tbuckley/cabot-search huggingface dataset:
Abstract P042: Association Between Covid-19 Pandemic Related Unemployment And Change In Sedentary Screen Time Among Previously Employed Adults
Authors: Jennifer L Mattingly, Megan E Petrov
Journal: Circulation (2021)

Association between COVID-19 Pandemic Related Unemployment and Change in Sedentary Screen Time among Previously Employed Adults Jennifer L. Mattingly, MPH &amp; Megan E. Petrov, PhD Introduction: Worldwide, the COVID-19 pandemic has resulted in widespread job loss and disruptions in daily life. However, the role of job loss during the COVID-19 pandemic on health behaviors such as sedentary screen time (SST) is unknown. The purpose of this study was to determine the association between employment status change during the pandemic and change in SST. Methods: A 25-minute online survey was distributed through local and global social media from 5/21/2020-7/01/2020. A subsample of employed adults (n=417; M =38.45y, range: 18-75; 74.8.% women) provided complete self-reported pre-and during-COVID-19 employment status (categorized as remained employed and became unemployed), pre-and during-COVID-19 hours of daily SST for non-work-related purposes [low: &lt;5h; high: &gt;5]. Change in daily SST was categorized as low-low (ref), low-high, and high-high. The subsample of participants that changed from high to low SST in the sample was low and were removed from subsequent analyses. Multinomial logistic regression models were conducted to examine the association of change in employment status on change in SST while adjusting for age, gender, education level, body mass index, current minutes of physical activity per week, and current typical 24-hour sleep duration. Results: Of the 417 participants who were employed prior to the pandemic, 15.6% (n=675). Became Unemployed. The proportion of participants in the low-low, low-high, and high-high change in SST groups were 46.8% (n=195), 25.4% (n=106), and 27.8% (n=116), respectively. Relative to adults who remained employed, adults who became unemployed had a 3.02 greater odds (95%CI:1.51, 6.02) of being in the high-high change in SST group, and had a 2.54 greater odds (95%CI:1.23,5.25) of being in the low-high change in SST group relative to participants who were consistently low in SST. Conclusion: In this cross-sectional study of an international, online sample of adults, becoming unemployed was associated with a greater odds of both maintaining high levels of sedentary screen time, and increasing sedentary screen time to high levels. Action to protect people in the workforce from job loss and employment disruption in times of global economic upheaval may prevent increased adoption of maladaptive lifestyle behaviors, such as high levels of SST.
Significant Liver Injury During Hospitalization for COVID-19 Is Not Associated With Liver Insufficiency or Death
Authors: Michael Chew, Zeyu Tang, Christopher Radcliffe, Dennis Caruana, Natty Doilicho, Maria M. Ciarleglio, Yanhong Deng, Guadalupe Garcia-Tsao
Journal: Clinical Gastroenterology and Hepatology (2021)

Coronavirus-19 disease (COVID-19) is associated with hepatocellular liver injury of uncertain significance. We aimed to determine whether development of significant liver injury during hospitalization is related to concomitant medications or processes common in COVID-19 (eg, ischemia, hyperinflammatory, or hypercoagulable states), and whether it can result in liver failure and death.There were 834 consecutive patients hospitalized with COVID-19 who were included. Clinical, medication, and laboratory data were obtained at admission and throughout hospitalization using an identified database. Significant liver injury was defined as an aspartate aminotransferase (AST) level 5 or more times the upper limit of normal; ischemia was defined as vasopressor use for a minimum of 2 consecutive days; hyperinflammatory state was defined as high-sensitivity C-reactive protein value of 100 mg/L or more, and hypercoagulability was defined as D-dimer 5 mg/L or more at any time during hospitalization.A total of 105 (12.6%) patients developed significant liver injury. Compared with patients without significant liver injury, ischemia (odds ratio [OR], 4.3; range, 2.5-7.4; P < .0001) and tocilizumab use (OR, 3.6; range, 1.9-7.0; P = .0001) were independent predictors of significant liver injury. Although AST correlated closely with alanine aminotransferase (R = 0.89) throughout hospitalization, AST did not correlate with the international normalized ratio (R = 0.10) or with bilirubin level (R = 0.09). Death during hospitalization occurred in 136 (16.3%) patients. Multivariate logistic regression showed that significant liver injury was not associated with death (OR, 1.4; range, 0.8-2.6; P = .2), while ischemic (OR, 2.4; range, 1.4-4.0; P = .001), hypercoagulable (OR, 1.7; range, 1.1-2.6; P = .02), and hyperinflammatory (OR, 1.9; range, 1.2-3.1; P = .02) disease states were significant predictors of death.Liver test abnormalities known to be associated with COVID-19 are secondary to other insults, mostly ischemia or drug-induced liver injury, and do not lead to liver insufficiency or death.
Dynamic monitoring of circulating tumor DNA to predict prognosis and efficacy of adjuvant chemotherapy after resection of colorectal liver metastases
Authors: De-Shen Wang, Hui Yang, Xiao-Yun Liu, Zhi-Gang Chen, Yun Wang, William Pat Fong, Ming-Tao Hu, Yuan-Chao Zheng, Yun Zheng, Bin-Kui Li, Yun-Fei Yuan, Gong Chen, Zhi-Zhong Pan, Lele Song, Yu-Hong Li, Rui-Hua Xu
Journal: Theranostics (2021)

