bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Wastewater Sequencing Reveals Community and Variant Dynamics of the Collective Human Virome
Authors: Tisza Michael , Cregeen Sara Javornik , Avadhanula Vasanthi , Zhang Ping , Ayvaz Tulin , Feliz Karen , Hoffman Kristi L. , Clark Justin R. , Terwilliger Austen , Ross Matthew C. , Cormier Juwan , Henke David , Troisi Catherine , Wu Fuqing , Rios Janelle , Deegan Jennifer , Hansen Blake , Balliew John , Gitter Anna , Zhang Kehe , Li Runze , Bauer Cici X. , Mena Kristina D. , Piedra Pedro A. , Petrosino Joseph F. , Boerwinkle Eric , Maresso Anthony W. 
Published: May 2023

AbstractWastewater is a discarded human by-product but analyzing it may help us understand the health of communities. Epidemiologists first analyzed wastewater to track outbreaks of poliovirus decades ago, but so-called wastewater-based epidemiology was reinvigorated to monitor SARS-CoV-2 levels. Current approaches overlook the activity of most human viruses and preclude a deeper understanding of human virome community dynamics. We conducted a comprehensive sequencing-based analysis of 363 longitudinal wastewater samples from ten distinct sites in two major cities. Over 450 distinct pathogenic viruses were detected. Sequencing reads of established pathogens and emerging viruses correlated to clinical data sets. Viral communities were tightly organized by space and time. Finally, the most abundant human viruses yielded sequence variant information consistent with regional spread and evolution. We reveal the viral landscape of human wastewater and its potential to improve our understanding of outbreaks, transmission, and its effects on overall population health.One-Sentence SummaryWastewater contains a trickle of circulating human viruses, and now we can sequence them to better track community transmission.
Percutaneous coronary intervention has better in-hospital outcomes in severe renal failure patients
Authors: Li Renxi , Luo Qianyun 
Published: May 2023

AbstractBackgroundIn patients with severe renal failure, coronary artery bypass surgery (CABG) was found to have better long-term outcomes than percutaneous coronary intervention (PCI). This study aims to provide a retrospective analysis of short-term in-hospital peri-operative outcomes between PCI and CABG in patients with severe renal failure.MethodsPatients who underwent CABG and PCI in Q4 2015-2020 were identified in National Inpatient Sample (NIS) database. Patients of age<40 were excluded for congenital heart defects. Patients with comorbidity of severe renal failure were included. Between patients undergoing PCI and CABG, preoperative variables were compared and corrected in multivariable logistic regression examining their in-hospital peri-operative outcomes. Adjusted odds ratios (aOR) were estimated for mortality and morbidities.ResultsIn NIS, 4,512 CABG and 13,242 PCI cases were identified. Compared to CABG, patients who underwent PCI had lower mortality (4.24% vs 5.47%, aOR 0.725, p<0.0001) and lower morbidity including heart failure (0.14% vs 2.97%, aOR 0.044, p<0.0001), stroke (0.12% vs 0.47%, aOR 0.264, p<0.0001), respiratory complications (0.51% vs 7.34%, aOR 0.063, p<0.0001), renal complications (0.05% vs 0.49%, aOR 0.075, p<0.0001), acute kidney injury (8.67% vs 12.66%, aOR 0.646, p<0.0001), deep wound complications (0.02% vs 0.35%, aOR 0.042, p < 0.0001), shock (0.22% vs 0.95%, aOR 0.228, p<0.0001), and length of in-hospital stay over 7 days (24.75% vs 73.52%, aOR 0.106, p<0.0001).ConclusionNIS is a comprehensive database of nationwide providers, providing robust power in analysis. In patients with severe renal failure, PCI offers an advantage over CABG in terms of short-term in-hospital perioperative outcomes.
Development and Validation of Comorbidity Index to Predict In-hospital Mortality Risk for Patients with Steven-Johnson Syndrome
Authors: Li Renxi 
Published: May 2023

