tbuckley/cabot-search huggingface dataset:
Deconstructing Burnout to Define a Positive Path Forward
Authors: Thomas H. Lee, Deirdre E. Mylod
Journal: JAMA Internal Medicine (2019)

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Standards for MIC testing that apply to the majority of bacterial pathogens should also be enforced for Mycobacterium tuberculosis complex
Authors: T. Schön, E. Matuschek, S. Mohamed, M. Utukuri, S. Heysell, J.-W. Alffenaar, S. Shin, E. Martinez, V. Sintchenko, F.P. Maurer, P.M. Keller, G. Kahlmeter, C.U. Köser
Journal: Clinical Microbiology and Infection (2019)
KIR 2DS4 May Influence Autologous and Cord Blood(CB) Natural Killer (NK)Cell Mediated in Vitro Cytotoxicity Against Freshly Isolated Human Bone Marrow Myeloma Plasma Cells and Cell Lines
Authors: Pinar Yurdakul Mesutoglu, Hasan Yalim Akin, Merve Bunsuz, Eylul Turasan, Mustafa Merter, Cemalettin Ozturk, Klara Dalva, Meral Beksac
Journal: Blood (2018)
ACC/AHA 2002 Guideline Update for Exercise Testing: Summary Article
Authors: Raymond J. Gibbons, Gary J. Balady, J. Timothy Bricker, Bernard R. Chaitman, Gerald F. Fletcher, Victor F. Froelicher, Daniel B. Mark, Ben D. McCallister, Aryan N. Mooss, Michael G. O’Reilly, William L. Winters, Raymond J. Gibbons, Elliott M. Antman, Joseph S. Alpert, David P. Faxon, Valentin Fuster, Gabriel Gregoratos, Loren F. Hiratzka, Alice K. Jacobs, Richard O. Russell, Sidney C. Smith
Journal: Circulation (2002)

Heart Association (AHA) Task Force on Practice Guidelines regularly reviews existing guidelines to determine when an update or full revision is needed.This process gives priority to areas where major changes in text, and particularly recommendations, are mentioned on the basis of new understanding or evidence.Minor
Influence of body image in specific contexts of life of students of Pharmacy-Biochemistry: a validation study
Authors: J. A. D. B. Campos, W. R. Silva, B. G. Martins, J. Maroco
Journal: Psychotherapy and Psychosomatics (2015)

State Univ Julio de Mesquita Filho, Dept Food & Nutr, Fac Pharm Araraquara, Sao Paulo, Brazil
ARv7 Represses Tumor-Suppressor Genes in Castration-Resistant Prostate Cancer
Authors: Laura Cato, Jonas de Tribolet-Hardy, Irene Lee, Jaice T. Rottenberg, Ilsa Coleman, Diana Melchers, René Houtman, Tengfei Xiao, Wei Li, Takuma Uo, Shihua Sun, Nane C. Kuznik, Bettina Göppert, Fatma Ozgun, Martin E. van Royen, Adriaan B. Houtsmuller, Raga Vadhi, Prakash K. Rao, Lewyn Li, Steven P. Balk, Robert B. Den, Bruce J. Trock, R. Jeffrey Karnes, Robert B. Jenkins, Eric A. Klein, Elai Davicioni, Friederike J. Gruhl, Henry W. Long, X. Shirley Liu, Andrew C.B. Cato, Nathan A. Lack, Peter S. