tbuckley/cabot-search huggingface dataset:
Abstract P4-01-15: CTC with EMT phenotype are associated with PD-L1 expression in tumor associated stroma in primary breast cancer patients
Authors: Michal Mego, Katarina Kalavska, Marian Karaba, Gabriel Minarik, Juraj Benca, Tatiana Sedlackova, Denisa Manasova, Daniel Pindak, Jozef Mardiak, Zuzana Cierna
Journal: Cancer Research (2020)

Abstract Background: Circulating tumor cells (CTCs) play role in tumor dissemination and are an independent survival predictor in breast cancer (BC) patients. PD-L1 is prognostic factor in BC and PD-L1 inhibitors prolonged survival in metastatic triple-negative breast cancer. The aim of this study was to assess correlation between CTCs and tumor PD-L1 in BC. Methods: This study included 299 primary BC patients treated by surgery from March 2012 to February 2015. Peripheral blood mononuclear cells (PBMC) were depleted of hematopoietic cells using RossetteSepTM negative selection kit. RNA extracted from CD45-depleted PBMC was interrogated for expression of EMT (TWIST1, SNAIL1, SLUG, ZEB1) and epithelial (CK19) gene transcripts by qRT-PCR. Patient samples with higher epithelial and/or mesenchymal gene transcripts than those of healthy donors (n=60) were considered as CTC positive. Expression of PD-L1 in surgical specimens was evaluated by immunohistochemistry and quantified by multiplicative score (proportion of cells with staining x intensity of staining). Results: CTCs were detected in 75 (25.1%) of patients. CTCs exhibiting only epithelial markers were present in 28 (9.4%) of patients, whereas CTCs with only EMT markers were observed in 53 (17.7%) of patients. In 6 patients, CTCs exhibit both epithelial and EMT markers. Patients with EMT_CTCs had significantly higher mean ± SEM score of PD-L1 expression in tumor associated stroma than those of patients without EMT_CTCs (2.66 ± 0.62 vs. 0.88 ± 0.29, p=0.048). There was no association between CTCs and PD-L1 expression in cancer cells including CTCs subtypes. Tumors without PD-L1 expression had significantly better disease-free survival compared to patients with PD-L1 expression (HR = 0.50, 95%CI 0.29 - 0.86, P = 0.001), however, this prognostic value was restricted to CTC positive subpopulation (HR = 0.24, 95%CI 0.10 - 0.56, P = 0.002), while, in CTC negative patients PD-L1 lack prognostic value (HR = 0.77, 95%CI 0.39 - 1.54, P = 0.45) Conclusion: Our data suggest link between PD-L1 expression in tumor associated stroma and CTCs with EMT phenotype and thus further support connection between immunosuppression and EMT. PD-L1 expression is prognostic only in patients with detectable CTC in peripheral blood suggesting different biology of tumors with detectable CTCs. Citation Format: Michal Mego, Katarina Kalavska, Marian Karaba, Gabriel Minarik, Juraj Benca, Tatiana Sedlackova, Denisa Manasova, Daniel Pindak, Jozef Mardiak, Zuzana Cierna. CTC with EMT phenotype are associated with PD-L1 expression in tumor associated stroma in primary breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-01-15.
Abstract P5-12-12: Prospective evaluation of adherence to adjuvant aromatase inhibitor (AI) therapy among Hispanic/Latino women with breast cancer (BC) living in the border city of El Paso, Texas
Authors: Alexander Philipovskiy, Aleli Campbell, Brenda Castillo, Rosalinda Heydarian, Sumit Gaur, Alok Dwivedi, Zeina Nahleh
Journal: Cancer Research (2020)

