tbuckley/cabot-search huggingface dataset:
Mixed Individual-Aggregate Data on All-Cause Mortality in Bullous Pemphigoid
Authors: Billal Tedbirt, André Gillibert, Emilie Andrieu, Vivien Hébert, Sarah Bastos, Neil J. Korman, Mark B. Y. Tang, Jun Li, Luca Borradori, Begonia Cortés, Soo-Chan Kim, Adrià Gual, Ting Xiao, Carilyn N. Wieland, Janet A. Fairley, Khaled Ezzedine, Pascal Joly
Journal: JAMA Dermatology (2021)

The 1-year standardized mortality ratio (SMR) of bullous pemphigoid (BP) has been reported as 2.15 to 7.56 and lower in the US than in Europe.To estimate the worldwide 1-year SMR of BP.PubMed, Embase, Cochrane Library, Google Scholar, Lissa, and gray literature (eg, medRxiv) were screened for studies of BP published from inception to June 10, 2020, with review of reference lists.Retrospective and prospective studies reporting 1-year all-cause mortality rate in patients with BP and providing age statistics (eg, mean [SD]).Two reviewers independently extracted the data. The 1-year SMR was computed in studies reporting 1-year mortality by combining information on age obtained from studies with aggregate data and individual data. Risk of representativity, misclassification, and attrition bias were assessed by a custom tool.The primary end point was the worldwide 1-year SMR. Secondary analysis included comparison of 1-year SMRs between continents in a meta-regression.Three studies were performed in the US (n = 260), 1 in South America (n = 45), 16 in Asia (n = 1903), and 36 in Europe (n = 10 132) for a total of 56 unique studies and 12 340 unique patients included in the meta-analysis (mean [SD] age, 77.3 [12.7] years; 55.9% women). The mean (SD) patient age in the United States was 75.6 (13.7) years; in Asia, 73.8 (13.6) years; and in Europe, 78.1 (12.3) years. The worldwide 1-year SMR was estimated at 2.93 (95% CI, 2.59-3.28; I2 = 85.6%) for all 56 studies. The 1-year SMR in the US was 2.40 (95% CI, 0.89-3.90; I2 = 86.3%) for 3 studies; in Asia, 3.53 (95% CI, 2.85-4.20; I2 = 86.3%) for 16 studies; and in Europe, 2.77 (95% CI, 2.35-3.19; I2 = 86.3%) for 36 studies. After adjustment on the expected 1-year mortality rate, the European 1-year SMR did not differ significantly from the 1-year SMR in the United States (-0.48 vs Europe; 95% CI, -2.09 to 1.14; P = .56) and Asia (0.51 vs Europe; 95% CI, -0.56 to 1.58; P = .35). Risk of attrition bias was high (>10% censorship) in 16 studies (28.6%), low in 16 (28.6%), and unclear in 24 (42.9%). Only 4 studies (7.1%) had a sampling method guaranteeing the representativity of BP cases in a population.Although heterogeneity was high and overall quality of follow-up was poor, this meta-analysis confirms the high mortality rate among patients with BP.
Assessment of Concordance and Discordance Among Clinical Studies Posted as Preprints and Subsequently Published in High-Impact Journals
Authors: Xiaoting Shi, Joseph S. Ross, Nishita Amancharla, Joshua D. Niforatos, Harlan M. Krumholz, Joshua D. Wallach
Journal: JAMA Network Open (2021)

This cross-sectional study examines the concordance between clinical studies posted as preprints and subsequently published in high-impact journals, including key study characteristics, reported results, and study interpretations.
Face Transplantation in a Black Patient — Racial Considerations and Early Outcomes
Authors: Martin Kauke, Adriana C. Panayi, Bianief Tchiloemba, Yannick F. Diehm, Valentin Haug, Branislav Kollar, Bridget Perry, Dhruv Singhal, Indranil Sinha, Leonardo V. Riella, Donald J. Annino, Bohdan Pomahac
Journal: New England Journal of Medicine (2021)

