tbuckley/cabot-search huggingface dataset:
Abstract 15595: Missed Targets: United States Trends in Hypertension Prevalence, Control, and Treatment 2005-2018
Authors: Rahul Aggarwal, Nicholas Chiu, Rishi Wadhera, Changyu Shen, Robert W Yeh, Dhruv Kazi
Journal: Circulation (2020)

Introduction: Hypertension is a major risk factor for cardiovascular disease. The US government, through the Healthy People Initiative 2020, set targets to improve hypertension prevalence and treatment rates in US adults by a relative 10% from 2005 to 2020, and increase control rates by a relative 40%. We examined US progress towards this goal from 2005-2018. Methods: We analyzed data from 38,876 non-pregnant US adults from the NHANES 2005-2018 surveys to determine nationally representative estimates of hypertension prevalence, treatment rates, and control. Temporal trends in hypertension prevalence, treatment, and control were assessed using weighted linear regression after age adjustment to the 2000 US census (per the Healthy People Initiative approach). In the base case, we defined hypertension as blood pressure &gt;140/90 or on an antihypertensive; we used the ACC/AHA definition of blood pressure &gt;130/80 in sensitivity analyses. Results: In 2017-2018, 34.3% (±1.7) of US adults had hypertension, of these 69.7% (±1.5) were on treatment, and 43.7% (±1.6) were controlled. After age-adjustment, no statistically significant changes in hypertension prevalence, treatment rates, or control were observed from 2005-2018 (p for trend 0.91, ,0.98, 0.66, Figure 1). In sensitivity analyses, applying the ACC/AHA definition increased the estimated prevalence of hypertension during the period, but trends in prevalence remained unchanged. Conclusions: There has been no material progress in reducing the prevalence of hypertension or improving rates of treatment and control from 2005 to 2018. As planning is underway for Healthy People Initiative 2030, setting of hypertension targets must be accompanied with investments in cost-effective, scalable programs to improve blood pressure control nationwide, with a focus on high-risk populations.
GSH-sensitive polymeric prodrug: Synthesis and loading with photosensitizers as nanoscale chemo-photodynamic anti-cancer nanomedicine
Authors: Lei Luo, Yiming Qi, Hong Zhong, Shinan Jiang, Hu Zhang, Hao Cai, Yahui Wu, Zhongwei Gu, Qiyong Gong, Kui Luo
Journal: Acta Pharmaceutica Sinica B (2021)

Precisely delivering combinational therapeutic agents has become a crucial challenge for anti-tumor treatment. In this study, a novel redox-responsive polymeric prodrug (molecular weight, MW: 93.5 kDa) was produced by reversible addition-fragmentation chain transfer (RAFT) polymerization. The amphiphilic block polymer-doxorubicin (DOX) prodrug was employed to deliver a hydrophobic photosensitizer (PS), chlorin e6 (Ce6), and the as-prepared nanoscale system [NPs(Ce6)] was investigated as a chemo-photodynamic anti-cancer agent. The glutathione (GSH)-cleavable disulfide bond was inserted into the backbone of the polymer for biodegradation inside tumor cells, and DOX conjugated onto the polymer with a disulfide bond was successfully released intracellularly. NPs(Ce6) released DOX and Ce6 with their original molecular structures and degraded into segments with low MWs of 41.2 kDa in the presence of GSH. NPs(Ce6) showed a chemo-photodynamic therapeutic effect to kill 4T1 murine breast cancer cells, which was confirmed from a collapsed cell morphology, a lifted level in the intracellular reactive oxygen species, a reduced viability and induced apoptosis. Moreover, ex vivo fluorescence images indicated that NPs(Ce6) retained in the tumor, and exhibited a remarkable in vivo anticancer efficacy. The combinational therapy showed a significantly increased tumor growth inhibition (TGI, 58.53%). Therefore, the redox-responsive, amphiphilic block polymeric prodrug could have a great potential as a chemo-photodynamic anti-cancer agent.
