bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient Subtyping Analysis of Baseline Multi-omic Data Reveals Distinct Pre-immune States Predictive of Vaccination Responses
Authors: Bayrak Cigdem Sevim , Forst Christian , Jones Drew R. , Gresham David , Pushalkar Smruti , Wu Shaohuan , Vogel Christine , Mahal Lara , Ghedin Elodie , Ross Ted , García-Sastre Adolfo , Zhang Bin 
Published: January 2024

AbstractUnderstanding the molecular mechanisms that underpin diverse vaccination responses is a critical step toward developing efficient vaccines. Molecular subtyping approaches can offer valuable insights into the heterogeneous nature of responses and aid in the design of more effective vaccines. In order to explore the molecular signatures associated with the vaccine response, we analyzed baseline transcriptomics data from paired samples of whole blood, proteomics and glycomics data from serum, and metabolomics data from urine, obtained from influenza vaccine recipients (2019-2020 season) prior to vaccination. After integrating the data using a network-based model, we performed a subtyping analysis. The integration of multiple data modalities from 62 samples resulted in five baseline molecular subtypes with distinct molecular signatures. These baseline subtypes differed in the expression of pre-existing adaptive or innate immunity signatures, which were linked to significant variation across subtypes in baseline immunoglobulin A (IgA) and hemagglutination inhibition (HAI) titer levels. It is worth noting that these significant differences persisted through day 28 post-vaccination, indicating the effect of initial immune state on vaccination response. These findings highlight the significance of interpersonal variation in baseline immune status as a crucial factor in determining vaccine response and efficacy. Ultimately, incorporating molecular profiling could enable personalized vaccine optimization.
Current limitations in predicting mRNA translation with deep learning models
Authors: Schlusser Niels , González Asier , Pandey Muskan , Zavolan Mihaela 
Published: January 2024

AbstractBackgroundThe design of nucleotide sequences with defined properties is long-standing problem in bioengineering. An important application is protein expression, be it in the context of research or the production of mRNA vaccines. The rate of protein synthesis depends on the 5’ untranslated region (5’UTR) of the mRNAs, and recently, deep learning models were proposed to predict the translation output of mRNAs from the 5’UTR sequence. At the same time, large data sets of endogenous and reporter mRNA translation have become available.ResultsIn this study we use complementary data obtained in two different cell types to assess the accuracy and generality of currently available models of translation. We find that while performing well on the data sets on which they were trained, deep learning models do not generalize well to other data sets, in particular of endogenous mRNAs, which differ in many properties from reporter constructs.ConclusionsThese differences limit the ability of deep learning models to uncover mechanisms of translation control and to predict the impact of genetic variation. We suggest directions that combine high-throughput measurements and machine learning to unravel mechanisms of translation control and improve construct design.
Monitoring transcription of miR-15a and miR-124 in mesenchymal stem cells from adipose tissue origin differentiated into pancreatic beta-cells
Authors: Rajabi Hadi 
Published: January 2024

AbstractMicroRNAs are small noncoding pieces of nucleic acid with the potential to control mRNA translation. These sequences participate in the regulation of cell dynamic growth and differentiation. In this study, the expression of miR-15a and miR-124 was monitored in adipose-derived tissue stem cells committed to pancreatic β cellsin vitroover 28 days. In the current experiment, adipose-derived mesenchymal stem cells were incubated in an induction medium to accelerate differentiation toward endocrine pancreatic lineage for 28 days with a three-stage protocol. To confirm the efficient trans-differentiation of stem cells into pancreatic β cells, we performed a Dithizone staining, a zinc chelating agent, and pancreas-specific hormones (insulin and C peptide) examination via electrochemiluminescence. Real-time PCR analysis was done to assess the expression of miR-15a and miR-124. Dithizone staining confirmed a successful orientation of adipose-derived mesenchymal stem cells into pancreatic β cells indicating with red to strong brown appearance compared to negative control stem cells, indicating insulin positivity in differentiating cells. These effects were prominent by time and reached maximum level at day 28. Concurrently, the expression of both miR-15a and miR-124 was induced and reached a peak expression level at the end stage of the experiment compared to the stem cells (p<0.05).ConclusionThe dynamic of distinct miRNAs, in particular, miR-15a and miR-124 was induced during pancreatic β cells derivation of adipose-derived mesenchymal stem cells.
Conjugation related costs have reduced impact onin silicoplasmid persistence
Authors: Newbury Arthur 
Published: January 2024

