tbuckley/cabot-search huggingface dataset:
Abstract 970: Gender-specific stratification of survival following immune checkpoint inhibitor therapy based on intratumoral expression of a B cell gene signature
Authors: Adam K. Aragaki, Jean Hoffman-Censits, Noah M. Hahn, David J. McConkey, Burles Avner Johnson
Journal: Cancer Research (2021)

Abstract Despite intensive efforts there is still a great need to identify biomarkers that can accurately identify patients who will obtain the most clinical benefit from immune checkpoint inhibitor (ICI) therapy. High intratumoral CD8+ T cell gene signature (CD8TGS) expression, tumor mutational burden (TMB), and programmed death ligand 1 (PD-L1) expression all enrich for response to ICI treatment across multiple cancer subtypes. Although high intratumoral B cell gene expression also correlated with ICI response in melanoma, whether it adds predictive value in other cancers is unknown. We analyzed tumor RNA sequencing data from the IMvigor 210 phase 2 clinical trial of atezolizumab in patients with advanced urothelial carcinoma to examine potential relationships between B cell gene expression and clinical outcomes. Tumors with high levels of both signatures (BCGS/CD8TS or B8T high/high) had the highest overall survival (OS) of all B8T groups. Surprisingly, the subset of tumors with B8T high/low expression patterns were associated with the worst OS. Moreover, the B8T cell signature stratified patients with high TMB, or high PD-L1, into subsets with differential OS outcomes. Whereas the B8T high/high tumors were associated with the best clinical outcomes in ICI treated men, they were not associated with better OS in ICI treated women. Conversely, women with B8T high/high tumors had the best clinical outcomes in non-ICI treated muscle invasive bladder cancer. Collectively, these data suggest that the B8T signature can enhance OS stratification in patients with advanced urothelial carcinoma who were treated with ICI therapy, and that sex-specific differences in the tumor immune microenvironment may drive disparate outcomes. Citation Format: Adam K. Aragaki, Jean Hoffman-Censits, Noah M. Hahn, David J. McConkey, Burles Avner Johnson. Gender-specific stratification of survival following immune checkpoint inhibitor therapy based on intratumoral expression of a B cell gene signature [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 970.
Subepidermal blistering eruptions, including bullous pemphigoid, following COVID-19 vaccination
Authors: Mary M. Tomayko, William Damsky, Ramie Fathy, Devon E. McMahon, Noel Turner, Monica N. Valentin, Tena Rallis, Ohara Aivaz, Lindy P. Fox, Esther E. Freeman
Journal: Journal of Allergy and Clinical Immunology (2021)
MicroRNA-21 Controls Circadian Regulation of Apoptosis in Atherosclerotic Lesions
Authors: Andreas Schober, Richard M. Blay, Saffiyeh Saboor Maleki, Farima Zahedi, Anja E. Winklmaier, Mati Y. Kakar, Isabelle M. Baatsch, Mengyu Zhu, Claudia Geißler, Anja E. Fusco, Anna Eberlein, Nan Li, Remco T.A. Megens, Ramin Banafsche, Jörg Kumbrink, Christian Weber, Maliheh Nazari-Jahantigh
Journal: Circulation (2021)

The necrotic core partly formed by ineffective efferocytosis increases the risk of an atherosclerotic plaque rupture. Microribonucleic acids contribute to necrotic core formation by regulating efferocytosis and macrophage apoptosis. Atherosclerotic plaque rupture occurs at increased frequency in the early morning, indicating diurnal changes in plaque vulnerability. Although circadian rhythms play a role in atherosclerosis, the molecular clock output pathways that control plaque composition and rupture susceptibility are unclear.Circadian gene expression, necrotic core size, apoptosis, and efferocytosis in aortic lesions were investigated at different times of the day in Apoe-/-Mir21+/+ mice and Apoe-/-Mir21-/- mice after consumption of a high-fat diet for 12 weeks. Genome-wide gene expression and lesion formation were analyzed in bone marrow-transplanted mice. Diurnal changes in apoptosis and clock gene expression were determined in human atherosclerotic lesions.The expression of molecular clock genes, lesional apoptosis, and necrotic core size were diurnally regulated in Apoe-/- mice. Efferocytosis did not match the diurnal increase in apoptosis at the beginning of the active phase. However, in parallel with apoptosis, expression levels of oscillating Mir21 strands decreased in the mouse atherosclerotic aorta. Mir21 knockout abolished circadian regulation of apoptosis and reduced necrotic core size but did not affect core clock gene expression. Further, Mir21 knockout upregulated expression of proapoptotic Xaf1 (XIAP-associated factor 1) in the atherosclerotic aorta, which abolished circadian expression of Xaf1. The antiapoptotic effect of Mir21 was mediated by noncanonical targeting of Xaf1 through both Mir21 strands. Mir21 knockout in bone marrow cells also reduced atherosclerosis and necrotic core size. Circadian regulation of clock gene expression was confirmed in human atherosclerotic lesions. Apoptosis oscillated diurnally in phase with XAF1 expression, demonstrating an early morning peak antiphase to that of the Mir21 strands.Our findings suggest that the molecular clock in atherosclerotic lesions induces a diurnal rhythm of apoptosis regulated by circadian Mir21 expression in macrophages that is not matched by efferocytosis, thus increasing the size of the necrotic core.
