bluuebunny/crossref_metadata_2025_split huggingface dataset:
Telomerase RNA component knockout exacerbatesS. aureuspneumonia by extensive inflammation and dysfunction of T cells
Authors: Reisser Yasmina , Hornung Franziska , Häder Antje , Lauf Thurid , Nietzsche Sandor , Löffler Bettina , Deinhardt-Emmer Stefanie 
Published: June 2024

AbstractThe telomerase RNA component (Terc) constitutes a non-coding RNA critical for telomerase function, commonly associated with aging and pivotal in immunomodulation during inflammation.Our study unveils heightened susceptibility to pneumonia caused byStaphylococcus aureus (S. aureus)inTercknockout (Tercko/ko) mice compared to both young and old infected counterparts. The exacerbated infection in Tercko/komice correlates with heightened inflammation, manifested by elevated interleukin-1β (IL-1β) levels and activation of the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome within the lung.Employing mRNA sequencing methods alongsidein vitroanalysis of alveolar macrophages (AMs) and T cells, our study elucidates a compelling correlation between Tercko/ko, inflammation, and impaired T cell functionality.Tercdeletion results in compromised T cell function, characterized by dysregulation of the T cell receptor and absence of CD247, potentially compromising the host’s capacity to mount an effective immune response againstS. aureus.This investigation provides insights into the intricate mechanisms governing increased vulnerability to severe pneumonia in the context of Terc deficiency, which might also contribute to aging-related pathologies, while also revealing for the first time the influence of Terc on T cell function.Graphical abstract
Interdisciplinarity through internationality: results from a US-Mexico graduate course bridging computational and plant science
Authors: Chitwood Daniel H. , Rougon-Cardoso Alejandra , VanBuren Robert 
Published: June 2024

AbstractInterdisciplinarity is used to integrate and synthesize new research directions between scientific domains, but it is not the only means by which to generate novelty by bringing diverse perspectives together. Internationality draws upon cultural and linguistic diversity that can potentially impact interdisciplinarity as well. We created an interdisciplinary class originally intended to bridge computational and plant science that eventually became international in scope, including students from the US and Mexico. We administered a survey over four years designed to evaluate student expertise. The first year of the survey included only US students and demonstrated that biology and computational student groups have distinct expertise but can learn the skills of the other group over the course of a semester. Modeling of survey responses shows that biological and computational science expertise is equally distributed between US and Mexico student groups, but that nonetheless these groups can be predicted based on survey responses due to sub-specialization within each domain. Unlike interdisciplinarity, differences arising from internationality are mostly static and do not change with educational intervention and include unique skills such as working across languages. We end by discussing a distinct form of interdisciplinarity that arises through internationality and the implications of globalizing research and education efforts.
Head-to-head comparison of diagnostic accuracy of TB screening tests: Chest-X-ray, Xpert TB host response, and C-reactive protein
Authors: Crowder Rebecca , Thangakunam Balamugesh , Andama Alfred , Christopher Devasahayam J , Dalay Victoria , Dube-Nwamba Welile , Kik Sandra V. , Van Nguyen Dong , Nhung Nguyen Viet , Phillips Patrick PJ , Ruhwald Morten , Theron Grant , Worodria William , Yu Charles , Nahid Payam , Cattamanchi Adithya , Gupta-Wright Ankur , Denkinger Claudia M. ,   R2D2 TB Network
Published: June 2024

