bluuebunny/crossref_metadata_2025_split huggingface dataset:
The magnitude and cross reactivity of SARS-CoV-2 specific antibody responses in vaccinated and unvaccinated Sri Lankan children and association with nutrition status
Authors: Jeewandara Chandima , Karunananda Maneshka Vindesh , Fernando Suranga , Danasekara Saubhagya , Jayakody Gamini , Arulkumaran S. , Samaraweera N.Y. , Kumarawansha Sarathchandra , Sivaganesh Subramaniyam , Amarasinghe P. Geethika , Jayasinghe Chintha , Wijesekara Dilini , Marasinghe Manonath Bandara , Mambulage Udari , Wijayatilake Helanka , Senevirathne Kasun , Bandara A.D.P , Gallage C.P. , Colambage N.R. , Udayasiri A.A. Thilak , Lokumarambage Tharaka , Upasena Y. , Weerasooriya W.P.K.P. ,   seroprevalence study group, Tan Tiong Kit , Townsend Alain , Ogg Graham S. , Malavige Gathsaurie Neelika ,   Study groups, Perera Lahiru , Pushpakumara Pradeep , Gomes Laksiri , Jayamali Jeewantha , Aberathna Inoka Sepali , Nimasha Thashmi , Dissanayake Madushika , Ramu Shyrar , Peranantharajah Deneshan , Colambage Hashini , Wickramanayake Rivindu , Chathurangika Harshani , Bary Farha , Yatiwelle Sathsara , Harvie Michael , Deheragoda Maheli , Jayadas Tibutius , Ishara Shashini , Ariyaratne Dinuka , Dayarathna Shashika , Wijekulasuriya Ruwanthi , Ranathunga Chathura 
Published: December 2023

AbstractBackgroundWe investigated the seropositivity rates of Sri Lankan children in a large island wide serosurvey, to determine the magnitude and breadth of antibody responses to SARS-CoV-2 variants and the association with the vaccination and nutritional status to understand the likely impact of newer variants in Sri Lanka.MethodsUsing the WHO UNITY protocol, we recruited 5207 children, aged 10 to 20 years, representative of the 9 provinces of Sri Lanka, and assessed seropositive rates, ACE2 blocking antibodies and antibodies to BA.2.75 and XBB.1.5, in vaccinated and unvaccinated children. Anthropometric measurements were taken to determine the association between nutrition status and antibody levels.Results3111/3119 (99.7%) vaccinated and 2008/2088 (96.2%) of unvaccinated children, were seropositive for SARS-CoV-2. 2984/3111 (95.9%) of vaccinated children had ACE2 blocking antibodies above the cut-off threshold, compared to 1346/2008 (67.0%) of unvaccinated children. 27.2 % unvaccinated children had positive antibody responses to BA.2.75 and 30.7% to XBB.1.5, while 64.3% of vaccinated had a positive response to BA.2.75 and 43.1% to XBB.1.5. Vaccinated children had significantly higher titres of total antibodies, ACE2 blocking antibodies and antibodies to XBB.1.5 and BA.2.75 than unvaccinated children. However, the vaccinated had significantly higher responses to BA.2.75 (p<0.0001), than XBB.1.5. Unvaccinated children, with <3rd BMI centile had significantly lower ACE2 blocking antibodies than other groups.DiscussionThe high seropositivity rates and antibody titres to SARS-CoV-2 variants in unvaccinated children, suggests that they are likely to have been infected more than once with SARS-CoV-2. The implications of lower antibody levels in undernourished children should be further investigated.
Clinical Uncertainty In Large Vessel Occlusion Ischemic Stroke (CULVO): An Intrarater And Interrater Agreement Study
Authors: Diestro Jose Danilo B. , Fahed Robert , Omar Abdelsimar T. , Hawkes Christine , Hendriks Eef J. , Enriquez Clare Angeli , Eesa Muneer , Stotts Grant , Lee Hubert , Nagendra Shashank , Poppe Alexandre , Ducroux Célina , Lim Timothy , Narvacan Karl , Rizutto Michael , Alfalahi Afra , Nishi Hidehisa , Sarma Pragyan , Itsekzon-Hayosh Vladislav Ze’ev , Ignacio Katrina , Boisseau William , Pimenta Ribeiro Pontes Almeida Eduardo , Benomar Anass , Almekhlafi Mohammed A. , Milot Genvieve , Deshmukh Aviraj Satish , Kishore Kislay , Tampieri Donatella , Wang Jeffrey Z. , Srivastava Abhilekh , Roy Daniel , Carpani Federico , Kashani Nima , Candale-Radu Claudia , Singh Nishita , Bres Bullrich Maria , Sarmiento Robert , Muir Ryan , Parra-Farinas Carmen , Reiter Stephanie D. , Deschaintre Yan , Singh Ravinder-Jeet , Bodani Vivel , Katsanos Aristeidis , Agid Ronit , Zafar Atif , Mendes Pereira Vitor , Spears Julian , Marotta Thomas R. , Djiadeu Pascal , Sharma Sunjay , Farrokhyar Forough 
Published: December 2023

