bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leptospiraseroprevalence in dogs, cats and horses: the effect of cross-reactivity between serovars and vaccination status on seroprevalence estimates
Authors: McCreight Kellie A. , Barbosa Liana N. , Agricola Odoi , Reed Porsha , Rajeev Sreekumari 
Published: April 2024

AbstractIn this study, we estimated theLeptospiraseroprevalence in dogs (n = 376), horses (n = 88), and cats (n = 169) using Microscopic Agglutination Test (MAT) against 12Leptospiraserovars. We observed aLeptospiraseroprevalence of 29.41%, 47.73%, and 12.35% in dogs, horses, and cats, respectively. The highest seroprevalence was observed for serovar Autumnalis (74.55%) in dogs, and Bratislava in horses (95.24%) and cats (42.86%). We found a significant level of potential cross-reactivity between multipleLeptospiraserovars tested, with highest cross-reactivity to serovar Autumnalis in dogs. The dogs that were vaccinated againstLeptospirahad a significantly higher seroprevalence (45.92%) compared to unvaccinated dogs (16.28%; p < 0.001). A significant difference in seroprevalence was observed in vaccinated and unvaccinated dogs to all four serovars included in the canine vaccine (p < 0.001). Among the diagnostic samples submitted from 2021-2023, 40% (103/252) of the canine serum samples were positive by MAT, with the highest positivity rate for the serovar Autumnalis. OnLeptospiraPCR, 10.7 % (35/325) urine samples and 5.8% (15/257) blood samples were positive. Our study findings show evidence ofLeptospiraexposure and potential disease in the study area. The cross-reactivity between theLeptospiraserovars used in the MAT and vaccination status may also overestimate the levels of exposure.
Mosquito Tissue Ultrastructure-Expansion Microscopy (MoTissU-ExM) enables ultrastructural and anatomical analysis of malaria parasites and their mosquito
Authors: Liffner Benjamin , Alves e Silva Thiago Luiz , Vega-Rodriguez Joel , Absalon Sabrina 
Published: April 2024

AbstractStudy of malaria parasite cell biology is challenged by their small size, which can make visualisation of individual organelles difficult or impossible using conventional light microscopy. In recent years, the ﬁeld has attempted to overcome this challenge through the application of ultrastructure expansion microscopy (U-ExM), which physically expands a biological sample approximately 4.5-fold. To date, U-ExM has mostly been used to visualise blood-stage parasites and used exclusively on parasitesin vitro. Here we developMosquitoTissueU-ExM(MoTissU-ExM), a method for preparing dissected mosquito salivary glands and midguts by U-ExM. MoTissU-ExM preserves both host and parasite ultrastructure, enabling visualisation of oocysts and sporozoitesin situ. We validate that MoTissU-ExM samples expand as expected, provide a direct comparison of the same dissected tissues before and after MoTissU-ExM, and highlight some of the key host and parasite structures that can be visualised following MoTissU-ExM. Finally, we provide a point-by-point protocol for how to perform MoTissU-ExM, along with details on how best to image the expanded tissues, and how to troubleshoot common issues.
Dynamic Formation of the Protein-Lipid Pre-fusion Complex
Authors: Bykhovskaia Maria 
Published: April 2024