AbstractBackgroundStevens-Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN) is a spectrum of severe drug reactions that has a high in-hospital mortality from 5% to 20%. Early risk prediction for in-hospital mortality in SJS/TEN can be informative for clinical management. This study aimed to develop an in-hospital mortality risk calculator for SJS based on patient comorbidities.MethodsPatients who were diagnosed with SJS/TEN were identified in the National Inpatient Sample database between Q4 2015-2020. SJS patients were randomly sampled into two equal experimental and validation groups. The weight for each comorbidity was determined from a multivariable logistic regression to develop into a single SJS Index.ResultsThere were 4519 SJS (mortality rate 5.05%), 873 SJS-TEN (mortality rate 13.06%), and 759 TEN (mortality rate 17.00%) patients identified. The SJS Index had good discrimination power (c-statistic=0.704, 95% CI=0.656-0.753) and was well-calibrated (Brier score=0.049). SJS Index had similar performance in multivariable regression model with all comorbidities (DeLong p-value=0.621) and validation group (DeLong p-value=0.634). The index had significantly better discriminative power than Elixhauser Comorbidity Index (ECI) (DeLong p-value=0.001). Applying the SJS Index to SJS-TEN patients showed comparable discriminative powers (DeLong test p-value=0.284). In TEN patients, SJS Index remained good calibration (Brier score=0.062) but discriminative power decreased (DeLong p-value=0.005). After adjusting for age, race, and ethnicity, SJS Index had improved performance in all groups.ConclusionsThe SJS Index can effectively discriminate and predict in-hospital mortality in SJS and was externally validated in NIS. SJS/TEN often has emergent presentation and immediate intervention is required, this risk score can give an initial assessment of the mortality based on medical records alone and thus offer a quick insight for clinicians for management. In addition, this study demonstrated the possibility of the SJS Index being used as one composite metric to develop a more comprehensive risk-calculator score.
Availability and accessibility to latrine and handwashing facilities during working hours among “boda-boda” drivers in Mwanza city
Authors: Basinda Namanya , Chilipweli Peter , Kisaka Emmanuel B. , Shoo Maxwell P. , Tupa Theckla , Vingson Marystella Z , Laizer Julieth , Konje Eveline , Kapesa Anthony , Morona Dominica 
Published: May 2023

ABSTRACTBackgroundWater access and sanitation are two of the most fundamental critical urban services upon which people in cities depend. Lack of these services may pose a major threat of disease especially in low- and middle-income countries. Mwanza City in Tanzania faces serious challenges regarding to sanitation services to the public and occupational on mobile bases such as Boda-boda. Boda-boda drivers are mobile and often come up into contact with people which might lead to the spread of diseases through the fecal-oral route. Thus, the aim of this study was to determine the level of accessibility and the barriers to sanitation and hygiene among the boda-boda drivers in Mwanza city.MethodsThis was a community based cross sectional study carried out in Nyamagana District that involved a randomly selected 196 participants. Data were collected using a pretested questionnaire. Data was be analyzed for frequency distribution, proportion and percentages for quantitative variables, mean ± SD.ResultsAlmost a quarter(27.05%) had difficulties towards accessing latrines when they needed to use one. This was almost in parallel with 27.04% of the participants claiming latrines are not convenient in the community. Almost thirty percent (32.14%) were not satisfied with the availability of clean latrines, 67.35% claimed there are community laws or rules in place that make it more likely them to use a latrine every time they need to defecate or urinate. 84.69% showed great awareness towards realizing the importance of using latrines instead of the opposite.ConclusionOur results indicate that some of the Boda-boda drivers claims that latrines are not accessible and convenient but also habit has been a limiting factor which makes them to practice open defecation. Thus, there is inevitable need for the authority to build more clean latrines and run them as a business oriented low-cost facility i.e., pay per use. Together with making strict laws that enforces the use of latrine among the boda-boda drivers should be a priority.
A phenome-wide association study of methylated GC-rich repeats identifies a GCC repeat expansion inAFF3as a significant cause of intellectual disability
Authors: Jadhav Bharati , Garg Paras , van Vugt Joke J. F. A. , Ibanez Kristina , Gagliardi Delia , Lee William , Shadrina Mariya , Mokveld Tom , Dolzhenko Egor , Martin-Trujillo Alejandro , Gies Scott L. , Rocca Clarissa , Barbosa Mafalda , Jain Miten , Lahiri Nayana , Lachlan Katherine , Houlden Henry , Paten Benedict ,   Genomics England Research Consortium,   Project MinE ALS Sequencing Consortium, Veldink Jan , Tucci Arianna , Sharp Andrew J. 
Published: May 2023

