bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic discovery of protein interaction interfaces using AlphaFold and experimental validation
Authors: Lee Chop Yan , Hubrich Dalmira , Varga Julia K. , Schäfer Christian , Welzel Mareen , Schumbera Eric , Đokić Milena , Strom Joelle M. , Schönfeld Jonas , Geist Johanna L. , Polat Feyza , Gibson Toby J. , Keller Valsecchi Claudia Isabelle , Kumar Manjeet , Schueler-Furman Ora , Luck Katja 
Published: August 2023

AbstractStructural resolution of protein interactions enables mechanistic and functional studies as well as interpretation of disease variants. However, structural data is still missing for most protein interactions because we lack computational and experimental tools at scale. We thoroughly assessed AlphaFold-Multimer accuracy for structure prediction of interactions involving folded domains binding to short linear motifs from the ELM database. The structure predictions were highly sensitive but not very specific when using small protein fragments. Sensitivity decreased substantially when using long protein fragments or full length proteins with intrinsically disordered regions. We delineated a fragmentation strategy to optimize sensitivity and applied it to interactions between proteins associated with neurodevelopmental disorders. This enabled prediction of highly confident and likely disease-related novel interfaces, but also resulted in many high scoring false positive predictions. Experiments supported predicted interfaces between CREBZF-HCFC1, FBXO23-STX1B, STX1B-VAMP2, ESRRG-PSMC5, PEX3-PEX19, PEX3-PEX16, and SNRPB-GIGYF1 providing novel molecular insights for diverse biological processes. Our work highlights exciting perspectives, but also reveals clear limitations and the need for future developments to maximize the power of Alphafold-Multimer for interface predictions.
Learning interventions and training methods in health emergencies: A scoping review
Authors: Utunen Heini , Balaciano Giselle , Arabi Elham , Tokar Anna , Noyes Jane 
Published: August 2023

AbstractBackgroundKeeping the health workforce and the public informed with the latest evolving knowledge is critical to preventing, detecting and responding to infectious disease outbreaks or other health emergencies. Having a well informed, ready, willing, and skilled workforce and an informed public can help save lives, reduce diseases and suffering, and minimize socio-economic loss in affected communities and countries. Providing support and opportunities for learning in health emergencies is much needed for capacity building. In this paper, ‘learning intervention’ refers to the provision of ad-hoc, focused, or personalized training sessions with the goal of preparing the health workers for emergencies or filling specific knowledge or skill gaps. We refer to ‘training methods’ as instructional design strategies used to teach someone the necessary knowledge and skills to perform a task.MethodsWe conducted a scoping review to map and better understand what learning interventions and training methods have been used in the different types of health emergencies and with whom. Studies were identified by searching Pubmed/Medline, Embase and consulting with experts.ResultsOf the 319 records that were included, contexts related to COVID-19, disasters in general, Ebola and wars were most frequently covered. Four topic areas were identified: Knowledge acquisition, Emergency Plans, Impact of the learning intervention, and training methods. Much of the evidence was based on observational methods with few trials, which likely reflects the unique context of each health emergency. Evolution of methods was apparent, particularly in virtual learning. Learning during health emergencies appeared to improve knowledge, management, quality of life, satisfaction and clinical outcomes.ConclusionThis is the first scoping review to map the evidence, which serves as a first step to develop urgently needed global guidance to further improve the quality and reach of learning interventions and training methods in this context.
Identification of host endotypes using peripheral blood transcriptomics in a prospective cohort of patients with endocarditis
Authors: Duarte-Herrera Israel David , López-Martínez Cecilia , Rodríguez-García Raquel , Parra Diego , Martín-Vicente Paula , Exojo-Ramirez Sara M. , Miravete-Lagunes Karla , Iglesias Lisardo , González-Iglesias Marcelino , Fernández-Rodríguez Margarita , Carretero-Ledesma Marta , López-Alonso Inés , Gómez Juan , Coto Eliecer , Fernández Javier , Amado-Rodríguez Laura , Albaiceta Guillermo M 
Published: August 2023

