bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seroprevalence of Anti-SARS-CoV-2 Antibodies in a Cohort of New York City Metro Blood Donors using Multiple SARS-CoV-2 Serological Assays: Implications for Controlling the Epidemic and “Reopening”
Authors: Jin Daniel K. , Nesbitt Daniel. J. , Yang Jenny , Chen Haidee , Horowitz Julie , Jones Marcus , Vandergaast Rianna , Carey Timothy , Reiter Samantha , Russell Stephen J , Kyratsous Christos , Hooper Andrea , Hamilton Jennifer , Ferreira Manuel , Deng Sarah , Straus Donna , Baras Aris , Hillyer Christopher D. , Luchsinger Larry L. 
Published: November 2020

AbstractProjections of the stage of the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pandemic and local, regional and national public health policies designed to limit the spread of the epidemic as well as “reopen” cities and states, are best informed by serum neutralizing antibody titers measured by reproducible, high throughput, and statically credible antibody (Ab) assays. To date, a myriad of Ab tests, both available and authorized for emergency use by the FDA, has led to confusion rather than insight per se. The present study reports the results of a rapid, point-in-time 1,000-person cohort study using serial blood donors in the New York City metropolitan area (NYC) using multiple serological tests, including enzyme-linked immunosorbent assays (ELISAs) and high throughput serological assays (HTSAs). These were then tested and associated with assays for neutralizing Ab (NAb). Of the 1,000 NYC blood donor samples in late June and early July 2020, 12.1% and 10.9% were seropositive using the Ortho Total Ig and the Abbott IgG HTSA assays, respectively. These serological assays correlated with neutralization activity specific to SARS-CoV-2. The data reported herein suggest that seroconversion in this population occurred in approximately 1 in 8 blood donors from the beginning of the pandemic in NYC (considered March 1, 2020). These findings deviate with an earlier seroprevalence study in NYC showing 13.7% positivity. Collectively however, these data demonstrate that a low number of individuals have serologic evidence of infection during this “first wave” and suggest that the notion of “herd immunity” at rates of ∼60% or higher are not near. Furthermore, the data presented herein show that the nature of the Ab-based immunity is not invariably associated with the development of NAb. While the blood donor population may not mimic precisely the NYC population as a whole, rapid assessment of seroprevalence in this cohort and serial reassessment could aid public health decision making.
Engineering a Mobile Platform to Promote Sleep in the Pediatric Primary Care Setting
Authors: Mitchell Jonathan A. , Morales Knashawn H. , Williamson Ariel A. , Huffnagle Nicholas , Eck Casey , Jawahar Abigail , Juste Lionola , Fiks Alexander G. , Zemel Babette S. , Dinges David F. 
Published: November 2020

AbstractBackgroundPediatricians lack tools to support families at home for the promotion of childhood sleep. We are using the Multiphase Optimization Strategy (MOST) framework to guide the development of a mobile health platform for childhood sleep promotion.PurposeUnder the preparation phase of the MOST framework, to demonstrate feasibility of a mobile health platform towards treating children with insufficient sleep.MethodsChildren aged 10-12y were enrolled (Study #1: N=30; Study #2: N=43). Participants wore a sleep tracker to measure sleep duration. Data were retrieved by a mobile health platform, programmed to send introductory messages during run-in (2 weeks) and goal achievement messages during intervention (7 weeks) periods. In study #1, participants were randomized to control, gain-framed incentive or loss-framed incentive arms. In study #2, participants were randomized to control, loss-framed incentive, normative feedback or loss-framed incentive plus normative feedback arms.ResultsIn study #1, 1,514 nights of data were captured (69%) and sleep duration during the intervention was higher by an average of 21 (95% CI: -8, 51) and 34 (95% CI: 7, 61) minutes per night for the gain-framed and loss-framed arms, respectively, compared to controls. In study #2, 2,689 nights of data were captured (81%), with no major differences in average sleep duration between the control and the loss-framed or normative feedback arms.ConclusionWe have developed and deployed a mobile health platform that can capture sleep data and remotely communicate with families. Promising candidate intervention components will be further investigated under the optimization phase of the MOST framework.
Validation of home oxygen saturations as a marker of clinical deterioration in patients with suspected COVID-19
Authors: Inada-Kim Matthew , Chmiel Francis P. , Boniface Michael J. , Pocock Helen , Black John J. M. , Deakin Charles D. 
Published: November 2020