AbstractSynaptic vesicles (SVs) fuse with the presynaptic membrane (PM) to release neuronal transmitters. The SV protein Synaptotagmin 1 (Syt1) serves as a Ca2+sensor for evoked fusion. Syt1 is thought to trigger fusion by penetrating into PM upon Ca2+binding, however the mechanistic detail of this process is still debated. Syt1 interacts with the SNARE complex, a coiled-coil four-helical bundle that enables the SV-PM attachment. The SNARE-associated protein Complexin (Cpx) promotes the Ca2+-dependent fusion, possibly interacting with Syt1. We employed all-atom molecular dynamics (MD) to investigate the formation of the Syt1-SNARE-Cpx complex interacting with the lipid bilayers of PM and SV. Our simulations demonstrated that the PM-Syt1-SNARE-Cpx complex can transition to a “dead-end” state, wherein Syt1 attaches tightly to PM but does not immerse into it, as opposed to a pre-fusion state, which has the tips of the Ca2+-bound C2 domains of Syt1 inserted into PM. Our simulations unraveled the sequence of Syt1 conformational transitions, including the simultaneous Syt1 docking to the SNARE-Cpx bundle and PM, followed by the Ca2+chelation and the penetration of the tips of Syt1 domains into PM, leading to the pre-fusion state of the protein-lipid complex. Importantly, we found that the direct Syt1-Cpx interactions are required to promote these transitions. Thus, we developed the all-atom dynamic model of the conformational transitions that lead to the formation of the pre-fusion PM-Syt1-SNARE-Cpx complex. Our simulations also revealed an alternative “dead-end” state of the protein-lipid complex that can be formed if this pathway is disrupted.Statement of SignificanceNeurons communicate by releasing transmitter molecules. Transmitters are packed in synaptic vesicles (SVs) and released by the fusion of SVs with the presynaptic membrane (PM). This process is regulated by a dynamic complex of fusion proteins, including the coil-coiled SNARE bundle that attaches SV to PM, Synaptotagmin that serves as a Ca2+sensor for the release process, and Complexin that attaches to the SNARE bundle and promotes the Ca2+-dependent release. To understand how these proteins interact dynamically with the lipid bilayers of SV and PM, we employed molecular dynamics, a computational approach that enables simulating the behavior of proteins and lipids at the atomistic resolution. Our simulations enabled us to delineate the stages of the formation of prefusion protein-lipid complex.
Expected reward value and reward prediction errors reinforce but also interfere with human time perception
Authors: DiMarco Emily K. , Shipp Ashley Ratcliffe , Kishida Kenneth T. 
Published: April 2024

AbstractTime perception is often investigated in animal models and in humans using instrumental paradigms where reinforcement learning (RL) and associated dopaminergic processes have modulatory effects. For example, interval timing, which includes the judgment of relatively short intervals of time (ranging from milliseconds to minutes), has been shown to be modulated by manipulations of striatal dopamine. The ‘expected value of reward’ (EV) and ‘reward prediction errors’ (RPEs) are key variables described in RL-theory that explain dopaminergic signals during reward processing during instrumental learning. Notably, the underlying connection between RL-processes and time perception in humans is relatively underexplored. Herein, we investigated the impact of EV and RPEs on interval timing in humans. We tested the hypotheses that EV and RPEs modulate the experience of short time intervals. We demonstrate that expectations of monetary gains or losses increases the initial performance error for 1000ms intervals. Temporal learning over repeated trials is observed with accelerated learning of non-reinforced 1000ms intervals; however, RPEs – specifically about rewards and not punishments – appear to reinforce performance errors, which effectively interferes with the rate at which (reinforced) 1000ms intervals were learned. These effects were not significant for 3000ms and 5000ms intervals. Our results demonstrate that EV and RPEs influence human behavior about 1000ms time intervals. We discuss our results considering model-free ‘temporal difference RL-theory’, which suggests the hypothesis that interval timing may be mediated by dopaminergic signals that reinforce the learning and prediction of dynamic state-transitions which could be encoded without an explicit reference to ‘time’ intervals.
CRISPR knockout genome-wide screens identify the HELQ-RAD52 axis in regulating the repair of cisplatin-induced single stranded DNA gaps
Authors: Pale Lindsey M. , Khatib Jude B. , Nicolae Claudia M. , Moldovan George-Lucian 
Published: April 2024

