bluuebunny/crossref_metadata_2025_split huggingface dataset:
BA.2 omicron differs immunologically from both BA.1 omicron and pre-omicron variants
Authors: Rössler Annika , Netzl Antonia , Knabl Ludwig , Schäfer Helena , Wilks Samuel H. , Bante David , Falkensammer Barbara , Borena Wegene , von Laer Dorothee , Smith Derek , Kimpel Janine 
Published: May 2022

AbstractBackgroundSeveral studies have shown that SARS-CoV-2 BA.1 omicron is an immune escape variant and current vaccines and infection with pre-omicron variants provide limited protection against BA.1. Meanwhile, however, omicron BA.2 has become the dominant variant in many countries and has replaced BA.1. As BA.2 has several mutations especially in the receptor binding and the N terminal domain compared to BA.1, we analyzed whether BA.2 shows further immune escape relative to BA.1.MethodsWe characterized neutralization profiles against the new BA.2 omicron variant in plasma samples from a variety of individuals with different numbers of exposures to infection/vaccination, including samples from previously virus-naïve, BA.2 omicron-infected individuals. To illustrate antigenic differences of the two omicron sub-variants and pre-omicron variants we performed antigenic cartography and generated antibody landscapes.ResultsUnvaccinated individuals after a single exposure to BA.2 had limited cross-neutralizing antibodies to pre-omicron variants and to BA.1. Consequently, our antigenic map, which included all Variants of Concern and both BA.1 and BA.2 omicron sub-variants, showed that both omicron sub-variants are distinct to pre-omicron variants, but that the two omicron variant are also antigenically distinct from each other. The antibody landscapes illustrate that cross-neutralizing antibodies against the whole antigenic space, as described in our maps, are generated only after three or more exposures to antigenically close variants but also after two exposures to antigenically distinct variants.ConclusionsHere, we describe the antigenic space inhabited by the relevant SARS-CoV-2 variants, the understanding of which will have important implications for further vaccine strain adaptations.
VIGIL - Video In Geriatric Intervention Clinic: A randomised controlled feasibility trial protocol comparing face-to-face and video delivery of a specialist preoperative clinic for older people
Authors: Thorman Emma , Joughin Andrea , Carter Ben , Braude Philip 
Published: May 2022

AbstractThe Covid-19 pandemic resulted in significant challenges to the provision of face-to-face clinics in geriatric perioperative care (G-POC). There are no studies evaluating the use of telemedicine in this population. A pilot study at North Bristol NHS Trust demonstrated that delivery of GPOC clinics via video consultation was feasible, but did not record outcome measures to demonstrate effectiveness and was not compared to face to face clinic. This study aims to provide proof of concept examining the outcomes of virtual G-POC consultations, compared to a face-to-face clinic, using standardised perioperative outcomes. It will test the feasibility of the intervention with a view to developing a randomised controlled trial.
Risk factors for pneumococcal carriage in adults living with HIV on antiretroviral therapy in the infant pneumococcal vaccine era in Malawi
Authors: Thindwa Deus , Mwalukomo Thandie S , Msefula Jacquline , Jambo Kondwani C , Brown Comfort , Kamng’ona Arox , Mwansambo Charles , Ojal John , Flasche Stefan , French Neil , Heyderman Robert S , Swarthout Todd D 
Published: May 2022

AbstractObjectiveAdults living with HIV (ALWHIV) on antiretroviral therapy (ART) are at high risk of pneumococcal carriage and disease. To help evaluate carriage risk in African ALWHIV in the infant pneumococcal conjugate vaccination era, we assessed association between carriage and potential risk factors.MethodsNasopharyngeal swabs were collected from adults aged 18-40 years attending an ART clinic during rolling, cross-sectional surveys in Blantyre, Malawi between 2015-2019. We fitted generalised additive models to estimate the risk of sex, social economic status (SES), living with a child <5y, and ART duration on carriage.ResultsOf 2,067 adults, median age was 33y (range 28-37), 1,427 (69.0%) were females, 1,087 (61.4%) were in low-middle socio-economic-status (SES), 910 (44.0%) were living with a child <5y, and median ART duration was 3.0 years (range 0.004-17). We estimated 38.2% and 60.6% reductions in overall and vaccine-serotype carriage prevalence. Overall carriage was associated with low SES, living with a child <5y and shorter duration on ART. By contrast, vaccine-type carriage was associated with living without a child <5y and male sex.ConclusionDespite temporal reductions in overall and vaccine-serotype carriage, there is evidence of incomplete VT indirect protection. A targeted-vaccination campaign should be considered for ALWHIV, along with other public health measures to further reduce vaccine-serotype carriage and therefore disease.
CHARACTERISTICS AND OUTCOMES OF INDIVIDUALS WITH COVID-19: EVIDENCE FROM A HOSPITAL BASED STUDY
Authors: Simushi P. , Zambwe M. , Chipimo P.J. 
Published: May 2022

