bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular insights into mitoepigenetic stress response signaling in age-associated cardiovascular disease risk
Authors: Soni Nikita , Kaur Prasan , Gurjar Vikas , Bhargava Arpit , Tiwari Rajnarayan , Raghuwanshi Vinay Singh , Srivastava Rupesh K. , Mishra Pradyumna Kumar 
Published: March 2024

AbstractCardiovascular diseases (CVD) represent a major challenge for the elderly population and continue to be among the leading causes of mortality worldwide. The integrity of mitochondria in peripheral lymphocytes can indicate age-related degenerative disorders, revealing the balance between bioenergetics, inflammation, and senescence. The present study aims to investigate the impact of aging on mitochondrial-mediated epigenetic stress response mechanisms in both young and elderly individuals. Mitochondrial oxidative DNA damage, repair response, copy number, methylation, fusion, fission genes, electron transport chain enzyme complex activities, pro-inflammatory cytokine levels, and associated epigenetic mechanisms were studied. The results demonstrate that the elderly group experienced more significant disruption in the expression of mitochondrial genes, leading to impaired mitochondrial DNA (mtDNA) integrity intricately linked to mitochondrial-nuclear crosstalk, increasing their susceptibility to CVD. The findings highlight mitochondria’s crucial role in cellular dynamics, influencing stress responses and epigenetic mechanisms through fusion and fission cycles. Overall, these insights provide valuable information about the complex molecular processes linking mitochondrial dysfunction to age-related cardiovascular risks, paving the way for further exploration and potential interventions in aging-related health outcomes.Graphical AbstractFigure showing the molecular mechanisms underlying the mitoepigenetic stress response signaling pathways in age-associated cardiovascular diseases.
Substantial reduction in the clinical and economic burden of disease following variant-adapted mRNA COVID-19 vaccines in immunocompromised patients in France
Authors: Lee Amy , Davido Benjamin , Beck Ekkehard , Demont Clarisse , Joshi Keya , Kohli Michele , Maschio Michael , Uhart Mathieu , El Mouaddin Nadia 
Published: March 2024

ABSTRACTAn economic evaluation was conducted to predict the economic and clinical burden of vaccinating immunocompromised (IC) individuals aged ≥30 years with mRNA-1273 variant-adapted COVID-19 vaccines in Fall 2023 and Spring 2024 versus BNT162b2 variant-adapted vaccines in France. The number of symptomatic COVID-19 infections, hospitalizations, deaths, and long COVID cases, costs and quality-adjusted life years (QALYs) was estimated using a static decision-analytic model. Predicted vaccine effectiveness (VE) were based on real-world data from prior versions, suggesting higher protection against infection and hospitalization with mRNA-1273 vaccines. VE estimates were combined with COVID-19 incidence and probability of COVID-19 severe outcomes. Uncertainty surrounding VE, vaccine coverage, infection incidence, hospitalization and mortality rates, costs and QALYs were tested in sensitivity analyses. The mRNA-1273 variant-adapted vaccine is predicted to prevent an additional 3,882 infections, 357 hospitalizations, 81 deaths, and 326 long COVID cases when compared to BNT162b2 variant-adapted vaccines in 230,000 IC individuals. This translates to €10.1 million cost-savings from a societal perspective and 645 QALYs saved. Results were consistent across all analyses and most sensitive to variations surrounding VE and coverage. These findings highlight the importance of increasing vaccine coverage, and ability to induce higher levels of protection with mRNA-1273 formulations in this vulnerable population.
Seroprevalence and risk factors for SARS-CoV-2 infection in middle-sized cities of Burkina Faso: a descriptive cross-sectional study
Authors: Sana Adama , Djemaï Elodie , Vreyer Philippe De , Thivillon Thomas , Badolo Hermann , Berthé Abdramane , Kania Dramane 
Published: March 2024

