tbuckley/cabot-search huggingface dataset:
Abstract P4-07-21: High <i>Tinagl1</i> expression is a marker of good prognosis in breast cancer
Authors: Akiko Kato, Naoto Kondo, Yumi Wanifuchi-Endo, Takashi Fujita, Tomoko Asano, Tomoka Hisada, Yasuaki Uemoto, Mitsuo Terada, Tatsuya Toyama
Journal: Cancer Research (2022)

Abstract Background: Tubulointerstitial nephritis antigen-like 1 (Tinagl1) is reported to inhibit integrin and epidermal growth factor receptor (EGFR) and suppress tumor metastasis and growth in breast cancer. We investigated the association between Tinagl1 mRNA expression and clinicopathological factors and prognosis of breast cancer patients with long-term follow-up. The median follow-up period was 12.0 years. Materials and Methods: A total of 599 consecutive primary invasive breast cancer patients with available tissue from surgery in our hospital from 1992 to 2008 were included in this study. We examined the association between Tinagl1 mRNA expression and prognostic and clinicopathological factors using the TaqMan real-time PCR system. Statistical analysis was performed using the Kaplan-Meier method and the Cox proportional hazards model. Results: High expression of Tinagl1 mRNA was associated with significantly better disease-free survival (DFS) and overall survival (OS) than low expression (P=0.003 and P=0.01, respectively). In estrogen receptor (ER)-positive patients, DFS and OS were also better in the high Tinagl1 mRNA expression group (P=0.01 and P=0.03, respectively). However, there was no significant difference in DFS and OS in triple-negative breast cancer. Low Tinagl1 mRNA expression was positively associated with higher tumor grade. Multivariate analysis showed that low Tinagl1 mRNA expression, together with lymph node positivity, was an independent poor prognostic factor in DFS (HR 1.48; 95% CI 1.06-2.05, P=0.02). Conclusions: Our findings suggest that Tinagl1 has a role in the metastasis of breast cancer, and that its expression could be a promising candidate biomarker of prognosis in breast cancer patients. Variablesn(%)DSF Univariate P valueDFS Multivariate P valueHR (95% CI)Nodal status590Negative349 (59.2)1Positive241 (40.8)&amp;lt;0.0001&amp;lt;0.00013.16(2.25-4.45)Tinagl1 mRNA expression599High300 (50.1)1Low299 (49.9)0.0030.021.48(1.06-2.05) Citation Format: Akiko Kato, Naoto Kondo, Yumi Wanifuchi-Endo, Takashi Fujita, Tomoko Asano, Tomoka Hisada, Yasuaki Uemoto, Mitsuo Terada, Tatsuya Toyama. High Tinagl1 expression is a marker of good prognosis in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-21.
Humanistic and Economic Burden of Conversion Therapy Among LGBTQ Youths in the United States
Authors: Anna Forsythe, Casey Pick, Gabriel Tremblay, Shreena Malaviya, Amy Green, Karen Sandman
Journal: JAMA Pediatrics (2022)

<h3>Importance</h3> Sexual orientation and gender identity change efforts (SOGICE), also called<i>conversion therapy</i>, is a discredited practice attempting to convert lesbian, gay, bisexual, transgender, queer, or questioning (LGBTQ) individuals to be heterosexual and/or cisgender. <h3>Objectives</h3> To identify and synthesize evidence on the humanistic and economic consequences of SOGICE among LGBTQ youths in the US. <h3>Design, Setting, and Participants</h3> This study, conducted from December 1, 2020, to February 15, 2021, included a systematic literature review and economic evaluation. The literature review analyzed published evidence on SOGICE among LGBTQ individuals of any age. The economic model evaluated the use of SOGICE vs no intervention, affirmative therapy vs no intervention, and affirmative therapy vs SOGICE to estimate the costs and adverse outcomes for each scenario and to assess the overall US economic burden of SOGICE. Published literature and public sources were used to estimate the number of LGBTQ youths exposed to SOGICE, the types of therapy received, and the associated adverse events (anxiety, severe psychological distress, depression, alcohol or substance abuse, suicide attempts, and fatalities). <h3>Exposures</h3> SOGICE (licensed or religion-based