tbuckley/cabot-search huggingface dataset:
Role of Adherence to Enhanced Recovery After Surgery Programs in Mitigating Healthcare Disparities—Reply
Authors: Javier Ripollés-Melchor, José M Ramírez-Rodríguez, César Aldecoa
Journal: JAMA Surgery (2019)

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Platelet-activating factor (PAF) mediates NLRP3-NEK7 inflammasome induction independently of PAFR
Authors: Meng Deng, Haitao Guo, Jason W. Tam, Brandon M. Johnson, W. June Brickey, James S. New, Austin Lenox, Hexin Shi, Douglas T. Golenbock, Beverly H. Koller, Karen P. McKinnon, Bruce Beutler, Jenny P.-Y. Ting
Journal: The Journal of Experimental Medicine (2019)

The role of lipids in inflammasome activation remains underappreciated. The phospholipid, platelet-activating factor (PAF), exerts multiple physiological functions by binding to a G protein–coupled seven-transmembrane receptor (PAFR). PAF is associated with a number of inflammatory disorders, yet the molecular mechanism underlying its proinflammatory function remains to be fully elucidated. We show that multiple PAF isoforms and PAF-like lipids can activate the inflammasome, resulting in IL-1β and IL-18 maturation. This is dependent on NLRP3, ASC, caspase-1, and NEK7, but not on NLRC4, NLRP1, NLRP6, AIM2, caspase-11, or GSDMD. Inflammasome activation by PAF also requires potassium efflux and calcium influx but not lysosomal cathepsin or mitochondrial reactive oxygen species. PAF exacerbates peritonitis partly through inflammasome activation, but PAFR is dispensable for PAF-induced inflammasome activation in vivo or in vitro. These findings reveal that PAF represents a damage-associated signal that activates the canonical inflammasome independently of PAFR and provides an explanation for the ineffectiveness of PAFR antagonist in blocking PAF-mediated inflammation in the clinic.
Adverse events of exercise therapy in randomised controlled trials: a systematic review and meta-analysis
Authors: Andre Niemeijer, Hans Lund, Signe Nilssen Stafne, Thomas Ipsen, Cathrine Luhaäär Goldschmidt, Claus Thomas Jørgensen, Carsten B Juhl
Journal: British Journal of Sports Medicine (2019)

Objective To evaluate the relative risk (RR) of serious and non-serious adverse events in patients treated with exercise therapy compared with those in a non-exercising control group. Design Systematic review and meta-analysis. Data sources Primary studies were identified based on The Cochrane Database of Systematic Reviews investigating the effect of exercise therapy. Eligibility criteria At least two of the authors independently evaluated all identified reviews and primary studies. Randomised controlled trials were included if they compared any exercise therapy intervention with a non-exercising control. Two authors independently extracted data. The RR of serious and non-serious adverse events was estimated separately. Results 180 Cochrane reviews were included and from these, 773 primary studies were identified. Of these, 378 studies (n=38 368 participants) reported serious adverse events and 375 studies (n=38 517 participants) reported non-serious adverse events. We found no increase in risk of serious adverse events (RR=0.96 (95%CI 0.90 to 1.02, I 2 : 0.0%) due to exercise therapy. There was, however, an increase in non-serious adverse events (RR=1.19 (95%CI 1.09 to 1.30, I 2 : 0.0%). The number needed to treat for an additional harmful outcome for non-serious adverse events was 6 [95%CI 4 to 11). Conclusion Participating in an exercise intervention increased the relative risk of non-serious adverse events, but not of serious adverse events. Exercise therapy may therefore be recommended as a relatively safe intervention. PROSPERO registration number CRD42014014819.
TCT-508 Telemedicine Without Borders!
Authors: Sameer Mehta, Roberto Botelho, Jamil Cade, Marco Perin, Mauricio Prudente, Ricardo Cavalcanti, Cesar Dusilek, Rodolfo Cardoso, Nabil Hamdan, Luis Ignacio Calderon, Marco Alcocer-Gamba, Juan Carlos Perez Alva, Alfredo Estrada, Manuel De Los Rios Ibarra, Alejandro Ricalde, Mariana Ceschim, Rodrigo Jacobucci, Lorena Pisana, Jorge Mazzini, Samantha Quintero, José Aguilar, Genesis Del Nogal, Pedro Cruz, Lilly Prieto, Benjamin Wood, Juhee Lee
Journal: Journal of the American College of Cardiology (2019)
γ-Secretase inhibition increases efficacy of BCMA-specific chimeric antigen receptor T cells in multiple myeloma
Authors: Margot J. Pont, Tyler Hill, Gabriel O. Cole, Joe J. Abbott, Jessica Kelliher, Alexander I. Salter, Michael Hudecek, Melissa L. Comstock, Anusha Rajan, Bharvin K. R. Patel, Jenna M. Voutsinas, Qian Wu, Lingfeng Liu, Andrew J. Cowan, Brent L. Wood, Damian J. Green, Stanley R. Riddell
Journal: Blood (2019)
Heterogeneity of cancer-associated fibroblasts and roles in the progression, prognosis, and therapy of hepatocellular carcinoma
Authors: Zeli Yin, Chengyong Dong, Keqiu Jiang, Zhe Xu, Rui Li, Kun Guo, Shujuan Shao, Liming Wang
Journal: Journal of Hematology & Oncology (2019)