AbstractBackgroundLimited research exists regarding the impact of neuroimaging modality on endovascular thrombectomy (EVT) decisions for late window large vessel occlusion (LVO) stroke cases.PurposeThis study assesses whether perfusion CT imaging: 1) alters the proportion of recommendations for EVT, and 2) enhances the reliability of EVT decision-making compared to non-contrast CT and CT angiography.Materials and MethodsWe conducted an online survey using 30 patients drawn from an institutional database of 3144 acute stroke cranial CT scans. These cases were presented to 29 stroke or neurointerventional physicians from Canada across two sessions. Physicians evaluated each patient both with and without perfusion imaging and gave EVT recommendations. We used non-overlapping 95% confidence intervals and difference in agreement classification as criteria to suggest a difference between the Gwet AC1 statistics (κG). Our outcomes were: 1) the proportion of EVT recommendations, and 2) interrater and intrarater agreement, with or without perfusion imaging.ResultsIn the first round, 29 raters completed the assessment, with 28 finishing the second round. The percentage of EVT recommendations differed by 1.1% with or without perfusion imaging. However, individual decisions changed in 21.4% of cases, with 11.3% against EVT and 10.1% in favor. Interrater agreement (κG) among the 29 raters was similar between non-perfusion CT neuroimaging and perfusion CT neuroimaging (κG = 0.487; 95% CI 0.327, 0.647 and κG = 0.552; 95% CI 0.430, 0.675). The 95% CIs overlapped with moderate agreement in both. Intrarater agreement exhibited overlapping 95% CIs for all 28 raters. κG was either substantial or excellent (0.81-1) for 71.4% (20/28) of raters in both groups.ConclusionThe difference in EVT recommendations is minimal with either neuroimaing protocol. Regarding agreement we found that use of automated CT perfusion images does not significantly impact the reliability of EVT decisions for late window LVO patients.
Mathematical assessment of the role of intervention programs for malaria control
Authors: Korsah Maame Akua , Johnston Stuart T. , Tiedje Kathryn E. , Day Karen P. , Flegg Jennifer A. , Walker Camelia R. 
Published: December 2023

