bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of health as predictors for differential antibody responses following SARS-CoV-2 primary and booster vaccination in an at-risk, longitudinal cohort
Authors: Tribin Felipe Echeverri , Williams Erin , Testamarck Valeska , Carreño Juan Manuel , Bielak Dominika , Yellin Temima , Krammer Florian , Hoffer Michael , Pallikkuth Suresh , Pahwa Savita 
Published: September 2023

AbstractPost vaccine immunity following COVID-19 mRNA vaccination may be driven by extrinsic, or controllable and intrinsic, or inherent health factors. Thus, we investigated the effects of extrinsic and intrinsic on the peak antibody response following COVID-19 primary vaccination and on the trajectory of peak antibody magnitude and durability over time. Participants in a longitudinal cohort attended visits every 3 months for up to 2 years following enrollment. At baseline, participants provided information on their demographics, recreational behaviors, and comorbid health conditions which guided our model selection process. Blood samples were collected for serum processing and spike antibody testing at each visit. Cross-sectional and longitudinal models (linear-mixed effects models) were generated to assess the relationship between selected intrinsic and extrinsic health factors on peak antibody following vaccination and to determine the influence of these predictors on antibody over time. Following cross-sectional analysis, we observed higher peak antibody titers after primary vaccination in females, those who reported recreational drug use, younger age, and prior COVID-19 history. Following booster vaccination, females and Hispanics had higher peak titers after the 3rdand 4thdoses, respectively. Longitudinal models demonstrated that Moderna mRNA-1273 recipients, females, and those previously vaccinated had increased peak titers over time. Moreover, drug users and half-dose Moderna mRNA-1273 recipients had higher peak antibody titers over time following the first booster, while no predictive factors significantly affected post-second booster antibody responses. Overall, both intrinsic and extrinsic health factors play a significant role in shaping humoral immunogenicity after initial vaccination and the first booster. The absence of predictive factors for second booster immunogenicity suggests a more robust and consistent immune response after the second booster vaccine administration.
Activation induces shift in nutrient utilization that differentially impacts cell functions in human neutrophils
Authors: Britt Emily C. , Qing Xin , Votava James A. , Lika Jorgo , Wagner Andrew , Shen Simone , Arp Nicholas L. , Khan Hamidullah , Schieke Stefan M. , Fletcher Christopher D. , Huttenlocher Anna , Fan Jing 
Published: September 2023

AbstractNeutrophils – the first responders in innate immunity – perform a variety of effector functions associated with specific metabolic demand. To maintain fitness and support functions, neutrophils have been found to utilize extracellular glucose, intracellular glycogen, and other alternative substrates. However, the quantitative contribution of these nutrients under specific conditions and the relative dependence of various cell functions on specific nutrients remain unclear. Here, usingex vivoandin vivoisotopic tracing, we reveal that under resting condition, human peripheral blood neutrophils, in contrast toin vitrocultured human neutrophil-like cell lines, rely on glycogen as a major direct source of glycolysis and pentose phosphate pathway. Upon activation with a diversity of stimuli, neutrophils undergo a significant and often rapid nutrient preference shift, with glucose becoming the dominant metabolic source thanks to a multi-fold increase in glucose uptake mechanistically mediated by the phosphorylation and translocation of GLUT1. At the same time, cycling between gross glycogenesis and glycogenolysis is also substantially increased, while the net flux favors sustained or increased glycogen storage. The shift in nutrient utilization impacts neutrophil functions in a function-specific manner. The activation of oxidative burst specifically depends on the utilization of extracellular glucose rather than glycogen. In contrast, the release of neutrophil traps can be flexibly supported by either glucose or glycogen. Neutrophil migration and fungal control is promoted by the shift away from glycogen utilization. Together, these results quantitatively characterize fundamental features of neutrophil metabolism and elucidate how metabolic remodeling shapes neutrophil functions upon activation.
Alpha-synuclein expression in neuron modulates the Japanese encephalitis virus infection
Authors: Gupta Anjali , Mohapatra Anshuman , Kaur Harpreet , Sharma Ajanta , Chaudhary Nitin , Kumar Sachin 
Published: September 2023