AbstractObjectivesTo identify endotypes in patients with infective endocarditis.MethodsThirty-two consecutive patients with infective endocarditis were studied. Clinical data and a blood sample were collected at diagnosis, and RNA sequenced. Gene expression was used to identify two clusters, termed endocarditis endotypes (EE) 1 and 2. RNA sequencing was repeated after surgery. Transcriptionally active cell populations were identified by deconvolution. Differences between endotypes in clinical data, survival, gene expression and molecular pathways involved were assessed.Results18 and 14 patients were assigned to EE1 and EE2 respectively, with no differences in clinical data. Patients assigned to EE2 showed an enrichment in genes related to T-cell maturation and a decrease in the activation of the STAT pathway, with higher counts of active T-cells and lower counts of neutrophils. Fourteen patients (9 in EE1 and 5 in EE2) were submitted to surgery. Surgery in EE2 patients shifted gene expression towards a EE1-like profile. In-hospital mortality was higher in EE1 (56% vs 14%, p=0.027) with a hazard ratio of 12.987 (95% confidence interval 3.356 – 50] after adjustment by age and sex.ConclusionsGene expression reveals two endotypes in patients with acute endocarditis, with different underlying pathogenetic mechanisms, response to surgery and outcome.
A deep learning approach for cancer diagnosis exclusively from raw sequencing fragments of bisulfite-treated plasma cell-free DNA
Authors: Liu Jilei , Shen Hongru , Hu Jiani , Shen Xilin , Zhang Chao , Yang Yichen , Yang Meng , Wang Wei , Li Yang , Zhang Qiang , Yang Jilong , Chen Kexin , Li Xiangchun 
Published: August 2023

AbstractEarly cancer diagnosis from bisulfite-treated cell-free DNA (cfDNA) fragments require tedious data analytical procedures. Here, we present a Deep-learning-based approach for Early Cancer Interception and DIAgnosis (DECIDIA) that can achieve accurate cancer diagnosis exclusively from bisulfite-treated cfDNA sequencing fragments. DECIDIA relies on feature representation learning of DNA fragments and weakly supervised learning for classification. We systematically evaluate the performance of DECIDIA for cancer diagnosis and cancer-type prediction on a curated dataset of 5389 samples that consist of colorectal cancer (CRC, n = 1574), hepatocellular cell carcinoma (HCC, n = 1181), lung cancer (n = 654) and non-cancer control (n=1980). DECIDIA achieves an area under the receiver operating curve (AUROC) of 0.980 (95% CI, 0.976-0.984) in ten-fold cross validation settings on the CRC dataset, outperforming benchmarked methods that are based on fragmentation profiles and methylation intensities. Noticeably, DECIDIA achieves an AUROC of 0.910 (95% CI, 0.896-0.924) on the externally independent HCC testing set although there was no HCC data used in model development. In the settings of cancer-type classification, we observed that DECIDIA achieves a micro-average AUROC of 0.963 (95% CI, 0.960-0.966) and an overall accuracy of 82.8% (95%CI, 81.8% - 83.9%). In addition, we distilled four sequence signatures from the raw sequencing reads that exhibited differential patterns in cancer versus control and among different cancer types. Our approach represents a new paradigm towards eliminating the tedious data analytical procedures for liquid biopsy that uses bisulfite-treated cfDNA methylome.
Waning of post-vaccination neutralizing antibody responses against SARS-CoV-2, a systematic literature review and meta-analysis
Authors: Jacobsen Henning , Sitaras Ioannis , Katzmarzyk Maeva , Cobos Jiménez Viviana , Naughton Robert , Higdon Melissa M. , Deloria Knoll Maria 
Published: August 2023