AbstractDue to the important role they play in the antimicrobial resistance (AMR) crisis and in microbial evolution in general, a great deal of empirical and theoretical work is currently underway, trying to understand plasmid ecology. One of the key questions is how these often costly genetic elements persist in host populations. Here I show that when modelling plasmid population dynamics, it is not sufficient to treat them as always costly (or beneficial). I argue that conjugation related costs may be more important to plasmids in nature than they are in benign laboratory settings. Furthermore, I show that these conjugation related costs can be very severe and still not lead to extinction of a plasmid from a host population.
Blood Cholesterol and Triglycerides Associate with Right Ventricular Function in Pulmonary Hypertension
Authors: Fakhry Battoul , Peterson Laura , Comhair Suzy A.A. , Sharp Jacqueline , Park Margaret M. , Tang W.H. Wilson , Neumann Donald R. , DiFilippo Frank P. , Farha Samar , Erzurum Serpil C. , Mulya Anny 
Published: January 2024

ABSTRACTBackgroundBlood lipids are dysregulated in pulmonary hypertension (PH). Lower high-density lipoproteins cholesterol (HDL-C) and low-density lipoproteins cholesterol (LDL-C) are associated with disease severity and death in PH. Right ventricle (RV) dysfunction and failure are the major determinants of morbidity and mortality in PH. This study aims to test the hypothesis that dyslipidemia is associated with RV dysfunction in PH.MethodsWe enrolled healthy control subjects (n=12) and individuals with PH (n=30) (age: 18-65 years old). Clinical characteristics, echocardiogram, 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (PET) scan, blood lipids, including total cholesterol (TC), triglycerides (TG), lipoproteins (LDL-C and HDL-C), and N-terminal pro-B type Natriuretic Peptide (NT-proBNP) were determined.ResultsIndividuals with PH had lower HDL-C [PH, 41±12; control, 56±16 mg/dL,p<0.01] and higher TG to HDL-C ratio [PH, 3.6±3.1; control, 2.2±2.2, p<0.01] as compared to controls. TC, TG, and LDL-C were similar between PH and controls. Lower TC and TG were associated with worse RV function measured by RV strain (R=–0.43,p=0.02 andR=–0.37,p=0.05 respectively), RV fractional area change (R=0.51,p<0.01 andR=0.48,p<0.01 respectively), RV end-systolic area (R=–0.63,p<0.001 andR=–0.48,p<0.01 respectively), RV end-diastolic area:R=–0.58,p<0.001 andR=–0.41,p=0.03 respectively), and RV glucose uptake by PET (R=–0.46,p=0.01 andR=–0.30,p=0.10 respectively). NT-proBNP was negatively correlated with TC (R=–0.61,p=0.01) and TG (R=–0.62,p<0.02) in PH.ConclusionThese findings confirm dyslipidemia is associated with worse right ventricular function in PH.
Effect of Paxlovid Treatment During Acute COVID-19 on Long COVID Onset: An EHR-Based Target Trial Emulation from the N3C and RECOVER Consortia
Authors: Preiss Alexander , Bhatia Abhishek , Aragon Leyna V. , Baratta John M. , Baskaran Monika , Blancero Frank , Brannock M. Daniel , Chew Robert F. , Díaz Iván , Fitzgerald Megan , Kelly Elizabeth P. , Zhou Andrea , Carton Thomas W. , Chute Christopher G. , Haendel Melissa , Moffitt Richard , Pfaff Emily 
Published: January 2024