AbstractBackgroundSince March 2020, COVID-19 has evolved from a localized outbreak to a global pandemic. We assessed the seroprevalence of COVID-19 in three towns in the Centre Sud region of Burkina Faso.MethodsA population-based cross-sectional survey was conducted in three medium-sized towns in Burkina Faso’s Centre Sud region, from June to July 2021. Subjects aged 16 or over at the time of the survey were considered for this seroprevalence study. The Biosynex COVID-19 BSS rapid test was used to detect immunoglobulin G (IgG) and immunoglobulin M (IgM) against SARS-CoV-2. A standardized questionnaire was also administered to collect additional information.ResultsA total of 2449 eligible participants (age ≥ 16 years) were identified. Serological tests for COVID-19 were performed in 2155 individuals. Finally, 2143 valid tests were retained and analyzed. Out of the entire sample, 246 positive tests were observed, corresponding to a prevalence of 11.48%. Prevalence was 9.35% (58 cases) in Kombissiri, 12.86% (80 cases) in Manga and 11.99% (108 cases) in Pô. By gender, 13.37% of women (164 cases) tested positive, and 8.95% of men (82 cases). Women accounted for 66.67% of all positive test subjects. The results show a significantly higher seroprevalence in women (P = 0.007), people over 55 years old (P = 0.004), overweight or obese people (P =0.026) and those with drinking water sources at home (0.013).ConclusionsThe results of this study show that the COVID-19 virus also circulates in the population of medium-sized towns in Burkina Faso, far more than is officially reported in the country. The study also highlighted the greater vulnerability of women to the epidemic, and the challenge of access to water in the face of diseases such as COVID-19. The preventive measures put in place to fight the pandemic must take these different factors into account.
High throughput screening of nuclear receptors identifies NR4A1, a novel tumor suppressor with potential as a therapeutic target in gallbladder cancer
Authors: Sarkar Sajib Kumar , Minocha Rashmi , Das Prasenjit , Dash Nihar Ranjan , Dhar Ruby , Kumar Deepak , Kapoor Vinay Kumar , Shukla Ratnakar , Karmakar Subhradip 
Published: March 2024

AbstractIntroductionGallbladder cancer (GBC) is one of the most common cancer of the hepato-biliary tract, with a strikingly variable incidence and prevalence across different regions of the world. The Indo-Gangetic belt in Northern India is reported to have one of the highest incidences of about 21/100,000. GBC usually goes unnoticed due to the lack of any early symptoms with two third of GBC cases present late at inoperable stages and have very limited treatment options. Nuclear receptors, a family of 48 members are ligand dependent transcription factors. They are of particular interest in cancer research because of their established role in cancer pathogenesis and their excellent druggability that makes them a suitable therapeutic target.MethodologymRNA expression 48 nuclear receptors were assessed in GBC tissue samples (n=13) and chronic cholecystitis tissue samples by Nanostring nCounter. The screening identified orphan receptor NR4A1 to be significantly downregulated in GBC. Western blot were performed to further validate the same. We next interrogated the above findings in 2 different gallbladder cancer cell lines, the highly invasive NOZ and the non-invasive TGBC24TKB. In order to investigate the role of NR4A1 in GBC pathogenesis, NOZ cells were treated with cytosporone B (10µM for 24hours) an agonist of NR4A1. On the other hand NR4A1 was knocked down in TGBC24TKB by siRNA. Expression of different markers of proliferation, invasion and epithelial mesenchymal transition was assessed by qPCR. Cell cycle analysis was done using flow cytometry.ResultsNR4A1 was one of the top differentially expressed (down regulated) nuclear receptors in GBC both in RNA and protein level. Similar finding was observed in highly invasive cell line NOZ in comparison to TGBC24TKB. Cytosporone B treatment led to upregulation of NR4A1, which resulted in reduction of cell migration as evident by delayed wound healing, reduction in invasion with an increase in G0/G1 populations implying a growth arrest. NR4A1 knockdown in TGBC24TKB lead to reduction in G0/G1 fraction and also increase in proliferation markers like mki67.ConclusionNR4A1 in our study acts as a tumor suppressor, loss of which seems to provide a growth and survival advantage to GBC cells. NR4A1 activation by agonist reduced cell proliferation and invasion. We therefore propose NR4A1 as a novel biomarker in GBC with its loss associated with overall poor outcome. Hence its agonists may emerge as a potential candidate for neo-adjuvant therapy for advanced gallbladder cancer.
Investigating low birthweight and preterm birth as potential mediators in the relationship between prenatal infections and early child development: A linked administrative health data analysis
Authors: Hardie Iain , Murray Aja , King Josiah , Hall Hildigunnur Anna , Okelo Kenneth , Luedecke Emily , Marryat Louise , Thompson Lucy , Minnis Helen , Lombardo Michael , Wilson Philip , Auyeung Bonnie 
Published: March 2024

