tbuckley/cabot-search huggingface dataset:
Abstract 20243: Management Outcomes of Acute Type A Aortic Syndrome Presenting With Completely Thrombosed False Lumen in the Ascending Aorta
Authors: Hee Jung Kim, Ho Jin Kim, Won Chul Cho, Joon Bum Kim, Sung Ho Jung, Suk Jung Choo, Cheol Hyun Chung, Jae Won Lee
Journal: Circulation (2017)

Introduction: Although the prognosis of acute type A aortic dissection without urgent surgical treatment are known to be dismal, there have been arguments that there may be a subset of hemodynamica...
Cross-Reactive Dengue Virus Antibodies Augment Zika Virus Infection of Human Placental Macrophages
Authors: Matthew G. Zimmerman, Kendra M. Quicke, Justin T. O'Neal, Nitin Arora, Deepa Machiah, Lalita Priyamvada, Robert C. Kauffman, Emery Register, Oluwaseyi Adekunle, Dominika Swieboda, Erica L. Johnson, Sarah Cordes, Lisa Haddad, Rana Chakraborty, Carolyn B. Coyne, Jens Wrammert, Mehul S. Suthar
Journal: Cell Host & Microbe (2018)
Inhibition of C3 with APL-2 Results in Normalisation of Markers of Intravascular and Extravascular Hemolysis in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)
Authors: Raymond SM Wong, Humphrey W.H. Pullon, Pascal Deschatelets, Cedric G Francois, Mohamed Hamdani, Surapol Issaragrisil, Patrick Johnson, Pimjai Niparuck, Tontanai Numbenjapon, Jameela Sathar, Lisa Tan, Eric Tse, Federico Grossi
Journal: Blood (2018)
Abstract 16535: Angiotensin II Receptor Blocker (ARB) in Combination With Neprilysin Inhibition is Superior to ARB Alone in the Setting of Heart Failure
Authors: Rishi K Trivedi, David J Polhemus, Zhen Li, Daniel Yoo, Hiroshi Koiwaya, Craig Zibilich, Traci T Goodchild, David J Lefer
Journal: Circulation (2017)

Introduction: EntrestoTM (LCZ696) combines valsartan, an angiotensin receptor blocker (ARB), and sacubitril, a neprilysin inhibitor (NEPi). LCZ696 was recently approved for use in heart failure (HF...
Bone marrow–derived fibroblasts are a functionally distinct stromal cell population in breast cancer
Authors: Yael Raz, Noam Cohen, Ophir Shani, Rachel E. Bell, Sergey V. Novitskiy, Lilach Abramovitz, Carmit Levy, Michael Milyavsky, Leonor Leider-Trejo, Harold L. Moses, Dan Grisaru, Neta Erez
Journal: The Journal of Experimental Medicine (2018)

Cancer-associated fibroblasts (CAFs) are highly prominent in breast tumors, but their functional heterogeneity and origin are still largely unresolved. We report that bone marrow (BM)-derived mesenchymal stromal cells (MSCs) are recruited to primary breast tumors and to lung metastases and differentiate to a distinct subpopulation of CAFs. We show that BM-derived CAFs are functionally important for tumor growth and enhance angiogenesis via up-regulation of Clusterin. Using newly generated transgenic mice and adoptive BM transplantations, we demonstrate that BM-derived fibroblasts are a substantial source of CAFs in the tumor microenvironment. Unlike resident CAFs, BM-derived CAFs do not express PDGFRα, and their recruitment resulted in a decrease in the percentage of PDGFRα-expressing CAFs. Strikingly, decrease in PDGFRα in breast cancer patients was associated with worse prognosis, suggesting that BM-derived CAFs may have deleterious effects on survival. Therefore, PDGFRα expression distinguishes two functionally unique CAF populations in breast tumors and metastases and may have important implications for patient stratification and precision therapeutics.
Identification of Jun loss promotes resistance to histone deacetylase inhibitor entinostat through Myc signaling in luminal breast cancer
Authors: Maki Tanioka, Kevin R. Mott, Daniel P. Hollern, Cheng Fan, David B. Darr, Charles M. Perou
Journal: Genome Medicine (2018)

