tbuckley/cabot-search huggingface dataset:
Abstract 11234: The Impact of Median Yearly Income on Structural Heart Disease Procedural Outcomes
Authors: Helena Dickens, Manoj Ambalavanan, Aamir Twing, Elliott Groves, Dhairya Jarsania, Sanket Gokhale, Nicole Cho, Brody D Slostad, Mayank Kansal, Adhir R Shroff
Journal: Circulation (2021)

Introduction: The association of socioeconomic status with health outcomes is well known. This study used zip codes as a surrogate for income and compared outcomes post-procedure and at 6 and 12 months following TAVR at an urban hospital. Methods: We performed a retrospective study on patients undergoing TAVR at the University of Illinois-Chicago(UIC) in Chicago, Illinois between March 2018 and June 2020. Using income data from the US Census Bureau, patients were placed into 2 groups: zip codes with a median income less than the national urban mean income of $54,296 (LMI) and greater than the average urban mean yearly income (GMI).Primary outcomes included composite MACE (CV death, MI and/or CVA), length of stay, and all-cause death. Secondary outcomes included CHF exacerbation, and repeat revascularization. Outcomes were analyzed at hospital discharge, 6 months and 12 months. T and Chi square tests were used to analyze continuous/categorical variables, respectively. Results: We analyzed 114 patients, 84 patients were categorized as LMI and 30 patients were categorized as GMI. 94.3% of the LMI group was Black, while only 62% of the GMI group was Black. Age and gender distributions were similar between groups. Initial post procedural outcomes showed no statistical difference between the LMI and GMI. The LMI group trended towards a longer length of stay than the GMI group (p=0.1). A history of heart failure was greater in the LMI group (p = 0.025). At 6 months there was a lower repeat revascularization rate in the LMI group compared to the GMI group (0% vs. 1.8%, p = 0.017). However, other outcomes including composite MACE (9.6% vs. 1.8%, p=0.3) and all cause death (6.1% vs. 0.9%p=0.4) were statistically similar. At 12 months only 112 patients had recorded outcomes. At this time, repeat revascularization was still significantly different (0% vs. 2.6%, p = 0.005) but all other outcomes remained nonsignificant. Results: Post TAVR, patients in the GMI group experienced a higher rate of repeat coronary revascularization as compared to the LMI group, although, the composite event rate was similar. Further investigation into this observation is warranted; however, overall outcomes between patients from poorer communities seems to be similar to wealthier communities.
Evaluation of mRNA-1273 SARS-CoV-2 Vaccine in Adolescents
Authors: Kashif Ali, Gary Berman, Honghong Zhou, Weiping Deng, Veronica Faughnan, Maria Coronado-Voges, Baoyu Ding, Jacqueline Dooley, Bethany Girard, William Hillebrand, Rolando Pajon, Jacqueline M. Miller, Brett Leav, Roderick McPhee
Journal: New England Journal of Medicine (2021)

BackgroundThe incidence of coronavirus disease 2019 (Covid-19) among adolescents between 12 and 17 years of age was approximately 900 per 100,000 population from April 1 through June 11, 2021. The safety, immunogenicity, and efficacy of the mRNA-1273 vaccine in adolescents are unknown.MethodsIn this ongoing phase 2–3, placebo-controlled trial, we randomly assigned healthy adolescents (12 to 17 years of age) in a 2:1 ratio to receive two injections of the mRNA-1273 vaccine (100 μg in each) or placebo, administered 28 days apart. The primary objectives were evaluation of the safety of mRNA-1273 in adolescents and the noninferiority of the immune response in adolescents as compared with that in young adults (18 to 25 years of age) in a phase 3 trial. Secondary objectives included the efficacy of mRNA-1273 in preventing Covid-19 or asymptomatic severe acute respiratory syndrome coronavirus 2 infection.ResultsA total of 3732 participants were randomly assigned to receive mRNA-1273 (2489 participants) or placebo (1243 participants). In the mRNA-1273 group, the most common solicited adverse reactions after the first or second injections were injection-site pain (in 93.1% and 92.4%, respectively), headache (in 44.6% and 70.2%, respectively), and fatigue (in 47.9% and 67.8%, respectively); in the placebo group, the most common solicited adverse reactions after the first or second injections were injection-site pain (in 34.8% or 30.3%, respectively), headache (in 38.5% and 30.2%, respectively), and fatigue (in 36.6% and 28.9%, respectively). No serious adverse events related to mRNA-1273 or placebo were noted. The geometric mean titer ratio of pseudovirus neutralizing antibody titers in adolescents relative to young adults was 1.08 (95% confidence interval [CI], 0.94 to 1.24), and the absolute difference in serologic response was 0.2 percentage points (95% CI, −1.8 to 2.4), which met the noninferiority criterion. No cases of Covid-19 with an onset of 14 days after the second injection were reported in the mRNA-1273 group, and four cases occurred in the placebo group.ConclusionsThe mRNA-1273 vaccine had an acceptable safety profile in adolescents. The immune response was similar to that in young adults, and the vaccine was efficacious in preventing Covid-19. (Funded by Moderna and the Biomedical Advanced Research and Development Authority; Teen COVE ClinicalTrials.gov number, NCT04649151.) Visual Abstract Evaluation of mRNA-1273 SARS-CoV-2 Vaccine in Adolescents
Abstract P181: The Genetic Epidemiology Of Longitudinal Blood Pressure Traits From Adolescence To Early Adulthood In Latinos
Authors: Samson Okello, Daaeun Kim, Aylin Memili, Mohammad Yaser, Heather Highland, Mariaelisa Graff, Nora Franceschini, Kari E North
Journal: Circulation (2022)

