tbuckley/cabot-search huggingface dataset:
Real world effects of COPD medications: a cohort study with validation against results from randomised controlled trials
Authors: Kevin Wing, Elizabeth Williamson, James R. Carpenter, Lesley Wise, Sebastian Schneeweiss, Liam Smeeth, Jennifer K. Quint, Ian Douglas
Journal: European Respiratory Journal (2020)

Real-world data provide the potential for generating evidence on drug treatment effects in groups excluded from trials, but rigorous, validated methodology for doing so is lacking. We investigated whether non-interventional methods applied to real-world data could reproduce results from the landmark TORCH COPD trial. We performed a historical cohort study (2000–2017) of COPD drug treatment effects in the UK Clinical Practice Research Datalink (CPRD). Two control groups were selected from CPRD by applying TORCH inclusion/exclusion criteria and 1:1 matching to TORCH participants, as follows. Control group 1: people with COPD not prescribed fluticasone propionate (FP)-salmeterol (SAL); control group 2: people with COPD prescribed SAL only. FP-SAL exposed groups were then selected from CPRD by propensity score matching to each control group. Outcomes studied were COPD exacerbations, death from any cause and pneumonia. 2652 FP-SAL exposed people were propensity score matched to 2652 FP-SAL unexposed people while 991 FP-SAL exposed people were propensity score matched to 991 SAL exposed people. Exacerbation rate ratio was comparable to TORCH for FP-SAL versus SAL (0.85, 95% CI 0.74–0.97 versus 0.88, 0.81–0.95) but not for FP-SAL versus no FP-SAL (1.30, 1.19–1.42 versus 0.75, 0.69–0.81). In addition, active comparator results were consistent with TORCH for mortality (hazard ratio 0.93, 0.65–1.32 versus 0.93, 0.77–1.13) and pneumonia (risk ratio 1.39, 1.04–1.87 versus 1.47, 1.25–1.73). We obtained very similar results to the TORCH trial for active comparator analyses, but were unable to reproduce placebo-controlled results. Application of these validated methods for active comparator analyses to groups excluded from randomised controlled trials provides a practical way for contributing to the evidence base and supporting COPD treatment decisions.
Additional Concerns Regarding Children With Coronavirus Disease 2019
Authors: Silvia Salvatore, Maddalena Marinoni, Massimo Agosti
Journal: JAMA Pediatrics (2020)

Riccardo Castagnoli, MD; Martina Votto, MD; Amelia Licari, MD; Ilaria Brambilla, MD, PhD; Raffaele Bruno, MD; Stefano Perlini, MD; Francesca Rovida, PhD; Fausto Baldanti, MD; Gian Luigi Marseglia, MD
Audio Interview: Tocilizumab and Covid-19
Authors: Eric J. Rubin, Lindsey R. Baden, Stephen Morrissey
Journal: New England Journal of Medicine (2020)

Tocilizumab and Covid-19 In this audio interview conducted on October 21, 2020, the editors discuss the results of a new clinical trial of tocilizumab, a monoclonal antibody that blocks the activit...
A matrigel-free method to generate matured human cerebral organoids using 3D-Printed microwell arrays
Authors: Cheng Chen, Venkatakrishnan Rengarajan, Andrew Kjar, Yu Huang
Journal: Bioactive Materials (2020)

The current methods of generating human cerebral organoids rely excessively on the use of Matrigel or other external extracellular matrices (ECM) for cell micro-environmental modulation. Matrigel embedding is problematic for long-term culture and clinical applications due to high inconsistency and other limitations. In this study, we developed a novel microwell culture platform based on 3D printing. This platform, without using Matrigel or external signaling molecules (i.e., SMAD and Wnt inhibitors), successfully generated matured human cerebral organoids with robust formation of high-level features (i.e., wrinkling/folding, lumens, neuronal layers). The formation and timing were comparable or superior to the current Matrigel methods, yet with improved consistency. The effect of microwell geometries (curvature and resolution) and coating materials (i.e., mPEG, Lipidure, BSA) was studied, showing that mPEG outperformed all other coating materials, while curved-bottom microwells outperformed flat-bottom ones. In addition, high-resolution printing outperformed low-resolution printing by creating faithful, isotropically-shaped microwells. The trend of these effects was consistent across all developmental characteristics, including EB formation efficiency and sphericity, organoid size, wrinkling index, lumen size and thickness, and neuronal layer thickness. Overall, the microwell device that was mPEG-coated, high-resolution printed, and bottom curved demonstrated the highest efficacy in promoting organoid development. This platform provided a promising strategy for generating uniform and mature human cerebral organoids as an alternative to Matrigel/ECM-embedding methods.
Graft-versus-host disease depletes plasmacytoid dendritic cell progenitors to impair tolerance induction
Authors: Yuanyuan Tian, Lijun Meng, Ying Wang, Bohan Li, Hongshuang Yu, Yan Zhou, Tien Bui, Ciril Abraham, Alicia Li, Yongping Zhang, Jian Wang, Chenchen Zhao, Shin Mineishi, Stefania Gallucci, David Porter, Elizabeth Hexner, Hong Zheng, Yanyun Zhang, Shaoyan Hu, Yi Zhang
Journal: Journal of Clinical Investigation (2020)