AbstractMalaria remains a global health problem despite the many attempts to control and eradicate it. There is an urgent need to understand the current transmission dynamics of malaria and to determine the interventions necessary to control malaria. In this paper, we seek to develop a fit-for-purpose mathematical model to assess the interventions needed to control malaria in an endemic setting. To achieve this, we formulate a malaria transmission model to analyse the spread of malaria in the presence of interventions. A sensitivity analysis of the model is performed to determine the relative impact of the model parameters on disease transmission. We explore how existing variations in the recruitment and management of intervention strategies affect malaria transmission. Results obtained from the study imply that the discontinuation of existing interventions has a significant effect on malaria prevalence. Thus, the maintenance of interventions is imperative for malaria elimination and eradication. In a scenario study aimed at assessing the impact of long-lasting insecticidal nets (LLINs), indoor residual spraying (IRS), and localized individual measures, our findings indicate that increased LLINs utilization and extended IRS coverage (with longer-lasting insecticides) cause a more pronounced reduction in symptomatic malaria prevalence compared to a reduced LLINs utilization and shorter IRS coverage. Additionally, our study demonstrates the impact of localized preventive measures in mitigating the spread of malaria when compared to the absence of interventions.
The Status of Indian Cancer Record Keeping and Study of Mesothelioma Cases to Ascertain Asbestos Exposure in India
Authors: Singh Raja , Frank Arthur L. 
Published: December 2023

AbstractSettingAsbestos exposure causes mesothelioma which is classified as a malignancy and recorded by cancer registries which currently covers only16% of the population in India. The accurate number of mesothelioma cases may not be available for decision making as India still uses asbestos and it is important to ascertain its health impact, especially mesothelioma.ObjectiveThis study aims to find the cases of mesothelioma from 83 hospitals across India from 2012 onwards till 2022-2023. The study also compares the national registry reported cases to the ones found in this study.DesignThe study uses the Right to Information Act 2005 to find data from various hospitals and reporting the same. The data from the voluntary national registry was also collected. This was compiled and compared.ResultsOverall, the study shows 2213 cases of mesothelioma 2012 onwards in India from 83 hospitals. In the comparison period of 2012-2016, the registry reported cases were 54, while the study shows 1126 cases. Only 21% of hospitals in this study were part of the national registry programme.ConclusionMesothelioma cases in India are more frequent than reported and the current recordkeeping for all cancers does not fully cover the expanse of India and needs to be revamped.
Integrative proteogenomic analyses provide novel interpretations of type 1 diabetes risk loci through circulating proteins
Authors: Lu Tianyuan , Manousaki Despoina , Sun Lei , Paterson Andrew D. 
Published: December 2023

AbstractType 1 diabetes (T1D) requires new preventive measures and interventions. Circulating proteins are promising biomarkers and drug targets. Leveraging genome-wide association studies (GWASs) of T1D (18,942 cases and 501,638 controls) and circulating protein abundances (10,708 individuals), the associations between 1,565 circulating proteins and T1D risk were assessed through Mendelian randomization, followed by multiple sensitivity and colocalization analyses, examinations of horizontal pleiotropy, and replications. Genetically increased circulating abundances of CTSH, IL27RA, SIRPG, and PGM1 were associated with an increased risk of T1D, consistently replicated in other cohorts. Bulk tissue and single-cell gene expression profiles revealed strong enrichment ofCTSH, IL27RA, and SIRPG in immune system-related tissues, andPGM1in muscle and liver tissues. Among immune cells,CTSHwas enriched in B cells and myeloid cells, whileSIRPGwas enriched in T cells and natural killer cells. These proteins warrant exploration as T1D biomarkers or drug targets in relevant tissues.
Effectivity and Safety Profile of Tenapanor, a Sodium-Hydrogen Exchanger Isoform 3 Inhibitor, as an Innovative Treatment for Hyperphosphatemia in Chronic Kidney Disease, a Systematic Review of Clinical Studies
Authors: Suciangto William , Rasyid Haerani , Vicente Anastasya Angelica , Suciangto Winny 
Published: December 2023