Face Transplantation in a Black Patient This letter describes early outcomes and challenges associated with a face transplantation in a Black patient.
Abstract 15027: The TIMI Risk Score for Secondary Prevention for Myocardial Infarction Applied to Patients With Peripheral Artery Disease: A Collaborative Analysis for the Chronic Kidney Disease Prognosis Consortium and the Risk Validation Scientific Committee
Authors: Yejin Mok, Shoshana H Ballew, Lori D Bash, Deepak L Bhatt, Marc P Bonaca, Juan Jesus Carrero, Josef Coresh, D’AgostinoRalph B, F Gerry R Fowkes, Sun Ha Jee, Timothy Kenealy, Csaba P Kovesdy, Kenneth W Mahaffey, Yingying Sang, Kunihiro Matsushita
Journal: Circulation (2018)

Objective: The TIMI Risk Score for secondary prevention (TRS2°P), a simple scoring system based on presence/absence of nine clinical factors, was developed to stratify the risk of secondary events ...
A cross-talk between CAR T cell subsets and the tumor microenvironment is essential for sustained cytotoxic activity
Authors: Morgane Boulch, Marine Cazaux, Yann Loe-Mie, Ronan Thibaut, Béatrice Corre, Fabrice Lemaître, Capucine L. Grandjean, Zacarias Garcia, Philippe Bousso
Journal: Science Immunology (2021)

Chimeric antigen receptor (CAR) T cell therapy relies on the activity of a large pool of tumor-targeting cytotoxic effectors. Whether CAR T cells act autonomously or require interactions with the tumor microenvironment (TME) remains incompletely understood. Here, we report an essential cross-talk between CAR T cell subsets and the TME for tumor control in an immunocompetent mouse B cell lymphoma model of anti-CD19 CAR T cell therapy. Using single-cell RNA sequencing, we revealed substantial modification of the TME during CAR T cell therapy. Interferon-γ (IFN-γ) produced by CAR T cells not only enhanced endogenous T and natural killer cell activity but was also essential for sustaining CAR T cell cytotoxicity, as revealed by intravital imaging. CAR T cell-derived IFN-γ facilitated host interleukin-12 production that supported host immune and CAR T cell responses. Compared with CD8+ CAR T cells, CD4+ CAR T cells were more efficient at host immune activation but less capable of direct tumor killing. In summary, CAR T cells do not act independently in vivo but rely instead on cytokine-mediated cross-talk with the TME for optimal activity. Invigorating CAR T cell interplay with the host represents an attractive strategy to prevent relapses after therapy.
Abstract 13957: TNF-α/MiR-133a Involved in Myocardial Leukocytes Infiltration and Cardiac Dysfunction on the Early Phase of Coronary Microembolization
Authors: Zhangwei Chen, Yuanyuan Cao, Juying Qian, Jianying Ma, Yunzeng Zou, Junbo Ge
Journal: Circulation (2015)