AbstractJapanese encephalitis virus (JEV) stands as a prominent vector-borne zoonotic pathogen, displaying neurotropism and eliciting Parkinson’s disease (PD)-like symptoms among most symptomatic survivors. A characteristic feature of PD is aggregation of mutated α-synuclein (α-syn) that damages the dopaminergic neurons. Considering this link between JEV-induced PD-like symptoms and α-syn pathogenesis, we explored the role of α-syn in JEV infectivity in neuronal cells. Our investigation revealed significant increase in endogenous α-syn expression in JEV-infected cells. Additionally, treatment with exogenous α-syn (Exoα-syn) led to a substantial reduction in JEV replication, suggesting its anti-JEV effect. Furthermore, Exoα-syn treatment led to the upregulation of superoxide dismutase 1 (SOD1) and reduction in reactive oxygen species (ROS). The results were validated by endogenous α-syn-silencing, that decreased SOD1 level and raised ROS level in neuronal cells. Similarly, the SOD1 inhibition via LCS-1 also intensified ROS and JEV infection. Overall, our results suggest that α-syn exerts an anti-JEV effect by regulating protein involved in oxidative stress inside neuronal cells. This study contributes valuable insights into the interplay between α-syn expression and JEV infectivity, shedding light on avenues to further investigate the potential role of α-syn in JEV pathogenesis.ImportanceJapanese encephalitis virus (JEV) poses significant threat particularly to children. Despite extensive research efforts, the development of effective treatments against JEV has been impeded. One of the major setbacks is a lack of comprehensive understanding of neurotropism. The study focuses on alpha synuclein (α-syn), a neuronal protein, and aims to determine its role in JEV pathogenesis. Present study reveals that host cell upregulates α-syn in response of JEV infection. α-syn restrains JEV propagation by modulating superoxide dismutase 1 (SOD1) expression which further blocks JEV-induced ROS generation. Endogenous α-syn silencing led to decrease in SOD1 expression and increased viral titer. α-syn plays crucial role in counteracting oxidative stress through SOD1, which is essential for limiting JEV replication. This study provides broader implications for antiviral strategies and its possible role in neurodegenerative diseases; however, there is still much to explore, particularly regarding its aggregation kinetics in JEV infection.
Genomic surveillance ofClostridioides difficiletransmission and virulence in a healthcare setting
Authors: Newcomer Erin P. , Fishbein Skye R. S. , Zhang Kailun , Hink Tiffany , Reske Kimberly A. , Cass Candice , Iqbal Zainab H. , Struttmann Emily L. , Dubberke Erik R. , Dantas Gautam 
Published: September 2023

AbstractClostridioides difficileinfection (CDI) is a major cause of healthcare-associated diarrhea, despite the widespread implementation of contact precautions for patients with CDI. Here, we investigate strain contamination in a hospital setting and genomic determinants of disease outcomes. Across two wards over six months, we selectively culturedC. difficilefrom patients (n=384) and their environments. Whole-genome sequencing (WGS) of 146 isolates revealed that mostC. difficileisolates were from clade 1 (131/146, 89.7%), while only one isolate of the hypervirulent ST1 was recovered. Of culture-positive admissions (n=79), 19 (24%) of patients were colonized with toxigenicC. difficileon admission to the hospital. We defined 25 strain networks at ≤ 2 core gene SNPs; 2 of these networks contain strains from different patients. Strain networks were temporally linked (p<0.0001). To understand genomic correlates of disease, we conducted WGS on an additional cohort ofC. difficile(n=102 isolates) from the same hospital and confirmed that clade 1 isolates are responsible for most CDI cases. We found that while toxigenicC. difficileisolates are associated with the presence ofcdtR, nontoxigenic isolates have an increased abundance of prophages. Our pangenomic analysis of clade 1 isolates suggests that while toxin genes (tcdABER and cdtR) were associated with CDI symptoms, they are dispensable for patient colonization. These data indicate toxigenic and nontoxigenicC. difficilecontamination persists in a hospital setting and highlight further investigation into how accessory genomic repertoires contribute toC. difficilecolonization and disease.
An unsupervised machine learning approach to predict recovery from traumatic spinal cord injury
Authors: Brüningk Sarah C. , Bourguignon Lucie , Lukas Louis P. ,   EMSCI study group, Maier Doris , Abel Rainer , Weidner Norbert , Rupp Rüdiger , Geisler Fred , Kramer John L.K. , Guest James , Curt Armin , Jutzeler Catherine R. 
Published: September 2023

