bluuebunny/crossref_metadata_2025_split huggingface dataset:
The crystal structure of the Shethna Protein II (FeSII) fromAzotobacter vinelandiisuggests a domain swap
Authors: Kabasakal Burak V. , Mcfarlane Ciaran R. , Cotton Charles A. R. , Schmidt Anna , Kung Andrea , Lieber Lucas , Murray James W. 
Published: February 2024

ABSTRACTTheAzotobacter vinelandiiFeSII protein forms an oxygen resistant complex with the nitrogenase MoFe and Fe proteins. FeSII is an adrenodoxin type ferredoxin, forming a dimer in solution. Previously, the crystal structure was solved (Schlesier et al., 2016), with 5 copies in the asymmetric unit. One copy is a normal adrenodoxin domain, forming a dimer with its crystallographic symmetry mate. The other four copies are in an “open” conformation with a loop flipped out exposing the 2Fe-2S cluster. The open and closed conformations were interpreted as oxidised and reduced, and the large conformational change in the open configuration allowed binding to nitrogenase. We have independently solved the structure of FeSII in the same crystal form. Our positioning of the atoms in the unit cell is similar to the earlier report. However, our interpretation of the structure is different. We interpret the “open” conformation as the product of a crystallization-induced domain swap. The 2Fe-2S cluster is not exposed to solvent, but in the crystal its interacting helix is replaced by the same helix residues from a crystal symmetry mate. The domain swap is complicated, as it is unusual in being in the middle of the protein rather than at a terminus, and it creates arrangements of molecules that can be interpreted in multiple ways. We caution that crystal structures should be interpreted in terms of the contents of the entire crystal rather than one asymmetric unit.
A constraint-based framework to reconstruct interaction networks in microbial communities
Authors: Oftadeh Omid , Sahin Asli , Vayena Evangelia , Hatzimanikatis Vassily 
Published: February 2024

AbstractMicrobial communities live in diverse habitats and significantly impact our health and the environment. However, the principles that govern their formation and evolution remain poorly understood. A crucial step in studying microbial communities is to identify the potential metabolic interactions between the community members, such as competition for nutrients or cross-feeding. Due to the size and complexity of the metabolic network of each organism, there may be a variety of connections between each pair of organisms, which poses a challenge to unraveling the metabolic interactions. Here, we present ReMIND, a computational framework to reconstruct the interaction networks in microbial communities based on the metabolic capabilities of individual organisms. We applied ReMIND to a well-studied uranium-reducing community and the honeybee gut microbiome. Our results provide new perspectives on the evolutionary forces that shape these ecosystems and the trade-off between metabolite exchange and biomass yield. By enumerating alternative interaction networks, we systematically identified the most likely metabolites to be exchanged and highlighted metabolites that could mediate competitive interactions. We envision that ReMIND will help characterize the metabolic capacity of individual members and elucidate metabolic interactions in diverse communities, thus holds the potential to guide many applications in precision medicine and synthetic ecology.
Somatic gene delivery for flexiblein vivomodeling of high-risk sarcoma
Authors: Imle Roland , Blösel Daniel , Kommoss Felix K.F. , Zhao Eric Stutheit , Autry Robert , Blume Christina , Lupar Dmitry , Schmitt Lukas , Winter Claudia , Wagner Lena , Placke Sara , von Eicke Malte , Hertwig Michael , Peterziel Heike , Oehme Ina , Scheuerman Sophia , Seitz Christian , Geyer Florian H. , Cidre-Aranaz Florencia , Grünewald Thomas G. P. , Vokuhl Christian , Chudasama Priya , Scholl Claudia , Schmidt Claudia , Günther Patrick , Sill Martin , Jones Kevin B. , Pfister Stefan M. , Banito Ana 
Published: February 2024

