tbuckley/cabot-search huggingface dataset:
Clinical impact and quality of randomized controlled trials involving interventions evaluating artificial intelligence prediction tools: a systematic review
Authors: Qian Zhou, Zhi-hang Chen, Yi-heng Cao, Sui Peng
Journal: npj Digital Medicine (2021)

The evidence of the impact of traditional statistical (TS) and artificial intelligence (AI) tool interventions in clinical practice was limited. This study aimed to investigate the clinical impact and quality of randomized controlled trials (RCTs) involving interventions evaluating TS, machine learning (ML), and deep learning (DL) prediction tools. A systematic review on PubMed was conducted to identify RCTs involving TS/ML/DL tool interventions in the past decade. A total of 65 RCTs from 26,082 records were included. A majority of them had model development studies and generally good performance was achieved. The function of TS and ML tools in the RCTs mainly included assistive treatment decisions, assistive diagnosis, and risk stratification, but DL trials were only conducted for assistive diagnosis. Nearly two-fifths of the trial interventions showed no clinical benefit compared to standard care. Though DL and ML interventions achieved higher rates of positive results than TS in the RCTs, in trials with low risk of bias (17/65) the advantage of DL to TS was reduced while the advantage of ML to TS disappeared. The current applications of DL were not yet fully spread performed in medicine. It is predictable that DL will integrate more complex clinical problems than ML and TS tools in the future. Therefore, rigorous studies are required before the clinical application of these tools.
METTL3-mediated m <sup>6</sup> A modification of ATG7 regulates autophagy-GATA4 axis to promote cellular senescence and osteoarthritis progression
Authors: Xiang Chen, Wang Gong, Xiaoyan Shao, Tianshu Shi, Lei Zhang, Jian Dong, Yong Shi, Siyu Shen, Jianghui Qin, Qing Jiang, Baosheng Guo
Journal: Annals of the Rheumatic Diseases (2021)

Objective The aim of the study was to investigate the role and regulatory mechanisms of fibroblast-like synoviocytes (FLSs) and their senescence in the progression of osteoarthritis (OA). Methods Synovial tissues from normal patients and patients with OA were collected. Synovium FLS senescence was analysed by immunofluorescence and western blotting. The role of methyltransferase-like 3 (METTL3) in autophagy regulation was explored using N6-methyladenosine (m 6 A)-methylated RNA and RNA immunoprecipitation assays. Mice subjected to destabilisation of the medial meniscus (DMM) surgery were intra-articularly injected with or without pAAV9 loaded with small interfering RNA (siRNA) targeting METTL3. Histological analysis was performed to determine cartilage damage. Results Senescent FLSs were markedly increased with the progression of OA in patients and mouse models. We determined that impaired autophagy occurred in OA-FLS, resulting in the upregulation of senescence-associated secretory phenotype (SASP). Re-establishment of autophagy reversed the senescent phenotype by suppressing GATA4. Further, we observed for the first time that excessive m 6 A modification negatively regulated autophagy in OA-FLS. Mechanistically, METTL3-mediated m 6 A modification decreased the expression of autophagy-related 7, an E-1 enzyme crucial for the formation of autophagosomes, by attenuating its RNA stability. Silencing METTL3 enhanced autophagic flux and inhibited SASP expression in OA-FLS. Intra-articular injection of synovium-targeted METTL3 siRNA suppressed cellular senescence propagation in joints and ameliorated DMM-induced cartilage destruction. Conclusions Our study revealed the important role of FLS senescence in OA progression. Targeted METTL3 inhibition could alleviate the senescence of FLS and limit OA development in experimental animal models, providing a potential strategy for OA therapy.