Introduction: Blood pressure (BP) is known to rise during developmental stages from childhood to adulthood, and that those with higher BP trajectories are more likely to develop hypertension and CVD. Yet, there is a paucity of studies that have evaluated trajectories of BP change or the genetic factors involved in the BP changes from childhood to adulthood. Epidemiological and genetic epidemiological studies of longitudinal BP changes through the life-course may enable a better understanding of the pathogenesis of hypertension and may lead to the identification of loci associated with BP trajectories and CVD risk during this critical period. Methods: We leverage multiple self-identified Hispanic/Latino populations with longitudinal BP and genomic data across the lifecourse, in particular between adolescence and young adulthood. We present herein preliminary results from the Santiago longitudinal study (SLS) that enrolled infants of Hispanic ancestry and measured BP at late adolescence (average age of 16 years) and early adulthood (average age of 22 years) to identify genetic variants associated with trajectories of BP traits (systolic BP, diastolic BP, mean arterial pressure and pulse pressure). We conducted a complete case analysis excluding participants taking antihypertensive medications and those whose BP measures were statistical outliers. Linear mixed models were used to assess the trajectories of individual BP traits between late adolescence and early adulthood (n = 1236), adjusting for age, sex and BMI. We assessed the relationship between residuals and genetic variants adjusting for two ancestral principal components using SUGEN software. Results: Males constituted 51% of the total SLS cohort. Interestingly, with each year increase in age, we observed downward trajectories of both mean systolic BP (-0.3 mmHg, 95% CI (-0.4, -0.2)) and mean diastolic BP (-0.1 mmHg, 95% CI (-0.2, -0.04)) adjusted for BMI and sex. We identified evidence for five known BP loci and two suggestive new signals. Our most significant finding is rs10894989 [beta (SE) = 6.57 (1.26), p =1.86x10 -7 , minor allele frequency (EAF = 0.94)] near the ARHGAP42 gene, an established locus for hypertension. However, this variant is not in linkage disequilibrium with the commonly reported SNP rs604723 (r 2 = 0.04). Ancestry-specific allele frequencies differed with rs604723 more common in East Asians and Europeans and rs10894989 commonest in Africans. Conclusion: Our longitudinal analyses of BP from late adolescence to early adulthood replicated BP loci and identified novel suggestive loci associated with BP trajectories supporting a need for further GWAS of longitudinal BP. We are currently conducting a meta-analysis of longitudinal BP trajectories in 3,000 young adults self-identified as Hispanic Latino in the Population Architecture using Genomics and Epidemiology (PAGE) study.
Transmission dynamics of COVID-19 in household and community settings in the United Kingdom, January to March 2020
Authors: Jamie Lopez Bernal, Nikolaos Panagiotopoulos, Chloe Byers, Tatiana Garcia Vilaplana, Nicki Boddington, Xu-Sheng Zhang, Andre Charlett, Suzanne Elgohari, Laura Coughlan, Rosie Whillock, Sophie Logan, Hikaru Bolt, Mary Sinnathamby, Louise Letley, Pauline MacDonald, Roberto Vivancos, Obaghe Edeghere, Charlotte Anderson, Karthik Paranthaman, Simon Cottrell, Jim McMenamin, Maria Zambon, Gavin Dabrera, Mary Ramsay, Vanessa Saliba
Journal: Eurosurveillance (2022)

