bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation and performance evaluation of a novel interferon-γ release assay for the detection of SARS-CoV-2 specific T-cell response
Authors: Huzly Daniela , Panning Marcus , Smely Franziska , Enders Martin , Komp Johanna , Steinmann Daniel 
Published: July 2021

AbstractBackgroundThe reliable detection of the T-cell mediated response to COVID-19 or COVID-19 vaccination is important for individual patient care and for monitoring the immune response e.g. in COVID-19 vaccine trials in a standardized fashion.MethodsWe used blood samples from health care workers (HCW) with or without history of COVID-19 to define test accuracy of a novel interferon-release assay. Usefulness of qualitative and quantitative results after COVID-19 vaccination was examined in HCW receiving homologous or heterologous vaccination regimens. For a real-life performance evaluation, we analysed interferon-response to complete vaccination in 149 patients receiving immunosuppressive or immune modulating therapies.ResultsUsing a double-cut-off strategy integrating the result of background stimulation the assay had a specificity of 100%. Sensitivity of the IGRA was 83.5 and 100% in HCW after SARS-CoV-2 infection more or less than 6 months ago. Quantitative results showed significant differences between first and second vaccine dose, but no difference between homologous and heterologous vaccination regimen. The majority of immunocompromised patients showed no immune response or isolated T-cell or antibody response to complete vaccination.ConclusionsThe novel IGRA proved to be a highly specific and sensitive tool to detect the SARS-CoV-2 specific T-cell response to COVID-19 as well as COVID-19 vaccination. In perspective, it may serve as a standardized tool in COVID-19 vaccine trials and in clinical care of immunosuppressed patients.
Plasma cell-free DNA promise disease monitoring and tissue injury assessment of COVID-19
Authors: Jin Xin , Wang Yanqun , Xu Jinjin , Li Yimin , Cheng Fanjun , Luo Yuxue , Zhou Haibo , Lin Shanwen , Xiao Fei , Zhang Lu , Lin Yu , Zhang Zhaoyong , Jin Yan , Zheng Fang , Chen Wei , Zhu Airu , Tao Ye , Zhao Jingxian , Kuo Tingyou , Li Yuming , Li Lingguo , Wen Liyan , Ou Rijing , Li Fang , Lin Long , Zhang Yanjun , Sun Jing , Yuan Hao , Zhuang Zhen , Sun Haixi , Chen Zhao , Li Jie , Zhuo Jianfen , Chen Dongsheng , Zhang Shengnan , Sun Yuzhe , Wei Peilan , Yuan Jinwei , Xu Tian , Yang Huanming , Wang Jian , Xu Xun , Zhong Nanshan , Xu Yonghao , Sun Kun , Zhao Jincun 
Published: July 2021

AbstractCOVID-19 is a huge threat to global health. Due to the lack of definitive etiological therapeutics currently, effective disease monitoring is of high clinical value for better healthcare and management of the large number of COVID-19 patients. In this study, we recruited 37 COVID-19 patients, collected 176 blood samples upon diagnosis and during treatment, and analyzed cell-free DNA (cfDNA) in these samples. We report gross abnormalities in cfDNA of COVID-19 patients, including elevated GC content, altered molecule size and end motif patterns. More importantly, such cfDNA characteristics reflect patient-specific physiological conditions during treatment. Further analysis on tissue origin tracing of cfDNA reveals frequent tissue injuries in COVID-19 patients, which is supported by clinical diagnoses. Hence, we demonstrate the translational merit of cfDNA as valuable analyte for effective disease monitoring, as well as tissue injury assessment in COVID-19 patients.
Better individual-level risk models can improve the targeting and life-saving potential of early-mortality interventions
Authors: Hazlett Chad , Ramos Antonio P. , Smith Stephen 
Published: July 2021

