tbuckley/cabot-search huggingface dataset:
Inhibition of integrin αvβ6 sparks T-cell antitumor response and enhances immune checkpoint blockade therapy in colorectal cancer
Authors: Philipp Busenhart, Ana Montalban-Arques, Egle Katkeviciute, Yasser Morsy, Chiara Van Passen, Larissa Hering, Kirstin Atrott, Silvia Lang, Jesus Francisco Glaus Garzon, Elisabeth Naschberger, Arndt Hartmann, Gerhard Rogler, Michael Stürzl, Marianne Rebecca Spalinger, Michael Scharl
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Integrin αvβ6 is a heterodimeric cell surface protein whose cellular expression is determined by the availability of the integrin β6 subunit (ITGB6). It is expressed at very low levels in most organs during tissue homeostasis but shows highly upregulated expression during the process of tumorigenesis in many cancers of epithelial origin. Notably, enhanced expression of integrin αvβ6 is associated with aggressive disease and poor prognosis in numerous carcinoma entities. Integrin αvβ6 is one of the major physiological activators of transforming growth factor-β (TGF-β), which has been shown to inhibit the antitumor T-cell response and cause resistance to immunotherapy in mouse models of colorectal and mammary cancer. In this study, we investigated the effect of ITGB6 expression and antibody-mediated integrin αvβ6 inhibition on the tumor immune response in colorectal cancer. Methods Using orthotopic and heterotopic tumor cell injection, we assessed the effect of ITGB6 on tumor growth and tumor immune response in wild type mice, mice with defective TGF-β signaling, and mice treated with anti-integrin αvβ6 antibodies. To examine the effect of ITGB6 in human colorectal cancer, we analyzed RNAseq data from the colon adenocarcinoma dataset of The Cancer Genome Atlas (TCGA-COAD). Results We demonstrate that expression of ITGB6 is an immune evasion strategy in colorectal cancer, causing inhibition of the antitumor immune response and resistance to immune checkpoint blockade therapy by activating latent TGF-β. Antibody-mediated inhibition of integrin αvβ6 sparked a potent cytotoxic T-cell response and overcame resistance to programmed cell death protein 1 (PD-1) blockade therapy in ITGB6 expressing tumors, provoking a drastic increase in anti-PD-1 treatment efficacy. Further, we show that the majority of tumors in patients with colorectal cancer express sufficient ITGB6 to provoke inhibition of the cytotoxic T-cell response, indicating that most patients could benefit from integrin αvβ6 blockade therapy. Conclusions These findings propose inhibition of integrin αvβ6 as a promising new therapy for colorectal cancer, which blocks tumor-promoting TGF-β activation, prevents tumor exclusion of cytotoxic T-cells and enhances the efficacy of immune checkpoint blockade therapy.
Nonmedical Transdisciplinary Perspectives of Black and Racially and Ethnically Diverse Individuals About Antiracism Practices: A Qualitative Study
Authors: Megha Shankar, Joy Cox, Juliana Baratta, Gisselle De Leon, Jonathan G. Shaw, Sonoo Thadaney Israni, Donna M. Zulman, Cati G. Brown-Johnson
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Overwhelming evidence that anti-Black racism is associated with health inequities is driving clinician demand for antiracism practices that promote health equity. <h3>Objective</h3> To investigate how nonmedical professionals address personally mediated, institutional, and internalized racism and to adapt these practices for the clinical setting. <h3>Design, Setting, and Participants</h3> Using an approach from human-centered design for this qualitative study, virtual qualitative interviews were conducted among 40 professionals from nonmedical fields to investigate antiracism practices used outside of medicine. Inductive thematic analysis was conducted to identify latent themes and practices that may be adaptable to health care, subsequently using an established theoretical framework describing levels of racism to interpret and organize themes. Convenience and purposive sampling was used to recruit participants via email, social media, and electronic flyers. <h3>Main Outcomes and Measures</h3> Antiracism practices adapted to medicine. <h3>Results</h3> Among 40 professionals from nonmedical fields, most were younger than age 40 years (23 individuals [57.5%]) and there were 20 (50.0%) women; there were 25 Black or African American individuals (62.5%); 4 East Asian, Southeast Asian, or South Asian individuals (10.0%); 3 individuals with Hispanic, Latinx, or Spanish origin (7.5%); and 3 White individuals. Participants described personally mediated, institutional, and internalized antiracism practices that may be adaptable to promote health equity for Black patients. Personally mediated antiracism practices included dialogue and humble inquiry, building trust, and allyship and shared humanity; clinicians may be able to adopt these practices by focusing on patient successes, avoiding stigmatizing language in the electronic health record, and using specific phrases to address racism in the moment. Institutional antiracism practices included education, representation, and mentorship; in the health care setting, clinics may be able to develop staff affiliate groups, focus on improving racial health equity outcomes, and conduct antiracism trainings. Internalized antiracism practices centered on authenticity; clinicians may be able to write positionality statements reflecting their identity and the expertise they bring to clinical encounters. <h3>Conclusions and Relevance</h3> This study's findings suggest that antiracism practices from outside the health care sector may offer innovative strategies to promote health equity by addressing personally mediated, institutional, and internalized racism in clinical care.
Narrow Complex Tachycardias—Therapeutic and Diagnostic Role of Adenosine
Authors: Rahul Kumar, Anunay Gupta, Hermohander Singh Isser
Journal: JAMA Internal Medicine (2022)