Graft-versus-host disease (GVHD) causes failed reconstitution of donor plasmacytoid dendritic cells (pDCs) that are critical for immune protection and tolerance. We used both murine and human systems to uncover the mechanisms whereby GVHD induces donor pDC defects. GVHD depleted Flt3-expressing donor multipotent progenitors (MPPs) that sustained pDCs, leading to impaired generation of pDCs. MPP loss was associated with decreased amounts of MPP-producing hematopoietic stem cells (HSCs) and oxidative stress–induced death of proliferating MPPs. Additionally, alloreactive T cells produced GM-CSF to inhibit MPP expression of Tcf4, the transcription factor essential for pDC development, subverting MPP production of pDCs. GM-CSF did not affect the maturation of pDC precursors. Notably, enhanced recovery of donor pDCs upon adoptive transfer early after allogeneic HSC transplantation repressed GVHD and restored the de novo generation of donor pDCs in recipient mice. pDCs suppressed the proliferation and expansion of activated autologous T cells via a type I IFN signaling–dependent mechanism. They also produced PD-L1 and LILRB4 to inhibit T cell production of IFN-γ. We thus demonstrate that GVHD impairs the reconstitution of tolerogenic donor pDCs by depleting DC progenitors rather than by preventing pDC maturation. MPPs are an important target to effectively bolster pDC reconstitution for controlling GVHD.
TCT CONNECT-457 Reduction of Rates of Permanent Pacemaker Implantation With 34-MM Evolut R Using Cusp Overlap Technique
Authors: Hemal Gada, Amit Vora, Saima Siddique, Yijin Wert, Iassen Michev, Nicolo Piazza, Gilbert Tang
Journal: Journal of the American College of Cardiology (2020)
Enacted stigma experiences and protective factors are strongly associated with mental health outcomes of transgender people in Aotearoa/New Zealand
Authors: Kyle K. H. Tan, Gareth J. Treharne, Sonja J. Ellis, Johanna M. Schmidt, Jaimie F. Veale
Journal: International Journal of Transgender Health (2020)

Introduction International evidence has found large mental health inequities among transgender people and demonstrates that mental health outcomes are associated with enacted stigma experiences and protective factors. This study aimed to examine the extent of associations of enacted stigma experiences specific to transgender people alongside protective factors with mental health of transgender people in Aotearoa/New Zealand.Methods The 2018 Counting Ourselves survey was a nationwide community-based study of transgender people (N = 1178, Mage = 29.5) living in Aotearoa/New Zealand. The survey assessed a wide range of gender minority stress experiences and protective factors that comprised primary (support from friends and family) and secondary social ties (neighborhood and transgender community belongingness). We calculated the predicted probabilities that transgender people exhibit very high psychological distress level, non-suicidal self-injury, and suicidal risks with different combinations and exposure profiles of enacted stigma and protective factors.Results Our findings demonstrated that enacted stigma was associated with negative mental health, and support of friends and family was linked to better outcomes across all mental health measures. Beyond primary social ties, sense of belongingness to neighborhood and transgender communities were linked to reduced odds of psychological distress and suicidal ideation. For those scoring high on enacted stigma and low on protective factors, our model revealed a 25% probability of attempting suicide in the last year compared to 3% for those scoring low on enacted stigma and high on protective factors.Conclusions Echoing previous findings, this study demonstrates that transgender people across Aotearoa/New Zealand are less likely to manifest life-threatening mental health outcomes if they experience low levels of enacted stigma and high levels of access to protective factors. Our findings suggest a need to address the enacted stigma that transgender people face across interpersonal and structural settings, and also to enhance social supports that are gender affirmative for this population.
Clinical features and survival outcomes in IgD myeloma: a study by Asia Myeloma Network (AMN)
Authors: Jin Liu, Xiaoxia Hu, Yanchun Jia, Jin Lu, Jae Hoon Lee, Kihyun Kim, Wenming Chen, Aijun Liu, Yang Liu, Qi Chen, Chunyang Zhang, Cheolwon Suh, Min Kyoung Kim, Fan Zhou, Wee Joo Chng, Shaji K. Kumar, Brian Durie, Jian Hou, Weijun Fu, Juan Du
Journal: Leukemia (2020)

