anticipation of real or potential threats. Anxiety disorders are the most prevalent psychiatric illnesses globally and increase the risk of developing comorbid conditions that negatively impact the brain and body. The etiology of anxiety disorders remains unresolved, limiting improvement of therapeutic strategies to alleviate anxiety-related symptoms with increased specificity and efficacy. Here, we applied novel intersectional tools to identify a discrete population of brainstem adrenergic neurons, named C1 cells, that promote aversion and anxiety-related behaviors via projections to the periaqueductal gray matter (PAG). While C1 cells have traditionally been implicated in modulation of autonomic processes, rabies tracing revealed that they receive input from brain areas with diverse functions. Calcium-based in vivo imaging showed that activation of C1 cells enhances excitatory responses in vlPAG, activity that is exacerbated in times of heightened stress. Furthermore, inhibition of C1 cells impedes the development of anxiety-like behaviors in response to stressful situations. Overall, these findings suggest that C1 neurons are positioned to integrate complex information from the brain and periphery for the promotion of anxiety-like behaviors.
Electromagnetic waves destabilize the SARS-CoV-2 Spike protein and reduce SARS-CoV-2 Virus-Like Particle (SC2-VLP) infectivity
Authors: Granatir Skyler , Acosta Francisco M. , Pantoja Christina , Tailor Johann , Fuori Angus , Dower Bill , Marr Henry , Ramirez Peter W. 
Published: September 2024

AbstractInfection and transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to pose a global public health concern. Using electromagnetic waves represents an alternative strategy to inactivate pathogenic viruses such as SARS-CoV-2 and reduce overall transmission. However, whether electromagnetic waves reduce SARS-CoV-2 infectivity is unclear. Here, we adapted a coplanar waveguide (CPW) to identify electromagnetic waves that could neutralize SARS-CoV-2 virus-like particles (SC2-VLPs). Treatment of SC2-VLPs, particularly at frequencies between 2.5-3.5 GHz at an electric field of 400 V/m for 2 minutes, reduced infectivity. Exposure to a frequency of 3.1 GHz decreased the binding of SC2-VLPs to antibodies directed against the Spike S1 subunit receptor binding domain (RBD). These results suggest that electromagnetic waves alter the conformation of Spike, thereby reducing viral attachment to host cell receptors. Overall, this data provides proof-of-concept in using electromagnetic waves for sanitation and prevention efforts to curb the transmission of SARS-CoV-2 and potentially other pathogenic enveloped viruses.
Demographic responses to climatic changes during the Final Palaeolithic in Europe
Authors: Schmidt Isabell , Gehlen Birgit , Winkler Katja , Arrizabalaga Alvaro , Arts Nico , Bicho Nuno , Crombé Philippe , Eriksen Berit Valentin , Grimm Sonja B. , Kapustka Katarina , Langlais Mathieu , Mevel Ludovic , Naudinot Nicolas , Nerudová Zdeňka , Niekus Marcel , Peresani Marco , Riede Felix , Sauer Florian , Schön Werner , Sobkowiak-Tabaka Iwona , Vandendriessche Hans , Weber Mara-Julia , Zander Annabell , Zimmermann Andreas , Maier Andreas 
Published: September 2024

AbstractThe European Final Palaeolithic witnessed marked changes in almost all societal domains. Despite a rich body of evidence, our knowledge of palaeodemographic processes and regional population dynamics still needs to be improved. In this study, we present regionally differentiated estimates of absolute numbers and population densities for the Greenland Interstadial 1d-a (GI-1d-a; 14-12.7 ka BP) and the Greenland Stadial 1 (GS-1; 12.7-11.6 ka BP) for Southern, Western, Northern and Central Europe. The data were obtained by applying the Cologne Protocol, a geostatistical approach for estimating prehistoric population size and density, to a newly compiled dataset of Final Palaeolithic sites. On a large spatio-temporal scale, we observe a shift of the main areas of human occupation from the Franco-Cantabrian region, which was intensely occupied during most phases of the preceding Upper Palaeolithic, to regions north of the Alps. At smaller scales, we observe divergent regional trends in the Final Palaeolithic meta-population: during GI 1d-a, a decreasing population in southwestern Europe and an increasing population in north-eastern Central Europe. For the first time since the dispersal of anatomically modern humans into Europe, we see that Central Europe becomes the dominant demographic growth area. Subsequently, the climatic cooling of GS-1 coincides with a pronounced population decline in most parts of the study area. An apparent increase in population density occurs only in north-eastern Central Europe and north-eastern Italy. Our estimates suggest that the total population was reduced by half. Similar results, with a relationship between decreasing temperatures and decreasing populations, have already been observed for the late phase of the Gravettian, when populations were reduced to only one third of those estimated for the early phase. Yet, in contrast to the collapse of local populations during the late Gravettian, the increase in population densities in Central Europe during GS-1 indicates population movements eastwards, possibly in response to deteriorating climatic conditions, particularly in western regions during the Younger Dryas.
Somatic evolution of cancer genes in sex chromosomes
Authors: Akachukwu Amarachi C. , Ratcliff Jasmine S. , Marco Antonio 
Published: September 2024

