bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensory Adaptations: Insights into the Vomeronasal System of the Iberian Wolf
Authors: Ortiz-Leal Irene , Torres Mateo V. , Barreiro-Vázquez José-Daniel , López-Beceiro Ana , Fidalgo Luis , Sanchez-Quinteiro Pablo 
Published: September 2023

ABSTRACTWolves, like other canids, extensively use chemical signals for various aspects of communication, including territory maintenance, reproductive synchronization, and social hierarchy signaling. Pheromone-mediated chemical communication operates unconsciously among individuals, acting as a mysterious sixth sense that regulates both their physiology and behavior. Despite their crucial role in the life of the wolf, there is a surprising lack of comprehensive research on the neuroanatomical and physiological bases of chemical communication in wolves.This study delves into the Iberian wolf vomeronasal system (VNS) and examines potential changes brought about by dog domestication. Our findings show that the Iberian wolf possesses a fully functional VNS vital for pheromone-mediated communication. While macroscopic similarities between the wolf and domestic dog VNS are observed, there are notable microscopic differences. These include the presence of neuronal clusters associated with the sensory epithelium of the vomeronasal organ (VNO) and a higher differentiation degree of the accessory olfactory bulb (AOB). Immunohistochemical markers reveal the expression of the two main families of vomeronasal receptors (V1R and V2R) in the VNO. However, only the V1R family is expressed in the AOB.These findings not only provide deep insights into the VNS of the wolf but also hint at how domestication might have altered neural configurations that underpin species-specific behaviors. This understanding has implications for innovative strategies, such as employing semiochemicals for wolf population management, aligning with modern conservation goals.
Dendriticatoh1a+cells serve as transient intermediates during zebrafish Merkel cell development and regeneration
Authors: Craig Evan W. , Black Erik C. , Goo Camille E.A. , Swearer Avery Angell , Yee Nathaniel G. , Rasmussen Jeffrey P. 
Published: September 2023

ABSTRACTSensory cells often adopt specific morphologies that aid in the detection of external stimuli. Merkel cells encode gentle touch stimuli in vertebrate skin and adopt a reproducible shape characterized by spiky, actin-rich microvilli that emanate from the cell surface. The mechanism by which Merkel cells acquire this stereotyped morphology from basal keratinocyte progenitors is unknown. Here, we establish that dendritic Merkel cells (dMCs) expressatonal homolog 1a (atoh1a), extend dynamic filopodial processes, and arise in transient waves during zebrafish skin development and regeneration. We find that dMCs share molecular similarities with both basal keratinocytes and Merkel cells, yet display mesenchymal-like behaviors, including local cell motility and proliferation within the epidermis. Furthermore, dMCs can directly adopt the mature, microvilliated Merkel cell morphology through substantial remodeling of the actin cytoskeleton. Loss of Ectodysplasin A signaling alters the morphology of dMCs and Merkel cells within specific skin regions. Our results show that dMCs represent an intermediate state in the Merkel cell maturation program and identify Ectodysplasin A signaling as a key regulator of Merkel cell morphology.
ULK1-dependent phosphorylation of PKM2 antagonizes O-GlcNAcylation and inhibits the Warburg effect in breast cancer
Authors: Zhou Zibin , Zheng Xiyuan , Zhao Jianxin , Yuan Aiyun , Shao Guangcan , Peng Bin , Dong Meng-Qiu , Xu Quan , Xu Xingzhi , Li Jing 
Published: September 2023

AbstractPyruvate kinase M2 (PKM2) is a central metabolic enzyme driving the Warburg effect in tumor growth. Previous investigations have demonstrated that PKM2 is subject to O-linked β-N-acetylglucosamine (O-GlcNAc) modification, which is a nutrient-sensitive post-translational modification. Here we found that unc-51 like autophagy activating kinase 1 (ULK1), a glucose-sensitive kinase, interacts with PKM2 and phosphorylates PKM2 at Ser333. Ser333 phosphorylation antagonizes PKM2 O-GlcNAcylation, promotes its tetramer formation and enzymatic activity, and decreases its nuclear localization. By downregulating glucose consumption and lactate production, PKM2 pS333 attenuates the Warburg effect. Through mouse xenograft assays, we demonstrate that the phospho-deficient PKM2-S333A mutant promotes tumor growthin vivo.In conclusion, we identified a ULK1-PKM2-c-Myc axis in inhibiting breast cancer, and a glucose-sensitive phosphorylation of PKM2 in modulating the Warburg effect.
Characterization of Novel Human β-glucocerebrosidase Antibodies for Parkinson Disease Research
Authors: Jong Tiffany , Gehrlein Alexandra , Sidransky Ellen , Jagasia Ravi , Chen Yu 
Published: September 2023