Objectives: MicroRNAs are small non-coding RNAs that regulate gene expression at the post-transcriptional level by either degradation or translational repression of a target mRNA. It has been demonstrated that miR-133a plays a critical role on inflammatory response after acute myocardial infarction. However, it is unknown about myocardial expression of miR-133a after coronary microembolization (CME) in mini-pigs. Methods: Ten mini-pigs were enroll in this study, including sham-operation group (n=5), CME group (n=7) and adalimumab pre-treatment group (n=6) (TNF-α antibody, 2mg/kg intracoronary injection before CME). Magnetic resonance imaging (3.0-T) was performed at baseline, 6th hour and one week after procedure. Serum TNF-α and troponin T were also detected. Myocardial expressions of miR-133a were detected by realtime-PCR method. Myocardium specimens were embedded in paraffin for hematoxylin and eosin (HE) staining, while number of leukocytes infiltration were analyzed by Leica DFC 320 digital soft. Results: Compared with sham-operation group, serum level of troponin T and TNF-α were increased significantly in CME group, while leukocyte infiltration on microembolization associated myocardium was also increased. Interestingly, myocardial expression of miR-133a was increased significantly after CME (2.33±0.62 vs. 1.28±0.68, P&lt;0.05). Cardiac function detected by MRI was decreased in CME group (LVEF at 6th hour: 55.2% vs. 61.4%, P&lt;0.05; LVEF at one week: 56.4% vs. 62.8%, P&lt;0.05). We found that pre-treatment with adalimumab not only significantly improved LVEF after CME (6th hour: 59.3% vs. 55.2%, P&lt;0.05; one week: 60.2% vs. 56.4%, P&lt;0.05), but also decreased myocardial expression of miR-133a (1.36±0.58 vs. 2.33±0.62, P&lt;0.05), which had a positive relation with the average number of leukocytes infiltration on microembolization area (r=0.364, P&lt;0.05) . Conclusions: TNF-α/miR-133a expression might be involved in cardiac dysfunction after CME, which was associated with the process of leukocytes infiltration.
P47.06 Delta-Radiomics Features for Assessment of Individualized Therapeutic Response in Small Cell Lung Cancer – A Pilot Study
Authors: J. Araujo Filho, Y. Murciano-Goroff, P. Gibbs, R. Perez-Johnston, W.V. Lai, C. Rudin, B. Li, M. Ginsberg
Journal: Journal of Thoracic Oncology (2021)
A B-Cell like Phenotype Is Associated with Sensitivity to Venetoclax in Multiple Myeloma
Authors: Vikas A. Gupta, Benjamin Barwick, Scott Newman, Jonathan J. Keats, Daniel Auclair, Shannon Matulis, Michael R. Rossi, Ajay K. Nooka, Jonathan L. Kaufman, Sagar Lonial, Lawrence H. Boise
Journal: Blood (2017)
Phase 2 study of ibrutinib in classic and variant hairy cell leukemia
Authors: Kerry A. Rogers, Leslie A. Andritsos, Lai Wei, Eric M. McLaughlin, Amy S. Ruppert, Mirela Anghelina, James S. Blachly, Timothy Call, Dai Chihara, Anees Dauki, Ling Guo, S. Percy Ivy, Lacey R. James, Daniel Jones, Robert J. Kreitman, Gerard Lozanski, David M. Lucas, Apollinaire Ngankeu, Mitch Phelps, Farhad Ravandi, Charles A. Schiffer, William E. Carson, Jeffrey A. Jones, Michael R. Grever
Journal: Blood (2021)
MA12.03 Prognostic Value of Clinical Staging According to TNM in SCLC Patients; A Real-World SEER Database Analysis.
Authors: E. Arriola Aperribay, J. Trigo Pérez, A. Sánchez Gastaldo, A. Navarro Mendivil, L. Crama, P. Ruiz Gracia, S. Ponce Aix
Journal: Journal of Thoracic Oncology (2021)
P44.04 Evaluating Lung Cancer Screening in People Living With HIV
Authors: S. Jindal, M. Serrano, S. Baron, S. Rikin, V. Mehta, M. Alexander, M. Stuart, J. Galeas, S. Packer, R. Grossberg, B. Halmos, L. Haramati
Journal: Journal of Thoracic Oncology (2021)
FP07.13 Clinical Characteristics and Outcomes in Patients With KRAS G12C Mutated Non-Small Cell Lung Cancer
Authors: B. Pellini, V. Ganesan, F. Wan, S. Sankararaman, S. Manyanont, N. Akhave, M. Baggstrom, J. Ward, S. Waqar, D. Morgensztern, R. Govindan, S. Devarakonda
Journal: Journal of Thoracic Oncology (2021)
From nonalcoholic fatty liver disease to metabolic-associated fatty liver disease: Big wave or ripple?
Authors: Seong Hee Kang, Yuri Cho, Soung Won Jeong, Seung Up Kim, Jin-Woo Lee
Journal: Clinical and Molecular Hepatology (2021)