Based on promising phase II data, the histone deacetylase inhibitor entinostat is in phase III trials for patients with metastatic estrogen receptor-positive breast cancer. Predictors of sensitivity and resistance, however, remain unknown. A total of eight cell lines and nine mouse models of breast cancer were treated with entinostat. Luminal cell lines were treated with or without entinostat at their IC50 doses, and MMTV/Neu luminal mouse tumors were untreated or treated with entinostat until progression. We investigated these models using their gene expression profiling by microarray and copy number by arrayCGH. We also utilized the network-based DawnRank algorithm that integrates DNA and RNA data to identify driver genes of resistance. The impact of candidate drivers was investigated in The Cancer Genome Atlas and METABRIC breast cancer datasets. Luminal models displayed enhanced sensitivity to entinostat as compared to basal-like or claudin-low models. Both in vitro and in vivo luminal models showed significant downregulation of Myc gene signatures following entinostat treatment. Myc gene signatures became upregulated on tumor progression in vivo and overexpression of Myc conferred resistance to entinostat in vitro. Further examination of resistance mechanisms in MMTV/Neu tumors identified a portion of mouse chromosome 4 that had DNA copy number loss and low gene expression. Within this region, Jun was computationally identified to be a driver gene of resistance. Jun knockdown in cell lines resulted in upregulation of Myc signatures and made these lines more resistant to entinostat. Jun-deleted samples, found in 17–23% of luminal patients, had significantly higher Myc signature scores that predicted worse survival. Entinostat inhibited luminal breast cancer through Myc signaling, which was upregulated by Jun DNA loss to promote resistance to entinostat in our models. Jun DNA copy number loss, and/or high MYC signatures, might represent biomarkers for entinostat responsiveness in luminal breast cancer.
Review: In coronary artery disease, PCI reduces 30-day and 5-year risk for stroke compared with CABG
Authors: Eric R. Bates
Journal: Annals of Internal Medicine (2018)

ACP Journal Club20 November 2018Review: In coronary artery disease, PCI reduces 30-day and 5-year risk for stroke compared with CABGEric R. Bates, MDEric R. Bates, MDUniversity of Michigan, Ann Arbor, Michigan, USA (E.R.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2018-169-10-055 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationHead SJ, Milojevic M, Daemen J, et al. Stroke rates following surgical versus percutaneous coronary revascularization. J Am Coll Cardiol. 2018;72:386-98. https://pubmed.ncbi.nlm.nih.gov/30025574Clinical Impact RatingsGIM/FP/GP: Hospitalists: Cardiology: Neurology: References1 Neumann FJ, Sousa-Uva M, Ahlsson A, et al; ESC Scientific Document Group. 2018 ESC/EACTS Guidelines on myocardial infarction. Eur Heart J. 2018. [Epub ahead of print]. Google Scholar2 Head SJ, Milojevic M, Daemen J, et al. Mortality after coronary artery bypass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data. Lancet. 2018;391:939-48. [PMID: 29478841] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Michigan, Ann Arbor, Michigan, USA (E.R.B.)This article was published at Annals.org on 6 November 2018. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 20 November 2018Volume 169, Issue 10Page: JC55KeywordsCoronary artery bypass graftingDeath ratesMortalityMyocardial infarctionNeurologyPercutaneous coronary interventionRevascularizationStable coronary artery diseaseStent implantationStroke ePublished: 20 November 2018 Issue Published: 20 November 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
NCCN Guidelines Insights: Cancer-Associated Venous Thromboembolic Disease, Version 2.2018
Authors: Michael B. Streiff, Bjorn Holmstrom, Dana Angelini, Aneel Ashrani, Paula L. Bockenstedt, Carolyn Chesney, John Fanikos, Randolph B. Fenninger, Annemarie E. Fogerty, Shuwei Gao, Samuel Z. Goldhaber, Krishna Gundabolu, Paul Hendrie, Alfred I. Lee, Jason T. Lee, Janelle Mann, Brandon McMahon, Michael M. Millenson, Colleen Morton, Thomas L. Ortel, Sadat Ozair, Rita Paschal, Sanford Shattil, Tanya Siddiqi, Kristi J. Smock, Gerald Soff, Tzu-Fei Wang, Eliot Williams, Anaadriana Zakarija, Lydia Hammond, Mary A. Dwyer, Anita M. Engh
Journal: Journal of the National Comprehensive Cancer Network (2018)

Venous thromboembolism (VTE) is common in patients with cancer and increases morbidity and mortality. VTE prevention and treatment are more complex in patients with cancer. The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of VTE in adult patients diagnosed with cancer or in whom cancer is clinically suspected. These NCCN Guidelines Insights explain recent changes in anticoagulants recommended for the treatment of cancer-associated VTE.
Gastrointestinal Malabsorption of Thyroxine
Authors: Camilla Virili, Alessandro Antonelli, Maria Giulia Santaguida, Salvatore Benvenga, Marco Centanni
Journal: Endocrine Reviews (2018)