ABSTRACTBackgroundAccessible, accurate screening tests are necessary to advance tuberculosis (TB) case finding and early detection in high-burden countries. We compared the diagnostic accuracy of available TB triage tests.MethodsWe prospectively screened consecutive adults with ≥2 weeks of cough presenting to primary health centers in the Philippines, Vietnam, South Africa, Uganda, and India. All participants received the index tests: chest-X-ray (CXR), venous or capillary Cepheid Xpert TB Host Response (HR) testing, and point-of-care C-reactive protein (CRP) testing (Boditech iChroma II). CXR images were processed using computer-aided detection (CAD) algorithms. We assessed diagnostic accuracy against a microbiologic reference standard (sputum Xpert Ultra, culture). Optimal cut-points were chosen to achieve sensitivity ≥90% and maximize specificity. Two-test screening algorithms were considered, using two approaches: 1) sequential negative serial screening in which the second screening test is conducted only if the first is negative and positive is defined as positive on either test and 2) sequential positive serial screening, in which the second screening test is conducted only if the first is positive and positive is defined as positive on both tests.ResultsBetween July 2021 and August 2022, 1,392 participants with presumptive TB had valid results on index tests and the reference standard, and 303 (22%) had confirmed TB. In head-to-head comparisons, CAD4TB v7 showed the highest specificity when using a cut-point that achieves 90% sensitivity (70.3% vs. 65.1% for Xpert HR, difference 95% CI 1.6 to 8.9; 49.7% for CRP, difference 95% CI 17.0 to 24.3). Among the possible two-test screening algorithms, three met WHO target product profile (TPP) minimum accuracy thresholds and had higher accuracy than any test alone. At 90% sensitivity, the specificity was 79.6% for Xpert HR-CAD4TB [sequential negative], 75.9% for CRP-CAD4TB [sequential negative], and 73.7% for Xpert HR-CAD4TB [sequential positive].ConclusionsCAD4TB achieves TPP targets and outperforms Xpert HR and CRP. Combining screening tests further increased accuracy. Cost and feasibility of two-test screening algorithms should be explored.RegistrationNCT04923958
segcsvdWMH: A convolutional neural network-based tool for quantifying white matter hyperintensities in heterogeneous patient cohorts
Authors: Gibson Erin , Ramirez Joel , Woods Lauren Abby , Ottoy Julie , Berberian Stephanie , Scott Christopher J.M. , Yhap Vanessa , Gao Fuqiang , Coello Roberto Duarte , Valdes Hernandez Maria , Lang Anthony E. , Tartaglia Carmela M. , Kumar Sanjeev , Binns Malcolm A. , Bartha Robert , Symons Sean , Swartz Richard H. , Masellis Mario , Singh Navneet , Moody Alan , MacIntosh Bradley J. , Wardlaw Joanna M. , Black Sandra E. ,   ONDRI Investigators, ADNI, CAIN Investigators, colleagues from the Foundation Leducq Transatlantic Network of Excellence, Lim Andrew SP , Goubran Maged 
Published: June 2024

AbstractWhite matter hyperintensities (WMH) of presumed vascular origin are an MRI-based biomarker of cerebral small vessel disease (CSVD). WMH are associated with accelerated cognitive decline and increased risk of stroke and dementia, and are commonly observed in aging, vascular cognitive impairment, Alzheimer’s and Parkinson’s disease, and related dementias. The accurate, reliable, and rapid measurement of WMH in large-scale multi-site clinical studies with heterogeneous patient populations remains challenging. The diversity of MRI protocols and image characteristics across different studies as well as the diverse nature of WMH, in terms of their highly variable shape, size, distribution, and underlying pathology, adds additional complexity to this task. Here, we present segcsvdWMH, a novel convolutional neural network-based tool for quantifying WMH. segcsvdWMHis specifically designed for accurate and robust performance when applied to diverse clinical patient datasets. Central to the development of this tool is the curation of a large patient dataset (>700 scans) sourced from seven multi-site studies, encompassing a wide range of clinical populations, WMH burden, and imaging parameters. The performance of segcsvdWMHis evaluated against three widely used WMH segmentation tools, where we demonstrate significantly enhanced accuracy and robustness across a range of challenging conditions and datasets.
The association between NfL and Cognitive Functioning in older adults diagnosed diabetes: a cross-sectional analysis from NHANES
Authors: LiLi  , Li Cheng-Bo , Zhu Li , Zhu Jiang 
Published: June 2024