AbstractBackgroundNeurological and functional recovery after traumatic spinal cord injury (SCI) is highly heterogeneous, challenging outcome predictions in rehabilitation and clinical trials. We propose k-nearest neighbour (k-NN) matching as a data-driven, interpretable solution.MethodsThis study used acute-phase International Standards for Neurological Classification of SCI exams to forecast 6-month recovery motor function as primary evaluation endpoint. Secondary endpoints included severity grade improvement, independent walking, and self-care ability. Different similarity metrics were explored for NN matching within 1267 patients from the European Multicenter Study about Spinal Cord Injury before validation in 411 patients from the Sygen trial.ResultsWe obtained a population-wide root-mean-squared error (RMSE) in motor score sequence of 0.76(0.14, 2.77) and competitive functional score predictions (AUCwalker=0.92, AUCself-carer=0.83). The validation cohort showed comparable results (RMSE = 0.75(0.13, 2.57), AUCwalker=0.92). Prediction performance in AIS grade B and C patients (∼30%) showed the largest deviations from true recovery scores, in line with large SCI heterogeneity.ConclusionsOur approach provides detailed predictions of neurological and functional recovery based on a highly interpretable unsupervised machine learning concept. The k-NN matching strategy further enables the integration of historical control data into the evaluation of clinical trials and provides a data-driven digital twin for recovery trajectory exploration.
Immunologic predictors of vaccine responsiveness in patients with lymphoma and CLL
Authors: Chong Elise A. , Kumashie Kingsley Gideon , Chong Emeline R. , Fabrizio Joseph , Gupta Aditi , Svoboda Jakub , Barta Stefan K. , Walsh Kristy M. , Napier Ellen B. , Lundberg Rachel K. , Nasta Sunita D. , Gerson James N. , Landsburg Daniel J. , Gonzalez Joyce , Gaano Andrew , Weirick Madison E. , McAllister Christopher M. , Awofolaju Moses , John Gavin N. , Kammerman Shane C. , Novaceck Josef , Pajarillo Raymone , Lundgreen Kendall A. , Tanenbaum Nicole , Gouma Sigrid , Drapeau Elizabeth M. , Adamski Sharon , D’Andrea Kurt , Pattekar Ajinkya , Hicks Amanda , Korte Scott , Sharma Harsh , Herring Sarah , Williams Justine C. , Hamilton Jacob T. , Bates Paul , Hensley Scott E. , Luning Prak Eline T. , Greenplate Allison R. , Wherry E. John , Schuster Stephen J. , Ruella Marco , Vella Laura A. 
Published: September 2023

ABSTRACTPatients with B-cell lymphomas have altered cellular components of vaccine responses due to the malignancies and therapies. The optimal timing of vaccine administration relative to chemotherapy and immunotherapy remains unknown. The SARS-CoV-2 vaccine campaign created a unique opportunity to gather insights into vaccine timing because patients were challenged with a novel antigen across multiple phases of lymphoma management. We studied retrospective and prospective cohorts of patients with lymphoma and CLL who received an mRNA-based vaccine and paired serologic response with treatment dates, clinical immune parameters, and deep immunophenotyping. Reduced serologic response was observed more frequently during active therapies but nonresponders were also identified within observation and post-treatment groups. Clinical immunologic profiling demonstrated that total IgA and IgM near the time of vaccination correlated with ability to coordinate vaccine response. In individuals treated with CART-19, high-parameter immunophenotyping demonstrated that nonresponse was associated with reduced participation in B cell clusters and clusters of T follicular helper cells required for vaccine response. Together these data suggest that predictors of vaccine responsiveness vary by disease and therapeutic group. Further studies of immune health during and after cancer therapies will allow clinicians to individualize the timing of vaccines and define immunologic vulnerabilities.
Genomic Insights into Pediatric Intestinal Inflammatory and Eosinophilic Disorders using Single-sell RNA-sequencing
Authors: Keever-Keigher Marissa R. , Harvey Lisa , Williams Veronica , Vyhlidal Carrie A. , Ahmed Atif A. , Johnston Jeffery J. , Louiselle Daniel A. , Grundberg Elin , Pastinen Tomi , Friesen Craig A. , Chevalier Rachel , Smail Craig , Shakhnovich Valentina 
Published: September 2023