ABSTRACTA particular challenge hampering therapeutic advancements for high-risk sarcoma patients is the broad spectrum of molecularly distinct sarcoma entities and the corresponding lack of suitable model systems to recapitulate and study these diseases. To overcome this predicament, we developed a novel genetically-controlled, yet versatile mouse modeling platform allowing delivery of different genetic lesions by electroporation (EPO) of the thigh muscle wildtype mice. This optimized sarcoma EPO-GEMM (EPO-based genetically engineered mouse model) platform allowed the generation of ten biologically distinct sarcoma entities, including Synovial Sarcoma (SS), fusion-positive and fusion-negative Rhabdomyosarcoma (RMS), Alveolar Soft Part Sarcoma (ASPS), Undifferentiated Pleomorphic Sarcoma (UPS) and Infantile Fibrosarcoma (IFS). Comprehensive molecular profiling and cross-species analyses confirmed faithful recapitulation of the human disease, including the expression of relevant immunotherapy targets. Syngeneic allografting enabled reliable preservation and scalability of Sarcoma-EPO-GEMMs for treatment trials, such as B7-H3-directed CAR-T cell therapy in an immunocompetent background.
ViraLM: Empowering Virus Discovery through the Genome Foundation Model
Authors: Peng Cheng , Shang Jiayu , Guan Jiaojiao , Wang Donglin , Sun Yanni 
Published: February 2024

AbstractMotivationViruses, with their ubiquitous presence and high diversity, play pivotal roles in ecological systems and have significant implications for public health. Accurately identifying these viruses in various ecosystems is essential for comprehending their variety and assessing their ecological influence. Metagenomic sequencing has become a major strategy to survey the viruses in various ecosystems. However, accurate and comprehensive virus detection in metagenomic data remains difficult. Limited reference sequences prevent alignment-based methods from identifying novel viruses. Machine learningbased tools are more promising in novel virus detection but often miss short viral contigs, which are abundant in typical metagenomic data. The inconsistency in virus search results produced by available tools further highlights the urgent need for a more robust tool for virus identification.ResultsIn this work, we develop a Viral Language Model, named ViraLM, to identify novel viral contigs in metagenomic data. By employing the latest genome foundation model as the backbone and training on a rigorously constructed dataset, the model is able to distinguish viruses from other organisms based on the learned genomic characteristics. We thoroughly tested ViraLM on multiple datasets and the experimental results show that ViraLM outperforms available tools in different scenarios. In particular, ViraLM improves the F1-score on short contigs by 22%.AvailabilityThe source code of ViraLM is available via:https://github.com/ChengPENG-wolf/ViraLM.Contactyannisun@cityu.edu.hk
PHACTboost: A Phylogeny-aware Boosting Algorithm to Compute the Pathogenicity of Missense Mutations
Authors: Dereli Onur , Kuru Nurdan , Akkoyun Emrah , Bircan Aylin , Tastan Oznur , Adebali Ogün 
Published: February 2024

AbstractMost algorithms that are used to predict the effects of variants rely on evolutionary conservation. However, a majority of such techniques compute evolutionary conservation by solely using the alignment of multiple sequences while overlooking the evolutionary context of substitution events. We had introduced PHACT, a scoring-based pathogenicity predictor for missense mutations that can leverage phylogenetic trees, in our previous study. By building on this foundation, we now propose PHACTboost, a gradient boosting tree-based classifier that combines PHACT scores with information from multiple sequence alignments, phylogenetic trees, and ancestral reconstruction. The results of comprehensive experiments on carefully constructed sets of variants demonstrated that PHACTboost can outperform 40 prevalent pathogenicity predictors reported in the dbNSFP, including conventional tools, meta-predictors, and deep learning-based approaches as well as state-of-the-art tools, AlphaMissense, EVE, and CPT-1. The superiority of PHACTboost over these methods was particularly evident in case of hard variants for which different pathogenicity predictors offered conflicting results. We provide predictions of 219 million missense variants over 20,191 proteins. PHACTboost can improve our understanding of genetic diseases and facilitate more accurate diagnoses.
Characteristics of vicarious touch reports in a general population
Authors: Smit Sophie , Crossley Matthew J. , Zopf Regine , Rich Anina N. 
Published: February 2024

