bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cryo-PRO facilitates whole blood cryopreservation for single-cell RNA sequencing of immune cells from clinical samples
Authors: DuBois Alyssa K. , Ankomah Pierre O. , Campbell Alexis C. , Hua Renee , Nelson Olivia K. , Zeuthen Christopher A. , Das M. Kartik , Mann Shira , Mauermann Abigail , Parry Blair A. , Shapiro Nathan I. , Filbin Michael R. , Bhattacharyya Roby P. 
Published: September 2024

ABSTRACTSingle-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) has enhanced our understanding of host immune mechanisms in small cohorts, particularly in diseases with complex and heterogeneous immune responses such as sepsis. However, PBMC isolation from blood requires technical expertise, training, and approximately two hours of onsite processing using Ficoll density gradient separation (‘Ficoll’) for scRNA-seq compatibility, precluding large-scale sample collection at most clinical sites. To minimize onsite processing, we developed Cryo-PRO (Cryopreservation with PBMC Recovery Offsite), a method of PBMC isolation from cryopreserved whole blood that allows immediate onsite sample cryopreservation and subsequent PBMC isolation in a central laboratory prior to sequencing. We compared scRNA-seq results from samples processed using Cryo-PRO versus standard onsite Ficoll separation in 23 patients with sepsis. Critical scRNA-seq outputs including cell substate fractions and marker genes were similar for each method across multiple cell types and substates, including an important monocyte substate enriched in patients with sepsis (Pearson correlation 0.78, p<0.001; 70% of top marker genes shared). Cryo-PRO reduced onsite sample processing time from >2 hours to <15 minutes and was reproducible across two enrollment sites, thus demonstrating potential for expanding scRNA-seq in multicenter studies of sepsis and other diseases.
A New Algorithm for Incidental Pancreatic Cyst Detection
Authors: Berbís M. Álvaro , Moreno-Vedia Juan , Paulano-Godino Félix , Viteri Ainhoa , Riera-Marín Meritxell , Cañadas-Gómez Daniel , Trotta Romina , Forastero Beatriz , Luna Luis , López Javier García , Luna Antonio , Rodríguez-Comas Júlia 
Published: September 2024

ABSTRACTObjectivesTo develop an accurate, state-of-the-art algorithm for the incidental detection of pancreatic cystic lesions (PCLs) on computerized tomography (CT) and magnetic resonance imaging (MRI) scans.MethodsA SwinT-Unet-based architecture was developed for the incidental detection of PCLs. The algorithm was trained and validated on a robust dataset of retrospective CT and MRI studies collected from HT Médica centers located in eight different cities using scanners fabricated by four different manufacturers.ResultsOur algorithm was able to detect 91.6% of the confirmed PCLs in the initial dataset with 91.6% sensitivity and 92.3% specificity, while 91.7% of the healthy controls were also correctly identified. Furthermore, our tool was remarkably capable of classifying these PCLs as mucinous or non-mucinous, determining their location within the pancreas with an accuracy of 88.5%, and identifying the presence of calcifications or scars within the PCLs with an accuracy of 96%.ConclusionsBy integrating radiological data and state-of-the-art artificial intelligence techniques, we have developed an efficient tool for the incidental identification and initial characterization of PCLs, which present a substantial prevalence within the global population. Our algorithm facilitates early diagnosis of pancreatic abnormalities, which could have a profound impact on patient management and prognosis, particularly in the case of PCLs with malignant potential.
Alignment of Large Language Models in Solving Medical Ethical Dilemmas
Authors: Sorin Vera , Glicksberg Benjamin S. , Korfiatis Panagiotis , Collins Jeremy D. , Yeow Mei-Ean E. , Brandeland Megan , Nadkarni Girish N. , Klang Eyal 
Published: September 2024

AbstractDeontology and utilitarianism are two philosophical approaches to ethical decision-making, often illustrated by the well-known “Trolley” dilemma. We evaluated fourteen large language models (LLMs), including GPT-o1-preview and DeepSeek-R1-Distill-Llama, across five medical versions of this dilemma. While some models adhered to established ethical standards, others showed inconsistencies. All models occasionally favored a utilitarian approach over a deontological approach, with some reaching up to 80% of decisions. In certain instances, LLMs endorsed actions that would uniformly be considered unethical, such as amputating a limb without consent. These findings raise concerns about the real-world risks of using LLMs in clinical decision-making, particularly regarding patient autonomy and safety, and highlight the need for further investigation into how these models align with current medical ethical standards.
Randomised Badger Culling Trial lacks evidence for proactive badger culling effect on tuberculosis in cattle: comment on Mills et al. 2024, Parts I & II
Authors: Torgerson PR , Hartnack S , Rasmussen P , Lewis F , O’Donnell P , Langton TES 
Published: September 2024

