bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term intrinsic cycling in human life-course antibody responses to influenza A(H3N2)
Authors: Yang Bingyi , Garcia-Carreras Bernardo , Lessler Justin , Read Jonathan M. , Zhu Huachen , Metcalf C. Jessica E. , Hay James A. , Kwok Kin On , Shen Ruiyin , Jiang Chao Qiang , Guan Yi , Riley Steven , Cummings Derek A.T. 
Published: June 2022

ABSTRACTOver a life-course, human adaptive immunity to antigenically mutable pathogens exhibits competitive and facilitative interactions. We hypothesize that such interactions may lead to cyclic dynamics in immune responses over a lifetime. Here, we demonstrated a long-term periodicity (about 24 years) in individual antibody responses, by analyzing hemagglutination inhibition titers against 21 historical influenza A(H3N2) strains spanning 47 years from a cohort in Guangzhou, China. The reported cycles were robust to analytic and sampling approaches. Simulations suggested that individual-level cross-reaction between antigenically similar strains likely explain the reported cycle. We showed that the reported cycles are predictable at both individual and birth-cohort level and that cohorts show a diversity of phases of these cycles. Phase of cycle was associated with the risk of response to circulating strains, after accounting for age and pre-existing titers of the circulating strains. Our findings reveal the existence of long-term periodicities in individual antibody responses to A(H3N2). We hypothesize that these cycles are driven by pre-existing antibody responses blunting responses to antigenically similar pathogens (by preventing infection and/or robust antibody responses upon infection), leading to reductions in antigen specific responses over time until individual’s increasing risk leads to an infection with an antigenically distant enough virus to generate a robust immune response. These findings could help disentangle cohort-effects from individual-level exposure histories, improve our understanding of observed heterogeneous antibody responses to immunizations, and inform targeted vaccine strategy.
Birth Weight and Associated Factors among Host and Refugee Neonates at Health Facilities in Gambella Region: A facility based Comparative Cross-sectional Study
Authors: Nhial Bang Chuol , Wedajo Shambel , Tadesse Sisay Eshete 
Published: June 2022

AbstractBackgroundBirth weight remains as one of the facing factors and one of the leading causes of child suffering worldwide. This is a major problem especially in low and middle income countries and most importantly in vulnerable populations like refugee. However, there is a limited evident as yet in the study area.ObjectiveThe aim of this study was to assess the birth weight and associated factors among host and refugee neonates at health facilities in Gambella Region.MethodsA facility based comparative cross-sectional study was applied in host and refugee settings. A total of five hundred ninety six neonates were included in this study from February 1st, 2020 to March 31st, 2020 through multi-stages sampling technique. The data were collected using structured interview and documents review methods with structured questionnaires as instruments. Pretesting of the tool and training of data collectors and field supervision were made. Using statistical package for social science version 25, variables with p≤0.05 from multiple linear regression analysis were declared as factors significantly associated with the birth weight. Furthermore, independent samples t-test was computed to compare the mean birth weights.ResultsThe study resulted in 100% response rate. The mean birth weights were found to be significantly difference between host and refugee neonates with means of 3282.55±415.97 grams and 3109.40±635.10 grams respectively (m1-m2 = 173.15, 95% CI: (86.75, 259.56)). Several factors such as number of fetuses (β = -148.35, 95% CI: (-234.86, -61.83)), gestational age at delivery (β = 90.83, 95% CI: (66.72, 114.93)), household food security status (β = 166.33, 95% CI: (100.68, 231.97)), individual dietary diversity score (β = 88.75, 95% CI: (68.69, 108.81)) and pregnancy induced hypertension (β = -148.35, 95% CI: (-234.86, -61.83)) were found to be the most influential factors significantly associated with the birth weight.ConclusionsIn the study area, host neonates have larger mean birth weight than the refugee neonates. Number of fetuses, gestational age at delivery, household food security, individual dietary diversity score and pregnancy induced hypertension were factors influencing the birth weight.
Characteristics, clinical outcomes, and mortality of older adults living with HIV receiving antiretroviral treatment in the sub-urban and rural areas of northern Thailand
Authors: Aurpibul Linda , Sripan Patumrat , Paklak Wason , Tangmunkongvorakul Arunrat , Rerkasem Amaraporn , Rerkasem Kittipan , Srithanaviboonchai Kriengkrai 
Published: June 2022

