bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exposure to a gradient of warming and acidification highlights physiological, molecular, and skeletal tolerance thresholds inPocillopora acutarecruits
Authors: Ashey Jill , Scucchia Federica , Huffmyer Ariana S. , Putnam Hollie M. , Mass Tali 
Published: January 2025

AbstractOcean warming and acidification are among the biggest threats to the persistence of coral reefs. Organismal stress tolerance thresholds are life stage specific, can vary across levels of biological organization, and also depend on natural environmental variability. Here, we exposed the early life stages ofPocillopora acutain Kāne‘ohe Bay, Hawai‘i, USA, a common reef-building coral throughout the Pacific, to projected ocean warming and acidification scenarios. We measured ecological, physiological, biomineralization, and molecular responses across the critical transition from larvae to newly settled recruits following 6 days of exposure to diel fluctuations in temperature and pH in Control (26.8-27.9°C, 7.82-7.96 pHTotal), Mid (28.4-29.5°C, 7.65-7.79 pHTotal) and High conditions (30.2-31.5°C, 7.44-7.59 pHTotal). We found thatP. acutaearly life stages are capable of survival, settlement, and calcification under all scenarios. The High conditions, however, caused a significant reduction in survival and settlement capacity, with changes in the skeletal fiber deposition patterns. In contrast to a limited impact on the expression of biomineralization genes, the dominant transcriptomic response to the High conditions relative to the two other treatments included depressed metabolism, reduced ATP production and increased activity of DNA damage-repair processes. Collectively, our findings indicate that corals living in environments with large diurnal fluctuations in seawater temperature and pH, such as Kāne‘ohe Bay, can tolerate exposure to moderate projected increased temperature and reduced pH. However, under more severe environmental conditions significant negative effects on coral cellular metabolism and overall organismal survival jeopardize species fitness and recruitment.
OcuPair, a novel photo-crosslinkable dendrimer-hyaluronic acid hydrogel bandage/bioadhesive for corneal injuries and temporary corneal repair
Authors: Kambhampati Siva P. , Sharma Rishi , Lin Hui , Appiani Santiago , Cleland Jeffrey L. , Yiu Samuel C , Kannan Rangaramanujam M. 
Published: January 2025

AbstractTraumatic corneal injuries are a leading cause of blindness among military personnel. These injuries need immediate attention at the combat zone, but treatment options are limited as life-saving measures are often prioritized. To address this critical gap, we have developed OcupairTM, a two-component hydrogel system that consists of (i) an injectable viscoelastic filler that stabilizes the ocular cavity and prevents hypotony. (ii) Anin-situphoto-curable adhesive hydrogel comprising of methacrylated PAMAM dendrimer and hyaluronic acid engineered to form a transparent, flexible and robust bandage within 90 seconds, adhering to corneal surface and ensuring a water-tight seal securing full-thickness corneal wounds.Ex vivostudies demonstrated that the adhesive hydrogel is mechanically robust and withstands intraocular pressures beyond physiological range. In a rabbit corneal injury model, OcuPair™ effectively seals complex full thickness wounds and preserves the eye with favorable clinical outcomes for 5 days with no toxicity over 30 days. In this study, we have validated the pilot scale synthesis, formulation optimization, GMP scale-up and IDE-enabling GLP toxicity, essential for clinical translation as a battlefield-ready solution.
PSME3 Regulates Migration and Differentiation of Myoblasts
Authors: Kuhn Kenneth D , Cho Ukrae H , Hetzer Martin 
Published: January 2025

AbstractThe acquisition of cellular identity requires large-scale alterations in cellular state. The non-canonical proteasome activator PSME3 is known to regulate diverse cellular processes, but its importance for differentiation remains unclear. Here, we demonstrate that PSME3 binds dynamically to highly active promoters over the course of differentiation. However, loss of PSME3 does not globally affect mRNA transcription. We find instead that PSME3 interacts with the HSP90 co-chaperone NUDC and regulates the levels of several cell adhesion-related proteins, such that loss of PSME3 results in increased cell motility. Further, we show that PSME3 facilitates myoblast differentiation in a proteasome-independent manner. Our findings reveal several new facets of PSME3 functionality and highlight its particular importance for the differentiation of myogenic cells.
An autoantibody-based machine learning classifier for the detection of early-stage non-small cell lung cancer
Authors: Kung Andrew F , Didigu Chukwuka A , Wang Chung-Yu , Saxena Aditi , Castillo-Rojas Bryan , Mitchell Anthea M , Mann Sabrina A , Murillo Alyssa , Zorn Kelsey C , Bod Lloyd , Jablons David M , Kratz Johannes R , DeRisi Joseph L 
Published: January 2025