Patient-Reported Symptom Burden and Peripheral Blood Counts Among Patients with Polycythemia Vera: An Analysis from the Reveal Study
Authors: Michael Richard Grunwald, John M. Burke, David J Kuter, Aaron T. Gerds, Brady Lee Stein, Michael R. Savona, Mark A. Walshauser, Ahmad B. Naim, Philomena Colucci, Dilan Chamikara Paranagama, Ruben A Mesa
Journal: Blood (2017)
Abstract 479: mRNA <i>in situ</i> expression of candidate genes for progression risk tissue biomarkers, in premalignant cervical lesions
Authors: Ines Benedetti, Felipe Ruiz, Reinhard Rodríguez
Journal: Cancer Research (2021)

Abstract Background Comparing the in situ differences in mRNA expression of candidate genes between normal cervical tissue and premalignant lesions, could contribute to detect progression risk biomarkers. Use of RNAscope chromogenic in situ hybridization (CISH) that amplifies specific mRNA signals and detects molecules as points that can be quantified, could help the detection of these biomarkers. Methods A tissue microarray was constructed from cervical samples (conization and histerectomy). Representative areas of normal cervix, low-grade (LSIL), and high-grade squamous intraepithelial lesions (HSIL) were chosen. RNAscope 2.5HD Red HPV-HR18 assay that detect E6/E7 mRNA for eighteen high-risk (HR) HPV genotypes, and RNAscope 2.5HD Red assays to detect mRNA from: KRT16, TMEM45A and RBP1, were performed. The stainings were scored by two pathologist from 0 to 4 in a semi-quantitative analysis based on the average number of dots per cell; mean score values were compared using GraphPad Prism 7.0. A p&amp;lt;0.05 was considered statistically significant. Results A total of 390 cervical tissues cores from 169 patients with mean age 36.08 years (SD ±10.48) were included. Mean mRNA expression of HR-HPV E6/E7, TMEM45A and RBP1 were significantly higher in HSIL compared to LSIL and normal cervix squamous epithelium. KRT16 mRNA expression scores in normal cervix squamous epithelium, LSIL, and HSIL, were not significantly different (Table 1). Conclusions CISH allowed to detect E6/E7 mRNA molecules for eighteen HR-HPV genotypes in routinely processed tissues, and to evaluate the expression of the described candidate genes in their context without destroying the tissue morphology. Identification of differential expression between normal cervical tissue and HSIL supports the possible role of TMEM45A and RBP1 in cervical cancer progression and its potential use as progression risk tissue biomarkers. Table 1.Biomarkers candidate genes expression profiles in normal cervix, LSIL and HSILCISH scoresMean (±SD)95% CINormal cervixLSILHSILp valueHR-HPV E6/E7 mRNAn=640.4098(±0.7611)0.2149-0.6048n=640.4098 (±0.7611)0.2149-0.6048n=1381.294 (±1.189)1.078-1.51&amp;lt;0.0001*TMEM45A mRNAn=761.105 (± 1.322)0.8031-1.407n=691.232 (±1.477)0.8771-1.587n=2381.514(± 1.491)1.264-1.7650.046*RBP1 mRNAn=660.4242(±0.7658)0.236-0.6125n=740.5135 (±0.9826)0.2859-1.159n=1301.3 (±1.186)1.094-1.506&amp;lt;0.0001*KRT16 mRNAn=840.9524(±1.15)0.7028-1.202n=770.8831 (±1.214)0.6076-1.159n=1571.115 (±1.41)0.8924-1.3370.573* Citation Format: Ines Benedetti, Felipe Ruiz, Reinhard Rodríguez. mRNA in situ expression of candidate genes for progression risk tissue biomarkers, in premalignant cervical lesions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 479.