AbstractChronic inflammation of the gastrointestinal tissues underlies gastrointestinal inflammatory disorders, leading to tissue damage and a constellation of painful and debilitating symptoms. These disorders include inflammatory bowel diseases (Crohn’s disease and ulcerative colitis), and eosinophilic disorders (eosinophilic esophagitis and eosinophilic duodenitis). Gastrointestinal inflammatory disorders can often present with overlapping symptoms necessitating the use of invasive procedures to give an accurate diagnosis. This study used peripheral blood mononuclear cells from individuals with Crohn’s disease, ulcerative colitis, eosinophilic esophagitis, and eosinophilic duodenitis to better understand the alterations to the transcriptome of individuals with these diseases and identify potential markers of active inflammation within the peripheral blood of patients that may be useful in diagnosis. Single-cell RNA-sequencing was performed on peripheral blood mononuclear cells isolated from the blood samples of pediatric patients diagnosed with gastrointestinal disorders, including Crohn’s disease, ulcerative colitis, eosinophilic esophagitis, eosinophilic duodenitis, and controls with histologically healthy gastrointestinal tracts. We identified 730 (FDR < 0.05) differentially expressed genes between individuals with gastrointestinal disorders and controls across eight immune cell types. There were common patterns among GI disorders, such as the widespread upregulation ofMTRNR2L8across cell types, and many differentially expressed genes showed distinct patterns of dysregulation among the different gastrointestinal diseases compared to controls, including upregulation ofXISTacross cell types among individuals with ulcerative colitis and upregulation of Th2-associated genes in eosinophilic disorders. These findings indicate both overlapping and distinct alterations to the transcriptome of individuals with gastrointestinal disorders compared to controls, which provide insight as to which genes may be useful as markers for disease in the peripheral blood of patients.
Analysis of Potential Risk Factors of COVID-19 Based on Variants: Omicron, Delta, and Alpha
Authors: Kannan Dharshini , Muppiri Sreenidhi , Reid Maren 
Published: September 2023

AbstractThe coronavirus disease 2019 (COVID-19) pandemic has changed which affects the risk of COVID-19 infection for specific subgroups. We focused on the subgroups based on the factors (sex, age, and vaccination) and COVID-19 strains (Alpha, Delta, and Omicron). Past studies focused on analyzing these factors based on one geographic region or one COVID-19 strain. Therefore, there is a need to understand these factors’ association with risk of COVID-19 infection through analyzing data from various geographic regions and strains. The association between COVID-19 strains and the factors was assessed through chi-square test and odds ratio tests. Sex, vaccination, age had a significant association with testing positive for the COVID-19 strains of interest in most geographies. The biggest difference was unvaccinated individuals have 3.14 higher odds of getting Alpha than vaccinated individuals in Canada. These findings provide insights into the groups that are more susceptible to contracting specific strains of COVID-19.SummaryThis manuscript offers a broad examination of key factors that may impact the risk of COVID-19 infection across various geographic regions. Results provide evidence about potential risk factors for COVID-19 infection around the world for certain sub-groups as COVID-19 mutates.
A curriculum-based approach to make healthcare inclusive for the transgender population: challenges and lessons from Pakistan
Authors: Ahuja Akash Kumar , Abbas Manzar , Haroon Mian Arsam , Javed Muhammad Abdullah , Memon Areeba , Irfan Rida , Karim Zohair , Bhatti Areesh , Hashim Mehsa , Hamid Janeeta , Nafees Asaad 
Published: September 2023