AbstractInfant mortality remains high and uneven in much of sub-Saharan Africa. Even low-cost, highly effective therapies can only save lives in proportion to how successfully they can be targeted to those children who, absent the treatment, would have died. This places great value on maximizing the accuracy of any targeting or means-testing algorithm. Yet, the interventions that countries deploy in hopes of reducing mortality are often targeted based on simple models of wealth or income or a few additional variables. Examining 22 countries in sub-Saharan Africa, we illustrate the use of flexible (machine learning) risk models employing up to 25 generally available pre-birth variables from the Demographic and Health Surveys. Using these models, we construct risk scores such that the 10 percent of the population at highest risk account for 15-30 percent of infant mortality, depending on the country. Successful targeting in these models turned on several variables other than wealth, while models that employ only wealth data perform little or no better than chance. Consequently, employing such data and models to predict high-risk births in the countries studied flexibly could substantially improve the targeting and thus the life-saving potential of existing interventions.
Investigating the causal relationship between physical activity and chronic back pain: a bidirectional two-sample Mendelian randomization study
Authors: Gao Shaowei , Zhou Huaqiang , Luo Siyu , Cai Xiaoying , Ye Fang , He Qiulan , Huang Chanyan , Zheng Xiaoyang , Li Ying , Du Zhanxin , Wang Yaqing , Qi Zhihui , Wang Zhongxing 
Published: July 2021

AbstractBackgroundRecent observational studies have reported a negative association between physical activity and chronic back pain (CBP), but the causality of the association remains unknown. We introduce bidirectional Mendelian randomization (MR) to assess potential causal inference between physical activity and CBP.MethodsThe two-sample MR was used with independent genetic variants associated with physical activity phenotypes and CBP as genetic instruments from large genome-wide association studies (GWASs) on individuals of European ancestry. The effects of both directions (physical activity to CBP and CBP to physical activity) were examined. Inverse variance-weighted meta-analysis and alternate methods (weighted median and MR-Egger) were used to combine the MR estimates of the genetic instruments. Multiple sensitivity analyses were conducted to examine the robustness of the results.ResultsFor primary analysis, instrumental variables were extracted from 337,234 participants for physical activity (the same as the outcome cohort) and 158,025 participants (29,531 cases) for CBP, while the outcome cohort for CBP included 117,404 participants (80,588 cases). No evidence of a causal relationship was found in the direction of physical activity to CBP (odds ratio [OR], 0.98; 95% CI, 0.85-1.13; P = 0.81). In contrast, a negative causal relationship in the direction of CBP to physical activity was detected (β = -0.07; 95% CI, -0.12 to -0.01; P = 0.02), implying a reduction in moderate-vigorous physical activity (approximately 146 MET-minutes/week) for participants with CBP relative to controls.ConclusionsThe negative relationship between physical activity and CBP is probably derived from the reduced physical activity of patients experiencing CBP rather than the protective effect of physical activity on CBP.Highlights➢ Previous studies found a negative relationship between physical activity and chronic back pain, but the causal inference behind the relationship is lacking in evidences.➢ We applied Mendelian randomization and revealed that the negative relationship probably derived from the fact that patients experiencing CBP tend to reduce their physical activities.➢ If the negative relationship between physical activity and CBP is truly a reverse causality, the concept that patients with CBP should be engaging in activity, which is recommended by current guidelines, may need to be reconsidered.
Interaction-based feature selection algorithm outperforms polygenic risk score in predicting Parkinson’s Disease status
Authors: Klinger Jörn E. , Ravarani Charles N. J. , Baukmann Hannes A. , Cope Justin L. , Böttinger Erwin P. , Konigorski Stefan , Schmidt Marco F. 
Published: July 2021

AbstractPolygenic risk scores (PRS) aggregating results from genome-wide association studies are state of the art to predict the susceptibility to complex traits or diseases. Novel machine learning algorithms that use large amounts of data promise to find gene-gene interactions in order to build models with better predictive performance than PRS. Here, we present a data preprocessing step by using data-mining of contextual information to reduce the number of features, enabling machine learning algorithms to identify gene-gene interactions. We applied our approach to the Parkinson’s Progression Markers Initiative (PPMI) dataset, an observational clinical study of 471 genotyped subjects (368 cases and 152 controls). With an AUC of 0.85 (95% CI = [0.72; 0.96]), the interaction-based prediction model outperforms the PRS (AUC of 0.58 (95% CI = [0.42; 0.81])). Furthermore, feature importance analysis of the model provided insights into the mechanism of Parkinson’s Disease. For instance, the model revealed an interaction of previously described drug target candidate genesTMEM175andGAPDHP25. These results demonstrate that interaction-based machine learning models can improve genetic prediction models and might provide an answer to the missing heritability problem.
Australia’s worsening mental health – what’s next?
Authors: Enticott Joanne , Dawadi Shrinkhala , Shawyer Frances , Inder Brett , Fossey Ellie , Teede Helena , Rosenberg Seb , Ozol Ingrid , Meadows Graham 
Published: July 2021