AbstractRe-evaluation of statistical analysis of the Randomised Badger Culling Trial (RBCT) by Torgerson et al. 2024 was rebutted by Mills et al. 2024 Parts I and II. The rebuttal defended the use of count rather than rate when considering bovine tuberculosis herd incidence. The defence makes biologically implausible use of Information Criterion for appraisal diagnostics; overfits data; and has erroneous Bayesian analyses. It favours ‘goodness of fit’ over ‘predictive power’, for a small data set, when the study was to inform application. Importantly, for ‘total’ bTB breakdown: (‘confirmed’ (OTF-W) +’unconfirmed’ (OTF-S)), where modern interpretation of the main diagnostic bTB test better indicates the incidence rate of herd breakdown, there is no effect in cull and neighbouring areas, across all statistical models. The RBCT was a small, single experiment with unknown factors. With respect to the paradigm of reproducibility and the FAIR principles, the original RBCT analysis and recent efforts to support it are wholly unconvincing. The 2006 conclusion of the RBCT that “badger culling is unlikely to contribute positively to the control of cattle TB in Britain” is supported, but the route to such a position is revised in the light of modern veterinary understanding and statistical reappraisal.
SARS-CoV-2 Survival on Skin and its Transfer from Contaminated Surfaces
Authors: Pitol Ana K. , Venkatesan Samiksha , Richards Siobhan , Hoptroff Michael , Majumdar Amitabha , Hughes Grant 
Published: September 2024

ABSTRACTUnderstanding the transmission dynamics of SARS-CoV-2, particularly its transfer from contaminated surfaces (fomites) to human skin, is crucial for mitigating the spread of COVID-19. While extensive research has examined the persistence of SARS-CoV-2 on various surfaces, there is limited understanding of how efficiently it transfers to human skin, and how long it survives on the skin. This study investigates two key aspects of SARS-CoV-2 transmission: (1) the transfer efficiency of SARS-CoV-2 from non-porous (plastic and metal) and porous (cardboard) surfaces to a 3D human skin model (LabSkin), and (2) the survival of SARS-CoV-2 on the skin under different temperature conditions. First, we validated LabSkin as a suitable surrogate for human skin by comparing the transfer efficiency of the bacteriophage Phi 6 from surfaces to LabSkin and to human volunteers’ fingers. No significant differences were observed, confirming LabSkin’s suitability for these studies. Subsequently, the transfer of SARS-CoV-2 from surfaces to LabSkin was assessed, showing that plastic and metal surfaces had similar transfer efficiencies (∼13%), while no transfer occurred from cardboard once the inoculum had dried on the surface. Finally, the survival of SARS-CoV-2 on skin was assessed, showing a rapid decay at higher temperatures, with a half-life ranging from 2.8 to 17.8 hours depending on the temperature. These findings enhance our understanding of viral transmission via fomites and inform public health strategies to reduce the risk of SARS-CoV-2 transmission through surface contact.
A virus associated with the zoonotic pathogenPlasmodium knowlesicausing human malaria is a member of a diverse and unclassified viral taxon
Authors: Petrone Mary E. , Charon Justine , Grigg Matthew J , William Timothy , Rajahram Giri S , Westaway Jacob , Piera Kim A , Shi Mang , Anstey Nicholas M. , Holmes Edward C. 
Published: September 2024