SummaryBackgroundMass COVID-19 vaccination and the continuous introduction of new viral variants of SARS-CoV-2, especially of Omicron subvariants, has resulted in an increase in the proportion of the population with hybrid immunity at various stages of waning protection. We systematically reviewed waning of post-vaccination neutralizing antibody titers in different immunological settings to investigate potential differences.MethodsWe searched for studies providing data for post-vaccination neutralizing antibody responses against SARS-CoV-2 in PubMed, bioRxiv, and medRxiv from Dec 15, 2021, to Jan 31, 2023, using keywords related to COVID-19, vaccination, and antibody neutralization. We used random effects meta-regression to estimate the average fold-reduction in post-vaccination neutralizing antibody titers against the Index strain or Omicron BA.1. from month 1 to month 6 post last dose, stratified by vaccination regimen (primary or booster) and infection-naïve vs hybrid-immune status.FindingsIn total, 26 studies reporting longitudinal post-vaccination neutralizing antibody titers were included. Neutralization titers against the Index variant were available from all studies for infection-naïve participants, and from nine for hybrid-immune participants. Against Omicron BA.1, nine and eight studies were available for infection-naïve and hybrid-immune cohorts, respectively. In infection-naïve cohorts, post-vaccination neutralization titers against the Index strain waned 5.1-fold (95% CI 3.4-7.8) from month 1 to month 6 following primary regimen and 3.8-fold (95% CI 2.4-5.9) following the booster. Titers against Omicron BA.1 waned 5.9-fold (95% CI 3.8-9.0) in infection-naïve, post-booster cohorts. In hybrid-immune, post-primary vaccination cohorts, titers waned 3.7-fold (95% CI 1.7-7.9) against the Index strain and 5.0-fold (95% CI 1.1-21.8) against Omicron BA.1.InterpretationNo obvious differences in waning between post-primary or post-boost vaccination were observed for vaccines used widely to date, nor between infection-naïve and hybrid-immune participants. Titers against Omicron BA.1 may wane faster compared to Index titers, which may worsen for more recent Omicron sub-variants and should be monitored. Relatively small datasets limit the precision of our current analysis; further investigation is needed when more data become available. However, based on our current findings, striking differences in waning for the analyzed and future comparisons are unlikely.
The Extent of Edgetic Perturbations in the Human Interactome Caused by Population-Specific Mutations
Authors: Cui Hongzhu , Srinivasan Suhas , Gao Ziyang , Korkin Dmitry 
Published: August 2023

ABSTRACTUntil recently, efforts in population genetics have been focused primarily on people of European ancestry. To attenuate the bias, global population studies, such as the 1,000 Genomes Project, have revealed differences in genetic variation across ethnic groups. How much of these differences would attribute to the population-specific traits? To answer this question, the mutation data must be linked with the functional outcomes. A new “edgotype” concept has been proposed that emphasizes the interaction-specific, “edgetic”, perturbations caused by mutations in the interacting proteins. In this work, we performed a systematicin-silicoedgetic profiling of ∼50,000 non-synonymous SNVs (nsSNVs) from 1,000 Genomes Project by leveraging our semi-supervised learning approach SNP-IN tool on a comprehensive set of over 10,000 protein interaction complexes. We interrogated functional roles of the variants and their impact on the human interactome and compared the results with the pathogenic variants disrupting PPIs in the same interactome. Our results demonstrated that a considerable number of nsSNVs from healthy populations could rewire the interactome. We also showed that the proteins enriched with the interaction-disrupting mutations were associated with diverse functions and had implications in a broad spectrum of diseases. Further analysis indicated that distinct gene edgetic profiles among major populations could shed light on the molecular mechanisms behind the population phenotypic variances. Finally, the network analysis revealed that the disease-associated modules surprisingly harbored a higher density of interaction-disrupting mutations from the healthy populations. The variation in the cumulative network damage within these modules could potentially account for the observed disparities in disease susceptibility, which are distinctly specific to certain populations. Our work demonstrates the feasibility of a large-scalein-silicoedgetic study and reveals insights into the orchestrated play of the population-specific mutations in the human interactome.
TMEM165 acts as a proton-activated Ca2+importer in lysosomes
Authors: Zajac Matthew , Mukherjee Sourajit , Anees Palapuravan , Oettinger Daphne , Henn Katharine , Srikumar Jainaha , Zou Junyi , Saminathan Anand , Krishnan Yamuna 
Published: August 2023