AbstractObjectivesTo examine trends in psychological distress in Australia between 2001 to 2017-18, including analysis by age, sex, and location.Design, setting and participantsSecondary analysis of six successive national health surveys of representative samples of the working age population (18-64 years).Main outcome measuresPrevalence of psychological distress at very-high symptom level (defined by a Kessler Psychological Distress Scale [K10] score of 30 or more) and combined high/very-high level (K10 score of 22 or more).ResultsThe latest survey showed 5.1% of Australians reporting very-high level distress and 14.8% combined high/very-high level - both the largest rates recorded this century. The greatest increase from 2001 to 2017-18 was in women aged 55-64 with very-high distress significantly increasing from 3.5% (95% CI: 2.5-4.5%) to 7.2% (5.9-8.5%), and; high/very-high distress from 12.4% (10.5-14.2%) to 18.7% (16.7-20.7%). Men aged 25-34 had very-high distress increase from 2.1% (1.4-2.8) to 4.0% (2.9-5.1%); and combined high/very-high distress remained stable at 10.6% (9.1-12.1%) to 11.5% (9.7-13.3%). In 2017-18, greatest distress was in women aged 18-24 years (very-high 8.0% (5.9-10.2%); high/very-high 22.1% (18.8-25.3%)). Overall, distress was significantly more prevalent in inner regional Australia than elsewhere (very-high level 4.8% (4.4-5.1%); high/very-high 14.4% (13.8-15%)).ConclusionsAustralia’s annual mental health expenditure over this period has doubled, yet population level psychological distress has increased. A whole of government approach and targeted strategies focusing on groups with the poorest mental health such as older working aged women, younger people, particularly women, and those outside of major cities are indicated.Box“The known” Previous examinations of national health surveys had suggested that population mental health was stable as measured by psychological distress.“The new” Examining six consecutive national surveys we provide evidence that mental health has significantly deteriorated between 2001 and 2018. The latest survey showed 5.1% of Australians reporting very-high distress and 14.8% combined high/very-high distress, which are the largest rates reported this century.“The implications” Whole of government approach and targeted strategies focusing on groups with the poorest mental health such as older working aged women, younger people particularly women, and those outside of major cities are indicated.
Low CD4/CD8 ratio predicts cancer risk among adults with HIV
Authors: Castilho Jessica L. , Bian Aihua , Jenkins Cathy A. , Shepherd Bryan E. , Sigel Keith , Gill M. John , Kitahata Mari M. , Silverberg Michael J. , Mayor Angel M. , Coburn Sally B. , Wiley Dorothy , Achenbach Chad J. , Marconi Vincent C. , Bosch Ronald J. , Horberg Michael A. , Rabkin Charles , Napravnik Sonia , Novak Richard M. , Mathews W. Christopher , Thorne Jennifer E. , Sun Jing , Althoff Keri N. , Moore Richard D. , Sterling Timothy R. , Sudenga Staci L. ,   the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of the International Epidemiology Databases to Evaluate AIDS (IeDEA)
Published: July 2021

AbstractBackgroundIndependent of CD4 cell count, low CD4/CD8 ratio in people with HIV (PWH) is associated with deleterious immune senescence, activation, and inflammation, which may contribute to carcinogenesis and excess cancer risk. We examined whether low CD4/CD8 ratios predicted cancer among PWH in the USA and Canada.MethodsWe examined all cancer-free PWH with one or more CD4/CD8 values from NA-ACCORD observational cohorts with validated cancer diagnoses between 1998-2016. We evaluated the association between time-lagged CD4/CD8 ratio and risk of specific cancers in multivariable, time-updated Cox proportional hazard models using restricted cubic spines.Models were adjusted for age, sex, race/ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness.ResultsAmong 83,893 PWH, there were 5,628 incident cancers, including lung cancer (n=755), Kaposi sarcoma (KS, n=501), non-Hodgkin lymphoma (NHL, n=497), and anal cancer (n=439). Median age at cohort entry was 43 years, 87% were male, and 43% were white. Overall median six-month lagged CD4/CD8 ratio was 0.52 (interquartile range: 0.30-0.82). Compared with six-month lagged CD4/CD8=0.80, CD4/CD8=0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 [95% confidence interval: 1.14-1.35]). CD4/CD8 ratio was also inversely associated with NHL, KS, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all p<0.05). Results were similar using 12-, 18-, and 24-month lagged CD4/CD8 values.ConclusionsLow CD4/CD8 ratio up to 24 months prior to cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker.
Protocol for a prospective, hospital-based registry of pregnant women with SARS-CoV-2 infection in India: PregCovid Registry study
Authors: Gajbhiye Rahul K , Mahajan Niraj N , Waghmare Rakesh , Surve Suchitra , Howal Prashant , Bhurke Aishwarya , Pious Merlin , Modi Deepak N , Mahale Smita D 
Published: July 2021