Abstract 14781: Computational Prediction of Protein Subdomain Stability as a Novel Approach to Cardiac Myosin Binding ProteinC Variant Adjudication and Clinical Risk Stratification in Hypertrophic Cardiomyopathy
Authors: Andrea D Thompson, Adam S Helms, Anamika Kannan, Jaime Yob, Neal K Lakdawala, Samuel Wittekind, Alexandre D Pereira, Daniel L Jacoby, Steven D Colan, Sara Saberi, James S Ware, Jodie Ingles, Christopher Semsarian, Michelle Michels, Francesco Mazzarotto, iacopo olivotto, Carolyn Ho, Sharlene Day
Journal: Circulation (2020)

Introduction: Patients with HCM and a pathogenic sarcomere variant have a higher risk of adverse clinical outcomes compared to those without a sarcomere gene variant. Pathogenic truncating variants in MYBPC3 (encoding cardiac myosin binding protein C, MYBP-C) cause loss-of-function and are the most common genetic cause of HCM. However, a substantial number of patients carry missense variants in MYBPC3 that cannot be clearly classified as either pathogenic or benign. Interpretation of these variants of uncertain significance (VUS) remain a significant challenge. Hypothesis: We hypothesize that a structural-based algorithm, STRUM, which estimates the effect of missense variants on subdomain protein folding, will enable clinical risk stratification of patients with HCM and a MYBPC3 VUS. Methods and Results: Among the 7,963 patients in the multi-center Sarcomeric Human Cardiomyopathy Registry (SHaRe), 19 unique missense pathogenic variants and 120 missense VUSs in MYBPC3 were identified. Within SHaRe and GnomAD, 110 benign missense variants (allele frequency &gt; 4e-05) were identified. Following structural modeling of each MyBP-C domain, variants were predicted to cause subdomain misfolding if ΔΔG &lt; = -1.2 kcal/mol (STRUM+). 93% of benign variants were predicted to be STRUM (-). Time-event analysis for an overall composite clinical endpoint [defined as the first occurrence of ventricular arrhythmia, heart failure, all-cause mortality, atrial fibrillation (AF), or stroke] demonstrated that patients carrying a STRUM+ MYBPC3 VUS exhibited a higher rate of adverse events compared to those with a STRUM- VUS (Hazard Ratio=2.29, P=0.0282). Of the 120 missense VUSs, 34 (28%) were STRUM+. In silico saturation mutagenesis of MYBPC3 identified 4,943/23,427 (21%) missense variants predicted to cause subdomain misfolding. Conclusions: STRUM is capable of clinically risk stratifying HCM patients with a MYBPC3 VUSs . These findings support the routine use of STRUM in variant interpretation algorithms and clinical decision making.
The Bone Marrow Niche Uses Mir-300 As a Biological Rheostat to Selectively Control Stem Cell-Driven Malignant Hematopoiesis and Innate Anti-Cancer Immunity
Authors: Giovannino Silvestri, Lorenzo Stramucci, Justin Ellis, Jason Harb, Paolo Neviani, Bin Zhang, Klara Srutova, Carlo Gambacorti-Passerini, Gabriel Pineda, Catriona Jamieson, Bruno Calabretta, Fabio Stagno, Paolo Vigneri, G. Nteliopoulos, Philippa May, Alistair Reid, Ramiro Garzon, Denis-Claude Roy, Martin Guimond, Peter Hokland, Michael W. Deininger, Garrett Fitzgerald, Chris Harman, Francesco Dazzi, Dragana Milojkovic, Jane F. Apperley, Guido Marcucci, Jianfei Qi, Kateřina Machová Poláková, Xiaoxuan Fan, Maria R. Baer, Rossana Trotta, Danilo Perrotti
Journal: Blood (2017)
Cationic Tricyclic AIEgens for Concomitant Bacterial Discrimination and Inhibition
Authors: Bingnan Wang, Haozhong Wu, Rong Hu, Xiaolin Liu, Zhiyang Liu, Zhiming Wang, Anjun Qin, Ben Zhong Tang
Journal: Advanced Healthcare Materials (2021)