AbstractTreatment with genotoxic agents, such as platinum compounds, is still the mainstay therapeutical approach for the majority of cancers. Our understanding of the mechanisms of action of these drugs is however imperfect, and continuously evolving. Recent advances in the field highlighted single stranded DNA (ssDNA) gap accumulation as a potential determinant underlying cisplatin chemosensitivity, at least in some genetic backgrounds, such as BRCA mutations. Cisplatin-induced ssDNA gaps form upon the arrest of replication forks at sites of cisplatin adducts, and restart of DNA synthesis downstream of the lesion through repriming catalyzed by the PRIMPOL enzyme. Here, we show that PRIMPOL overexpression in otherwise wildtype cells results in accumulation of cisplatin-induced ssDNA gaps without sensitizing cells to cisplatin, suggesting that ssDNA gap accumulation does not confer cisplatin sensitivity in BRCA-proficient cells. To understand how ssDNA gaps may cause cellular sensitivity, we employed CRISPR-mediated genome-wide genetic screening to identify factors which enable the cytotoxicity of cisplatin-induced ssDNA gaps. We found that the helicase HELQ specifically suppresses cisplatin sensitivity in PRIMPOL-overexpressing cells, and this is associated with reduced ssDNA accumulation. We moreover identify RAD52 as a mediator of this pathway, and show that RAD52 promotes ssDNA gap accumulation through a BRCA-mediated mechanism. Our work identified the HELQ-RAD52-BRCA axis as a regulator of ssDNA gap processing, shedding light on the mechanisms of cisplatin sensitization in cancer therapy.
Sickness behaviour within cleaning interactions
Authors: Marquês Tânia , Pereira Beatriz , Marques Mélanie , Repolho Tiago , Paula José Ricardo 
Published: April 2024

AbstractWhen facing diseases, strategies such as social distancing have proven effective in preventing disease spread. Cleaning interactions are social interactions where cleaner organisms remove ectoparasites from clients. These interactions can be potential vectors of infectious diseases in reef fishes. Here, we aimed to determine if cleaner wrasses (Labroides dimidiatus) employ social distancing and other behavioural tactics to prevent disease spread within the context of cleaning interactions. To this end, we used bacterial lipopolysaccharides (LPS) immunostimulation to induce “sickness” behaviour in cleaners. After LPS injection, we performed four behavioural trials: social preference (from cleaner and client perspectives), social interaction, and bystander cooperativeness tests. In the social preference test, LPS-injected cleaners showed lower activity rates but no change in their social preference. However, some clients preferred “sick” cleaners. Contrarily, during the social interaction test, cleaners reduced the number of interactions, despite clients’ willingness to interact. For the bystander test, LPS-injected cleaners were unable to adjust their behaviour to be more cooperative. Reduced activity levels revealed lethargy, which may lead to passive self-isolation, allowing for some social distancing of healthy individuals. This suggests that immune-stimulated cleaners undergo changes in their behaviour which can be viewed as a passive social distancing preventing disease spread.
Purifying selection and intraspecies recombination may drive the speciation in Crassostrea: evidence from complete mitochondria sequence ofCrassostrea hongkongensisand comparative genomic analysis
Authors: Sahu Basanta Pravas , Fazil Mohamed Madhar , Panda Subhasmita , Thiyagarajan Vengatesen 
Published: April 2024

AbstractRepeat dynamics and recombination play a crucial role during the evolution of the mitochondrial genome in plants and animals. However, this phenomenon has got less attention within Crassostrea, a complex marine species found worldwide having high commercial value as well as efficient carbon neutralizer. During this study, we characterized the whole mitochondrial genomes ofC. hongkongensisretrieved from transcriptome data (GenBank acc. no. MZ073671). The current mitochondrial genome (18,616 bp) was composed of a non-coding control region (D-loop region), 2 ribosomal RNA (rRNA genes), 12 protein-coding genes (PCGs), and 23 transfer RNA (tRNA). Furthermore, comparative genomics analysis revealed that the present isolate is closely related to the Chinese isolate (NC_011518) with 99.82% similarity. Microsatellite analysis within the mitochondrial genome revealed its bias towards mononucleotide repeat A/T, di-nucleotide AG followed by AT and AC, trinucleotide AAT followed by AAG, ATC, and ATG. The recombination analysis deciphered the lack of interspecific recombination, but the presence of intraspecific recombination within ND1, ND2, and ND4L of Crassostrea species. Selection pressure analysis revealed the presence of purifying selection within maximum genes which drive the evolution of the species.
Harmonization of the fastest and densest responses embodies the humanlike reaction time of mice
Authors: Kim Chan Hee 
Published: April 2024

