tbuckley/cabot-search huggingface dataset:
Abstract 14879: Heart Failure With Preserved Ejection Fraction Patients Do Not Augment Longitudinal Pumping During Exercise
Authors: James P Macnamara, Kevin Tayon, William K Cornwell, Erin Howden, Michinari Hieda, JUstin Lawley, Benjamin D LEVINE, Satyam Sarma
Journal: Circulation (2020)

Introduction: Left ventricular (LV) pumping from longitudinal motion is highly efficient and a major contributor to stroke volume (SV). Patients with heart failure with preserved ejection fraction (HFpEF) have diminished longitudinal ventricular motion but the effect on LV pumping is unknown. This study aimed to determine the contribution of longitudinal pumping in HFpEF compared to healthy age-matched controls at rest and submaximal exercise when exercise induced SV reserve is maximal. Methods: Cardiopulmonary exercise testing with concurrent 3D echocardiography was performed in 30 subjects (HFpEF n = 20, age 69±5 years, Senior Control (CON): n = 10, age 70±4 years) at rest and during exercise at a targeted heart rate of 100 bpm (HFpEF 66±18% VO 2 Max, CON: 49±13% VO 2 Max, p = 0.014). LV volumes and mitral annular excursion (MAE), a novel metric of systolic function, were measured using multi-beat 3D acquisition at rest and during sub-maximal exercise. MAE volume (MAEV) was measured by multiplying MAE by short axis area at the base of the ventricle. Relative longitudinal pumping was calculated as the quotient of MAEV and SV (%). Results: Mitral annular excursion (MAE) at rest was lower in HFpEF (Figure) and increased significantly less during sub-maximal exercise compared to controls (CON Δ3.3mm vs HFpEF Δ1.1mm, group p = 0.002, group x exercise p = 0.011). MAEV was similar in HFpEF compared to controls at reest but did not augment in HFpEF compared to controls (CON Δ7.1 ml vs HFpEF Δ1.9 ml, group x exercise p = 0.002). Relative longitudinal pumping increased significantly with exercise in CON but remained unchanged in HFpEF (CON Δ7.9% vs HFpEF Δ-0.7%, group x exercise p = 0.043). Conclusions: Longitudinal pumping does not increase in HFpEF patients despite exercising at a higher relative metabolic demand than their healthy peers. This lack of longitudinal pumping reserve may contribute to and help identify cardiac limitations during exercise commonly seen in HFpEF patients.
Multimodality Intravascular Imaging of High-Risk Coronary Plaque
Authors: Jiawen Li, Nicholas J. Montarello, Ayla Hoogendoorn, Johan W. Verjans, Christina A. Bursill, Karlheinz Peter, Stephen J. Nicholls, Robert A. McLaughlin, Peter J. Psaltis
Journal: JACC. Cardiovascular imaging (2021)
ASSOCIATION BETWEEN BASELINE CARDIOVASCULAR RISK AND SLEEP DURATION IN AMBULATORY US ADULTS: INSIGHTS FROM THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY
Authors: Kartik Gupta, Shivaraj Nagalli, Rajat Kalra, Wunan Zhou, Rishab Gupta, Sumanth Prabhu, Navkaranbir Bajaj
Journal: Journal of the American College of Cardiology (2021)
Nanotechnology: Breaking the Current Treatment Limits of Lung Cancer
Authors: Shilin Li, Shanshan Xu, Xiaoyu Liang, Yueguang Xue, Jie Mei, Yongfu Ma, Yang Liu, Ying Liu
Journal: Advanced Healthcare Materials (2021)