practitioners) or affirmative therapy (licensed practitioners). <h3>Main Outcomes and Measures</h3> Total incremental costs and quality-adjusted life-years (QALYs) vs no intervention and total economic burden of SOGICE. <h3>Results</h3> Among 28 published studies, which included 190 695 LGBTQ individuals, 12% (range, 7%-23%) of youths experienced SOGICE, initiated at a mean age of 25 years (range, 5-58 years), with a mean (SD) duration of 26 (29) months. At least 2 types of SOGICE were administered to 43% of recipients. Relative to LGBTQ individuals who did not undergo SOGICE, recipients experienced serious psychological distress (47% vs 34%), depression (65% vs 27%), substance abuse (67% vs 50%), and attempted suicide (58% vs 39%). In the economic analysis, over a lifetime horizon with a 3% annual discount rate, the base-case model estimated additional $97 985 lifetime costs per individual, with SOGICE associated with 1.61 QALYs lost vs no intervention; affirmative therapy yielded cost savings of $40 329 with 0.93 QALYs gained vs no intervention. With an estimated 508 892 youths at risk for SOGICE in 2021, the total annual cost of SOGICE is estimated at $650.16 million (2021 US dollars), with associated harms totaling an economic burden of $9.23 billion. <h3>Conclusions and Relevance</h3> This economic evaluation study suggests that there is a high economic burden and high societal costs associated with SOGICE and identifies additional research questions regarding the roles of private and public funding in supporting this harmful practice.
Empagliflozin Improves Cognitive Impairment in Frail Older Adults With Type 2 Diabetes and Heart Failure With Preserved Ejection Fraction
Authors: Pasquale Mone, Angela Lombardi, Jessica Gambardella, Antonella Pansini, Gaetano Macina, Maria Morgante, Salvatore Frullone, Gaetano Santulli
Journal: Diabetes Care (2022)

To assess whether the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin improves cognitive impairment in frail older adults with diabetes and heart failure with preserved ejection fraction (HFpEF).We designed a prospective study to assess cognitive and physical function in consecutive frail older adults with diabetes and HFpEF, comparing the effects of empagliflozin, metformin, and insulin.A total of 162 frail older adults with HFpEF and diabetes successfully completed the study. Montreal Cognitive Assessment scores at baseline and after 1 month were 19.80 ± 3.77 vs. 22.25 ± 3.27 (P < 0.001) in the empagliflozin group, 19.95 ± 3.81 vs. 20.71 ± 3.56 (P = 0.26) in the metformin group, and 19.00 ± 3.71 vs. 19.1 ± 3.56 (P = 0.81) in the insulin group. A multivariable regression analysis confirmed the beneficial effects of empagliflozin. Additionally, we observed a marked amelioration of physical impairment, assessed by the 5-m gait speed test, in the empagliflozin and metformin groups but not in the insulin group.This study is the first to show significant beneficial effects of the SGLT2 inhibitor empagliflozin on cognitive and physical impairment in frail older adults with diabetes and HFpEF.
Hide and seek: for HIV-infected CD4+ T cells, playing well comes with maturity
Authors: Louise Leyre, R. Brad Jones
Journal: Journal of Clinical Investigation (2022)

Antiretroviral therapy suppresses HIV replication but leaves a population of infected CD4+ T cells with integrated proviruses. While most of these proviruses contain defects, such as deletions, some intact proviruses persist and can reinitiate viral replication. In this issue of the JCI, Duette, Hiener, and colleagues performed a tour de force proviral landscape analysis on clinical samples collected over many years with in vitro functional assays. The researchers showed that effector memory CD4+ T cells provide partial sanctuary to intact proviruses from CD8+ T cells and this was associated with superior Nef-mediated MHC-I downregulation relative to less mature CD4+ T cell populations. This finding implicates differential immunoevasion as a cell-intrinsic property, influencing proviral persistence, and highlights Nef as a therapeutic target.