Selection of eligible participants for screening for lung cancer using primary care data
Authors: Emma L O'Dowd, Kevin ten Haaf, Jaspreet Kaur, Stephen W Duffy, William Hamilton, Richard B Hubbard, John K Field, Matthew Ej Callister, Sam M Janes, Harry J de Koning, Janette Rawlinson, David R Baldwin
Journal: Thorax (2021)

Lung cancer screening is effective if offered to people at increased risk of the disease. Currently, direct contact with potential participants is required for evaluating risk. A way to reduce the number of ineligible people contacted might be to apply risk-prediction models directly to digital primary care data, but model performance in this setting is unknown. Method The Clinical Practice Research Datalink, a computerised, longitudinal primary care database, was used to evaluate the Liverpool Lung Project V.2 (LLP v2 ) and Prostate Lung Colorectal and Ovarian (modified 2012) (PLCO m2012 ) models. Lung cancer occurrence over 5–6 years was measured in ever-smokers aged 50–80 years and compared with 5-year (LLP v2 ) and 6-year (PLCO m2012 ) predicted risk. Results Over 5 and 6 years, 7123 and 7876 lung cancers occurred, respectively, from a cohort of 842 109 ever-smokers. After recalibration, LLP V2 produced a c-statistic of 0.700 (0.694–0.710), but mean predicted risk was over-estimated (predicted: 4.61%, actual: 0.9%). PLCO m2012 showed similar performance (c-statistic: 0.679 (0.673–0.685), predicted risk: 3.76%. Applying risk-thresholds of 1% (LLP v2 ) and 0.15% (PLCO m2012 ), would avoid contacting 42.7% and 27.4% of ever-smokers who did not develop lung cancer for screening eligibility assessment, at the cost of missing 15.6% and 11.4% of lung cancers. Conclusion Risk-prediction models showed only moderate discrimination when applied to routinely collected primary care data, which may be explained by quality and completeness of data. However, they may substantially reduce the number of people for initial evaluation of screening eligibility, at the cost of missing some lung cancers. Further work is needed to establish whether newer models have improved performance in primary care data.
TCT-84 Serial NIRS-IVUS Assessment of Changes in Coronary Lumen Area During 2-Year Follow-Up: Insights From the PROSPECT ABSORB Trial
Authors: Mitsuaki Matsumura, Akiko Maehara, Gary Mintz, Ori Ben-Yehuda, Michael Maeng, Lars Kjoller-Hansen, Thomas Engstroem, Ole Fröbert, Jonas Persson, Rune Wiseth, Alf Inge Larsen, Lisette Okkels Jensen, Jan Erik Nordrehaug, Oyvind Bleie, Elmir Omerovic, Zhipeng Zhou, Claes Held, Stefan James, Ziad Ali, David Erlinge, Gregg Stone
Journal: Journal of the American College of Cardiology (2021)
Effect of Immunomodulatory Drugs (IMiDs) on Immune Effectors after Autologous Stem Cell Transplantation (ASCT) in Multiple Myeloma
Authors: David M Foureau, Manisha Bhutani, Qing Zhang, Myra M Robinson, Adina Wynn, Nury M Steuerwald, Lawrence J Druhan, Fei Guo, Katherine Rigby, Mitchell Turner, Reed Friend, Shebli Atrash, Chelsea Sprouse, Ami Ndiaye, James T Symanowski, Belinda Rene Avalos, Edward A Copelan, Peter M. Voorhees, Saad Z Usmani
Journal: Blood (2017)
TCT-450 Systolic Heart Failure Is Associated With Higher Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Michael Fatuyi, Leanne Pereira, Vahid Namdarizandi, Awfa Zain Elabidin, Vivek Sharma, Oluwafunmilayo Fatuyi, Oluwasegun Akinti, Rukayat Otulana, Emmanuel Akuna, Kamal Shemisa
Journal: Journal of the American College of Cardiology (2021)
NIAID workshop on secondary vaccine effects
Authors: Aaron M. Joffe, Eun-Chung Park, Alison Augustine, Chao Jiang, Mercy PrabhuDas, Nancy Vazquez-Maldonado, Peter Aaby, Galit Alter, Maziar Divangahi, Peter Hotez, Shabaana Khader, Mihai G. Netea, William A. Petri, Stanley Plotkin, Kimberly M. Thompson