Abstract Lung cancer is one of the most rapidly growing malignancies in terms of morbidity and mortality. Although traditional treatments have been used for more than 50 years, it is still far from solving the problems of postoperative risks and systemic toxicity. Emerging targeting and immunotherapy are developing continuously and are gaining recognition; eventually, they face the inevitable challenge of drug resistance. Nanotechnology has several important effects on lung cancer treatment, owing to its unique properties. Several nanoparticle‐based treatments have successfully become cancer treatments. Good biocompatibility with higher specific surface area can carry substantial amounts of lung cancer treatment medications while avoiding medication toxicity; editable and modified characteristics give rise to multifunctional nanomedicines; excellent photoelectric effects make lung cancer a multimodal treatment. This article summarizes the breakthroughs achieved by nanotechnology, targeted therapy, and immunotherapy, reflecting the importance and necessity of nanotechnology in the treatment of lung cancer.
食物探索の持続的調節は迷走神経介在ドーパミンニューロン活性に依存する【JST・京大機械翻訳】
Authors: B Fernandes Ana, Alves da Silva Joaquim, Almeida Joana, Cui Guohong, R Gerfen Charles, M Costa Rui, J Oliveira-Maia Albino
Journal: Neuron (2020)
Bifunctional iRGD-anti-CD3 enhances antitumor potency of T cells by facilitating tumor infiltration and T-cell activation
Authors: Shujuan Zhou, Fanyan Meng, Shiyao Du, Hanqing Qian, Naiqing Ding, Huizi Sha, Mei Zhu, Xiaoxiao Yu, Lifeng Wang, Baorui Liu, Jia Wei
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Poor infiltration and limited activation of transferred T cells are fundamental factors impeding the development of adoptive cell immunotherapy in solid tumors. A tumor-penetrating peptide iRGD has been widely used to deliver drugs deep into tumor tissues. CD3-targeting bispecific antibodies represent a promising immunotherapy which recruits and activates T cells. Methods T-cell penetration was demonstrated in tumor spheroids using confocal microscope, and in xenografted tumors by histology and in vivo real-time fluorescence imaging. Activation and cytotoxicity of T cells were assessed by flow cytometry and confocal microscope. Bioluminescence imaging was used to evaluate in vivo antitumor effects, and transmission electron microscopy was used for mechanistic studies. Results We generated a novel bifunctional agent iRGD-anti-CD3 which could immobilize iRGD on the surface of T cells through CD3 engaging. We found that iRGD-anti-CD3 modification not only facilitated T-cell infiltration in 3D tumor spheroids and xenografted tumor nodules but also induced T-cell activation and cytotoxicity against target cancer cells. T cells modified with iRGD-anti-CD3 significantly inhibited tumor growth and prolonged survival in several xenograft mouse models, which was further enhanced by the combination of programmed cell death protein 1 (PD-1) blockade. Mechanistic studies revealed that iRGD-anti-CD3 initiated a transport pathway called vesiculovacuolar organelles in the endothelial cytoplasm to promote T-cell extravasation. Conclusion Altogether, we show that iRGD-anti-CD3 modification is an innovative and bifunctional strategy to overcome major bottlenecks in adoptive cell therapy. Moreover, we demonstrate that combination with PD-1 blockade can further improve antitumor efficacy of iRGD-anti-CD3-modified T cells.
Abstract 12640: Energy Drinks Prolong Early Repolarization (J-T <sub>Peak</sub> ) Phase in a Healthy Population
Authors: Samuel R Kaplan, Ghufran Syed, Teri Kozik
Journal: Circulation (2020)