AbstractVicarious touch refers to the phenomenon where individuals experience tactile sensations when observing another person being touched. This study explored vicarious touch reports in 422 undergraduate students using videos from the Validated Touch-Video Database (VTD), rated for hedonic qualities, arousal, and perceived threat levels. A surprisingly large majority (84%) of participants reported vicarious sensations such as touch, tingling, pressure, and pain, predominantly matching the location of touch to the hands observed in the videos. Contrary to previous studies, we found that vicarious touch was more prevalent in women than men. Additionally, while earlier research suggested a correlation between vicarious sensations and emotional empathy, our data did not support this relationship. The nature and intensity of reported sensations varied strongly with the emotional content of the videos: pleasant touches evoked ticklish or warm sensations, while unpleasant touches often resulted in pain or pressure. Participants often described their sensations as either pleasant or unpleasant, indicating that the affective qualities of observed touch were mirrored in their experiences. Arousal and threat ratings taken from the VTD for each video strongly correlated with the prevalence and intensity of vicarious touch measured here, with painful, highly arousing touches eliciting the strongest responses. Even touch involving non-human objects occasionally triggered similar vicarious sensations. Using a new clustering approach, we identified three distinct profiles of vicarious touch, each characterised by unique sensory experiences, variations in the localisation and intensity of sensations, and differences in responses to human versus object touch. Overall, our results challenge the traditional view that conscious vicarious touch experiences are a rare phenomenon and underscore the diversity of vicarious sensory perception.
Endogenous labeling empowers accurate detection of m6A from single long reads of direct RNA sequencing
Authors: Guo Wenbing , Ren Zhijun , Huang Xiang , He Jialiang , Zhang Jie , Wu Zehong , Guo Yang , Zhang Zijun , Cun Yixian , Wang Jinkai 
Published: February 2024

ABSTRACTAlthough plenty of machine learning models have been developed to detect m6A RNA modification sites using the electric current signals of ONT direct RNA sequencing (DRS) reads, the landscape of m6A on different RNA isoforms is still a mystery due to their limited capacity to distinguish the m6A on individual long reads and RNA isoforms. The primary challenge in training the model with single-read accuracy is the difficulty of obtaining the training data from individual DRS reads that comprehensively represent the m6A on endogenous RNAs. Here, we endogenously label the methylated m6A sites on single ONT DRS reads by APOBEC1-YTH induced C-to-U mutations, strategically positioned 10-100 nt away from the known m6A sites on the same reads. Adopting a semi-supervised leaning strategy, we obtain 700,438 reliable 5-mer single-read level m6A signals, providing a comprehensive representation of m6A on endogenous RNAs. Leveraging this dataset, we develop m6Aiso, a deep residual neural network model that not only accurately identifies and quantifies known m6A sites but also reveals unknown, subtly methylated m6A sites responsive to METTL3 depletion. Analyzing m6Aiso-determined m6A on single reads and isoforms uncovers distance-dependent linkages of m6A sites along single molecules, as well as differential methylation of identical m6A sites on different isoforms. Moreover, we find wide-spread functionally important dynamic changes of m6A sites on specific isoforms during epithelial-mesenchymal transition (EMT). The pivotal utilization of the endogenous labeling strategy empowers m6Aiso to achieve remarkable precision in pinpointing m6A on individual molecules, underscores its effectiveness in elucidating the intricate dynamics and complexities of m6A across RNA isoforms.
Outcrossing increases resistance against coevolving parasites
Authors: Slowinski Samuel P. , Gresham Jennifer D. , Penley McKenna J. , Lively Curtis M. , Morran Levi T. 
Published: February 2024

AbstractDespite substantial costs, biparental sex is the dominant mode of reproduction across plant and animal taxa. The Red Queen hypothesis (RQH) posits that coevolutionary interactions with parasites can favor biparental sex in hosts, despite the costs. In support of the RQH, previous studies found that coevolutionary interactions with virulent bacterial parasites maintained high outcrossing rates in populations of the androdioecious nematode hostCaenorhabditis elegans. Here we test three non-mutually exclusive mechanisms that could explain how coevolving parasites maintain outcrossing rates inC. eleganshosts: 1) short-term parasite exposure induces plastic increases in the hosts’ propensity to outcross, 2) hosts evolve increased outcrossing propensity in response to selection imposed by coevolving parasites, and 3) outcrossed offspring incur less parasite-mediated fitness loss than selfed offspring, increasing host male frequencies and opportunities for outcrossing. We find no evidence that parasites cause plastic or evolved changes in host outcrossing propensity. However, parental outcrossing significantly increases survival of host offspring in the F2 generation when exposed to a coevolving parasite. Hence, coevolving parasites maintain outcrossing in host populations by selecting against selfed offspring, rather than by inducing changes in the propensity to outcross.
Identification, antimicrobial resistance and molecular detection of Shiga toxin-producingE. coli(STEC) isolated from raw milk of cattle in Chitwan, Nepal
Authors: Shrestha Sunita , Bhattarai Rebanta Kumar , Basnet Hom Bahadur , Luitel Himal , Bastola Sirjan 
Published: February 2024

