bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotype and function of IL-10 producing NK cells in individuals with malaria experience
Authors: McNitt Sarah A. , Dick Jenna K. , Hernandez Castaneda Maria , Sangala Jules A. , Pierson Mark , Macchietto Marissa , Burrack Kristina S. , Crompton Peter D. , Seydel Karl B. , Hamilton Sara E. , Hart Geoffrey T. 
Published: May 2024

ABSTRACTPlasmodium falciparuminfection can trigger high levels of inflammation that lead to fever and sometimes severe disease. People living in malaria-endemic areas gradually develop resistance to symptomatic malaria and control both parasite numbers and the inflammatory response. We previously found that adaptive natural killer (NK) cells correlate with reduced parasite load and protection from symptoms. We also previously found that murine NK cell production of IL-10 can protect mice from experimental cerebral malaria. Human NK cells can also secrete IL-10, but it was unknown what NK cell subsets produce IL-10 and if this is affected by malaria experience. We hypothesize that NK cell immunoregulation may lower inflammation and reduce fever induction. Here, we show that NK cells from subjects with malaria experience make significantly more IL-10 than subjects with no malaria experience. We then determined the proportions of NK cells that are cytotoxic and produce interferon gamma and/or IL-10 and identified a signature of adaptive and checkpoint molecules on IL-10-producing NK cells. Lastly, we find that co-culture with primary monocytes,Plasmodium-infected RBCs, and antibody induces IL-10 production by NK cells. These data suggest that NK cells may contribute to protection from malaria symptoms via IL-10 production.
Quantifying Normal Diaphragmatic Motion and Shape and their Developmental Changes via Dynamic MRI
Authors: Hao You , Udupa Jayaram K. , Tong Yubing , Wu Caiyun , McDonough Joseph M. , Gogel Samantha , Mayer Oscar H. , Alnoury Mostafa , Cahill Patrick J. , Anari Jason B. , Torigian Drew A. 
Published: May 2024

AbstractBackgroundThe diaphragm is a critical structure in respiratory function, yet in-vivo quantitative description of its motion available in the literature is limited.Research QuestionHow to quantitatively describe regional hemi-diaphragmatic motion and curvature via free-breathing dynamic magnetic resonance imaging (dMRI)?Study Design and MethodsIn this prospective cohort study we gathered dMRI images of 177 normal children and segmented hemi-diaphragm domes in end-inspiration and end-expiration phases of the constructed 4D image. We selected 25 points uniformly located on each 3D hemi-diaphragm surface. Based on the motion and local shape of hemi-diaphragm at these points, we computed the velocities and sagittal and coronal curvatures in 13 regions on each hemi-diaphragm surface and analyzed the change in these properties with age and gender.ResultsOur cohort consisted of 94 Females, 6-20 years (12.09+3.73), and 83 Males, 6-20 years (11.88+3.57). We observed velocity range: ∼2mm/s to ∼13mm/s; Curvature range –Sagittal: ∼3m-1to ∼27m-1; Coronal: ∼6m-1to ∼20m-1. There was no significant difference in velocity between genders, although the pattern of change in velocity with age was different for the two groups. Strong correlations in velocity were observed between homologous regions of right and left hemi-diaphragms. There was no significant difference in curvatures between genders or change in curvatures with age.InterpretationRegional motion/curvature of the 3D diaphragmatic surface can be estimated using free-breathing dynamic MRI. Our analysis sheds light on here-to-fore unknown matters such as how the pediatric 3D hemi-diaphragm motion/shape varies regionally, between right and left hemi-diaphragms, between genders, and with age.
Estimating lung volumetric parameters via rapid, limited-slice, free-breathing thoracic dynamic MRI
Authors: Hao You , Udupa Jayaram K. , Tong Yubing , Wu Caiyun , McDonough Joseph M. , Gogel Samantha , Biko David M. , Anari Jason B. , Torigian Drew A. , Cahill Patrick J. 
Published: May 2024