AbstractThe humoral immune system plays a significant role in the immune response to cancer but is challenging to study at scale. We used programmable phage immunoprecipitation sequencing (PhIP-Seq) to profile the autoantibody repertoire in non-small cell lung cancer (NSCLC) patients for the purpose of training a machine learning-based classifier to distinguish NSCLC patients from healthy controls using 301 primarily early-stage, asymptomatic NSCLC patients and 352 healthy controls. The classifier performed well in cross-validation (average ROC-AUC = 0.94) and in an independently analyzed clinical validation cohort of 134 NSCLC patients and 96 healthy controls (ROC-AUC = 0.84). Classification performance can be maintained with only a few hundred target peptides, provided a sufficiently large cohort is used for optimal training. Our findings suggest the existence of a measurable autoreactive humoral profile in NSCLC and demonstrate the potential for serum-based early detection of cancer independent of nucleic acids.
High Prevalence of Molecular Markers Associated with Artemisinin, Sulphadoxine and Pyrimethamine Resistance in Northern Namibia
Authors: Eloff Lydia , Aranda-Díaz Andrés , Routledge Isobel , Wesolowski Amy , Chisenga Mukosha , Mangena Brighton , Chimumbwa John , Sikaala Chadwick , Uusiku Petrina , Katokele Stark , Raman Jaishree , Smith Jennifer , Mumbengegwi Davis R. 
Published: January 2025

AbstractArtemisinin-based combination therapies are a cornerstone of Namibia’s efforts to eliminate malaria, which has had an over 90% reduction in cases since their introduction in 2005. However, their efficacy has not been routinely monitored, with malaria outbreaks regularly reported since 2016. The recent emergence of artemisinin partial resistance in Africa has highlighted the role of malaria molecular surveillance in complementing efficacy studies. This cross-sectional genomic surveillance study was nested within Namibia’s routine surveillance system and aimed to determine the prevalence of antimalarial drug resistance markers in northern Namibia. Dried blood spots (DBS) and epidemiological data were collected from confirmedPlasmodium falciparumcases presenting at health facilities in the highest malaria-burden regions (Zambezi, Kavango East, Kavango West, Ohangwena, and Omusati) from April to September 2023. 12 genes associated with resistance to 7 antimalarial drugs were genotyped from 264 DBS using multiplexed targeted amplicon sequencing. Multiplepfk13mutations associated with artemisinin partial resistance were identified: the P441L candidate marker was the most abundant, at 33.2%, and the validated markers P574L and A675V were observed at 1.2%. The chloroquine resistance markerpfcrtCVIET haplotype was observed at 1%, while thepfmdr1N86 genotype, selected by lumefantrine use, was found in all samples. Although sulphadoxine-pyrimethamine is not used in Namibia, a high proportion of sulphadoxine-pyrimethamine resistance-associated mutations in thepfdhpsandpfdhfrgenes were observed. This study underscores the need for routine genomic surveillance to monitor emerging drug resistance markers and calls for further research to define their clinical implications.
Prevalence and Risk Factors of Comorbidities in Epilepsy Patients: A Meta-Analysis of Observational Studies in Asia
Authors: Hussain Zahabia Altaf , Aaqil Syeda Ilsa , Wen Cher Phoh , Khan Uneeb Ullah , Kaleem Safa , Tariq Rabeet , Ahmad Faizan 
Published: January 2025