AbstractBACKGROUNDMutations inGBA1, which encodes the lysosome enzyme β-glucocerebrosidase (also referred to as acid β-glucosidase or GCase), are the most common genetic risk factor for Parkinson disease (PD) and dementia with Lewy bodies (DLB). Evidence also suggests that loss of GCase activity is implicated in PD withoutGBA1mutations. Consequently, therapies targeting GCase are actively being pursued as potential strategies to modify the progression of PD and related synucleinopathies. Despite this significant interest in GCase as a therapeutic target, the lack of well-characterized GCase antibodies continues to impede progress in the development of GCase-targeted therapies.OBJECTIVEThis study aims to independently evaluate human GCase (hGCase) antibodies to provide recommendations for western blot, immunofluorescence, immunoprecipitation, and AlphaLISA (Amplified Luminescent Proximity Homogeneous Assay) assays.METHODSTwo mouse monoclonal antibodies, hGCase-1/17 and hGCase-1/23, were raised against hGCase using imiglucerase, the recombinant enzyme used to treat patients, as the antigen. These novel antibodies, alongside commonly used antibodies in the field, underwent evaluation in a variety of assays.RESULTSThe characterization of hGCase-1/17 and hGCase-1/23 using genetic models includingGBA1loss-of-function human neuroglioma H4 line and neurons differentiated from human embryonic stem cells (hESCs) revealed their remarkable specificity and potency in immunofluorescence and immunoprecipitation assays. Furthermore, a hGCase AlphaLISA assay with excellent sensitivity, a broad dynamic range, and suitability for high throughput applications was developed using hGCase-1/17 and hGCase-1/23, which enabled a sandwich assay configuration.CONCLUSIONSThe hGCase immunofluorescence, immunoprecipitation, and AlphaLISA assays utilizing hGCase-1/17 and hGCase-1/23 will not only facilitate improved investigations of hGCase biology, but can also serve as tools to assess the distribution and effectiveness of GCase-targeted therapies for PD and related synucleinopathies.
Protocol and rationale for the International PANS Registry (IPR; pediatric acute onset neuropsychiatric syndrome)
Authors: Masterson Erin E. , Gavin Jessica M. 
Published: September 2023

AbstractThe International PANS Registry (IPR) is the first centralized, epidemiologic database of children with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and PANS-like features and their siblings. PANS is a relatively new umbrella syndrome that lacks diagnostic biomarkers and is characterized by a set of working criteria. The failure to find a diagnostic biomarker is likely due to underpowered studies and inherent biological heterogeneity within PANS. Until the IPR was established, a critical barrier to large-scale longitudinal studies had been the absence of a large-scale epidemiologic study and a centralized database of children with PANS and PANS-like features. The IPR was created to serve as a translational health tool to accelerate research on the broad spectrum of complex pediatric neuroimmune conditions with the long-term goal of enabling a paradigm shift in this field from symptom-based evaluation and treatment towards biology-based diagnoses, treatments, screening, and surveillance. To date, the IPR has registered 1,666 families (3,247 children) and is the largest database in the world that gathers in-depth information on children with PANS and PANS-like features and their siblings. Enrollment in the IPR is open and ongoing; longitudinal follow up is planned. Participating families enroll their children with PANS and PANS-like features and their healthy siblings in the IPR via an online survey platform. The selection criteria for IPR enrollment are intentionally less restrictive than the current working criteria for PANS to generate a large recruitment pool and enable study of the broad spectrum of PANS-like conditions. The IPR is designed to enable ancillary study recruitment based on detailed selection criteria and to grow and expand in scope in the future. The IPR team is committed to data sharing and invites collaborators who will leverage existing data from the IPR database and extend knowledge in an area beyond the original scope of the IPR.
Status of Soil-Transmitted Helminthiasis Among Adolescents in Anaocha Local Government Area, Anambra State, Nigeria: Prevalence, Associated Factors, and Future Directions After a Decade of Ongoing Mass Administration of Medicines
Authors: Aribodor Ogechukwu B. , Jacob Eunice C. , Azugo Nwadiuto O. , Ngenegbo Uche C. , Obika Ifeanyi , Obikwelu Emmanuel M. , Nebe Obiageli J. 
Published: September 2023