ABSTRACTApicomplexa are single-celled eukaryotes that can infect humans and include the mosquito-borne parasitePlasmodium, the cause of malaria. Increasing rates of drug resistance in human-onlyPlasmodiumspecies are reducing the efficacy of control efforts and antimalarial treatments. There are also rising cases ofP. knowlesi, the only zoonoticPlasmodiumspecies that causes severe disease and death in humans. Thus, there is a need to develop additional innovative strategies to combat malaria. Viruses that infect non-Plasmodiumspp. disease-causing protozoa have been shown to affect pathogen life cycle and disease outcomes. However, only one virus (Matryoshka RNA virus 1) has been identified inPlasmodium, and none have been identified in zoonoticPlasmodiumspecies. The rapid expansion of the known RNA virosphere using structure- and artificial intelligence-based methods suggests that this dearth is due to the divergent nature of RNA viruses that infect protozoa. We leveraged these newly uncovered data sets to explore the virome of human-infectingPlasmodiumspecies collected in Sabah, east (Borneo) Malaysia. We identified a highly divergent RNA virus in two human-infectingP. knowlesiisolates that is related to the unclassified group ‘ormycoviruses’. By characterising fifteen additional ormycoviruses identified in the transcriptomes of arthropods we show that this group of viruses exhibits a complex ecology at the arthropod-mammal interface. Through the application of artificial intelligence methods, we then demonstrate that the ormycoviruses are part of a diverse and unclassified viral taxon. This is the first observation of an RNA virus in a zoonoticPlasmodiumspecies. By linking small-scale experimental data to large-scale virus discovery advances, we characterise the diversity and genomic architecture of an unclassified viral taxon. This approach should be used to further explore the virome of disease-causing Apicomplexa and better understand how protozoa-infecting viruses may affect parasite fitness, pathobiology, and treatment outcomes.
Bovhyaluronidase azoximer for long-term pulmonary sequelae of COVID-19: a randomized, double-blind, placebo-controlled trial
Authors: Avdeev Sergey N. , Ignatova Galina L. , Drapkina Oxana M. , Popova Veronica B. , Melnikova Ekaterina V. , Chudinovskikh Tatiana I. , Ryabova Olga V. , Egorova Natalia V. , Rubanik Tamara V. , Shvarts Yury G. , Polyakova Svetlana A. , Dzutseva Vitalina , Antonova Anna V. , Zubkov Dmitry A. , Khmelevskii Mikhail S. , Khomyakova Nadezhda F. , Tsyferov Mikhail A. , Hardman Tim C. , Tikhonov Anton A. 
Published: September 2024

AbstractBackgroundHyaluronan is an emerging target for COVID-19 and lung fibrosis. In an open-label study the hyaluronidase bovhyaluronidase azoximer (BA) was associated with improved pulmonary function and exercise tolerance in patients with pulmonary sequelae of COVID-19. In this randomized, double-blind, placebo-controlled trial we evaluated the effect of BA on patients up to 12 months after COVID-19, characterized by reduced pulmonary function, dyspnea, and decreased oxygen saturation.MethodsPatients (n=392) were randomized 1:1 to receive BA (3000U) or placebo every 5 days for 71 days. Percent of predicted forced vital capacity (ppFVC), respiratory symptoms, and exercise tolerance indicators were assessed at baseline and on days 71 and 180. The primary endpoint was a change from baseline in ppFVC by Day 71.ResultsOn Day 71, BA was associated with a significant reduction in the proportion of patients with exertional desaturation (OR=0.35, p=0.0051) and dyspnea (OR=0.62, p=0.043). There were no significant intergroup differences in the ppFVC growth rate. Analysis of sub-populations revealed that by Day 180, BA was associated with increased ppFVC in patients with cardiovascular comorbidities (diff=3.31%, p=0.042) and those with earlier SARS-CoV-2 infection (diff=4.17%, p=0.021). BA was generally safe and well-tolerated.ConclusionIn patients with long-term pulmonary sequelae of COVID-19, BA was associated with increased exercise tolerance. There was evidence of shorter pulmonary function recovery time following BA in patients with cardiovascular comorbidities and those with earlier COVID-19 disease.
Antimicrobial Potential and Characterization of Silver Nanoparticles Synthesized fromOcimum SanctumExtract
Authors: Sulaiman Mustapha , Muhammad Ma’aruf Abdulmumin , Sulaiman Aminu Shehu , Abubakar Amina Lawan , Sharma Ritu , Shuaibu Abubakar Musa , Aliyu Mamudu , Mustapha Ibrahim Tasi’u , Tiwari Raksha 
Published: September 2024