ABSTRACTBackgroundThe early identification of deterioration in suspected COVID-19 patients managed at home enables a more timely clinical intervention, which is likely to translate into improved outcomes. We undertook an analysis of COVID-19 patients conveyed by ambulance to hospital to investigate how oxygen saturation and measurements of other vital signs correlate to patient outcomes, to ascertain if clinical deterioration can be predicted with simple community physiological monitoring.MethodsA retrospective analysis of routinely collected clinical data relating to patients conveyed to hospital by ambulance was undertaken. We used descriptive statistics and predictive analytics to investigate how vital signs, measured at home by ambulance staff from the South Central Ambulance Service, correlate to patient outcomes. Information on patient comorbidities was obtained by linking the recorded vital sign measurements to the patient’s electronic health record at the Hampshire Hospitals NHS Foundation Trust. ROC analysis was performed using cross-validation to evaluate, in a retrospective fashion, the efficacy of different variables in predicting patient outcomes.ResultsWe identified 1,080 adults with a COVID-19 diagnosis who were conveyed by ambulance to either Basingstoke & North Hampshire Hospital or the Royal Hampshire County Hospital (Winchester) between March 1st and July 31st and whose diagnosis was clinically confirmed at hospital discharge. Vital signs measured by ambulance staff at first point of contact in the community correlated with patient short-term mortality or ICU admission. Oxygen saturations were the most predictive of mortality or ICU admission (AUROC 0.772 (95 % CI: 0.712-0.833)), followed by the NEWS2 score (AUROC 0.715 (95 % CI: 0.670-0.760), patient age (AUROC 0.690 (95 % CI: 0.642-0.737)), and respiration rate (AUROC 0.662 (95 % CI: 0.599-0.729)). Combining age with the NEWS2 score (AUROC 0.771 (95 % CI: 0.718-0.824)) or the measured oxygen saturation (AUROC 0.820 (95 % CI: 0.785-0.854)) increased the predictive ability but did not reach significance.ConclusionsInitial oxygen saturation measurements (on air) for confirmed COVID-19 patients conveyed by ambulance correlated with short-term (30-day) patient mortality or ICU admission, AUROC: 0.772 (95% CI: 0.712-0.833). We found that even small deflections in oxygen saturations of 1-2% below 96% confer an increased mortality risk in those with confirmed COVID at their initial community assessments.
Longitudinal Physiological Data from a Wearable Device Identifies SARS-CoV-2 Infection and Symptoms and Predicts COVID-19 Diagnosis
Authors: Hirten Robert P. , Danieletto Matteo , Tomalin Lewis , Choi Katie Hyewon , Zweig Micol , Golden Eddye , Kaur Sparshdeep , Helmus Drew , Biello Anthony , Pyzik Renata , Nabeel Ismail , Charney Alexander , Glicksberg Benjamin , Levin Matthew , Reich David , Charney Dennis , Bottinger Erwin P , Keefer Laurie , Suarez-Farinas Mayte , Nadkarni Girish N. , Fayad Zahi A. 
Published: November 2020

ABSTRACTBackgroundChanges in autonomic nervous system function, characterized by heart rate variability (HRV), have been associated with and observed prior to the clinical identification of infection. We performed an evaluation of this metric collected by wearable devices, to identify and predict Coronavirus disease 2019 (COVID-19) and its related symptoms.MethodsHealth care workers in the Mount Sinai Health System were prospectively followed in an ongoing observational study using the custom Warrior Watch Study App which was downloaded to their smartphones. Participants wore an Apple Watch for the duration of the study measuring HRV throughout the follow up period. Survey’s assessing infection and symptom related questions were obtained daily.FindingsUsing a mixed-effect COSINOR model the mean amplitude of the circadian pattern of the standard deviation of the interbeat interval of normal sinus beats (SDNN), a HRV metric, differed between subjects with and without COVID-19 (p=0.006). The mean amplitude of this circadian pattern differed between individuals during the 7 days before and the 7 days after a COVID-19 diagnosis compared to this metric during uninfected time periods (p=0.01). Significant changes in the mean MESOR and amplitude of the circadian pattern of the SDNN was observed between the first day of reporting a COVID-19 related symptom compared to all other symptom free days (p=0.01).InterpretationLongitudinally collected HRV metrics from a commonly worn commercial wearable device (Apple Watch) can identify the diagnosis of COVID-19 and COVID-19 related symptoms. Prior to the diagnosis of COVID-19 by nasal PCR, significant changes in HRV were observed demonstrating its predictive ability to identify COVID-19 infection.FundingSupport was provided by the Ehrenkranz Lab For Human Resilience, the BioMedical Engineering and Imaging Institute, The Hasso Plattner Institute for Digital Health at Mount Sinai, The Mount Sinai Clinical Intelligence Center and The Dr. Henry D. Janowitz Division of Gastroenterology.
Unraveling the relationship of loneliness and isolation in schizophrenia: Polygenic dissection and causal inference
Authors: Andreu-Bernabeu A. , Díaz-Caneja C.M. , Costas J. , de Hoyos L. , Stella C. , Gurriarán X. , Alloza C. , Fañanás L. , Bobes J. , González Pinto A. , Crespo-Facorro B. , Martorell L. , Vilella E. , Muntane G. , Nacher J. , Molto M.D. , Aguilar E.J. , Parellada M. , Arango C. , González-Peñas J. 
Published: November 2020