Abstract New ionic compounds with aggregation‐induced emission (AIE) feature has been widely studied. These AIE‐based luminogens (AIEgens) not only effectively resolve aggregation‐caused quenching (ACQ) problems that are encountered for most of conventional fluorescent dyes, but also exhibit promising applications in biological imaging, potentially for a wide variety of diseases. However, such an AIE system needs to be further developed. In this work, a series of novel cationic AIEgens that are comprised of tricyclic 2‐aminopyridinium derivatives with seven‐membered rings are designed and synthesized via a simple, multicomponent reaction. Notably, these AIEgens exhibit the ability to specifically stain gram‐positive bacteria. Moreover, a specific AIEgen, BMTAP‐7, possesses highly efficient bacteriostatic ability for Staphylococcus aureus ( S. aureus ) in both liquid medium and solid agar plates, which have a minimum inhibitory concentration (MIC) between 4 and 8 µg mL −1 . Using live‐cell imaging and a wash‐free process, it is observed that hydrophilic AIEgens are localized to mitochondria, whereas lipophilic AIEgens display specific staining of lysosomes. These AIEgens with bacteriostatic activity hold great promise for distinguishing between bacterial types and inhibiting bacterial infections in situ.
Digital CRISPR-based method for the rapid detection and absolute quantification of nucleic acids
Authors: Xiaolin Wu, Joshua K. Tay, Chuan Keng Goh, Cheryl Chan, Yie Hou Lee, Stacy L. Springs, De Yun Wang, Kwok Seng Loh, Timothy K. Lu, Hanry Yu
Journal: Biomaterials (2021)
Abstract 009: Incremental Predictive Utility Of Subclinical Disease Measures For Cardiovascular Disease Risk
Authors: Rebecca J Song, Vasan S Ramachandran, Vanessa Xanthakis
Journal: Circulation (2021)

Introduction: The Framingham Risk Score (FRS) has been widely used to predict cardiovascular disease (CVD) risk. However, a comparison of the incremental prognostic utility of different subclinical disease (SubDz) measures is not clear. Methods: We evaluated participants aged 40-79 years (mean age 55 years, 56% women) from the Framingham Offspring (Exam 8, 2005-2008) and Third Generation cohorts (Exam 1, 2002-2005), free of CVD and diabetes, with data on coronary artery calcium (CAC, n=2497), and two measures of target organ damage: urine albumin-to-creatinine ratio (UACR, n=4011) and left ventricular mass (LVM, n=3770). We categorized FRS: &lt;10%, 10-19%, and ≥20% and defined high CAC as CAC≥100, microalbuminuria (MA) as UACR ≥25mg/g in men and ≥35mg/g in women, and left ventricular hypertrophy (LVH) as LVM/body surface area&gt;115 g/m 2 (men) and &gt;95g/m 2 (women). We created 6 cross-classified groups: FRS &lt;10%-No SubDz; FRS &lt;10% + SubDz; FRS 10-19%-No SubDz; FRS 10-19% + SubDz; FRS ≥20%-No SubDz; and FRS ≥20% + SubDz. We related the groups to CVD risk using Cox regression adjusting for age, sex, and cohort and plotted Kaplan-Meier curves to display CVD cumulative incidence by each SubDz cross-classified group. Results: Over a median follow-up of 12 years, 7% of participants developed CVD. Comparing FRS 10-19%-No SubDz and FRS 10-19% + SubDz to FRS &lt;10%-No SubDz (referent), we observed hazards ratios (95% CI) for CVD of 1.68 (0.99-2.83) and 6.50 (3.64-11.61) for high CAC; 1.33 (0.95-1.85) and 2.15 (1.10-4.18) for MA; and 1.43 (0.99-2.07) and 2.18 (1.33-3.57) for LVH. Each SubDz measure predicted CVD risk incrementally over the FRS. In a sub-sample with all three SubDz measures, the model c-statistic with FRS only was 0.725, increasing to 0.773, 0.726, and 0.728 when adding CAC, MA, and LVH, respectively. Conclusion: Presence of a high CAC score outperformed other measures of target organ damage (MA or LVH) for predicting CVD risk, regardless of FRS. Additional studies of larger multi-ethnic samples are warranted to confirm our findings.