AbstractBackgroundPrenatal infections are associated with childhood developmental outcomes such as reduced cognitive abilities, emotional problems and other developmental vulnerabilities. However, there is currently a lack of research examining whether this arises due to potential intermediary variables like low birthweight or preterm birth, or due to some other mechanisms of maternal immune activation arising from prenatal infections.MethodsAdministrative data from the National Health Service (NHS) health board of Greater Glasgow & Clyde, Scotland, was used, linking birth records to hospital records and universal child health review records for 55,534 children born from 2011-2015, and their mothers. Causal mediation analysis was conducted to examine the extent to which low birthweight and preterm birth mediate the relationship between hospital-diagnosed prenatal infections and having developmental concern(s) identified by a health visitor during 6-8 week or 27-30 month child health reviews.ResultsModel estimates suggest that 5.18% [95% CI: 3.77-7.65%] of the positive association observed between hospital diagnosed prenatal infections and developmental concern(s) was mediated by low birthweight, whilst 7.37% [95% CI: 5.36-10.88%] was mediated by preterm birth.ConclusionLow birthweight and preterm birth appear to mediate the relationship between prenatal infections and childhood development, but only to a small extent. Maternal immune activation mechanisms unrelated to low birthweight and preterm birth remain the most likely explanation for associations observed between prenatal infections and child developmental outcomes, although other factors (e.g. genetic factors) may also be involved.
Physical basis for the interaction betweenDrosophilaROS1 and the GPCR BOSS
Authors: Zhang Jianan , Tsutsui Yuko , Li Hengyi , Li Tongqing , Wang Yueyue , Klein Daryl E. 
Published: March 2024

Abstract/SummaryDrosophilaROS1 (dROS1, Sevenless) is a receptor tyrosine kinase (RTK) essential for the differentiation ofDrosophilaR7 photoreceptor cells1, 2. Activation of dROS1 is mediated by binding to the extracellular region (ECR) of the GPCR (G protein coupled receptor) BOSS (Bride Of Sevenless) on adjacent cells1, 3, 4. Genetic evidence together within vitroactivity assays confirmed the activation of dROS1 by BOSS and identified subsequent downstream signaling pathways including SOS (Son of Sevenless)1, 5. However, the physical basis for how dROS1 interacts with the GPCR BOSS has long remained unknown. Here we provide the first structure, using Cryo-Electron Microscopy (CryoEM), of dROS1’s extracellular region, which mediates ligand binding. We show that the N-terminal region of dROS1 adopts a folded-over conformation harboring a novel structural domain. We further narrowed down the interacting binding epitopes on both dROS1 and BOSS. This includes a beta-strand in dROS1’s third Fibronectin type III (FNIII) domain and the C-terminal portion of BOSS’ ECR. Our mutagenesis studies, coupled with AlphaFold complex predictions, support a binding interaction mediated by a hydrophobic interaction and beta-strand augmentation between these regions. Our findings provide a fundamental understanding of the regulatory function of dROS1 and further provide mechanistic insight into the human ortholog and oncogene ROS1.
Whole protein sequencing and quantification without proteolysis, terminal residue cleavage, or purification: A computational model
Authors: Sampath G. 
Published: March 2024

AbstractSequencing and quantification of whole proteins in a sample without separation, terminal residue cleavage, or proteolysis are modeled computationally. Similar to recent work on DNA sequencing (PNAS113, 5233–5238, 2016), a high-volume conjugate is attached to every instance of amino acid (AA) type AAi, 1 ≤ i ≤ 20, in an unfolded whole protein, which is then translocated through a nanopore. From the volume excluded by 2L residues in a pore of length L nm (a proxy for the blockade current), a partial sequence containing AAiis obtained. Translocation is assumed to be unidirectional, with residues exiting the pore at a roughly constant rate of ∼1/μs (Nature Biotechnology41, 1130–1139, 2023). The blockade signal is sampled at intervals of 1 μs and digitized with a step precision of 70 nm3; the positions of the AAis are obtained from the positions of well-defined quantum jumps in the signal. This procedure is applied to all 20 standard AA types, the resulting 20 partial sequences are merged to obtain the whole protein sequence. The complexity of subsequence computation is O(N) for a protein with N residues. The method is illustrated with a sample protein from the human proteome (Uniprot id UP000005640_9606). A mixture of M’ protein molecules (including multiple copies) can be sequenced by constructing an M’ × 20 array of partial sequences from which proteins occurring multiple times are first isolated and their sequences obtained separately. The remaining M singly-occurring molecules are detected from M disjoint paths through the 20 columns of the reduced M × 20 array. Detection complexity is O(M20), which is nominally in polynomial time but practical only for small M; to use this method a sample may be subdivided into subsamples down to this level. Quantification of proteins can be done by sorting their computed sequences on the sequence strings and counting the number of duplicates. The possibility of translating this procedure into practice and related implementation issues are discussed.
Metagenomic next-generation sequencing of cerebrospinal fluid for diagnosis of central nervous system infections: 7-year performance of a clinically validated test
Authors: Benoit Patrick , Brazer Noah , Kelly Emily , Servellita Venice , Oseguera Miriam , Nguyen Jenny , Tang Jack , de Lorenzi-Tognon Mikael , Omura Charles , Streithorst Jessica , Hillberg Melissa , Ingebrigtsen Danielle , Zorn Kelsey , Wilson Michael , Blicharz Tim , Wong Amy P. , O’Donovan Brian , Murray Brad , Miller Steve , Chiu Charles Y. 
Published: March 2024

