tbuckley/cabot-search huggingface dataset:
Transcriptomic profiling across the nonalcoholic fatty liver disease spectrum reveals gene signatures for steatohepatitis and fibrosis
Authors: Olivier Govaere, Simon Cockell, Dina Tiniakos, Rachel Queen, Ramy Younes, Michele Vacca, Leigh Alexander, Federico Ravaioli, Jeremy Palmer, Salvatore Petta, Jerome Boursier, Chiara Rosso, Katherine Johnson, Kristy Wonders, Christopher P. Day, Mattias Ekstedt, Matej Orešič, Rebecca Darlay, Heather J. Cordell, Fabio Marra, Antonio Vidal-Puig, Pierre Bedossa, Jörn M. Schattenberg, Karine Clément, Michael Allison, Elisabetta Bugianesi, Vlad Ratziu, Ann K. Daly, Quentin M. Anstee
Journal: Science Translational Medicine (2020)

A 25-gene expression signature associates with progression of fibrosing steatohepatitis in independent NAFLD cohorts.
Assessing the Benefits of Atrial Fibrillation Ablation—Nothing Succeeds Like Success
Authors: Stacey J. Howell, Eric C. Stecker
Journal: JAMA Network Open (2020)

Maria Terricabras, MD; Roberto Mantovan, MD, PhD; Chen-yang Jiang, MD; Timothy R. Betts, MBChB; Jian Chen, MD; Isabel Deisenhofer, MD; Laurent Macle, MD; Carlos A. Morillo, MD; Wilhelm Haverkamp, MD, PhD; Rukshen Weerasooriya, MBBS; Jean-Paul Albenque, MD; Stefano Nardi, MD; Endrj Menardi, MD; Paul Novak, MD; Prashanthan Sanders, MBBS, PhD; Atul Verma, MD; Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial–Part II (STAR AF II) Investigators
Abstract 13294: Sphingosine Kinase 2 Inhibits Macrophage Cholesterol Accumulation and Atherosclerosis via Autophagy Stimulation
Authors: Kazuhiro Ishimaru, Yoh Takuwa
Journal: Circulation (2018)

Atherosclerosis is a major cause of coronary heart disease and is characterized by the infiltration of cholesterol-accumulating macrophages in the vascular wall. Although sphingolipids are implicat...
TREM-1 orchestrates angiotensin II–induced monocyte trafficking and promotes experimental abdominal aortic aneurysm
Authors: Marie Vandestienne, Yujiao Zhang, Icia Santos-Zas, Rida Al-Rifai, Jeremie Joffre, Andreas Giraud, Ludivine Laurans, Bruno Esposito, Florence Pinet, Patrick Bruneval, Juliette Raffort, Fabien Lareyre, Jose Vilar, Amir Boufenzer, Lea Guyonnet, Coralie Guerin, Eric Clauser, Jean-Sébastien Silvestre, Sylvie Lang, Laurie Soulat-Dufour, Alain Tedgui, Ziad Mallat, Soraya Taleb, Alexandre Boissonnas, Marc Derive, Giulia Chinetti, Hafid Ait-Oufella
Journal: Journal of Clinical Investigation (2020)