Abstract Hepatocellular carcinoma (HCC) is a lethal disease, and recurrence and metastasis are the major causes of death in HCC patients. Cancer-associated fibroblasts (CAFs), a major stromal cell type in the HCC microenvironment, promote HCC progression, and have gradually become a hot research topic in HCC-targeted therapy. This review comprehensively describes and discusses the heterogeneous tissue distribution, cellular origin, phenotype, and biological functions of HCC-associated fibroblasts. Furthermore, the possible use of CAFs for predicting HCC prognosis and in targeted therapeutic strategies is discussed, highlighting the critical roles of CAFs in HCC progression, diagnosis, and therapy.
Oral steroid-sparing effect of high-dose inhaled corticosteroids in asthma
Authors: Ingrid Maijers, Nethmi Kearns, James Harper, Mark Weatherall, Richard Beasley
Journal: European Respiratory Journal (2019)

Background The proportion of the efficacy of high-dose inhaled corticosteroids (ICS) in oral corticosteroid-dependent asthma that is due to systemic effects is uncertain. This study aimed to estimate the ICS dose–response relationship for oral corticosteroid-sparing effects in oral corticosteroid-dependent asthma, and to determine the proportion of oral corticosteroid-sparing effects due to their systemic effects, based on the comparative dose–response relationship of ICS versus oral corticosteroids on adrenal suppression. Methods Systematic review and meta-analysis of randomised controlled trials reporting oral corticosteroid-sparing effects of high-dose ICS in oral corticosteroid-dependent asthma. In addition, reports of oral corticosteroid to ICS dose-equivalence in terms of adrenal suppression were retrieved. The primary outcome was the proportion of the oral corticosteroid-sparing effect of ICS that could be attributed to systemic absorption, per 1000 µg increase of ICS, expressed as a ratio. This ratio estimates the oral corticosteroid sparing effect of ICS due to systemic effects. Results 11 studies including 1283 participants reporting oral corticosteroid-sparing effects of ICS were identified. The prednisone dose decrease per 1000 µg increase in ICS varied from 2.1 mg to 4.9 mg, depending on the type of ICS. The ratio of the prednisone-sparing effect due to the systemic effects per 1000 µg of fluticasone propionate was 1.02 (95% CI 0.68–2.08) and for budesonide was 0.93 (95% CI 0.63–1.89). Conclusion In patients with oral corticosteroid-dependent asthma, the limited available evidence suggests that the majority of the oral corticosteroid-sparing effect of high-dose ICS is likely to be due to systemic effects.
A Phage Protein Aids Bacterial Symbionts in Eukaryote Immune Evasion
Authors: Martin T. Jahn, Ksenia Arkhipova, Sebastian M. Markert, Christian Stigloher, Tim Lachnit, Lucia Pita, Anne Kupczok, Marta Ribes, Stephanie T. Stengel, Philip Rosenstiel, Bas E. Dutilh, Ute Hentschel
Journal: Cell Host & Microbe (2019)
TCT-318 Hemodynamics of High-Risk Percutaneous Coronary Intervention With and Without Mechanical Circulatory Support: A Pilot Study With Pressure Volume Loop Analysis
Authors: Michael Brener, Hannah Rosenblum, Mir Basir, Amirali Masoumi, Ajay Jayant Kirtane, William O'Neill, Dimitri Karmpaliotis, Daniel Burkhoff, Mohammad Alqarqaz
Journal: Journal of the American College of Cardiology (2019)
GPs facing two week delay to flu vaccine supplies
Authors: Gareth Iacobucci
Journal: BMJ (2019)

