bluuebunny/crossref_metadata_2025_split huggingface dataset:
Household transmission of SARS-CoV-2 from adult index cases living with and without HIV in South Africa, 2020-2021: a case-ascertained, prospective observational household transmission study
Authors: Kleynhans Jackie , Walaza Sibongile , Martinson Neil A. , Neti Mzimasi , Gottberg Anne von , Bhiman Jinal N. , Toi Dylan , Amoako Daniel G. , Buys Amelia , Ndlangisa Kedibone , Wolter Nicole , Genade Leisha , Maloma Lucia , Chewparsad Juanita , Lebina Limakatso , de Gouveia Linda , Kotane Retshidisitswe , Tempia Stefano , Cohen Cheryl 
Published: April 2022

AbstractBackgroundIn South Africa 19% of the adult population aged 15-49 years are living with HIV (LWH). Few data on the influence of HIV on SARS-CoV-2 household transmission are available.MethodsWe performed a case-ascertained, prospective household transmission study of symptomatic index SARS-CoV-2 cases LWH and HIV-uninfected adults and their contacts in South Africa. Households were followed up thrice weekly for 6 weeks to collect nasal swabs for SARS-CoV-2 testing. We estimated household cumulative infection risk (HCIR), duration of SARS-CoV-2 positivity (at cycle threshold value<30 as proxy for high viral load), and assessed associated factors.ResultsWe recruited 131 index cases and 457 household contacts. HCIR was 59% (220/373); not differing by index HIV status (60% [50/83] in cases LWH vs 58% [173/293] in HIV-uninfected cases, OR 1.0, 95%CI 0.4-2.3). HCIR increased with index case age (35-59 years: aOR 3.4 95%CI 1.5-7.8 and ≥60 years: aOR 3.1, 95%CI 1.0-10.1) compared to 18-34 years, and contacts’ age, 13-17 years (aOR 7.1, 95%CI 1.5-33.9) and 18-34 years (aOR 4.4, 95%CI 1.0-18.4) compared to <5 years. Mean positivity duration at high viral load was 7 days (range 2-28), with longer positivity in cases LWH (aHR 0.3, 95%CI 0.1-0.7).ConclusionsHIV-infection was not associated with higher HCIR, but cases LWH had longer positivity duration at high viral load. Adults aged >35 years were more likely to transmit, and individuals aged 13-34 to acquire SARS-CoV-2 in the household. Health services must maintain HIV testing with initiation of antiretroviral therapy for those HIV-infected.SummaryIn this case-ascertained, prospective household transmission study, household cumulative infection risk was 59% from symptomatic SARS-CoV-2 index cases, not differing based on index HIV status. Index cases living with HIV were positive for SARS-CoV-2 for longer at higher viral loads.
Data and care integration for post-acute intensive care program of stroke patients: effectiveness assessment using a disease-matched comparator cohort
Authors: Vela Emili , Plaza Aina , Carot-Sans Gerard , Contel Joan C. , Salvat-Plana Mercè , Fabà Marta , Giralt Andrea , Ribera Aida , Santaeugènia Sebastià , Piera-Jiménez Jordi ,   the REDOM group
Published: April 2022

AbstractPurposeTo assess the effectiveness of an integrated care program for post-acute care of stroke patients, the return home program (RHP program), deployed in Barcelona (North-East Spain) between 2016 and 2017 in a context of health and social care information systems integration.DesignThe health outcomes and resource use of the RHP program participants were compared with a population-based matched control group built from central healthcare records of routine care data.FindingsThe study included 92 stroke patients attended within the RHP program and their matched-controls. Patients in the intervention group received domiciliary care service, home rehabilitation, and telecare significantly earlier than the matched-controls. Within the first two years after the stroke episode, recipients of the RHP program were less frequently institutionalized in a long-term care facility (5% vs. 15%). The use of primary care services, non-emergency transport, and telecare services were more frequent in the RHP group.OriginalityOur analysis shows that an integrated care program can effectively promote and accelerate delivery of key domiciliary care services, reducing institutionalization of stroke patients in the mid-term. The integration of health and social care information allows not only a better coordination among professionals but also to monitor health and resource use outcomes of care delivery
A protocol for a multicentre observational study across an integrated care system to understand the effect of living with frailty on access to video consultations
Authors: Shorthose Matthew , Watts Nick , Carter Ben , Evans Bekah , Jeynes Samuel , Wensley Sue , Braude Philip 
Published: April 2022