ABSTRACTGenes on sex chromosomes have higher evolutionary rates than those on autosomes. However, this does not necessarily apply to somatic evolution in cancer. Many dominant mutations have been described in the so-called proto-oncogenes (OGs), while recessive mutations are typically described in tumor-suppressor genes (TSGs). Evidence indicates that mutations in X-chromosome TSGs are more likely to contribute to cancer than those in autosomal TSGs. Here, we formalize this in several dynamic models and predict, as expected, that mutations spread faster in TSGs located on the X chromosome than on autosomes (faster-X effect). Conversely, mutations in OGs spread faster on autosomes than on the X chromosome, but under high selective pressure, this difference is negligible. Published genomic screenings of cancer samples show evidence of the faster-X effect in TSGs. This pattern is observed in both sexes, suggesting that the maintenance of X-chromosome inactivation during cancer progression plays an important role in the evolution of TSGs. Strikingly, the relative mutation incidence in X-linked TSGs among females across individual studies is bimodal, with one group of studies showing a faster-X effect and another group showing similar incidences for X-linked and autosomal TSGs. This differentiation between cancer samples is not associated with the specific type of cancer or the tissue of origin. This may indicate that X-chromosome inactivation plays a differential role in the involvement of X-linked TSGs across individual cancers.
Harnessing Synaptic Vesicle Release and Recycling Mechanism for Molecule Delivery to Neurons
Authors: Yee Karen Kar Lye , Kumamoto Junichi , Inomata Daijiro , Suzuki Naoki , Harada Ryuhei , Yumoto Norihiro 
Published: September 2024

SummaryNeurodegenerative clinical trials often fail due to insufficient drug doses in reaching targeted cells and the unintended delivery to non-targeted cells. This study demonstrates an alternative neuron-selective drug delivery system, which utilizes the synaptic vesicle release and recycling mechanism (SVRM) by antibody shuttles targeting synaptic vesicle transmembrane proteins for molecule delivery. Using Synaptotagmin-2 (SYT2), we exemplify that intravenously administered anti-SYT2 antibodies localize to neuromuscular junctions, undergo uptake, and retrograde transport toChAT-positive motor neurons (MNs) in the spinal cord and brainstem. The delivery of anti-microtubule agent andMalat1gapmer antisense oligonucleotide to MNs with anti-SYT2 antibodies induces axon degeneration and reduction of Malat1 RNA expression, respectively. This approach circumvents the blood-spinal cord barrier, enabling selective delivery of therapeutic molecules to neurons while minimizing effects in non-targeted cells. Thus harnessing SVRM presents a promising strategy for enhancing drug concentrations in neurons and improving treatment efficacy for neurodegenerative diseases.
Pediatric Kidney Injury in Communities Impacted by Chronic Kidney Disease of Unknown Etiology (CKDu): A Comprehensive Systematic Review of Epidemiologic Studies
Authors: Strasma Anna , Gerber Anisha , Agi Maluli Isabela , Blackwood Elizabeth R. , Gunasekara Sameera , De Silva P. Mangala C S , Kamath Nivedita , Gonzalez-Quiroz Marvin , Sanders Alison P. , Wyatt Christina , Jayasundara Nishad 
Published: September 2024