ABSTRACTBackgroundPreventing and treating post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, has become a public health priority. Researchers have begun to explore whether Paxlovid treatment in the acute phase of COVID-19 could help prevent the onset of PASC.Methods and FindingsWe used electronic health records from the National Covid Cohort Collaborative (N3C) to define a cohort of 426,352 patients who had COVID-19 since April 1, 2022, and were eligible for Paxlovid treatment due to risk for progression to severe COVID-19. We used the target trial emulation (TTE) framework to estimate the effect of Paxlovid treatment on PASC incidence. We estimated overall PASC incidence using a computable phenotype. We also measured the onset of novel cognitive, fatigue, and respiratory symptoms in the post-acute period. Paxlovid treatment did not have a significant effect on overall PASC incidence (relative risk [RR] = 0.98, 95% confidence interval [CI] 0.95-1.01). However, it had a protective effect on cognitive (RR = 0.90, 95% CI 0.84-0.96) and fatigue (RR = 0.95, 95% CI 0.91-0.98) symptom clusters.ConclusionsIn this cohort, Paxlovid had a weaker preventative effect on PASC than in prior observational studies. Differing effects by symptom cluster suggest that the etiology of cognitive and fatigue symptoms may be more closely related to viral load than that of respiratory symptoms. Ongoing clinical trials will help clarify Paxlovid’s overall effect on PASC, and future research should explore potential heterogeneous treatment effects across PASC subphenotypes.
Prognostic significance of circulating exosomal PD-L1 in various malignant tumors: A systematic review and meta-analysis
Authors: Li Wentao , Cui Qian , Ge Ting , Wang Shuangcui , Wang Dong , He Guixin , Yu Jianchun 
Published: January 2024

AbstractAlthough the prognostic significance of exosomal PD-L1 (exoPD-L1) has been previously reported, its value is still controversial. For the first time, we conducted a meta-analysis to systematically evaluate the prognostic value of exoPD-L1 in various types of cancer. The pooled hazard ratio (HR) and 95% confidence interval (CI) in these studies were used to explore the relationship between these indexes and overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS). Utilizing the NewcastleLJOttawa Scale (NOS), the quality of the listed studies was assessed. Heterogeneity was explored by subgroup analyses. Begg’s and Egger’s tests assessed publication bias. This meta-analysis included 11 trials involving 964 cancer cases. The pooled results indicate that high-level pre-treatment exoPD-L1 in circulation was associated with worse OS (HR = 2.10, 95% CI 1.51–2.91, P < 0.001), RFS (HR = 1.67, 95% CI 1.18–2.37, P < 0.01) and PFS (HR = 3.49, 95% CI 2.60–4.68, P < 0.001) compared to those with low-level pre-treatment exoPD-L1. However, high fold changes in circulating exoPD-L1 after receiving immune checkpoint inhibitors (ICIs) were correlated with significantly superior OS (HR = 0.19, 95% CI 0.10–0.38, P < 0.001) and PFS (HR = 0.35, 95% CI 0.23–0.52, P < 0.001). Through this meta-analysis, we found that pre-treatment with high levels of exoPD-L1 is associated with a poor prognosis. However, a high fold change in circulating exoPD-L1 following immunotherapy was correlated with a superior prognosis. ExoPD-L1 may have important clinical significance for assessing the prognosis of cancer patients.
Elucidating the Role of Primary and Secondary Sphere Zn2+Ligands in the Cyanobacterial CO2Uptake Complex NDH-14: The Essentiality of Arginine in Zinc Coordination and Catalysis
Authors: Walker Ross M. , Zhang Minquan , Burnap Robert L. 
Published: January 2024

AbstractThe uptake of inorganic carbon in cyanobacteria is facilitated by an energetically intensive CO2-concentrating mechanism (CCM). Specialized Type-1 NDH complexes function as a part of this mechanism to couple photosynthetic energy generated by redox reactions of the electron transport chain (ETC) to CO2hydration. This active site of CO2hydration incorporates an arginine side chain as a Zn ligand, diverging from the typical histidine and/or cysteine residues found in standard CAs. In this study, we focused on mutating three amino acids in the active site of the constitutively expressed NDH-14CO2hydration complex inSynechococcussp. PCC7942: CupB-R91, which acts as a zinc ligand, and CupB-E95 and CupB-H89, both of which are in close interaction with the arginine ligand. These mutations aimed to explore how they affect the unusual metal ligation by CupB-R91 and potentially influence the unusual catalytic process. The most severe defects in activity among the targeted residues are due to a substitution of CupB-R91 and the ionically interacting E95 since both proved essential for the structural stability of the CupB protein. On the other hand, CupB-H89 mutations show a range of catalytic phenotypes indicating a role of this residue in the catalytic mechanism of CO2-hydration, but no evidence was obtained for aberrant carbonic anhydrase activity that would have indicated uncoupling of the CO2-hydration activity from proton pumping. The results are discussed in terms of possible alternative CO2hydration mechanisms.
Automated single-cell proteomics providing sufficient proteome depth to study complex biology beyond cell type classifications
Authors: Ctortecka Claudia , Clark Natalie M. , Boyle Brian , Seth Anjali , Mani D. R. , Udeshi Namrata D. , Carr Steven A. 
Published: January 2024