Immunoglobulin D (IgD) myeloma is a rare isotype that comprises 1-2% of multiple myeloma (MM) patients [1-3], which has significantly inferior survival for a median overall survival (OS) between 13 and 21 months [4][5][6].Given the lack of large cohort with comprehensive clinical and cytogenetic assessment, knowledge about IgD myeloma is obtained mostly from a limited sample size [7].Therefore, we carried out a multicenter retrospective study to evaluate the prevalence, clinical features, prognosis, and to develop and validate a prognostic model, including 356 patients with IgD myeloma from 14 centers of Asian Myeloma Network (AMN).Data were collected from China, Korea, and Singapore diagnosed from 2002 to 2019 (Supplementary Table 1).Ethical committee approvals were obtained and study protocol
TCT CONNECT-276 A “Real-World” Multicenter Registry Evaluating Safety and Clinical Performance of Biodegradable Polymer-Coated Ultra-thin Everolimus-Eluting Stents: 3-Year Results From the PERFORM-EVER Registry
Authors: Sridhar Kasturi, Sanjeev Kumar, Vinod Kumar Mustyala, Srinivas Polasa, Ganeshwar Reddy, Mohammad Ali, Praveen Kumar, Thejanandan Reddy, Chaitanya Nichenamatla, Shailender Singh, Vijay Kumar Reddy, Sunil Shewale
Journal: Journal of the American College of Cardiology (2020)
Scientific and Ethical Principles Underlying Recommendations From the Advisory Committee on Immunization Practices for COVID-19 Vaccination Implementation
Authors: Beth P. Bell, José R. Romero, Grace M. Lee
Journal: JAMA (2020)

The continued global spread of the coronavirus disease 2019 (COVID-19) pandemic highlights the pressing need for safe and effective COVID-19 vaccines.Vaccine development efforts of unprecedented scale and speed are being pursued.Since June 2020, the Advisory Committee on Immunization Practices (ACIP) has held 4 public meetings to lay the groundwork for public health recommendations for COVID-19 vaccines.This Viewpoint summarizes the approach ACIP is taking in formulating recommendations, with a focus on the ethical principles and potential groups for allocation of vaccine doses when supply is limited.Recommendations will be issued after reviewing safety and effectiveness data and vaccines are licensed or authorized under Emergency Use Authorization by the Food and Drug Administration (FDA).The ACIP is an independent federal advisory committee body composed of experts external to the federal government from diverse medical and public health fields, as well as a consumer representative.The committee is charged with recommending how FDAlicensed or authorized vaccines should be used in the US civilian population. 1 These recommendations are provided to the director of the Centers for Disease Control and Prevention (CDC).If the CDC director approves the recommendations, they become official CDC recommendations for immunizations in the US.ACIP recommendations determine the vaccines that are covered under the Vaccines for Children program, which provides vaccines at no cost for Medicaid-insured, underinsured, and uninsured children.Under the provi-sionsoftheAffordableCareAct(ACA),recommendedvaccines are covered by health insurers and employersponsored health plans established after passage of the ACA. 1 Hence, while not binding, recommendations determinehowvaccinesareusedinthepublicsectorandsetthe standard for clinical practice in the private sector.ACIP meetings are open to the public and committee documents are publicly available, ensuring transparency in decision-making.The development of recommendations adheres to a rigorous and transparent process.Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methods facilitate a standardized approach to evaluating scientific evidence. 1The Evidence to Recommendations framework evaluates factors including feasibility and acceptability. 1 Hence, the ACIP aims to produce national vaccine recommendations that are both evidence-based and implementable.Implementing COVID-19 vaccination presents a number of unique, interrelated challenges.During its public meetings, the ACIP has characterized guiding principles, assembled and reviewed available data, and summarized considerations for allocation of initial doses.
TCT CONNECT-410 Impact of Real-Time Optical Coherence Tomography-Angio Co-Registration (OCT-ACR) on Physician Decision Making During Percutaneous Coronary Intervention: A Multicenter, Prospective Study (iOPTICO study)
Authors: Rony Mathew, Jabir Abdullakutty, Tejas Patel, R. Sivakumar, Balbir Singh, Nagendra Chouhan, Fazila-Tun Nesa Malik, M.S. Hiremath, Sengottuvelu Gunasekaran, Samuel Mathew, Viveka Kumar, Vijayakumar Subban
Journal: Journal of the American College of Cardiology (2020)
Evaluating Non–Statistically Significant Results From Trials in Practice—Reply
Authors: Paul J. Young, Christopher P. Nickson, Anders Perner
Journal: JAMA (2020)

