tbuckley/cabot-search huggingface dataset:
Paid Parental Leave Policies Among <i>U.S. News &amp; World Report</i> 2020-2021 Best Hospitals and Best Hospitals for Cancer
Authors: Diana J. Lu, Benjamin King, Howard M. Sandler, Nancy J. Tarbell, Mitchell Kamrava, Katelyn M. Atkins
Journal: JAMA Network Open (2021)

This cross-sectional study examines paid parental leave policies for faculty and staff physicians at leading US hospitals and cancer centers.
Abstract 15290: 4D-flow MRI Intracardiac Flow Hemodynamic Patterns Can Phenotype Different Subtypes of Pulmonary Hypertension
Authors: Lexie K Ross, Alex J Barker, Benjamin S Frank, Kendall S Hunter, Gareth Morgan, Max B Mitchell, Dunbar D IVY, Brett E Fenster, Michal Shafer
Journal: Circulation (2020)

Introduction: Idiopathic Pulmonary Arterial Hypertension (PH-Type I) and PH due to pulmonary disease (PH-Type III) arise from different pathophysiologic processes, yet they both culminate in increased right ventricular (RV) afterload and eventual RV failure. Previous work has demonstrated that 4D-Flow MRI-derived intracardiac vorticity (ω) correlates with markers of ventricular interdependency and diastolic dysfunction in PH. However, no investigation has attempted to use both ω and standard markers of ventricular function to phenotype PH subgroups. Hypothesis: 4D-Flow MRI can detect differences in diastolic dysfunction that make it possible to phenotype patients with Type I and Type III PH. Methods: Type I PH patients (n=12, mean age 61yrs), Type III PH patients (n=15, mean age 63yrs), and healthy controls (n=10, mean age 58yrs) underwent standard cardiac MRI as well as 4D-Flow MRI to determine RV intracardiac flow markers including early (ω-E) and late (ω-A) diastolic vorticity. Standard MRI-based RV and LV size and function markers were also collected. Results: ω-E was decreased in the Type I PH group compared to the Type III PH group (P=0.035) and to controls (P&lt;0.001). There was no difference in ω-E between the Type III group and controls (P=0.216). RVEF was decreased in both the Type I (P&lt;0.001) and Type III (P=0.012) group compared to controls. There was no difference in RVEF between the Type I and Type III groups (P=0.917). RVEDV was increased in both the Type I (P=0.008) and Type III (P=0.006) groups compared to controls. No significant differences were noted between groups when assessing (ω-A) and other RV or LV standard volume and functional indices. Conclusion: Our results indicate that 4D-Flow MRI can distinguish among different PH subtypes using intracardiac diastolic vorticity. Comparative studies with standard echocardiography and catheterization are necessary to assess the sensitivity of 4D-Flow MRI to detect diastolic dysfunction.
Impact of lipid nanoparticle size on mRNA vaccine immunogenicity
Authors: Kimberly J. Hassett, Jaclyn Higgins, Angela Woods, Becca Levy, Yan Xia, Chiaowen Joyce Hsiao, Edward Acosta, Örn Almarsson, Melissa J. Moore, Luis A. Brito
Journal: Journal of Controlled Release (2021)

Lipid nanoparticles (LNP) are effective delivery vehicles for messenger RNA (mRNA) and have shown promise for vaccine applications. Yet there are no published reports detailing how LNP biophysical properties can impact vaccine performance. In our hands, a retrospective analysis of mRNA LNP vaccine in vivo studies revealed a relationship between LNP particle size and immunogenicity in mice using LNPs of various compositions. To further investigate this, we designed a series of studies to systematically change LNP particle size without altering lipid composition and evaluated biophysical properties and immunogenicity of the resulting LNPs. While small diameter LNPs were substantially less immunogenic in mice, all particle sizes tested yielded a robust immune response in non-human primates (NHP).
Abstract 14880: Single-cell Transcriptomes Identify Unique Endothelial Subpopulation (FABP4 <sup>+</sup> TMEM100 <sup>-</sup> ) With Lipid Metabolism Dysfunction in Pulmonary Arterial Hypertension
Authors: BIN LIU, Jingbo Dai, Li Shuai, Dan Yi, Youyang Zhao, Zhiyu Dai
Journal: Circulation (2020)

