bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Machine Learning Models for Aqueous Solubility Prediction in Drug Discovery
Authors: Xue Nian , Zhang Yuzhu , Liu Sensen 
Published: June 2024

AbstractDetermining the aqueous solubility of the chemical compound is of great importancein-silicodrug discovery. However, correctly and rapidly predicting the aqueous solubility remains a challenging task. This paper explores and evaluates the predictability of multiple machine learning models in the aqueous solubility of compounds. Specifically, we apply a series of machine learning algorithms, including Random Forest, XG-Boost, LightGBM, and CatBoost, on a well-established aqueous solubility dataset (i. e., the Huuskonen dataset) of over 1200 compounds. Experimental results show that even traditional machine learning algorithms can achieve satisfactory performance with high accuracy. In addition, our investigation goes beyond mere prediction accuracy, delving into the interpretability of models to identify key features and understand the molecular properties that influence the predicted outcomes. This study sheds light on the ability to use machine learning approaches to predict compound solubility, significantly shortening the time that researchers spend on new drug discovery.
Atrioventricular nodal reentrant tachycardia onset, sustainability, and spontaneous termination in rabbit atrioventricular node model with autonomic nervous system control
Authors: Ryzhii Maxim , Ryzhii Elena 
Published: June 2024

ABSTRACTAtrioventricular nodal reentrant tachycardia (AVNRT) is one of the most common types of paroxysmal supraventricular tachycardia. The autonomic nervous system (ANS) activity is known to affect sudden episodes of AVNRT, but the detailed underlying mechanism is not fully understood. In this work, we update our recent compact multifunctional model of the rabbit atrioventricular node (AV) with ANS control to simulate AVNRT. The refractoriness of model cells is modulated by one ANS coefficient, causing a change in the effective refractory periods, conduction delays, and intrinsic frequency of pacemaker cells. Using the model, we examine the onset, sustainability, and spontaneous termination of typical slow-fast and atypical fast-slow forms of AVNRT under ANS modulation. The conditions for the onset and sustainability of AVNRT can occur independently of each other in various combinations. Differences in the effective refractory periods of the slow and fast pathways of the AV node during anterograde and retrograde conduction determine the form of AVNRT. For the first time, the possibility of identifying hidden processes occurring inside the AV node using a computer model is shown, allowing us to come closer to understanding the role of ANS control during AVNRT. The results obtained are consistent with clinical and experimental data and represent a new tool for studying the electrophysiological mechanisms of this type of arrhythmia.
Exome Sequencing of 963 Chinese Families Identifies Novel Epilepsy Candidate Genes
Authors: Ma Yu , Su Ke , Zhou Mingshan , Liu Yihan , Lu Guangqin , Wang Jie , Li Chengjie , Wang Tianqi , Li Yingfeng , Zhang Qi , Guan Xia , Han Xiong , Li Wenling , Ren Rongna , Zhong Min , Ding Ding , Jiang Yonghui , Peng Gang , Wang Yi , Wu Qihui , Fan Shaohua 
Published: June 2024

AbstractEpilepsy, a prevalent neurodevelopmental disorder in children, is often accompanied by detrimental psychological consequences and other comorbidities. We performed exome sequencing on 963 patient-parent trios, revealing differences in genetic epidemiology between Chinese and European epilepsy cohorts. The diagnostic yield for known epilepsy genes was 40%. Pathogenic variants were most commonly found in SCN1A, KCNQ2, and DEPDC5. Additionally, we identified 15 novel monogenic epilepsy candidates in at least two patients diagnosed with developmental and epileptic encephalopathy, non-acquired focal epilepsy, or genetic generalized epilepsy, includingADCY2, BCAR3, CDC45, CHRNG, CRTC2, CSMD1, CSMD2, KDM6B, KIF1B, PLEKHM3, PPP4R1, RASGRP2, SGSM2, SYNE1, andZFHX3. Aside fromADCY2, which was implicated in the GABAergic synapse pathway based on KEGG analysis, these candidates do not belong to known epilepsy pathways. Local field potential recordings in zebrafish and calcium imaging experiments validated associations for 11 of these genes, excluding those unsuitable for functional analyses. Furthermore, we found thatCRTC2overexpression leads to hippocampal neuronal hyperactivity using multi-electrode arrays and electrophysiology. We have documented the first-line medications prescribed for patients harboring variants in the novel candidate genes. This study expands our understanding of the genetic underpinnings of epilepsy and provides opportunities for early diagnosis and personalized medicine approaches.
TransferGWAS of T1-weighted Brain MRI Data from the UK Biobank
Authors: Rakowski Alexander , Monti Remo , Lippert Christoph 
Published: June 2024