Rationale: Hepatectomy and adjuvant chemotherapy after resection of colorectal liver metastases (CRLM) may improve survival, however, patients which may benefit cannot currently be identified. Postoperative circulating tumor DNA (ctDNA) analysis can detect minimal residual disease (MRD) and predict the prognosis and efficacy of adjuvant chemotherapy. Our study aims to determine the impact of serial ctDNA analysis to predict the outcome among patients undergoing resection of CRLM. Methods: Between May 2018 and October 2019, 91 CRLM patients were prospectively enrolled. Whole exome sequencing was performed in 50 primary and 48 metastatic liver tissues. Targeted sequencing of 451 cancer relevant genes was performed in 50 baseline plasma to determine plasma-tissue concordance. We prospectively investigated changes in the amount and constitution of ctDNA in 271 serial plasma samples taken at different time points (baseline, pre-operation, post-operation, post-operative adjuvant chemotherapy (post-ACT) and recurrence) during the treatment of CRLM. Results: Detected molecular alterations were highly consistent among baseline ctDNA, primary and liver metastases tissue. Patients with a higher variant allele frequency (VAF) level at baseline ctDNA represent a higher tumor burden, and decreased ctDNA during pre-operative chemotherapy predicted better tumor response. Patients with detectable post-operative and post-ACT ctDNA were associated with significantly shorter recurrence-free survival (RFS). ROC analysis showed that post-ACT ctDNA status was superior to post-operative ctDNA status in predicting RFS with an AUROC of 0.79. A significant difference in overall recurrence rate was observed in patients with detectable vs undetectable levels of ctDNA after resection of CRLM (79.4% vs 41.7%) and after completion of adjuvant chemotherapy (77.3% vs 40.7%). During adjuvant chemotherapy, patients with decreased ctDNA VAF after adjuvant chemotherapy had a recurrence rate of 63.6%, compared to 92.3% in patients with increased ctDNA VAF. Conclusions: We envision that dynamic ctDNA analysis, especially in a post-ACT setting, might be used to not only reflect MRD but also to determine rational personalized adjuvant therapy after the resection of CRLM.
Abstract 15742: An Open-label, Multicenter Study of Flecainide Acetate Oral Inhalation Solution Shows Acute Conversion of Recent-onset, Symptomatic Atrial Fibrillation to Sinus Rhythm in a Dose- and Concentration-dependent Manner
Authors: Harry Crijns, Jeremy N Ruskin, Arif Elvan, Nadea Al-Windy, Ype Tuininga, Erik Badings, Ismail Aksoy, Isabelle C Van Gelder, John Camm, Peter R Kowey, Luiz Belardinelli
Journal: Circulation (2020)