AbstractMass spectrometry (MS)-based single-cell proteomics (SCP) has gained massive attention as a viable complement to other single cell approaches. The rapid technological and computational advances in the field have pushed the boundaries of sensitivity and throughput. However, reproducible quantification of thousands of proteins within a single cell at reasonable proteome depth to characterize biological phenomena remains a challenge. To address some of those limitations we present a combination of fully automated single cell sample preparation utilizing a dedicated chip within the picolitre dispensing robot, the cellenONE. The proteoCHIP EVO 96 can be directly interfaced with the Evosep One chromatographic system for in-line desalting and highly reproducible separation with a throughput of 80 samples per day. This, in combination with the Bruker timsTOF MS instruments, demonstrates double the identifications without manual sample handling. Moreover, relative to standard high-performance liquid chromatography, the Evosep One separation provides further 2-fold improvement in protein identifications. The implementation of the newest generation timsTOF Ultra with our proteoCHIP EVO 96-based sample preparation workflow reproducibly identifies up to 4,000 proteins per single HEK-293T without a carrier or match-between runs. Our current SCP depth spans over 4 orders of magnitude and identifies over 50 biologically relevant ubiquitin ligases. We complement our highly reproducible single-cell proteomics workflow to profile hundreds of lipopolysaccharide (LPS)-perturbed THP-1 cells and identified key regulatory proteins involved in interleukin and interferon signaling. This study demonstrates that the proteoCHIP EVO 96-based SCP sample preparation with the timsTOF Ultra provides sufficient proteome depth to study complex biology beyond cell-type classifications.
Strand asymmetry of DNA damage tolerance mechanisms
Authors: Cañas Juan Carlos , Jurado-Santiago Dolores , Al Mamun Mohammed , Sacristán María P. , Morafraile Esther C. , Zamarreño Javier , Fujiki Katsunori , Shirahige Katsuhiko , Bueno Avelino , Bermejo Rodrigo 
Published: January 2024

AbstractDNA damage tolerance mechanisms are crucial for timely and accurate chromosomal replication in response to DNA polymerase stalling. Ubiquitylation of the replicative sliding clamp PCNA drives major tolerance pathways, error-free homologous recombination template switching and error-prone translesion synthesis, though their dynamics at forks and pathway choice determinants are poorly understood. Using strand-specific genomics we revealed an asymmetric nature of tolerance pathways, characterized by preferential template switching-driven recombinase engagement of stalled nascent lagging strands and translesion synthesis usage in response to leading strand polymerase stalling. This asymmetry, determined by a strand-dynamic interplay between PCNA-ubiquitin writers and erasers, likely stems from necessities dictated by leading and lagging strand replication mechanisms and has implications for asymmetric mutation inheritance.One-Sentence SummaryDNA damage tolerance mechanisms respond asymmetrically to leading or lagging strand polymerase blocks.
Automated stratification of trauma injury severity across multiple body regions using multi-modal, multi-class machine learning models
Authors: Gao Jifan , Chen Guanhua , O’Rourke Ann P. , Caskey John , Carey Kyle , Oguss Madeline , Stey Anne , Dligach Dmitriy , Miller Timothy , Mayampurath Anoop , Churpek Matthew M. , Afshar Majid 
Published: January 2024

AbstractThe timely stratification of trauma injury severity can enhance the quality of trauma care but it requires intense manual annotation from certified trauma coders. There is a need to establish an automated tool to identify the severity of trauma injuries across various body regions. We gather trauma registry data from a Level I Trauma Center at the University of Wisconsin-Madison (UW Health) between 2015 and 2019. Our study utilizes clinical documents and structured electronic health records (EHR) variables linked with the trauma registry data to create two machine learning models with different approaches to representing text. The first one fuses concept unique identifiers (CUIs) extracted from free text with structured EHR variables, while the second one integrates free text with structured EHR variables. Both models demonstrate impressive performance in categorizing leg injuries, achieving high accuracy with macro-F1 scores of around 0.8. Additionally, they show considerable accuracy, with macro- F1 scores exceeding 0.6, in assessing injuries in the areas of the chest and head. Temporal validation is conducted to ensure the models’ temporal generalizability. We show in our variable importance analysis that the most important features in the model have strong face validity in determining clinically relevant trauma injuries.
Study of
Bs0→TT(a2(1320), K2*(1430), f2(1270), f2′(1525))
in the perturbative QCD approach
Authors: Dai Jing , Yu Xian-Qiao 
Published: January 2024