AbstractRisks for digital exclusion include older age, disability, and deprivation. No literature exists examining frailty as an additional possible risk factor. Many studies have shown frailty to be a more accurate predictor of adverse outcome in healthcare than age alone. Understanding risk factors for digital exclusion may help healthcare services appropriately tailor interventions. The Healthier Together integrated care system (HTICS) in Bristol is developing video consultations for clinics. The aim of this prospective observational cross-sectional study is to identify whether living with frailty is a risk factor of digital exclusion from video consultation. Data will be collected using a structured survey including patients from three sites across the Heal secondary care services at North Bristol Trust, and then two subsequent sites will be included across HTICS. Data will be collected on known risk factors for digital exclusion, frailty using the Clinical Frailty Scale, and will cover four domains for digital exclusion as defined by NHS Digital: access, skill, motivation, and confidence. Data will be presented with descriptive statistics. The association between frailty and outcomes will be analysed with a multivariable logistic regression.Key Study ContactsStudy SummaryFunding and Support in KindRole of Study Sponsor and FunderThe pilot at North Bristol Trust (NBT) is overseen by Neuromusculoskeletal (NMSK) Division governance. NBT NMSK Division takes responsibility for ensuring that the design of the study meets appropriate standards and that arrangements are in place to ensure appropriate conduct and reporting. Governance oversight for Hospital at Home was registered with NBT NMSK, and for primary care with Horfield Health Centre.Roles and ResponsibilitiesStudy Flow Chart
Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure
Authors: Rasooly Danielle , Peloso Gina M , Pereira Alexandre C , Dashti Hesam , Giambartolomei Claudia , Wheeler Eleanor , Aung Nay , Ferolito Brian R , Pietzner Maik , Farber-Eger Eric H , Wells Quinn Stanton , Kosik Nicole M , Gaziano Liam , Posner Daniel C , Bento A Patrícia , Hui Qin , Liu Chang , Aragam Krishna , Wang Zeyuan , Charest Brian , Huffman Jennifer E , Wilson Peter W.F. , Phillips Lawrence S , Whittaker John , Munroe Patricia B , Petersen Steffen E , Cho Kelly , Leach Andrew R , Magariños María Paula , Gaziano John Michael ,   VA Million Veteran Program, Langenberg Claudia , Sun Yan V , Joseph Jacob , Casas Juan P 
Published: April 2022

AbstractWe conduct a large-scale meta-analysis of heart failure genome-wide association studies (GWAS) consisting of over 90,000 heart failure cases and more than 1 million control individuals of European ancestry to uncover novel genetic determinants for heart failure. Using the GWAS results and blood protein quantitative loci, we perform Mendelian randomization and colocalization analyses on human proteins to provide putative causal evidence for the role of druggable proteins in the genesis of heart failure. We identify 39 genome-wide significant heart failure risk variants, of which 18 are previously unreported. Using a combination of Mendelian randomization proteomics and genetic cis-only colocalization analyses, we identify 10 additional putatively causal genes for heart failure. Findings from GWAS and Mendelian randomization-proteomics identify seven (CAMK2D,PRKD1,PRKD3,MAPK3,TNFSF12,APOC3andNAE1) proteins as potential targets for interventions to be used in primary prevention of heart failure.
Effectiveness and waning of protection with different SARS-CoV-2 primary and booster vaccines during the Delta pandemic wave in 2021 in Hungary (HUN-VE 3 study)
Authors: Vokó Zoltán , Kiss Zoltán , Surján György , Surján Orsolya , Barcza Zsófia , Wittmann István , Molnár Gergő Attila , Nagy Dávid , Müller Veronika , Bogos Krisztina , Nagy Péter , Kenessey István , Wéber András , Polivka Lőrinc , Pálosi Mihály , Szlávik János , Rokszin György , Müller Cecília , Szekanecz Zoltán , Kásler Miklós 
Published: April 2022