AbstractBackgroundChronic kidney disease (CKD) is a major global health problem. Hyperphosphatemia is frequent in CKD and a reason for increased morbidity and mortality as it generates hyperparathyroidism, high fibroblast growth factor 23 (FGF23), and hypocalcemia. Available hyperphosphatemia therapies still have limitations, including risk of metal overload, cardiovascular calcification, and systemic adverse effects (AEs). Tenapanor is a new hyperphosphatemia treatment in CKD with sodium-hydrogen exchanger isoform 3 (NHE3) inhibition mechanism and low systemic AEs.ObjectivesDiscovering the effectivity and safety of tenapanor as hyperphosphatemia management in CKD.MethodLiterature searching is performed by using “pubmed” and “science direct” with “tenapanor”, “chronic kidney disease”, and “hyperphosphatemia” as keywords. The literatures were selected using PRISMA algorithm version 2020. Literature was screened based on Population, Intervention, Comparison, and Outcome (PICO) criteria which are: CKD patients requiring dialysis as population, tenapanor or its combination with dialysis or phosphate binders as intervention, placebo or other phosphate binders without tenapanor as comparison, and serum phosphate, safety profile, and other pleiotropic benefits related to hyperphosphatemia management as the outcome. The included studies then assessed for risk of bias and qualitatively reviewed.OutcomeTenapanor was able to reduce serum phosphate, generally in a dose-dependent manner. Tenapanor also suppressed FGF23 and parathyroid hormone, probably due to decreased serum phosphate. The frequent AEs was transient mild-to-moderate diarrhea in a dose-dependent manner. Tenapanor was generally well-tolerated with low systemic AEs due to its non-calcium, metal-free, and low-absorbed properties.ConclusionTenapanor is an effective and safe option for hyperphosphatemia management in CKD.
Patients with Type 2 Diabetes and aGCKvariant are still at risk for T2D-related secondary complications
Authors: Schiabor Barrett Kelly M. , Telis Natalie , McEwen Lisa M. , Burrows Evanette K. , Judge Daniel P. , Pawloski Pamala A. , Grzymski Joseph J. , Washington Nicole L. , Bolze Alexandre , Cirulli Elizabeth T. 
Published: December 2023

AbstractNatural HbA1c levels inGCK-MODY patients often sit above the diagnostic threshold for type 2 diabetes (T2D). Standard treatments to lower HbA1c levels are ineffective in these individuals, yet in case studies to date,GCK-MODY patients often evade secondary T2D complications. Given these deviations from a more typical T2D disease course, genetic screening ofGCKmay be clinically useful, but population studies are needed to more precisely quantify T2D-related outcomes inGCKvariant carriers. Using a state-of-the-art variant interpretation strategy based on glucose elevations, we genotyped all individuals in two real-world cohorts (n~535,000) forGCKrisk variants and examined rates of T2D and T2D-complications from seven disease categories.We identified 439 individuals withGCKvariants predicted to increase glucose (~1/1200). Aligning with their glucose elevations,GCK-MODY variant carriers were 12x as likely, and all otherGCKrisk carriers 4x as likely, to receive a T2D diagnosis, compared to non-GCKcarriers. Surprisingly,GCKrisk carriers with T2D develop a range of T2D-related complications at rates comparable to non-GCKT2D patients. Although the penetrance for secondary complications is lower than that for glucose elevations,GCKrisk carriers remain at elevated risk of T2D and secondary complications.
Challenges in the case-based surveillance of infectious diseases
Authors: Eales Oliver , McCaw James M. , Shearer Freya M. 
Published: December 2023