AbstractPurposeWe present an observational study involving free-breathing short-scan-time dynamic MRI (dMRI) method that can be routinely used for computing dynamic lung volumes accurately.Materials and Methods(i) Full-resolution free-breathing sagittally-acquired 2D dMRI scans are gathered from 45 normal children via True-FISP sequence. Sparse dMRI (s-dMRI) scans are simulated from these datasets by subsampling in the spatio-temporal domains via a limited numberNSSof selected sagittal locations andTSSof time instances (respectively,NFSandTFSfor full scan). (ii) A 4D image is constructed from both full and sparse scans. Lungs are segmented from 4D image, and their volumes from full (VF) and sparse dMRI (VS) scans are computed. (iii) A regression model is fit forVFas a function ofVSon a training set, and the full-resolution volumeVPpredicted by the model is estimated fromVS. (iv) The deviation ofVPfromVFis analyzed on both synthesized sparse dMRI scans from a separate full-resolution test set and actual s-dMRI scans prospectively acquired from 10 normal children.ResultsWithNSS=5 (per lung) andTSS=40, the deviation ofVPfromVFwas ∼2% with a total scan-time of ∼9 min (45-60 min for the full scan withNFS=15-22 (per lung) andTFS=80). These metrics become 0.4%, and <20 min for s-dMRI withNSS=15-22 (per lung) andTSS=40.Conclusions-dMRI is a practical approach for computing dynamic lung volumes that can be used routinely with no radiation concern, especially on patients who cannot tolerate long scan times.
Assessment of knowledge, Attitudes and Practices regarding Hepatitis B virus among Nurses in Bangladesh: a cross-sectional study
Authors: Rahman Salekur , Das Sadhan Kumar , Farhana Zaki , Bakkar Siddik Md Abu , Roy Anjan Kumar , Dey Piue , Kundu Shuvojit Kumar , Hossain Md Anwar , Islam S M Shahinul , Kamil Anton Abdulbasah , Khanam Jahan Ara , Rahman Mohammad Meshbahur 
Published: May 2024

AbstractBackgroundHepatitis B virus (HBV) infection is a worldwide issue. Nurses are particularly at risk of occupational HBV contamination. In Bangladesh, there is little understanding of the knowledge, attitude, and practices (KAP) of nurses regaarding HBV. Therefore, the study aimed to assess the KAP of nurses regarding HBV.MethodsThis cross-sectional study was conducted among 120 nurses through face-to-face interviews through a semi-structured questionnaire using a convenient sample technique. Different statistical tools including frequency distribution, Pearson Chi-square test, and t-tests were used in data analysis.ResultsThe average age of the participants was 34.5 years where majority of them were 31-40 years old (50.0%) and female (83%). This study revealed that 25.0% had good knowledge, 43.3% exhibited a good (positive) attitude, and 56.7% of nurses demonstrated good practices regarding HBV. Conversely, nurses exhibit a poor knowledge rate of 30.0%, a poor attitude rate of 30.8%, and a poor practice rate of 29.2% regarding HBV. The independent sample t-test and one-way ANOVA demonstrated that nurses’ from rural residences had a significantly higher knowledge [0.80 (0.79-0.82) versus 0.78 (0.77-0.79)]; p=0.001] regarding HBV. Similarly, female [mean attitude score: 0.88 (0.85-0.91) versus 0.77 (0.86-0.69); p=0.009] and nurses from Muslim [0.79(0.61-0.97) versus 0.79(0.76-0.83); p=0.035] faiths has significantly higher positive attitude and good practice behaviors compared to their counterparts.ConclusionsIncreasing the vaccination coverage rate of all nurses, as well as implementing additional techniques for preventing exposure in the workplace, training programs on HBV infection, including PEP, comes highly recommended.
ILC2s navigate tissue redistribution during infection using stage-specific S1P receptors
Authors: Ito Takamasa , Ishida Yoshihiro , Zhang Yingyu , Guichard Vincent , Zhang Wanwei , Han Richard , Guckian Kevin , Chun Jerold , Que Jianwen , Smith Allen , Urban Joseph F. , Huang Yuefeng 
Published: May 2024

AbstractLymphocytes can circulate as well as take residence within tissues. While the mechanisms by which circulating populations are recruited to infection sites have been extensively characterized, the molecular basis for the recirculation of tissue-resident cells is less understood. Here, we show that helminth infection- or IL-25-induced redistribution of intestinal group 2 innate lymphoid cells (ILC2s) requires access to the lymphatic vessel network. Although the secondary lymphoid structure is an essential signal hub for adaptive lymphocyte differentiation and dispatch, it is redundant for ILC2 migration and effector function. Upon IL-25 stimulation, a dramatic change in epigenetic landscape occurs in intestinal ILC2s, leading to the expression of sphingosine-1-phosphate receptors (S1PRs). Among the various S1PRs, we found that S1PR5 is critical for ILC2 exit from intestinal tissue to lymph. By contrast, S1PR1 plays a dominant role in ILC2 egress from mesenteric lymph nodes to blood circulation and then to distal tissues including the lung where the redistributed ILC2s contribute to tissue repair. The requirement of two S1PRs for ILC2 migration is largely due to the dynamic expression of the tissue-retention marker CD69, which mediates S1PR1 internalization. Thus, our study demonstrates a stage-specific requirement of different S1P receptors for ILC2 redistribution during infection. We therefore propose a fundamental paradigm that innate and adaptive lymphocytes utilize a shared vascular network frame and specialized navigation cues for migration.
Acceleration of genome rearrangement in clitellate annelids
Authors: Schultz Darrin T. , Heath-Heckman Elizabeth A.C. , Winchell Christopher J. , Kuo Dian-Han , Yu Yun-sang , Oberauer Fabian , Kocot Kevin M. , Cho Sung-Jin , Simakov Oleg , Weisblat David A. 
Published: May 2024