EXPLORING OUTCOMES FOR PATIENTS WITH CARDIOGENIC SHOCK THROUGH THE LENS OF THE “JULY EFFECT” FROM THE NATIONAL INPATIENT SAMPLE
Authors: Tushar Mishra, Dhruvil Patel, Neiberg de Alcantara Lima, Irfan Shafi, Woosun Kang, Rhea Green, John Dawdy, Manmohan Singh, Anupama Kottam
Journal: Journal of the American College of Cardiology (2022)
RADIATION-INDUCED VALVULAR HEART DISEASE IN A COMMUNITY BASED EPIDEMIOLOGICAL STUDY WITH A FOLLOW-UP RANGE OF UP TO 21 YEARS
Authors: Mariana Garcia-Arango, Carolyn Larsen, Renzo Mogollon, Juan Andres Quintero-Martinez, Sandra Cordova-Madera, James R. Cerhan, Tufia C. Haddad, Vuyisile Tlhopane Nkomo, Carrie A. Thompson, Hector R. Villarraga
Journal: Journal of the American College of Cardiology (2022)
Thoracic ultrasound influences physiotherapist’s clinical decision-making in respiratory management of critical care patients: a multicentre cohort study
Authors: Aymeric Le Neindre, Louise Hansell, Johan Wormser, Andreia Gomes Lopes, Carlos Diaz Lopez, Christophe Romanet, Gerald Choukroun, Maxime Nguyen, François Philippart, Pierre-Grégoire Guinot, Hergen Buscher, Bélaid Bouhemad, George Ntoumenopoulos
Journal: Thorax (2022)

Background The potential influence of thoracic ultrasound on clinical decision-making by physiotherapists has never been studied. The aim of this study was to assess the impact of thoracic ultrasound on clinical decision-making by physiotherapists for critical care patients. Methods This prospective, observational multicentre study was conducted between May 2017 and November 2020 in four intensive care units in France and Australia. All hypoxemic patients consecutively admitted were enrolled. The primary outcome was the net reclassification improvement (NRI), quantifying how well the new model (physiotherapist’s clinical decision-making including thoracic ultrasound) reclassifies subjects as compared with an old model (clinical assessment). Secondary outcomes were the factors associated with diagnostic concordance and physiotherapy treatment modification. Results A total of 151 patients were included in the analysis. The NRI for the modification of physiotherapist’s clinical decisions was—40% (95% CI (−56 to −22%), p=0.02). Among the cases in which treatment was changed after ultrasound, 41% of changes were major (n=38). Using a multivariate analysis, the physiotherapist’s confidence in their clinical diagnosis was associated with diagnostic concordance (adjusted OR=3.28 95% CI (1.30 to 8.71); p=0.014). Clinical diagnosis involving non-parenchymal conditions and clinical signs reflecting abolished lung ventilation were associated with diagnostic discordance (adjusted OR=0.06 95% CI (0.01 to 0.26), p&lt;0.001; adjusted OR=0.26 95% CI (0.09 to 0.69), p=0.008; respectively). Conclusion Thoracic ultrasound has a high impact on the clinical decision-making process by physiotherapists for critical care patients. Trial registration number NCT02881814 ; https://clinicaltrials.gov .