AbstractSince the introduction of antiretroviral treatment (ART), people living with HIV worldwide live into older age. This study described the characteristics, clinical outcomes, and mortality of older adults living with HIV (OALHIV) receiving ART from the National AIDS program in northern Thailand. Participants aged ≥ 50 years were recruited from the HIV clinics in 12 community hospitals. Data were obtained from medical records and face-to-face interviews. In 2015, 362 OALHIV were enrolled; their median (interquartile range) age and ART duration were 57 years (54-61), and 8.8 years (6.4-11.2), respectively. At study entry, 174 (48.1%) had CD4 counts ≥ 500 cells/mm3; 357 of 358 (99.6%) with available HIV RNA results were virologic-suppressed. At the year 5 follow-up, 39 died, 11 were transferred to other hospitals, 3 were lost to follow-up, and 40 did not contribute data for this analysis, but remained in care. Among the 269 who appeared, 149 (55%) had CD4 counts ≥ 500 cells/mm3, and 227/229 tested (99%) were virologic-suppressed. The probability of 5-year overall survival (OS) was 89.2% (95% confidence interval, CI 85.4-92.1%). A significantly low 5-year OS (66%) was observed in OALHIV with CD4 counts < 200 cells/mm3 at study entry. The most common cause of death was organ failures in 11 (28%), followed by malignancies in 8 (21%), infections in 5 (13%), mental health-related conditions in 2 (5%), and unknown in 13 (33%). In OALHIV with stable HIV outcomes, monitoring of organ functions, cancer surveillance, and mental health screening are warranted.
Infectious and Clinical Tuberculosis Trajectories: Bayesian modeling with case finding implications
Authors: Ryckman Theresa S , Dowdy David W , Kendall Emily A 
Published: June 2022

AbstractBackgroundThe importance of finding people with undiagnosed tuberculosis (TB) hinges on their clinical and infectious trajectories. Assays for systematic screening should be optimized to find those whose TB will contribute most to future transmission or morbidity.MethodsWe constructed a mathematical model which tracks the disease trajectories of individuals with TB, classifying them over time by bacterial burden (smear positive/negative) and symptom status (symptomatic/subclinical). We used Bayesian methods to calibrate this model to historical survival data and notification, mortality, and prevalence survey data from five countries. We combined the resulting individual disease trajectories with evidence on infectiousness, to compare how much different subsets of prevalent TB contribute to future transmission events.ResultsNearly all (89% [95% uncertainty range 83-93%]) smear-negative subclinical TB resolved before diagnosis or treatment, typically after a short disease course (4.3 [3.3-6.7] months). In contrast, people with smear-positive subclinical TB had a longer overall duration of undiagnosed disease (15.5 [11.0-21.3] months), and most eventually developed symptoms. Despite accounting for only 11-20% of prevalent disease, smear-positive subclinical TB accounted for 37-48% of future transmission – a greater contribution than symptomatic TB or smear-negative TB.ConclusionsSubclinical TB with a high bacterial burden accounts for a disproportionate share of future transmission. Priority should be given to developing inexpensive, easy-to-use assays for screening both symptomatic and asymptomatic individuals at scale – akin to rapid antigen tests for other diseases – even if these assays lack the sensitivity to detect paucibacterial disease.
Contracting the Private Health Sector in Thailand’s Universal Health Coverage
Authors: Marshall Aniqa Islam , Witthayapipopsakul Woranan , Chotchoungchatchai Somtanuek , Wangbanjongkun Waritta , Tangcharoensathien Viroj 
Published: June 2022