ABSTRACTComparisons of multiple metazoan genomes have revealed the existence of ancestral linkage groups (ALGs), genomic scaffolds sharing sets of orthologous genes that have been inherited from ancestral animals for hundreds of millions of years (Simakov et al. 2022; Schultz et al. 2023) These ALGs have persisted across major animal taxa including Cnidaria, Deuterostomia, Ecdysozoa and Spiralia. Notwithstanding this general trend of chromosome-scale conservation, ALGs have been obliterated by extensive genome rearrangements in certain groups, most notably including Clitellata (oligochaetes and leeches), a group of easily overlooked invertebrates that is of tremendous ecological, agricultural and economic importance (Charles 2019; Barrett 2016). To further investigate these rearrangements, we have undertaken a comparison of 12 clitellate genomes (including four newly sequenced species) and 11 outgroup representatives. We show that these rearrangements began at the base of the Clitellata (rather than progressing gradually throughout polychaete annelids), that the inter-chromosomal rearrangements continue in several clitellate lineages and that these events have substantially shaped the evolution of the otherwise highly conserved Hox cluster.
Analysis of differential expression of matrix metalloproteins and defensins in the nasopharyngeal milieu of mild and severe COVID-19 cases
Authors: Imtiaz Khekashan , Farooqui Nida , Ahmed Khalid , Zhamalbekova Alnara , Anwar Muhammad Faraz , Gul Khitab , Hussain Azhar , Sarría-Santamera Antonio , Abidi Syed Hani 
Published: May 2024

AbstractIntroductionA subset of COVID-19 disease patients suffers a severe form of the illness, however, underlying early pathophysiological mechanisms associated with the severe form of COVID-19 disease remain to be fully understood. Several studies showed the association of COVID-19 disease severity with the changes in the expression profile of various matrix metalloproteinases (MMPs) and defensins. However, the link between the changes in the expression of matrix metalloproteinase (MMPs) and defensins (DA) in the nasopharyngeal milieu, during early phases of infection, and disease severity remains poorly understood. Therefore, we performed differential gene expression analysis of matrix metalloproteinases (MMPs) and defensins in the nasopharyngeal swab samples collected from mild and severe COVID-19 cases within three days of infection and examined the association between MMP and DA expression and disease severity.Material and MethodA total of 118 previously collected nasopharyngeal samples from mild and severe COVID-19 patients (as per the WHO criteria) were used in this study. To determine the viral loads and assess the mRNA expression of matrix metalloproteinase (MMPs) and defensins, a real-time qPCR assay was used. To assess statistically significant differences in the mean expression of viral loads and the cytokines in between the severe and mild groups, an unpaired T-test was applied. The Pearson correlation test was used to assess the correlation between cytokine expressions. In addition, a multivariable logistic regression analysis was carried out with all the variables from the data set using ‘severity’ as the outcome variable.ResultsOur results showed that the expression of DA3 and MMP2 to be considerably lower in the severe group than in the mild group. Furthermore, there was a significant association between MMP1 and DA4 and DA6 (r=0.5, p=0.0001); as well as between MMP7 and DA1 and DA6 (r=0.5, p=0.00). Additionally, the regression analysis shows a significant correlation (p 0.05) between MMP2 and the severity of COVID-19 disease.ConclusionThe early detection of changes in the expression of MMPs and defensins may act as a useful biomarker/predictor for possible severe COVID-19 disease, which may be useful in the clinical management of patients to reduce COVID-19-associated morbidity and mortality.
Enhancing data integrity in Electronic Health Records: Review of methods for handling missing data
Authors: Vahdati Amin , Cotterill Sarah , Marsden Antonia , Kontopantelis Evangelos 
Published: May 2024