GP practices in England are facing waits for flu vaccine supplies of up to two weeks after the manufacturer Sanofi Pasteur said it had experienced an unexpected delay at its main manufacturing plant in France.

The company supplies around a third of the three million flu vaccines administered in England each year.

The shortage relates to Sanofi’s quadrivalent non-adjuvanted vaccine for at risk-groups aged 16 to 65.

The company said around 40% of the first deliveries of the vaccine would be delayed by one to two weeks.

This is the second delay Sanofi has faced …
TCT-30 Ultra-Low Contrast Coronary Angiography in Patients With Advanced Chronic Kidney Disease: Feasibility and Outcomes Compared With Conventional Angiography
Authors: Navdeep Bhatti, Hussein Rahim, Shmuel Chen, Aaron Crowley, Ajay Jayant Kirtane, Dimitri Karmpaliotis, Jeffrey W. Moses, Gary Mintz, Akiko Maehara, Ori Ben-Yehuda, Gregg Stone, Russell Crew, Geoffrey Dube, Mark Hardy, Lloyd Ratner, Sumit Mohan, David Cohen, Martin Leon, Ziad Ali
Journal: Journal of the American College of Cardiology (2019)
Response by Upadhyay et al to Letter Regarding Article, “Intracardiac Delineation of Septal Conduction in Left Bundle-Branch Block Patterns: Mechanistic Evidence of Left Intrahisian Block Circumvented by His Bundle Pacing”
Authors: Gaurav A. Upadhyay, Tharian Cherian, Dalise Y. Shatz, Andrew D. Beaser, Zaid Aziz, Cevher Ozcan, Michael T. Broman, Hemal Nayak, Roderick Tung
Journal: Circulation (2019)
TCT-687 Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement With or Without Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis
Authors: Muhammad Khan, Naser Yamani, Salil Deo, Noman Lateef, Haris Riaz, Safi Khan, Hafeez Hassan, Anmar Kanaa’n, Grant Reed, Amar Krishnaswamy, Cleveland Puri, Samir Kapadia
Journal: Journal of the American College of Cardiology (2019)
Anti-CD45 Radioimmunotherapy Followed By Haploidentical Allogeneic Hematopoietic Cell Transplantation for Advanced Acute Leukemia or High-Risk MDS
Authors: Johnnie J. Orozco, Ted Gooley, Joseph G. Rajendran, Darrell R. Fisher, H. Joachim Deeg, Rainer F. Storb, Raya Mawad, Mazyar Shadman, Ryan D. Cassaday, Damian J. Green, Ajay K. Gopal, Brian G. Till, Solomon Graf, Robyn Haaf, Sally J. Lundberg, Paul O'Donnell, Oliver W. Press, Frederick R. Appelbaum, John M. Pagel, Brenda M. Sandmaier
Journal: Blood (2017)
TCT-597 A Novel Superior Vena Caval Occlusion Catheter System Reduces Biventricular Filling Pressures While Maintaining Cardiac Output in a Model of Acute Congestive Heart Failure
Authors: Navin Kapur, Lara Reyelt, Paige Crowley, Sarah Newman, Peter Natov, Tim Lenihan, Daniel Burkhoff, Richard Karas
Journal: Journal of the American College of Cardiology (2019)
Trends in Dietary Carbohydrate, Protein, and Fat Intake and Diet Quality Among US Adults, 1999-2016
Authors: Zhilei Shan, Colin D. Rehm, Gail Rogers, Mengyuan Ruan, Dong D. Wang, Frank B. Hu, Dariush Mozaffarian, Fang Fang Zhang, Shilpa N. Bhupathiraju
Journal: JAMA (2019)