The triggering receptor expressed on myeloid cells 1 (TREM-1) drives inflammatory responses in several cardiovascular diseases but its role in abdominal aortic aneurysm (AAA) remains unknown. Our objective was to explore the role of TREM-1 in a mouse model of angiotensin II-induced (AngII-induced) AAA. TREM-1 expression was detected in mouse aortic aneurysm and colocalized with macrophages. Trem1 gene deletion (Apoe-/-Trem1-/-), as well as TREM-1 pharmacological blockade with LR-12 peptide, limited both AAA development and severity. Trem1 gene deletion attenuated the inflammatory response in the aorta, with a reduction of Il1b, Tnfa, Mmp2, and Mmp9 mRNA expression, and led to a decreased macrophage content due to a reduction of Ly6Chi classical monocyte trafficking. Conversely, antibody-mediated TREM-1 stimulation exacerbated Ly6Chi monocyte aorta infiltration after AngII infusion through CD62L upregulation and promoted proinflammatory signature in the aorta, resulting in worsening AAA severity. AngII infusion stimulated TREM-1 expression and activation on Ly6Chi monocytes through AngII receptor type I (AT1R). In human AAA, TREM-1 was detected and TREM1 mRNA expression correlated with SELL mRNA expression. Finally, circulating levels of sTREM-1 were increased in patients with AAA when compared with patients without AAA. In conclusion, TREM-1 is involved in AAA pathophysiology and may represent a promising therapeutic target in humans.
Galectin-3 in Cardiovascular Disease: A Possible Window Into Early Myocardial Fibrosis⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: David A. Morrow, Michelle L. O'Donoghue
Journal: Journal of the American College of Cardiology (2012)
Dextran-modified Quercetin-Cu(II)/hyaluronic acid nanomedicine with natural poly(ADP-ribose) polymerase inhibitor and dual targeting for programmed synthetic lethal therapy in triple-negative breast cancer
Authors: Hung-Wei Cheng, Chih-Sheng Chiang, Hsin-Yao Ho, Syun-Hong Chou, Yen-Ho Lai, Woei-Cherng Shyu, San-Yuan Chen
Journal: Journal of Controlled Release (2020)
Case 37-2020: A 35-Year-Old Man with Lymphadenopathy and Petechiae
Authors: Philippe Armand, Allen P. Heeger, Sanjat Kanjilal, Melissa Krystel-Whittemore
Journal: New England Journal of Medicine (2020)

A 35-year-old man was admitted to the hospital with lymphadenopathy and thrombocytopenia (platelet count, 0 per microliter). Four months earlier, painless lymphadenopathy had developed in the groin area; a biopsy specimen of an enlarged lymph node showed necrosis, fibrosis, and inflammation but no malignant cells. A diagnostic procedure was performed.
<i>QuickStats:</i> Age-Adjusted Pedestrian* Death Rates,† by Race/Ethnicity — National Vital Statistics System, United States, 2009 and 2018
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

0 1 2 3 4 Total White, non-Hispanic Black, non-Hispanic Hispanic Deaths per 100,000 population Race/Ethnicity
Comparison of PD-L1 protein expression between primary tumors and metastatic lesions in triple negative breast cancers
Authors: Mariya Rozenblit, Richard Huang, Natalie Danziger, Priti Hegde, Brian Alexander, Shakti Ramkissoon, Kim Blenman, Jeffrey S Ross, David L Rimm, Lajos Pusztai
Journal: Journal for ImmunoTherapy of Cancer (2020)