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Reply
Authors: Zhen Wang, Jie Yu, Ping Liang
Journal: Hepatology (2022)

We appreciate the communication of international counterparts, and we consider the following aspects to answer their questions. In the past decade, the wide application of noninvasive detection technology in China has made it possible for more and more patients with liver disease to receive early diagnosis and treatment, which directly leads to a significant decrease in the proportion of HCC patients with portal hypertension.[1,2] Next, all patients receiving radical treatment underwent strict preoperative evaluation (97.1% of patients with Child‐Pugh A and 2.9% with Child‐Pugh B), and the perioperative management is more scientific and effective, which has greatly reduced the incidence of bleeding, liver failure, HE, and other complications. Furthermore, because of the inherent limitations of retrospective studies, it is difficult to collect the exact location of the tumor, and we look forward to answering these questions in ongoing prospective studies. Second, all patients in our study underwent strict preoperative planning, with two or three ablation needles placed multiple times during microwave ablation (MWA) to ensure that the ablation thermal field adequately covered the tumor, and all patients achieved clinically complete ablation, confirmed by enhanced imaging, within 1–2 months after ablation. The study confirmed that MWA combined with transarterial chemoembolization (TACE) presented an exciting clinical efficacy in the treatment of 3‐ to 5‐cm HCC.[3] However, because of the retrospective study design, it was difficult to track accurate and complete treatment information of MWA + TACE in our study, which is expected to be reported in future prospective studies. Finally, the reason for the 40% antiviral treatment rate may be that most patients have low viral load after effective antiviral treatment, and regular review meets the criteria of temporary drug withdrawal.[4,5] Some patients were not aware of their chronic hepatitis before the discovery of HCC. Whether these results can be applied to liver cancer resulting from other causes, such as alcohol use and MAFLD, is still worthy of further exploration. In addition, 12.9% of the missing data referred to the data of local recurrence after MWA and recurrence at the resection margin after laparoscopic liver resection; we summarized the two recurrence cases to the disease‐free survival analysis of the overall sample, which did not affect the reliability of the analysis results. FUNDING INFORMATION Supported by the National Scientific Foundation Committee of China (91859201, 92159305, 81971625, 82030047). CONFLICT OF INTEREST Nothing to report. AUTHOR CONTRIBUTIONS Concept and design: Ping Liang and Jie Yu. Writing of article: Zhen Wang and Jie Yu.
Sex-dependent GOAL screening performance in adults at risk for obstructive sleep apnea
Authors: R.L.M. Duarte, F.J. Magalhães-da-Silveira, D. Gozal
Journal: Pulmonology (2022)

To evaluate possible sex-related differences in the performance of the GOAL, a 4-item obstructive sleep apnea (OSA) screening instrument in adults.
A 49-Year-Old Woman With Progressive Dyspnea
Authors: Hai-Long Dai, Wei-Hua Zhang, Xue-Feng Guang
Journal: JAMA Cardiology (2022)