AbstractGenome-wide association studies (GWAS) traditionally analyze single traits, e.g., disease diagnoses or biomarkers. Nowadays, large-scale cohorts such as the UK Biobank (UKB) collect imaging data with sample sizes large enough to perform genetic association testing. Typical approaches to GWAS on high-dimensional modalities extract predefined features from the data, e.g., volumes of regions of interest. This limits the scope of such studies to predefined traits and can ignore novel patterns present in the data. TransferGWAS employs deep neural networks (DNNs) to extract low-dimensional representations of imaging data for GWAS, eliminating the need for predefined biomarkers. Here, we apply transferGWAS on brain MRI data from the UKB. We encoded 36, 311 T1-weighted brain magnetic resonance imaging (MRI) scans using DNN models trained on MRI scans from the Alzheimer’s Disease Neuroimaging Initiative, and on natural images from the ImageNet dataset, and performed a multivariate GWAS on the resulting features. Furthermore, we fitted polygenic scores (PGS) of the deep features and computed genetic correlations between them and a range of selected phenotypes. We identified 289 independent loci, associated mostly with bone density, brain, or cardiovascular traits, and 14 regions having no previously reported associations. We evaluated the PGS in a multi-PGS setting, improving predictions of several traits. By examining clusters of genetic correlations, we found novel links between diffusion MRI traits and type 2 diabetes.1Author SummaryGenome-wide association studies are a popular framework for identifying regions in the genome influencing a trait of interest. At the same time, the growing sample sizes of medical imaging datasets allow for their incorporation into such studies. However, due to high dimensionalities of imaging modalities, association testing cannot be performed directly on the raw data. Instead, one would extract a set of measurements from the images, typically using predefined algorithms, which has several drawbacks - it requires specialized software, which might not be available for new or less popular modalities, and can ignore features in the data, if they have not yet been defined. An alternative approach is to extract the features using pretrained deep neural network models, which are well suited for complex high-dimensional data and have the potential to uncover patterns not easily discoverable by manual human analysis. Here, we extracted deep feature representations of brain MRI scans from the UK Biobank, and performed a genome-wide association study on them. Besides identifying genetic regions with previously reported associations with brain phenotypes, we found novel regions, as well as ones related to several other traits such as bone mineral density or cardiovascular traits.
Role of type I hypersensitivity reaction in the development of overall and uncomplicated acute appendicitis: a systematic review and meta-analysis
Authors: Montero Javier Arredondo , Jiménez María Rico , Riveros Blanca Paola Pérez , Atuan Rafael Fernández , Pakkasjärvi Niklas , Krishnan Nellai , Delgado-Miguel Carlos , Anand Sachit 
Published: June 2024