Robot-assisted vesico-vaginal fistula cure: Preliminary results of a multicenter series
Authors: P. Lecoanet, A. Mauger De Varennes, C. Mazouin, A. Manunta, N. Hubert, A. Mellouki, I. Bentellis, B. Tibi, J. Hascoet, J. Hubert, T. Tricard, B. Peyronnet
Journal: European Urology (2021)
Clinician Well-Being—Addressing Global Needs for Improvements in the Health Care Field: A Joint Opinion From the American College of Cardiology, American Heart Association, European Society of Cardiology, and the World Heart Federation
Authors: Laxmi S. Mehta, Mitchell S.V. Elkind, Stephan Achenbach, Fausto J. Pinto, Athena Poppas
Journal: Circulation (2021)
Physician Use of Stigmatizing Language in Patient Medical Records
Authors: Jenny Park, Somnath Saha, Brant Chee, Janiece Taylor, Mary Catherine Beach
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Negative attitudes toward patients can adversely impact health care quality and contribute to health disparities. Stigmatizing language written in a patient's medical record can perpetuate negative attitudes and influence decision-making of clinicians subsequently caring for that patient. <h3>Objective</h3> To identify and describe physician language in patient health records that may reflect, or engender in others, negative and positive attitudes toward the patient. <h3>Design, Setting, and Participants</h3> This qualitative study analyzed randomly selected encounter notes from electronic medical records in the ambulatory internal medicine setting at an urban academic medical center. The 600 encounter notes were written by 138 physicians in 2017. Data were analyzed in 2019. <h3>Main Outcomes and Measures</h3> Common linguistic characteristics reflecting an overall positive or negative attitude toward the patient. <h3>Results</h3> A total of 138 clinicians wrote encounter notes about 507 patients. Of these patients, 350 (69%) were identified as female, 406 (80%) were identified as Black/African American, and 76 (15%) were identified as White. Of 600 encounter notes included in this study, there were 5 major themes representing negative language and 6 themes representing positive language. The majority of negative language was not explicit and generally fell into one or more of the following categories: (1) questioning patient credibility, (2) expressing disapproval of patient reasoning or self-care, (3) stereotyping by race or social class, (4) portraying the patient as difficult, and (5) emphasizing physician authority over the patient. Positive language was more often more explicit and included (1) direct compliments, (2) expressions of approval, (3) self-disclosure of the physician's own positive feelings toward the patient, (4) minimization of blame, (5) personalization, and (6) highlighting patient authority for their own decisions. <h3>Conclusions and Relevance</h3> This qualitative study found that physicians express negative and positive attitudes toward patients when documenting in the medical record. Although often not explicit, this language could potentially transmit bias and affect the quality of care that patients subsequently receive. These findings suggest that increased physician awareness when writing and reading medical records is needed to prevent the perpetuation of negative bias in medical care.