Abstract Background: Adjuvant therapy with AI improve survival and is recommended to all postmenopausal women with hormone receptor-positive BC. A typical duration of the therapy is from 5 to 10 years. Despite clinically proven efficacy early discontinuation rate approaching 10% per year. The purpose of this study was to determine the adherence level through the Morisky Medication Adherence Scale (MMAS-8) among women with breast cancer treated at Texas Tech University Health Sciences Center El Paso (TTUHSC EP). Methods: Institutional review board approval was obtained prior to initiating this prospective study. 133 postmenopausal women were consented and participated in this study. Patients seen at the TTUHSC EP who was diagnosed with stage I-III breast cancer and who were on adjuvant AIs, were given the MMAS-8 questionnaire, and a demographics questionnaire. In order to identify reasons for non-adherence to AIs, all patients were also asked to identify the reason why they did not take their medication if applicable.Results: One hundred thirty-three patients were enrolled, median age 64 (range 41 - 89), 110 (90.2%) identified themselves as Hispanic/Latino. 58.2% have an income of 15K or less. 39% completed eighth grade or less, 34.5% completed high school, and 12% obtained a technical degree. Mean duration of AI therapy was 6.5 years. The majority of patients have high or intermediate levels of adherence 88%. Only 12 % had a low level of adherence. 7 (5.6%) patients scored two or below in the intentional adherence scale, and 18 (13.5%) scored two or below in the unintentional adherence scale (maximum scale is four). Conclusions: Our results indicate that the majority of patients treated at TTUHSC EP have a high or intermediate level of adherence to AI therapy. The main reason listed for non-adherence were mostly unintentional: forgetfulness and missing getting refills on time. Citation Format: Alexander Philipovskiy, Aleli Campbell, Brenda Castillo, Rosalinda Heydarian, Sumit Gaur, Alok Dwivedi, Zeina Nahleh. Prospective evaluation of adherence to adjuvant aromatase inhibitor (AI) therapy among Hispanic/Latino women with breast cancer (BC) living in the border city of El Paso, Texas [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-12-12.
Hyperglycaemia, ejection fraction and the risk of heart failure or cardiovascular death in patients with type 2 diabetes and a recent acute coronary syndrome
Authors: Sung‐Hee Shin, Brian Claggett, Marc A. Pfeffer, Hicham Skali, Jiankang Liu, David Aguilar, Rafael Diaz, Kenneth Dickstein, Hertzel C. Gerstein, Lars V. Køber, Francesca C. Lawson, Eldrin F. Lewis, Aldo P. Maggioni, John J.V. McMurray, Jeffrey L. Probstfield, Matthew C. Riddle, Jean‐Claude Tardif, Scott D. Solomon
Journal: European Journal of Heart Failure (2020)
Racial Regional Variations in Prostate Cancer Survival Must Be Viewed in the Context of Overall Racial Disparities in Prostate Cancer
Authors: Willie Underwood
Journal: JAMA Network Open (2020)

Sean A. Fletcher, MD; Maya Marchese, MS; Alexander P. Cole, MD; Brandon A. Mahal, MD; David F. Friedlander, MD; Marieke Krimphove, MD; Kerry L. Kilbridge, MD; Stuart R. Lipsitz, ScD; Paul L. Nguyen, MD; Toni K. Choueiri, MD; Adam S. Kibel, MD; Quoc-Dien Trinh, MD
Aromatase is a novel neosubstrate of cereblon responsible for immunomodulatory drug–induced thrombocytopenia
Authors: Taro Tochigi, Toshihiro Miyamoto, Kiwamu Hatakeyama, Teppei Sakoda, Daisuke Ishihara, Hidetoshi Irifune, Takahiro Shima, Koji Kato, Takahiro Maeda, Takumi Ito, Hiroshi Handa, Koichi Akashi, Yoshikane Kikushige
Journal: Blood (2020)
Identification of Kidney Transplant Recipients with Coronavirus Disease 2019
Authors: Hui Zhang, Yan Chen, Quan Yuan, Qiu-Xiang Xia, Xian-Peng Zeng, Jing-Tao Peng, Jing Liu, Xing-Yuan Xiao, Guo-Song Jiang, Han-Yu Xiao, Liang-Bo Xie, Jing Chen, Jia-Li Liu, Xiong Xiao, Hua Su, Chun Zhang, Xiao-Ping Zhang, Hua Yang, Heng Li, Zhen-Di Wang
Journal: European Urology (2020)
Abstract 157: The Association Between Serum Magnesium Levels and Qt Interval Duration During Therapeutic Hypothermia and its Effects on Neurological Outcomes
Authors: Manish Kumar, William Perucki, Brett Hiendlmayr, David O’Sullivan, Silya Mazigh, Antonio B Fernandez
Journal: Circulation (2019)