Introduction: Pulmonary arterial hypertension (PAH) is a disaster disease characterized by obliterative vascular remodeling and persistent increase of vascular resistance, leading to right heart failure and premature death. Understanding the cellular and molecular mechanisms will help develop novel therapeutic approaches for PAH patients. Hypothesis: We hypothesis that endothelial plasticity or distinct cell populations are critical for obstructive vascular remodeling in the pathogenesis of PAH. Methods: Here we applied single-cell RNA sequencing (ScRNA-seq) to profile the pulmonary cells in a severe mouse model ( Egln1 Tie2Cre mice) of PAH. Human hPAEC from idiopathic PAH patients and healthy donors were used to measure FABP4 and FABP5 expression. siRNA mediated knockdown of FABP4 and FABP5 was performed to study cell proliferation and apoptosis. Mice with Fabp4 and Fabp5 deletion ( Fabp45 -/- ) and wild type (WT) mice were incubated with hypoxia (10% O 2 ) to induced PAH. Egln1 Tie2Cre mice were bred with Fabp45 -/- mice to generate Egln1 Tie2Cre / Fabp45 -/- mice. Results: We identified five distinct EC subpopulations in both WT and Egln1 Tie2Cre mice via scRNA-seq. Unexpectedly, the number of Cluster (EC2, 49.8%) was markedly increased in Egln1 Tie2Cre lung compared with WT lung (2.8%). EC2 cluster (mainly from Egln1 Tie2Cre lung) was characterized by little expression of Tmem100 , Cldn5 , Tspan7 , Calcrl and Foxf1 and high expression of Fabp4, Cdh13, Sparl1 and Fabp5 . Fatty acid-binding protein (FABP) 4 and FABP5 (FABP4-5) were highly induced in PAECs from IPAH patients. Knockdown of FABP4-5 reduced EC proliferation and starvation-induced Caspase 3/7 activity. Fabp45 -/- mice were protected from hypoxia-induced PAH compared to WT mice. Moreover, Egln1 Tie2Cre / Fabp45 -/- mice also exhibited a reduction of RVSP and RV hypertrophy compared to Egln1 Tie2Cre mice. Conclusions: ScRNA-seq analysis identifies a unique endothelial population (FABP4 + TMEM100 - ) highly enriched in the lung of severe PAH mice. Knockdown of FABP4-5 reduces EC proliferation starvation-induced injury. Genetic deletion of FABP4-5 protects from hypoxia and Egln1 deficiency-induced PAH in mice.
Abstract 13424: Demographic and Echocardiographic Predictors of Later-onset Cardiac Variant of Fabry Disease Among Chinese Patients With Left Ventricular Hypertrophy
Authors: Tsz Ngai Chan, Josie Tsz ying Chow, Kevin Ka Ho Kam, Bun Sheng, YITING FAN, Ka Tak Wong, Tong Mei Po Mabel, Paul CL Choi, Erik Fung, Joseph YS Chan, Wai Kin Chi, Alex Pui-Wai Lee
Journal: Circulation (2020)