Journal: Nature Immunology (2021)
Are aerosols generated during lung function testing in patients and healthy volunteers? Results from the AERATOR study
Authors: Sadiyah Sheikh, Fergus W Hamilton, George W Nava, Florence K A Gregson, David T Arnold, Colleen Riley, Jules Brown, Jonathan P Reid, Bryan R Bzdek, Nicholas A Maskell, James William Dodd
Journal: Thorax (2021)

Pulmonary function tests are fundamental to the diagnosis and monitoring of respiratory diseases. There is uncertainty around whether potentially infectious aerosols are produced during testing and there are limited data on mitigation strategies to reduce risk to staff. Healthy volunteers and patients with lung disease underwent standardised spirometry, peak flow and FE NO assessments. Aerosol number concentration was sampled using an aerodynamic particle sizer and an optical particle sizer. Measured aerosol concentrations were compared with breathing, speaking and voluntary coughing. Mitigation strategies included a standard viral filter and a full-face mask normally used for exercise testing (to mitigate induced coughing). 147 measures were collected from 33 healthy volunteers and 10 patients with lung disease. The aerosol number concentration was highest in coughs (1.45–1.61 particles/cm 3 ), followed by unfiltered peak flow (0.37–0.76 particles/cm 3 ). Addition of a viral filter to peak flow reduced aerosol emission by a factor of 10 without affecting the results. On average, coughs produced 22 times more aerosols than standard spirometry (with filter) in patients and 56 times more aerosols in healthy volunteers. FE NO measurement produced negligible aerosols. Cardiopulmonary exercise test (CPET) masks reduced aerosol emission when breathing, speaking and coughing significantly. Lung function testing produces less aerosols than voluntary coughing. CPET masks may be used to reduce aerosol emission from induced coughing. Standard viral filters are sufficiently effective to allow guidelines to remove lung function testing from the list of aerosol-generating procedures.
Monoclonal Antibodies for COVID-19 Preexposure Prophylaxis Can’t Come Fast Enough for Some People
Authors: Rita Rubin
Journal: JAMA (2021)

Caroline L. Behr, AB; Karen E. Joynt Maddox, MD, MPH; Ellen Meara, PhD; Arnold M. Epstein, MD, MA; E. John Orav, PhD; Michael L. Barnett, MD, MS
TCT-322 Prevention of Radial Artery Occlusion After Transradial Access Using Nitroglycerin (Patens Trial)
Authors: Roberto Léo da Silva, Rodrigo Joaquim, Pedro Beraldo, Alexandre Abizaid, Ramiro Vieira, Vanderlei Pereira, Renata Viana, Amanda Sousa, Fausto Feres, Jose Costa
Journal: Journal of the American College of Cardiology (2021)
TCT-44 The Impact of Transcatheter Aortic Valve Replacement on Gastrointestinal Bleeding in Aortic Stenosis
Authors: James Brown, Ibrahim Sultan, Jordann Lewis, Floyd Thoma, Dustin Kliner, Derek Serna-Gallegos, Saurabh Sanon, Suresh Mulukutla, Forozan Navid, Catalin Toma
Journal: Journal of the American College of Cardiology (2021)
Prediction of Personal Glycemic Responses to Food for Individuals With Type 1 Diabetes Through Integration of Clinical and Microbial Data
Authors: Smadar Shilo, Anastasia Godneva, Marianna Rachmiel, Tal Korem, Dmitry Kolobkov, Tal Karady, Noam Bar, Bat Chen Wolf, Yitav Glantz-Gashai, Michal Cohen, Nehama Zuckerman Levin, Naim Shehadeh, Noah Gruber, Neriya Levran, Shlomit Koren, Adina Weinberger, Orit Pinhas-Hamiel, Eran Segal
Journal: Diabetes Care (2021)