Introduction: Oral and intravenous (IV) flecainide are recommended as first line therapy for pharmacological cardioversion of recent-onset atrial fibrillation (AF) in patients without known relevant structural heart disease. In the present open-label, dose-escalation study, the feasibility of using flecainide acetate inhalation solution (FlecIH) for acute conversion of recent-onset AF to sinus rhythm (SR) was evaluated. Hypothesis: We hypothesized that FlecIH quickly gives rise to plasma concentrations sufficient to rapidly restore SR in patients with recent-onset AF. Methods: Patients (n=95) with symptomatic AF (for ≤ 48 hours) were enrolled and self-administered FlecIH using a breath-actuated nebulizer (30 mg [n=10], 60 mg [n=20], 90 mg [n=21], 120 mg [n=17], and 120 mg in a formulation containing saccharin [n=27]). Blood samples were collected for flecainide plasma concentrations, electrocardiograms were obtained, cardiac rhythm with a 4-hour Holter and vital signs were monitored, and adverse events (AEs) were recorded. Patients who did not convert to SR were offered alternative treatment per the investigator’s discretion. Results: Conversion rates increased with dose and maximum plasma concentrations (C max ) of flecainide. At the highest dose, 45% of patients converted to normal SR. Patients with C max &gt; 300 ng/mL had a conversion rate of 53% whereas those with C max &lt; 200 ng/mL had a conversion rate of 33%. The median time to conversion was 3.5 min after FlecIH administration. AEs were typically mild and transient. Commonly reported AEs associated with inhalation of flecainide included: cough, throat pain, and throat irritation; at the highest dose with the formulation containing saccharin, these AEs were reported for 37%, 11%, and 4% of patients, respectively. Cardiac AEs consistent with those observed with oral and IV flecainide and considered serious were uncommon and included 2 post-conversion pauses and 1 bradycardia, and 1 atrial flutter with 1:1 atrioventricular conduction; none required treatment and all resolved without sequelae. Conclusions: FlecIH was well tolerated. Inhalation of FlecIH at the 120 mg dose yielded therapeutic plasma levels and conversion rates within the range reported for oral and IV administration.
Cultural evolution of genetic heritability
Authors: Ryutaro Uchiyama, Rachel Spicer, Michael Muthukrishna
Journal: Behavioral and Brain Sciences (2021)

Behavioral genetics and cultural evolution have both revolutionized our understanding of human behavior - largely independent of each other. Here, we reconcile these two fields under a dual inheritance framework, offering a more nuanced understanding of the interaction between genes and culture. Going beyond typical analyses of gene-environment interactions, we describe the cultural dynamics that shape these interactions by shaping the environment and population structure. A cultural evolutionary approach can explain, for example, how factors such as rates of innovation and diffusion, density of cultural subgroups, and tolerance for behavioral diversity impact heritability estimates, thus yielding predictions for different social contexts. Moreover, when cumulative culture functionally overlaps with genes, genetic effects become masked, unmasked, or even reversed, and the causal effects of an identified gene become confounded with features of the cultural environment. The manner of confounding is specific to a particular society at a particular time, but a WEIRD (western, educated, industrialized, rich, and democratic) sampling problem obscures this boundedness. Cultural evolutionary dynamics are typically missing from models of gene-to-phenotype causality, hindering generalizability of genetic effects across societies and across time. We lay out a reconciled framework and use it to predict the ways in which heritability should differ between societies, between socioeconomic levels, and other groupings within some societies but not others, and over the life course. An integrated cultural evolutionary behavioral genetic approach cuts through the nature-nurture debate and helps resolve controversies in topics such as IQ.
Micro–Computed Tomography Analysis of the Human Tuberculous Lung Reveals Remarkable Heterogeneity in Three-dimensional Granuloma Morphology
Authors: Gordon Wells, Joel N. Glasgow, Kievershen Nargan, Kapongo Lumamba, Rajhmun Madansein, Kameel Maharaj, Robert L. Hunter, Threnesan Naidoo, Llelani Coetzer, Stephan le Roux, Anton du Plessis, Adrie J. C. Steyn
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Our current understanding of tuberculosis (TB) pathophysiology is limited by a reliance on animal models, the paucity of human TB lung tissue, and traditional histopathological analysis, a destructive two-dimensional approach that provides limited spatial insight. Determining the three-dimensional (3D) structure of the necrotic granuloma, a characteristic feature of TB, will more accurately inform preventive TB strategies.
Abstract 15563: Association of Weight With Ablation Outcomes in Pediatric Wolff-Parkinson-White Syndrome: Analysis of the NCDR® IMPACT Registry
Authors: Christopher M Janson, Maully J Shah, kevin kennedy, Ramesh Iyer, Shashank P Behere, Tammy Sweeten, Michael L O’Byrne
Journal: Circulation (2020)