ABSTRACTBackgroundThis systematic review aimed to analyze the potential etiopathogenic role of a type I hypersensitivity reaction in the development of overall acute appendicitis (AA), non-complicated acute appendicitis (NCAA), and complicated acute appendicitis (CAA).MethodsThis review was prospectively registered in PROSPERO (CRD42024516547). We included both prospective and retrospective original clinical studies that examined the role of immunoallergic processes in the development of acute appendicitis (AA). A comprehensive search was conducted in PubMed, Web of Science, Scopus, and OVID, using the following search terms and keywords: (allergy OR allergic OR immunoallergy OR immunoallergic OR immunomediated) AND (appendicitis OR appendectomy) AND (IgE OR “IgE-mediated” OR hypersensitivity OR “type I”). Two independent reviewers meticulously selected the articles and extracted relevant data. The methodological quality of the studies was rigorously assessed using the Newcastle-Ottawa index. A synthesis of the results, a standardization of the metrics, and seven random-effect meta-analyses were performed.ResultsThis review included nineteen studies. A random-effects meta-analysis including six articles (6370 patients with NCAA and 2000 patients with CAA) showed that patients with any documented history of IgE-mediated allergy had a lower risk of developing CAA (OR 0.52, 95%CI [0.38-0.72], p<0.0001). The random-effect meta-analysis for serum Interleukin-9 (NCAA vs. CAA) included two articles (177 patients with NCAA and 101 patients with CAA) and resulted in a significant mean difference [95% CI] of –0.38 [-0.67,-0.08] pg/mL (p=0.01). The random-effect meta-analysis for serum Interleukin-13 (NCAA vs. CAA) included two articles (177 patients with NCAA and 101 patients with CAA) and resulted in a significant mean difference [95% CI] of –11.32 [-13.90,-8.75] pg/mL (p=<0.00001). The random-effect meta-analysis for total eosinophil count (NCAA vs. CAA) included three articles (455 NCAA and 303 CAA) and resulted in a significant mean difference [95% CI] of –0.06 [-0.09,-0.04] eosinophils x 109/L (p=<0.00001).ConclusionsThe present study demonstrates an association between a type I hypersensitivity reaction and the development of NCAA. Additionally, our meta-analytic model shows significantly higher levels of eosinophils peripheral blood in patients with NCAA than in patients with CAA. These findings suggest a potential immunoallergic mediation in the development of NCAA. Future prospective studies must validate these findings since these patients may benefit from specific therapeutic targets.FundingNoneRegistrationPROSPERO (CRD42024516547).
LT4SG@SMM4H’24: Tweets Classification for Digital Epidemiology of Childhood Health Outcomes Using Pre-Trained Language Models
Authors: Athukoralage Dasun , Atapattu Thushari , Thilakaratne Menasha , Falkner Katrina 
Published: June 2024

AbstractThis paper presents our approaches for the SMM4H’24 Shared Task 5 on the binary classification of English tweets reporting children’s medical disorders. Our first approach involves fine-tuning a single RoBERTa-large model, while the second approach entails ensembling the results of three fine-tuned BERTweet-large models. We demonstrate that although both approaches exhibit identical performance on validation data, the BERTweet-large ensemble excels on test data. Our best-performing system achieves an F1-score of 0.938 on test data, out-performing the benchmark classifier by 1.18%.
Artificial cells with all-aqueous droplet-in-droplet structures for spatially separated transcription and translation
Authors: Tomohara Kanji , Minagawa Yoshihiro , Noji Hiroyuki 
Published: June 2024

AbstractThe design of functional artificial cells involves compartmentalizing biochemical processes to mimic cellular organization. To emulate the complex chemical systems in biological cells, it is necessary to incorporate an increasing number of cellular functions into single compartments. Artificial organelles that spatially segregate reactions inside artificial cells will be beneficial in this context by rectifying biochemical pathways. In our study, we developed artificial cells featuring all-aqueous droplet-in-droplet structures that separate transcription and translation processes, mimicking the nucleus and cytosol in eukaryotic cells. This droplet-in-droplet architecture utilizes intrinsically disordered protein (IDP) to form coacervate droplets for the inner compartments, and aqueous two-phase systems (ATPS) for the outer compartments, with the outer interfaces stabilized by colloidal emulsifiers. The inner droplet was designed to enrich DNA and RNA polymerase to conduct transcription, which was coupled to translation at the outer droplet, realizing the cascade reaction mediated by mRNA. We also demonstrate that these processes proceed independently within each artificial cell compartment, maintaining the correspondence between genotype and phenotype. The modular configuration of these artificial organelles could be extended to other enzymatic reactions. Coupled with the ease of manufacturing these artificial cells, which only requires simple agitation in an all-aqueous mixture, this approach provides a practical and accessible tool for exploring complex systems of artificial organelles within large ensembles of artificial cells.
Mimosaspecies endemic to acidic soils in central Brazil are nodulated by a high diversity ofParaburkholderiagenotypes, but widespread species are nodulated byParaburkholderia,CupriavidusorRhizobiumdepending on soil characteristics
Authors: Rouws Luc , Barauna Alexandre , Beukes Chrizelle , Rouws Janaina R. C. , de Faria Sergio Miana , Gross Eduardo , dos Reis Junior Fabio Bueno , Simon Marcelo F. , Maluk Marta , Odee David W. , Fordeyn Stephanie , Kenicer Gregory , Young J. Peter W. , Reis Veronica M. , Zilli Jerri , James Euan K. 
Published: June 2024