AbstractObjectiveThis research aimed to explore the correlation between serum Neurofilament Light Chain (NfL) levels and Cognitive Function in diabetic participants.MethodsUtilizing cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2013 to 2014, 173 individuals aged 60 years and above with diabetes were included in the analysis. Cognitive function was measured using the Animal Fluency exercise. Weighted multivariate linear regression analysis and a restricted cubic spline model were employed to assess the association between serum NfL levels and Animal Fluency Score (CFDAST) in diabetic patients.ResultsSerum NfL was categorized into weighted tertiles, with participants divided into groups Q1, Q2, and Q3. Significant differences in serum NfL were observed among the groups (P < 0.01). Participants in group Q3 exhibited higher levels of hemoglobin A1c and were older compared to groups Q1 and Q2 (P < 0.01). Furthermore, when serum NfL was treated as a continuous variable, it was found to have a negative correlation with CFDAST score (P < 0.01). Group Q1 had a higher CFDAST score than group Q3, as well as group Q2 (p for trend = 0.0021). A nonlinear relationship was observed between serum NfL and CFDAST score, displaying an inverted ‘U-shaped’ curve (P-overall = 0.01, P-for-non-linear = 0.0026).ConclusionsSerum NfL has the potential to serve as a clinical biomarker for early detection of cognitive impairment in diabetic individuals aged over 60 years.HighlightsStudy about biomarkers for diabetes-associated cognitive decline is limited.We found that there is an inverted U-shaped association between serum NfL and cognitive score.Serum NfL may be a biomarker for early detection of cognitive decline in elderly diabetics.
WITHDRAWN: Deep Learning Solutions for Pneumonia Detection: Performance Comparison of Custom and Transfer Learning Models
Authors: Zhong Yihao , Liu Yanan , Gao Erdi , Wei Changsong , Wang Zhuoyue , Yan Chao 
Published: June 2024

Withdrawal StatementThe authors have withdrawn this manuscript because of the following reasons:Significant Methodological Errors: Upon further review of our work, we discovered critical methodological errors in the data preprocessing stage that affect the reliability and reproducibility of the results. These errors could mislead other researchers if left unaddressed.Inaccurate Data Interpretation: In addition, we have found that some of the interpretations of the results, especially concerning model performance, were not adequately supported by the data. This misinterpretation has led to conclusions that do not align with our current understanding of the study.Ethical Considerations: After further reflection, we have recognized the need to clarify certain ethical aspects of our data collection process, especially regarding the dataset used. This issue needs to be addressed in compliance with ethical guidelines before the findings can be deemed credible and citable.New Research Developments: Finally, new developments in related research have emerged, which contradict some of the conclusions presented in our manuscript. As we plan to pursue a different direction that incorporates these new findings, we feel that it is necessary to retract the current manuscript.After careful reconsideration, my co-authors and I have identified several issues that we believe warrant the withdrawal of the manuscript. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Implementation of a “people-like-me” tool for personalized rehabilitation after total knee arthroplasty: A mixed methods pilot study
Authors: Graber Jeremy , Hinrichs-Kinney Lauren , Churchill Laura , Matlock Daniel D , Kittelson Andrew , Lutz Adam , Bade Michael , Stevens-Lapsley Jennifer 
Published: June 2024