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Acute liver failure is regulated by MYC- and microbiome-dependent programs
Authors: Aleksandra A. Kolodziejczyk, Sara Federici, Niv Zmora, Gayatree Mohapatra, Mally Dori-Bachash, Shanni Hornstein, Avner Leshem, Debby Reuveni, Ehud Zigmond, Ana Tobar, Tomer Meir Salame, Alon Harmelin, Amir Shlomai, Hagit Shapiro, Ido Amit, Eran Elinav
Journal: Nature Medicine (2020)
FoxM1 insufficiency hyperactivates Ect2–RhoA–mDia1 signaling to drive cancer
Authors: Jazeel F. Limzerwala, Karthik B. Jeganathan, Jake A. Kloeber, Brian A. Davies, Cheng Zhang, Ines Sturmlechner, Jian Zhong, Raul Fierro Velasco, Alan P. Fields, Yaxia Yuan, Darren J. Baker, Daohong Zhou, Hu Li, David J. Katzmann, Jan M. van Deursen
Journal: Nature Cancer (2020)
TCT CONNECT-110 Transcatheter Versus Surgical Aortic Valve Replacement in Acute Cardiogenic Shock
Authors: Lena Trager, Sainath Asokan, Edward Percy, Morgan Harloff, Sameer Hirji, Paige Newell, Alexandra Malarczyk, Ashraf Sabe, Pinak Shah, Thomas Gleason, Tsuyoshi Kaneko
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-148 Impact of Foreshortening in SAPIEN 3 Balloon-Expandable Transcatheter Heart Valve Implantation
Authors: Shuichi Kegai, Katsumasa Sato, Kenji Goto, Takaya Ozawa, Tomonari Kimura, Kazunari Kobayashi, Yuetsu Kikuta, Masahito Taniguchi, Shigeki Hiramatsu, Hideo Takebayashi, Seiichi Haruta, Shogo Mukai
Journal: Journal of the American College of Cardiology (2020)
Developing new therapeutic approaches for treating infections caused by multi-drug resistant Acinetobacter baumannii
Authors: Peter Gallagher, Stephen Baker
Journal: Journal of Infection (2020)

Antimicrobial resistance (AMR) represents a major challenge to global health. This problem is most apparent in healthcare facilities, with a comparatively small number of pathogens being responsible for a substantial burden of hospital acquired infections globally. One of the key pathogens is the Gram-negative coccobacilli, Acinetobacter baumannii. It has been estimated that between 47% and 93% of A. baumannii infections are associated with multi-drug resistance (MDR), which is facilitated through a variety of well documented mechanisms (β-lactamases, efflux pumps, aminoglycoside-modifying enzymes, permeability defects, and target modifications). As our current pool of antimicrobial treatments becomes increasingly less effective, it is vital to identify new targets that can aid in the development novel treatments and strategies. In this we review we outline the key virulence mechanisms in A. baumannii (gene acquisition and adaptation, resistance to stresses, biofilm formation, and host interaction) and discuss their potential as targets for new therapeutics to reduce the impact of infections caused by MDR A. baumannii.
Association of Rurality With Availability of Youth Mental Health Facilities With Suicide Prevention Services in the US
Authors: Janessa M. Graves, Demetrius A. Abshire, Jessica L. Mackelprang, Solmaz Amiri, Ashley Beck
Journal: JAMA Network Open (2020)