AbstractBackgroundPrivate sector plays an import role in health service provision, therefore the engagement of private health facilities is important for ensuring access to health services. In Thailand, two of the three public health insurance schemes, Universal Coverage Scheme and Social Health Insurance, contract with private health facilities to fill gaps of public providers for the provision of health services under Universal Health Coverage. The National Health Security Office (NHSO) and Social Security Office (SSO), which manage the schemes respectively, have designed their own contractual agreements for private facilities.MethodsThis qualitative descriptive case study was conducted through document review and in-depth interviews with key informants to better understand the current situation of contracting private health facilities within UHC by comparing the two purchasing agencies on how they contract private primary care facilities, service types, duration of contract, standard and quality requirement and renewal and termination of contracts.ResultsSocial Security Office (SSO) have adopted capitation-based contract model since 1991. The National Health Security Office (NHSO) applies capitation payments for outpatient services and Diagnostic Related Group systems payment for inpatient services. NHSO classified contractor providers in 3 categories for seamless referral services: main contracting units, primary care units, and referral units. External evaluations and certifications from the Healthcare Accreditation Institute are required for standardization of care. Both purchasing agencies conduct auditing to monitor quality of care while NHSO additionally provides incentives to private facilities for continuous quality improvement.ConclusionContracting of private healthcare facilities is needed to fill the gap of public healthcare facilities, especially in urban settings. To ensure access to quality of care, in contracting with private-for-profit providers strong regulatory enforcement and auditing measures with financial incentives in necessary.
Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics
Authors: Arora Abishek , Becker Martin , Marques Cátia , Oksanen Marika , Li Danyang , Mastropasqua Francesca , Watts Michelle Evelyn , Arora Manish , Falk Anna , Daub Carsten Oliver , Lanekoff Ingela , Tammimies Kristiina 
Published: June 2022

ABSTRACTResearch continues to identify genetic variation, environmental exposures, and their mixtures underlying different diseases and conditions. There is a need for screening methods to understand the molecular outcomes of such factors. Here, we investigate a highly efficient and multiplexable, fractional factorial experimental design (FFED) to study six environmental factors and four human induced pluripotent stem cell line derived differentiating human neural progenitors. We showcase the FFED coupled with RNA-sequencing to identify the effects of low-grade exposures to these environmental factors and analyse the results in the context of autism spectrum disorder (ASD). We performed this after five-day exposures on differentiating human neural progenitors accompanied by a layered analytical approach and detected several convergent and divergent, gene and pathway level responses. We revealed significant upregulation of pathways related to synaptic function and lipid metabolism following lead and fluoxetine exposure, respectively. The lipid changes were validated using mass spectrometry- based metabolomics after fluoxetine exposure. Our study demonstrates that the FFED can be used for multiplexed transcriptomic analyses to detect relevant pathway-level changes in human neural development caused by low-grade environmental risk factors. Future studies will require multiple cell lines with different genetic backgrounds for characterising the effects of environmental exposures in ASD.
Determination of expression profiles for Drosophila ovarian Follicle Stem Cells (FSCs) using single-cell RNA sequencing
Authors: Dong Zhi , Pang Lan , Liu Zhiguo , Sheng Yifeng , Thibault Xavier , Reilein Amy , Kalderon Daniel , Huang Jianhua 
Published: June 2022

SummaryDrosophila ovarian Follicle Stem Cells (FSC) present an excellent paradigm for understanding how a community of active stem cells maintained by population asymmetry is regulated. Here we describe single-cell RNA sequencing studies of a pre-sorted population of cells that include FSCs and the neighboring cell types, Escort Cells (ECs) and Follicle Cells (FCs), which they support. Cell-type assignment relies on anterior-posterior (AP) location within the germarium. We clarify the previously determined location of FSCs and use spatially targeted lineage studies as further confirmation. The scRNA profiles among four clusters are consistent with an AP progression from anterior ECs through posterior ECs and then FSCs, to early FCs. Several genes with graded profiles from ECs to FCs are highlighted as candidate effectors of the inverse gradients of the two principal signaling pathways, Wnt and JAK-STAT, that guide FSC differentiation and division.
Bioluminescence-based reporters for characterizing inhibitors and activators of human Sonic Hedgehog protein autoprocessing in live cells at high throughput
Authors: Ciulla Daniel A , Dranchak Patricia , Pezzullo John L , Mancusi Rebecca A , Psaras Alexandra Maria , Rai Ganesha , Giner José-Luis , Inglese James , Callahan Brian P 
Published: June 2022