ABSTRACTThere is increasing recognition of the association between loneliness and social isolation (LNL-ISO) with schizophrenia. Here, we demonstrate significant LNL-ISO polygenic score prediction on schizophrenia in an independent case-control sample (N=3,488). We then dissect schizophrenia predisposing variation into subsets of variants based on their effect on LNL-ISO. Genetic variation with concordant effects in both phenotypes show significant SNP-based heritability enrichment, higher polygenic predictive ability in females and positive covariance with other mental disorders such as depression, anxiety, attention-deficit hyperactivity, alcohol use disorder, and autism. Conversely, genetic variation with discordant effects is only predictive in males and negatively correlated with those disorders. This correlation pattern is not observed for bipolar and obsessive-compulsive disorders. Mendelian randomization analyses demonstrate a plausible bi-directional causal relationship between LNL-ISO and schizophrenia, with a greater effect of LNL-ISO liability on schizophrenia. These results illustrate the genetic footprint of LNL-ISO on schizophrenia and suggest its role as a potential target for early intervention.
Trends in body mass index and blood pressure associations from 1989 to 2018: co-ordinated analysis of 145,399 participants
Authors: Bann David , Scholes Shaun , Hardy Rebecca , O’Neill Dara 
Published: November 2020

BackgroundHigh body mass index (BMI) is an important contributor to higher blood pressure (BP) levels and its deleterious consequences. However, the strength of this association may be context-specific and differ across time due to increases in medication use or secular changes in body composition. Thus, we utilised two independent data sources to investigate if associations between BMI and systolic BP (SBP) in Britain changed from 1989-2018.MethodsWe used 23 repeated cross-sectional datasets—the Health Survey for England (HSE) at ≥25 years (1994–2018; N=126,742); and three British birth cohorts (born 1946, 1958, and 1970) with outcomes available at 43-46 years (N=18,657). Anthropometry and BP were measured using standard protocols. We used linear and quantile regression to investigate cross-sectional associations between BMI and SBP.ResultsIn HSE, associations were weaker in subsequent years, and this trend was most pronounced amongst older adults—after accounting for sex, treatment and education, the mean difference in SBP per 1 kg/m2 increase in BMI amongst adults ≥55 years was 0.75mmHg (95% CI: 0.60, 0.90) in 1994, 0.66mmHg (0.46, 0.85) in 2003, and 0.53mmHg (0.35, 0.71) in 2018. In cohorts, BMI and SBP associations were of similar magnitude in 1958 and 1970 cohorts and weaker in the 1946 cohort. Quantile regression analyses suggested that associations between BMI and SBP were present both below and above the hypertension threshold.ConclusionThe consequences of BMI may differ across time and by age —associations between BMI and SBP appear to have weakened in recent decades, particularly in older ages. Thus, at older ages, this weakening strength of association may partly offset the public health impacts of increases in obesity prevalence. However, BMI remains positively associated with SBP in all adult age groups, highlighting the potential adverse consequences of the ongoing obesity epidemic.
Mitochondrial DNA haplogroups and trajectories of cardiometabolic risk factors during childhood and adolescence: a prospective cohort study
Authors: O’Neill Kate N , Aubrey Emily , Howe Laura D , Stergiakouli Evie , Rodriguez Santiago , Kearney Patricia M , O’Keeffe Linda M 
Published: November 2020