Levothyroxine, a largely prescribed drug with a narrow therapeutic index, is often a lifelong treatment. The therapeutic efficacy of T4 may be marred by behavioral, pharmacologic, and pathologic issues acting as interfering factors. Despite a continuous search for an optimal T4 treatment, a significant number of patients fail to show a complete chemical and/or clinical response to this reference dose of T4. Gastrointestinal malabsorption of oral T4 represents an emerging cause of refractory hypothyroidism and may be more frequent than previously reputed. In this review, we examine the pharmacologic features of T4 preparations and their linkage with the intestinal absorption of the hormone. We have stressed the major biochemical and pharmacologic characteristics of T4 and its interaction with the putative transporter at the intestinal level. We have examined the interfering role of nutrients, foods, and drugs on T4 absorption at the gastric and intestinal levels. The impact of gastrointestinal disorders on T4 treatment efficacy has been also analyzed, in keeping with the site of action and the interfering mechanisms. Based on the evidence obtained from the literature, we also propose a schematic diagnostic workup for the most frequent and often hidden gastrointestinal diseases impairing T4 absorption.
Epidermal Growth Factor Receptor (EGFR) tyrosine kinase activity attenuates TNF-stimulated intestinal cell apoptosis
Authors: Toshimitsu Yamaoka, Rebecca S. Dise, Wei Tong, D Brent Polk
Journal: Cancer Research (2006)

181  Background. Epidermal Growth Factor Receptor (EGFR) tyrosine kinase activity, through cytokine and growth factor stimulation, is upregulated in ulcerative colitis and colon cancer, suggesting that the activation of EGFR is a response to colitis and colon cancer in humans. We previously presented that EGFR activation reverses TNF-mediated colon epithelial cell apoptosis. In the present study, we tested the hypothesis that EGFR tyrosine kinase regulates cytokine-mediated colon epithelial cell survival. Method. Young adult mouse colon (YAMC) cells, colon cancer HT-29 cells, EGFR-null mouse colonic epithelial (EGFR-/-MCE) cells, and stable clonal cell lines expressing either wild-type (wt) or kinase-inactive (ki) EGFR were developed by transfecting EGFR-/-MCE cells with either wt or ki cDNA, and controls consisting of vector (v) only were used for these studies. Cells were treated with cytokines only, which include TNF (100 ng/ml), IL-1 (10 ng/ml) and IFN-γ (100 ng/ml), or in the presence of either a PI 3-kinase inhibitor (wortmannin 100 nM or LY294002 5 μM), MAP kinase inhibitor (U0126 10 μM), MMP inhibitor (GM6001 50μM or TAPI-1) or EGFR tyrosine kinase inhibitor (AG1478 150 nM). Apoptosis and signal transduction pathway activation were determined by TUNEL staining and Western blot analysis, respectively. Results. In EGFR-/-MCE, ki and v cells, TNF induced apoptosis 3-, 5- fold compared to YAMC or wt cells. Furthermore treatment of YAMC or wt cells with TNF in the presence of the EGFR tyrosine kinase inhibitor increased apoptosis 10-fold. Similarly, treatment of YAMC or wt cells with TNF failed to increase apoptosis except in the presence of either PI 3-kinase inhibitor, which increased the apoptotic response 10-fold. In the HT-29 cells, TNF enhanced apoptosis 10-fold in the presence of EGFR tyrosine kinase inhibitor, but not other cytokines, IL-1 and IFN-γ. Although treatment of YAMC and wt cells with TNF in the presence of U0126, blocked ERK1/2 MAP kinase activation, there was no induction of apoptosis. TNF stimulated AKT/PKB activation via EGFR tyrosine kinase activation in wt cells but not in ki or v cells, and this EGFR transactivation by TNF is blocked with either MMP inhibitor, suggesting TNF-stimulated EGFR transactivation abrogates TNF-induced intestinal cell apoptosis. Conclusion. Loss of EGFR signals and EGFR tyrosine kinase activity significantly increases TNF-initiated colon epithelial cell apoptosis and conversely, EGFR tyrosine kinase activation blocks TNF-induced apoptosis. These effects should be mediated through activation of the PI 3-kinase/AKT pathway. This novel observation has significant implications for understanding the role of EGFR regulation in maintaining intestinal epithelial cell homeostasis in an environment of chronic inflammation, injury and repair, such as inflammatory bowel disease and tumorigenesis.
Efficacy and safety of epidermal growth factor receptor (EGFR) - Tyrosine kinase inhibitors (TKI) in elderly patients with EGFR mutation-positive non-small cell lung cancer (NSCLC)
Authors: Y. Takeyasu, Y. Goto, R. Morita, J. Sato, S. Murakami, H. Horinouchi, Y. Fujiwara, S. Kanda, N. Yamamoto, Y. Ohe
Journal: Annals of Oncology (2018)
Surgical Resection in HCC
Authors: Kevin Labadie, Kevin M. Sullivan, James O. Park
Journal: Liver Cancer (2018)