Introduction: Guidelines for electrophysiology study (EPS) and catheter ablation in Wolff-Parkinson-White syndrome (WPW) are based on age. Size is an established factor in ablation risk and may be the more appropriate factor to consider when deciding timing of EPS. Hypothesis: Weight &lt;30 kg is associated with higher rates of major adverse events (MAE) and deferred ablation, and lower rates of success. Methods: A multicenter retrospective cohort study was performed on children age 1-21 years with WPW and first-time EPS data in IMPACT from 4/16-12/19, excluding those with congenital heart disease, cardiomyopathy, and &gt; 1 ablation target. MAE were defined as cardiac arrest, stroke, tamponade, permanent pacemaker, or unplanned cardiac / vascular surgery. Ablation success was evaluated in those with attempts. Multivariable logistic regression models were used to adjust for measurable confounders - accessory pathway (AP) type, AP location, and use of cryoablation (cryo). Results: 4456 subjects from 84 centers were evaluated, with 14% &lt;30 kg. Subjects &lt;30 kg were more likely to have pre-operative SVT (45% vs. 29%, p&lt;0.001) and inducible SVT (71% vs. 61%, p&lt;0.001), more likely to have left non-septal APs (46% vs. 37%, p&lt;0.001), and less likely to have right septal APs (25% vs. 33%, p&lt;0.001, Table). No difference was seen in the likelihood of deferred ablation based on weight (9.5% vs. 12%, p=0.07). Ablation success was higher in &lt;30 kg: 95% vs. 92% (p=0.009). This effect persisted after adjusting for measurable covariates (OR 1.7, 95% CI 1.03-2.7, p = 0.04). Left non-septal AP location was also associated with success (OR 2.9, CI 1.9-4.2, p &lt;0.0001), and cryo was negatively associated (OR 0.4, CI 0.3-0.5, p&lt;0.0001). MAE were rare, though with higher incidence in &lt;30 kg (0.3% vs. 0.05%, p=0.04). Conclusions: In this analysis of WPW patients with ablation data in IMPACT, weight &lt;30 kg was associated with increased ablation success; a higher incidence of MAE (which were rare) was observed.
The Lancet women and cardiovascular disease Commission: reducing the global burden by 2030
Authors: Birgit Vogel, Monica Acevedo, Yolande Appelman, C Noel Bairey Merz, Alaide Chieffo, Gemma A Figtree, Mayra Guerrero, Vijay Kunadian, Carolyn S P Lam, Angela H E M Maas, Anastasia S Mihailidou, Agnieszka Olszanecka, Jeanne E Poole, Clara Saldarriaga, Jacqueline Saw, Liesl Zühlke, Roxana Mehran
Journal: The Lancet (2021)
Abstract 17323: Personalizing Cholesterol Management Therapy Using Electronic Medical Records and Machine Learning
Authors: Andrew T Ward, Jiang Li, Ashish Sarraju, Areli Valencia, David Scheinker, Fatima Rodriguez
Journal: Circulation (2020)

Introduction: Optimal statin treatment decisions for primary prevention of atherosclerotic cardiovascular disease (ASCVD) rely on shared decision-making between patient and provider. We sought to develop a machine learning-based algorithm to personalize cholesterol treatment decisions using electronic medical record (EMR) data. Methods: We included EMR data for adults aged 40 to 79 with no prior ASCVD or statin therapy from an outpatient Northern California system between January 1, 2009 and December 31, 2018 with at least two visits at least 1 year apart and at least two low density lipoprotein cholesterol (LDL-C) values. The outcome was the LDL-C measured closest to one year after a patient’s second visit. We modeled four different treatment decisions: no statin use, low-intensity statin use, moderate-intensity statin use, and high-intensity statin use. We trained weighted-K-nearest-neighbor (wKNN) regression models to identify similar patients using each line of therapy to a candidate patient. The algorithm compared outcomes of these similar patients and recommended the treatment which predicted the lowest LDL-C after one year. Results: Our study cohort consisted of 50,911 patients (age 54.6 ± 9.84 years, baseline LDL-C 122 ± 34.2 mg/dL, follow-up LDL-C 121 ± 35.9 mg/dL) including 54% female, 47% Non-Hispanic White, 32% Asian, and 7.5% Hispanic patients. Among 8,551 test patients visiting in 2015 or later, 96.9%, 3.08%, and 0.05% were recommended to begin high-intensity, moderate-intensity, and low-intensity statins, respectively. With these recommendations, the LDL-C values at 1-year follow-up were predicted to be 21.5 ± 43.5 mg/dL (17.6%) lower per patient, on average (Figure). Conclusions: EMR-trained wKNN models are able to determine patient LDL-C trajectories under different lines of statin therapy. Machine learning models leveraging real-world datasets may provide useful statin therapy treatment recommendations for primary ASCVD prevention.
Phase II study evaluating the efficacy, safety, and pharmacodynamic correlative study of dual antiangiogenic inhibition using bevacizumab (B) in combination with sorafenib (S) in patients (pts) with advanced malignant melanoma.
Authors: D. Mahalingam, M. Beeram, J. Rodon, K. K. Sankhala, A. C. Mita, D. Benjamin, J. Michalek, A. W. Tolcher, J. J. Wright, J. Sarantopoulos
Journal: Journal of Clinical Oncology (2010)