AbstractBackgroundMitochondria are organelles responsible for converting glucose into energy. Mitochondrial DNA is exclusively maternally inherited by offspring. The role of mitochondrial DNA haplogroups in the aetiology of cardiometabolic disease risk is not well understood.MethodsWe examined the sex-specific association between European mitochondrial DNA haplogroups and trajectories of nine cardiometabolic risk factors from birth to 18 years in a prospective English birth cohort. Mitochondrial haplogroups were analysed according to common European haplogroups; H,U,J,T,K,V,W,I and X. Nine cardiometabolic risk factors measured over varying times from birth/mid-childhood to age 18 years included body mass index (BMI), fat mass and lean mass, systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate, high-density lipoprotein cholesterol (HDL-c), non HDL-c and triglycerides. Fractional polynomial and linear spline multilevel models stratified by sex explored the sex-specific association between haplogroups and risk factor trajectories.ResultsAmong 6,360-7,954 participants with 22,864-79,178 repeated measures per outcome, we found no strong evidence that haplogroups U,T,J,K and W were associated with trajectories of cardiometabolic risk factors across childhood and adolescence compared to haplogroup H. In females, haplogroup V was associated with 4.0% (95% CI: 1.4, 6.7) lower BMI at age 7 years and 9.3% (95% CI: 1.9, 16.7) lower fat mass at age 9, though differences did not persist at age 18. Haplogroup X was associated with 1.3kg (95% CI: 0.5, 2.2) lower lean mass and 16.4% (95% CI: 3.5, 29.3) lower fat mass at age 9; associations with lower lean mass persisted at 18 years whereas associations with fat mass did not. In males, haplogroup I was associated with 2.4% (95% CI: 0.2, 4.6) higher BMI at age 7; this difference widened to 5.1% (95% CI: 0.9,9.3) at 18 years.ConclusionOur study demonstrated some evidence of sex-specific associations between mitochondrial DNA haplogroups V, I and X and trajectories of adiposity during childhood and adolescence.
Predicting the impact of disruptions in lymphatic filariasis elimination programmes due to the outbreak of coronavirus disease (COVID-19) and possible mitigation strategies
Authors: Prada Joaquín M. , Stolk Wilma A. , Davis Emma L. , Touloupou Panayiota , Sharma Swarnali , Muñoz Johanna , Caja Rivera Rocio M. , Reimer Lisa J. , Michael Edwin , de Vlas Sake J , Hollingsworth T Déirdre 
Published: November 2020

AbstractBackgroundIn view of the current global COVID-19 pandemic, mass drug administration interventions for neglected tropical diseases, including lymphatic filariasis, have been halted. We used mathematical modelling to estimate the impact of delaying or cancelling treatment rounds and explore possible mitigation strategies.MethodsWe used three established lymphatic filariasis transmission models to simulate infection trends in settings with annual treatment rounds and programme delays in 2020 of 6, 12, 18 or 24 months. We then evaluated the impact of various mitigation strategies upon resuming activities.ResultsThe delay in achieving the elimination goals is on average similar to the number of years the treatment rounds are missed. Enhanced interventions implemented for as little as one year can allow catch-up on the progress lost, and if maintained throughout the programme can lead to acceleration of up to 3 years.ConclusionsIn general, a short delay in the programme does not cause major delay in achieving the goals. Impact is strongest in high endemicity areas. Mitigation strategies such as biannual treatment or increased coverage are key to minimizing the impact of the disruption once the programme resumes; and lead to potential acceleration, should these enhanced strategies be maintained.
Ex vivoosteochondral test system with control over cartilage defect depth – a pilot study to investigate the effect of oxygen tension and chondrocyte-based treatments in chondral and full thickness defects in an organ model
Authors: Schwab Andrea , Buss Alexa , Pullig Oliver , Ehlicke Franziska 
Published: November 2020