Programmed Death Ligand 1 (PD-L1) positivity rates differ between different metastatic sites and the primary tumor. Understanding PD-L1 expression characteristics could guide biopsy procedures and motivate research to better understand site-specific differences in the tumor microenvironment. The purpose of this study was to compare PD-L1 positivity on immune cells and tumor cells in primary and metastatic triple negative breast cancer (TNBC) tumors. Retrospective study utilizing the PD-L1 database of Foundation Medicine containing the SP142 companion diagnostic immunohistochemistry assay (SP142 CDx) and Food and Drug Administration guidelines for scoring. 340 TNBC cases (179 primary tumors and 161 unmatched metastatic lesions) were evaluated. The primary outcome measures were PD-L1 positivity rates in immune cells and tumor cells. χ 2 test was used for comparisons. Spearman’s correlation coefficient was used for correlations. More primary tumors were positive for PD-L1 expression on immune cells than metastatic lesions (114 (63.7%) vs 68 (42.2%), p&lt;0.0001). This was driven by the lower PD-L1 positivity rates in skin (23.8%, 95% CI: 8.22% to 47.2%), liver (17.4%, 95% CI: 5.00% to 38.8%) and bone (16.7%, 95% CI: 2.10% to 48.4%) metastases. Lung (68.8%, 95% CI: 41.3% to 90.0%), soft tissues (65.2%, 95% CI: 42.7% to 83.6%) and lymph nodes (51.1%, 95% CI: 35.8% to 66.3%) had PD-L1 % positivity rates similar to primary tumors. PD-L1 expression was rare on tumor cells in both the breast and metastatic sites (8.3% vs 4.3%, p=0.13). The rate of PD-L1 positivity varies by metastatic location with substantially lower positivity rates in liver, skin and bone metastases compared with primary breast lesions or lung, soft tissue or lymph node metastases. This difference in PD-L1 positivity rates between primary tumors and different metastatic sites should inform physicians when choosing sites to biopsy and suggests a difference in the immune microenvironment across metastatic sites.
79O Clinical performance of Immunoscore® in early colon cancer in the Asian population
Authors: J. Galon, Y. Kawakami, T. Torigoe, Y. Wang, P.S. Patel, H. Vora, B. Mlecnik, F. Marliot, C.B. Bifulco, A. Lugli, I.D. Nagtegaal, A. Hartmann, M. van den Eynde, M.H.A. Roehrl, P.S. Ohashi, E. Zavadova, F. Marincola, P.A. Ascierto, B.A. Fox, F. Pagès
Journal: Annals of Oncology (2020)
161P Adjuvant tegafur/gimeracil/oteracil (S-1) versus platinum-based chemotherapies for resectable gastric cancer: Real-world experience and a propensity score matching analysis
Authors: C.C. Yen, Y.S. Shan, T.K. Liao, Y.J. Chao, I.T. Liu, C.J. Yen
Journal: Annals of Oncology (2020)
FRI0199 Evaluation of quality of life in patients with systemic sclerosis by the sf-36 questionnaire
Authors: S Zeni, R Cossutta, A Belotti Masserini, P Colombelli, A Soldi, F Fantini
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To evaluate the quality of life of patients affected by systemic sclerosis (SSc) through the application of SF-36 questionnaire and to correlate the results with the disability index of HAQ (DI) and the systemic involvement. <h3>Methods</h3> We studied 100 (3 M, 97 F) patients affected by SSc (mean age 60 years, range 39–83, mean duration of disease 6 years, range 1–34). The organic involvement was evaluated by skin score, chest HRCT, electrocardiography according to Holter, Doppler-echocardiography and oesofagogram. <h3>Results</h3> In the Table 1 are shown the results of the mean values of the 8 question groups in the control population and in the patients. The 8 question groups are: PA = physical activity, RP = role of physical activity, BP = bodily pain, GH = general health, VT = vitality, SA = social activities, EP = emotional problems, MH = mental health. A very good correlation was found between the DI and all the scores of SF-36. The skin involvement showed a statistically significant correlation with both the DI (r = 0.3304; p = 0.0008) and the PA score of the SF-36 (r = 0.2635; p = 0.0081). No other statistically significant correlation was found between any of the SF-36 dimensions and involvement of a specific organ. <h3>Conclusion</h3> SF-36 showed to be a valid instrument to evaluate the quality of life and the disability of patients with SSc and it seems to correlate with extent of skin involvement. <h3>References</h3> Apolone G, <i>et al</i>. Questionario sullo stato di salute SF-36; manuale d?uso e guida all?interpretazione dei risultati. Guerini e Associati. Milano, 1997 Poole JL, Steen VD. Arthritis Care Res. 1991;<b>4</b>:27–31 Ruof J, <i>et al</i>. Rheumatology 1999;38:535–42 Silman A, <i>et al</i>. J Rheumatol. 1998;25:79–83 Steen VD, Medsger TA. Arthritis Rheum. 1997;<b>40</b>:1984–91 Stewart Al, <i>et al</i>. J Am Med Ass. 1989;262:907–13 Steward AL, <i>et al</i>. Med Care 1988;26:724–35 Ware JE, <i>et al</i>. Med Care 1992;30:473–83
68Ga-DOTATATE Uptake in Primary Breast Cancer
Authors: Mary S. Guirguis, Beatriz E. Adrada, Devaki Shilpa Surasi, Mark J. Dryden
Journal: Clinical Nuclear Medicine (2020)