AbstractBackgroundIn late 2021, the pandemic wave was dominated by the Delta SARS-CoV-2 variant in Hungary. Booster vaccines were offered starting from August 2021.MethodsThe nationwide HUN-VE 3 study examined the effectiveness and durability of primary immunization and single booster vaccinations on SARS-CoV-2-related infection, hospitalization and mortality during the Delta wave.ResultsThe study population included 8,087,988 individuals aged 18–100 years at the beginning of the pandemic. During the Delta wave, after adjusting for age, sex, calendar day, and chronic diseases, vaccine effectiveness (VE) of primary vaccination against registered SARS-CoV-2 infection was between 11% to 77% and 18% to 79% 14–120 days after primary immunization in the 16–64 and 65–100 years age cohort respectively, while it decreased to close to zero in the younger age group and around 40% or somewhat less in the elderly after 6 months for almost all vaccine types. In the population aged 65–100 years, we found high, 88.1%–92.5% adjusted effectiveness against Covid-19 infection after the Pfizer-BioNTech, and 92.2%–95.6% after the Moderna booster dose, while Sinopharm and Janssen booster doses provided 26.5%–75.3% and 72.9%–100.0% adjusted VE, respectively. Adjusted VE against Covid-19 related hospitalization was high within 14–120 days for Pfizer-BioNTech: 76.6%, Moderna: 83.8%, Sputnik-V: 78.3%, AstraZeneca: 73.8%, while modest for Sinopharm: 45.7% and Janssen: 26.4%. The waning of protection against Covid-19 related hospitalization was modest and booster vaccination with mRNA vaccines or the Janssen vaccine increased adjusted VE up to almost 100%, while the Sinopharm booster dose proved to be less effective. VE against Covid-19 related death after primary immunization was high or moderate: for Pfizer-BioNTech: 81.5%, Moderna: 93.2%, Sputnik-V: 100.0%, AstraZeneca: 84.8%, Sinopharm: 58.6%, Janssen: 53.3%). VE against this outcome also showed moderate decline over time, while booster vaccines restored effectiveness up to almost 100%, except for the Sinopharm booster.ConclusionsThe HUN-VE 3 study demonstrated waning VE with all vaccine types for all examined outcomes during the Delta wave and confirmed the outstanding benefit of booster vaccination with the mRNA or Janssen vaccines. This is the first study to provide comparable effectiveness results for six different booster types during the Delta pandemic wave.
Causal effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation study
Authors: Zhao Jian , Stewart Isobel D , Baird Denis , Mason Dan , Wright John , Zheng Jie , Gaunt Tom R , Evans David M , Freathy Rachel M , Langenberg Claudia , Warrington Nicole M , Lawlor Deborah A , Borges Maria Carolina 
Published: April 2022

AbstractAmino acids are key to protein synthesis, energy metabolism, cell signaling and gene expression; however, the contribution of specific maternal amino acids to fetal growth is unclear. We explored the effect of maternal circulating amino acids on fetal growth, proxied by birthweight, using two-sample Mendelian randomization and summary data from a genome-wide association study (GWAS) of serum amino acids levels (sample 1, n = 86,507) and a maternal GWAS of offspring birthweight, adjusting for fetal genotype effects (sample 2, n = 406,063 with maternal and/or fetal genotype effect estimates). A total of 106 independent single nucleotide polymorphisms (SNPs) robustly associated with 19 amino acids (p < 4.9 × 10−10) were used as genetic instrumental variables. Our results provide evidence that maternal circulating glutamine (59 g offspring birthweight increase per SD increase in maternal amino acid level, 95% CI: 7, 110) and serine (27 g, 95% CI: 9, 46) raise, while leucine (−59 g, 95% CI: -106, -11) and phenylalanine (−25 g, 95% CI: -47, -4) lower offspring birthweight. Our findings strengthen evidence for key roles of maternal circulating amino acids in healthy fetal growth.
In Silico transcriptional analysis of asymptomatic and severe COVID-19 patients reveals the susceptibility of severe patients to other comorbidities and non-viral pathological conditions
Authors: Sen Poonam , Kaur Harpreet 
Published: April 2022