Introduction: Sudden cardiac arrest is a major cause of mortality in the United States and globally. Therapeutic hypothermia (TH) has demonstrated success in improving neurological outcomes in post-cardiac arrest patients. TH causes several physiologic ECG changes, including QTc prolongation. TH also decreases serum magnesium levels. These changes may lead to malignant ventricular arrhythmia and poor neurological outcome. We aimed to evaluate the association between the QTc interval during TH, magnesium levels, and neurologic outcomes. Methods: We reviewed the electrocardiograms of 366 patients who underwent TH at various intervals corresponding to pre-cooling, maintenance of targeted temperature management, and rewarming periods. We reviewed the change in the corrected QT segment (QTc) and evaluated their relationship with the patients’ magnesium levels and neurologic outcomes. Results: 71.3% of the patients had a significant increase in QTc interval defined as &gt;60 ms or any QTc&gt;500 ms during TH. Patients with persistent prolongation of QTc after rewarming had poor neurological outcomes (p&lt;0.05). Magnesium level showed a positive correlation with QTc interval at presentation (R=0.240, p&lt;0.05) and at 48 hours (R=0.225, p= &lt;0.05). Patients who had poor neurological outcomes tended to have higher magnesium levels at presentation (p&lt;0.05). The majority of patients who received supplemental Mg did not have any significant change in their QTc. Conclusion: TH is independently associated with QTc prolongation. Patients with a persistent increase in QTc interval during the rewarming phase should be promptly evaluated for QTc-prolonging factors given its association with worse neurological outcomes. The inverse correlation between magnesium levels and poor neurological outcomes deserves further investigation.
Strategies for the prevention and management of coronavirus disease 2019
Authors: Wei-jie Guan, Rong-chang Chen, Nan-shan Zhong
Journal: European Respiratory Journal (2020)

Since the outbreak in Wuhan city in December 2019, there has been a surge of newly diagnosed cases with coronavirus disease 2019 (COVID-19) globally [1–4]. The total number has reached to 101 927 laboratory-confirmed cases as of 8 March, 2020 [5]. An increasing number of countries have issued alerts of the highest level. Early protection, early identification, early diagnosis, and early isolation are crucial to combat COVID-19 outbreaks <https://bit.ly/38ZZYQg> We thank W. Ian Lipkin (Mailman School of Public Health, Columbia University, New York, NY, USA) for his insightful suggestions.
Dying tumor cell-derived exosomal miR-194-5p potentiates survival and repopulation of tumor repopulating cells upon radiotherapy in pancreatic cancer
Authors: Ming-jie Jiang, Yi-yun Chen, Juan-juan Dai, Dian-na Gu, Zhu Mei, Fu-rao Liu, Qian Huang, Ling Tian
Journal: Molecular Cancer (2020)