68Ga-DOTA peptides have revolutionized the imaging of neuroendocrine tumors because the agents are specific to somatostatin receptors. However, other tumors, including breast cancer, have been shown to express somatostatin receptors. We present the case of a 74-year-old woman with primary cardiac paraganglioma, who was found to have 68Ga-DOTATATE activity in the breast on staging PET/CT. Subsequent breast imaging workup and biopsy confirmed primary invasive lobular breast cancer, which was not 18F-FDG-avid on prior FDG PET/CT. Our case is in alignment with prior studies that suggest that 68Ga-DOTA peptides may play a future role in imaging breast cancer patients.
Menopause Transition and Cardiovascular Disease Risk: Implications for Timing of Early Prevention: A Scientific Statement From the American Heart Association
Authors: Samar R. El Khoudary, Brooke Aggarwal, Theresa M. Beckie, Howard N. Hodis, Amber E. Johnson, Robert D. Langer, Marian C. Limacher, JoAnn E. Manson, Marcia L. Stefanick, Matthew A. Allison
Journal: Circulation (2020)

Cardiovascular disease (CVD) is the leading cause of death in women, who have a notable increase in the risk for this disease after menopause and typically develop coronary heart disease several years later than men. This observation led to the hypothesis that the menopause transition (MT) contributes to the increase in coronary heart disease risk. Over the past 20 years, longitudinal studies of women traversing menopause have contributed significantly to our understanding of the relationship between the MT and CVD risk. By following women over this period, researchers have been able to disentangle chronological and ovarian aging with respect to CVD risk. These studies have documented distinct patterns of sex hormone changes, as well as adverse alterations in body composition, lipids and lipoproteins, and measures of vascular health over the MT, which can increase a woman's risk of developing CVD postmenopausally. The reported findings underline the significance of the MT as a time of accelerating CVD risk, thereby emphasizing the importance of monitoring women's health during midlife, a critical window for implementing early intervention strategies to reduce CVD risk. Notably, the 2011 American Heart Association guidelines for CVD prevention in women (the latest sex-specific guidelines to date) did not include information now available about the contribution of the MT to increased CVD in women. Therefore, there is a crucial need to discuss the contemporary literature on menopause and CVD risk with the intent of increasing awareness of the significant adverse cardiometabolic health-related changes accompanying midlife and the MT. This scientific statement provides an up-to-date synthesis of the existing data on the MT and how it relates to CVD.
16428 Lebrikizumab, a high-affinity interleukin-13 inhibitor, improves clinical manifestations in moderate to severe atopic dermatitis: Time course of response from a randomized, double-blinded, placebo-controlled, dose-ranging, phase 2b study
Authors: Emma Guttman-Yassky, Andrew Blauvelt, Lawrence F. Eichenfield, Amy Paller, April W. Armstrong, Janice S. Drew, Ramanan Gopalan, Eric L. Simpson
Journal: Journal of the American Academy of Dermatology (2020)
Inhibition of Triggered Activities in Pulmonary Veins: Do Statins Have a Direct and Clinically Relevant Antiarrhythmic Effect?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Gan-Xin Yan, Zuyi Yuan
Journal: Journal of the American College of Cardiology (2011)
15115 The patient-reported disease burden in pediatric patients with atopic dermatitis: A cross-sectional study in the United States, Canada, Europe, and Japan
Authors: Stephan Weidinger, Eric L. Simpson, Laurent Eckert, Jonathan I. Silverberg, Paola Mina-Osorio, Ana Beatris Rossi, Isabelle Guillemin, Marine Pellan, Kantar Health, Abhijit Gadkari
Journal: Journal of the American Academy of Dermatology (2020)
Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2
Authors: Philip J Mease, Apinya Lertratanakul, Jaclyn K Anderson, Kim Papp, Filip Van den Bosch, Shigeyoshi Tsuji, Eva Dokoupilova, Mauro Keiserman, Xin Wang, Sheng Zhong, Reva M McCaskill, Patrick Zueger, Aileen L Pangan, William Tillett
Journal: Annals of the Rheumatic Diseases (2020)