AbstractRationaleWhile there are numerous tools available to inform if and when to use total knee arthroplasty (TKA), very few tools exist to help guide the recovery period after surgery.Aims and ObjectivesWe piloted a decision support tool that promotes a “people-like-me” (PLM) approach to rehabilitation after total knee arthroplasty (TKA). The PLM approach encourages person-centered care by “using historical outcomes data from similar (past) patients as a template of what to expect for a new patient”. In this study, we evaluated how successfully the PLM tool was implemented and examined contextual factors that may have influenced its implementation.MethodsTwo outpatient physical therapy clinics (Clinics A and B) piloted the PLM tool from September 2020 – December 2022. We gathered data related to its implementation from multiple sources including the electronic health record, the tool itself, and surveys and interviews with patients and clinicians. We used an explanatory sequential mixed methods design to analyze the data overall and separately by each clinic.ResultsOverall, the clinics met most pre-specified implementation targets, but did not use the tool as frequently as intended. Both clinics identified time, technology, and scheduling barriers to using the tool, but Clinic A scored higher in nearly every implementation outcome. Clinic A’s success may have been related to its clinicians’ higher level of experience, more positive attitudes towards the tool, and more active approach to implementation compared to Clinic B.ConclusionsThe clinics met most of our implementation targets, but Clinic A experienced more success than Clinic B. Future efforts to implement this PLM tool should (1) engage clinicians as active participants in the implementation process, (2) explore whether incorporating treatment recommendations into the PLM tool and/or using alternative training strategies can enhance its ability to alter clinician behavior, (3) integrate the tool within the EHR to complement existing workflows and mitigate implementation barriers, and (4) include randomized controlled trials that evaluate the tool’s effectiveness and scalability across diverse clinical settings.
Advances in methods for characterizing dietary patterns: A scoping review
Authors: Hutchinson Joy M. , Raffoul Amanda , Pepetone Alexandra , Andrade Lesley , Williams Tabitha E. , McNaughton Sarah A. , Leech Rebecca M. , Reedy Jill , Shams-White Marissa M. , Vena Jennifer E. , Dodd Kevin W. , Bodnar Lisa M. , Lamarche Benoît , Wallace Michael P. , Deitchler Megan , Hussain Sanaa , Kirkpatrick Sharon I. 
Published: June 2024

AbstractThere is a growing focus on better understanding the complexity of dietary patterns and how they relate to health and other factors. Approaches that have not traditionally been applied to characterize dietary patterns, such as machine learning algorithms and latent class analysis methods, may offer opportunities to measure and characterize dietary patterns in greater depth than previously considered. However, there has not been a formal examination of how this wide range of approaches has been applied to characterize dietary patterns. This scoping review synthesized literature from 2005-2022 applying methods not traditionally used to characterize dietary patterns, referred to as novel methods. MEDLINE, CINAHL, and Scopus were searched using keywords including machine learning, latent class analysis, and least absolute shrinkage and selection operator (LASSO). Of 5274 records identified, 24 met the inclusion criteria. Twelve of 24 articles were published since 2020. Studies were conducted across 17 countries. Nine studies used approaches that have applications in machine learning to identify dietary patterns. Fourteen studies assessed associations between dietary patterns that were characterized using novel methods and health outcomes, including cancer, cardiovascular disease, and asthma. There was wide variation in the methods applied to characterize dietary patterns and in how these methods were described. The extension of reporting guidelines and quality appraisal tools relevant to nutrition research to consider specific features of novel methods may facilitate complete and consistent reporting and enable evidence synthesis to inform policies and programs aimed at supporting healthy dietary patterns.
Discovery of a novel antifungal compound, ilicicolin K, through genetic activation of the ilicicolin biosynthetic pathway inTrichoderma reesei
Authors: Burger Isabella , Schmal Matthias , Peikert Kathrin , Fourtis Lukas , Suster Christoph , Stanetty Christian , Schnalzer Dominik , Birner-Gruenberger Ruth , Mach Robert L , Mach-Aigner Astrid R. , Schittmayer Matthias , Zimmermann Christian 
Published: June 2024

AbstractIn the quest to discover novel antifungal agents and new antifungal production processes, we investigated the biosynthetic gene cluster (BGC) for ilicicolin H in the fungusTrichoderma reesei. While the BGC is silent under standard cultivation conditions, we achieved to activate it by over-expressing its transcription factor TriliR. Successful BGC activation was confirmed by RT-qPCR, proteomic and metabolomic analyses. Metabolomic profiling upon BGC expression revealed high-yield production of the supposed main product ilicicolin H. To elucidate the functionality of this BGC, we employed a combination of overexpression and deletions of individual biosynthetic gene cluster constituents. Deletion oftriliA, encoding for the core polyketide synthase TriliA, completely ceased product formation, as expected. In contrast to previous heterologous expression experiments, we could demonstrate that the epimerase TriliE is necessary for the formation of ilicicolin H in the native host. While we hardly observed any of the previously reported side- or shunt products associated with heterologous ilicicolin H expression, we discovered a novel member of the ilicicolin family using a metabolomic molecular networking approach. This new compound, which we termed ilicicolin K, is expressed in substantial amounts in the genetically engineeredTrichoderma reesei, enabling us to elucidate its structure by NMR. The structure of ilicicolin K is similar to that of ilicicolin H but differs by an additional hydroxylation and an intramolecular etherification of the hydroxyl group at the pyridone towards the tyrosine moiety of the molecule. Initial tests of ilicicolin K showed antifungal activity againstSaccharomyces cerevisiaeandAspergillus nidulanswith a similar minimum inhibitory concentration as ilicicolin H.
Genetic diversity and cross-species transmissibility of bat-associated picornaviruses from Spain
Authors: Carrascosa-Sàez Marc , Buigues Jaime , Viñals Adrià , Andreu-Moreno Iván , Martínez-Recio Raquel , Soriano-Tordera Clàudia , Monrós Juan S. , Cuevas José M. , Sanjuán Rafael 
Published: June 2024