There is some dissatisfaction with the term “nonalcoholic fatty liver disease (NAFLD),” which overemphasizes alcohol and underemphasizes the importance of metabolic risk factors in this disease. Recently, a consensus recommended “metabolic (dysfunction)-associated fatty liver disease (MAFLD)” as a more appropriate term to describe fatty liver diseases (FLD) associated with metabolic dysfunction. During the definition change from NAFLD to MAFLD, subjects with FLD and metabolic abnormalities, together with other etiologies of liver diseases such as alcohol, virus, or medication who have been excluded from the NAFLD criteria, were added to the MAFLD criteria, while subjects with FLD but without metabolic abnormality, who have been included in the NAFLD criteria, were excluded from the MAFLD criteria. This means that there is an emphasis on the metabolic dysfunction in MAFLD which may underestimate the prognostic value of hepatic steatosis itself, whereas the MAFLD criteria might better identify subjects who are at a higher risk of hepatic or cardiovascular outcomes. However, non-metabolic risk NAFLD subjects who are excluded from the MAFLD criteria are missed from the diagnosis, and their potential risk can be the cause of future diseases. Although huge controversies remain, this review focused on summarizing recent studies that compared the clinical and prognostic characteristics between subjects with NAFLD and MAFLD.
FP14.03 Osimertinib + Savolitinib in pts with EGFRm MET-Amplified/Overexpressed NSCLC: Phase Ib TATTON Parts B and D Final Analysis
Authors: J. Han, L. Sequist, M. Ahn, B.C. Cho, H. Yu, S. Kim, J.C. Yang, J.S. Lee, W. Su, D.M. Kowalski, S. Orlov, M. Cantarini, S. Ren, P. Frewer, X. Ou, P. Janne
Journal: Journal of Thoracic Oncology (2021)
The role of short-chain fatty acids in the interplay between gut microbiota and diet in cardio-metabolic health
Authors: Ana Nogal, Ana M. Valdes, Cristina Menni
Journal: Gut Microbes (2021)

The gut microbiota plays an important role in cardio-metabolic diseases with diet being among the strongest modulators of gut microbiota composition and function. Resistant dietary carbohydrates are fermented to short-chain fatty acids (SCFAs) by the gut bacteria. Fiber and omega-3 rich diets increase SCFAs production and abundance of SCFA-producing bacteria. Likewise, SCFAs can improve gut barrier integrity, glucose, and lipid metabolism, regulate the immune system, the inflammatory response, and blood pressure. Therefore, targeting the gut microbiota with dietary strategies leading to increased SCFA production may benefit cardio-metabolic health. In this review, we provide an overview of the association between diet, SCFAs produced by the gut microbiota and cardio-metabolic diseases. We first discuss the association between the human gut microbiota and cardio-metabolic diseases, then investigate the role of SCFAs and finally explore the beneficial effects of specific dietary interventions that can improve cardio-metabolic outcomes through boosting the SCFA production.
Abstract S06-04: Telehealth experiences of adolescent and young adult cancer patients and survivors during the COVID-19 pandemic
Authors: Karely Mann, Austin R. Waters, Perla L. Vaca Lopez, Echo L. Warner, Judy Ou, Heydon Kaddas, Joemy Ramsay, Nicole Ray, Tomoko Tsukamoto, Douglas B. Fair, Joseph M. Letourneau, Mark A. Lewis, David Gill, Lauri Linder, Anne C. Kirchhoff
Journal: Clinical Cancer Research (2021)