SummaryLysosomal calcium (Ca2+) release is critical to cell signaling and is mediated by well-known lysosomal Ca2+channels. Yet, how lysosomes refill their Ca2+remains hitherto undescribed. Here, from an RNAi screen, we identify an evolutionarily conserved gene,lci-1, that facilitates lysosomal Ca2+entry inC. elegansand in mammalian cells. Its human homolog TMEM165, previously designated as a Golgi-resident Ca2+/H+exchanger (CAX), has a minor lysosomal population of unknown function. Using genetics, lysosomal Ca2+imaging and electrophysiology, we show that TMEM165 acts as a proton-activated, lysosomalCa2+importer in lysosomes. Defects in lysosomal Ca2+channels cause several neurodegenerative diseases, and knowledge of lysosomal Ca2+importers may provide new avenues to explore the physiology of Ca2+channels.
A bacterial sialidase mediates early life colonization by a pioneering gut commensal
Authors: Buzun Ekaterina , Hsu Chia-Yun , Sejane Kristija , Oles Renee E. , Ayala Adriana Vasquez , Loomis Luke R. , Zhao Jiaqi , Rossitto Leigh-Ana , McGrosso Dominic , Gonzalez David J. , Bode Lars , Chu Hiutung 
Published: August 2023

ABSTRACTThe early microbial colonization of the gastrointestinal tract can lead to long-term impacts in development and overall human health. Keystone species, includingBacteroides spp., play a crucial role in maintaining the structure, diversity, and function of the intestinal ecosystem. However, the process by which a defined and resilient community is curated and maintained during early life remains inadequately understood. Here, we show that a single sialidase, NanH, inBacteroides fragilismediates stable occupancy of the intestinal mucosa and regulates the commensal colonization program during the first weeks of life. This program is triggered by sialylated glycans, including those found in human milk oligosaccharides and intestinal mucus. After examining the dynamics between pioneer gutBacteroidesspecies in the murine gut, we discovered that NanH enables vertical transmission from dams to pups and promotesB. fragilisdominance during early life. Furthermore, we demonstrate that NanH facilitates commensal resilience and recovery after antibiotic treatment in a defined microbial community. Collectively, our study reveals a co-evolutionary mechanism between the host and the microbiota mediated through host-derived glycans to promote stable intestinal colonization.
CD20 is a mammalian odorant receptor expressed in a subset of olfactory sensory neurons that mediates innate avoidance of predators
Authors: Jiang Hao-Ching , Park Sung Jin , Wang I-Hao , Bear Daniel M. , Nowlan Alexandra , Greer Paul L. 
Published: August 2023

SummaryThe mammalian olfactory system detects and discriminates between millions of odorants to elicit appropriate behavioral responses. While much has been learned about how olfactory sensory neurons detect odorants and signal their presence, how specific innate, unlearned behaviors are initiated in response to ethologically relevant odors remains poorly understood. Here, we show that the 4-transmembrane protein CD20, also known as MS4A1, is expressed in a previously uncharacterized subpopulation of olfactory sensory neurons in the main olfactory epithelium of the murine nasal cavity and functions as a mammalian odorant receptor that recognizes compounds produced by mouse predators. While wild-type mice avoid these predator odorants, mice genetically deleted of CD20 do not appropriately respond. Together, this work reveals a novel CD20-mediated odor-sensing mechanism in the mammalian olfactory system that triggers innate behaviors critical for organismal survival.
A strict requirement in proteasome substrates for spacing between ubiquitin tag and degradation initiation elements
Authors: Davis Caroline , Spaller B. L. , Choi Erin , Kurrasch Joseph , Chong Haemin , Elsasser Suzanne , Finley Daniel , Matouschek Andreas 
Published: August 2023