ABSTRACTOver the past decade, Anambra State, Nigeria, has implemented mass administration of medicines (MAMs) to combat soil-transmitted helminthiasis (STH), a significant public health challenge in low-income regions. Nevertheless, these efforts have predominantly focused on pre-school and school-aged children, leaving a notable gap in understanding STH infection rates and the efficacy of these campaigns among secondary school adolescents, who have been excluded from this initiative. Our study aimed to address this critical knowledge gap by assessing soil-transmitted helminthiasis (STH) prevalence and contextual factors hindering effective control among adolescents in Anambra State, Nigeria. We actively engaged 443 adolescents with a mean age of 14 years in a school-based cross-sectional study in selected communities within the Anaocha Local Government Area from 8 February to 7 July 2023 following informed consent and assent procedures. Employing a stratified random sampling technique, we collected demographic data and assessed STH risk factors using a structured questionnaire hosted on the Kobo Toolbox platform. For quantitative analysis of STH infections, the Kato-Katz technique was used. Analysis was performed using SPSS version 25, incorporating descriptive statistics and multinomial logistic regression, with statistical significance set at p<0.05. Of the 443 (213 males (48.0%) and 230 females (52.0%) adolescents studied, the overall prevalence of STH observed was 35.2% (156/443).Ascaris lumbricoideswas the prevalent STH species (16.9%), followed byTrichuris trichiura(1.4%) and hookworm (0.5%). Only light-intensity infection was observed. Mixed infections were observed in 16.5% of adolescents, involvingA. lumbricoidesand hookworm (10.8%), followed byA. lumbricoidesandT. trichiura(3.2%) and all three STH (2.5%). The observed overall prevalence was not statistically significant with respect to gender (OR: 0.961; 95% CI: 0.651-1.420; p > 0.05) or age (OR: 0.686; 95% CI: 0.459-1.025; p>0.05). Class (grade level) (OR = 1.75, 95% CI: 1.25 - 2.45, p = 0.003), knowledge and transmission of STH infection (OR = 0.60, 95% CI: 0.42 - 0.86, p = 0.008), parental occupation (OR = 1.90, 95% CI: 1.35 - 2.67, p < 0.001), parents’ literacy level (OR = 0.68, 95% CI: 0.48 - 0.96, p = 0.027), and the type of toilet (OR = 2.15, 95% CI: 1.54 - 3.00, p < 0.001) were all significantly correlated with STH infection. These findings highlight the role of adolescents in sustaining soil-transmitted helminthiasis (STH) transmission. Coupled with school-based deworming expansion, innovative improvements in water, sanitation, hygiene, and awareness can provide a cost-effective, sustainable solution for combatting STH infections in Anambra State.
Global, regional, and national levels and trends in burden of urticaria: a systematic analysis for the global burden of disease 2019 study
Authors: Pu Yuanchun , He Liyu , Wang Xiangyu , Zhang Yaodong , Zhao Shidi , Fan Jinhai 
Published: September 2023

AbstractBackgroundUrticaria causes a significant burden on individuals and society due to its pervasiveness. The aim of this study was to evaluate the burden of urticaria in different regions and nations by analyzing data from the Global Burden of Disease Study 2019 (GBD 2019) to provide a reference for healthcare policymakers.MethodsUsing the GBD 2019 database, this study analyzed incidence, prevalence, disability-adjusted life year (DALY), and corresponding ASRs and EAPC globally and in 204 countries and regions, and stratified the data by age, sex, and sociodemographic index (SDI).ResultsIn 2019, the global incidence cases of urticaria increased to 114708912.2, the prevalence cases increased to 65139886.6, and the global DALY burden increased to 3898838.6. The distribution of the burden was markedly geographically heterogeneous. Burden indicators were generally higher in females than in males. There was a slight positive correlation between urticaria burden and regional SDI.InterpretationThe burden of urticaria has been increasing globally from 1990 to 2019. This study identified multiple determinants that influence the burden of urticaria, such as geographic location and SDI. Despite the limitations of the GBD 2019 data, these discoveries provide a valuable resource for the development of future public health strategies aimed at reducing the burden of urticaria.
Stasis Imaging Predicts the Risk of Cardioembolic Stroke Related to Acute Myocardial Infarction
Authors: Rodríguez-González Elena , Martínez-Legazpi Pablo , Mombiela Teresa , González-Mansilla Ana , Delgado-Montero Antonia , Guzmán-De-Villoria Juan A. , Díaz-Otero Fernando , Prieto-Arévalo Raquel , Juárez Miriam , García del Rey Maria del Carmen , Fernández-García Pilar , Flores Oscar , Postigo Andrea , Yotti Raquel , García-Villalba Manuel , Fernández-Avilés Francisco , del Álamo Juan C , Bermejo Javier 
Published: September 2023