ABSTRACTObjectiveTo determine the characteristics and outcomes of Covid-19 patients at Livingstone teaching hospital.MethodsA database cross sectional review of COVID 19 patients at Livingstone Teaching Hospital. Data on demographics and clinical characteristics were obtained along with the comorbidities presented with by the patients using a structured data collection form. Data were analysed using STATA 64. Mann-Whitney and t-test were used on continuous independent variables. Chi-square test was used to determine associations between two categorical variables. Logistic regression was used to control for confounders.ResultsA total of 222 (62.54%) were male and 133 (37.46%) were female. Discharged were 274 (77.18%), while 81 (22.82%) died. Among those who died were the older clients with a median age of 65 (p <0.001). The median interquartile range (IQR)] age was 48.5 years. Patients presented with a cough 180 (50.7%), chest pain 123 (34.65%) and shortness of breath 121 (34.04%). Statistically significant comorbidities recorded included Hypertension 121 (34.08%), Diabetes mellitus 69 (19.44%), and HIV 38 (10.7%). The most prevalent underlying condition observed was hypertension 121 (34.08).ConclusionHIV positive and diabetics had an increased odds of succumbing to COVID-19 death. It is recommended that targeted policies should be considered the risky groups.
Effect modification in network meta-analyses of treatments for relapsing refractory multiple myeloma (RRMM): systematic review, meta-analysis, and simulation
Authors: Rose Christopher James , Ohm Ingrid Kristine , Giske Liv , Næss Gunn Eva , Fretheim Atle 
Published: May 2022

ABSTRACTAimsNetwork meta-analysis (NMA) has been used in several systematic reviews on relapsing refractory multiple myeloma (RRMM). NMAs have been questioned on the basis that effect modification may invalidate the underpinning assumptions. We aimed to systematically review and meta-analyze the evidence for effect modification of hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) with respect to refractory status and number of treatment lines.MethodsWe extracted stratified HR estimates from 42 phase 2 and 3 randomized controlled trials (RCTs). We tested for within-study effect modification and used meta-analyses to estimate ratios of hazard ratios (RHRs) across trial under assumptions that strongly favor the modification hypothesis. RHR estimates were used in simulations to estimate how many NMA results would be expected to differ in the presence versus absence of effect modification.ResultsMost (95%) publications could have reported stratified estimates but only 14% (OS) and 43% (PFS) did. Within-study evidence for effect modification is very weak (p > 0.05 for 47 of 49 sets of stratified estimates). The largest RHR estimated was 1.31 (95% CI 1.16–1.47), for the modifying effect of refractory status on HR for PFS. Simulations suggest that, in the worst case, effect modification would result in 4.48% (95% CI 4.42%–4.53%) of NMA estimates differing statistically significantly in the presence versus absence of effect modification.ConclusionsEffect modification is essentially undetectable in phase 2 and 3 trials. In the worst case, it is unlikely to affect more than about 5% of random-effects NMA estimates.
Identifying key multifunctional components shared by critical cancer and normal liver pathways via sparseGMM
Authors: Bakr Shaimaa , Brennan Kevin , Mukherjee Pritam , Argemi Josepmaria , Hernaez Mikel , Gevaert Olivier 
Published: May 2022