AbstractBackgroundEmerging zoonotic diseases arise from cross-species transmission events between wild or domesticated animals and humans, with bats being one of the major reservoirs of zoonotic viruses. Viral metagenomics has led to the discovery of many viruses, but efforts have mainly been focused on some areas of the world and on certain viral families.MethodsWe set out to describe full-length genomes of new picorna-like viruses by collecting feces from hundreds of bats captured in different regions of Spain. Viral sequences were obtained by high-throughput Illumina sequencing and analyzed phylogenetically to classify them in the context of known viruses. Linear discriminant analysis (LDA) was performed to infer likely hosts based on genome composition.ResultsWe found five complete or nearly complete genomes belonging to the familyPicornaviridae, including a new species of the subfamilyEnsavirinae. LDA suggested that these were true vertebrate viruses, rather than viruses from the bat diet. Some of these viruses were related to picornaviruses previously found in other bat species from distant geographical regions. We also found a calhevirus genome that most likely belongs to a proposed new family within the orderPicornavirales, and for which genome composition analysis suggested a plant host.ConclusionsOur findings describe new picorna-like viral species and variants circulating in the Iberian Peninsula, illustrate the wide geographical distribution and interspecies transmissibility of picornaviruses, and suggest new hosts for calheviruses.
The amniote-conserved DNA-binding domain of CGGBP1 restricts cytosine methylation of transcription factor binding sites in proximal promoters to regulate gene expression
Authors: Morbia Ishani , Kumar Praveen , Satish Aditi Lakshmi , Mudgal Akanksha , Datta Subhamoy , Singh Umashankar 
Published: June 2024

AbstractCGGBP1 is a GC-rich DNA-binding protein which is important for genomic integrity, gene expression and epigenome maintenance through regulation of CTCF occupancy and cytosine methylation. It has remained unclear how CGGBP1 integrates multiple diverse functions with its simple architecture of only a DNA-binding domain tethered to a C-terminal tail with low structural rigidity. We have used truncated forms of CGGBP1 with or without the DNA-binding domain (DBD) to assay cytosine methylation and global gene expression. Proximal promoters of CGGBP1-repressed genes, although significantly GC-poor, contain GC-rich transcription factor binding motifs and exhibit base compositions indicative of low C-T transition rates due to prevention of cytosine methylation. Genome-wide analyses of cytosine methylation and binding of CGGBP1 DBD show that CGGBP1 restricts cytosine methylation in a manner that depends on its DBD and its DNA-binding. The CGGBP1-repressed genes show an increase in promoter cytosine methylation alongside a decrease in transcript abundance when the DBD-deficient CGGBP1 is expressed. Our findings suggest that CGGBP1 protects transcription factor binding sites (TFBS) from cytosine methylation-associated loss and thereby regulates gene expression. By analysing orthologous promoter sequences we show that restriction of cytosine methylation is a function of CGGBP1 progressively acquired during vertebrate evolution. A superimposition of our results and evolution of CGGBP1 suggests that mitigation of cytosine methylation is majorly achieved by its N-terminal DBD. Our results position CGGBP1 DNA-binding as a major evolutionarily acquired mechanism through which it keeps cytosine methylation under check and regulates TFBS retention and gene activity.