Hepatocellular carcinoma (HCC) is a deadly disease. Its incidence is rising worldwide without significant improvement in survival in spite of improving therapies. A wide array of treatment options for HCC exist and include surgery, catheter-based therapies, radiation and systemic therapy. These modalities are often used in combination for optimal management in a multidisciplinary approach. Surgical resection remains one of the only curative therapeutic options for HCC, although it is indicated in select patients with localized disease. Herein, we cover the role of surgical resection in the management of HCC, reviewing the perioperative and operative considerations, in addition to highlighting the advances in minimally invasive surgery and novel navigation technologies.
A Hitherto Undescribed Von Hippel Lindau Polymorphism Induced/Related Polycythemia Entity, Clinical Features, Cancer Association and Familiar Characteristics, Preliminary Data
Authors: Udvardy Miklos, Miklos Egyed, Imre Bodó, Gyula Remenyi, Zsuzsanna Bereczky, Aniko Ujfalusi, Arpad Illes
Journal: Blood (2018)
More Is More: Semiannual Breast MRI Screening in BRCA1 Mutation Carriers
Authors: Christiane K. Kuhl, Simone Schrading
Journal: Clinical Cancer Research (2018)

Although annual MRI screening has improved early diagnosis of hereditary breast cancer, fast growth rates of BRCA1-associated cancers can still lead to interval cancers and/or node-positive disease. Using MRI with shorter screening intervals helps to effectively avoid both interval cancers and node-positive stages, whereas there is no role for mammography in these women.See related article by Guindalini et al., p. 1786.
Utility of Gallium-68 PSMA PET/CT scan for staging and treatment of prostate cancer in contemporary era: Study from a tertiary care cancer centre in a developing country
Authors: A. Gupta, S.M. Hussain, P. Ahluwalia, G. Gautam, A. Punnakal, H. Chaturvedi, A. Rajput, J. Bal, P. Dougall
Journal: Annals of Oncology (2018)
In pursuit of the ‘Unbreakable’ Athlete: what is the role of moderating factors and circular causation?
Authors: Tim J Gabbett, Rasmus Oestergaard Nielsen, Michael Lejbach Bertelsen, Natália Franco Netto Bittencourt, Sérgio T Fonseca, Shane Malone, Merete Møller, Eric Oetter, Evert Verhagen, Johann Windt
Journal: British Journal of Sports Medicine (2018)

The goal for sports medicine practitioners is to develop robust athletes, capable of withstanding high training and competition loads. For sports medicine professionals, understanding the workload–capacity relationship is central to achieving this goal. This editorial discusses how two different methodological frameworks—(1) moderation and (2) circular causation—align to develop physical capacity and injury resilience in athletes.

The Arab proverb ‘ the straw that broke the camel’s back’ refers to a camel carrying a haystack that was so heavy a single piece of additional straw broke its back. In a sport setting, the ‘camel’ is the athlete, the ‘load of hay’ represents the maximal workload the athlete can tolerate safely (load capacity), and the ‘additional straw’ represents overload resulting in injury (capacity exceeded). The inherent biological qualities of the camel (eg, age, strength and so on) determine its cumulative straw -carrying capacity.