AbstractThe growing resistance of microbes to conventional antibiotics and the environmental impact of chemical synthesis methods highlight the urgent need for effective and sustainable antimicrobial agents. In this study, we address these challenges by synthesizing silver nanoparticles (AgNPs) usingOcimum sanctumleaf extract, a green and efficient method. We confirmed AgNPs synthesis through UV-vis spectroscopy, observing a Surface Plasmon Resonance (SPR) peak centered at 420 nm. X-ray Diffraction (XRD) analysis showed intense peaks at 37.81°, 45.01°, 63.91°, and 78.0°, corresponding to Bragg’s reflections at 111, 200, 220, and 311, respectively, with an average particle size of approximately 18 nm calculated using Scherrer’s formula. The reduction of Ag+was monitored using Atomic Absorption Spectroscopy (AAS), which revealed a rapid decrease from 2.73 ppm to 0.023 ppm within four minutes, driven by the active reducing agents in theO. sanctumextract. The Scanning Electron Microscope (SEM) image confirmed the spherical shape of the AgNPs, with an average size of 23.82 ± 4.17 nm. Fourier Transform Infrared (FTIR) spectroscopy identified absorption peaks at 1635 cm-1and 3430 cm-1, associated with the amide I bond of proteins and OH stretching in alcohols and phenolic compounds, respectively. The synthesized AgNPs exhibited significant antimicrobial activity, demonstrated by a dose-dependent inhibitory effect against bacterial strains. The inhibition zone measured 6 mm at the lowest concentration of 5 µg/L and increased progressively to 14 mm at the highest concentration of 25 µg/L, indicating strong antimicrobial potential even at low dosages.
Potential Cancer Biomarkers: Mitotic Intra-S DNA Damage Checkpoint Genes
Authors: Agarwal Kashvi , Liu Hengrui 
Published: September 2024

ABSTRACTBACKGROUNDThe mitotic intra-S DNA damage checkpoint signaling gene set is potentially involved in cancers where the genes play an important role. 17 total genes are involved in this gene set: ATF2, CHEK2, EME1, EME2, FANCD2, HUS1, HUS1B, MDC1, MRE11, MSH2, MUS81, NEK11, RAD17, RAD9A, RAD9B, TIPIN, XPC. The aim of this study is to complete a pan-cancer profile of each gene in the mitotic intra-S DNA damage checkpoint signaling gene set in order to determine potential diagnostic and prognostic purposes, while also determining how they could be used in a clinical setting as therapeutic targets to help patients.METHODSMultiomic data was acquired for the 17 genes; over 9000 samples of 33 types of cancer were analyzed to create pan-cancer profiles of CNV, mRNA expression, and pathway analysis.RESULTSThe CNVs of some of these genes are associated with the survival of MESO, PCPG, BLCA, SKCM, LUAD, HNSC, LUSC, OV, and BRCA could be affected by the mRNA expression of the genes which can involve regulation of copy number.CONCLUSIONWith sufficient investigation, the genes involved in mitotic intra-S DNA damage checkpoint signaling may contribute to the development of cancer and may be used as biomarkers for cancer prognosis and diagnosis. To prove their clinical use for diagnosis and prognosis, however, and to create workable applications in clinical settings, further work is required. However, these pan-cancer profiles provide a more comprehensive knowledge of the mitotic intra-S DNA damage checkpoint signaling gene set in cancer as well as valuable information for future reference.
The human ribosome modulates multidomain protein biogenesis by delaying cotranslational domain docking
Authors: Pellowe Grant A. , Voisin Tomas B. , Karpauskaite Laura , Maslen Sarah L. , Roeselová Alžběta , Skehel J. Mark , Roustan Chloe , George Roger , Nans Andrea , Kjær Svend , Taylor Ian A. , Balchin David 
Published: September 2024

AbstractProteins with multiple domains are intrinsically prone to misfold, yet fold efficiently during their synthesis on the ribosome. This is especially important in eukaryotes, where multidomain proteins predominate. Here, we sought to understand how multidomain protein folding is modulated by the eukaryotic ribosome. We used cryo-electron microscopy and hydrogen/deuterium exchange-mass spectrometry to characterise the structure and dynamics of partially-synthesised intermediates of a model multidomain protein. We find that nascent subdomains fold progressively during synthesis on the human ribosome, templated by interactions across domain interfaces. The conformational ensemble of the nascent chain is tuned by its unstructured C-terminal segments, which keep interfaces between folded domains in dynamic equilibrium until translation termination. This contrasts with the bacterial ribosome, on which domain interfaces form early and remain stable during synthesis. Delayed domain docking may avoid interdomain misfolding to promote the maturation of multidomain proteins in eukaryotes.
Disulfide-mediated tetramerization of TRAP1 fosters its antioxidant and pro-neoplastic activities
Authors: Faienza Fiorella , Laquatra Claudio , Castelli Matteo , Rizza Salvatore , Guarra Federica , Dashtmian Azam Roshani , Giglio Paola , Pecorari Chiara , Ferrone Lavinia , Moroni Elisabetta , Pacello Francesca , Battistoni Andrea , Colombo Giorgio , Rasola Andrea , Filomeni Giuseppe 
Published: September 2024