Neurodegenerative diseases: a hotbed for splicing defects and the potential therapies
Authors: Dunhui Li, Craig Stewart McIntosh, Frank Louis Mastaglia, Steve Donald Wilton, May Thandar Aung-Htut
Journal: Translational Neurodegeneration (2021)

Abstract Precursor messenger RNA (pre-mRNA) splicing is a fundamental step in eukaryotic gene expression that systematically removes non-coding regions (introns) and ligates coding regions (exons) into a continuous message (mature mRNA). This process is highly regulated and can be highly flexible through a process known as alternative splicing, which allows for several transcripts to arise from a single gene, thereby greatly increasing genetic plasticity and the diversity of proteome. Alternative splicing is particularly prevalent in neuronal cells, where the splicing patterns are continuously changing to maintain cellular homeostasis and promote neurogenesis, migration and synaptic function. The continuous changes in splicing patterns and a high demand on many cis- and trans- splicing factors contribute to the susceptibility of neuronal tissues to splicing defects. The resultant neurodegenerative diseases are a large group of disorders defined by a gradual loss of neurons and a progressive impairment in neuronal function. Several of the most common neurodegenerative diseases involve some form of splicing defect(s), such as Alzheimer’s disease, Parkinson’s disease and spinal muscular atrophy. Our growing understanding of RNA splicing has led to the explosion of research in the field of splice-switching antisense oligonucleotide therapeutics. Here we review our current understanding of the effects alternative splicing has on neuronal differentiation, neuronal migration, synaptic maturation and regulation, as well as the impact on neurodegenerative diseases. We will also review the current landscape of splice-switching antisense oligonucleotides as a therapeutic strategy for a number of common neurodegenerative disorders.
Abstract P197: Household And Neighborhood Context As Contributors To Racial Disparities In Sleep Among Adolescents
Authors: Ryan Saelee, Regine Haardörfer, Dayna A Johnson, Julie A Gazmararian, Shakira F Suglia
Journal: Circulation (2021)

Background: Short sleep duration (e.g., &lt;9 hours (hrs) for 6-12 years and &lt;8 hrs for 13-18 years) is highly prevalent and associated with cardiometabolic risk among adolescents. Significant racial disparities in sleep duration among adolescents have been found. Investigating mechanisms driving sleep disparities is important for informing interventions to reduce disparities. Neighborhood and household stressors may contribute to racial disparities in sleep among adolescents as prior literature have found them to be patterned by race/ethnicity and associated with sleep duration. This study examined neighborhood and household context as mediators in the association between race/ethnicity (a proxy for sociocultural factors such as racism) and sleep duration among adolescents. Methods: Participants (n=13,019) were from Waves I and II of the National Longitudinal Study of Adolescent to Adult Health, a nationally representative multi-ethnic sample of adolescents and their health in adulthood. Sleep duration was self-reported in whole hours per day and categorized based on age-specific cut-offs for short sleep (6-12 years: &lt;9 hrs, 13-18 years: &lt;8 hrs, 19-25 years: &lt;7 hrs) vs. recommended (6-13 years: 9-11 hrs, 14-17 years: 8-10 hrs, 18-25 years: 7-9 hrs). Neighborhood factors included neighborhood socioeconomic status (SES) (e.g. census tract measures: proportions of female-headed households, individuals below the poverty threshold, individuals receiving public assistance, adults with &lt; high school education, and adults unemployed), perceived safety and social cohesion. Household factors included living in a single parent household and household SES (e.g. highest parental education, income, and occupation). Structural equation modeling (SEM) was used to simultaneously assess mediation of neighborhood and household context in the association between race/ethnicity and short sleep duration adjusting for age and sex. Results: The sample was 4% Asian, 15% African American (AA), 2% American Indian (AI), 12% Hispanic, and 66% non-Hispanic White (NHW) and mean age 15 years (SD=.1). In SEM, AAs (β=.055, p&lt;.001) and Asians (β=.047, p=.047) were more likely to have short sleep duration than NHW. Higher household SES was associated with a greater probability for short sleep duration (β=.061, p=.004) in the total sample. Only household SES was a significant mediator, explaining 11.6%, 9.9%, and 42.4% of AA-NHW, AI-NHW, and Hispanic-NHW differences, respectively. Conclusion: Although household SES partially explained racial disparities, improving household SES conditions for racial/ethnic minority adolescents may not reduce disparities, given that higher household SES was positively associated with short sleep duration. Future studies should explore buffers for racial/ethnic minority adolescents in the context of SES to inform interventions and reduce disparities in sleep.