e19008 Background: Melanomas are highly vascular tumors and are known to have high incidence of B-Raf mutations driving tumor proliferation. Inhibition of VEGF signaling at the ligand and receptor level has the potential for enhanced antitumor efficacy. This hypothesis was tested in a NCI-sponsored phase 2 trial of sorafenib (inhibitor of VEGFR and RAS/RAF/MEK/ERK) and bevacizumab in pts with advanced melanoma. Methods: Pts with measurable advanced melanoma, adequate organ function, PS 0-2, ≤ 2 prior therapies in the advanced setting were eligible; pts with active brain metastases were excluded. S at 200 mg BID days 1-5 q 7 days and B at 5 mg/kg q 14 days on a 28 day cycle. Dose reduction of S permitted, but no dose reduction of B. The primary objective of the study was to determine clinical biological activity (defined as CR + PR+ SD > 16 wks). Secondary objectives included safety, tolerability, median time to progression (TTP). Pharmacodynamic studies analyzing S-100β protein, circulating melanoma cells (CMC) and endothelial cells (CEC) of serum and plasma at baseline, C1D15 and C2D1. Results: Final ITT Stage 1 analysis, 14 patients with metastatic melanoma treated (median age 61 years [43-77]; 64% male). No RECIST responses were observed, although 6 (42.9%) patients had SD for more than > 16 weeks, 3 of these pts had SD ≥ 1 year, 5 (35.7%) had PD at or prior to 16 weeks (3/2), 3 unevaluable for tumor response. Median TTP was 18.6 months (95% CI 4.7-32.7 mo). The most frequently reported drug-related adverse events (AEs) were hand-foot skin reaction (HFS) 57.1%, rash 14.2%; fatigue 57.1%, anorexia 28.6%; hypertension (HTN) 64.3%; proteinuria 35.7%; nausea 14.2%, diarrhea 21.4%; bleeding 14.2%. Grade 3/4 drug-related AEs were HTN 14.2%, HFS 7%, proteinuria 7% and thrombocytopenia 7%. Dose reduction of S required in 6 (42.9%) patients (4 due to grade 2/3 HFS, 1 each for HTN and proteinuria). Conclusions: Combined VEGF/ VEGFR blockade employing S in combination with B was safe and tolerable. Although objective responses were not observed, 43% of the patients with advanced melanoma had clinical biological activity. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Chemotherapy Foundation Bayer, Genentech
Do exercise-based prevention programmes reduce non-contact musculoskeletal injuries in football (soccer)? A systematic review and meta-analysis with 13 355 athletes and more than 1 million exposure hours
Authors: Italo Ribeiro Lemes, Rafael Zambelli Pinto, Vitor N Lage, Bárbara A B Roch, Evert Verhagen, Caroline Bolling, Cecilia Ferreira Aquino, Sérgio T Fonseca, Thales R Souza
Journal: British Journal of Sports Medicine (2021)

Objective The aim of this systematic review was to investigate the effect of exercise-based programmes in the prevention of non-contact musculoskeletal injuries among football players in comparison to a control group. Design Systematic review and meta-analysis of randomised controlled trials. Data sources MEDLINE, EMBASE, CENTRAL, CINAHL, PEDro and SPORTDiscus databases were searched from the earliest record to January 2021. Eligibility criteria Studies were eligible if they (1) included football players aged 13 years or older, (2) used exercise-based programmes as intervention, (3) presented the number of non-contact musculoskeletal injuries (ie, defined as any acute sudden onset musculoskeletal injury that occurred without physical contact) and exposure hours for each group, and (4) had a control group (eg, usual training, minimal intervention, education). All types of exercise-based prevention programmes were eligible for inclusion. Risk of bias for each included study and overall quality of evidence for the meta-analysis were assessed. Results Ten original randomised controlled trials with 13 355 football players and 1 062 711 hours of exposure were selected. Pooled injury risk ratio showed very low-quality evidence that exercise-based prevention programmes reduced the risk of non-contact musculoskeletal injuries by 23% (0.77 (95% CI 0.61 to 0.97)) compared with a control group. Conclusion Exercise-based prevention programmes may reduce the risk of non-contact musculoskeletal injuries by 23% among football players. Future high-quality trials are still needed to clarify the role of exercise-based programmes in preventing non-contact musculoskeletal injuries among football players. PROSPERO registration number CRD42020173017.