AbstractTo effectively inform infectious disease control strategies, accurate knowledge of the pathogen’s transmission dynamics is required. The infection incidence, which describes the number of new infections in a given time interval (e.g., per day or per week), is fundamental to understanding transmission dynamics, and can be used to estimate the time-varying reproduction number and the severity (e.g., the infection fatality ratio) of a disease. The timings of infections are rarely known and so estimates of the infection incidence often rely on measurements of other quantities amenable to surveillance. Case-based surveillance, in which infected individuals are identified by a positive test, is the pre-dominant form of surveillance for many pathogens, and was used extensively during the COVID-19 pandemic. However, there can be many biases present in case-based surveillance indicators due to, for example, test sensitivity and specificity, changing testing behaviours, and the co-circulation of pathogens with similar symptom profiles. Without a full understanding of the process by which surveillance systems generate data, robust estimates of the infection incidence, time-varying reproduction number, and severity based on these data cannot be made. Here we develop a mathematical description of case-based surveillance of infectious diseases. By considering realistic epidemiological parameters and situations, we demonstrate potential biases in common surveillance indicators based on case-based surveillance data. The description is highly general and could be applied to a diverse set of pathogens and situations. The mathematical description could be used to inform inference of infection incidence using existing data, with a full understanding of where bias and uncertainty will be present in any such analysis. Future surveillance strategies could be designed to minimise these sources of bias and uncertainty, providing more accurate estimates of a pathogen’s transmission dynamics and, ultimately, more targeted application of public health measures.
Epigenetic scores indicate differences in the proteome of preterm infants
Authors: Mckinnon Katie , Conole Eleanor L.S. , Vaher Kadi , Hillary Robert F. , Gadd Danni A. , Binkowska Justyna , Sullivan Gemma , Stevenson Anna J. , Corrigan Amy , Murphy Lee , Whalley Heather C. , Richardson Hilary , Marioni Riccardo E. , Cox Simon R. , Boardman James P. 
Published: December 2023

AbstractBackgroundEpigenetic scores (EpiScores), reflecting DNA methylation (DNAm)-based surrogates for complex traits, have been developed for multiple circulating proteins. EpiScores for pro-inflammatory proteins, such as C-reactive protein (DNAm CRP), are associated with brain health and cognition in adults and with inflammatory comorbidities of preterm birth in neonates. Social disadvantage can become embedded in child development through inflammation, and deprivation is over-represented in preterm infants. We tested the hypotheses that preterm birth and socioeconomic status (SES) are associated with alterations in a set of EpiScores enriched for inflammation-associated proteins.Results104 protein EpiScores were derived from saliva samples of 332 neonates born at gestational age (GA) 22.14 to 42.14 weeks. Saliva sampling was between 36.57 and 47.14 weeks. Forty-three (41%) EpiScores were associated with low GA at birth (standardised estimates |0.14 to 0.88|, Bonferroni-adjustedp-value <8.3×10−3). These included EpiScores for chemokines, growth factors, proteins involved in neurogenesis and vascular development, cell membrane proteins and receptors, and other immune proteins. Three EpiScores were associated with SES, or the interaction between birth GA and SES: afamin, intercellular adhesion molecule 5 and hepatocyte growth factor-like protein (standardised estimates |0.06 to 0.13|, Bonferroni-adjustedp-value <8.3×10−3). In a preterm sub-group (n=217, median [range] GA 29.29 weeks [22.14 to 33.0 weeks]), SES-EpiScore associations did not remain statistically significant after adjustment for sepsis, bronchopulmonary dysplasia, necrotising enterocolitis, and histological chorioamnionitis.ConclusionsLow birth GA is substantially associated with a set of EpiScores. The set was enriched for inflammatory proteins, providing new insights into immune dysregulation in preterm infants. SES had fewer associations with EpiScores; these tended to have small effect sizes and were not statistically significant after adjusting for inflammatory comorbidities. This suggests that inflammation is unlikely to be the primary axis through which SES becomes embedded in the development of preterm infants in the neonatal period.
Future HIV epidemic trajectories in South Africa and long-term consequences of reductions in general HIV testing: a mathematical modelling study
Authors: Rautenbach Stefan P , Whittles Lilith K , Meyer-Rath Gesine , Jamieson Lise , Chidarikire Thato , Johnson Leigh F , Imai-Eaton Jeffrey W 
Published: December 2023