Identification of IRF-1-binding protein, which could interfere anti-oncogenic function of IRF-1 and is overexpressed in hematological malignancies.
Authors: Kondo T, Tanaka N, Minamino N, Inouenagamura T, Suzuki S, Kurosawa M, Okabe M, Taniguchi T, Asaka M
Journal: Blood (1996)
Abstract 002: Assessing Profiles Of Cardiometabolic Risk Among South Asians Living In The United States Using A Syndemic Framework And Acculturation
Authors: Francisco A Montiel Ishino, Katia M Canenguez, Jeffrey H Cohen, Belinda Needham, Namratha Kandula, Faustine Williams, Alexandra E Shields, Alka M Kanaya
Journal: Circulation (2021)

Background: South Asians (SA) are the second largest US immigrant group and have excess cardiometabolic (CM) disease. While acculturation is associated with increased CM risk among immigrants and refugees, the role of acculturation on SA CM risk is relatively unknown. CM disease presents as a syndemic or synergistic epidemic involving multiple disease clusters as well as the biological, social, and psychological interactions from the acculturative process to worsen morbidity within subgroups. Methods: We used latent class analysis to identify SA CM risk based on acculturation subgroups using data from adults aged 40-84 in the Mediators of Atherosclerosis in South Asians Living in America study (N=771). The distal outcome of CM risk was constructed using hypertension, type 2 diabetes, and body mass index. Proxies of acculturation included years lived in the US, English proficiency, cuisine eaten at home, cultural traditions, ethnicity of friends, social and neighborhood support, and experienced discrimination; as well as mental health indicators, which included depression, trait anxiety, anger, and positive and negative spiritual coping. Covariates included demographic characteristics, family income, education, study site, exercise, smoking, alcohol use, religiosity and spirituality. Results: Four CM risk profiles and acculturation subgroups were identified: 1) lowest risk [73.8%] were the most integrated with both SA and US culture; 2) intermediate-low risk [13.4%] had high mental health distress and discrimination and separated from SA and US culture; 3) intermediate-high risk [8.9%] were more assimilated with US culture; and 4) highest risk [3.9%] were more assimilated with US culture [Figure]. Conclusion: Our approach identified distinct nuanced profiles of syndemic CM risk to understand how acculturation and sociocultural factors cluster with health in US South Asians. Our syndemic framework will further understanding of CM risk among SA to best design tailored prevention and intervention programs.