ABSTRACTNeotropical Beta-rhizobia have a particular affinity to the large legume (Fabaceae) genusMimosaand some of its relatives in the tribe Mimosae of the Caesalpinioideae subfamily. However, little is still known about the ecology of this interaction, especially the relationship between the rhizobia of “widespread” pan-tropicalMimosaspecies likeM. pudicaand the rhizobia that nodulate endemicMimosaspecies that are very restricted in their habitats. The objective of this study was to examine the microsymbionts ofMimosaspp. and some other mimosoids in climates ranging from tropical to subtropical, humid to semi-arid, with varied soil characteristics and altitudes, with the aim of testing the hypothesis that widespread species have more cosmopolitan symbiont preferences than endemic ones. Nodules were sampled from more than 40Mimosaspp. and related taxa in eleven Brazilian states, many endemics or biome-restricted, but particular attention was paid to sample nodules from the widespread speciesM. pudicaat all locations. TheMimosasymbionts comprised 19 potential 16S rRNA andrecAgroups at the species level, with 16 belonging to the genusParaburkholderia, including six lineages that may represent new species. The remaining genotypes consisted of 14 strains in two lineages ofCupriavidusthat were mainly isolated fromM. pudicagrowing at low altitudes, plus a single lineage ofRhizobiumalso fromM. pudica. It is concluded that a high diversity ofParaburkholderiastrains dominate as symbionts ofMimosain the acidic soils of its main center of radiation in Central Brazil but thatCupriavidusandRhizobiumcomprise a significant minority of symbionts of widespreadMimosaspp., especiallyM. pudica, in lowland or disturbed areas with less acidic soils.Mimosasymbiont diversity is thus driven either by edapho-climatic characteristics for widespread species and/or by co-evolution of the symbiotic partners for endemic species.
LEVERAGING CITIZEN SCIENCE TO ASSESS RICHNESS, DIVERSITY, AND ABUNDANCE IN ANT COMMUNITIES
Authors: Szewczyk Tim M. , Lavanchy Guillaume , Freitag Anne , Dépraz Aline , Avril Amaury , Broennimann Olivier , Guisan Antoine , Bertelsmeier Cleo , Schwander Tanja 
Published: June 2024

AbstractCitizen science is a key resource in overcoming the logistical challenges of monitoring biodiversity. While datasets collected by groups of volunteers typically have biases, recent methodological and technological advances provide approaches for accounting for such biases, particularly in the context of modelling species distributions and diversity. Specifically, data integration techniques allow for the combination of scientifically collected datasets with haphazardly sampled presence-only datasets created by most citizen science initiatives. Here, we use a hierarchical Bayesian framework to integrate a set of ant presences collected by citizen scientists in the Vaud canton (Switzerland) with ant colony density data collected concurrently in the same region following a scientific sampling design. The community-level Poisson point process model included species-specific responses to the local (1.2 m2) and regional (1 km2) environment, with the presence-only samples incorporated at the regional scale to predict local and regional ant communities. At the regional scale, species richness followed a hump-shaped pattern and peaked near 1000 m while abundance increased with elevation. Low elevation and montane ant communities were composed of distinct species assemblages. At the local scale, the link between elevation and richness, diversity, and abundance was weak. At low elevations, local plots varied both in total abundance and species composition, while at higher elevations, the species composition was less variable. The citizen science dataset showed a general tendency toward under-representation of certain species, and heavy spatial sampling bias. Nonetheless, the inclusion of the citizen science data improved predictions of local communities, and also reduced susceptibility to over-fitting. Additionally, the citizen science dataset included many rare species not detected in the structured abundance dataset. The model described here illustrates a framework for capitalizing on the efforts of citizen scientists to better understand the patterns and distribution of biodiversity.
Contribution of the Type 3 Secretion System to immunogenicity of a liveYersinia pseudotuberculosisplague vaccine
Authors: Derbise Anne , Guillas Chloé , Rivera Hebert Echenique , Carniel Elisabeth , Gerke Chris , Cerdá Javier Pizarro , Demeure Christian E. 
Published: June 2024