BackgroundHouseholds appear to be the highest risk setting for COVID-19 transmission. Large household transmission studies in the early stages of the pandemic in Asia reported secondary attack rates ranging from 5 to 30%.AimWe aimed to investigate the transmission dynamics of COVID-19 in household and community settings in the UK.MethodsA prospective case-ascertained study design based on the World Health Organization FFX protocol was undertaken in the UK following the detection of the first case in late January 2020. Household contacts of cases were followed using enhanced surveillance forms to establish whether they developed symptoms of COVID-19, became confirmed cases and their outcomes. We estimated household secondary attack rates (SAR), serial intervals and individual and household basic reproduction numbers. The incubation period was estimated using known point source exposures that resulted in secondary cases.ResultsWe included 233 households with two or more people with 472 contacts. The overall household SAR was 37% (95% CI: 31-43%) with a mean serial interval of 4.67 days, an R0 of 1.85 and a household reproduction number of 2.33. SAR were lower in larger households and highest when the primary case was younger than 18 years. We estimated a mean incubation period of around 4.5 days.ConclusionsRates of COVID-19 household transmission were high in the UK for ages above and under 18 years, emphasising the need for preventative measures in this setting. This study highlights the importance of the FFX protocol in providing early insights on transmission dynamics.
Is the neuroscientist's grandmother in the notebook? Integrated information and reference frames in the search for consciousness
Authors: Giuseppe Riva
Journal: Behavioral and Brain Sciences (2022)

Abstract This commentary suggests that the physical substrate of integrated information is dependent on the reference frame used to observe it. Furthermore, it uses a thought experiment – can a neuroscientist, locked in a closed room and connected through Zoom with his grandmother to demonstrate that the consciousness of his grannie is NOT in the PC? – to underline the problems that neglecting reference frames may cause to consciousness research.
Abstract EP40: Effects Of Ketone Salt Supplementation On Blood Pressure In Adults Diagnosed With Post-traumatic Stress Disorder
Authors: Angelia M Holland-Winkler, Jordan Locklin, Andrew Moore
Journal: Circulation (2022)

Individuals diagnosed with post-traumatic stress disorder (PTSD) are often in a state of hyperarousal due to overactive sympathetic nervous system activity. This in turn causes resting blood pressure to increase which leads to chronic hypertension. Those diagnosed with PTSD are at an increased risk for developing hypertension and cardiovascular disease. Beta-hydroxybutyrate, a ketone body, has been shown to directly inhibit sympathetic drive at the receptor site. Beta-hydroxybutyrate is both a fuel source and signaling molecule that is produced by the liver from partially broken-down fat. In addition to endogenous sources, beta-hydroxybutyrate can be paired with salt and consumed exogenously. Exogenous ketone salt supplementation has been shown to decrease systolic blood pressure (SBP) in healthy populations. Therefore, the primary purpose of this study was to determine if supplementing with ketone salts for 6-weeks altered SBP or diastolic blood pressure (DBP) in adults diagnosed with PTSD compared to a placebo supplement. This clinical trial included a randomized, double-blinded, parallel-arm and placebo-controlled design. Participants included males and females previously diagnosed with PTSD that were between the ages of 21-65 years. Sixteen participants completed the study; nine consumed ketone salts for six-weeks and seven consumed the placebo supplement. Thirteen subjects were included in the analyses due to incomplete data. Blood pressure was measured in a fasted and rested state immediately before and after the six-week supplementation period. Two 2X2 mixed ANOVAs were used to analyze the SBP and DBP between group and time points. Although the ketone supplementation group experienced an average lowering of SBP (6.14 mmHg) and DBP (4 mmHg) following the supplementation period, no significant interaction was found for SBP, F (1, 11) = 1.18, p = .30, η 2 = .10, or DBP, F (1, 11) = 1.24, p = .29, η 2 = .10. The results demonstrated that 6-weeks of ketone salt supplementation did not significantly alter SBP or DBP in this population. However, the sample size for this study was small and thus, this study should be repeated in a larger sample for verification of this finding.
Inflammatory cytokine–regulated tRNA-derived fragment tRF-21 suppresses pancreatic ductal adenocarcinoma progression
Authors: Ling Pan, Xudong Huang, Ze-Xian Liu, Ying Ye, Rui Li, Jialiang Zhang, Guandi Wu, Ruihong Bai, Lisha Zhuang, Lusheng Wei, Mei Li, Yanfen Zheng, Jiachun Su, Junge Deng, Shuang Deng, Lingxing Zeng, Shaoping Zhang, Chen Wu, Xu Che, Chengfeng Wang, Rufu Chen, Dongxin Lin, Jian Zheng
Journal: Journal of Clinical Investigation (2021)