Introduction: The genetic mutation IVS4+919G&gt;A commonly found among Chinese is associated with later-onset cardiac variant of Fabry disease (FD). Patients with left ventricular hypertrophy (LVH) may be screened for FD by measuring plasma α-galactosidase activity. Objective: The aim of our study is to determine the prevalence of FD among Chinese LVH patients and to define demographic and echocardiographic predictors of FD. Methods: We measured plasma α-galactosidase activity using dried blood spot test in 500 Hong Kong Chinese patients with LVH (defined as maximal left ventricular septal or posterior wall thickness ≥13 mm on transthoracic echocardiography). LVH and deficiency in α-galactosidase activity prompted genetic analysis of galactosidase alpha gene. Demographic and echocardiographic predictors of FD were analysed. Results: There are 9 (1.8%) of 500 LVH patients (all men, age 53–74 years) had low α-galactosidase activity (0.64±0.32 μmol/L wb/hr) and all were confirmed to have the FD genotype IVS4+919G&gt;A. Among these 9 FD patients, 6 (66.7%) could be traced to the ancestral home Chaozhou (southern part of China), 4 had hypertension, but none exhibited extracardiac manifestations of FD. The left ventricular mass of FD patients ranged from 64.91–811.81 g. Ancestral home Chaozhou (odds ratio, 10.28; 95% confidence Interval, 2.52–41.94; p=0.001) and LVM ≥290 g (odds ratio, 7.39; 95% confidence Interval, 1.94–28.20; p=0.003) were predictors of FD. On receiver operating characteristic curve analysis, sensitivity and specificity of LVM ≥290 g to diagnose FD vs non-FD LVH are 67% and 86.4% respectively (area under curve, 0.8; p=0.002). Conclusion: There is a high prevalence of later-onset cardiac variant FD among Hong Kong Chinese LVH patients that is associated with IVS4+919G&gt;A genotype. Male patients with ancestral home Chaozhou and LVM ≥290 g are at an increased risk of FD among Chinese LVH patients and should be screened with dried blood spot test.
Abstract 15117: The Catheter Uncertainty Principle: Does the Presence of a Catheter Alter Hemodynamics?
Authors: Michael Kaplan, Madhurima Vardhan, Amanda RANDLES
Journal: Circulation (2020)

Introduction: Catheters are an essential component of measuring invasive hemodynamic quantities. However, by the very nature of a catheter's presence, it acts to disturb the normal flow field, potentially altering measured pressures and derived quantities, such as FFR. Computational fluid dynamic simulations are performed to explore how vessel lumenal area and catheter size effect pressures. Methods: Patient-specific anatomical reconstructions are coupled with HARVEY, a massively parallel lattice-Boltzmann fluid solver, to calculate 3D blood flow around simulated catheters. We explore the effects of catheter size in vessels ranging from 5 mm in diameter, a right ventricle to pulmonary artery shunt (RVPAS) in a patient with HLHS, and smaller, in coronary arteries. Pressures sampled at the location corresponding to the distal end of the catheter are compared and FFR is calculated for the coronary models. Results: Figure 1A illustrates the calculated pressure waveforms for simulated catheter sizes in a RVPAS. In this case, the catheter does not significantly alter the pressure field unless unrealistically large catheters, such as a 13 Fr, are used. For adult coronary arteries (Figure 1B), reasonable catheter sizes result in appreciable decreases in sampled pressures and, consequently, in calculated FFR (Figure 1C). Conclusion: The presence of a sufficiently large catheter (&gt;50% of the vessel lumenal area) causes a noticeable decrease in the pressures at the tip of the catheter. While unlikely to occur in larger vessels, this can occur during left heart catheterizations of diseased coronary arteries. This causes an artificial decrease in FFR, which can potentially alter clinical decision making. While catheters are the gold standard for pressure measurements, an improved understanding of the inherent sensitivity of their measurements to unobstructed vessel lumenal area is important for interpreting the results of catheter-based diagnostic procedures.
CD4 <sup>+</sup> T cells are essential for the development of destructive thyroiditis induced by anti–PD-1 antibody in thyroglobulin-immunized mice
Authors: Yoshinori Yasuda, Shintaro Iwama, Daisuke Sugiyama, Takayuki Okuji, Tomoko Kobayashi, Masaaki Ito, Norio Okada, Atsushi Enomoto, Sachiko Ito, Yue Yan, Mariko Sugiyama, Takeshi Onoue, Taku Tsunekawa, Yoshihiro Ito, Hiroshi Takagi, Daisuke Hagiwara, Motomitsu Goto, Hidetaka Suga, Ryoichi Banno, Masahide Takahashi, Hiroyoshi Nishikawa, Hiroshi Arima
Journal: Science Translational Medicine (2021)

CD4 + T cells are essential for development of thyroiditis induced by anti–PD-1 antibody treatment in thyroglobulin-immunized mice.
Long non-coding RNAs in brain tumors: roles and potential as therapeutic targets
Authors: Sung-Hyun Kim, Key-Hwan Lim, Sumin Yang, Jae-Yeol Joo
Journal: Journal of Hematology & Oncology (2021)