AbstractBackgroundTransgender people experience significant healthcare inequalities due to stigma and lack of acceptance. Physicians and medical students have reported knowledge gaps regarding transgender health care (TGHC). Therefore, we conducted this study to assess the perceived need for and preferred approaches of medical students towards incorporation of TGHC in curriculum and any possible barriers that can arise.MethodsA cross-sectional survey was conducted amongst medical students from accredited medical colleges in Pakistan. Google forms were used to collect data including three outcome variables: need, preferred modalities, and barriers towards TGHC. The outcome variables were analyzed and compared using SPSS version 25.0.ResultsA total of 436 medical students from all over the Pakistan responded to the questionnaire. Of those, 264 (60.6%) were female. A majority of participants were from the southern provinces of Pakistan (n = 302; 69.3%). An overwhelming majority (98.4 %) of participants (n=429) felt there was a need to teach transgender healthcare (TGHC) education at the undergraduate level. This is contrasted by only 5% of participants (n=23) reporting being taught transgender health as part of their curriculum. Of these 5%, knowledge was mostly assessed either on multiple choice or essay questions. Majority students reported never having had any interaction with transgender patient during their clinical rotations. 82.8% students identified that education provided at their institute regarding transgender health education is inadequate while 80.8% students revealed that transgender health education was not an official part of their institute’s curriculum. The biggest barrier identified was TGHC not being identified as a problem, followed by cultural and logistic barriers. The most recommended mode of TGHC education delivery as suggested by students was the use of small group discussions followed by student presentations and use of films and documentaries.ConclusionA clear gap exists regarding transgender health education in the medical curriculum in Pakistan. The study highlights important barriers and recommends possible modes of delivery to inculcate TGHC education in the curriculum.
Programmatic considerations for chikungunya vaccine introduction in countries at risk of chikungunya outbreaks: stakeholder analysis
Authors: Auzenbergs Megan , Maure Clara , Kang Hyolim , Brady Oliver , Sahastrabuddhe Sushant , Abbas Kaja 
Published: September 2023

AbstractChikungunya can have longstanding effects on health and quality of life. Alongside the licensing of new chikungunya vaccines in the pipeline, it is important to understand the perspectives of stakeholders before vaccine rollout. Our study aim is to identify key programmatic considerations for chikungunya vaccine introduction in countries at risk of chikungunya outbreaks. We used purposive and snowball sampling to identify global, national, and subnational stakeholders from outbreak prone areas, including Latin America, Asia, and Africa. Semi-structured in-depth interviews were conducted and analysed using qualitative descriptive methods. We found that perspectives varied between tiers of stakeholders and geographies. Unknown disease burden, diagnostics, non-specific disease surveillance, undefined target populations for vaccination, and low disease prioritisation were critical challenges identified by stakeholders that need to be addressed to facilitate rolling out a chikungunya vaccine. Future investments should address these challenges to generate useful evidence for decision-making on new chikungunya vaccine introduction.
Comparison of NAFLD, MAFLD, MASLD and pure-MASLD characteristics and mortality outcomes in United States adults
Authors: Song Rui , Li Zhao , Zhang Yingzhi , Tan Jiahe , Chen Zhiwei 
Published: September 2023

AbstractBackgroundAfter metabolic dysfunction-associated fatty liver disease (MAFLD), non-alcoholic fatty liver disease (NAFLD) has recently been redefined again as metabolic dysfunction-associated steatotic liver disease (MASLD). However, the distinctions in characteristics and mortality outcomes between NAFLD, MAFLD, MASLD, and pure-MASLD are still unclear.MethodsWe analyzed data from 6,708 participants in the third National Health and Nutrition Examination Surveys 1988-1994 of United States (US) and their linked mortality through 2019. NAFLD, MAFLD, MASLD and pure MASLD were defined based on respective criteria. Survey-weight adjusted multivariable Cox proportional model was used to study the mortality of the four terms.ResultsThe overall prevalence of NAFLD, MAFLD, MASLD and pure-MASLD was 28.9% (n=1,937), 26.1% (n=1,753), 29.0% (n=1,948), and 26.0% (n=1,741), respectively. For NAFLD, 81.3%, 89.9% and 89.9% fulfilled the criteria for MAFLD, MASLD and pure MASLD. For MAFLD, all were classified into the MASLD, and 89.8% were met the criteria of pure-MASLD. During a median follow-up of 27 years, both individuals with MAFLD and MASLD had higher risk of all-cause mortality (adjusted hazard ratio [aHR]: 1.21, 95% CI 1.09-1.352; and 1.11, 1.00-1.23, respectively). NAFLD and pure-MASLD were not associated with all-cause mortality. All the four terms were associated with increased all-cause mortality in individuals with advanced fibrosis (aHR: 1.66-1.83). Subgroup analyses showed that higher risk of all-cause mortality of NAFLD, MAFLD, MASLD and pure-MASLD were observed in female, age 41-55 years, non-Hispanic white, and never smoking subgroups when focused on moderate-severe hepatic steatosis.ConclusionsIn this US population-based study, MASLD could identify more individuals with all-cause mortality risk than MAFLD, meanwhile, NAFLD and pure-MASLD had similar characteristics and mortality outcomes.