ABSTRACTDespite the abundance of multi-modal data, suitable statistical models that can improve our understanding of diseases with genetic underpinnings are challenging to develop. Here we present SparseGMM, a novel statistical approach for gene regulatory network discovery. SparseGMM uniquely uses latent variable modeling with sparsity constraints regulators to learn gaussian mixtures from multi-omic data. By combining co-expression patterns with a Bayesian framework, sparseGMM quantitatively measures confidence in regulators and uncertainty in target gene assignment by computing gene entropy. We apply SparseGMM to liver cancer and normal liver tissue data and evaluate the discovered gene modules in an independent scRNA-seq dataset. sparseGMM identifies PROCR as a regulator of angiogenesis, and PDCD1LG2 and HNF4A as regulators of immune response and blood coagulation in cancer, respectively. Additionally, we show that more genes have significantly higher entropy in cancer compared to normal liver; among high entropy genes are key multifunctional components shared by critical pathways, such as p53 and estrogen signaling.Software availabilityThe software is available athttps://hub.docker.com/r/shaimaabakr/sparse_gmmOne-sentence summaryA novel statistical approach for gene regulatory network discovery recovers modules and corresponding regulators of diverse normal liver functions, important liver cancer processes, as well as shared biology between liver cancer and normal tissue.
Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma
Authors: Hamel Andrew R. , Yan Wenjun , Rouhana John M. , Monovarfeshani Aboozar , Jiang Xinyi , Mehta Puja A. , Advani Jayshree , Luo Yuyang , Liang Qingnan , Rajasundaram Skanda , Shrivastava Arushi , Duchinski Katherine , Mantena Sreekar , Wang Jiali , van Zyl Tavé , Pasquale Louis R. , Swaroop Anand , Gharahkhani Puya , Khawaja Anthony P. , MacGregor Stuart ,   International Glaucoma Genetics Consortium (IGGC), Chen Rui , Vitart Veronique , Sanes Joshua R. , Wiggs Janey L. , Segrè Ayellet V. 
Published: May 2022

AbstractPrimary open-angle glaucoma (POAG), characterized by retinal ganglion cell death, is a leading cause of irreversible blindness worldwide; however, the molecular and cellular causes are not well understood. Elevated intraocular pressure (IOP) is a major risk factor, but many patients have normal IOP. Colocalization and Mendelian randomization analysis of >240 POAG and IOP GWAS loci and of overlapping eQTLs and sQTLs in 49 GTEx tissues and retina prioritized causal genes for 60% of loci. These genes were enriched in pathways implicated in extracellular matrix organization, cell adhesion, and vascular development. Analysis of single-nucleus RNA-seq of glaucoma-relevant eye tissues revealed that the colocalizing genes and genome-wide POAG and IOP associations were enriched in specific cell types in the aqueous outflow pathways, retina, optic nerve head, peripapillary sclera, and choroid. This study nominated IOP-dependent and independent regulatory mechanisms, genes, and cell types that may contribute to POAG pathogenesis.
What are effective strategy to constrain COVID-19 pandemic crisis? lessons learned from a comparative policy analysis between Italian regions to cope with next pandemic impact
Authors: Coccia Mario , Benati Igor 
Published: May 2022

AbstractThe pandemic of Coronavirus Disease 2019 (COVID-19) and its variants is rapidly spreading all over the world, generating a high number of infections, deaths and negative impact on socioeconomic system of countries. As vaccines and appropriate drugs for treatment of the COVID-19 can reduce the effectiveness in the presence of variants and/or new viral agents, one of the questions in social studies of medicine is effective public policy responses to reduce the impact of COVID-19 global pandemic and similar infectious diseases on health of people and on economies. This study analyzes public policy responses to the pandemic crisis across Italian regions that were the first areas to experience a rapid increase in confirmed cases and deaths of COVID-19. The analysis of regional strategies, from January to July 2020, reveals differences in public policy responses to delay and reduce the height of epidemic peak and to afford health-care systems more time to expand and respond to this new emergency. Veneto Region in North-East Italy has managed health policy responses with: a) a timely and widespread testing of individuals, b) units of epidemiological investigation for tracing all contacts of infected people in an effective contact tracing system. This public policy response has reduced total deaths and the final size of COVID-19 pandemic on health of people. Other regions have done public interventions without a clear strategy and goals to cope with diffusion of COVID-19 and as a consequence, they have had a higher negative impact on public health. Lesson learned can be important to design an effective public policy that can be generalized in different regional and national systems to prevent and/or reduce future epidemics or pandemics similar to the COVID-19.
Neutralization Escape by the SARS-CoV-2 Omicron Variants BA.2.12.1 and BA.4/BA.5
Authors: Hachmann Nicole P. , Miller Jessica , Collier Ai-ris Y. , Ventura John D. , Yu Jingyou , Rowe Marjorie , Bondzie Esther Apraku , Powers Olivia , Surve Nehalee , Hall Kevin , Barouch Dan H. 
Published: May 2022