Abstract Brain tumors are associated with adverse outcomes despite improvements in radiation therapy, chemotherapy, and photodynamic therapy. However, treatment approaches are evolving, and new biological phenomena are being explored to identify the appropriate treatment of brain tumors. Long non-coding RNAs (lncRNAs), a type of non-coding RNA longer than 200 nucleotides, regulate gene expression at the transcriptional, post-transcriptional, and epigenetic levels and are involved in a variety of biological functions. Recent studies on lncRNAs have revealed their aberrant expression in various cancers, with distinct expression patterns associated with their instrumental roles in cancer. Abnormal expression of lncRNAs has also been identified in brain tumors. Here, we review the potential roles of lncRNAs and their biological functions in the context of brain tumors. We also summarize the current understanding of the molecular mechanisms and signaling pathways related to lncRNAs that may guide clinical trials for brain tumor therapy.
Abstract 17019: Obesity and Cardiovascular Health in Young American Adults
Authors: Sarabjeet S Suri, Vibhu Parcha, Rajat Kalra, Garima Arora, Pankaj Arora
Journal: Circulation (2020)

Background: The growing epidemic of obesity in the United States (US) is associated with cardiovascular (CV) morbidity and mortality. We evaluated the impact of the increasing obesity prevalence on the CV health of young American adults. Methods: The age-adjusted weighted prevalence of hypertension, diabetes, and hypercholesterolemia was estimated from the 2008-2018 National Health and Nutrition Examination Survey (NHANES) in American adults aged 18-44 years, stratified by the presence of obesity. The trends were evaluated using a piecewise linear regression approach. The odds for CV risk factors were estimated using multivariable-adjusted logistic regression models. Results: Among 14,919 young adults, the prevalence of obesity was 33.9% (95% CI: 32.6-35.3%). Obese young adults were more likely to be non-Hispanic Blacks and in lower socioeconomic and educational attainment strata (p&lt;0.05 for all). Obese young adults had a greater risk of having hypertension (adjusted odds ratio [aOR]: 3.0 [95% CI: 2.7-3.4]), diabetes (aOR: 4.3 [95% CI: 3.3-5.6]), and hyperlipidemia (aOR: 1.47 [95% CI: 1.3-1.7]). Among obese, hypertension increased from 36.5% (33.9-39.1%) in 2007-2010 to 39.4% (35.6-43.1%) in 2015-2018 (p= 0.07) and diabetes increased from 4.7% (3.6-5.8%) in 2007-2010 to 7.1% (5.3-9.0%) in 2015-2018 (p=0.11). A modest increase in diabetes was seen in non-obese individuals ( Table ). Hypercholesterolemia prevalence remained unchanged from 12.6% (95% CI: 10.6-14.7%) 2007-2010 to 10.9% (95% CI: 9.0-12.8%) in 2015-2018 (p=0.27) among obese young adults. Non-obese young adults showed a decline in hypercholesterolemia from 9.5% (95% CI: 8.0-11.0%) in 2007- 2010 to 7.1% (95% CI: 5.8-8.4%) in 2015-2018 (p=0.002). Conclusions: Nearly one-in-every three young American adults have obesity, which is accompanied by a two-fold higher prevalence of CV risk factors. The CV morbidity in young adults is expected to increase with an increasing prevalence of obesity..
Abstract P049: Diabetes And The Risk Of Hospitalization With Infection
Authors: Michael Fang, Junichi Ishigami, Justin Echouffo-Tcheugui, Pamela L Lutsey, James S Pankow, Elizabeth Selvin
Journal: Circulation (2021)