AbstractGC-rich tandem repeat expansions (TREs) are often associated with DNA methylation, gene silencing and folate-sensitive fragile sites and underlie several congenital and late-onset disorders. Through a combination of DNA methylation profiling and tandem repeat genotyping, we identified 24 methylated TREs and investigated their effects on human traits using PheWAS in 168,641 individuals from the UK Biobank, identifying 156 significant TRE:trait associations involving 17 different TREs. Of these, a GCC expansion in the promoter ofAFF3was linked with a 2.4-fold reduced probability of completing secondary education, an effect size comparable to several recurrent pathogenic microdeletions. In a cohort of 6,371 probands with neurodevelopmental problems of suspected genetic etiology, we observed a significant enrichment ofAFF3expansions compared to controls. With a population prevalence that is at least 5-fold higher than the TRE that causes fragile X syndrome,AFF3expansions represent a significant cause of neurodevelopmental delay.
Antenatal care attendance, intermittent preventive treatment in pregnancy and knowledge on malaria: A cross sectional study in a government and a private district Hospitals
Authors: Ahiabor Charity , Courtin David , Anyan William , Mama Atikatou , Frempong Naa Adjeley , Kusi Kwadwo A. , Ofori Michael F. , Adu Bright , Lawson Bernard W. , Anang Abraham K. , Ndam Nicaise T. 
Published: May 2023

AbstractGhana has made significant strides in maternal healthcare under the National Health Insurance Scheme, but more effort is required to achieve the Sustainable Development Goal 3.1 target of <70 deaths/100,000 live births from the current 308 deaths/100,000. This study sought to investigate knowledge about ANC, ANC attendance, knowledge about malaria and IPTp among pregnant women, visiting a government Hospital in Mafi-Adidome (a rural community) and a private Hospital in Battor-Dugame (a rural-urban community) in the Volta region (a high malaria endemic area in Ghana).A total of 1295 consenting pregnant women participated in the study. Information on sociodemographic characteristics, knowledge about ANC, IPTp and knowledge about malaria were collected by questionnaire. Chi-square tests were used to compare proportions of variables across the two study sites.Higher proportion (70.8%) of participants accessing Battor Catholic Hospital showed adequate knowledge about ANC than 38.1% in Adidome Government Hospital (X2(7) =105.11; p<0.001). Also, higher numbers (46.6%) in Battor Catholic Hospital showed adequate knowledge on the timing for IPTp administration than 21.1% in Adidome Government Hospital (X2(2) =83.37; p<0.001). Although knowledge about malaria was generally low (0–33.3%) at both health centres, high proportions of participants (>80%) possess and use mosquito bed nets for malaria prevention. A lower proportion (46.6%) of participants in Battor Catholic Hospital made the WHO recommended 4-7 visits compared to 50.2% participants in Adidome Government Hospital. Age, marital status, employment and education influenced utilization of antenatal and delivery services. More sensitization on the importance of ANC and hospital delivery is needed in the study areas.
Perceptions about male circumcision among HIV vaccine efficacy trial participants in Soweto, South Africa: a qualitative study
Authors: Sibiya Mbalenhle , Laher Fatima , Mulaudzi Mamakiri , Makhale Lerato M. , Salami Taibat , Hornschuh Stefanie , Tieu Hong-Van , Dietrich Janan J. 
Published: May 2023

AbstractMale circumcision has both health benefits and significance to some cultures. We sought to understand perceptions about male circumcision as part of the HIV prevention toolkit among participants enrolled in a preventive HIV vaccine efficacy trial in South Africa. We conducted a qualitative study with 28 people aged 18-35 years old who self-reported that they were not living with HIV, provided informed consent, and who were participating in the HVTN 702 vaccine efficacy trial in Soweto. Using a semi-structured guide, we facilitated four focus group discussions (FGDs) stratified by age, gender, and sexual orientation. FGDs were audio-recorded, transcribed verbatim, translated into English, and thematically analysed. Four main themes emerged. (1) Everyone had accurate knowledge about what male circumcision is, and some participants stated that it partially reduces acquisition of HIV and sexually transmitted infections. (2) There was an emerging distrust of cultural circumcision because of perceived lack of transparency and adverse events. (3) There was a perception that circumcision boosted masculinity. (4) The choice to circumcise was influenced by parents, family, and female partners. In conclusion, the study found that young South African HIV vaccine trial participants accurately understand the HIV prevention benefits of male circumcision, but uptake decisions are embedded within a context that is informed by culture, sexuality and masculinity norms and values.
Defining and emulating target trials of the effects of postexposure vaccination using observational data
Authors: Boyer Christopher , Lipsitch Marc 
Published: May 2023