AbstractBackgroundFollowing successful intensive interventions to rapidly increase HIV awareness, antiretroviral therapy (ART) coverage, and viral suppression, HIV programmes in eastern and southern Africa must now consider whether to scale-back certain programmes, such as widespread general population HIV testing services (general HTS), without risking a resurging epidemic or substantially increasing long-term ART need through slowed incidence declines.MethodsWe used a mathematical model (Thembisa) to project the South African HIV epidemic to 2100 under current epidemiologic and programmatic conditions. We assessed the epidemiological impact and cost of implementing general HTS reductions at different times between 2025 and 2050, while maintaining antenatal, symptom-based, and risk-based testing modalities and other HIV prevention. We considered how future uncertainty interacted with testing reductions by assuming positive or negative changes in ART interruption rates and condom usage over 2025–2035.FindingsUnder the status quo scenario, HIV incidence (15-49 years) steadily declined from 4.95/1000 (95% CI: 4.40–5.34) in 2025 to 0.14/1000 (0.05–0.31) in 2100, attaining <1/1000 in 2055 (2051–2060). When general HTS was scaled-back in 2025, incidence continued declining, but time to <1/1000 was delayed by 5, 13, and 35 years for a 25%, 50%, or 75% reduction in general HTS, and not attained by 2100 with full cessation. Reducing general HTS by 25% to 100% from 2025 resulted in 10% (8–12%) to 65% (53–77%) more new HIV infections and 7% (5–8%) to 46% (38–53%) more AIDS-related deaths over 50 years. Delaying general HTS reductions for 5 to 25 years mitigated some impacts. HIV testing accounted for only 5% of total programmatic costs at baseline. Reducing testing modestly reduced short-term total costs, but increased long-term costs. Changes in ART interruption rates and condom usage levels affected incidence decline rates and general HTS levels required to control transmission but did not cause rapid resurgent incidence.InterpretationScaling-back general HTS did not result in resurging HIV infections, but it delayed attainment of incidence reduction targets and increased long-term expected infections, deaths, ART provision, and costs. HIV programmes face decisions balancing near-term health system resource savings by reducing intensive HIV programmes with epidemic control objectives over several decades.FundingBMGF, Wellcome, UKRI
Molecular heterogeneity of quiescent melanocyte stem cells revealed by single-cell RNA-sequencing
Authors: Palmer Joseph W. , Kumar Nilesh , An Luye , White Andrew C. , Mukhtar M. Shahid , Harris Melissa L. 
Published: December 2023

AbstractMelanocyte stem cells (McSCs) of the hair follicle are a rare cell population within the skin and are notably underrepresented in whole-skin, single-cell RNA sequencing (scRNA-seq) datasets. Using a cell enrichment strategy to isolate KIT+/CD45-cells from the telogen skin of adult female C57BL/6J mice, we evaluated the transcriptional landscape of quiescent McSCs (qMcSCs) at high resolution. Through this evaluation, we confirmed existing molecular signatures for qMcCS subpopulations (e.g.,Kit+, Cd34+/-,Plp1+, Cd274+/-, Thy1+, Cdh3+/-) and identified novel qMcSC subpopulations, including two that differentially regulate their immune privilege status. Within qMcSC subpopulations, we also predicted melanocyte differentiation potential, neural crest potential, and quiescence depth. Taken together, the results demonstrate that the qMcSC population is heterogenous and future studies focused on investigating changes in qMcSCs should consider changes in subpopulation composition.SignificanceSingle cell transcriptomics has revolutionized our ability to interrogate the dynamic nature of tissues. Here we provide a high-resolution map of the melanocyte stem cell population during quiescence. This map provides one of few examples highlighting broad heterogeneity in stem cells during the quiescent cell state. The map also unifies previous observations using other cell, molecular and functional analyses to define the unique features of the quiescent melanocyte stem cell population. This data provides a valuable resource to individuals interested in further evaluating aspects of cellular quiescence in stem cells broadly or melanocyte stem cells specifically.