AbstractReaction time (RT) is important in evaluating delayed latency in behavior. Unlike that of humans, the RT of animals, in which the stimulus–response relationship is not one-to-one due to repeated responses per trial, may exhibit two peaks of the fastest and densest responses in a distribution of responses. We determined whether the two peak latencies are aligned for a single RT by controlling stimulus duration. In delay conditioning with mice using sound cues of 10, 5, and 2s, the 2s group exhibited the strongest positive correlations between the two peaks, as well as responses’ number and accuracy rate, suggesting coupling of the fastest and densest responses, and a one-to-one relationship between stimulus and response, respectively. We propose the use of harmonization of the two peaks, elicited by stimuli that induce minimal responses, as a criterion for designing animal experiments to mimic humanlike RT.
Selective attention and sensitivity to auditory disturbances in a virtually-real Classroom: Comparison of adults with and without AD(H)D
Authors: Levy Orel , Libman Hackmon Shirley , Zvilichovsky Yair , Korisky Adi , Bidet-Caulet Aurelie , Schweitzer Julie B. , Zion Golumbic Elana 
Published: April 2024

AbstractMany people, and particularly individuals with Attention Deficit (Hyperactivity) Disorder (AD(H)D), find it difficult to maintain attention during classroom learning. However, traditional paradigms used to evaluate attention do not capture the complexity and dynamic nature of real-life classrooms. Using a novel Virtual Reality platform, coupled with measurement of neural activity, eye-gaze and skin conductance, here we studied the neurophysiological manifestations of attention and distractibility, under realistic learning conditions. Individuals with AD(H)D exhibited higher neural responses to irrelevant sounds and reduced speech tracking of the teacher, relative to controls. Additional neurophysiological measures, such the power of alpha-oscillations and frequency of gaze-shifts away from the teacher, contributed to explaining variance in self-reported AD(H)D symptoms across the sample. These ecologically-valid findings provide critical insight into the neurophysiological mechanisms underlying individual differences in the capacity for sustained attention and the proneness to distraction and mind-wandering, experienced in real-life situations.
scCaT: an explainable capsulating architecture for sepsis diagnosis transferring from single-cell RNA sequencing
Authors: Zheng Xubin , Meng Dian , Chen Duo , Wong Wan-Ki , To Ka-Ho , Zhu Lei , Wu JiaFei , Liang Yining , Leung Kwong-Sak , Wong Man-Hon , Cheng Lixin 
Published: April 2024

AbstractSepsis is a life-threatening condition characterized by an exaggerated immune response to pathogens, leading to organ damage and high mortality rates in the intensive care unit. Although deep learning has achieved impressive performance on prediction and classification tasks in medicine, it requires large amounts of data and lacks explainability, which hinder its application to sepsis diagnosis. We introduce a deep learning framework, called scCaT, which blends the capsulating architecture with Transformer to develop a sepsis diagnostic model using single-cell RNA sequencing data and transfers it to bulk RNA data. The capsulating architecture effectively groups genes into capsules based on biological functions, which provides explainability in encoding gene expressions. The Transformer serves as a decoder to classify sepsis patients and controls. Our model achieves high accuracy with an AUROC of 0.93 on the single-cell test set and an average AUROC of 0.98 on seven bulk RNA cohorts. Additionally, the capsules can recognize different cell types and distinguish sepsis from control samples based on their biological pathways. This study presents a novel approach for learning gene modules and transferring the model to other data types, offering potential benefits in diagnosing rare diseases with limited subjects.Author summaryDeep learning models used in disease diagnosis usually suffer from insufficient data for training and the lack of explainability, especially in rare diseases. These shortages hinder their application to sepsis diagnosis. Here we propose a diagnostic framework name scCaT(https://github.com/Kimxbzheng/CaT), which transfers knowledge learned from single-cell RNA-seq, for diseases with insufficient bulk data. The framework uses capsulating architecture to group genes into capsules and provide explainability to the deep learning model for sepsis diagnosis. ScCaT achieves robust and outstanding performance for sepsis diagnosis in both scRNA-seq and bulk RNA datasets. This architecture offers potential approaches in diagnosing rare diseases with limited subjects with explainability.
Dental Caries Prevalence and Prevention Behaviour Related Factors among Adolescents in Nigeria: A Systematic Review and Meta-analysis
Authors: Afolabi Adebukunola O. , Ehizele Adebola O. , Nnawuihe Ukachi Chiwendu , Nwaokorie Francisca O. , Nwaozuru Ucheoma , Owotade Foluso , Lusher Joanne , Eleje George Uchenna , Alade Omolola T. , Akinsolu Folahanmi T. , Ezechi Oliver C. , Folayan Morenike O. 
Published: April 2024