AbstractThe causative agent of plague,Yersinia pestis, remains a treat for public health worldwide. In the perspective to develop effective and safe vaccines, we present here a derived version of ourY. pseudotuberculosisVTnF1 live attenuated vaccine candidate that lacks the pYV virulence plasmid coding for the Type 3 Secretion system (T3SS) and no antibiotic resistance cassettes. This strain, called VpYV-, was safe for immunodeficient mice, and thus can be considered as deeply attenuated. It still has tropism for lymphatic tissues (Peyer’s patches, Mesenteric lymph nodes) but hardly reaches the spleen and liver. It elicits IgG to the F1 antigen as efficiently as VTnF1 but less directed to other Yersinia antigens. A single oral dose induced 100% protection against bubonic and pneumonic forms of plague, but this protection decreased faster with time than that of VTnF1. In the same line, VpYV-was 30% less protective against a F1-negativeY. pestis, revealing that the tools encoded by pYV are mandatory to obtain a large spectrum protection. Finally, VTnF1 like theY. pestisvaccine EV76 can induce protection against co-infectedY. pestisrelying on ‘host iron nutritional immunity”, indicating a potential use as therapeutics of recent infection. In contrast VpYV-failed to do so, revealing an importance of the T3SS in this mechanism. Overall, VpYV- and its parental strain VTnF1 offer a choice between more attenuation and safety or vaccine performances. They give an alternative and may represent useful tools to prevent and treatY. pestisinfection in healthy or immunosuppressed individuals.
Echinocandins have an alternative mode of action on biomimetic membranes that is not directly related to the functioning of (1,3) beta-glucan synthase
Authors: Malykhina Anna I. , Efimova Svetlana S. , Vodopyanova Ekaterina V. , Grammatikova Natalia E. , Tevyashova Anna N. , Shchekotikhin Andrey E. , Ostroumova Olga S. 
Published: June 2024

AbstractEchinocandins, one of five main classes of antifungal agents, are FDA-approved drugs for therapy of invasive candidiasis and aspergillosis. The exact mechanisms of echinocandins action are still under debates, in particular the role of target cell membranes in their function. In present study we analyzed the molecular mechanisms of action of echinocandins (anidulafungin, caspofungin, and micafungin) on the sterol-enriched lipid bilayers mimicking fungal and mammalian membranes. Calcein release assay and molecular dynamics simulations demonstrated the relation of the membrane permeability and echinocandin type. Moreover, we have shown for the first time the ability of echinocandins to form ion-permeable pores in sterol-containing membranes. Differential scanning microcalorimetry of the gel-to-liquid-crystalline lipid phase transition and confocal fluorescent microscopy of lipid domains revealed the ability of echinocandins to enhance phase segregation in membrane. Thus, echinocandins might affect the (1,3) beta-glucan synthase functioning by alteration in lipid microenvironment of target protein and cellular membrane permeability via formation of ion-selective leakage channels. We also found that small natural molecule, phloretin, potentiated the pore-forming activity of micafungin in the ergosterol-containing bilayers and significantly reduced the minimum inhibitory concentration of micafungin against fluconazole-resistantCandida albicans, C. tropicalis, andC.krusei.
Minimizing command timing volatility is a key factor in skilled actions
Authors: Takagi Atsushi , Ito Sho , Gomi Hiroaki 
Published: June 2024

AbstractVariability between movements prevents the best athletes from making a perfect shot every time. While fluctuations in the amplitude of neural sensory inputs and motor outputs are thought to be primarily responsible, they only account for a fraction of the observed variability. Here, we propose that a significant portion of the variability is due to imprecisely timed motor commands. This command timing volatility theory best explained the three peaks observed in the force variability’s time-series in discrete reaching movements and during periodic force control. Furthermore, we show how the timing volatility in the non-dominant arm’s muscles is larger than in the dominant arm, then develop a variability index that estimates the arm’s timing volatility via its variability during circle tracing. The difference in the variability index between the left and right hands accurately predicts the Edinburgh Quotient, suggesting a relationship between handedness and the command timing volatility of the left- and right-hands. Lastly, we constructed a simulation of reaching movements made by an arm controlled by muscles whose command timing was made incrementally more volatile. As timing volatility increased, aiming became less precise and movements jerkier. Such impairments during reaching are reported in patients with different neuronal diseases that damage any brain regions critical to motor timing, suggesting that essential aspects of these symptoms may be caused by excessive timing volatility. Our theory provides a unifying computational perspective of movement variability in healthy and diseased individuals that is essential to understanding the control of movements.