AbstractBackgroundIn the setting of ST-segment elevation myocardial infarction (STEMI), imaging-based biomarkers could be useful for guiding oral anticoagulation for primary prevention of stroke.ObjectivesTo test the efficacy of intraventricular blood stasis imaging for predicting a composite primary endpoint of cardioembolic risk during the first 6 months after STEMI.MethodsThe Imaging Silent Brain Infarct in Acute Myocardial Infarction (ISBITAMI,NCT02917213) was a prospective clinical study including patients with a first STEMI, an EF ≤ 45% and without atrial fibrillation. Patients underwent ultrasound-based stasis imaging at enrollment followed by heart and brain magnetic resonance at 1-week and at 6-month visits. From the stasis maps, we calculated the average residence time,RT, of blood inside the LV and assessed its performance to predict the primary endpoint. Apical longitudinal strain was quantified by speckle tracking.ResultsA total of 68 patients were univocally assigned to the primary endpoint. Of them, 19 patients suffered one or more events: 3 strokes, 5 silent brain infarctions, and 15 mural thromboses. No systemic embolisms were observed.RT(OR: 3.28, 95% CI: 1.61-6.67, p=0.001) and apical strain (OR: 1.48, 95% CI: 1.14-1.92, p= 0.002) showed complementary prognostic value. The bivariate model showed a c-index= 0.84 (0.73-0.95) a negative predictive value of 1.00 (0.93-1.00) and positive predictive value of 0.45 (0.39 - 0.80). Results were confirmed in a multiple imputation sensitivity analysis. Conventional ultrasound-based metrics were of limited predictive value.ConclusionsIn patients with STEMI and LV systolic dysfunction in sinus rhythm, the risk of cardioembolic stroke can be accurately predicted by echocardiography combining stasis and strain imaging.
Accurate bacterial outbreak tracing with Oxford Nanopore sequencing and reduction of methylation-induced errors
Authors: Lohde Mara , Wagner Gabriel E. , Dabernig-Heinz Johanna , Viehweger Adrian , Braun Sascha D. , Monecke Stefan , Diezel Celia , Stein Claudia , Marquet Mike , Ehricht Ralf , Pletz Mathias W. , Brandt Christian 
Published: September 2023

AbstractOur study investigated the effectiveness of Oxford Nanopore Technologies for accurate outbreak tracing by resequencing 33 isolates of a three-year-longKlebsiella pneumoniaeoutbreak with Illumina short read sequencing data as the point of reference.We detected considerable base errors through cgMLST and phylogenetic analysis of genomes sequenced with Oxford Nanopore Technologies, leading to the false exclusion of some outbreak-related strains from the outbreak cluster. Nearby methylation sites cause these errors and can also be found in other species besidesK. pneumoniae. Based on this data, we explored PCR-based sequencing and a masking strategy, which both successfully addressed these inaccuracies and ensured accurate outbreak tracing. We offer our masking strategy as a bioinformatic workflow (MPOA is freely available on GitHub under the GNUv3 license:github.com/replikation/MPOA) to identify and mask problematic genome positions in a reference-free manner.Our research highlights limitations in using Oxford Nanopore Technologies for sequencing prokaryotic organisms, especially for investing outbreaks. For time-critical projects that cannot wait for further technological developments by Oxford Nanopore Technologies, our study recommends either PCR-based sequencing or using our provided bioinformatic workflow. We would advise that read mapping-based quality control of genomes should be provided when publishing results.
Molecular pathways and cellular subsets associated with adverse clinical outcomes in overlapping immune-related myocarditis and myositis
Authors: Siddiqui Bilal A. , Palaskas Nicolas L. , Basu Sreyashi , Dai Yibo , He Zhong , Yadav Shalini S. , Allison James P. , Sheth Rahul , Tummala Sudhakar , Buja L. Maximilian , Bhattacharjee Meenakshi , Iliescu Cezar A. , Rawther-Karedath Anishia , Deswal Anita , Wang Linghua , Sharma Padmanee , Subudhi Sumit K. 
Published: September 2023