AbstractCOVID-19 is a severe respiratory disease caused by SARS-CoV-2, a novel human coronavirus. The host response to SARS-CoV-2 infection is not clearly understood. Patients infected with SARS-CoV-2 exhibit heterogeneous intensity of symptoms, i.e., asymptomatic, mild, and severe. Moreover, effects on organs also vary from person to person. These heterogeneous responses pose pragmatic hurdles for implementing appropriate therapy and management of COVID-19 patients. Post-COVID complications pose another major challenge in managing the health of these patients. Thus, understanding the impact of disease severity at the molecular level is vital to delineate the precise host response and management. In the current study, we performed a comprehensive transcriptomics analysis of publicly available seven asymptomatic and eight severe COVID-19 patients. Exploratory data analysis using Principal Component Analysis (PCA) showed the distinct clusters of asymptomatic and severe patients. Subsequently, the differential gene expression analysis using DESeq2 identified 1,224 significantly upregulated genes (logFC>= 1.5, p-adjusted value <0.05) and 268 significantly downregulated genes (logFC<= -1.5, p-adjusted value <0.05) in severe samples in comparison to asymptomatic samples. Eventually, Gene Set Enrichment Analysis (GSEA) of upregulated genes revealed significant enrichment of terms, i.e., anti-viral and anti-inflammatory pathways, secondary infections, Iron homeostasis, anemia, cardiac-related, etc. Gene set enrichment analysis of downregulated genes indicates lipid metabolism, adaptive immune response, translation, recurrent respiratory infections, heme-biosynthetic pathways, etc. In summary, severe COVID-19 patients are more susceptible to other health issues/concerns, non-viral pathogenic infections, atherosclerosis, autoinflammatory diseases, anemia, male infertility, etc. And eventually, these findings provide insight into the precise therapeutic management of severe COVID-19 patients and efficient disease management.
Characterization of SARS-CoV-2 vaccine waning in Mexico
Authors: Hernandez-Suarez Carlos , Murillo-Zamora Efren 
Published: April 2022

1.AbstractWe use survival analysis to analyze the decay in the protection induced by eight vaccines using data from 44, 006 patients from the IMSS public health system in Mexico, including only previously vaccinated, confirmed SARS-CoV-2 positive with a PCR test. We analyze three groupings: all data, complete vs. incomplete dose and less than 60 years or older. We found that a Weibull distribution fits very well the complete dose data. Only three vaccines still had 30% of their initial strength after 32 weeks. In two-dose vaccines, we found that the average protection time of a complete dose increases 2 to 3 times compared to that of an incomplete dose.
PERMISSIVE OMICRON BREAKTHROUGH INFECTIONS IN INDIVIDUALS WITH BINDING OR NEUTRALIZING ANTIBODIES TO ANCESTRAL SARS-CoV-2
Authors: Williams Erin , Colson Jordan , Valiathan Ranjini , Carreño Juan Manuel , Krammer Florian , Hoffer Michael , Pallikkuth Suresh , Pahwa Savita , Andrews David 
Published: April 2022

ABSTRACTBackgroundBreakthrough infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) has occurred in populations with high vaccination rates. These infections are due to sequence variation in the spike protein leading to a reduction in protection afforded by the current vaccines, which are based on the original Wuhan-Hu-1 strain, or by natural infection with pre-Omicron strains.MethodsIn a longitudinal cohort study, pre-breakthrough infection sera for Omicron breakthroughs (n=12) were analyzed. Assays utilized include a laboratory-developed solid phase binding assay to recombinant spike protein, a commercial assay to the S1 domain of the spike protein calibrated to the World Health Organization (WHO) standard, and a commercial solid-phase surrogate neutralizing activity (SNA) assay. All assays employed spike protein preparations based on sequences from the Wuhan-Hu-1 strain. Participant demographics and clinical characteristics were captured.ResultsPre-breakthrough binding antibody (bAB) titers ranged from 1:800-1:51,200 for the laboratory-developed binding assay, which correlated well and agreed quantitatively with the commercial spike S1 domain WHO calibrated assay. SNA was detected in 10/12 (83%) samples.ConclusionsNeither high bAB nor SNA were markers of protection from Omicron infection/re-infection. Laboratory tests with antigen targets based on Wuhan-Hu-1 may not accurately reflect the degree of immune protection from variants with significant spike protein differences. Omicron breakthrough infections are likely due to high sequence variation of the spike protein and reflect incomplete immune protection from previous infection with strains that preceded Omicron or with vaccinations based on the original Wuhan-Hu-1 strain.
From menarche to menopause: the impact of reproductive factors on the metabolic profile of over 65,000 women
Authors: Clayton Gemma L , Borges Maria Carolina , Lawlor Deborah A 
Published: April 2022