Abstract Background Tumor repopulation is a major cause of radiotherapy failure. Previous investigations highlighted that dying tumor cells played vital roles in tumor repopulation through promoting proliferation of the residual tumor repopulating cells (TRCs). However, TRCs also suffer DNA damage after radiotherapy, and might undergo mitotic catastrophe under the stimulation of proliferative factors released by dying cells. Hence, we intend to find out how these paradoxical biological processes coordinated to potentiate tumor repopulation after radiotherapy. Methods Tumor repopulation models in vitro and in vivo were used for evaluating the therapy response and dissecting underlying mechanisms. RNA-seq was performed to find out the signaling changes and identify the significantly changed miRNAs. qPCR, western blot, IHC, FACS, colony formation assay, etc. were carried out to analyze the molecules and cells. Results Exosomes derived from dying tumor cells induced G1/S arrest and promoted DNA damage response to potentiate survival of TRCs through delivering miR-194-5p, which further modulated E2F3 expression. Moreover, exosomal miR-194-5p alleviated the harmful effects of oncogenic HMGA2 under radiotherapy. After a latent time, dying tumor cells further released a large amount of PGE2 to boost proliferation of the recovered TRCs, and orchestrated the repopulation cascades. Of note, low-dose aspirin was found to suppress pancreatic cancer repopulation upon radiation via inhibiting secretion of exosomes and PGE2. Conclusion Exosomal miR-194-5p enhanced DNA damage response in TRCs to potentiate tumor repopulation. Combined use of aspirin and radiotherapy might benefit pancreatic cancer patients.
Epigenetic modulations of noncoding RNA: a novel dimension of Cancer biology
Authors: Xiao Yang, Ming Liu, Mengmeng Li, Sen Zhang, Hong Hiju, Jing Sun, Zhihai Mao, Minhua Zheng, Bo Feng
Journal: Molecular Cancer (2020)

Abstract Empowered by recent advances of sequencing techniques, transcriptome-wide studies have characterized over 150 different types of post-transcriptional chemical modifications of RNA, ranging from methylations of single base to complex installing reactions catalyzed by coordinated actions of multiple modification enzymes. These modifications have been shown to regulate the function and fate of RNAs and further affecting various cellular events. However, the current understanding of their biological functions in human diseases, especially in cancers, is still limited. Once regarded as “junk” or “noise” of the transcriptome, noncoding RNA (ncRNA) has been proved to be involved in a plethora of cellular signaling pathways especially those regulating cancer initiation and progression. Accumulating evidence has demonstrated that ncRNAs manipulate multiple phenotypes of cancer cells including proliferation, metastasis and chemoresistance and may become promising biomarkers and targets for diagnosis and treatment of cancer. Importantly, recent studies have mapped plenty of modified residues in ncRNA transcripts, indicating the existence of epigenetic modulation of ncRNAs and the potential effects of RNA modulation on cancer progression. In this review, we briefly introduced the characteristics of several main epigenetic marks on ncRNAs and summarized their consecutive effects on cancer cells. We found that ncRNAs could act both as regulators and targets of epigenetic enzymes, which indicated a cross-regulating network in cancer cells and unveil a novel dimension of cancer biology. Moreover, by epitomizing the knowledge of RNA epigenetics, our work may pave the way for the design of patient-tailored therapeutics of cancers.
Hypertrophic Cardiomyopathy With Left Ventricular Systolic Dysfunction
Authors: Peter Marstrand, Larry Han, Sharlene M. Day, Iacopo Olivotto, Euan A. Ashley, Michelle Michels, Alexandre C. Pereira, Samuel G. Wittekind, Adam Helms, Sara Saberi, Daniel Jacoby, James S. Ware, Steven D. Colan, Christopher Semsarian, Jodie Ingles, Neal K. Lakdawala, Carolyn Y. Ho
Journal: Circulation (2020)

The term "end stage" has been used to describe hypertrophic cardiomyopathy (HCM) with left ventricular systolic dysfunction (LVSD), defined as occurring when left ventricular ejection fraction is <50%. The prognosis of HCM-LVSD has reportedly been poor, but because of its relative rarity, the natural history remains incompletely characterized.
Systemic Therapy for Melanoma: ASCO Guideline
Authors: Rahul Seth, Hans Messersmith, Varinder Kaur, John M. Kirkwood, Ragini Kudchadkar, Jennifer Leigh McQuade, Anthony Provenzano, Umang Swami, Jeffrey Weber, Krishna C. Alluri, Sanjiv Agarwala, Paolo A. Ascierto, Michael B. Atkins, Nancy Davis, Marc S. Ernstoff, Mark B. Faries, Jason S. Gold, Samantha Guild, David E. Gyorki, Nikhil I. Khushalani, Michael O. Meyers, Caroline Robert, Mario Santinami, Amikar Sehdev, Vernon K. Sondak, Gilliosa Spurrier, Katy K. Tsai, Alexander van Akkooi, Pauline Funchain
Journal: Journal of Clinical Oncology (2020)