OBJECTIVE Despite technological advances, results from various clinical trials have repeatedly shown that many individuals with type 1 diabetes (T1D) do not achieve their glycemic goals. One of the major challenges in disease management is the administration of an accurate amount of insulin for each meal that will match the expected postprandial glycemic response (PPGR). The objective of this study was to develop a prediction model for PPGR in individuals with T1D. RESEARCH DESIGN AND METHODS We recruited individuals with T1D who were using continuous glucose monitoring and continuous subcutaneous insulin infusion devices simultaneously to a prospective cohort and profiled them for 2 weeks. Participants were asked to report real-time dietary intake using a designated mobile app. We measured their PPGRs and devised machine learning algorithms for PPGR prediction, which integrate glucose measurements, insulin dosages, dietary habits, blood parameters, anthropometrics, exercise, and gut microbiota. Data of the PPGR of 900 healthy individuals to 41,371 meals were also integrated into the model. The performance of the models was evaluated with 10-fold cross validation. RESULTS A total of 121 individuals with T1D, 75 adults and 46 children, were included in the study. PPGR to 6,377 meals was measured. Our PPGR prediction model substantially outperforms a baseline model with emulation of standard of care (correlation of R = 0.59 compared with R = 0.40 for predicted and observed PPGR respectively; P &amp;lt; 10−10). The model was robust across different subpopulations. Feature attribution analysis revealed that glucose levels at meal initiation, glucose trend 30 min prior to meal, meal carbohydrate content, and meal’s carbohydrate-to-fat ratio were the most influential features for the model. CONCLUSIONS Our model enables a more accurate prediction of PPGR and therefore may allow a better adjustment of the required insulin dosage for meals. It can be further implemented in closed loop systems and may lead to rationally designed nutritional interventions personally tailored for individuals with T1D on the basis of meals with expected low glycemic response.
TCT-473 Impact of Major Infections on 10-Year Mortality After Revascularization in Patients With Complex Coronary Artery Disease
Authors: Masafumi Ono, Hideyuki Kawashima, Hironori Hara, Massimo Mancone, Michael Mack, David Holmes, Marie-Claude Morice, Pieter Kappetein, Daniel Thuijs, Thilo Noack, Friedrich-Wilhelm Mohr, Piroze Davierwala, Yoshinobu Onuma, Patrick Serruys
Journal: Journal of the American College of Cardiology (2021)
Integrins regulate stemness in solid tumor: an emerging therapeutic target
Authors: Jiangling Xiong, Lianlian Yan, Cheng Zou, Kai Wang, Mengjie Chen, Bin Xu, Zhipeng Zhou, Dingxiao Zhang
Journal: Journal of Hematology & Oncology (2021)

Abstract Integrins are the adhesion molecules and transmembrane receptors that consist of α and β subunits. After binding to extracellular matrix components, integrins trigger intracellular signaling and regulate a wide spectrum of cellular functions, including cell survival, proliferation, differentiation and migration. Since the pattern of integrins expression is a key determinant of cell behavior in response to microenvironmental cues, deregulation of integrins caused by various mechanisms has been causally linked to cancer development and progression in several solid tumor types. In this review, we discuss the integrin signalosome with a highlight of a few key pro-oncogenic pathways elicited by integrins, and uncover the mutational and transcriptomic landscape of integrin-encoding genes across human cancers. In addition, we focus on the integrin-mediated control of cancer stem cell and tumor stemness in general, such as tumor initiation, epithelial plasticity, organotropic metastasis and drug resistance. With insights into how integrins contribute to the stem-like functions, we now gain better understanding of the integrin signalosome, which will greatly assist novel therapeutic development and more precise clinical decisions.