Background Upadacitinib is a Janus kinase inhibitor under evaluation for the treatment of psoriatic arthritis (PsA). We evaluated upadacitinib in patients with PsA and prior inadequate response or intolerance to at least one biologic disease-modifying antirheumatic drug (DMARD). Methods In this 24-week randomised, placebo-controlled, double-blind, phase 3 trial, 642 patients were randomised (2:2:1:1) to once per day upadacitinib 15 mg or 30 mg, placebo followed by upadacitinib 15 mg or placebo followed by upadacitinib 30 mg at week 24. The primary endpoint was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at week 12. Achievement of minimal disease activity (MDA) was assessed at week 24. Treatment-emergent adverse events are reported for all patients who received at least one dose of trial drug. Results At week 12, significantly more patients receiving upadacitinib 15 mg and 30 mg versus placebo achieved ACR20 (56.9% and 63.8% vs 24.1%; p&lt;0.001 for both comparisons). At week 24, MDA was achieved by more upadacitinib 15 mg-treated (25.1%) and 30 mg-treated patients (28.9%) versus placebo (2.8%; p&lt;0.001 for both comparisons). Generally, the rates of treatment-emergent adverse events were similar with placebo and upadacitinib 15 mg and higher with upadacitinib 30 mg at week 24. Rates of serious infections were 0.5%, 0.5% and 2.8% with placebo, upadacitinib 15 mg and upadacitinib 30 mg, respectively. Conclusion In this trial of patients with active PsA who had inadequate response or intolerance to at least one biologic DMARD, upadacitinib 15 mg and 30 mg was more effective than placebo over 24 weeks in improving signs and symptoms of PsA. Clinical trial registration number NCT03104374
Trainees call for transparency over raised pass marks for Royal College of Surgeons exam
Authors: Clara Munro
Journal: BMJ (2020)

Over 1300 doctors have signed a petition voicing concerns over changes to the Membership of the Royal College of Surgeons (MRCS) exam.

The petition has received 1332 signatures. It calls for transparency after the MRCS exam pass mark, which has never been higher than 71.9%, was raised to 76.9% for the exam that took place in September 2020.

It also describes other changes made to the exam as a result of the covid-19 pandemic, as well as poor communication from the college before and after the exam and poor delivery and commencement of the exam.1

Candidates were also frustrated by a delay …
396P Efficacy and safety of S-1 in elderly patients with advanced non-small cell lung cancer previously treated with platinum-based chemotherapy: A subgroup analysis of the EAST-LC
Authors: J.C-H. Yang, T.S.K. Mok, S. Lu, K. Nakagawa, N. Yamamoto, Y-K. Shi, L. Zhang, R.A. Soo, S. Morita, T. Tamura
Journal: Annals of Oncology (2020)
miR-10a as a therapeutic target and predictive biomarker for MDM2 inhibition in acute myeloid leukemia
Authors: Thi Thanh Vu, Friedrich Stölzel, Kristy W. Wang, Christoph Röllig, Melinda L. Tursky, Timothy J. Molloy, David D. Ma
Journal: Leukemia (2020)