AbstractWe explored the relation between age at menarche, parity and age at natural menopause with 249 metabolic traits, measured using nuclear magnetic resonance (NMR), in up to 65,487 UK Biobank women using multivariable regression (MV), Mendelian randomization (MR) and a male negative control (parity only). Older age of menarche was related to a less atherogenic metabolic profile in MV and MR, which was largely attenuated when accounting for adult body mass index. In MV, higher parity related to complex changes in lipoprotein-related traits; these were not observed in male negative controls and were imprecisely estimated in MR. In MV and MR, older age at natural menopause was related to lower concentrations of inflammation markers, but inconsistent results were observed for LDL-related traits due to chronological age-specific effects. Our findings support a role of reproductive traits on later life metabolic profile and provide insights into identifying novel markers for the prevention of adverse cardiometabolic outcomes in women.Summary boxWhat is new?Markers of women’s reproductive health are associated with several common chronic conditions. Whilst some attempts have been made to explore the extent to which these associations are causal, metabolites could act as mediators of the relationship between reproductive markers and chronic diseases.Older age of menarche was related to a less atherogenic metabolic profile in multivariable regression and Mendelian randomization, however, this was largely attenuated when accounting for adult body mass index.In multivariable regression, higher parity related to complex changes in lipoprotein-related traits. Whilst these were not observed in male negative controls, suggesting a potential causal effect in females, they were not replicated in the Mendelian randomization, possibly due to imprecise estimates.Older age at natural menopause was related to lower concentrations of inflammation markers in both multivariable regression and Mendelian randomization. Consistent results were observed for LDL-related traits when stratified by chronological age.ImplicationsGiven that the age at menarche results were largely attenuated to the null when accounting for adult BMI, it is likely that age at menarche itself may not causally relate to the metabolic profile.These results, particularly for parity and age at menopause, could contribute to identifying novel markers for the prevention of adverse cardiometabolic outcomes in women and/or methods for accurate risk prediction. For example, consistent with other studies, higher parity was associated with unfavourable (e.g. higher number of particles and lipid content in VLDL and higher glycine) changes in the metabolic profile. Similarly, older age at menopause was related to higher lipid content in HDL particles and lower systemic inflammation, as proxied by GlycA.
The SARS-CoV-2 Omicron BA.1 spike G446S potentiates HLA-A*24:02-restricted T cell immunity
Authors: Motozono Chihiro , Toyoda Mako , Tan Toong Seng , Hamana Hiroshi , Aritsu Yoshiki , Miyashita Yusuke , Oshiumi Hiroyuki , Nakamura Kimitoshi , Okada Seiji , Udaka Keiko , Kitamatsu Mizuki , Kishi Hiroyuki , Ueno Takamasa 
Published: April 2022

AbstractAlthough the Omicron variant of the SARS-CoV-2 virus is resistant to neutralizing antibodies, it retains susceptibility to cellular immunity. Here, we characterized vaccine-induced T cells specific for various SARS-CoV-2 variants and identified HLA-A*24:02-restricted CD8+ T cells that strongly suppressed Omicron BA.1 replication. Mutagenesis analyses revealed that a G446S mutation, located just outside the N-terminus of the cognate epitope, augmented TCR recognition of this variant. In contrast, no enhanced suppression of replication was observed against cells infected with the prototype, Omicron BA.2, and Delta variants that express G446. The enhancing effect of the G446S mutation was lost when target cells were treated with inhibitors of tripeptidyl peptidase II, a protein that mediates antigen processing. These results demonstrate that the G446S mutation in the Omicron BA.1 variant affects antigen processing/presentation and potentiates antiviral activity by vaccine-induced T cells, leading to enhanced T cell immunity towards emerging variants.
Evolution of self-sustained circadian rhythms requires seasonal change of daylight
Authors: Seki Motohide , Ito Hiroshi 
Published: April 2022

AbstractsSelf-sustained oscillation is a fundamental property of circadian rhythms and has been repeatedly tested since the early days of circadian research, resulting in the discovery of almost all organisms possessing self-sustained circadian oscillations. However, the evolutionary advantage of self-sustainability has been only speculatively discussed. In this theoretical study, we sought the environmental constraints and selection pressure that drive the acquisition or degeneration of self-sustainability through the process of evolution. We considered a random gene regulatory network dynamics under light cycles and optimized the network structure using an evolutionary algorithm. By designing the fitness function in the evolutionary algorithm, we investigated the environmental conditions that led to the evolution of the self-sustained oscillators. Then, we found that (i) networks showing self-sustained oscillation under constant light conditions are much rarer than those showing damped oscillation and hourglass-type behaviour, and (ii) among several types of fitness-based optimization, networks with self-sustainability property have a markedly high fitness score, especially when we assume that a network has to generate a constantly periodic expression profile regardless of day length. This study was the first to show that seasonality facilitated the evolution of the self-sustained circadian clock, which was consistent with empirical records.