Association of BNT162b2 mRNA and mRNA-1273 Vaccines With COVID-19 Infection and Hospitalization Among Patients With Cirrhosis
Authors: Binu V. John, Yangyang Deng, Andrew Scheinberg, Nadim Mahmud, Tamar H. Taddei, David Kaplan, Mabel Labrada, Gio Baracco, Bassam Dahman
Journal: JAMA Internal Medicine (2021)

<h3>Importance</h3> Two mRNA-based vaccines against coronavirus disease 2019 (COVID-19) were found to be highly efficacious in phase 3 clinical trials in the US. However, patients with chronic illnesses, including cirrhosis, were excluded from clinical trials. Patients with cirrhosis have immune dysregulation that is associated with vaccine hyporesponsiveness. <h3>Objective</h3> To study the association of receipt of the Pfizer BNT162b2 mRNA or the Moderna mRNA-1273 vaccines in patients with cirrhosis compared with a propensity-matched control group of patients at similar risk of infection and severe disease from COVID-19. <h3>Design, Setting, and Participants</h3> We performed a retrospective cohort study of patients with cirrhosis who received at least 1 dose of a COVID-19 mRNA vaccine at the Veterans Health Administration. Patients who received at least 1 dose of the vaccine (n = 20 037) were propensity matched with 20 037 controls to assess the associations of vaccination with new COVID-19 infection and COVID-19 hospitalization and death. <h3>Exposures</h3> Receipt of at least 1 dose of the BNT162b2 mRNA or the mRNA-1273 vaccines between December 18, 2020, and March 17, 2021. <h3>Main Outcomes and Measures</h3> COVID-19 infection as documented by a positive result for COVID-19 by polymerase chain reaction, hospitalization, and death due to COVID-19 infection. <h3>Results</h3> The median (interquartile range) age of the vaccinated individuals in the study cohort was 69.1 (8.4) years and 19 465 (97.2%) of the participants in each of the vaccinated and unvaccinated groups were male, consistent with a US veteran population. The mRNA-1273 vaccine was administered in 10 236 (51%) and the BNT162b2 mRNA in 9801 (49%) patients. Approximately 99.7% of patients who received the first dose of either vaccine with a follow-up of 42 days or more received a second dose. The number of COVID-19 infections in the vaccine recipients was similar to the control group in days 0 to 7, 7 to 14, 14 to 21, and 21 to 28 after the first dose. After 28 days, receipt of 1 dose of an mRNA vaccine was associated with a 64.8% reduction in COVID-19 infections and 100% protection against hospitalization or death due to COVID-19 infection. The association of reduced COVID-19 infections after the first dose was lower among patients with decompensated (50.3%) compared with compensated cirrhosis (66.8%). Receipt of a second dose was associated with a 78.6% reduction in COVID-19 infections and 100% reduction in COVID-19–related hospitalization or death after 7 days. <h3>Conclusions and Relevance</h3> This cohort study of US veterans found that mRNA vaccine administration was associated with a delayed but modest reduction in COVID-19 infection but an excellent reduction in COVID-19–related hospitalization or death in patients with cirrhosis.
Prevalence of Germline Alterations on Targeted Tumor-Normal Sequencing of Esophagogastric Cancer
Authors: Geoffrey Y. Ku, Yelena Kemel, Steve B. Maron, Joanne F. Chou, Vignesh Ravichandran, Zarina Shameer, Anna Maio, Elizabeth S. Won, David P. Kelsen, David H. Ilson, Marinela Capanu, Vivian E. Strong, Daniela Molena, Smita Sihag, David R. Jones, Daniel G. Coit, Yaelle Tuvy, Kendall Cowie, David B. Solit, Nikolaus Schultz, Jaclyn F. Hechtman, Kenneth Offit, Vijai Joseph, Diana Mandelker, Yelena Y. Janjigian, Zsofia K. Stadler
Journal: JAMA Network Open (2021)

Among patients with esophagogastric cancers, only individuals who present with known features of heritable cancer syndromes are referred for genetic testing. Broader testing might identify additional patients with germline alterations.To examine the prevalence of likely pathogenic or pathogenic (LP/P) germline alterations among patients with esophagogastric cancer and to assess associations between germline variant prevalence and demographic and clinicopathologic features.This cross-sectional study was performed at a tertiary referral cancer center from January 1, 2014, to December 31, 2019, in 515 patients with esophagogastric cancer who consented to tumor and blood sequencing.Presence or absence of LP/P variants in up to 88 genes associated with cancer predisposition syndromes as identified by targeted sequencing (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets).Among 515 