AbstractBackgroundPatients with epilepsy often present with multiple comorbidities, which can exacerbate the progression of the disease and reduce their quality of life. Despite the clinical significance, there is a scarcity of collective data to estimate the prevalence of comorbidities among patients with epilepsy in the Asian setting.MethodsWe conducted a comprehensive literature search in PubMed, Scopus, and Google Scholar to identify observational studies conducted in Asia that reported the prevalence of comorbidities among patients diagnosed with epilepsy. Only studies focusing on epilepsy patients were included, and participants were required to have epilepsy confirmed through clinical diagnosis or International Classification of Diseases (ICD) codes. Other neurological conditions, such as non-epileptic seizures, brain tumors, or stroke without concurrent epilepsy, were excluded from this analysis to maintain focus on epilepsy-specific outcomes.ResultsA total of nine studies were included in the meta-analysis based on inclusion criteria. The most prevalent comorbidities among patients with epilepsy in Asia were hypertension (28.6%, 95% CI: 25.3%–32.0%) and diabetes mellitus (16.2%, 95% CI: 12.5%–20.2%). Factors such as gender, alcohol use, family history, and education level were significantly lower in comparison to other factors.ConclusionsOur study identified hypertension and diabetes mellitus as the most common comorbid conditions among epilepsy patients in Asian settings. These findings highlight the necessity for targeted interventions and comprehensive management strategies to address the high prevalence of comorbidities, ultimately improving patient outcomes. Further research is warranted to explore the underlying mechanisms and develop effective prevention strategies.
Machine learning-guided deconvolution of plasma protein levels
Authors: Pietzner Maik , Beuchel Carl , Demircan Kamil , Hoffman Anton Julian , Zeng Wenhuan , Römisch-Margl Werner , Yasmeen Summaira , Uluvar Burulça , Zoodsma Martijn , Koprulu Mine , Kastenmüller Gabi , Carrasco-Zanini Julia , Langenberg Claudia 
Published: January 2025

ABSTRACTProteomic techniques now measure thousands of circulating proteins at population scale, driving a surge in biomarker studies and biological clocks. However, their potential impact, generalisability, and biological relevance is hard to assess without understanding the origins and role of the thousands of proteins implicated in these studies. Here, we provide a data-driven identification of the foundations of protein variation that underly their links to ageing and diseases, differ between sexes and ancestries, and help guide protein biomarker and drug target discovery. We use machine learning to systematically identify and quantify the foundations of plasma levels of ∼3,000 protein targets among 43,240 participants of the UK Biobank. Out of >1,700 participant and sample characteristics, we identify a median of 19 factors (range: 1-36) that jointly explained an average of 23.7% (max. 79.9%) of the variance in plasma levels across protein targets. Proteins segregated into distinct clusters according to their explanatory factors, with modifiable characteristics explaining more variance compared to genetic variation (13.3% vs 9.8%). We identify proteins for which the factors underlying their variation differed by sex (n=1414 proteins) or across ancestries (n=86 proteins). We establish a knowledge graph that integrates our findings with genetic studies and drug characteristics to guide identification of potential markers of target engagement. We demonstrate the value of our resource 1) by identifying disease-specific biomarkers, like matrix metalloproteinase 12 for abdominal aortic aneurysm, and 2) by developing a framework for phenotype enrichment of protein signatures from independent studies to identify underlying sources of variation. All results are explorable via an interactive web portal (https://omicscience.org/apps/prot_foundation) and can be readily integrated into ongoing studies using an associatedRpackage.
Direct Health Care Costs Associated with Asthma Hospitalizations Before and During the Covid-19 Pandemic in the United States: A Nationwide Inpatient Sample Analysis
Authors: Solanki N. , Fakhry B. F. , Zhang P. , Attaway A. , Zein J. , Tsuang W. 
Published: January 2025

AbstractBackgroundAsthma, a chronic inflammatory airway disorder, can increase the risk of hospitalizations in individuals with viral infections such as COVID-19. The impact of the COVID-19 pandemic on asthma-related hospitalizations in the United States remains unknown.ObjectiveWe hypothesized that the COVID-19 pandemic led to an increase in economic burden to society and a decrease in hospitalization rates for asthma.MethodsWe analyzed weighted data from National Inpatient Sample (NIS) between January 1, 2018, and December 31, 2020. The outcomes were asthma hospitalization rates, length of stay (LOS), in-hospital mortality rates, and hospital admission costs.ResultsMore people were admitted with a primary diagnosis of asthma in 2018 and 2019 compared to 2020 (hospitalization rate per 100,000: 2018: 38.6 versus (vs) 2019:37.0 vs 2020: 21.4; P <0.001). Hospital costs increased (2018: median [IQR] 5,251 [ 3,426, 8,278]; 2019:5,677 [3,725, 8.969]; 2020: 5,881 [3,920-9,216]; P <0.001). Additionally, in-patient mortality rates slightly increased in 2020, rising to 0.44%, compared to 0.20% in 2018 and 0.30% in 2019 (P <0.001). When comparing geographic divisions, the mid-Atlantic division had the highest hospitalization rates, and the Pacific division had the highest hospitalization costs from 2018-2020 (P <0.05).ConclusionAsthma hospitalizations decreased in 2020 compared to previous years. Those admitted during the pandemic had slightly higher mortality and significantly increased hospital costs. This investigation provides valuable insights for policy makers about shifts in healthcare utilization during the pandemic.
A Mean Field Theory for Pulse-Coupled Oscillators based on the Spike Time Response Curve
Authors: Canavier Carmen C 
Published: January 2025