Mortality after acute kidney injury and acute interstitial nephritis in patients prescribed immune checkpoint inhibitor therapy
Authors: Megan L Baker, Yu Yamamoto, Mark A Perazella, Nazli Dizman, Anushree C Shirali, Navid Hafez, Jason Weinstein, Michael Simonov, Jeffrey M Testani, Harriet M Kluger, Lloyd G Cantley, Chirag R Parikh, F Perry Wilson, Dennis G Moledina
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background In patients receiving immune checkpoint inhibitor (ICI) therapy, acute kidney injury (AKI) is common, and can occur either from kidney injury unrelated to ICI use or from immune activation resulting in acute interstitial nephritis (AIN). In this study, we test the hypothesis that occurrence of AIN indicates a favorable treatment response to ICI therapy and therefore among patients who develop AKI while on ICI therapy, those with AIN will demonstrate greater survival compared with others with AKI. Methods In this observational cohort study, we included participants initiated on ICI therapy between 2013 and 2019. We tested the independent association of AKI and estimated AIN (eAIN) with mortality up to 1 year after therapy initiation as compared with those without AKI using time-varying Cox proportional hazard models controlling for demographics, comorbidities, cancer type, stage, and therapy, and baseline laboratory values. We defined eAIN as those with a predicted probability of AIN &gt;90th percentile derived from a recently validated diagnostic model. Results Of 2207 patients initiated on ICIs, 617 (28%) died at 1 year and 549 (25%) developed AKI. AKI was independently associated with higher mortality (adjusted HR, 2.28 (95% CI 1.90 to 2.72)). Those AKI patients with eAIN had more severe AKI as reflected by a higher peak serum creatinine (3.3 (IQR 2.1–6.1) vs 1.4 (1.2–1.9) mg/dL, p&lt;0.001) but exhibited lower mortality than those without eAIN in univariable analysis (HR 0.43 (95% CI 0.21 to 0.89)) and after adjusting for demographics, comorbidities, and cancer type and severity (adjusted HR 0.44 (95% CI 0.21 to 0.93)). Conclusion In patients treated with ICI, mortality was higher in those with AKI unrelated to ICI but lower in those where the underlying etiology was AIN. Future studies could evaluate the association of biopsy-proven or biomarker-proven AIN with mortality in those receiving ICI therapy.
CHARACTERISTICS AND OUTCOMES OF ADULTS WITH CONGENITAL HEART DISEASE IN THE CARDIAC INTENSIVE CARE UNIT: INSIGHTS FROM THE CRITICAL CARE CARDIOLOGY TRIALS NETWORK REGISTRY
Authors: Ryan R. Keane, Payton Kendersky, Jeong-Gun Park, Daniel Loriaux, Kelly Arps, Kelly Brown, Jeffrey Dixson, Vivian Baird-Zars, Robert W. Harrison, Emily Echols, Richard A. Krasuski, Sean Van Diepen, David A. Morrow, Christopher B. Granger, Jason Neil Katz, L. Kristin Newby, Anthony Carnicelli
Journal: Journal of the American College of Cardiology (2022)
Lessons from behaviorism: The problem of construct-led science
Authors: Thomas E Dickins, Qazi Rahman
Journal: Behavioral and Brain Sciences (2022)

Abstract Yarkoni makes a number of valid points in his critical analysis of psychology, but he misses an opportunity to expose the root of its problems. That root is the poor practice around the derivation of explanatory constructs. We make comment on this with an example from behaviorist history and relate this to the recent discussion of scientific understanding in the philosophy of science.
43P MRTX-500: Phase II trial of sitravatinib (sitra) + nivolumab (nivo) in patients (pts) with non-squamous (NSQ) non-small cell lung cancer (NSCLC) progressing on or after prior checkpoint inhibitor (CPI) therapy
Authors: T.A. Leal, D. Berz, I. Rybkin, W.T. Iams, D. Bruno, C. Blakely, A. Spira, M. Patel, D.M. Waterhouse, D. Richards, A. Pham, R. Jotte, E.B. Garon, D.S. Hong, R. Shazer, X. Yan, L. Latven, K. He
Journal: Annals of Oncology (2022)
The Role of Cardioprotection in Cancer Therapy Cardiotoxicity
Authors: Torbjørn Omland, Siri Lagethon Heck, Geeta Gulati
Journal: JACC CardioOncology (2022)

Cardiotoxicity is a relatively frequent and potentially serious side effect of traditional and targeted cancer therapies. Both general measures and specific pharmacologic cardioprotective interventions as well as imaging- and biomarker-based surveillance strategies to identify patients at high risk have been tested in randomized controlled trials to prevent or attenuate cancer therapy-related cardiotoxic effects. Although meta-analyses including early trials suggest an overall beneficial effect, there is substantial heterogeneity in results. Recent randomized controlled trials of neurohormonal inhibitors in patients receiving anthracyclines and/or human epidermal growth factor receptor 2-targeted therapies have shown a lower rate of cancer therapy-related cardiac dysfunction than previously reported and a modest or no sustained effect of the interventions. Data on preventive cardioprotective strategies for novel cancer drugs are lacking. Larger, prospective multicenter randomized clinical trials testing traditional and novel interventions are required to more accurately define the benefit of different cardioprotective strategies and to refine risk prediction and identify patients who are likely to benefit.