AbstractProteins are typically targeted to the proteasome for degradation through the attachment of ubiquitin chains and the proteasome initiates degradation at a disordered region within the target protein. Yet some proteins with ubiquitin chains and disordered regions escape degradation. Here we investigate how the position of the ubiquitin chain on the target protein relative to the disordered region modulates degradation and show that the distance between the two determines whether a protein is degraded efficiently. This distance depends on the type of the degradation tag and is likely a result of the separation on the proteasome between the receptor that binds the tag and the site that engages the disordered region.
Intrinsic Susceptibility Of The Left Vs Right Recurrent Laryngeal Nerve To Paralysis: A Systematic Review
Authors: Oswald Aaron , Pitman Michael J 
Published: August 2023

AbstractObjectiveUnilateral vocal fold paralysis (UVFP) occurs more commonly on the left than right, a difference historically attributed to greater left recurrent laryngeal nerve (RLN) length and its presence in the thorax with consequential increased exposure to injury. However, considering the importance of mRNA locally transcribed in the distal nerve after nerve injury, there may be other intrinsic neuromuscular reasons for this discrepancy. To investigate whether intrinsic neuromuscular issues influence laterality, this study investigates the rate of paralysis relative to side in idiopathic and short-term intubation cases, excluding cases due to identifiable disease and surgery.Data SourcesEmbase and PubMed databaseReview MethodsA systematic literature search was performed to capture articles published up until May 2022. Articles were included if laterality and etiology of paralysis were reported. Demographic data was extracted for patients diagnosed with idiopathic paralysis or paralysis after intubation for procedures performed outside the head, neck, and thorax. Study design was collected from included articles.ResultsTwenty-one studies were included, from which 702 patients were drawn for analysis. Within the idiopathic group, 69.2% were left-sided. Within the post-intubation group, 67.9% were left-sided.ConclusionsThe available evidence indicates that left-sided paralysis is more common in patients with idiopathic or short-term intubation related UVFP. This suggests intrinsic neuromuscular differences contribute to the left RLN being more susceptible than the right to damage and dysfunction. Further study is needed to identify these differences, which may provide insights into the pathophysiology of RLN paralysis as well possible therapeutic options.
Global Approaches to Older Abuse Research in Institutional Care Settings: A Systematic Review
Authors: Agaliotis Maria , Morris Tracey , Katz Ilan , Greenfield David 
Published: August 2023

AbstractObjectiveOver the last two decades, authors have argued the rate of abuse among older adults in institutional settings has been underestimated due to challenges in defining and responding to the issue. The purpose of this systematic review is to provide an in-depth analysis of empirical studies examining methodologies measuring abuse of older people residing in a long-term institutional care facility (nursing homes, independent living and assisted living facilities), specifically staff-to-resident abuse.MethodsGuided by PRISMA guidelines, 10 databases were searched from 2005 till July 2023. This review inclusion criteria were any type of abuse, as defined by the World Health Organization reported by staff and residents, family and relatives, and public anonymous registries. This article also includes a methodological critical assessment of studies which has not been conducted before. To direct the review, we use four guiding questions: a) what are the study characteristics? b) what are the methods and measurement tools that have been used? c) what has been the impact of methodology on the results? and d) what is the quality of these studies?ResultsIn the last 18 years, 22 studies from eight counties undertook cross-sectional examinations of staff-to-resident abuse. The review identified a heterogeneity of definitions of abuse and variations with who reported abuse, measurement tools and recall periods. We found the quality of studies varied significantly, with no consistency.DiscussionThese variations in study methodologies impacted the ability to synthesise the findings making it difficult to estimate a global prevalence rate of aged care abuse. From the analysis, we develop an Aged Care Abuse Research Checklist (ACARC) as a first step towards achieving a global standardized, evidence-based methodology for this field. Doing so will normalize processes within organizations and the community, allowing early interventions to change practices, reduce the risk of recurrence and improve resident quality of care and workplace cultures.Systematic Review Registration NumberPROSPERO registry number: CRD42018055484,https://www.crd.york.ac.uk/PROSPERO.