Timing of SARS-CoV-2 vaccination during the third trimester of pregnancy and transplacental antibody transfer: a prospective cohort study
Authors: Amihai Rottenstreich, Gila Zarbiv, Esther Oiknine-Djian, Olesya Vorontsov, Roy Zigron, Geffen Kleinstern, Dana G. Wolf, Shay Porat
Journal: Clinical Microbiology and Infection (2021)
Indoleamine 2,3-dioxygenase-1, a Novel Therapeutic Target for Post-Vascular Injury Thrombosis in CKD
Authors: Joshua A. Walker, Sean Richards, Stephen A. Whelan, Sung Bok Yoo, Teresa L. Russell, Nkiruka Arinze, Saran Lotfollahzadeh, Marc A. Napoleon, Mostafa Belghasem, Norman Lee, Laura M. Dember, Katya Ravid, Vipul C. Chitalia
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement Patients with CKD are at a markedly higher risk of thrombosis after vascular procedures. Uremic solutes, such as indoxyl sulfate and kynurenine, are important contributors to this complication through tissue factor (TF), a trigger of the extrinsic coagulation cascade. This study examines the role of indoleamine 2,3-dioxygenase-1 (IDO-1), a key enzyme in kynurenine biogenesis, in thrombotic complications in CKD. Using genomic and pharmacological approaches, this study demonstrates that IDO-1 is a critical regulator of TF and thrombosis after vascular injury in CKD mice. Indoxyl sulfate upregulates IDO-1, creating a feedback-forward loop. IDO-1 activity was higher in patients with CKD, who developed thrombosis after vascular interventions. This study identifies IDO-1 as a therapeutic target and uncovers crosstalk between uremic solutes, perpetuating their toxic effect. Background CKD, characterized by retained uremic solutes, is a strong and independent risk factor for thrombosis after vascular procedures . Urem ic solutes such as indoxyl sulfate (IS) and kynurenine (Kyn) mediate prothrombotic effect through tissue factor (TF). IS and Kyn biogenesis depends on multiple enzymes, with therapeutic implications unexplored. We examined the role of indoleamine 2,3-dioxygenase-1 (IDO-1), a rate-limiting enzyme of kynurenine biogenesis, in CKD-associated thrombosis after vascular injury. Methods IDO-1 expression in mice and human vessels was examined. IDO-1 −/− mice, IDO-1 inhibitors, an adenine-induced CKD, and carotid artery injury models were used. Results Both global IDO-1 −/− CKD mice and IDO-1 inhibitor in wild-type CKD mice showed reduced blood Kyn levels, TF expression in their arteries, and thrombogenicity compared with respective controls. Several advanced IDO-1 inhibitors downregulated TF expression in primary human aortic vascular smooth muscle cells specifically in response to uremic serum. Further mechanistic probing of arteries from an IS-specific mouse model, and CKD mice, showed upregulation of IDO-1 protein, which was due to inhibition of its polyubiquitination and degradation by IS in vascular smooth muscle cells. In two cohorts of patients with advanced CKD, blood IDO-1 activity was significantly higher in sera of study participants who subsequently developed thrombosis after endovascular interventions or vascular surgery. Conclusion Leveraging genetic and pharmacologic manipulation in experimental models and data from human studies implicate IS as an inducer of IDO-1 and a perpetuator of the thrombotic milieu and supports IDO-1 as an antithrombotic target in CKD.