VP3-2021: A randomized phase II study of second-line osimertinib (Osi) and bevacizumab (Bev) versus Osi in advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) and T790M mutations (mt): Results from the ETOP BOOSTER trial
Authors: R. Soo, J-Y. Han, G. Dimopoulou, B.C. Cho, C.M. Yeo, E. Nadal, E. Carcereny, J. de Castro, M.A. Sala, R. Bernabe, L. Coate, M. Provencio, R. Garcia Campelo, S. Cuffe, S. Hashemi, M. Früh, B. Ruepp, H. Roschitzki-Voser, R. Stahel, S. Peters
Journal: Annals of Oncology (2021)
Abstract 17031: Incidence of Life-Threatening Events in Children With Wolff-Parkinson-White Syndrome
Authors: Christopher M Janson, Marisa E Millenson, Dingwei Dai, Reina Bianca Tan, V. Ramesh Iyer, Victoria L Vetter, R. Lee Vogel, Maully J Shah, Michael L O’Byrne
Journal: Circulation (2018)

Introduction: Life-threatening events (LTE) in patients with Wolff-Parkinson-White Syndrome (WPW) are rare, with considerable variation in published rates. Existing data on LTE incidence represent selected populations or tertiary referral-based cohorts. Access to large observational datasets allows, for the first time, measurement of the risk of LTE in an unselected, contemporary WPW population. Methods: A retrospective cohort study was conducted using administrative claims from Truven Health Analytics (MarketScan ® ) to identify all WPW patients (aged ≤18 years) from both inpatient and outpatient encounters between January 2013 and December 2016. Prevalence of WPW was measured. A composite outcome, LTE, was defined as an episode that included ventricular fibrillation or cardiac arrest. Secondary outcomes included diagnoses of atrial fibrillation (AF) and supraventricular tachycardia (SVT). Factors associated with LTE were evaluated by creating multivariable models. Results: The prevalence of WPW in the study population was 0.025% (4,717/18,884,579). Subjects with WPW were 57% male, had a median age of 13 yrs (IQR 7-16 yrs), with coincident Ebstein’s anomaly in 1.9%, other congenital heart disease (CHD) in 12%, and cardiomyopathy (CM) in 2%. Over the study period, SVT was reported in 20.3% (n=957/4,717), and AF in 1.3% (n=61/4,717) of subjects. Patients with AF were 79% male (n=48/61), with median age 16 yrs (IQR 14-17 yrs), with CHD in 25% (n=15/61) and CM in 7% (n=4/61). LTE occurred in 23 subjects: 70% male (n=16/23), at median age 16 yrs (IQR 7-17 yrs), with CHD in 9% (n=2/23) and CM in 13% (n=3/23); AF was reported in 3 patients with LTE. The incidence of LTE was 1.4 events per 1000 person years of follow up (23/16,514). In a multivariate model including age, gender, CHD, and CM, the only independent predictor of LTE was CM (OR 10.2, 95% CI 2.4-31.1, p&lt;0.001). Conclusions: Use of a large claims dataset allowed for evaluation of LTE risk in an unselected pediatric WPW population. This WPW-related LTE estimate of 1.4/1000 person years can serve as a benchmark for assessment of risk reduction interventions on a population level. Incidence of LTE in this unselected contemporary cohort is consistent with observed rates in prior reports from selected populations.
SARS-CoV-2 exacerbates proinflammatory responses in myeloid cells through C-type lectin receptors and Tweety family member 2
Authors: Qiao Lu, Jia Liu, Shuai Zhao, Maria Florencia Gomez Castro, Maudry Laurent-Rolle, Jianbo Dong, Xiaojuan Ran, Payal Damani-Yokota, Hongzhen Tang, Triantafyllia Karakousi, Juhee Son, Maria E. Kaczmarek, Ze Zhang, Stephen T. Yeung, Broc T. McCune, Rita E. Chen, Fei Tang, Xianwen Ren, Xufeng Chen, Jack C.C. Hsu, Marianna Teplova, Betty Huang, Haijing Deng, Zhilin Long, Tenny Mudianto, Shumin Jin, Peng Lin, Jasper Du, Ruochen Zang, Tina Tianjiao Su, Alberto Herrera, Ming Zhou, Renhong Yan, Jia Cui, James Zhu, Qiang Zhou, Tao Wang, Jianzhu Ma, Sergei B. Koralov, Zemin Zhang, Iannis Aifantis, Leopoldo N. Segal, Michael S. Diamond, Kamal M. Khanna, Kenneth A. Stapleford, Peter Cresswell, Yue Liu, Siyuan Ding, Qi Xie, Jun Wang
Journal: Immunity (2021)