The tumorigenic mechanism for pancreatic ductal adenocarcinoma (PDAC) is not clear, although chronic inflammation is implicated. Here, we identified an inflammatory cytokine–regulated transfer RNA–derived (tRNA-derived) fragment, tRF-21-VBY9PYKHD (tRF-21), as a tumor suppressor in PDAC progression. We found that the biogenesis of tRF-21 could be inhibited by leukemia inhibitory factor and IL-6 via the splicing factor SRSF5. Reduced tRF-21 promoted AKT2/1-mediated heterogeneous nuclear ribonucleoprotein L (hnRNP L) phosphorylation, enhancing hnRNP L to interact with dead-box helicase 17 (DDX17) to form an alternative splicing complex. The provoked hnRNP L-DDX17 activity preferentially spliced Caspase 9 and mH2A1 pre-mRNAs to form Caspase 9b and mH2A1.2, promoting PDAC cell malignant phenotypes. The tRF-21 levels were significantly lower in PDACs than in normal tissues, and patients with low tRF-21 levels had a poor prognosis. Treatment of mouse PDAC xenografts or patient-derived xenografts (PDXs) with tRF-21 mimics repressed tumor growth and metastasis. These results demonstrate that tRF-21 has a tumor-suppressive effect and is a potential therapeutic agent for PDAC.
Governance of Emerging Technologies in Health and Medicine — Creating a New Framework
Authors: Debra J.H. Mathews, Celynne A. Balatbat, Victor J. Dzau
Journal: New England Journal of Medicine (2022)

In the face of a rapidly changing technology landscape, the National Academy of Medicine has formed the Committee on Emerging Science, Technology, and Innovation in health and medicine to convene diverse stakeholders to reenvision governance in health and medicine and drive collective action.
Claudin-5 binder enhances focused ultrasound-mediated opening in an <i>in vitro</i> blood-brain barrier model
Authors: Liyu Chen, Ratneswary Sutharsan, Jonathan LF Lee, Esteban Cruz, Blaise Asnicar, Tishila Palliyaguru, Joanna M Wasielewska, Arnaud Gaudin, Jae Song, Gerhard Leinenga, Jürgen Götz
Journal: Theranostics (2022)

Rationale:The blood-brain barrier (BBB) while functioning as a gatekeeper of the brain, impedes cerebral drug delivery.An emerging technology to overcome this limitation is focused ultrasound (FUS).When FUS interacts with intravenously injected microbubbles (FUS +MB ), the BBB opens, transiently allowing the access of therapeutic agents into the brain.However, the ultrasound parameters need to be tightly tuned: when the acoustic pressure is too low there is no opening, and when it is too high, tissue damage can occur.We therefore asked whether barrier permeability can be increased by combining FUS +MB with a second modality such that in a clinical setting lower acoustic pressures could be used.Methods: Given that FUS +MB achieves BBB opening in part by disruption of tight junction (TJ) proteins such as claudin-5 of brain endothelial cells, we generated a stable MDCK (Madin-Darby Canine Kidney) II cell line (eGFP-hCldn5-MDCK II) that expresses fluorescently tagged human claudin-5.Two claudin-5 binders, the peptide mC5C2 and cCPEm (truncated form of an enterotoxin), reported previously to weaken the barrier, were synthesized and assessed for their abilities to enhance the permeability of cellular monolayers.We then performed a comparative analysis of single and combination treatments, measuring transendothelial electrical resistance (TEER) and cargo leakage, combined with confocal image analysis.Results: We successfully generated a novel cell line that formed functional monolayers as validated by an increased TEER reading and a low (< 0.2%) permeability to sodium fluorescein (376 Da).We found that the binders exerted a time-and concentration-dependent effect on barrier opening when incubated over an extended period, whereas FUS +MB caused a rapid opening followed by recovery after 12 hours within the tested pressure range.Importantly, preincubation with cCPEm prior to FUS +MB treatment resulted in greater barrier opening compared to either FUS +MB or cCPEm alone as measured by reduced TEER values and an increased permeability to fluorescently labelled 40 kDa dextran (FD40). Conclusion:The data suggest that pre incubation with clinically suitable binders to TJ proteins may be a general strategy to facilitate safer and more effective ultrasound-mediated BBB opening in cellular and animal systems and potentially also for the treatment of human diseases of the brain.
Abstract P017: Development And Validation Of A Body Composition-based Prediction Model For Cardiovascular Outcomes Among Older Adults
Authors: Chenkai Wu, Lihui Chen, Xinran Wang
Journal: Circulation (2022)