Basketball superstar Kobe Bryant had strong training ethic, well-developed physical qualities and was largely injury-free in the early stages of his career. He was a strong ‘camel’ accustomed to carrying large loads with ease. We speculate that his athletic pursuits in childhood and adolescence contributed to his high load capacity in adulthood. Indeed, weight-bearing physical activity during childhood and early puberty has a positive, and possibly enduring effect on bone strength.1 Furthermore, after a certain age, the eccentric heart hypertrophic adaptation …
RAS P21 Protein Activator 3 (RASA3) Specifically Promotes Pathogenic T Helper 17 Cell Generation by Repressing T-Helper-2-Cell-Biased Programs
Authors: Bing Wu, Song Zhang, Zengli Guo, Gang Wang, Ge Zhang, Ling Xie, Jitong Lou, Xian Chen, Di Wu, Wolfgang Bergmeier, Junnian Zheng, Yisong Y. Wan
Journal: Immunity (2018)
Testing for HCV Infection: An Update of Guidance for Clinicians and Laboratorians
Authors: Jane P. Getchell, Kelly E. Wroblewski, Alfred DeMaria, Christine L. Bean, Monica M. Parker, Mark Pandori, D. Robert Dufour, Michael P. Busch, Mark E. Brecher, William A. Meyer, Rick L. Pesano, Chong-Gee Teo, Geoffrey A. Beckett, Aufra C. Araujo, Bernard M. Branson, Jan Drobeniuc, Rikita Hatia, Scott D. Holmberg, Saleem Kamili, John W. Ward
Journal: MMWR Morbidity and Mortality Weekly Report (2013)
Undertreatment of High-Risk Localized Prostate Cancer in the California Latino Population
Authors: Daphne Y. Lichtensztajn, John T. Leppert, James D. Brooks, Sumit A. Shah, Weiva Sieh, Benjamin I. Chung, Scarlett L. Gomez, Iona Cheng
Journal: Journal of the National Comprehensive Cancer Network (2018)

Background: The NCCN Clinical Practice Guidelines in Oncology recommend definitive therapy for all men with high-risk localized prostate cancer (PCa) who have a life expectancy >5 years or who are symptomatic. However, the application of these guidelines may vary among ethnic groups. We compared receipt of guideline-concordant treatment between Latino and non-Latino white men in California. Methods: California Cancer Registry data were used to identify 2,421 Latino and 8,636 non-Latino white men diagnosed with high-risk localized PCa from 2010 through 2014. The association of clinical and sociodemographic factors with definitive treatment was examined using logistic regression, overall and by ethnicity. Results: Latinos were less likely than non-Latino whites to receive definitive treatment before (odds ratio [OR], 0.79; 95% CI, 0.71–0.88) and after adjusting for age and tumor characteristics (OR, 0.84; 95% CI, 0.75–0.95). Additional adjustment for sociodemographic factors eliminated the disparity. However, the association with treatment differed by ethnicity for several factors. Latino men with no health insurance were considerably less likely to receive definitive treatment relative to insured Latino men (OR, 0.34; 95% CI, 0.23–0.49), an association that was more pronounced than among non-Latino whites (OR, 0.63; 95% CI, 0.47–0.83). Intermediate-versus high-grade disease was associated with lower odds of definitive treatment in Latinos (OR, 0.75; 95% CI, 0.59–0.97) but not non-Latino whites. Younger age and care at NCI-designated Cancer Centers were significantly associated with receipt of definitive treatment in non-Latino whites but not in Latinos. Conclusions: California Latino men diagnosed with localized high-risk PCa are at increased risk for undertreatment. The observed treatment disparity is largely explained by sociodemographic factors, suggesting it may be ameliorated through targeted outreach, such as that aimed at younger and underinsured Latino men.
Benign oral mucosal lesions: Clinical and pathological findings
Authors: Mayra B.C. Maymone, Robert O. Greer, Lauren K. Burdine, Anh Dao-Cheng, Samantha Venkatesh, Priya Cherukuri Sahitya, Alexandre C. Maymone, Jeffery Kesecker, Neelam A. Vashi
Journal: Journal of the American Academy of Dermatology (2018)
Pathology Characterization and Detection of Human Papillomavirus Type 16 in Rectal Squamous Cell Carcinomas
Authors: Anna E. Coghill, Andrew M. Bellizzi, Charles F. Lynch, Meredith S. Shiels, Freda R. Selk, Maura Gillison, Brenda Y. Hernandez, Owen T.M. Chan, Eric A. Engels
Journal: Clinical Gastroenterology and Hepatology (2018)
Reconsidering the central role of mucins in dry eye and ocular surface diseases
Authors: Christophe Baudouin, Maurizio Rolando, Jose M. Benitez Del Castillo, Elisabeth M. Messmer, Francisco C. Figueiredo, Murat Irkec, Gysbert Van Setten, Marc Labetoulle
Journal: Progress in Retinal and Eye Research (2018)