AbstractIntroductionElectronic Health Records (EHRs) are vital repositories of patient information for medical research, but the prevalence of missing data presents an obstacle to the validity and reliability of research. This study aimed to review and category ise methods for handling missing data in EHRs, to help researchers better understand and address the challenges related to missing data in EHRs.Materials and MethodsThis study employed scoping review methodology. Through systematic searches on EMBASE up to October 2023, including review articles and original studies, relevant literature was identified. After removing duplicates, titles and abstracts were screened against inclusion criteria, followed by full-text assessment. Additional manual searches and reference list screenings were conducted. Data extraction focused on imputation techniques, dataset characteristics, assumptions about missing data, and article types. Additionally, we explored the availability of code within widely used software applications.ResultsWe reviewed 101 articles, with two exclusions as duplicates. Of the 99 remaining documents, 21 underwent full-text screening, with nine deemed eligible for data extraction. These articles introduced 31 imputation approaches classified into ten distinct methods, ranging from simple techniques like Complete Case Analysis to more complex methods like Multiple Imputation, Maximum Likelihood, and Expectation-Maximization algorithm. Additionally, machine learning methods were explored. The different imputation methods, present varying reliability. We identified a total of 32 packages across the four software platforms (R, Python, SAS, and Stata) for imputation methods. However, it’s significant that machine learning methods for imputation were not found in specific packages for SAS and Stata. Out of the 9 imputation methods we investigated, package implementations were available for 7 methods in all four software platforms.ConclusionsSeveral methods to handle missing data in EHRs are available. These methods range in complexity and make different assumptions about the missing data mechanisms. Knowledge gaps remain, notably in handling non-monotone missing data patterns and implementing imputation methods in real-world healthcare settings under the Missing Not at Random assumption. Future research should prioritize refining and directly comparing existing methods.
Early Life Domains as Predictors of Obesity and Hypertension Comorbidity: Findings from the 1970 British Cohort Study (BCS70)
Authors: Stannard S , Owen RK , Berrington A , Ziauddeen N , Fraser SDS , Paranjothy S , Hoyle RB , Alwan N A 
Published: May 2024

AbstractBackgroundObesity and hypertension are major public health problems and are associated with adverse health outcomes. To model realistic prevention scenarios and inform policy, it may be helpful to conceptualise early lifecourse domains of risk and incorporate such information when predicting comorbidity outcomes. We identify exposures across five pre-hypothesised childhood domains and explore them as predictors of obesity and hypertension comorbidity in adulthood.MethodsThe analytical sample included 7858 participants in the 1970 British Cohort Study. The outcome was obesity (BMI of ≥30) and hypertension (blood pressure>140/90mm Hg or self-reported doctor’s diagnosis) comorbidity at age 46. Early life domains included: ‘prenatal, antenatal, neonatal and birth’, ‘developmental attributes and behaviour’, ‘child education and academic ability’, ‘socioeconomic factors’ and ‘parental and family environment’. We conducted prediction analysis of the outcome in three stages:(1) stepwise backward elimination to select variables for inclusion for each domain (2) calculation of predicted risk scores of obesity-hypertension for each cohort member within each domain (3) multivariable logistic regression analysis including domain-specific risk scores, sex and ethnicity to assess how well the outcome could be predicted. We additionally included potential adult predictors of obesity-hypertension comorbidity as sensitivity analysis.ResultsIncluding all domain-specific risk scores in the same model, all five domains were significant predictors of obesity-hypertension comorbidity. The predictive power of the model, measured by the area under the curve (AUC), was 0.63 (95%CI 0.61-0.65). Including adult predictors increase the AUC to 0.68 (95%CI 0.66-0.70), and three early life domains - the parental and family environment domain (OR 1.11 95%CI 1.05-1.17) the socioeconomic factors domain (OR 1.09 95%CI 1.04-1.16), and the education and academic ability domain (OR 1.07 95%CI 1.02-1.13) remained predictors of obesity-hypertension comorbidity.ConclusionsWe found three robust domains for predicting obesity-hypertension comorbidity. Interventions that address these early life factors could reduce the burden of comorbidity.
Retention in care and antiretroviral therapy adherence among Medicaid beneficiaries with HIV, 2001-2015
Authors: Rudolph Jacqueline E. , Calkins Keri L. , Zhang Xueer , Zhou Yiyi , Xu Xiaoqiang , Wentz Eryka L. , Joshu Corinne E. , Lau Bryan 
Published: May 2024