<h3>Importance</h3> Changes in the economy, nutrition policies, and food processing methods can affect dietary macronutrient intake and diet quality. It is essential to evaluate trends in dietary intake, food sources, and diet quality to inform policy makers. <h3>Objective</h3> To investigate trends in dietary macronutrient intake, food sources, and diet quality among US adults. <h3>Design, Setting, and Participants</h3> Serial cross-sectional analysis of the US nationally representative 24-hour dietary recall data from 9 National Health and Nutrition Examination Survey cycles (1999-2016) among adults aged 20 years or older. <h3>Exposure</h3> Survey cycle. <h3>Main Outcomes and Measures</h3> Dietary intake of macronutrients and their subtypes, food sources, and the Healthy Eating Index 2015 (range, 0-100; higher scores indicate better diet quality; a minimal clinically important difference has not been defined). <h3>Results</h3> There were 43 996 respondents (weighted mean age, 46.9 years; 51.9% women). From 1999 to 2016, the estimated energy from total carbohydrates declined from 52.5% to 50.5% (difference, −2.02%; 95% CI, −2.41% to −1.63%), whereas that of total protein and total fat increased from 15.5% to 16.4% (difference, 0.82%; 95% CI, 0.67%-0.97%) and from 32.0% to 33.2% (difference, 1.20%; 95% CI, 0.84%-1.55%), respectively (all<i>P</i> &lt; .001 for trend). Estimated energy from low-quality carbohydrates decreased by 3.25% (95% CI, 2.74%-3.75%;<i>P</i> &lt; .001 for trend) from 45.1% to 41.8%. Increases were observed in estimated energy from high-quality carbohydrates (by 1.23% [95% CI, 0.84%-1.61%] from 7.42% to 8.65%), plant protein (by 0.38% [95% CI, 0.28%-0.49%] from 5.38% to 5.76%), saturated fatty acids (by 0.36% [95% CI, 0.20%-0.51%] from 11.5% to 11.9%), and polyunsaturated fatty acids (by 0.65% [95% CI, 0.56%-0.74%] from 7.58% to 8.23%) (all<i>P</i> &lt; .001 for trend). The estimated overall Healthy Eating Index 2015 increased from 55.7 to 57.7 (difference, 2.01; 95% CI, 0.86-3.16;<i>P</i> &lt; .001 for trend). Trends in high- and low-quality carbohydrates primarily reflected higher estimated energy from whole grains (0.65%) and reduced estimated energy from added sugars (−2.00%), respectively. Trends in plant protein were predominantly due to higher estimated intake of whole grains (0.12%) and nuts (0.09%). <h3>Conclusions and Relevance</h3> From 1999 to 2016, US adults experienced a significant decrease in percentage of energy intake from low-quality carbohydrates and significant increases in percentage of energy intake from high-quality carbohydrates, plant protein, and polyunsaturated fat. Despite improvements in macronutrient composition and diet quality, continued high intake of low-quality carbohydrates and saturated fat remained.
TCT-780 Randomized Comparison of Hemostasis Times Following Transradial Access With a Kaolin-Based Hemostatic Pad (QuikClot® Radial®) vs. Mechanical Compression (TR Band®)
Authors: Jonathan Roberts, Jianli Niu, Sunay Shah, Eduardo Cianferra, Juan Pastor-Cervantes
Journal: Journal of the American College of Cardiology (2019)
TCT-699 Preoperative Frailty Parameters as Predictors for Outcomes After Transcatheter Aortic Valve Implantation: A Systematic Review and Meta-Analysis
Authors: M.S. van Mourik, Vincent Lanting, Jacqualine Limpens, Jan Piek, Jan Baan, Jose P.S. Henriques, M. Marije Vis
Journal: Journal of the American College of Cardiology (2019)
TCT-401 Long-Term Efficacy of Extended Dual Antiplatelet Therapy After Left Main Coronary Artery Bifurcation Stenting
Authors: Sungsoo Cho, Jung-Sun Kim, Tae Soo Kang, Sung-Jin Hong, Dong-Ho Shin, Chul-Min Ahn, Byeong-Keuk Kim, Young-Guk Ko, Donghoon Choi, Young Bin Song, Joo-Yong Hahn, Seung-Hyuk Choi, Hyeon-Cheol Gwon, Myeong-Ki Hong, Yangsoo Jang
Journal: Journal of the American College of Cardiology (2019)
Ublituximab and umbralisib in relapsed/refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia
Authors: Matthew Lunning, Julie Vose, Loretta Nastoupil, Nathan Fowler, Jan A. Burger, William G. Wierda, Marshall T. Schreeder, Tanya Siddiqi, Christopher R. Flowers, Jonathon B. Cohen, Peter Sportelli, Hari P. Miskin, Michael S. Weiss, Susan O’Brien
Journal: Blood (2019)
What are the respiratory effects of e-cigarettes?
Authors: Jeffrey E Gotts, Sven-Eric Jordt, Rob McConnell, Robert Tarran
Journal: BMJ (2019)