Use of Electronic Consent and Navigating the Ethical and Governance Issues: Experience from the NightLife study
Authors: Niamh A. Quann, Victoria Cluley, Katherine L. Hull, James Burton
Journal: Journal of the American Society of Nephrology (2021)

Background: UK Government COVID-19 restrictions have necessitated rethinking the conduct of healthcare research. Obtaining informed, written consent remains a necessity that requires adaptation to accommodate the virtual environment. Here we report the experience of implementing electronic consent as part of the NightLife study. NightLife is a randomised controlled trial assessing the effectiveness of thrice weekly, extended, in-centre nocturnal haemodialysis. Continuation of the qualitative workstream during the COVID-19 pandemic resulted in the implementation of electronic consent where face-to-face consent was unfeasible. Methods: As electronic consent was not part of the original study design, the proposal to use DocuSign to obtain electronic consent was discussed with the Trial Management Group (TMG), patient representatives and study Sponsor;a substantial protocol amendment was submitted. The study team liaised with the University's Information Governance (IG) and IT Risk and Continuity departments to mitigate potential data protection issues. A data protection impact assessment was completed to outline the data handling, management and storage arrangements. The functionality and practicality of the DocuSign portal was trialled and the Database Development team confirmed it integrated well with the clinical study database. Results: The substantial protocol amendment was reviewed by the Research Ethics Committee, Health Research Authority and Confidentiality Advisory Group and received regulatory approvals less than three weeks after submission. As part of capacity and capability assessments at participating centres, approval was sought from local Privacy and Data Protection Officers with no issues identified. Conclusions: Implementation of DocuSign as an electronic consent platform highlighted the importance of early and effective dialogue with the TMG, patient representatives, Sponsor, IG and Data Protection departments. While advantageous in the COVID-19 climate, face-to-face consent is still favoured and will recommence once restrictions are lifted. Integrating electronic consent is feasible from an ethical and governance perspective and represents an alternative for other studies that now require virtual engagement.
Understanding Risks and Our Responsibility to Living Donors
Authors: John S. Gill, Jesse Schold, Bruce Kaplan
Journal: Journal of the American Society of Nephrology (2021)

Nearly 70 years after the first living donor kidney transplant, the practice of living donation continues despite incomplete information about the long-term risks of donation and the absence of resources for lifelong postdonation care. As members of the kidney community, we have a responsibility to
TCT-86 Anatomic and Functional Discordance Among Patients With Nonobstructive Coronary Disease
Authors: Jennifer Rymer, Hidenobu Takagi, Angela Lowenstern, Mark Rabbat, Timothy Fairbairn, Kavitha Chinnaiyan, Pamela Douglas, Lynne Koweek, Daniel Berman, Bernard De Bruyne, Jeroen Bax, Takashi Akasaka, Tetsuya Amano, Koen Nieman, Campbell Rogers, Hironori Kitabata, Niels Peter Rønnow Sand, Tomohiro Kawasaki, Sarah Mullen, Hitoshi Matsuo, Bjarne Norgaard, Jonathon Leipsic, Manesh Patel, Melissa Daubert
Journal: Journal of the American College of Cardiology (2021)
TCT-497 Rate of 30-Day Readmission and Economic Burden in Patients With Protein-Energy Malnutrition Undergoing Transcatheter Aortic Valve Replacement
Authors: Michael Fatuyi, Leanne Pereira, Vahid Namdarizandi, Awfa Zain Elabidin, Emmanuel Akuna, Rukayat Otulana, Oluwasegun Akinti, Oluwafunmilayo Fatuyi, Olukayode Busari, Asimul Ansari, Puvi Seshiah, Kamal Shemisa
Journal: Journal of the American College of Cardiology (2021)
DNA methylation profiling as a model for discovery and precision diagnostics in neuro-oncology
Authors: Drew Pratt, Felix Sahm, Kenneth Aldape
Journal: Neuro-Oncology (2021)

Abstract Recent years have witnessed a shift to more objective and biologically-driven methods for central nervous system (CNS) tumor classification. The 2016 world health organization (WHO) classification update (“blue book”) introduced molecular diagnostic criteria into the definitions of specific entities as a response to the plethora of evidence that key molecular alterations define distinct tumor types and are clinically meaningful. While in the past such diagnostic alterations included specific mutations, copy number changes, or gene fusions, the emergence of DNA methylation arrays in recent years has similarly resulted in improved diagnostic precision, increased reliability, and has provided an effective framework for the discovery of new tumor types. In many instances, there is an intimate relationship between these mutations/fusions and DNA methylation signatures. The adoption of methylation data into neuro-oncology nosology has been greatly aided by the availability of technology compatible with clinical diagnostics, along with the development of a freely accessible machine learning-based classifier. In this review, we highlight the utility of DNA methylation profiling in CNS tumor classification with a focus on recently described novel and rare tumor types, as well as its contribution to refining existing types.