PURPOSE To provide guidance to clinicians regarding the use of systemic therapy for melanoma. METHODS ASCO convened an Expert Panel and conducted a systematic review of the literature. RESULTS A systematic review, one meta-analysis, and 34 additional randomized trials were identified. The published studies included a wide range of systemic therapies in cutaneous and noncutaneous melanoma. RECOMMENDATIONS In the adjuvant setting, nivolumab or pembrolizumab should be offered to patients with resected stage IIIA/B/C/D BRAF wild-type cutaneous melanoma, while either of those two agents or the combination of dabrafenib and trametinib should be offered in BRAF-mutant disease. No recommendation could be made for or against the use of neoadjuvant therapy in cutaneous melanoma. In the unresectable/metastatic setting, ipilimumab plus nivolumab, nivolumab alone, or pembrolizumab alone should be offered to patients with BRAF wild-type cutaneous melanoma, while those three regimens or combination BRAF/MEK inhibitor therapy with dabrafenib/trametinib, encorafenib/binimetinib, or vemurafenib/cobimetinib should be offered in BRAF-mutant disease. Patients with mucosal melanoma may be offered the same therapies recommended for cutaneous melanoma. No recommendation could be made for or against specific therapy for uveal melanoma. Additional information is available at www.asco.org/melanoma-guidelines .
Management of Coronary Disease in Patients with Advanced Kidney Disease
Authors: Sripal Bangalore, David J. Maron, Sean M. O’Brien, Jerome L. Fleg, Evgeny I. Kretov, Carlo Briguori, Upendra Kaul, Harmony R. Reynolds, Tomasz Mazurek, Mandeep S. Sidhu, Jeffrey S. Berger, Roy O. Mathew, Olga Bockeria, Samuel Broderick, Radoslaw Pracon, Charles A. Herzog, Zhen Huang, Gregg W. Stone, William E. Boden, Jonathan D. Newman, Ziad A. Ali, Daniel B. Mark, John A. Spertus, Karen P. Alexander, Bernard R. Chaitman, Glenn M. Chertow, Judith S. Hochman
Journal: New England Journal of Medicine (2020)

Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease.
Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19)
Authors: Riccardo M. Inciardi, Laura Lupi, Gregorio Zaccone, Leonardo Italia, Michela Raffo, Daniela Tomasoni, Dario S. Cani, Manuel Cerini, Davide Farina, Emanuele Gavazzi, Roberto Maroldi, Marianna Adamo, Enrico Ammirati, Gianfranco Sinagra, Carlo M. Lombardi, Marco Metra
Journal: JAMA Cardiology (2020)