AbstractPostexposure vaccination has the potential to prevent or modify the course of clinical disease among those exposed to a pathogen. However, due to logistical constraints, postexposure vaccine trials have been difficult to implement in practice. In place of trials, investigators have used observational data to estimate the effectiveness or optimal timing window for postexposure vaccines, but the relationship between these analyses and those that would be conducted in a trial is often unclear. Here, we define several possible target trials for postexposure vaccination and show how, under certain conditions, they can be emulated using observational data. We emphasize the importance of the incubation period and the timing of vaccination in trial design and emulation. As an example, we specify a protocol for postexposure vaccination against mpox and provide a step-by-step description of how to emulate it using data from a healthcare database or contact tracing program. We further illustrate some of the benefits of the target trial approach through simulation.
COVID-19 risk variant associations with chromatin remodelling, DNA maintenance and surfactant genes are infection dependent in the lung
Authors: Jaros Rachel K. , Golovina Evgeniia , O’Sullivan Justin M. 
Published: May 2023

AbstractDuring viral infection the structure of host chromatin is modified. It is generally assumed that these chromatin modifications will affect variant-gene mapping, and therefore gene expression. What is not clear is how limitations imposed by host germline risk affect the expression changes that occur with infection induced chromatin remodelling. Critically, this lack of information extends to how germline variants associated with severe SARS-CoV-2 impact on tissue-specific gene expression changes in response to infection-induced chromatin conformation changes. Here we combined temporal chromatin conformation data from SARS-CoV-2 stimulated cells with a lung spatial-eQTL gene expression analysis to contextualise the functional effects and contributions of germline risk on the severe phenotypes observed in SARS-CoV-2. We identify changes in lung-specific SARS-CoV-2 risk variant-gene mapping across the infection time course. Our results provide evidence for infection-induced chromatin remodelling that impacts the regulation of genes associated with the severity of SARS-CoV-2 infection. The gene targets we identified are functionally involved in host chromatin modifications and maintenance and the expression of these genes is amplified by SARS-CoV-2-induced epigenetic remodelling. The effect of this remodelling includes transcriptional changes to gene targets such asSMARCA4, NCOR1, DNMT1, DNMT3a, DAXX, andPIAS4, all critical components of epigenetic control mechanisms and SARS-CoV-2 antiviral activity, along with several genes involved in surfactant metabolism. We show how severe-phenotype-associated eQTLs form and break in an infection time-course-dependent manner that mimics positive feedback loops connecting germline variation with the process of viral infection and replication. Our results provide a novel bridge between existing COVID-19 epigenetic research and demonstrate the critical role of epigenomics in understanding SARS-CoV-2-risk-associated gene regulation in the lung.
Single-cell RNA analysis reveals the cell atlas of human intracranial aneurysm and rupture-related inflammation features
Authors: Ji Hang , Li Yue , Sun Haogeng , Chen Ruiqi , Zhou Ran , Xiao Anqi , Yang Yongbo , Wang Rong , You Chao , Liu Yi 
Published: May 2023

AbstractBackgroundIntracranial aneurysms (IA) is a common condition and may ultimately result in life-threatening hemorrhagic strokes. A precise understanding of the cellular and gene expression perturbations in human IA tissue may enlighten additional therapeutics for unruptured IA.MethodsA total of 21,332 qualified cells were obtained from four cell-sparse ruptured and unruptured human IA tissues. Detailed cell atlas and dynamics, gene expression perturbations, and inflammation features were thoroughly investigated using multiple machine learning-based algorithms.ResultsEndothelial cells, smooth muscle cells (SMCs), fibroblasts and, for the first time, pericytes have been identified in human IA tissue. A significant proportion of immune cells are also identified, with the number of monocyte/macrophages and neutrophils being notably higher in ruptured IA. By leveraging external datasets, macrophages characterized by transcriptional activation of NF-κB and HIVEP2 is most strongly associated with IA rupture. Interestingly, the recruitment and activation of macrophages and their functional characteristics in terms of TNFα and chemokine production remain consistent between unruptured and ruptured IA.ConclusionsThis study provides insights into the pathophysiology and molecular underpinnings of the IA wall and may motivate novel therapeutic options for unruptured IA.
Neuronal damage and inflammatory biomarkers are associated with the affective and chronic fatigue-like symptoms due to end-stage renal disease
Authors: Al-Hakeim Hussein Kadhem , Al-Raheem Twaij Basim Abd , Al-Naqeeb Tabarek Hadi , Moustafa Shatha Rouf , Maes Michael 
Published: May 2023