ABSTRACTThe Sonic hedgehog (SHh) precursor protein undergoes biosynthetic autoprocessing to cleave off and cholesterylate the SHh signaling ligand, a vital morphogen and oncogenic effector protein. Autoprocessing is self-catalyzed by SHhC, the SHh precursor’s enzymatic domain. Here we describe the development and validation of the first cellular reporter to monitor human SHhC autoprocessing non-invasively in high-throughput compatible plates. The assay couples intracellular SHhC autoprocessing to the extracellular secretion of the bioluminescent nanoluciferase enzyme. We developed a wild-type (WT) SHhC reporter line for evaluating potential autoprocessing inhibitors by concentration response-dependent suppression of extracellular bioluminescence. A conditional mutant SHhC (D46A) reporter line was developed for identifying potential autoprocessing activators by a concentration response-dependent gain of extracellular bioluminescence. The D46A mutation removes a conserved general base that is critical for the substrate activity of cholesterol. Inducibility of the D46A reporter was established using a synthetic sterol, 2-α carboxy cholestanol, designed to bypass the defect through intra-molecular general base catalysis. To facilitate direct nanoluciferase detection in the cell culture media of 1536-well plates, we designed a novel membrane-impermeable nanoluciferase substrate, CLZ-2P. This new reporter system offers a long-awaited resource for small molecule discovery for cancer and for developmental disorders where SHh ligand biosynthesis is dysregulated.Abstract Figure
Extravascular spaces are the primary reservoir of antigenic diversity inTrypanosoma bruceiinfection
Authors: Beaver Alexander K. , Keneskhanova Zhibek , Cosentino Raúl O. , Weiss Brian L. , Awuoche Erick O. , Smallenberger Gretchen M. , Buenconsejo Gracyn Y. , Crilly Nathan P. , Smith Jaclyn E. , Hakim Jill M.C. , Zhang Bailin , Bobb Bryce , Rijo-Ferreira Filipa , Figueiredo Luisa M. , Aksoy Serap , Siegel T. Nicolai , Mugnier Monica R. 
Published: June 2022

Summary paragraphThe protozoan parasiteTrypanosoma bruceievades clearance by the host immune system through antigenic variation of its dense variant surface glycoprotein (VSG) coat, periodically “switching” expression of the VSG using a large genomic repertoire of VSG-encoding genes1–6. Recent studies of antigenic variation in vivo have focused near exclusively on parasites in the bloodstream4,7,8, but research has shown that many, if not most, parasites reside in the interstitial spaces of tissues9–13. We sought to explore the dynamics of antigenic variation in extravascular parasite populations using VSG-seq7, a high-throughput sequencing approach for profiling VSGs expressed in populations ofT. brucei. Here we show that tissues, not the blood, are the primary reservoir of antigenic diversity during both needle- and tsetse bite-initiatedT. bruceiinfections, with more than 75% of VSGs found exclusively within extravascular spaces. We found that this increased diversity is correlated with slower parasite clearance in tissue spaces. Together, these data support a model in which the slower immune response in extravascular spaces provides more time to generate the antigenic diversity needed to maintain a chronic infection. Our findings reveal the important role that extravascular spaces can play in pathogen diversification.
Group B Streptococcus Adaptation Promotes Survival in a Hyperinflammatory Diabetic Wound Environment
Authors: Keogh Rebecca A. , Haeberle Amanda L. , Langouët-Astrié Christophe J. , Kavanaugh Jeffrey S. , Schmidt Eric P. , Moore Garrett D. , Horswill Alexander R. , Doran Kelly S. 
Published: June 2022