AbstractImmune checkpoint therapies (ICTs) can induce life-threatening immune-related adverse events, including myocarditis and myositis, which are rare but often concurrent. The molecular pathways and immune subsets underlying these toxicities remain poorly understood. To address this need, we obtained heart and skeletal muscle biopsies for single-cell RNA sequencing in living patients with cancers treated with ICTs admitted to the hospital with myocarditis and /or myositis (overlapping myocarditis plus myositis, n=10; myocarditis-only, n=1) compared to ICT-exposed patients ruled out for toxicity utilized as controls (n=9) within 96 hours of clinical presentation. Analyses of 58,523 cells revealed clonally expanded CD8+T cells with a cytotoxic phenotype expressing activation/exhaustion markers in both myocarditis and myositis. Furthermore, the analyses identified a population of tissue-resident myeloid cells expressed FcγRIIIa, which is known to bind IgG and regulate complement activation. Immunohistochemistry of affected cardiac and skeletal muscle tissues revealed protein expression of pan-IgG and complement product C4d that were associated with the presence of high-titer serum autoantibodies against muscle antigens in a subset of patients. We further identified a population of inflammatory IL-1B+TNF+myeloid cells specifically enriched in myocarditis and associated with greater toxicity severity and poorer clinical outcomes. These results are the first to recognize these myeloid subsets in human immune-related myocarditis and myositis tissues and nominate new targets for investigation into rational treatments to overcome these high-mortality toxicities.Graphical Abstract
A cerebellar disinhibitory circuit supports synaptic plasticity
Authors: Park Changjoo , Gim Jawon , Bahn Sangkyu , Kim Gyu Hyun , Im Yoonseok , Lee Sang-Hoon , Lee Kisuk , Kim Min-Soo , Lee Kea Joo , Kim Jinseop S. 
Published: September 2023

AbstractHow does the cerebellum learn how to control motion? The cerebellar motor learning critically depends on the long-term depression of the synapses between granule cells and Purkinje cells, which encode motor commands and inhibitory modifications to motor outputs, respectively, for simultaneous granule cell inputs and climbing fibre inputs, the latter of which encode the error signals1–3. However, recent studies have revealed that inhibitory inputs to Purkinje cells may disrupt long-term depression4–8, and it is not clear how long-term depression can occur without disruption. In search of a clue, we investigated the synaptic connectivity among the neurons reconstructed from serial electron microscopy images of the cerebellar molecular layer9,10. We discovered synapses between climbing fibres and a subset of inhibitory interneurons, which synapse onto the remaining interneurons, which in turn synapse onto Purkinje cells. Such connectivity redefines the interneuron types, which have been defined morphologically or molecularly11–13. Together with climbing fibres to Purkinje cell connections, those cell types form a feedforward disinhibitory circuit14. We argued that this circuit secures long-term depression by suppressing inhibition whenever climbing fibre input is provided and long-term depression needs to occur15, and we validated the hypothesis through a computational model. This finding implies a general principle of circuit mechanism in which disinhibition supports synaptic plasticity16,17.
SACNet: A Multiscale Diffeomorphic Convolutional Registration Network with Prior Neuroanatomical Constraints for Flexible Susceptibility Artifact Correction in Echo Planar Imaging
Authors: Zeng Zilong , Zhang Jiaying , Liang Xinyuan , Sun Lianglong , Zhang Yihe , Men Weiwei , Wang Yanpei , Chen Rui , Zhang Haibo , Tan Shuping , Gao Jia-Hong , Qin Shaozheng , Tong Qiqi , He Hongjian , Tao Sha , Dong Qi , He Yong , Zhao Tengda 
Published: September 2023

AbstractSusceptibility artifacts (SAs), inevitable in brain diffusion MR (dMRI) scans acquired using single-shot echo planar imaging (EPI), severely compromise the accurate detection of human brain structure. Existing SA correction (SAC) methods offer inadequate correction quality and limited applicability across diverse datasets with varied acquisition protocols. To address these challenges, we proposed SACNet, a SAC framework based on unsupervised registration convolutional networks, featuring: i) a novel diffeomorphism regularization function to avoid unnatural SAC warps, modified from a potential well function; ii) an integration with prior neuroanatomical constraints and coarse-to-fine processing strategy to enables multi-scale geometric and intensity recoveries in severe distorted areas; iii) a unified registration framework that incorporates multiple phase-encoding (PE) EPI images and structural images, ensuring compatibility with both single- and inverse-PE protocols, with or without field maps. Utilizing simulated dMRI images and over 2000 brain scans from neonatal, child, adult and traveling participants, our method consistently demonstrates state-of-the-art correction performance. Notably, SACNet effectively reduces SAs-related multicenter effects compared to existing methods. We have developed user-friendly tools using containerization techniques, hope to facilitate SAC correction quality across extensive neuroimaging studies.