AbstractObjectiveCartilage defect treatment strategies are dependent on the lesion size and severity. Osteochondral explants models are a platform to test cartilage repair strategiesex vivo. Current models lack in mimicking the variety of clinically relevant defect scenarios. In this controlled laboratory study, an automated device (artificial tissue cutter, ARTcut®) was implemented to reproducible create cartilage defects with controlled depth. In a pilot study, the effect of cartilage defect depth and oxygen tension on cartilage repair was investigated.DesignOsteochondral explants were isolated from porcine condyles. 4 mm chondral and full thickness defects were treated with either porcine chondrocytes (CHON) or co-culture of 20 % CHON and 80 % MSC (MIX) embedded in collagen hydrogel. Explants were cultured with tissue specific media (without TGF-β) under normoxia (20 % O2) and physiological hypoxia (2 % O2). After 28 days, immune-histological stainings (Collagen II and X, Aggrecan) were scored (modified Bern-score, 3 independent scorer) to quantitatively compare treatments outcome.ResultsARTcut®represents a software-controlled device for creation of uniform cartilage defects. Comparing the scoring results of the MIX and the CHON treatment, a positive relation between oxygen tension and defect depth was observed. Low oxygen tension stimulated cartilaginous matrix deposition in MIX group in chondral defects and CHON treatment in full thickness defects.ConclusionARTcut®has proved a powerful tool to create cartilage defects and thus opens a wide range of novel applications of the osteochondral model, including the relation between oxygen tension and defect depth on cartilage repair.
Single-cell analysis of human primary prostate cancer reveals the heterogeneity of tumor-associated epithelial cell states
Authors: Song Hanbing , Weinstein Hannah N.W. , Allegakoen Paul , Wadsworth Marc H. , Xie Jamie , Yang Heiko , Feng Felix Y. , Carroll Peter R. , Wang Bruce , Cooperberg Matthew R. , Shalek Alex K. , Huang Franklin W. 
Published: November 2020

AbstractProstate cancer is the second most common malignancy in men worldwide and consists of a mixture of tumor and non-tumor cell types. To characterize the prostate cancer tumor microenvironment, we performed single-cell RNA-sequencing on prostate biopsies, prostatectomy specimens, and patient-derived organoids from localized prostate cancer patients. We identify a population of tumor-associated club cells that may act as progenitor cells and uncover heterogeneous cellular states in prostate epithelial cells marked by high androgen signaling states that are enriched in prostate cancer.ERG- tumor cells, compared toERG+ cells, demonstrate shared heterogeneity with surrounding luminal epithelial cells and appear to give rise to common tumor microenvironment responses. Finally, we show that prostate epithelial organoids recapitulate tumor-associated epithelial cell states and are enriched with distinct cell types and states from their parent tissues. Our results provide diagnostically relevant insights and advance our understanding of the cellular states associated with prostate carcinogenesis.
Recurrent chromosomal imbalances provide selective advantage to human embryonic stem cells under enhanced replicative stress conditions
Authors: Mus Liselot M. , Van Haver Stéphane , Popovic Mina , Trypsteen Wim , Lefever Steve , Zeltner Nadja , Ogando Yudelca , Jacobs Eva Z. , Denecker Geertrui , Sanders Ellen , Van Neste Christophe , Vanhauwaert Suzanne , Decaesteker Bieke , Deforce Dieter , Van Nieuwerburgh Filip , Mestdagh Pieter , Vandesompele Jo , Menten Björn , De Preter Katleen , Studer Lorenz , Heindryckx Björn , Durinck Kaat , Roberts Stephen , Speleman Frank 
Published: November 2020

ABSTRACTHuman embryonic stem cells (hESCs) and embryonal tumors share a number of common features including a compromised G1/S checkpoint. Consequently, these rapidly dividing hESCs and cancer cells undergo elevated levels of replicative stress which is known to induce genomic instability causing chromosomal imbalances. In this context, it is of interest that long-termin vitrocultured hESCs exhibit a remarkable high incidence of segmental DNA copy number gains, some of which are also highly recurrent in certain malignancies such as 17q gain (17q+). The selective advantage of DNA copy number changes in these cells has been attributed to several underlying processes including enhanced proliferation. We hypothesized that these recurrent chromosomal imbalances become rapidly embedded in the cultured hESCs through a replicative stress driven Darwinian selection process. To this end, we compared the effect of hydroxyurea induced replicative stress versus normal growth conditions in an equally-mixed cell population of isogenic euploid and 17q+ hESCs. We could show that 17q+ hESCs rapidly overtook normal hESCs. Our data suggest that recurrent chromosomal segmental gains provide a proliferative advantage to hESCs under increased replicative stress, a process that may also explain the highly recurrent nature of certain imbalances in cancer.