Introduction: Mechanistic research suggests that diabetes may increase susceptibility to infection. However, few epidemiologic studies have examined this association. Hypothesis: We hypothesize that adults with diabetes will have a higher risk for infection compared to those without diabetes. Methods: We conducted a prospective cohort analysis of diabetes and incident hospitalization with infection using data from the Atherosclerosis Risk in Communities (ARIC) Study. We used Cox regression models with adjustments for demographics, health behaviors, and cardiometabolic and kidney functioning measures. Diabetes status at baseline (1987-1989) was defined as a fasting glucose ≥126 mg/dL or non-fasting glucose ≥200 mg/dL, or self-report of a diagnosis of diabetes, or current diabetes medication use. First hospitalization with any infection and specific types of infections (respiratory, urinary, foot, sepsis, and postoperative wound) were ascertained from ICD-9 codes in hospital discharge records, with follow-up to September 30, 2015. Results: We included 13,356 participants (mean age, 55; 26% black; 54% female). During a median follow-up of 18.8 years, there were 7,791 incident hospitalizations with infection. Compared to those without diabetes at baseline, those with diabetes had a greater risk for hospitalization with any infection (adjusted HR: 1.55 [95% CI: 1.45-1.66], Table ). Results were generally consistent across infection type, and differences were especially pronounced for foot infections (adjusted HR: 6.35 [95% CI: 5.27-7.64]). Conclusion: The COVID-19 pandemic has heightened interest in the link between diabetes and susceptibility to infection. Our study suggests diabetes confers significant risk for infection. Enhancing diabetes prevention and management may reduce infection-related morbidity and mortality.
Different Clinical and Angiographic Outcomes between Paclitaxel- and Everolimus-Eluting Stent Implantation for Patients with Hemodialysis
Authors: Makino Nobuhiko, Nishino Masami, Nushiro Yu, Masuyama Kiyoshi, Idemoto Akiko, Kato Taishi, Ishino Ayano, Onishi Hiroyuki, Sakatani Akiya, Tanaka Akihiro, Mori Naoki, Yoshimura Takahiro, Nakamura Daisuke, Taniike Masayuki, Egami Yasuyuki, Shutta Ryu, Morita Hisaki, Tanouchi Jun
Journal: Circulation (2014)
Abstract 15295: Clinical Characteristics, Treatment Patterns, and Short-term Outcomes in Patients With Isolated Distal Deep Vein Thrombosis
Authors: Cesar Caraballo, Behnood Bikdeli, Javier Trujillo-Santos, Jean-Philippe Galanaud, Pierpaolo di Micco, Vladimir Rosa, Gemma Vidal-Cusidó, Sebastian Schellong, Meritxell Mellado, Maria del Valle Morales, Olga Gavin, Harlan M Krumholz, Manuel Monreal
Journal: Circulation (2020)

Background: Isolated distal deep vein thrombosis (IDDVT) is a common form of venous thromboembolism (VTE). Limited data exist about the clinical characteristics, initial treatment, and short-term outcomes of these patients. Methods: Using the data from the RIETE registry (05/2001-02/2019), we identified patients with IDDVT without pulmonary embolism (PE). We determined the clinical presentation, initial treatment, and 30-day and 90-day outcomes. We compared the findings with patients with proximal DVT without PE. Results: We identified 5,359 patients with IDDVT (mean age 61±17 years, 50% women). The most prevalent comorbidities were hypertension (39%), anemia (28%), prior VTE (14%), active cancer (12%), heart failure (6.7%), and diabetes (6.6%). Recent surgery was reported in 16%. Most participants received anticoagulation (99%), most commonly with low-molecular-weight heparin (88%). No patient received thrombolytics and use of vena cava filters was rare (0.4%). At 30 days, 59 patients (1.1% [99% CI, 0.8%-1.5%]) died, including only 3 from PE (0.1% [99% CI, 0.01%-0.2%]), 44 (0.8% [99% CI, 0.5%-1.2%]) had nonfatal VTE recurrence, and 31 (0.6% [99% CI, 0.4%-0.9%]) had major bleeding. At 90 days, 2.9% (99% CI, 2.4%-3.6%) died (no additional death from PE), 1.5% (99% CI, 1.1%-2.0%) had nonfatal VTE recurrence, and 0.9% (99% CI, 0.6%-1.3%) had major bleeding. When compared with 25,420 individuals with proximal DVT without PE, those with IDDVT had lower co-morbidity burden including diabetes, heart failure, and cancer, but were more likely to have had recent surgery (P&lt;0.001 for all). Patients with IDDVT also had lower odds of 30-day and 90-day death and major bleeding in bivariate and multivariable analyses (Figure). Conclusions: In a large multinational study, IDDVT occurred in patients with low comorbidity burden. Most patients with IDDVT received anticoagulation. Fatal PE was rare, and patients had a more benign prognosis compared with those with proximal DVT.
간세포암종 환자의 5년 생존율 -단일기관의 904명 코호트 연구
Authors: 박경우, Joong-Won Park, 김태현, 최준일, 김성훈, Hong Suk Park, 박상재, 이우진, Shin Hai Rim, 김창민
Journal: Clinical and Molecular Hepatology (2007)