Background: Cardiovascular disease (CVD) has long been a leading cause of death in the world and a major public health concern. Precise stratification of cardiovascular risk is critically important to deliver person-centered treatment decisions. Several risk prediction models of CVD have been developed, mainly focusing on demographics, healthy lifestyles, and blood-based biomarkers (mostly lipids). Recent evidence suggests that components of body composition are associated with the risk of CVD. However, it remains unknown whether the use of body composition data could improve the performance of a well-established CVD prediction model. Objectives: We aimed to derive and validate a model for predicting the risk of incident CVD based on body composition assessed by the Dual-energy X-ray absorptiometry (DXA) among older black and white adults. Methods: Participants were 1,994 adults initially free of CVD from the Health, Aging, and Body Composition Study. We developed and validated a model for risk of myocardial infarction, stroke, heart failure, and cardiovascular death over 10 years based on body composition data. We used the LASSO and stepwise backward elimination for variable selection of body composition data in the Cox model. Weibull accelerated failure time model was used to obtain the risk score. We compared the model performance (goodness-of-fit, discrimination, and calibration) between the body composition model and the Framingham model, in which sex, age, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, diabetes, and smoking were included. We also examined whether the inclusion of body composition data in the Framingham model could improve model performance. Results: The average age was 73.0 years (SD=2.8 years); 1,118 (56.1%) were females and 802 (41.3%) were black. A total of 8 body composition variables were retained after variable selection (8-DXA model). The C statistics were 0.608 and 0.616 for the 8-DXA model and the Framingham model, respectively. The 8-DXA plus Framingham model significantly improved the C-statistic by 0.026 (95% CI: 0.011, 0.042). When compared with the Framingham model, the 8-DXA plus Framingham model had an integrated discrimination index of 0.016 (95% CI: 0.009, 0.023) indicating an absolute increase of 12% in average risk for participants with events compared with those without. the 8-DXA plus Framingham model had a net reclassification index (NRI) of 0.167 (95% CI: 0.008, 0.259), with event-specific NRI of 0.018 (95% CI: -0.063, 0.094) and no event-specific NRI of 0.149 (95% CI: 0.098, 0.205). Conclusion: Among older adults free of CVD, the inclusion of body composition data assessed by DXA could moderately improve the prediction performance of a well-established CVD prediction model. Future research is needed to validate the usefulness of body composition data in predicting the risk of CVD in other cohorts.
Accelerating progress on early childhood development for children under 5 years with disabilities by 2030
Authors: Bolajoko O. Olusanya, Nem Yun Boo, M.K.C. Nair, Maureen E. Samms-Vaughan, Mijna Hadders-Algra, Scott M. Wright, Cecilia Breinbauer, Nihad Almasri, Marisol Moreno-Angarita, Jalal Arabloo, Narendra K. Arora, Sandra S. Block, Brad D. Berman, Gwen Burchell, Olaf Kraus de Camargo, Gwen Carr, Christie del Castillo-Hegyi, Vivian G. Cheung, Ricardo Halpern, Rosa Hoekstra, Paul Lynch, Mphelekedzeni C. Mulaudzi, Angelina Kakooza-Mwesige, Felix A. Ogbo, Jacob O. Olusanya, Valeria Rojas-Osorio, Amira Shaheen, Andrew N. Williams, Chiara Servili, Melissa Gladstone, Hannah Kuper, Donald Wertlieb, Adrian C. Davis, Charles R.J.C. Newton
Journal: The Lancet Global Health (2022)

The likelihood of a newborn child dying before their fifth birthday (under-5 mortality rate) is universally acknowledged as a reflection of the social, economic, health, and environmental conditions in which children (and the rest of society) live, but little is known about the likelihood of a newborn child having a lifelong disability before their fifth birthday if he or she survives. Available data show that globally the likelihood of a child having a disability before their fifth birthday was ten times higher than the likelihood of dying (377·2 vs 38·2 per 1000 livebirths) in 2019. However, disability funding declined by 11·4% between 2007 and 2016, and only 2% of the estimated US$79·1 billion invested in early childhood development during this period was spent on disabilities. This funding pattern has not improved since 2016. This paper highlights the urgent need to prioritise early childhood development for the beneficiaries of global child survival initiatives who have lifelong disabilities, especially in low-income and middle-income countries, as envisioned by the Sustainable Development Goals agenda. This endeavour would entail disability-focused programming and monitoring approaches, economic analysis of interventions services, and substantial funding to redress the present inequalities among this cohort of children by 2030.