Abstract Purpose: To describe adolescent and young adult (AYA) cancer patients’ and survivors’ experiences with telehealth during the COVID-19 pandemic. Methods: Eligible participants were identified through the Huntsman Intermountain Adolescent and Young Adult Cancer Care Program, which provides age-specific programming and patient navigation to AYA cancer patients and survivors in Utah and surrounding Mountain West states. Participants were emailed an online survey if they were currently age 18 or older and had been diagnosed with cancer between the ages of 15-39 years. We applied descriptive statistics to summarize demographics, comfortability with technology, access to reliable internet connection, and perceived quality of care while using telehealth. Results: AYAs (N=280) were an average of 29.4 years old at survey (range 18-58); 65.2% were female and 82.4% non-Hispanic white. Over half (54.2%) had received cancer treatment since March 2020. All participants reported owning a computer, tablet, and/or smart phone they could use for telehealth appointments. The majority (93.5%) reported almost always or always having a reliable internet connection. AYAs felt most comfortable having a telehealth appointment in their own home (96.4%); only 12.5% felt comfortable using telehealth at work. Since March 2020, (N=183) 65.4% had a health care visit moved to a telehealth platform due to COVID-19. Of those who recently moved to telehealth, 60.1% had an oncology visit, 33.9% had a primary care visit, and 31.1% had a mental health visit. Additionally over one-third (35.2%) reported the quality of their medical care had decreased since moving to telehealth. This was most commonly due to 1) troubles with audio, video, or connecting through telehealth platforms; 2) telehealth visits feeling impersonal; and 3) feeling that providers more easily dismissed or did not fully address their symptoms. Conclusions: Although AYAs are digital natives, over one-third of AYAs feel the quality of their medical care has decreased since moving to telehealth for COVID-19. Further research should explore medical provider training in using telehealth systems and encourage telehealth practices that help AYAs feel more supported and understood. Citation Format: Karely Mann, Austin R. Waters, Perla L. Vaca Lopez, Echo L. Warner, Judy Ou, Heydon Kaddas, Joemy Ramsay, Nicole Ray, Tomoko Tsukamoto, Douglas B. Fair, Joseph M. Letourneau, Mark A. Lewis, David Gill, Lauri Linder, Anne C. Kirchhoff. Telehealth experiences of adolescent and young adult cancer patients and survivors during the COVID-19 pandemic [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr S06-04.
Biden’s choice and FDA’s loosening standards of evidence
Authors: Jeanne Lenzer
Journal: BMJ (2021)

<h3>Abstract</h3> Nonsense-mediated RNA decay (NMD) is well recognized as an RNA surveillance pathway that targets aberrant mRNAs with premature translation termination codons (PTCs) for degradation; however, its molecular mechanisms and roles in health and disease remain incompletely understood. In this study, we developed a novel reporter system that can accurately measure NMD activity in individual cells. By carrying out a genome-wide CRISPR/Cas9 knockout screen using this reporter system, we identified novel NMD-promoting factors, including multiple components of the SF3B complex and other U2 spliceosome factors. Interestingly, we also found that cells with mutations in the U2 spliceosome genes <i>SF3B1</i> and <i>U2AF1—</i>which are commonly found in myelodysplastic syndrome (MDS) and cancers<i>—</i>have overall attenuated NMD activity. Furthermore, we found that compared to wild type cells, <i>SF3B1</i> and <i>U2AF1</i> mutant cells are more sensitive to NMD inhibition, a phenotype that is accompanied by elevated DNA replication obstruction, DNA damage and chromosomal instability. Remarkably, the sensitivity of spliceosome mutant cells to NMD inhibition could be rescued by overexpression of RNase H1, which removes R-loops in the genome. Together, our findings shed new light on the functional interplay between NMD and RNA splicing and suggest a novel strategy for the treatment of MDS and cancers with spliceosome mutations.
Abstract 14348: Risk Stratification for Critical Limb Ischemia and Amputation in Patients With Atherosclerosis: Insights From the TRA2P-TIMI 50 Trial
Authors: Marc P Bonaca, Arman Qamar, Mark A Creager, Jeong-Gun Park, Benjamin M Scirica, David A Morrow, Marc S Sabatine
Journal: Circulation (2019)

Introduction: Critical limb ischemia and amputation (CLI/AMP) are major morbidities of atherosclerosis and diabetes (DM). Risk stratification may enable targeting of more intensive preventive strat...
Predisplacement Abuse and Postdisplacement Factors Associated With Mental Health Symptoms After Forced Migration Among Rohingya Refugees in Bangladesh
Authors: Ahmed Hossain, Redwan Bin Abdul Baten, Zeeba Zahra Sultana, Taifur Rahman, Mirza Asif Adnan, Moynul Hossain, Taifur Aziz Khan, Muzakkir Kamar Uddin
Journal: JAMA Network Open (2021)