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Assessment of Implicit Gender Bias During Evaluation of Procedural Competency Among Emergency Medicine Residents
Authors: Ashley See, Michael Pallaci, Adam R. Aluisio, Jenny Beck-Esmay, Michael Menchine, Michael Weinstock, Chun Nok Lam, Jeff Riddell
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Gender disparities exist throughout medicine. Recent studies have highlighted an attainment gap between male and female residents in performance evaluations on Accreditation Council for Graduate Medical Education (ACGME) milestones. Because of difficulties in blinding evaluators to gender, it remains unclear whether these observed disparities are because of implicit bias or other causes. <h3>Objective</h3> To estimate the magnitude of implicit gender bias in assessments of procedural competency in emergency medicine residents and whether the gender of the evaluator is associated with identified implicit gender bias. <h3>Design, Setting, and Participants</h3> A cross-sectional study was performed from 2018 to 2020 in which emergency medicine residency faculty assessed procedural competency by evaluating videos of residents performing 3 procedures in a simulated environment. They were blinded to the intent of the study. Proceduralists were filmed performing each procedure from 2 different viewpoints simultaneously by 2 different cameras. One was a gender-blinded (ie, hands-only) view, and the other a wide-angled gender-evident (ie, whole-body) view. The faculty evaluators viewed videos in a random order and assessed procedural competency on a global rating scale with extensive validity evidence for the evaluation of video-recorded procedural performance. <h3>Main Outcomes and Measures</h3> The primary outcome was to determine if there was a difference in the evaluation of procedural competency based on gender. The secondary outcome was to determine if there was a difference in the evaluations based on the gender of the evaluator. <h3>Results</h3> Fifty-one faculty evaluators enrolled from 19 states, with 22 male participants (43.1%), 29 female participants (56.9%), and a mean (SD) age of 37 (6.4) years. Each evaluator assessed all 60 procedures: 30 gender-blinded (hands-only view) videos and 30 identical gender-evident (wide angle) videos. There were no statistically significant differences in the study evaluators' scores of the proceduralists based on their gender, and the gender of the evaluator was not associated with the difference in mean scores. <h3>Conclusions and Relevance</h3> In this study, we did not identify a difference in the evaluation of procedural competency based upon the gender of the resident proceduralist or the gender of the faculty evaluator.
Subject Index
Authors: L Wang, S Ward, D Watanabe, S Watanabe, T Watanabe, S Watkins, H Witt, Z Xie, A Xu, Y Xu, C Yanagimoto, J Yano, P Yao, M Zabala, G Zabbialini, L Zancan, M Zanello, H Zentgraf, M Zeremski, B.-H Zhang, H.-Y Zhang, W Zhang, Z Zhang, L Zhou, P.-Y Zhuang, T Zilker, A Zimmermann
Journal: Journal of Hepatology (2007)
Gynecomastia and Urinary Estrogens in Skin Disease
Journal: JAMA (1963)

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Convergence Retraction Nystagmus
Journal: JAMA (1963)

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Association News
Journal: JAMA (1934)

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Resignation Inquiry
Authors: Mike Mitka
Journal: JAMA (2005)

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Glioma targeted therapy: insight into future of molecular approaches
Authors: Keyang Yang, Zhijing Wu, Hao Zhang, Nan Zhang, Wantao Wu, Zeyu Wang, Ziyu Dai, Xun Zhang, Liyang Zhang, Yun Peng, Weijie Ye, Wenjing Zeng, Zhixiong Liu, Quan Cheng
Journal: Molecular Cancer (2022)

Gliomas are the common type of brain tumors originating from glial cells. Epidemiologically, gliomas occur among all ages, more often seen in adults, which males are more susceptible than females. According to the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), standard of care and prognosis of gliomas can be dramatically different. Generally, circumscribed gliomas are usually benign and recommended to early complete resection, with chemotherapy if necessary. Diffuse gliomas and other high-grade gliomas according to their molecule subtype are slightly intractable, with necessity of chemotherapy. However, for glioblastoma, feasible resection followed by radiotherapy plus temozolomide chemotherapy define the current standard of care. Here, we discuss novel feasible or potential targets for treatment of gliomas, especially IDH-wild type glioblastoma. Classic targets such as the p53 and retinoblastoma (RB) pathway and epidermal growth factor receptor (EGFR) gene alteration have met failure due to complex regulatory network. There is ever-increasing interest in immunotherapy (immune checkpoint molecule, tumor associated macrophage, dendritic cell vaccine, CAR-T), tumor microenvironment, and combination of several efficacious methods. With many targeted therapy options emerging, biomarkers guiding the prescription of a particular targeted therapy are also attractive. More pre-clinical and clinical trials are urgently needed to explore and evaluate the feasibility of targeted therapy with the corresponding biomarkers for effective personalized treatment options.
STAPHYLOTOXINS.
Journal: JAMA (1901)

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Fetal effects of maternal alcohol use
Journal: JAMA (1983)

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