Paediatric post-concussive symptoms: symptom clusters and clinical phenotypes
Authors: Todd W Lyons, Rebekah Mannix, Ken Tang, Keith Owen Yeates, Gurinder Sangha, Emma CM Burns, Darcy Beer, Alexander S Dubrovsky, Isabelle Gagnon, Jocelyn Gravel, Stephen B Freedman, William Craig, Kathy Boutis, Martin H Osmond, Gerard Gioia, Roger Zemek
Journal: British Journal of Sports Medicine (2022)

To assess the co-occurrence and clustering of post-concussive symptoms in children, and to identify distinct patient phenotypes based on symptom type and severity.We performed a secondary analysis of the prospective, multicentre Predicting and Preventing Post-concussive Problems in Pediatrics (5P) cohort study, evaluating children 5-17 years of age presenting within 48 hours of an acute concussion. Our primary outcome was the simultaneous occurrence of two or more persistent post-concussive symptoms on the Post-Concussion Symptom Inventory at 28 days post-injury. Analyses of symptom and patient clusters were performed using hierarchical cluster analyses of symptom severity ratings.3063 patients from the parent 5P study were included. Median age was 12.1 years (IQR: 9.2-14.6 years), and 1857 (60.6%) were male. Fatigue was the most common persistent symptom (21.7%), with headache the most commonly reported co-occurring symptom among patients with fatigue (55%; 363/662). Headache was common in children reporting any of the 12 other symptoms (range: 54%-72%). Physical symptoms occurred in two distinct clusters: vestibular-ocular and headache. Emotional and cognitive symptoms occurred together more frequently and with higher severity than physical symptoms. Fatigue was more strongly associated with cognitive and emotional symptoms than physical symptoms. We identified five patient groups (resolved/minimal, mild, moderate, severe and profound) based on symptom type and severity.Post-concussive symptoms in children occur in distinct clusters, facilitating the identification of distinct patient phenotypes based on symptom type and severity. Care of children post-concussion must be comprehensive, with systems designed to identify and treat distinct post-concussion phenotypes.
ABLATION GUIDED BY PROPAGATIONAL ANALYSIS FOR ARRHYTHMOGENIC CONDUCTION ELIMINATION TO PREVENT ATRIAL FLUTTER AND FIBRILLATION (PANACEA- AF STUDY): A NOVEL STRATEGY TO TARGET WAVEFRONT DISCONTINUITIES
Authors: Hemal M. Nayak, Zaid Aziz, Andrew D. Beaser, Gaurav A. Upadhyay, Cevher Ozcan, Roderick Tung
Journal: Journal of the American College of Cardiology (2022)
The HOME Core outcome set for clinical trials of atopic dermatitis
Authors: Hywel C. Williams, Jochen Schmitt, Kim S. Thomas, Phyllis I. Spuls, Eric L. Simpson, Christian J. Apfelbacher, Joanne R. Chalmers, Masutaka Furue, Norito Katoh, Louise A.A. Gerbens, Yael A. Leshem, Laura Howells, Jasvinder A. Singh, Maarten Boers
Journal: Journal of Allergy and Clinical Immunology (2022)

Core outcome sets are critically important outcomes that should be measured in clinical trials. Their absence in atopic dermatitis is a form of research waste and impedes combining evidence to inform patient care. Here, we articulate the rationale for core outcome sets in atopic dermatitis and review the work of the international Harmonising Outcome Measures for Eczema group from its inception in Munich, 2010. We describe core domain determination (what should be measured), to instrument selection (how domains should be measured), culminating in the complete core outcome measurement set in Tokyo, 2019. Using a "road map," Harmonising Outcome Measures for Eczema includes diverse research methods including Delphi and nominal group techniques informed by systematic reviews of properties of candidate instruments. The 4 domains and recommended instruments for including in all clinical trials of atopic dermatitis are patient symptoms, measured by Patient-Oriented Eczema Measure and peak Numerical Rating Scale 11 for itch intensity over 24 hours, clinical signs measured using the Eczema Area and Severity Index, quality of life measured by the Dermatology Life Quality Index series for adults, children, and infants, and long-term control measured by either Recap of atopic eczema or Atopic Dermatitis Control Tool.