Introduction: Energy drinks continue to be the fastest growing beverage market with sales expected to reach $60 billion in the next few years, yet have demonstrated adverse cardiovascular effects such as prolongation of the QTc interval on EKG. While QTc prolongation observed with certain drugs has long been used as an indicator of increased risk of torsade de pointes, recent data has identified the early repolarization interval J-T peak (JTp) as a more specific marker for proarrhythmic potential. Drugs that selectively block the human ether-a-go-go related (hERG) potassium ion channel prolong QTc by prolonging both early repolarization (JTp) and late repolarization (T peak -T end [Tpe] interval), and are associated with an increased risk of torsade. In contrast, drugs that additionally block inward late sodium and L-type calcium prolong QTc by prolonging Tpe but not JTp, and have demonstrated reduced risk of torsade. In 2018, the C-Energy-X study demonstrated QTc prolongation in 22 healthy subjects (mean age 28 ± 7yrs) who consumed energy drink while at rest and following short periods of exercise. Our study provides a secondary analysis of this data in terms of its effect on JTp, a potentially more specific marker for torsade risk. Methods: Using H-Scribe software, two evaluators independently measured JTp and RR intervals from C-Energy-X subjects pre- and post-energy drink consumption in the rest and exercise phases. Values were corrected for heart rate using the linear correction formula JTpc=JTp + 0.150(1-RR), where RR is R-to-R interval. Mean JTpc values from each phase were analyzed using a paired sample two-tailed t -test. Results: In the resting phase following energy drink consumption (PCr), there was a statistically significant increase in JTpc intervals for 77% of subjects by a mean of 10.5ms (baseline=234 ± 21.3ms; PCr=245 ± 22.0ms; p =0.015). In the exercise phase following energy drink consumption (PCe), 64% of subjects increased JTpc intervals by a mean of 0.8ms which was not significant (baseline=225 ± 15.7ms; PCe=226 ± 17.9ms; p =0.845). Conclusion: In the resting phase, energy drink consumption was associated with statistically significant prolongation of JTpc, suggesting a theoretical increased risk of torsade de pointes.
Abstract 16946: Radial versus Femoral Access for Coronary Procedures in Patients With Prior Coronary Artery Bypass Grafting Surgery: An Updated Study-Level Meta-Analysis
Authors: Ilias Nikolakopoulos, Evangelia Vemmou, Iosif Xenogiannis, Judit Karacsonyi, Bavana V Rangan, Sunil V Rao, Khaldoon Alaswad, Grigorios Tsigkas, Milkas Anastasios, Steven M Bradley, Mario Goessl, Yale Wang, Ivan Chavez, Santiago Garcia, M. Nicholas Burke, Emmanouil S Brilakis
Journal: Circulation (2020)

Introduction: The preferred access site for cardiac catheterization in patients with prior coronary artery bypass surgery (CABG) continues to be debated. Methods: We performed a systematic review and meta-analysis of two randomized trials and eighteen observational studies, including 58,237 patients with prior CABG (27,063 in the radial group; 31,174 in the femoral group) that underwent cardiac catheterization with or without intervention. Outcomes included (1) access-site complications rate; (2) crossover rate to a different vascular access; (3) procedure time; and (4) contrast volume. Data were extracted by two independent authors; using a random effects model, standardized mean differences (SMD) and 95% confidence interval (CI) were calculated for continuous outcomes, whereas odds ratio (OR) and 95% CI were calculated for binary outcomes. Results: Among randomized trials, the crossover rate (OR:12.63; 95% CI: 1.57,101.62; p=0.021) was higher in the radial group, while contrast volume (SMD: 0.15; 95% CI: -0.52, 0.82, p=0.66), procedure time (SMD: 0.49; 95% CI: -0.64, 1.62, p=0.4) and the incidence of access site complications (OR:1.21; 95% CI: 0.36, 4.07; p=0.76) and were similar. Among observational studies, access site complication rates (OR:0.46; 95% CI: 0.25,0.86; p&amp;lt;0.001) and contrast volume (SMD: -0.14; 95% CI: -0.20, -0.07; p=0.03) were lower and crossover rates were higher (OR: 4.79; 95% CI: 1.99, 11.52, p=0.02) in the radial group, while procedure time was similar (SMD: 0.13; 95% CI: -0.08, 0.34, p=0.02). Conclusions: Most data published for radial vs. femoral access in prior CABG patients are observational with only two randomized-controlled trials performed to date. Radial access is associated with lower vascular access complication rates and contrast volume in observational studies and higher rates of crossover to femoral access in both observational and randomized studies.
Abstract 13384: Cangrelor Pk / Pd Analysesin Neonates After Palliation of Congenital Heart Disease (chd)
Authors: Thomas G Diacovo, Diana Vargas, Hairu Zhou, Xinren Yu, Scott L Diamond, Justin Yeh, Vivekanand Allada, Ganga Krishnamurthy, Joseph Schmidhofer, Jacqueline Kreutzer, Julie A Vincent, Victor Morell, Emile Bacha
Journal: Circulation (2020)