Electronic cigarettes (e-cigarettes) are alternative, non-combustible tobacco products that generate an inhalable aerosol containing nicotine, flavors, propylene glycol, and vegetable glycerin. Vaping is now a multibillion dollar industry that appeals to current smokers, former smokers, and young people who have never smoked. E-cigarettes reached the market without either extensive preclinical toxicology testing or long term safety trials that would be required of conventional therapeutics or medical devices. Their effectiveness as a smoking cessation intervention, their impact at a population level, and whether they are less harmful than combustible tobacco products are highly controversial. Here, we review the evidence on the effects of e-cigarettes on respiratory health. Studies show measurable adverse biologic effects on organ and cellular health in humans, in animals, and in vitro. The effects of e-cigarettes have similarities to and important differences from those of cigarettes. Decades of chronic smoking are needed for development of lung diseases such as lung cancer or chronic obstructive pulmonary disease, so the population effects of e-cigarette use may not be apparent until the middle of this century. We conclude that current knowledge of these effects is insufficient to determine whether the respiratory health effects of e-cigarette are less than those of combustible tobacco products.
TCT-79 Multimodality Assessment of Prosthetic Valve Regurgitation to Predict Reverse Cardiac Remodeling and Long-Term Clinical Outcomes After Transcatheter Aortic Valve Replacement: Results From the Prospective POST-TAVI Registry
Authors: Mohammad Abdelghani, Rayyan Hemetsberger, Martin Landt, Ralph Toelg, Mohamed Abdel-Wahab, Constanze Merten, Gert Richardt
Journal: Journal of the American College of Cardiology (2019)
Radiotherapy and Immunotherapy Promote Tumoral Lipid Oxidation and Ferroptosis via Synergistic Repression of SLC7A11
Authors: Xueting Lang, Michael D. Green, Weimin Wang, Jiali Yu, Jae Eun Choi, Long Jiang, Peng Liao, Jiajia Zhou, Qiang Zhang, Ania Dow, Anjali L. Saripalli, Ilona Kryczek, Shuang Wei, Wojciech Szeliga, Linda Vatan, Everett M. Stone, George Georgiou, Marcin Cieslik, Daniel R. Wahl, Meredith A. Morgan, Arul M. Chinnaiyan, Theodore S. Lawrence, Weiping Zou
Journal: Cancer Discovery (2019)