AbstractA mean field method for pulse-coupled oscillators with delays used a self-connected oscillator to represent a synchronous cluster of N-1 oscillators and a single oscillator assumed to be perturbed from the cluster. A periodic train of biexponential conductance input was divided into a tonic and a phasic component representing the mean field input. A single cycle of the phasic conductance from the cluster was applied to the single oscillator embedded in the tonic component at different phases to measure the change in the cycle length which the perturbation was initiated, that is, the first order phase response curve (PRC), and the second order PRC in the following cycle. A homogeneous network of 100 biophysically calibrated inhibitory interneurons with either shunting or hyperpolarizing inhibition tested the predictive power of the method. A self-consistency criterion predicted the oscillation frequency of the network from the PRCs as a function of the synaptic delay. The major determinant of the stability of synchrony was the sign of the slope of the first order PRC of the single oscillator in response to an input from the self-connected cluster at a phase corresponding to the delay value. For most short delays, first order PRCs correctly predicted the frequency and stability of simulated network activity. However, considering the second order PRC improved the frequency prediction and resolved an incorrect prediction of stability of global synchrony at delays close to the free running period of single neurons in which a discontinuity in the PRC precluded existence of 1:1 self-locking.
CONSERVED NUCLEAR MORPHOLOGY IDENTIFIES FUNCTIONAL RADIAL GLIA NEURAL PROGENITORS
Authors: Soriano J.P. , Borau C. , Sortino R. , Garma L. , Ortega J.A. , Asín J. , Alcántara S. 
Published: January 2025

SUMMARYRadial glia (RG) progenitor cells are the principal neural progenitors of the embryonic brain, giving rise to neurons and glial cells. RG apical-basal polarity and anchorage are crucial for maintaining their integrity and function. By using a biomimetic substrate that reproduces RG surface properties and mechanical anisotropy, we previously described the dedifferentiation of cultured astrocytes into functional RG, although the underlying mechanotransducive components remain largely unknown. Here we analyzed the role of nuclear morphology in mechanically driven RG induction, as nuclear deformation is critical for driving gene expression and cell fate changes in response to mechanical signals. A multivariate logistic regression model developed for fitting RG probability revealed the existence of intrinsic nuclear constraints, allowing a precise range of permitted RG nuclear morphologies, which are associated with calcium dynamics and conservedin vivo,in vitroand through evolution. Moreover, nuclear deformation predicts astrocyte or RG fate acquisition in response to mechanical signals.
The RING Finger E3 Ligase RNF25 Protects DNA Replication Forks Independently of its Canonical Roles in Ubiquitin Signaling
Authors: Chiou Lilly F. , Jayaprakash Deepika , Droby Gaith N. , Zhang Xingyuan , Yang Yang , Mills C. Allie , Webb Thomas S. , Barker Natalie K. , Wu Di , Herring Laura E. , Bowser Jessica , Vaziri Cyrus 
Published: January 2025

AbstractThe DNA damage response (DDR) mechanisms that allow cells to tolerate DNA replication stress are critically important for genome stability and cell viability. Using an unbiased genetic screen we identify a role for the RING finger E3 ubiquitin ligase RNF25 in promoting DNA replication stress tolerance. In response to DNA replication stress, RNF25-deficient cells generate aberrantly high levels of single-stranded DNA (ssDNA), accumulate in S-phase and show reduced mitotic entry. Using single-molecule DNA fiber analysis, we show that RNF25 protects reversed DNA replication forks generated by the fork remodeler HLTF from nucleolytic degradation by MRE11 and CtIP. Mechanistically, RNF25 interacts with the replication fork protection factor REV7 and recruits REV7 to nascent DNA after replication stress. The role of RNF25 in protecting replication forks is fully separable from its canonical functions in ubiquitin conjugation. This work reveals the RNF25-REV7 signaling axis as an important protective mechanism in cells experiencing replication stress.
Leading and lagging strand abasic sites differentially affect vertebrate replisome progression but involve analogous bypass mechanisms
Authors: Cranford Matthew T. , Dahmen Steven N , Cortez David , Dewar James M. 
Published: January 2025