Pharmacological inhibition of MDM2/4, which activates the critical tumor suppressor p53, has been gaining increasing interest as a strategy for the treatment of acute myeloid leukemia (AML). While clinical trials of MDM2 inhibitors have shown promise, responses have been confined to largely molecularly undefined patients, indicating that new biomarkers and optimized treatment strategies are needed. We previously reported that the microRNA miR-10a is strongly overexpressed in some AML, and demonstrate here that it modulates several key members of the p53/Rb network, including p53 regulator MDM4, Rb regulator RB1CC1, p21 regulator TFAP2C, and p53 itself. The expression of both miR-10a and its downstream targets were strongly predictive of MDM2 inhibitor sensitivity in cell lines, primary AML specimens, and correlated to response in patients treated with both MDM2 inhibitors and cytarabine. Furthermore, miR-10a inhibition induced synergy between MDM2 inhibitor Nutlin-3a and cytarabine in both in vitro and in vivo AML models. Mechanistically this synergism primarily occurs via the p53-mediated activation of cytotoxic apoptosis at the expense of cytoprotective autophagy. Together these findings demonstrate that miR-10a may be useful as both a biomarker to identify patients most likely to respond to cytarabine+MDM2 inhibition and also a druggable target to increase their efficacy.
13742 The role of interleukin-6 in anemia associated with hidradenitis suppurativa
Authors: Kayla M. Babbush, Mondana H. Ghias, Avigdor Nosrati, Kristen Pacific, Morayma Reyes Gil, Mark Chaitowitz, H. Dean Hosgood, Steven R. Cohen
Journal: Journal of the American Academy of Dermatology (2020)
Comprehensive Profiling of an Aging Immune System Reveals Clonal GZMK+ CD8+ T Cells as Conserved Hallmark of Inflammaging
Authors: Denis A. Mogilenko, Oleg Shpynov, Prabhakar Sairam Andhey, Laura Arthur, Amanda Swain, Ekaterina Esaulova, Simone Brioschi, Irina Shchukina, Martina Kerndl, Monika Bambouskova, Zhangting Yao, Anwesha Laha, Konstantin Zaitsev, Samantha Burdess, Susan Gillfilan, Sheila A. Stewart, Marco Colonna, Maxim N. Artyomov
Journal: Immunity (2020)
Abstract PO-016: Modulating cancer stem cell pathways to enhance systemic therapeutic efficacy
Authors: Pritam Sadhukhan, Masahiro Shibata, M. Talha Ugurlu, Rachel Goldberg, Mohammad O. Hoque
Journal: Cancer Research (2020)

Abstract Chemoresistance and poor immune sensitivity are one of the major challenges to treat different cancer types including lung, bladder and head &amp; neck. Different epigenetic regulators and cancer stem cells (CSCs) regulatory pathways play a critical role in the development of therapeutic resistance. Prolonged chemotherapy treatment enriches CSCs in the tumor microenvironment and in a previous study we have shown that inhibition of the CSCs regulatory pathway/s combined with chemotherapy decreased CSC properties and efficiently inhibit tumor growth in patient-derived xenografts (PDXs) models. The purpose of this study is to determine the chemo and immunotherapeutic efficacy in combination with several CSC pathway/s modulatory agent/agents to treat different solid tumors. To identify relevant CSC regulating pathways, we tested the therapeutic efficacy of different agents such as 5-Azacytidine (DNA methyltransferase 1 inhibitor), Vismodegib (SMO inhibitor), Romidepsin (HDAC1 inhibitor), Olaparib (PARP1 inhibitor), and GSK343 (EZH2 inhibitor) using different bladder and head &amp; neck cancer cell lines and also determined the numerous CSCs properties. Our data indicate that in vitro treatment with these potential therapeutic agents decreases cell viability, sphere formation and wound healing that suggest that, these drugs may be effective in reducing CSCs population when combined with chemo and/or immunotherapy. Our immunoblotting experiments indicate reduced expression of some CSCs markers and factors such as such as NANOG, OCT4, CD133 and CD24. Interestingly, after treating the cells with some of these agents and array analysis, we have found differential expression of some of the key genes regulating the immunogenic response. Further, to confirm the array-based data, selected candidate immune-associated genes were analyzed by qRT-PCR. Moreover, our preliminary data suggest that combination treatment with epigenetic drugs and an immune agent may effectively reduce tumor growth in vivo compared to either of these drugs. In conclusion, although comprehensive mechanistic studies are ongoing, our initial results highlight the importance of considering combination of epigenetic and immune therapy for patients with diverse cancer types that respond poorly to immune and chemotherapy. Citation Format: Pritam Sadhukhan, Masahiro Shibata, M. Talha Ugurlu, Rachel Goldberg, Mohammad O. Hoque. Modulating cancer stem cell pathways to enhance systemic therapeutic efficacy [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-016.