AbstractDiabetic wounds have poor healing outcomes due to the presence of numerous pathogens and a dysregulated immune response. Group BStreptococcus(GBS) is commonly isolated from diabetic wound infections, but the mechanisms of GBS virulence during these infections have not been investigated. Here, we develop a murine model of GBS diabetic wound infection, and using dual RNA-sequencing, demonstrate that GBS infection triggers an inflammatory response. GBS adapts to this hyperinflammatory environment by upregulating virulence factors including those known to be regulated by the two-component systemcovRS, such as the surface proteinpbsP, and thecyloperon which is responsible for hemolysin/pigmentation production. We recover hyperpigmented/hemolytic GBS colonies from the murine diabetic wound which we determined encode mutations incovR. We further demonstrate that GBS mutants incylEandpbsPare attenuated in the diabetic wound. This foundational study provides insight into the pathogenesis of GBS diabetic wound infections.TeaserThe Fight for Survival by the Bacterium Group B Streptococcus in the Diabetic Wound.
Craniofacial dysmorphology in Down Syndrome is caused by increased dosage of Dyrk1a and at least three other genes
Authors: Redhead Yushi , Gibbins Dorota , Lana-Elola Eva , Watson-Scales Sheona , Dobson Lisa , Krause Matthias , Liu Karen J. , Fisher Elizabeth M. C. , Green Jeremy B.A. , Tybulewicz Victor L.J. 
Published: June 2022

AbstractDown syndrome (DS), trisomy of human chromosome 21 (Hsa21), occurs in 1 in 800 live births and is the most common human aneuploidy. DS results in multiple phenotypes, including craniofacial dysmorphology, characterised by midfacial hypoplasia, brachycephaly and micrognathia. The genetic and developmental causes of this are poorly understood. Using morphometric analysis of the Dp1Tyb mouse model of DS and an associated genetic mouse genetic mapping panel, we demonstrate that four Hsa21-orthologous regions of mouse chromosome 16 contain dosage-sensitive genes that cause the DS craniofacial phenotype, and identify one of these causative genes as Dyrk1a. We show that the earliest and most severe defects in Dp1Tyb skulls are in bones of neural crest (NC) origin, and that mineralisation of the Dp1Tyb skull base synchondroses is aberrant. Furthermore, we show that increased dosage of Dyrk1a results in decreased NC cell proliferation and a decrease in size and cellularity of the NC-derived frontal bone primordia. Thus, DS craniofacial dysmorphology is caused by increased dosage of Dyrk1a and at least three other genes.Summary statementCraniofacial dysmorphology in mouse models of Down syndrome is caused by increased dosage of at least four genes including Dyrk1a, resulting in reduced proliferation of neural crest-derived cranial bone progenitors.
TANGO2 deficient iPSC-differentiated cardiomyocyte and dermal fibroblasts have normal mitochondrial OXPHOS function
Authors: Xu Weiyi , Cao Yingqiong , Cantú Lorren , Nasiotis Eleni , Lalani Seema R. , Miyake Christina Y. , Zhang Lilei 
Published: June 2022

ABSTRACTBi-allelic loss-of-function mutations in TANGO2 (Transport and Golgi Organization protein 2) cause a rare multiorgan genetic disorder. Despite normal cardiac function at baseline, patients may experience lethal cardiac arrhythmias during “crises” often associated with metabolic stresses such as fasting, viral illness and fever. The molecular function of TANGO2 remains largely unknown. Previous studies have suggested a functional association with the mitochondrion, however definitive evidence is lacking. Further, functional impact of TANGO2 deficiency on mitochondrial function has not been investigated in a cardiac model. In this study, we utilized a recently developed patient-derived induced pluripotent stem cell differentiated cardiomyocytes (iPSC-CM) model by our group, along with patient-derived dermal fibroblast model, to interrogate whether loss of TANGO2 function leads to defective mitochondrial function. Both baseline and fasting condition were investigated. Oxygen consumption rate (OCR) was measured in Seahorse assays to assess mitochondrial function in vitro. The results showed both TANGO2 deficient dermal fibroblasts and iPSC-CM had no apparent defects in mitochondrial oxidative phosphorylation (OXPHOS) function under either baseline or fasting condition. Based on our study, we conclude that the lethal cardiac arrhythmias in TANGO2 patients are unlikely to be related to impaired mitochondrial OXPHOS function in the cardiomyocytes.