ABSTRACTIntroductionPregnant women are at increased risk of contracting coronavirus disease 2019 (COVID-19) due to several factors and therefore require special attention. However, the consequences of the COVID-19 pandemic on pregnant women and their newborns remain uncharted. The PregCovid registry aims to document the impact of SARS-CoV-2 infection on pregnant, post-partum women and their newborns. The aim of the registry is also to determine mother-to-child transmission of SARS-CoV-2 infection in India.Methods and analysisPregCovid is a hospital-based registry for capturing information of pregnant, post-partum women with COVID-19 and their newborns in India. Medical case records of pregnant and post-partum women with laboratory-confirmed diagnoses of COVID-19 will be captured in real-time using an online electronic patient record (EPR) software. The frequency of each symptom will be calculated. The laboratory data will be analyzed for calculating the frequency of laboratory parameters consistently higher in women with COVID- The adverse pregnancy and neonatal outcomes will be analyzed and their frequency will be calculated. Response to treatment will be analyzed for frequency calculation (number of women treated with different treatment regimens). The mother-to-child transmission data will be analyzed from the RT-PCR and/ antibody data of neonatal and maternal samples tested wherever the information is available. The registry data will be crucial for developing strategies for reducing the adverse impact of COVID-19 on pregnant women and their new-born.Ethics and disseminationThe study is approved by the Institutional Ethics Committee of ICMR-National Institute for Research in Reproductive Health (#55/2020), BYL Nair Hospital, Mumbai, India (# 63/2020); and all the 18 participating study sites under Medical Education and Drugs Department of Government of Maharashtra. The Institutional Ethics Committees granted a waiver of consent as the data is collected from the medical case records.Trial registration numberCTRI/2020/05/025423Article summaryStrengths and limitations of this studyThe PregCovid registry is a hospital-based registry at dedicated COVID-19 hospitals in India. The registry will help to identify new epidemiological, clinical characteristics, obstetrics outcomes associated with pregnant women and/post-partum women with COVID-19 in India. The study will also generate information on clinical presentations and outcomes of neonatal born to mothers with COVID-19 in India.PregCovid registry will provide evidence of mother to child transmission of SARS-CoV-2 infection in Indian womenThe evidence on unusual presentations of COVID-19 in pregnant and post-partum women will be generated.The follow-up of participants is only till the discharge from the hospital. Long-term follow-up is not included in the study.
Patients treated with anti-CD20 therapy can mount robust T cell responses to mRNA-based COVID-19 vaccines
Authors: Madelon Natacha , Lauper Kim , Breville Gautier , Royo Irène Sabater , Goldstein Rachel , Andrey Diego O. , Grifoni Alba , Sette Alessandro , Siegrist Claire-Anne , Finckh Axel , Lalive Patrice H. , Didierlaurent Arnaud M. , Eberhardt Christiane S. 
Published: July 2021