ABSTRACTMultiple lineages of the SARS-CoV-2 Omicron variant (B.1.1.529) have emerged, and BA.1 and BA.2 have demonstrated substantial escape from neutralizing antibodies (NAbs). BA.2.12.1 has now become dominant in the United States, and BA.4 and BA.5 have become dominant in South Africa. Our data show that BA.2.12.1 and BA.4/BA.5 substantially escape NAbs induced by both vaccination and infection. Moreover, BA.4/BA.5 NAb titers, and to lesser extent BA.2.12.1 NAb titers, were lower than BA.1 and BA.2 NAb titers, suggesting that the SARS-CoV-2 Omicron variant has continued to evolve with increasing neutralization escape. These findings have important public health implications and provide immunologic context for the current surges with BA.2.12.1 and BA.4/BA.5 in populations with high rates of vaccination and BA.1/BA.2 infection.
A Randomized Phase 2/3 Study of Ensitrelvir, a Novel Oral SARS-CoV-2 3C-like Protease Inhibitor, in Japanese Patients With Mild-to-Moderate COVID-19 or Asymptomatic SARS-CoV-2 Infection: Results of the Phase 2a Part
Authors: Mukae Hiroshi , Yotsuyanagi Hiroshi , Ohmagari Norio , Doi Yohei , Imamura Takumi , Sonoyama Takuhiro , Fukuhara Takahiro , Ichihashi Genki , Sanaki Takao , Baba Keiko , Takeda Yosuke , Tsuge Yuko , Uehara Takeki 
Published: May 2022

ABSTRACTFor the treatment of coronavirus disease 2019 (COVID-19), antiviral agents that can achieve rapid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reduction are warranted. This double-blind, phase 2a part of a phase 2/3 study assessed the efficacy and safety of ensitrelvir, a novel oral SARS-CoV-2 3C-like protease inhibitor, in Japanese patients with mild-to-moderate COVID-19 or asymptomatic SARS-CoV-2 infection. Sixty-nine patients enrolled from 56 sites were randomized (1:1:1) to orally receive 5-day ensitrelvir fumaric acid (375 mg on day 1 followed by 125 mg daily or 750 mg on day 1 followed by 250 mg daily) or placebo and followed up until day 28. The primary outcome was change from baseline in SARS-CoV-2 viral titer. A total of 16, 14, and 17 patients in the ensitrelvir 125 mg, ensitrelvir 250 mg, and placebo groups, respectively, were included in the intention-to-treat population (mean age: 38.8, 40.4, and 38.0 years, respectively). On day 4, the change from baseline in SARS-CoV-2 viral titer (log10 50% tissue culture infectious dose/mL) in patients with positive viral titer and viral RNA at baseline was greater with ensitrelvir 125 mg (mean [standard deviation], −2.42 [1.42]; P = 0.0712) and 250 mg (−2.81 [1.21]; P = 0.0083) versus placebo (−1.54 [0.74]), and ensitrelvir treatment reduced SARS-CoV-2 RNA by −1.4 to −1.5 log10 copies/mL versus placebo. All adverse events were mild to moderate. Ensitrelvir treatment demonstrated rapid SARS-CoV-2 clearance and was well tolerated in patients with mild-to-moderate COVID-19 or asymptomatic SARS-CoV-2 infection (Japan Registry of Clinical Trials identifier: jRCT2031210350).
Effect of various hormonal and non-hormonal contraceptive methods on the vaginal milieu -A narrative review
Authors: Tandon Deepti , Patil Anushree D , Goriwale Mayuri 
Published: May 2022

AbstractGlobally the use of modern contraceptive methods has risen to 851 million. Use of these contraceptive methods does influence the vaginal health, which in turn affects the susceptibility towards acquiring RTI/STI. Methods to assess the vaginal health have also evolved over decades. The objective of this narrative review is to assess the influence of contraceptive methods on the vaginal health and also evaluate the methods used to assess the vaginal milieu. Suitable articles published in literature from 2007-2020 were identified from PubMed, Google Scholar using relevant keywords. Hormonal contraceptives included were combined oral contraceptive pills (COCP), Depot medroxyprogesterone acetate (DMPA)and Levonorgestrel IUCD(LNG-IUS). Non hormonal methods included were barrier methods, copper IUCD, diaphragm and vaginal sponge. Outcome parameter recorded were Nugent score, vaginal pH, bacterial vaginosis or defined microbiome profile.COCP have been shown to protect the vaginal ecosystem primarily due to their oestrogen component. The use of IUCD causes initial dysbiosis chiefly due to associated irregular bleeding but long term use of LNG IUS stabilizes the microbiome. Use of injectable DMPA though does not increase the susceptibility to HIV but can promote growth of anaerobic organisms. Literature regarding condom, diaphragm and sponge is very scanty to draw a meaningful conclusion. Hence contraceptive methods can affect the vaginal health. There is need to periodically assess the vaginal milieu using test which is appropriate as per available expertise, infrastructure and cost and treat vaginal dysbiosis in respective cohorts to prevent reproductive morbidity.
Towards individualized Medicine in Stroke – the TiMeS project: protocol of longitudinal, multi-modal, multi-domain study in stroke
Authors: Fleury L , Koch PJ , Wessel MJ , Bonvin C , San Millan D , Constantin C , Vuadens P , Adolphsen J , Cadic-Melchior AG , Brügger J , Beanato E , Ceroni M , Menoud P , de Leon Rodriguez D , Zufferey V , Meyer N , Egger P , Harquel S , Popa T , Raffin E , Girard G , Thiran JP , Vaney C , Alvarez V , Turlan J-L , Mühl A , Leger B , Morishita T , Micera S , Blanke O , Van de Ville D , Hummel FC 
Published: May 2022