AbstractStudies have shown that metagenomic next-generation sequencing (mNGS) testing of cerebrospinal fluid (CSF) in central nervous system (CNS) infections can improve diagnostic yields and provide actionable information. We analyzed the results of all CSF mNGS tests (n=4,828) performed at the University of California, San Francisco (UCSF) clinical microbiology laboratory from June 2016 to April 2023. We also assessed clinical metadata from a subset of samples that corresponded to a cohort of UCSF patients (n=1,164) who received CSF mNGS testing, and retrospectively evaluated performance compared to conventional microbiologic testing and adjudicated clinical diagnosis. Overall, 14.4% of CSF mNGS tests were positive for any microorganism. DNA viruses (7% of all samples) were detected most often, followed by RNA viruses (4.3%), bacteria (2.7%), fungi (1.4%), and parasites (0.5%). Using a composite gold standard obtained from clinical adjudication and all microbiological test results, sensitivity, specificity, and accuracy of CSF mNGS in the UCSF cohort who had clinically diagnosed infections were 56.5%, 98.8%, and 90.5%, respectively. The sensitivity of CSF mNGS testing (56.5%) was statistically higher than that from all direct detection testing from CSF (44.8%, p = 0.004), direct detection testing from samples other than CSF (15.2%, p<0.001), and indirect serologic testing (34%, p<0.001). When only considering diagnoses made by direct detection of pathogens on CSF, sensitivity of mNGS was 80.7%. These results justify the incorporation of CSF mNGS testing as part of the routine diagnostic workup in hospitalized patients presenting with potential CNS infection.
Forecasting Acute Kidney Injury and Resource Utilization in ICU patients using longitudinal, multimodal models
Authors: Tan Yukun , Dede Merve , Mohanty Vakul , Dou Jinzhuang , Hill Holly , Bernstam Elmer , Chen Ken 
Published: March 2024

AbstractBackgroundAdvances in artificial intelligence (AI) have realized the potential of revolutionizing healthcare, such as predicting disease progression via longitudinal inspection of Electronic Health Records (EHRs) and lab tests from patients admitted to Intensive Care Units (ICU). Although substantial literature exists addressing broad subjects, including the prediction of mortality, length-of-stay, and readmission, studies focusing on forecasting Acute Kidney Injury (AKI), specifically dialysis anticipation like Continuous Renal Replacement Therapy (CRRT) are scarce. The technicality of how to implement AI remains elusive.ObjectiveThis study aims to elucidate the important factors and methods that are required to develop effective predictive models of AKI and CRRT for patients admitted to ICU, using EHRs in the Medical Information Mart for Intensive Care (MIMIC) database.MethodsWe conducted a comprehensive comparative analysis of established predictive models, considering both time-series measurements and clinical notes from MIMIC-IV databases. Subsequently, we proposed a novel multi-modal model which integrates embeddings of top-performing unimodal models, including Long Short-Term Memory (LSTM) and BioMedBERT, and leverages both unstructured clinical notes and structured time series measurements derived from EHRs to enable the early prediction of AKI and CRRT.ResultsOur multimodal model achieved a lead time of at least 12 hours ahead of clinical manifestation, with an Area Under the Receiver Operating Characteristic Curve (AUROC) of 0.888 for AKI and 0.997 for CRRT, as well as an Area Under the Precision Recall Curve (AUPRC) of 0.727 for AKI and 0.840 for CRRT, respectively, which significantly outperformed the baseline models. Additionally, we performed a SHapley Additive exPlanation (SHAP) analysis using the expected gradients algorithm, which highlighted important, previously underappreciated predictive features for AKI and CRRT.ConclusionOur study revealed the importance and the technicality of applying longitudinal, multimodal modeling to improve early prediction of AKI and CRRT, offering insights for timely interventions. The performance and interpretability of our model indicate its potential for further assessment towards clinical applications, to ultimately optimize AKI management and enhance patient outcomes.
A signal processing tool for extracting features from arterial blood pressure and photoplethysmography waveforms
Authors: Pal R. , Rudas A. , Kim S. , Chiang J.N. , Cannesson M. 
Published: March 2024