ABSTRACTPatients treated with anti-CD20 therapy are particularly at risk of developing severe COVID-19, however little is known regarding COVID-19 vaccine effectiveness in this population. This study assesses humoral and T-cell responses to mRNA-based COVID-19 vaccines in patients treated with rituximab for rheumatic diseases or ocrelizumab for multiple sclerosis (n=37), compared to immunocompetent individuals (n=22). SARS-CoV-2-specific antibodies were detectable in only 69.4% of patients and at levels that were significantly lower compared to controls who all seroconverted. In contrast to antibodies, Spike (S)-specific CD4+ T cells were equally detected in immunocompetent and anti-CD20 treated patients (85-90%) and mostly of a Th1 phenotype. Response rates of S-specific CD8+T cells were higher in ocrelizumab (96.2%) and rituximab-treated patients (81.8%) as compared to controls (66.7%). Vaccine-specific CD4+and CD8+T cells were polyfunctional but expressed more IL-2 in patients than in controls. In summary, our study suggests that patients on anti-CD20 treatment are able to mount potent T-cell responses to mRNA COVID-19 vaccines, despite impaired humoral responses. This could play an important role in the prevention of severe COVID-19.
The COVID-19 pandemic and child malnutrition in sub-Saharan Africa: A scoping review
Authors: Sestito Paolo , Velásquez Sabina Rodriguez , Orel Erol , Keiser Olivia 
Published: July 2021

AbstractBackgroundAlthough the COVID-19 pandemic has resulted in lower reported number of cases and deaths within the paediatric population, indirect impacts on the health of children in Sub-Saharan Africa such as malnutrition are evident. Data on the socioeconomic factors affecting malnutrition in the under-age population of Sub-Saharan Africa brought by the COVID-19 pandemic remain limited. This paper assesses socioeconomic factors of malnutrition in relation with COVID-19 and potential mitigating measures.MethodsA scoping review of PubMed, Embase, and Web of Science from March 11, 2020, to May 1, 2021, was conducted. The included studies focused on COVID-19, children malnutrition, and Sub-Saharan Africa and adhered to the PRISMA guideline.ResultsAmong 73 total screened articles, 15 studies filled the inclusion criteria. The identified socioeconomic factors leading to malnutrition in children were reduction in average income or increase in unemployment rate, access to healthcare and food supplements, disrupted food supply chains and increased prices of food products, pauses in humanitarian responses, and reduced access to school-based meals. Potential mitigation measures were food subsidies, food price control measures, the identification of new vulnerable groups and the implementation of financial interventions.ConclusionMalnutrition amongst Sub-Saharan African children due to COVID-19 is a result of a combination of multiple socioeconomic factors. To stabilize household purchasing power and eventually malnutrition in children in SSA, a combined strategy of initial detection of newly developing vulnerable groups and efficient, rapid financial assistance through mobile phone transfers was suggested. These strategies were proposed in combination with other economical models.
Association of Sleep-Disordered Breathing With Cardiovascular Events and Death in patients With Ischemic Heart Disease: A systematic review and meta-analysis
Authors: Zhang Yaodan , Tan Jin , Miao Yuyang , Zhang Qiang 
Published: July 2021

AbstractObjectivePrevious studies have identified that sleep-disordered breathing is associated with the increased risk of cardiovascular disease. However, CPAP, the preferred treatment of sleep apnea, does not appear to reduce the risk of adverse cardiovascular events and deaths in ischemic heart disease. Our aim was to determine whether OSA can be a prognostic factor for cardiovascular adverse events and deaths in patients with ischemia heart disease.MethodsWe searched Medline via PubMed, Embase, and the Cochrane Library database for clinical studies reporting the major adverse cardiac outcomes of SDB in patients with myocardial ischemia. Sleep apnea tests is mainly performed with cardiorespiratory polygraphy or portable diagnostic device. Summary hazard ratio(HR) and 95% CIs were conducted using random-effects meta-analysis.ResultsEighteen literatures were included, with total participants of 9,138. Sixteen studies reported MACCEs, there was significant association of SDB with MACCES (HR, 1.66[95% CI, 1.41 to 1.94]; P< 0.0001), all-cause mortality (HR, 1.39[95% CI 1.12 to 1.73], P=0.0027) and cardiovascular mortality (HR, 2.12[95% CI 1.23 to 3.65], P=0.007). Subgroup analysis showed that one study was the cause of heterogeneity, while no correlation between SDB and outcomes for sleep apnea severity, follow-up time or whether surgery was performed.ConclusionSDB is associated with adverse cardiac outcomes in patients with ischemic heart disease, suggesting that sleep apnea can be screened for patients with ischemic heart disease, which can be used as a clinically relevant strategy of secondary prevention to reduce the risk of adverse outcomes.