AbstractBackgroundChronic kidney disease of unknown etiology (CKDu) is a tubulointerstitial disease that disproportionately affects young, primarily male, agricultural workers in Mesoamerica and South Asia who lack traditional risk factors for kidney disease. Extensive research in adult populations suggests the etiology is complex and indicates that early childhood exposures could have an integral role.ObjectivesTo systematically identify, summarize, and compare research in children living in CKDu endemic areas or with relevant CKDu-related exposures.MethodsA systematic literature search was conducted in six databases for studies that report kidney health outcomes of pediatric populations living in proximity to CKDu-affected areas with no limitations on geography or study design. Studies were independently screened for inclusion and underwent quality assessment using the Appraisal Tool for Cross-Sectional Studies (AXIS) or the JBI Critical Appraisal Tool for Cohort Studies based on the study design by at least two authors. Data are compared narratively and graphically.ResultsWe included twenty peer-reviewed publications and two meeting abstracts from eight different countries. The most common study design involved cross-sectional analysis of biological specimens from children in an established CKDu endemic area. Marked decreases in estimated glomerular filtration rate were generally not identified and prevalence of albuminuria differed widely between countries. Novel urinary biomarkers frequently demonstrated subclinical kidney damage, although the specific biomarker(s) varied between studies. Epidemiologic factors associated with evidence of subclinical kidney damage in children included proximity to agriculture or agrochemicals. Despite heterogenous study outcomes, all studies concluded that there were signs of kidney injury in children living in CKDu endemic areas or with a CKDu-relevant environmental exposure.ConclusionThis systematic review suggests that the pathophysiologic process leading to CKDu may begin prior to adulthood. Future longitudinal research aimed at elucidating the multifaceted factors and exposures impacting entire communities, including children, is imperative for disease prevention strategies.
Low-intensity focused ultrasound stimulation in stroke: An intensity escalation phase I safety and feasibility study
Authors: Huang Ziping , Charalambous Charalambos C. , Chen Mengyue , Kim Taewon , Sokhadze Estate , Song Allen , Jung Sin-Ho , Shekhar Shashank , Feld Jody , Jiang Xiaoning , Feng Wuwei 
Published: September 2024

AbstractBACKGROUNDLow-intensity focused ultrasound stimulation (LIFUS) has recently emerged as a promising neuromodulation tool for certain neuropsychiatric diseases. However, its safety and feasibility in stroke patients remains unknown. Intensity is a critical safety parameter for LIFUS. We aimed to determine the maximum safe and tolerable intensity of LIFUS in stroke patients, and to explore its effect on upper-extremity motor learning and corticospinal excitability.METHODSSubjects with first-ever stroke participated in this Phase I study. We adopted the classic 3+3 dose-escalation paradigm to sham/0, 1, 2, 4, 6, and 8 W/cm2spatial-peak pulse-average intensity (ISPPA, estimated in-vivo transcranial value; LOW: sham/0, 1 and 2 W/cm2, HIGH: 4, 6 and 8 W/cm2). Stopping rules (dose limiting toxicities) were pre-defined: ≥2nd-degree scalp burn, clinical seizures, ≥20% topical apparent diffusion coefficient change, or participant discontinuation due to any reason. A 12-minute LIFUS was applied over the ipsilesional motor cortex while participants were concurrently practicing three blocks of motor sequence learning (MSL) task using the affected hand. We collected the occurrences of pre-defined adverse events, post-minus-pre improvements in MSL response time, and post-minus-pre differences in corticospinal excitability quantified by motor evoked potentials.RESULTSISPPAwas escalated to 8 W/cm2with eighteen stroke participants without meeting stopping rules. Compared to the LOW, the HIGH performed significantly better on the MSL (24.7±13.3% vs. 13.2±10.9%,p=0.01). Similarly, the HIGH also showed signs of increased corticospinal excitability (32.0±34.3% vs. 12.9±48.0%) but did not reach significance,p=0.53.CONCLUSIONSOur Phase I safety study suggests that a single session of 12-minute LIFUS up to 8 W/cm2ISPPAis safe and feasible in stroke patients. Higher LIFUS intensities can induce greater MSL retention. The next logical step is to conduct a Phase II study to further test the efficacy of LIFUS and monitor its safety profiles in stroke patients.REGISTRATIONURL:https://www.clinicaltrials.gov; Unique identifier:NCT05016531
Prevalence of Common Respiratory Viruses in Children: Insights from Post-Pandemic Surveillance
Authors: Adu-Gyamfi Constance , Asamoah Jesse Addo , Frimpong James Opoku , Larbi Richard , Ansah Richard Owusu , Aryeetey Sherihane Naa Ayeley , Gorman Richmond , Acheampong Henry Kyeremateng , Nyarko-Afriyie Emmanuella , Hayford Manuella , Tetteh Henrietta Dede , Boampong Kwadwo , Barnor Veronica , Brenya Peter K. , Ayensu Frederick , Ayisi-Boateng NK. , El-Duah Philip , Drosten Christian , Phillips Richard Odame , Sylverken Augustina Angelina , Owusu Michael 
Published: September 2024