AbstractArterial blood pressure (ABP) and photoplethysmography (PPG) waveforms contain valuable clinical information and play a crucial role in cardiovascular health monitoring, medical research, and managing medical conditions. The features extracted from PPG waveforms have various clinical applications ranging from blood pressure monitoring to nociception monitoring, while features from ABP waveforms can be used to calculate cardiac output and predict hypertension or hypotension. In recent years, many machine learning models have been proposed to utilize both PPG and ABP waveform features for these healthcare applications. However, the lack of standardized tools for extracting features from these waveforms could potentially affect their clinical effectiveness. In this paper, we propose an automatic signal processing tool for extracting features from ABP and PPG waveforms. Additionally, we generated a PPG feature library from a large perioperative dataset comprising 17,327 patients using the proposed tool. This PPG feature library can be used to explore the potential of these extracted features to develop machine learning models for non-invasive blood pressure estimation.
Squeezing Oscillations in a Multimode Bosonic Josephson Junction
Authors: Zhang Tiantian , Maiwöger Mira , Borselli Filippo , Kuriatnikov Yevhenii , Schmiedmayer Jörg , Prüfer Maximilian 
Published: March 2024

Quantum simulators built from ultracold atoms promise to study quantum phenomena in interacting many-body systems. However, it remains a challenge to experimentally prepare strongly correlated continuous systems such that the properties are dominated by quantum fluctuations. Here, we show how to enhance the quantum correlations in a one-dimensional multimode bosonic Josephson junction, which is a quantum simulator of the sine-Gordon field theory. Our approach is based on the ability to track the nonequilibrium dynamics of quantum properties. After creating a bosonic Josephson junction at the stable fixed point of the classical phase space, we observe squeezing oscillations in the two conjugate variables. We show that the squeezing oscillation frequency can be tuned by more than one order of magnitude, and we are able to achieve a spin squeezing close to 10 dB by utilizing these oscillatory dynamics. The impact of improved spin squeezing is directly revealed by detecting enhanced spatial phase correlations between decoupled condensates. Our work provides new ways for engineering correlations and entanglement in the external degree of freedom of interacting many-body systems.

Published by the American Physical Society
2024
Research on mechanism of servant leadership on employees' customer-oriented deviance: the mediating role of psychological security and the moderating role of error management climate
Authors: Zhang Yi , Zhao Jingyi , Qin Jian 
Published: March 2024

PurposeIn the era of the service economy, the personalized needs of customers are increasing rapidly. It often occurs that front-line employees bend organizational rules to help customers. The study sought to explore the influence mechanism of servant leadership on specific dimensions of customer-oriented deviance from the manager’s perspective, examine the mediating role of psychological security, and the moderating role of error management climate in the process.Design/methodology/approachWe conducted an online survey study in China from April 10 to 29, 2023. We use online survey questionnaire technique and random sampling method for data collection. The authors collected 385 questionnaires from China and tested the model by SPSS 26.0 and AMOS 24.0.FindingsThe results show that servant leadership significantly promotes employees' deviant customer-oriented behaviors, psychological security plays a mediating role between servant leadership and deviant customer-oriented behaviors, and error management climate has a positive moderating effect between servant leadership and deviant customer-oriented behaviors.Originality/valueThis study explores the influence mechanism of servant leadership on deviant customer-oriented behaviors. The results of this study not only enrich the theoretical research on the formation mechanism of deviant customer-oriented behaviors but also provide a reference for leaders to correctly view and effectively manage employees' deviant customer-oriented behaviors.