AbstractBackgroundAdolescence is a critical period of life that has implications for oral health and wellbeing, however, the oral health profile of adolescents in Nigeria is undocumented. This systematic review and meta-analysis determined the prevalence of caries and identified the caries prevention behaviours among adolescents in Nigeria.MethodsIn August 2023, a literature search was conducted across PubMed, Google Scholar, Academic Info, Cochrane and Refseek databases to identify studies on dental caries prevalence and caries prevention behaviour among adolescents aged 10 to 19 years in Nigeria. Two reviewers used an independent and double-blind approach to extract data, with discrepancies resolved by a third reviewer. Heterogeneity was assessed using I2percentages, and a funnel plot was constructed to assess the potential for publication bias. The meta-analysis employed a random effects model to ascertain the prevalence of dental caries. Subgroup analysis was conducted to explore the variation in caries prevalence by sex. The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework guidelines while the Joanna Briggs Institute Critical Appraisal Checklist was used to critically appraise the quality and integrity of the included studies. Registration of this systematic review was completed on PROSPERO CRD42024458849.ResultsSixteen studies met the eligibility criteria. The pooled caries prevalence among adolescents in Nigeria was 23.0% (95% CI: 16, 30) with a pooled prevalence of 16.0% (p < 0.00001, 95% CI: 9 - 23) for males, and a pooled prevalence of 22.0% (p < 0.00001, 95% CI= 11 - 32) for females. The commonest caries prevention practices reported were daily tooth brushing, use of fluoride containing toothpastes and dental service utilization. Factors associated with caries among adolescents were a history of dental service utilization, poor oral hygiene practices and consumption of refined carbohydrates in-between-meals.ConclusionThe high prevalence of dental caries among adolescents in Nigeria warrants programmatic attention with an emphasis on improving oral hygiene practices and controlling the consumption of refined carbohydrates in-between-meals. Dental service utilization for caries prevention needs to be encouraged.
Improved Lymphangiogenesis around Vascularized Lymph Node Flaps by Periodic Injection of Hyaluronidase in a Rodent Model
Authors: Cheon Hwayeong , Chen Linhai , Kim Sang-Ah , Gelvosa Ma Nessa , Hong Joon Pio , Jeon Jae Yong , Suh Hyunsuk Peter 
Published: April 2024

AbstractBackgroundVascularized lymph node transfer (VLNT) is an advanced surgical approach for secondary lymphedema (SLE) treatment, but tissue fibrosis around the lymph node flap (VLNF) inhibiting lymphangiogenesis is the biggest challenge undermining its therapeutic efficacy. Hyaluronidase (HLD), which is an enzyme that breaks down hyaluronic acid, may have the efficacy of reducing fibrosis and increasing the chance of lymphangiogenesis in the injury site.Materials and methods52 Sprague–Dawley rats with VLNF were divided into a group injected periodically with HLD and a control group and followed up. A follow-up study was performed for 13 weeks starting 1 week after model formation was examined. The limb volume and dermal backflow pattern were observed to evaluate the degree of lymphedema. The real-time ICG fluorescence intensity changes were measured to evaluate the degree of lymphatic drainage to the flap. Lastly, the number of regenerative lymphatic vessels and the degree of fibrosis were investigated.ResultsIn the group injected with HLD periodically (VLNF+HLD group), swelling reduction and dermal backflow pattern recovery occurred rapidly in the 3rd week of follow-up compared to the only VLNF group. Moreover, the efficiency of lymphatic drainage into the flap was also improved in the VLNF+HLD group. They significantly had more newly formed lymphatic vessels along with a decrease in collagen fiber decomposition in the tissue around the VLNF by up to 26%.ConclusionThese encouraging results pave the way for developing a combination strategy for SLE treatment involving HLD and VLNT. Furthermore, this finding may guide future research on the development of new drugs that could enhance the efficacy of VLNT surgery for SLE patients.Graphic abstract