AbstractDespite recent improvements, complete motor recovery occurs in less than 15% of stroke patients. To improve the therapeutic outcomes, there is a strong need to tailor treatments to each individual patient. However, there is a lack of knowledge concerning the precise neuronal mechanisms underlying the degree and course of motor recovery and its individual differences, especially in the view of network properties despite the fact that it became more and more clear that stroke is a network disorder. The TiMeS project is a longitudinal exploratory study aiming at characterizing stroke phenotypes of a large, representative stroke cohort through an extensive, multi-modal and multi-domain evaluation. The ultimate goal of the study is to identify prognostic biomarkers allowing to predict the individual degree and course of motor recovery and its underlying neuronal mechanisms paving the way for novel interventions and treatment stratification for the individual patients. A total of up to 100 patients will be assessed at 4 timepoints over the first year after the stroke: during the first (T1) and third (T2) week, then three (T3) and twelve (T4) months after stroke onset. To assess underlying mechanisms of recovery with a focus on network analyses and brain connectivity, we will apply synergistic state-of-the-art systems neuroscience methods including functional, diffusion, and structural magnetic resonance imaging (MRI), and electrophysiological evaluation based on transcranial magnetic stimulation (TMS) coupled with electroencephalography (EEG) and electromyography (EMG). In addition, an extensive, multi-domain neuropsychological evaluation will be performed at each timepoint, covering all sensorimotor and cognitive domains. This project will significantly add to the understanding of underlying mechanisms of motor recovery with a strong focus on the interactions between the motor and other cognitive domains and multimodal network analyses. The population-based, multi-dimensional dataset will serve as a basis to develop biomarkers to predict outcome and promote personalized stratification towards individually tailored treatment concepts using neuro-technologies, thus paving the way towards personalized precision medicine approaches in stroke rehabilitation.
A longitudinal causal graph analysis investigating modifiable risk factors and obesity in a European cohort of children and adolescents
Authors: Foraita Ronja , Witte Janine , Börnhorst Claudia , Gwozdz Wencke , Pala Valeria , Lissner Lauren , Lauria Fabio , Reisch Lucia A , Molnár Dénes , De Henauw Stefaan , Moreno Luis , Veidebaum Toomas , Tornaritis Michael , Pigeot Iris , Didelez Vanessa 
Published: May 2022

AbstractChildhood obesity is a complex disorder that appears to be influenced by an interacting system of many factors. Taking this complexity into account, we aim to investigate the causal structure underlying childhood obesity. Our focus is on identifying potential early, direct or indirect, causes of obesity which may be promising targets for prevention strategies. Using a causal discovery algorithm, we estimate a cohort causal graph (CCG) over the life course from childhood to adolescence. We adapt a popular method, the so-called PC-algorithm, to deal with missing values by multiple imputation, with mixed discrete and continuous variables, and that takes background knowledge such as the time-structure of cohort data into account. The algorithm is then applied to learn the causal relations among 51 variables including obesity, early life factors, diet, lifestyle, insulin resistance, puberty stage and cultural background of 5,112 children from the European IDEFICS/I.Family cohort across three waves (2007-2014). The robustness of the learned causal structure is addressed in a series of alternative and sensitivity analyses; in particular, we use bootstrap resamples to assess the stability of aspects of the learned CCG. Our results suggest some but only indirect possible causal paths from early modifiable risk factors, such as audio-visual media consumption and physical activity, to obesity (measured by age- and sex-adjusted BMI z-scores) six years later.