Background: Thrombotic events contribute significantly to early mortality in neonates with CHD requiring a systemic-to-pulmonary artery shunt. However, thromboprophylaxis remains suboptimal with few pharmacological agents studied and shown to be of benefit. The P2Y 12 inhibitor cangrelor is effective in preventing early coronary artery stent thrombosis in adults. Cangrelor dosing and safety have yet to be established in neonates. Hypotheses: (1) Cangrelor administered by infusion will yield drug levels capable of inhibiting maximal platelet aggregation by &gt; 90% without causing an increase in bleeding. (2) A novel microfluidic technology can yield robust results related to inhibition of thrombus formation using significantly less blood than for LTA. Methods: This IRB approved, prospective, open-label, single-arm study was conducted between January 2017 and August 2019. Cangrelor, 0.5 μg/kg/min (n=7) or 0.25 μg/kg/min (n=8), was administered intravenously 6-10h after placement of a systemic-to-pulmonary artery shunt (n=8), right ventricle-to-pulmonary artery shunt (n=6), or ductal stent (n=1) for 1h. Plasma levels and PD properties of cangrelor were determined, the latter by light transmission aggregometry (LTA) and microfluidic assay (MFA). Informed consent was obtained (NCT02765633). Results: 15 participants that received cangrelor had single ventricle physiology (12 of 15) and underwent a Norwood procedure (11 of 15). Cangrelor 0.5 μg/kg/min dosing met all PD endpoints, yielding a higher level of platelet inhibition (mean ± SD) than the 0.25 μg/kg/min dose as assessed by LTA (89 ± 11.4% vs 73.3 ± 16.9%, respectively). Results from MF studies were comparable but required 3-fold less blood for testing. PK analysis revealed rapid drug clearance with 86.7% of participants having undetectable levels by 10 minutes post-infusion and 70% with full recovery in platelet function at 1 hour. SAEs and AEs that occurred were not related drug administration, including bleeding. Conclusion: Favorable PK and PD properties of cangrelor 0.5 μg/kg/min dosing and an acceptable safety profile warrant further evaluation in neonates following palliative cardiac procedures.
Clomethiazole inhibits cytochrome P450 2E1 and improves alcoholic liver disease
Authors: Nicolas Hohmann, Fabian Schröder, Bernardo Moreira, Haidong Teng, Jürgen Burhenne, Thomas Bruckner, Sebastian Mueller, Walter E Haefeli, Helmut K Seitz
Journal: Gut (2021)

In their article on recent advances in alcoholic liver disease (ALD), Avila and coworkers1 also mention the little-studied approach of inhibiting overexpressed cytochrome P450 2E1 (CYP2E1), which is induced by chronic ethanol consumption,2 causes generation of reactive oxidative species (ROS) and oxidative stress and stimulates hepatic steatosis and fibrosis.3 4 ROS also results in lipid peroxidation products such as 4-hydroxynonenal, which binds to DNA and generates highly carcinogenic etheno DNA adducts.4 In rodents, ALD can be partly prevented by CYP2E1 knock out5 or by administration of the strong noncompetitive CYP2E1 inhibitor clomethiazole.6 Conversely, ALD is enhanced in mice overexpressing CYP2E1,7 underlying the potential role of CYP2E1 activity in ALD.