This cross-sectional study uses 2017 to 2019 data from the US National Mental Health Services Survey and examines whether there are disparities in the availability of youth-serving mental health facilities associated with suicide risk in rural vs urban youth.
Long-term efficacy and safety of drug-coated balloons versus drug-eluting stents for small coronary artery disease (BASKET-SMALL 2): 3-year follow-up of a randomised, non-inferiority trial
Authors: Raban V Jeger, Ahmed Farah, Marc-Alexander Ohlow, Norman Mangner, Sven Möbius-Winkler, Daniel Weilenmann, Jochen Wöhrle, Georg Stachel, Sinisa Markovic, Gregor Leibundgut, Peter Rickenbacher, Stefan Osswald, Marco Cattaneo, Nicole Gilgen, Christoph Kaiser, Bruno Scheller, Peter Ammann, Belal Awad, Margarete Baumgartner, Michael Boehm, Steffen Bohl, Leonhard Bruch, Dominik Buckert, Peter Buser, Christian Butter, Yvonne P. Clever, Bodo Cremers, Florim Cuculi, Gudrun Dannberg, Paul Erne, Sebastian Ewen, Gregor Fahrni, Marcus Franz, Philipp Haager, Andrea Harder-Allgoewer, Andreas Hoffmann, Robert Höllriegel, Frank Hölschermann, Timo Jerichow, Lucas Joerg, Ioannis Kapos, Boris Keweloh, Behrouz Kherad, Michael Kühne, Bernward Lauer, Karsten Lenk, Corinna Lenz, Dirk Von Lewinski, Axel Linke, Olev Luha, Micha Maeder, Felix Mahfoud, Christian Mueller, Michael Neuss, Ella Niederl, Michel Noutsias, Dominique Nuessli, Ismet Oenal, Sylvia Otto, Rima Paliskyte, Sabine Perl, Burkert Pieske, Bjoern Plicht, Tudor C Poerner, Stefan Richter, Hans Rickli, Florian Riede, Hans Roelli, Alexandra Roettgen, Franziska Rohner, Stephan Schirmer, Albrecht Schmidt, Matthias Schreiber, Mirko Seidel, Frank-Peter Stephan, Christian Sticherling, Berthold Struck, Ralf Surber, Grit Tambor, Stefan Toggweiler, Lukas Trachsel, Raphael Twerenbold, Andreas Wagner, Bastian Wein, Sebastian Winkler, Ephraim Winzer, Alexander Wolf, Michael Zellweger, Florian Krackhardt, Robert Zweiker
Journal: The Lancet (2020)
Low impact of SARS-CoV-2 infection among paediatric acute respiratory disease hospitalizations
Authors: Maria Melé, Desiree Henares, Rosa Pino, Silvia Asenjo, Rocío Matamoros, Victoria Fumadó, Claudia Fortuny, Juan-José García-García, Iolanda Jordan, Pedro Brotons, Carmen Muñoz-Almagro, Mariona-Fernández de-Sevilla, Cristian Launes
Journal: Journal of Infection (2020)

This study describes the characteristics of children requiring admission with an acute lower-respiratory disease (ALRD) during the SARS-CoV-2 pandemics.Epidemiological, clinical, and microbiological data from patients with ALRD (pneumonia, bronchiolitis, bronchospasm) admitted to a reference paediatric hospital in Spain during the pandemic peak (week 11-20/2020) were prospectively analysed.110 patients were included. 7 were SARS-CoV-2(+) and they were older in comparison to SARS-CoV-2(-). Among SARS-CoV-2(+) patients, pneumonia was the main clinical diagnosis (6/7) and bronchospasm was absent. Only 1 of 29 infants diagnosed with bronchiolitis was SARS-CoV-2(+). Lower values of leucocytes, lymphocytes, neutrophils, and platelets and higher values of creatinine were found in SARS-CoV-2(+). Human-rhinovirus/enterovirus was the main detection (11/32). There were not differences in PICU admission rates between SARS-CoV-2(+) and (-).Most of the ALRD episodes identified during the pandemics were not related to SARS-CoV-2 infection. SARS-CoV-2 was mainly found causing pneumonia in older children.
TCT CONNECT-119 Outcomes of Transcatheter Aortic Valve Replacement in Patients With Mixed Aortic Valve Disease Versus Pure Aortic Stenosis
Authors: Raviteja Guddeti, Jai Parekh, Aravdeep Jhand, Ryan Walters, Sidakpal Panaich, Andrew Goldsweig, Venkata M. Alla
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-396 Predictive Modeling of the Primary Outcome of a Large-Scale Randomized Trial of Quantitative Flow Ratio Versus Angiography-Guided PCI Using Data Simulation
Authors: Yang Wang, Lei Song, Changdong Guan, Yanyan Zhao, Wei Li, Shengxian Tu, Martin Leon, Gregg Stone, Shubin Qiao, Bo Xu, Ajay Kirtane
Journal: Journal of the American College of Cardiology (2020)