In the present study, the calculations of two-body decays Bs0→TT [T denotes tensor mesons, a2(1320), K2*(1430), f2(1270), f2′(1525)] in the perturbative QCD approach are presented. The ensuing predictions encompass branching ratios, polarization fractions, and direct CP violations, all elucidated in comprehensive detail. It is discerned that (1) for pure annihilation decay, the longitudinal polarization is around 90.0%, whereas the transverse polarizations manifest comparatively diminutive magnitudes. (2) The direct CP asymmetry is directly proportional to the interference between the tree and penguin contributions. For most of the decays investigated within this discourse, the direct CP asymmetry remains modest in magnitude. (3) There are precisely six distinct categories of Feynman diagrams for Bs0→TT, because the tensor mesons cannot be produced through the (V±A) currents or (S±P) density, thereby prohibiting factorizable emission diagrams. The nonfactorizable and annihilation contributions are ascertained to be pivotal in these decay modes. The calculated branching ratios of our calculation for Bs0→TT are at the order of 10−6 and 10−7, which can be tested in the LHCb and Belle II experiments. (4) Mixing exists for the f2(1270) and f2′(1525), just as the η and η′ mixing, the branching ratios about the mixing angle θ are given in this work. However, it is different from f1(1285)−f1(1420), the mixing angle is notably small, thereby resulting in only marginal alterations in the decay branching ratios.

Published by the American Physical Society
2024
Detectable gravitational waves from preheating probes nonthermal dark matter
Authors: Ghoshal Anish , Saha Pankaj 
Published: January 2024

We describe the challenges and pathways when probing inflaton as dark matter with the stochastic gravitational waves (GWs) signal generated during the (p)reheating. Such scenarios are of utmost interest when no other interaction between the visible and dark sectors is present, therefore having no other detectability prospects. We consider the remnant energy in the coherently oscillating inflaton’s zeroth mode to contribute to the observed relic dark matter density in the Universe. To fully capture the nonlinear dynamics and the effects of backreactions during the oscillation, we resort to full nonlinear lattice simulation with pseudospectral methods to eliminate the differencing noises. We investigate for models whose behavior during the reheating era is of mΦ2Φ2 type and find the typical primordial stochastic GWs backgrounds spectrum from scatterings among highly populated inflaton modes behaving like matter. We comment on the challenges of constructing viable inflationary models such that the inflaton will account for the total dark matter of the Universe while the produced GWs are within the future GWs detectors e.g., BBO, DECIGO, PTA, AION-MAGIS, and CE. We also describe the necessary modifications to the standard perturbative reheating scenario to prevent the depletion of residual inflaton energy via perturbative decay.

Published by the American Physical Society
2024
Inclusive leader and job crafting: the role of work engagement and job autonomy in service sector organisations
Authors: Jaleel Aqsa , Sarmad Muhammad 
Published: January 2024

PurposeThe ever-demanding role of employees in the hospitality sector stimulates job crafting. This study examines the relationship between inclusive leadership and job-crafting dimensions under the mediating role of work engagement through the lens of conservation of resources (COR) theory. It also aims to analyse the boundary condition of job autonomy between inclusive leadership and work engagement.Design/methodology/approachThe data were collected in 3-time lags from 319 front-line workers in the hospitality sector. The adopted and adapted questionnaires were executed through a deductive approach and an applied research method. The data were analysed through SmartPLS by applying the structural equation modelling (SEM) technique.FindingsThis study provides evidence for a predictive relationship between inclusive leadership and job-crafting dimensions under the mediating psychological mechanism of work engagement. Additionally, the moderating role of job autonomy is established in the unique context of the hospitality sector of an underdeveloped country, Pakistan.Practical implicationsServices-based organisations need to endure the inclusive leadership style by establishing work engagement practices. Engaged employees result in better job-crafting behaviours through better training and subsequent performance.Originality/valueThis study established that work engagement and job autonomy are imperative forces that impact the relationship between inclusive leadership and job-crafting dimensions. The research study has time-lagged data and conveys meaningful theoretical and practical implications.