To study whether CYP2E1 inhibition also improves ALD in humans, we performed an open, randomised controlled clinical trial (EudraCT-Number 2012-005730-11, online supplemental materials 1–3), as approved by the responsible Ethics Committee of the Medical Faculty of Heidelberg University (AFmo-586/2014) (online supplemental material 4) and the German authorities (BfArM) in alcohol-dependent patients who were admitted to the hospital for alcohol detoxification therapy (ADT). After giving written informed consent (online supplemental material 5), ADT was performed either with clomethiazole …
Abstract P068: The Relationship Of Air Pollution And Menopause On The Progression Of Coronary Artery Calcification In Midlife Women: Study Of Women’s Health Across The Nation
Authors: Lei Zhu, Evelyn O Talbott, Karen Matthews, Jennifer Adibi, Rachel Broadwin, Ada Youk, Imke Janssen, Samar R El Khoudary
Journal: Circulation (2021)

Knowledge of the association between air pollution and atherosclerosis risk has been generated in the general population. Our study targeted middle-aged women during the menopause transition who might be vulnerable to PM2.5 on CAC risk, due to their unique physiological profiles. We assessed the association of PM2.5 and CAC presence/progression in menopause transition women.Women included had data of CAC Agatston score, menopause profile measures, and PM2.5 from the SWAN Heart Ancillary study. The yearly mean baseline PM2.5 was estimated based on monitors within 20km of the women’s home. Logistic regression model was used to estimate the association between PM2.5 and CAC presence (any) and progression (defined), and generalized linear mixed model was used for repeated measures of CAC, adjusting for confounders. Time-varing menopause status and baseline PM2.5 measure time to final menstrual period (FMP), were tested as modifiers by adding interaction terms into the final model.366 women averaging 51.3 years were identified (N=198 pre-/early peri- menopause, N=129 late peri-/natural post- menopause), and 21% women had CAC presence. For the 253 women with two CAC measures, 20.9% had progression. Overall mean PM2.5 was no difference by CAC (p=0.54). There was no association between PM2.5 and CAC presence/progression, in both cross-sectional and longitudinal analyses. The tested interactions were not statistically significant. Although those are non-significant, larger odds ratios with higher precision of PM2.5 to CAC progression were detected among women in late peri-/natural post- menopause (OR=1.08 95% CI 0.74, 1.58) and of 2 years after FMP (OR=1.03 95% CI 0.60, 1.92), as compared to premenopausal women and those within/prior to FMP with lower values of PM2.5. (Table)We observed no evidence that PM2.5 was associated with the CAC presence/progression among middle-aged women overall. The contrasts were sharpened among women after menopause transition. More methodologic work is needed to evaluate the relationships.
해외에서 유입된, 급성 간염을 동반한 뎅기열 1예
Authors: 서상준, Seo Yeon Seok, 안재홍, 박은범, Soonjae Lee, Jang-Wook Sohn, Soon-Ho Um
Journal: Clinical and Molecular Hepatology (2007)

뎅기열은 flaviviridae속에 속하는 뎅기바이러스에 의해서 발생되는 급성 발열질환으로 Aedes aegypti의 매개충에 의해 옮겨진다. 이 질환은 Aedes aegypti의 분포에 따라 동남아시아, 남태평양 지역, 인도, 아메리카의 아열대 지역에서 가장 많이 발생 하고 있다. 국내에서도 해외여행이 증가되면서 해외 유입 건수가 늘고 있다. 24세 여자 환자가 2주간 동남아 (캄보디아, 베트남)에서 기자로 근무하던 중 내원 7일 전 발열과 오한으로 현지 병원에서 치료받았으나 오심과 구토가 계속되어 귀국하였다. 간수치가 정상 상한치의 10배 이상 상승하여 급성 간염 의심하에 입원하여 1일 만에 전신에 반점상의 발진을 보였다. 대증치료와 수액요법으로 증상 및 혈청검사 모두 호전 되었으며, 국립보건원에 의뢰한 혈청검사를 통해 뎅기열로 진단하였다.
Abstract 019: Modifiable Lifestyle Factors And Plasma Branched Chain Amino Acids: An Analysis Of N=19,472 US Women
Authors: Rikuta Hamaya, Samia Mora, Patrick R Lawler, Nancy R Cook, Julie E Buring, I-min M Lee, JoAnn E Manson, Deirdre K Tobias
Journal: Circulation (2021)