AbstractIntroductionThe COVID-19 pandemic has significantly affected healthcare systems worldwide, impacting the occurrence and management of respiratory illnesses. This has also influenced respiratory infections’ role in childhood mortality. Surveillance of common respiratory viruses in Ghana is limited, making it crucial to assess the prevalence of respiratory viral infections, particularly in children, in the post-pandemic era. This study provides data on the prevalence of respiratory viruses and the associated risk factors in children aged 5 or younger in an urban paediatric hospital setting.MethodsThe study was a cross-sectional study with a convenience sampling method, conducted in four health facilities: Asokwa Children’s Hospital, HopeXchange Medical Centre, University Health Services-KNUST, and Kumasi South Hospital in Kumasi, Ghana, between August 2022 and June 2023. Recruitment was not done in parallel in each hospital. Oropharyngeal swabs were collected from children ≤ 5 years old and screened by RT-qPCR for common respiratory viruses.ResultsOut of the 303 patients enrolled in the study, 165 (54.4%) were male, and 122 (40.3%) were aged from 13 to 36 months. The median age of the patients was 19 months. The most common symptoms reported were cough (87.0%), runny nose (87.0%), and fever (72.0%). Respiratory viruses were detected in 100 (33.0%) of the samples, with 36 (12.0%) testing positive for Human metapneumovirus (HMPV), 27 (8.9%) for RSV, and 20 (6.6%) for Human Adenovirus (HAdV). In 8.0% of the cases, multiple viruses were detected, with HAdV being the most common (75.0%). Children under 6 months (AOR: 4.81, 95% CI: 1.20-24.60) had a higher risk of RSV detection compared to children aged 37 to 60 months. Furthermore, it was found that caregivers with tertiary education had a higher risk of HMPV detection (AOR: 6.91, 95% CI: 1.71-47.3).ConclusionThe study’s findings emphasize RSV infection in very young children and the potentially significant role of HMPV in causing respiratory infections among children in Ghana. Active surveillance of common respiratory viruses in healthcare facilities could enhance the management of viral respiratory infection cases in the paediatric population in Ghana.
A Systematic Review of the Etiology and Neurobiology of Intermittent Explosive Disorder
Authors: Paliakkara John , Ellenberg Stacy , Ursino Andrew , Smith Abigail A , Evans James , Strayhorn Joseph , Faraone Stephen V. , Zhang-James Yanli 
Published: September 2024

ABSTRACTIntermittent Explosive Disorder (IED) is characterized by repeated inability to control aggressive impulses. Although the etiology and neurobiology of impulsive anger and impulse control disorders have been reviewed, no systematic review on these aspects has been published for IED specifically. We conducted a systematic search in seven electronic databases for publications about IED, screened by two authors, and retained twenty-four studies for the review. Our findings highlight a multifactorial etiology and neurobiology of IED, emphasizing the role of the amygdala and orbitofrontal cortex in emotional regulation and impulse control, and supporting interventions that target serotonergic signaling. Research also shows that childhood trauma and adverse family environment may significantly contribute to the development of IED. Yet, genetic studies focusing on IED were largely lacking, despite many examining the genetics underlying aggression as a general trait or other related disorders. Future research using consistently defined IED as a phenotype is required to better understand the etiology and underlying mechanisms and assist in informing the development of more effective interventions for IED.