목적: 간세포암종은 국내 암 발생 등록분율 3위를 차지하고 예후 또한 매우 불량한 암종으로, 현재까지 국내 간세포암종 코호트를 대상으로 한 5년 생존율 보고는 없는 실정이다. 이에 연구자들은 국내 단일 기관에서 진단 및 치료된 간세포암종 코호트에서 병기, 간기능 및 치료법에 따른 5년 생존율을 구하고 예후인자를 조사하였다. 대상과 방법: 2000년 11월부터 2003년 11월부터 2003년 12월까지 국립암센터에서 간세포암종으로 진단 및 치료받은 904명을 2007년 2월까지 추적하여, 치료법에 따른 생존율을 구하고, 예후인자를 조사하였다. 결과: 904명의 평균 연령은 56세였고 남자가 80.9%였다. 전체 환자의 1년, 3년, 5년 생존율은 각각 54.0%, 31.3%, 23.9%였으며, modified 5th UICC 병기에 따른 5년 생존율은 I, II, III, IVa에서 각각 61.2%, 54.4%, 18.4%, 4.1%였으며, IVb군의 중앙생존기간은 3.7개월에 불과하였다. Modified 5th UICC 병기 I, II군과 IVa, IVb군 간에 생존율의 차이가 없었다. Child-Pugh 분류의 각 등급간에는 뚜렷한 생존율의 차이가 있었다. Modified 5th UICC 병기 I,II군에서 Child-Pugh 분류 A등급인 경우 수술 절제술 군과 경동맥화학색전술군 사이에 5년 생존율의 차이가 있었으며(80.1% vs 52.8%, p<.001), III군에서 더욱 큰 차이를 보였다(60.7% vs 17.0%, p< .001). Child-Pugh 분류 A등급인 경우 병기 IVa군에서 경동맥화학색전술군은 전신항암화학요법군에 비해 생존율이 높았으나(중앙생존기간 6.9 vs 4.0개월, p<.001), 병기 IVb군에서는 경동맥화학색전술, 전신항암화학요법, 차이가 없고(중앙생존기간 각각 8.6, 6.2, 6.5개월) 보존 치료군(중앙생존기간 2.6개월)에 비해 세 치료군 모두 유의하게 생존율이 높았다. 간세포암종 환자의 예후에 영향을 미치는 독립적 예후인자는 Child-Pugh 분류, modified 5th UICC 병기 분류, 문맥혈전증 여부 및 혈청 알파태아단백치로 3년 생존 분석 결과와 같았고, 여기에 종양 형태와 내 원 당시 증상이 포함되었다. 결론: 국내 단일기관 의 간세포암종 코호트의 5년 생존율과 독립적 예 후인자를 처음으로 구하였다.
19P A dichotomous oncogenic role of the splicing factor SF3A3 in MYC-driven triple-negative breast cancer
Authors: A. Bosch, M. Cieśla, P. Cao Thi Ngoc, S. Mutukumar, G. Honeth, J. Staaf, D. Incarnato, K. Pietras, C. Bellodi
Journal: Annals of Oncology (2021)
Covid-19: Why prioritising prevention matters in a pandemic of cures
Authors: Kamran Abbasi
Journal: BMJ (2021)

Covid-19: Why prioritising prevention matters in a pandemic of cures Kamran Abbasi executive editorPrevention is better than cure.Simple.Clear.Logical.Except that it is easily overcomplicated, clouded, and misplaced.When we forget that prevention is better than cure, primary care becomes an easy scapegoat, even though the pandemic has reinforced its importance in improving baseline population health, reducing health inequalities, delivering a vaccination strategy, and keeping people out of hospital.17