Background: Circulating branched-chain amino acids (BCAAs) are associated with insulin resistance and higher risk of incident type 2 diabetes (T2D); however, despite their potential as a target for T2D prevention, upstream determinants of plasma BCAAs are largely unknown. Therefore, we investigated modifiable lifestyle factors in relation to plasma BCAAs in the Women’s Health Study. Methods: We performed a cross-sectional analysis among N=19,472 women (mean age=54.9 [SD=7.2] years) free of T2D, cardiovascular disease, and cancer. BCAAs were quantified via NMR spectroscopy and log-transformed among women reporting ≥8 hours of fasting at baseline blood draw. Lifestyle factors were ascertained from self-reported questionnaires at study baseline: body mass index (BMI, kg/m 2 ), smoking, alcohol, physical activity [PA, MET-hrs/wk], and diet (Mediterranean diet pattern score [aMED], alternative Health Eating Index score [aHEI], dietary BCAA intake [g/d], and individual protein sources [servings/d]). We estimated % mean differences in BCAAs (95% CI) for each lifestyle factor categorically (linear regression models) and continuously to calculate R 2 from univariate cubic spline models. Multivariate models were mutually adjusted for the other lifestyle factors and other T2D risk factors. Results: Overall, we observed positive associations between BMI and dietary protein sources with plasma BCAAs, while alcohol and PA were inversely associated with BCAAs in multivariable-adjusted models. Smoking and aMED and aHEI dietary quality scores were not associated with BCAAs. Compared with women with BMI&lt;25.0, BCAAs were 8.2% (7.5, 8.8), 14.6% (13.8, 15.5), and 20.3% (17.8, 22.9) higher for BMI groups 25.0-29.9, 30.0-39.9, and ≥40.0, respectively (p-trend&lt;0.0001). Compared to never drinkers, women with moderate or high alcohol intake had -1.8% (-2.8, -0.9) and -2.7% (-3.9, -1.5) lower BCAA levels. There was a slightly lower (-1.2% [-2.0, -0.4]) BCAA level among highest vs. lowest quartiles of PA (p-trend=0.0002). Women with higher intakes of dietary BCAAs had modest incrementally higher plasma BCAAs (comparing Q5 vs. Q1: 2.9% [2.0, 3.7]; p-trend&lt;0.0001). Similarly, we observed dose-response relationships for higher intakes of major US protein sources (red meat, poultry, fish, eggs, dairy products) and higher plasma BCAAs. In continuous models, BMI explained 11.5% of the variability of plasma BCAAs, while the other modifiable factors each explained 0-1.1%. Conclusions: Our analysis in a large cohort of US women confirms prior evidence for a compelling relationship between BMI and plasma BCAAs. We also observed novel associations for dietary protein intake, alcohol, and PA, although the magnitudes of their contribution to BCAAs were small. Future clinical research on interventions to lower BCAAs for T2D prevention should consider body weight as a primary target for modification.
Rescue lumen-apposing metal stent to treat a perforation secondary to balloon dilation of a Crohn’s disease stenosis
Authors: Raphael Olivier, Stéphane Scheer, Jérémie Albouys, Marion Schaefer, Abdelkader Taibi, Sophie Geyl, Jérémie Jacques
Journal: Endoscopy (2021)

A 61-year-old woman was followed for ileocolic Crohnʼs disease (CD) with multi-complicated colonic and ano-perineal involvement, evolving over 17 years, with a subtotal colectomy protected by an upstream lateral ileostomy. Optimized adalimumab allowed control of the disease with healing of fistulas.
Adverse Health Effects in People with and without Preexisting Respiratory Conditions during Bushfire Smoke Exposure in the 2019/2020 Australian Summer
Authors: C. Raina MacIntyre, Phi-Yen Nguyen, Mallory Trent, Holly Seale, Abrar Ahmad Chughtai, Smita Shah, Guy B. Marks
Journal: American Journal of Respiratory and Critical Care Medicine (2021)