AbstractThe mitochondrial chaperone TRAP1 exerts a protective function in cells exposed to diverse stress conditions in both physiological and pathological contexts. In cancer cells, it contributes to neoplastic progression ensuing metabolic rewiring and protection from oxidative insults.TRAP1 works as a homodimer, but recent evidence has indicated that it can form tetramers whose functional effects remain elusive. Here, we find that TRAP1 forms redox-sensitive tetramers via disulfide bonds involving two critical cysteine residues, C261 and C573. TRAP1 tetramerization is elicited by oxidative stress and abrogated upon expression of the double C261S/C573R mutant. In cancer contexts, the expression of the TRAP1 C261S/C573R mutant is unable to inhibit the activity of its client succinate dehydrogenase and to confer protection against oxidative insults, and it hampers invasiveness of aggressive sarcoma cells.Our data indicate that TRAP1 undergoes tetramerization in response to oxidative stress and identify C261 and C573 as critical for TRAP1 structural rearrangement and for functions.
A systematic review of professional society-backed biology education DEI research: The groups, research methods, and levels of analyses comprising the field
Authors: Idlebird Candice , Campbell-Montalvo Rebecca , McDowell Gary S. , Blosser Emily , Harvey Richard , Marcette Jana 
Published: September 2024

AbstractThis integrative literature review analyzes the corpus of biology education research published in the main biology education journals of major professional societies. The goal of this analysis is to determine which approaches (including groups of focus, research methods, and settings/perspectives) from social science fields (i.e., psychology, sociology, and anthropology) are utilized in published peer-reviewed biology education research relating to diversity, equity and inclusion (DEI). Scoping how social science approaches are used in this area is important to understanding whether biology education research could benefit from complementary approaches that might advance praxis. This analysis found that research informing the biology education community draws heavily from psychological perspectives that are overwhelmingly not disaggregated (78% of articles identifying a group used a lumped together one), are by far more quantitative (58% used survey, 26% grades, 20% school data) than qualitative (17% used interview, 10% observation), and did not (72%) adopt structural approaches. The addition of missing contributions from social science is critical to advancing interventions to broaden STEM participation given that merging paradigms can offer more robust, multi-level explanations for observed phenomena. This has important implications for education, biology education, biology education research, social science, and research in related STEM fields.
Innate Immune Receptor NLRX1: Potential Modulator of Glioblastoma Pathophysiology
Authors: Meena Durgesh , Shivakumar Divya , Rajkhowa Sushmita , Bhattacharya Neermita , Solanki Priya , Chhipa Shalini , Janu Vikas , Garg Mayank , Gosal Jaskaran Singh , Jha Sushmita 
Published: September 2024

AbstractGliomas are primary brain tumors that develop from glial cells within the central nervous system and are among the deadliest human cancers. Glioblastoma (GBM) is the most malignant form of glioma. NLRX1 is an innate immune pattern recognition receptor that exhibits tumor-suppressive and tumor-promoting effects that may be cancer or cell-type, context-dependent, aided by differences in the microenvironment. Here, we report that NLRX1 is differentially expressed in microglia, astrocytes, GBM cell lines, and glioma patient tissues. siRNA-mediated silencing ofNlrx1decreases the ability of the GBM cell line, LN-229, to proliferate and migrate.Nlrx1-/-GBM cells exhibit attenuated ability to generate 3D spheroids and enhanced capability to form tunneling nanotubes. Moreover,Nlrx1-/-GBM cells show decreased expression of autophagy markers, suggesting that NLRX1 plays a role in maintaining autophagy in GBM. In summary, our findings indicate that NLRX1 may modulate GBM pathophysiology by regulating GBM cell proliferation, migration, and metabolism. We believe our understanding of NLRX1 in GBM pathophysiology paves the potential development of GBM-targeting therapeutics that may delay disease progression and/or improve survival.