CARDIOVASCULAR OUTCOME AMONG TRANSULNAR ARTERY VERSUS TRANSRADIAL ARTERY PERCUTANEOUS CORONARY ARTERY INTERVENTION
Authors: Muhammad Aamir, Yasar Sattar, Junaid Arshad, Anees Shahzad, Sharaad Latchana, Syed Moinuddin, Karthik Gonuguntla, Muhammad Khan, Dalvir Gill, Mohamed Zghouzi, M. Chadi Alraies
Journal: Journal of the American College of Cardiology (2022)
HSP90 Inhibition Overcomes Resistance to Molecular Targeted Therapy in <i>BRAFV600E</i>-mutant High-grade Glioma
Authors: Jo Sasame, Naoki Ikegaya, Masahito Kawazu, Manabu Natsumeda, Takahiro Hayashi, Masataka Isoda, Kaishi Satomi, Arata Tomiyama, Akito Oshima, Hirokuni Honma, Yohei Miyake, Katsuhiro Takabayashi, Taishi Nakamura, Toshihide Ueno, Yuko Matsushita, Hiromichi Iwashita, Yu Kanemaru, Hidetoshi Murata, Akihide Ryo, Keita Terashima, Shoji Yamanaka, Yukihiko Fujii, Hiroyuki Mano, Takashi Komori, Koichi Ichimura, Daniel P. Cahill, Hiroaki Wakimoto, Tetsuya Yamamoto, Kensuke Tateishi
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Molecular targeted therapy using BRAF and/or MEK inhibitors has been applied to BRAFV600E-mutant high-grade gliomas (HGG); however, the therapeutic effect is limited by the emergence of drug resistance. Experimental Design: We established multiple paired BRAFV600E-mutant HGG patient-derived xenograft models based on tissues collected prior to and at relapse after molecular targeted therapy. Using these models, we dissected treatment-resistant mechanisms for molecular targeted therapy and explored therapeutic targets to overcome resistance in BRAFV600E HGG models in vitro and in vivo. Results: We found that, despite causing no major genetic and epigenetic changes, BRAF and/or MEK inhibitor treatment deregulated multiple negative feedback mechanisms, which led to the reactivation of the MAPK pathway through c-Raf and AKT signaling. This altered oncogenic signaling primarily mediated resistance to molecular targeted therapy in BRAFV600E-mutant HGG. To overcome this resistance mechanism, we performed a high-throughput drug screening to identify therapeutic agents that potently induce additive cytotoxicity with BRAF and MEK inhibitors. We discovered that HSP90 inhibition combined with BRAF/MEK inhibition coordinately deactivated the MAPK and AKT/mTOR pathways, and subsequently induced apoptosis via dephosphorylation of GSK3β (Ser9) and inhibition of Bcl-2 family proteins. This mediated potent cytotoxicity in vitro and in vivo in refractory models with acquired resistance to molecular targeted therapy. Conclusions: The combination of an HSP90 inhibitor with BRAF or MEK inhibitors can overcome the limitations of the current therapeutic strategies for BRAFV600E-mutant HGG.
Correction: Effective use of image-enhanced endoscopy and endoscopic submucosal dissection for multiple flat non-polypoid colorectal neoplasms
Authors: Takeshi Uozumi, Yutaka Saito, Naoya Toyoshima, Hiroyuki Takamaru, Masau Sekiguchi, Masayoshi Yamada, Seiichiro Abe
Journal: Endoscopy (2022)

Correction to: Effective use of image-enhanced endoscopy and endoscopic submucosal dissection for multiple flat non-polypoid colorectal neoplasmsEndoscopy eFirstDOI: 10.1055/a-1753-9294