ABSTRACTShiga toxin-producingEscherichia coli(STEC) is one of the most common foodborne pathogens leading to gastroenteritis with symptoms of mild diarrhoea to the potential life-threatening haemolytic uremic syndrome. Serotype O157:H7 has been the most predominant type worldwide but there are an increasing number of outbreaks caused by non-O157:H7 STEC serotypes. This is the first study about STEC in milk used in Nepalese communities. A total of 267 raw milk samples were taken from different sites in Chitwan District, one of the major milk-producing districts of Nepal, using multi-stage sampling. The samples underwent microbiological and molecular analysis. The overall prevalence ofE. coliwas found to be 29.6% (79/267) in raw cattle milk.Z3276gene, a specific genetic marker ofE. coliO157:H7 was detected only in three isolates which also carriedstxgenes. The overall prevalence of STEC in raw cattle milk was 11.6% (31/267) whereas the prevalence of STEC amongE. coliisolates was 39.2% (31/79). The prevalence of O157:H7 STEC is 1.1% (3/267) and of non-O157:H7 STEC is 10.5% (28/267). Out of 12 antibiotics tested, the sensitivity of STEC to an antibiotic was highest with azithromycin, and levofloxacin, and the most resistant was with tetracycline, and doxycycline. The findings revealed that raw cattle milk was contaminated with STEC, posing a potential public health concern. The discovery of a greater occurrence ofstx2genes in this study highlights the possibility of more severe complications in humans. Molecular-based STEC surveillance is essential to minimize the risk of its transmission.
A “torn bag mechanism” of small extracellular vesicle release via limiting membrane rupture ofen blocreleased amphisomes (amphiectosomes)
Authors: Visnovitz Tamás , Lenzinger Dorina , Koncz Anna , Vizi Péter M , Bárkai Tünde , Vukman Krisztina V , Galinsoga Alicia , Németh Krisztina , Fletcher Kelsey , Komlósi Zsolt I , Cserép Csaba , Dénes Ádám , Lőrincz Péter , Valcz Gábor , Buzás Edit I 
Published: February 2024

AbstractRecent studies showed an unexpected complexity of extracellular vesicle (EV) biogenesis pathways. We previously found evidence that human colorectal cancer cellsin vivorelease large multivesicular body-like structuresen bloc. Here, we tested whether this large extracellular vesicle type is unique to colorectal cancer cells. We found that all cell types we studied (including different cell lines and cells in their original tissue environment) released multivesicular large EVs (MV-lEVs). We also demonstrated that upon spontaneous rupture of the limiting membrane of the MV-lEVs, their intraluminal vesicles (ILVs) escaped to the extracellular environment by a ”torn bag mechanism”. We proved that the MV-lEVs were released by ectocytosis of amphisomes (hence, we termed them amphiectosomes). Both ILVs of amphiectosomes and small EVs separated from conditioned media were either exclusively CD63 or LC3B positive. According to our model, upon fusion of multivesicular bodies with autophagosomes, fragments of the autophagosomal inner membrane curl up to form LC3B positive ILVs of amphisomes, while CD63 positive small EVs are of multivesicular body origin. Our data suggest a novel common release mechanism for small EVs, distinct from the exocytosis of multivesicular bodies or amphisomes, as well as the small ectosome release pathway.
New Reference Values for Thyroid Volume by Ultrasound in German Children and Adolescents Under Iodine-Sufficient Conditions from a Population-Based Study
Authors: Hirtz Raphael , Thamm Roma , Kuhnert Ronny , Liesenkötter Klaus-Peter , Thamm Michael , Grasemann Corinna 
Published: February 2024