ABSTRACTDisparities in HIV care by socioeconomic status, place of residence, and race/ethnicity prevent progress toward epidemic control. No study has comprehensively characterized the HIV care cascade among people with HIV enrolled in Medicaid – an insurance source for low-income individuals in the US. We analyzed data from 246,127 people with HIV enrolled in Medicaid 2001-2015, aged 18-64, living in 14 US states. We estimated monthly prevalence of four steps of the care cascade: retained in care/adherent to ART; retained/not adherent; not retained/adherent; not retained/not adherent. Beneficiaries were retained in care if they had an outpatient care encounter every six months. Adherence was based on medication possession ratio. We estimated prevalence using a non-parametric multi-state approach, accounting for death as a competing event and for Medicaid disenrollment using inverse probability of censoring weights. Across 2001-2015, the proportion of beneficiaries with HIV who were retained/ART adherent increased, overall and in all subgroups. By 2015, approximately half of beneficiaries were retained in care, and 42% of beneficiaries were ART adherent. We saw meaningful differences by race/ethnicity and region. Our work highlights an important disparity in the HIV care cascade by insurance status during this time period.
MultiSuSiE improves multi-ancestry fine-mapping in All of Us whole-genome sequencing data
Authors: Rossen Jordan , Shi Huwenbo , Strober Benjamin J , Zhang Martin Jinye , Kanai Masahiro , McCaw Zachary R. , Liang Liming , Weissbrod Omer , Price Alkes L. 
Published: May 2024

AbstractLeveraging data from multiple ancestries can greatly improve fine-mapping power due to differences in linkage disequilibrium and allele frequencies. We propose MultiSuSiE, an extension of the sum of single effects model (SuSiE) to multiple ancestries that allows causal effect sizes to vary across ancestries based on a multivariate normal prior informed by empirical data. We evaluated MultiSuSiE via simulations and analyses of 14 quantitative traits leveraging whole-genome sequencing data in 47k African-ancestry and 94k European-ancestry individuals from All of Us. In simulations, MultiSuSiE applied to Afr47k+Eur47k was well-calibrated and attained higher power than SuSiE applied to Eur94k; interestingly, higher causal variant PIPs in Afr47k compared to Eur47k were entirely explained by differences in the extent of LD quantified by LD 4th moments. Compared to very recently proposed multi-ancestry fine-mapping methods, MultiSuSiE attained higher power and/or much lower computational costs, making the analysis of large-scale All of Us data feasible. In real trait analyses, MultiSuSiE applied to Afr47k+Eur94k identified 579 fine-mapped variants with PIP > 0.5, and MultiSuSiE applied to Afr47k+Eur47k identified 44% more fine-mapped variants with PIP > 0.5 than SuSiE applied to Eur94k. We validated MultiSuSiE results for real traits via functional enrichment of fine-mapped variants. We highlight several examples where MultiSuSiE implicates well-studied or biologically plausible fine-mapped variants that were not implicated by other methods.
H3K18 & H3K23 acetylation directs establishment of MLL-mediated H3K4 methylation
Authors: Fox Geoffrey C. , Poncha Karl F. , Smith B. Rutledge , van der Maas Lara N. , Robbins Nathaniel N. , Graham Bria , Dowen Jill M. , Strahl Brian D. , Young Nicolas L. , Jain Kanishk 
Published: May 2024

AbstractIn an unmodified state, positively charged histone N-terminal tails engage nucleosomal DNA in a manner which restricts access to not only the underlying DNA, but also key tail residues subject to binding and/or modification. Charge-neutralizing modifications, such as histone acetylation, serve to disrupt this DNA-tail interaction, facilitating access to such residues. We previously showed that a polyacetylation-mediated chromatin “switch” governs the read-write capability of H3K4me3 by the MLL1 methyltransferase complex. Here, we discern the relative contributions of site-specific acetylation states along the H3 tail and extend our interrogation to other chromatin modifiers. We show that the contributions of H3 tail acetylation to H3K4 methylation by MLL1 are highly variable, with H3K18 and H3K23 acetylation exhibiting robust stimulatory effects, and that this extends to the related H3K4 methyltransferase complex, MLL4. We show that H3K4me1 and H3K4me3 are found preferentially co-enriched with H3 N-terminal tail proteoforms bearing dual H3K18 and H3K23 acetylation (H3{K18acK23ac}). We further show that this effect is specific to H3K4 methylation, while methyltransferases targeting other H3 tail residues (H3K9, H3K27, & H3K36), a methyltransferase targeting the nucleosome core (H3K79), and a kinase targeting a residue directly adjacent to H3K4 (H3T3) are insensitive to tail acetylation. Together, these findings indicate a unique and robust stimulation of H3K4 methylation by H3K18 and H3K23 acetylation and provide key insight into why H3K4 methylation is often associated with histone acetylation in the context of active gene expression.