Virus infection has been widely described as one of the most common causes of myocarditis. However, less is known about the cardiac involvement as a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.To describe the presentation of acute myocardial inflammation in a patient with coronavirus disease 2019 (COVID-19) who recovered from the influenzalike syndrome and developed fatigue and signs and symptoms of heart failure a week after upper respiratory tract symptoms.This case report describes an otherwise healthy 53-year-old woman who tested positive for COVID-19 and was admitted to the cardiac care unit in March 2020 for acute myopericarditis with systolic dysfunction, confirmed on cardiac magnetic resonance imaging, the week after onset of fever and dry cough due to COVID-19. The patient did not show any respiratory involvement during the clinical course.Cardiac involvement with COVID-19.Detection of cardiac involvement with an increase in levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T, echocardiography changes, and diffuse biventricular myocardial edema and late gadolinium enhancement on cardiac magnetic resonance imaging.An otherwise healthy 53-year-old white woman presented to the emergency department with severe fatigue. She described fever and dry cough the week before. She was afebrile but hypotensive; electrocardiography showed diffuse ST elevation, and elevated high-sensitivity troponin T and NT-proBNP levels were detected. Findings on chest radiography were normal. There was no evidence of obstructive coronary disease on coronary angiography. Based on the COVID-19 outbreak, a nasopharyngeal swab was performed, with a positive result for SARS-CoV-2 on real-time reverse transcriptase-polymerase chain reaction assay. Cardiac magnetic resonance imaging showed increased wall thickness with diffuse biventricular hypokinesis, especially in the apical segments, and severe left ventricular dysfunction (left ventricular ejection fraction of 35%). Short tau inversion recovery and T2-mapping sequences showed marked biventricular myocardial interstitial edema, and there was also diffuse late gadolinium enhancement involving the entire biventricular wall. There was a circumferential pericardial effusion that was most notable around the right cardiac chambers. These findings were all consistent with acute myopericarditis. She was treated with dobutamine, antiviral drugs (lopinavir/ritonavir), steroids, chloroquine, and medical treatment for heart failure, with progressive clinical and instrumental stabilization.This case highlights cardiac involvement as a complication associated with COVID-19, even without symptoms and signs of interstitial pneumonia.
Abstract PD5-04: Tumor-infiltrating lymphocytes evaluation using machine learning image analysis based on core needle biopsy in HER2-positive breast cancer
Authors: Norie Abe, Hirofumi Matsumoto, Reika Takamatsu, Kentaro Tamaki, Naoko Takigami, Kanou Uehara, Yoshihiko Kamada, Nobumitsu Tamaki, Tokiwa Motonari, Norihiro Nakada, Hisamitsu Zaha, Naoki Yoshimi
Journal: Cancer Research (2020)

Abstract Purpose: To evaluate tumor-infiltrating lymphocytes (TILs) quantitatively in breast cancer and to verify the utility of machine learning image analysis in TIL assessment. Methods: Stromal TILs in 105 Human epidermal growth factor receptor 2 (HER2)-positive invasive breast cancers, diagnosed from patients treated with neoadjuvant anti-HER2 therapy, were evaluated by image analysis of hematoxylin and eosin-stained slides from core needle biopsies. TIL level was determined as the number of TILs per square millimeter of stromal tissue. Associations of TIL level with clinicopathological parameters, pathological response, and clinical outcomes were assessed. Results: Median TIL level were 1287/mm2 (range, 123 - 8101/mm2). Higher TIL level was associated with higher histological grade (P = 0.02), estrogen receptor (ER) negativity (P = 0.036), and pathological complete response (pCR) (P&amp;lt; 0.0001). According to analysis of the receiver operating characteristic curve, a threshold TIL level of 2420/mm2 stroma best discriminated pCR from non-pCR. In multivariate analysis, high TIL levels (&amp;gt;2420/mm2) were significantly associated with pCR (P&amp;lt; 0.0001). On Kaplan-Meier analysis, prognosis was not associated with high or low TIL levels. However, high TIL levels tended to be associated with better prognosis in the HER2+/ER+ subgroup (P = 0.131), but not in the HER2+/ER- subgroup. Conclusions: A machine learning image analysis algorithm could assess TIL level as the number of TILs per square millimeter, contrary to semiquantitative evaluation. TIL level derived from this method could offer an independent predictor of pCR. Citation Format: Norie Abe, Hirofumi Matsumoto, Reika Takamatsu, Kentaro Tamaki, Naoko Takigami, Kanou Uehara, Yoshihiko Kamada, Nobumitsu Tamaki, Tokiwa Motonari, Norihiro Nakada, Hisamitsu Zaha, Naoki Yoshimi. Tumor-infiltrating lymphocytes evaluation using machine learning image analysis based on core needle biopsy in HER2-positive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD5-04.
循環器病の診断と治療に関するガイドライン(2001-2002年度合同研究班報告)感染性心内膜炎の予防と治療に関するガイドライン
Authors: 宮武邦夫, 赤石誠, 川副浩平, 中沢誠, 中村憲司, 丹羽公一郎, 吉川純一, 吉田清, 石塚尚子
Journal: Circulation (2003)