<h3>Importance</h3> At the end of August 2017, violence and persecution in Myanmar's Rakhine state forced nearly 1 million Rohingyas to flee to Bangladesh for their lives and seek shelter. Many refugees, after their traumatic experiences leaving Myanmar, experience mental health problems. <h3>Objectives</h3> To identify the prevalence of posttraumatic stress symptoms (PTSSs) among displaced Rohingya adults and investigate the association of predisplacement abuse and postdisplacement factors with PTSSs. <h3>Design, Setting, and Participants</h3> This cross-sectional analysis from a household survey of 1184 Rohingya adults aged 18 years or older was conducted in 8 refugee camps within Cox's Bazar, Bangladesh, from September 17, 2019, to January 11, 2020. <h3>Main Outcomes and Measures</h3> The Impact of Event Scale–Revised was used to assess PTSSs. The possible range of scores was 0 to 88; moderate PTSSs were classified using a score cutoff of 33 to 38 and severe PTSSs were classified using a score cutoff of 39 and above. Adjusted prevalence ratios (aPRs) were estimated using a multivariable logistic regression model adjusted for potential confounders. <h3>Results</h3> Of 1184 participants (625 men [52.8%]; mean [SD] age, 35.1 [13.4] years), 552 (46.6%) had severe PTSSs, and 274 (23.1%) had moderate PTSSs. In Bangladesh, refugees are not legally permitted to work in refugees camps, but 276 of 1165 respondents (23.7%) had temporary paid jobs. Moreover, 113 of the 276 working participants (40.9%) and 430 of the 889 nonworking participants (48.4%) reported severe PTSSs. A total of 496 respondents (41.9%) reported inadequate humanitarian aid for their families, and among them, 281 (56.7%) reported severe PTSSs. A total of 136 of 1177 respondents (11.6%) experienced both physical and sexual abuse in Myanmar, and 87 (64.0%) of them had severe PTSSs. The multivariable analysis showed a reduced risk of PTSSs with appropriate humanitarian assistance (aPR, 0.50; CI, 0.38-0.65). Experiencing both physical and sexual abuse before displacement had a significant association with PTSSs (aPR, 2.09; CI, 1.41-3.07). Opportunities for paid employment in refugee camps also reduced the risks of PTSSs (aPR, 0.69; CI, 0.52-0.91). <h3>Conclusions and Relevance</h3> The high prevalence of self-reported severe PTSSs in Rohingya refugees suggests that the trauma of displacement and the violent consequences of military crackdowns still exist. In the Rohingya camp settings of Bangladesh, employment opportunity and sufficient humanitarian aid hold promise as potential interventions to reduce the high prevalence of severe PTSSs. Mental health symptoms were more prevalent in adults who experienced physical abuse or physical and sexual abuse before displacement.
Sialylated immunoglobulin G: a promising diagnostic and therapeutic strategy for autoimmune diseases
Authors: Danqi Li, Yuchen Lou, Yamin Zhang, Si Liu, Jun Li, Juan Tao
Journal: Theranostics (2021)

Human immunoglobulin G (IgG), especially autoantibodies, has major implications for the diagnosis and management of a wide range of autoimmune diseases. However, some healthy individuals also have autoantibodies, while a portion of patients with autoimmune diseases test negative for serologic autoantibodies. Recent advances in glycomics have shown that IgG Fc N-glycosylations are more reliable diagnostic and monitoring biomarkers than total IgG autoantibodies in a wide variety of autoimmune diseases. Furthermore, these N-glycosylations of IgG Fc, particularly sialylation, have been reported to exert significant anti-inflammatory effects by upregulating inhibitory FcγRIIb on effector macrophages and reducing the affinity of IgG for either complement protein or activating Fc gamma receptors. Therefore, sialylated IgG is a potential therapeutic strategy for attenuating pathogenic autoimmunity. IgG sialylation-based therapies for autoimmune diseases generated through genetic, metabolic or chemoenzymatic modifications have made some advances in both preclinical studies and clinical trials.