Abstract A challenge in oncology is to rationally and effectively integrate immunotherapy with traditional modalities, including radiotherapy. Here, we demonstrate that radiotherapy induces tumor-cell ferroptosis. Ferroptosis agonists augment and ferroptosis antagonists limit radiotherapy efficacy in tumor models. Immunotherapy sensitizes tumors to radiotherapy by promoting tumor-cell ferroptosis. Mechanistically, IFNγ derived from immunotherapy-activated CD8+ T cells and radiotherapy-activated ATM independently, yet synergistically, suppresses SLC7A11, a unit of the glutamate–cystine antiporter xc−, resulting in reduced cystine uptake, enhanced tumor lipid oxidation and ferroptosis, and improved tumor control. Thus, ferroptosis is an unappreciated mechanism and focus for the development of effective combinatorial cancer therapy. Significance: This article describes ferroptosis as a previously unappreciated mechanism of action for radiotherapy. Further, it shows that ferroptosis is a novel point of synergy between immunotherapy and radiotherapy. Finally, it nominates SLC7A11, a critical regulator of ferroptosis, as a mechanistic determinant of synergy between radiotherapy and immunotherapy. This article is highlighted in the In This Issue feature, p. 1631
Allele-specific RNA interference prevents neuropathy in Charcot-Marie-Tooth disease type 2D mouse models
Authors: Kathryn H. Morelli, Laurie B. Griffin, Nettie K. Pyne, Lindsay M. Wallace, Allison M. Fowler, Stephanie N. Oprescu, Ryuichi Takase, Na Wei, Rebecca Meyer-Schuman, Dattatreya Mellacheruvu, Jacob O. Kitzman, Samuel G. Kocen, Timothy J. Hines, Emily L. Spaulding, James R. Lupski, Alexey Nesvizhskii, Pedro Mancias, Ian J. Butler, Xiang-Lei Yang, Ya-Ming Hou, Anthony Antonellis, Scott Q. Harper, Robert W. Burgess
Journal: Journal of Clinical Investigation (2019)

Gene therapy approaches are being deployed to treat recessive genetic disorders by restoring the expression of mutated genes. However, the feasibility of these approaches for dominantly inherited diseases — where treatment may require reduction in the expression of a toxic mutant protein resulting from a gain-of-function allele — is unclear. Here we show the efficacy of allele-specific RNAi as a potential therapy for Charcot-Marie-Tooth disease type 2D (CMT2D), caused by dominant mutations in glycyl-tRNA synthetase (GARS). A de novo mutation in GARS was identified in a patient with a severe peripheral neuropathy, and a mouse model precisely recreating the mutation was produced. These mice developed a neuropathy by 3–4 weeks of age, validating the pathogenicity of the mutation. RNAi sequences targeting mutant GARS mRNA, but not wild-type, were optimized and then packaged into AAV9 for in vivo delivery. This almost completely prevented the neuropathy in mice treated at birth. Delaying treatment until after disease onset showed modest benefit, though this effect decreased the longer treatment was delayed. These outcomes were reproduced in a second mouse model of CMT2D using a vector specifically targeting that allele. The effects were dose dependent, and persisted for at least 1 year. Our findings demonstrate the feasibility of AAV9-mediated allele-specific knockdown and provide proof of concept for gene therapy approaches for dominant neuromuscular diseases.