AbstractAbasic sites are one of the most frequent forms of DNA damage that interfere with DNA replication. However, abasic sites exhibit complex effects because they can be processed into other types of DNA damage. Thus, it remains poorly understood how abasic sites affect replisome progression, which replication-coupled repair pathways they elicit, and whether this is affected by the template strand that is damaged. UsingXenopusegg extracts, we developed an approach to analyze replication of DNA containing a site-specific, stable abasic site on the leading or lagging strand template. We show that abasic sites robustly stall synthesis of nascent DNA strands but exert different effects when encountered on the leading or lagging strand template. At a leading strand AP site, replisomes stall ∼100 bp from the lesion until it is bypassed or a converging fork triggers termination. At a lagging strand abasic site, replisome progression is unaffected and lagging strands are reprimed downstream, generating a post-replicative gap, which is then bypassed. Despite different effects on replisome progression, both leading and lagging strand abasic sites rely on translesion DNA synthesis for bypass. Our results detail similarities and differences between how leading and lagging strand AP sites affect vertebrate DNA replication.
Nucleolar Stress-inducing Compounds Influence rDNA occupancy of RNA Polymerase I Transcription Machinery
Authors: Yglesias Matthew V. , DeRose Victoria J. 
Published: January 2025

AbstractTranscription of ribosomal RNA (rRNA) by RNA Polymerase I (Pol I) is often upregulated in cancer to facilitate rapid cell growth and proliferation, and has emerged as a potential target for chemotherapeutic agents. BMH-21 and Pt(II) chemotherapeutic agent oxaliplatin are well documented as inhibitors of Pol I activity, however the underlying mechanisms for this inhibition are not completely understood. Here, we applied chromatin immunoprecipitation sequencing (ChIP-seq) techniques and immunofluorescence imaging to probe the influence of oxaliplatin and BMH-21 on Pol I machinery. We demonstrate oxaliplatin and BMH-21 induce early nucleolar stress leading to the formation of “nucleolar caps” containing Pol I and upstream binding factor (UBF) which corresponds with broad reductions in ribosomal DNA (rDNA) occupancy of Pol I. Distinct occupancy patterns for the two compounds are revealed in ChIP-seq experiments. Taken together, our findings suggest that in vivo, oxaliplatin does not induce Pol I inhibition via interrupting a specific step in Pol I transcription, while treatment with BMH-21 induced unique polymerase stalling at the promoter and terminator regions of the human ribosomal RNA gene.
Rigorous process for isolation of gut-derived extracellular vesicles and the effect on latent HIV
Authors: Anyanwu Nneoma C.J. , Premadasa Lakmini S. , Naushad Wasifa , Okeoma Bryson C. , Mahesh Mohan , Okeoma Chioma M. 
Published: January 2025

AbstractAimExtracellular particles (EPs) are produced/secreted by cells from all domains of life and are present in all body fluids, brain, and gut. EPs consist of extracellular vesicles (EVs) made up of exosomes, microvesicles, and other membranous vesicles; and extracellular condensates (ECs) that are non-membranous carriers of lipid-protein-nucleic acid aggregates. The purity of EVs|ECs, which ultimately depends on the isolation method used to obtain them is critical, particularly EVs|ECs from the gastrointestinal (GI) tract that is colonized by a huge number of enteric bacteria. Therefore, identifying GI derived EVs|ECs of bacterial and host origin may serve as a window into the pathogenesis of diseases and as a potential therapeutic target.MethodsHere, we describe the use of high-resolution particle purification liquid chromatography (PPLC) gradient-bead-column integrated with polyvinylpolypyrrolidone (PVPP)-mediated extraction of impurities to isolate GI-derived EPs.Results and ConclusionPVPP facilitates isolation of pure and functionally active, non-toxic EVs ColEVs from colonic contents. ColEVs are internalized by cells and they activate HIV LTR promoter. In the absence of PVPP, ColEVs have a direct reductive potential of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) absorbance in a cell-free system. Assessment of the origin of ColEVs reveals that they are composed of both bacteria and host particles. This protocol requires ∼12 hours (5 hours preprocessing, 7 hours isolation) to complete and should be used to purify EVs from sources contaminated with microbial agents to improve rigor. Additionally, this protocol provides a robust tool for researchers and clinicians investigating GI-derived EVs and the translational use of GI-derived EVs for diagnostic and therapeutic use.HighlightColEVs but not ColECs are present in colonic content (GI tract) and can be isolated with gradient or single bead PPLC column.ColEVs isolated without PVPP are toxic to cells and they have a direct reductive potential of MTT. Addition of PVPP treatment in the isolation protocol results in clean and non-toxic ColEVs that transactivate the HIV LTR promoter.