patients (median age, 59 years; range, 18-87 years; 368 [71.5%] male; 398 [77.3%] White), 243 (47.2%) had gastric cancer, 111 (21.6%) had gastroesophageal junction (GEJ) cancer, and 161 (31.3%) had esophageal cancer. A total of 48 patients with gastric cancer (19.8%), 16 (14.4%) with GEJ cancer, and 17 (10.6%) with esophageal cancer had LP/P germline variants. The number of LP/P variants in high- and moderate-penetrance genes was significantly higher in patients with gastric cancer (29 [11.9%]; 95% CI, 8.1%-16.7%) vs patients with esophageal cancer (8 [5.0%]; 95% CI, 2.2%-9.6%; P = .03), and the difference was greater for high-penetrance germline alterations in patients with gastric cancer (25 [10.3%]; 95% CI, 6.8%-14.8%) vs in patients with esophageal cancer (3 [1.9%]; 95% CI, 0.38%-5.3%; P = .001). The most frequent high- and moderate-penetrance LP/P alterations were in BRCA1/2 (14 [2.7%]), ATM (11 [2.1%]), CDH1 (6 [1.2%]), and MSH2 (4 [0.8%]). Those with early-onset disease (≤50 years of age at diagnosis) were more likely to harbor an LP/P germline variant (29 [21.0%]; 95% CI, 14.5%-28.8%) vs those with late-onset disease (patients >50 years of age at diagnosis) (52 [13.8%]; 95% CI, 10.5%-17.7%; P = .046). ATM LP/P variants occurred in 6 patients (4.3%; 95% CI, 1.6%-9.1%) with early-onset esophagogastric cancer vs 5 (1.3%; 95% CI, 0.4%-3.1%; P = .08) of those with late-onset esophagogastric cancer.These results suggest that pathogenic germline variants are enriched in gastric and early-onset esophagogastric cancer and that germline testing should be considered in these populations. The role of ATM alterations in esophagogastric cancer risk warrants further investigation.
Abstract 700: CellSig: A data-driven model of cytokine activity identifies therapeutic targets for severe COVID-19 and cancer immunotherapy-induced colitis
Authors: Peng Jiang, Yu Zhang, Beibei Ru, Eytan Ruppin, Kai Wucherpfennig
Journal: Cancer Research (2021)

Abstract Studies of cytokine activity are foundational to immunology research. However, the complexity and redundancy of cytokine functions have prevented systematic profiling of signaling activities in biological samples. To address these issues, we developed Cell Signaling Analyzer (CellSig, https://cellsig.ccr.cancer.gov), a data-driven infrastructure to model how cytokines cooperate with and antagonize each other in inflammation processes. We manually curated 20,591 transcriptomic profiles related to human cytokine, chemokine, and growth-factor response. CellSig revealed two main cytokine groups typified by NFKB and interferon-associated signals, respectively. The primary pro-inflammatory members of each group induce a distinct set of secondary signals and are repressed by different anti-inflammatory cytokines. CellSig can reliably predict target activities of 43 cytokines using the transcriptomic data from severe COVID-19 cases, cancer immunotherapy-induced colitis, and immune checkpoint blockade response. Among these clinical applications, the differential activities of the NFKB and interferon cytokine groups revealed potential therapeutic targets for alleviating adverse inflammation without compromising viral clearance or cancer treatment. Citation Format: Peng Jiang, Yu Zhang, Beibei Ru, Eytan Ruppin, Kai Wucherpfennig. CellSig: A data-driven model of cytokine activity identifies therapeutic targets for severe COVID-19 and cancer immunotherapy-induced colitis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 700.
Association of Chronic Kidney Disease and Diabetes Mellitus with 5-Year Outcomes after Acute Myocardial Infarction
Authors: Maruhashi T, Kagawa E, Matsushita J, Ikenaga H, Nakama Y, Kurisu S, Shimatani Y, Kawagoe T, Inoue I, Ishihara M, Dai K
Journal: Circulation (2008)
Abstract 17201: Influence of Renal Sympathetic Denervation on Orthostatic Function in Patients with Resistant Hypertension
Authors: Felix Mahfoud, Matthias Lenksi, Christian Ukena, Christine Barth, Amjad Razouk, Denise Fischer, Ulrich Laufs, Ingrid Kindermann, Michael Böhm
Journal: Circulation (2012)

Background Renal sympathetic denervation (RDN) is a novel treatment option for patients with resistant hypertension, proved to reduce renal and whole-body sympathetic activity and blood pressure (B...
Evaluation of the utility of lymphovascular invasion as a complementary or independent prognostic predictor of overall survival after radical prostatectomy
Authors: N. Rakic, J. Keeley, N. Corsi, A. Sood, C. Bronkema, M. Jamil, S. Arora, I. Palma-Zamora, J.O Peabody, C.G. Rogers, M. Menon, F. Abdollah
Journal: European Urology (2021)