AbstractContextReliable reference values for thyroid ultrasound measurements are essential to effectively guide individual diagnostics and direct health care measures at the population level, such as iodine fortification programs. However, the latest reference values for total thyroid volume (Tvol) provided by the WHO in 2004 only apply to the 6 to 12-year-old age group and are limited to countries with a long history of iodine sufficiency, which does not reflect the situation in most European countries, including Germany.ObjectiveThe present aims to derive up to date thyroid volume ultrasound reference values in German children and adolescents.DesignData from the baseline assessment of a nationwide study in German children and adolescents (KiGGS) conducted between 2003 and 2006 were used to determine sex-specific reference values for Tvol in thyroid-healthy participants aged 6 to 17 years by age and body surface area (BSA) according to the Lambda-Mu-Sigma (LMS) method.ResultsData from 5559 participants were available for reference chart construction (girls: 2509 (45.1%)). On average, the 97th percentile is 33.4% and 28.5% higher than the corresponding WHO’s reference values for boys and girls, respectively. These findings are consistent with most other studies in German and European children and adolescents at a similar time of investigation. Notably, the sample used for this study was iodine-sufficient according to WHO criteria.ConclusionsThe reference values provided by the WHO are overly conservative for this population and could potentially apply to apply to other European countries with a similar history of iodine supply.
Magnetocardiography for the diagnosis of coronary artery disease: a systematic review and meta-analysis
Authors: Yang Miao , Sun Chenxi , Zhao Biying , Wu Bo , Xiang Jing , Xu Man , Wu Teng , Zhang Jianwei , Xu Wei , Guo Hong 
Published: February 2024

AbstractBackgroundGlobally, coronary heart disease (CHD) is a major public health issue because it significantly increases mortality and medical expenses. In the recent years, magnetocardiography (MCG) has shown its potential as a new tool for diagnosing CHD. However, the quantitative assessment of MCG currently used for CHD diagnosis are insufficient, preventing its full integration into routine clinical practice.MethodsWe searched PubMed (including MEDLINE), Embase, Web of Science, Cochrane Library, Scopus, China National Knowledge Infrastructure (CNKI), Wanfang Data, and ClinicalTrials.gov for studies published up to March 4, 2023. We systematically searched for studies that compare MCG (as the index test) with coronary angiography (as the standard reference) for diagnosing CHD in suspected population. Three authors assessed the quality of the included studies independently using the QUADAS-2 tool. We calculated the pooled value of the sensitivity and specificity of MCG using the bivariate model. To investigate clinical and methodological factors that might contribute to the statistical heterogeneity, we used meta-regression and subgroup analysis. This systematic review and meta-analysis has been conformed to PRISMA guidelines and registered with PROSPERO (number CRD42022332272).ResultsBy searching, we found 174 studies, 18 of them included 2,571 subjects from 6 countries and regions and met the inclusion criteria. The combined values for sensitivity and specificity are 86% (95% CI: 80-91) and 79% (95% CI: 71-86), respectively. The summary receiver operating characteristic (SROC) curve’s area under the curve was 0.90. We found significant statistical heterogeneity between studies (for sensitivity, I2=94.22% (95% CI: 92.48-95.96), Q=294.11,P<0.01; for specificity, I2=88.98% (95% CI: 84.95-93.01), Q=154.26,P<0.01.ConclusionGiven its high sensitivity, MCG has a high value for diagnosing CHD, especially in primary screening. Further investigation is required to examine additional factors that may affect the performance of MCG considering the limited clinical trials and sample size.
Trends and Adverse Outcomes of Xylazine Misuse: A Digital Surveillance Study
Authors: Bhagavathula Akshaya Srikanth , Aldhaleei Wafa A. , Kim Seongjin 
Published: February 2024

AbstractBackgroundXylazine is an animal tranquilizer without approved medical use in humans that is increasingly being misused as an adulterant in illicit drugs. This study aimed to characterize national trends and adverse outcomes associated with the emerging misuse of xylazine using digital surveillance data.MethodsWe examined online search trends and social media discussions related to xylazine misuse in the U.S. from 2019-2023 using Google Searches data and conducted Joinpoint regression to assess trends. We also examined social media attention using Almetric attention score and analyzed reports on xylazine in the FDA Adverse Event Reporting System (FAERS) through September 2023 using logistic regression.ResultsOur analysis revealed an overall increasing trend in online searches for “xylazine” nationally, with an average monthly percentage change of 4.6% (95% CI: 3.9–5.1,Ptrend<0.001), indicating growing awareness. On social media, mentions of xylazine rose exponentially starting in late 2021. Analysis of the FAERS data identified 94 reports of adverse events related to xylazine, most of which involved men (70.2%), with a mean age of 36.5 ± 14.3 years. Alarmingly, these xylazine-linked adverse events had an 87.2% fatality rate, which increased over 40-fold with concurrent fentanyl use (reported OR: 40.5, 95% CI: 4.0–407.4,P=0.002).ConclusionsThese findings underscore the urgent need for greater public health awareness, harm reduction strategies, and enhanced surveillance targeting the worsening xylazine addiction and overdose crisis.