AbstractBackgroundMany biochemical, immunological, and neuropsychiatric changes are associated with end-stage renal disease (ESRD). Neuronal damage biomarkers such as glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), S100 calcium-binding protein B (S100B), ionized calcium-binding adaptor molecule-1 (IBA1), and myelin basic protein (MBP) are among the less-studied biomarkers of ESRD.AimWe examined the associations between these neuro-axis biomarkers, inflammatory biomarkers, e.g., C-reactive protein (CRP), interleukin (IL-6), IL-10, and zinc, copper, and neuropsychiatric symptoms due to ERSD.MethodsELISA techniques were used to measure serum levels of neuronal damage biomarkers in 70 ESRD patients, and 46 healthy controls.ResultsESRD patients have higher scores of depression, anxiety, fatigue, and physiosomatic symptoms than healthy controls. Aberrations in kidney function tests and the number of dialysis interventions are associated with the severity of depression, anxiety, fibro-fatigue and physiosomatic symptoms, peripheral inflammation, nestin, and NFL. Serum levels of neuronal damage biomarkers (NFL, MBP, and nestin), CRP, and interleukin (IL)-10 are elevated, and serum zinc is decreased in ESRD patients as compared with controls. The neuronal damage biomarkers NFL, nestin, S100B and MBP are associated with the severity of one or more neuropsychiatric symptom domains. Around 50% of the variance in the neuropsychiatric symptoms is explained by NFL, nestin, S00B, copper, and an inflammatory index.ConclusionsThe severity of renal dysfunction and/or the number of dialysis interventions may induce peripheral inflammation and, consequently, neurotoxicity to intermediate filament proteins, astrocytes, and the blood-brain barrier, leading to the neuropsychiatric symptoms of ESRD.
A time-resolved meta-analysis of consensus gene expression profiles during human T-cell activation
Authors: Rade Michael , Böhlen Sebastian , Neuhaus Vanessa , Löffler Dennis , Blumert Conny , Köhl Ulrike , Dehmel Susann , Sewald Katherina , Reiche Kristin 
Published: May 2023

BackgroundThe coordinated transcriptional regulation of activated T-cells is based on the complex dynamic behavior of signaling networks. Given an external stimulus, T-cell gene expression is characterized by impulse and sustained patterns over the course. Here, we analyzed the temporal pattern of activation across different T-cell populations to develop consensus gene signatures for T-cell activation.MethodsWe applied a meta-analysis of anti-CD3/CD28 induced CD4+ T-cell activation kinetics of publicly available transcriptomewide time series using a random effects model. We used non-negative matrix factorization, an unsupervised deconvolution method, to infer changes in biological patterns over time. For verification and to further map a wider variety of the T-cell landscape, we performed a time series of transcriptome-wide RNA sequencing on activated blood T-cells. Lastly, we matched the identified consensus biomarker signatures to single-cell RNA sequencing (scRNA-Seq) data of autologous anti-CD19 chimeric antigen receptor (CAR) T-cells from 24 patients with large B cell lymphoma (LBCL) to characterize activation status of the cell product before infusion.ResultsWe identified time-resolved gene expression profiles comprising 521 genes of up to 10 disjunct time points during activation and different polarization conditions. The gene signatures include central transcriptional regulators of T-cell activation, representing successive waves as well as sustained patterns of induction. They cover early, intermediate, and late response expression rates across multiple T-cell populations, thus defining consensus biomarker signatures for T-cell activation. Intermediate and late response activation signatures in CAR T-cell infusion products were correlated to immune effector cell-associated neurotoxicity syndrome.ConclusionIn conclusion, we describe temporally resolved gene expression patterns across T-cell populations. These biomarker signatures are a valuable source for e.g., monitoring transcriptional changes during T-cell activation with a reasonable number of genes, annotating T-cell states in single-cell transcriptome studies or assessing dysregulated functions of human T-cell immunity.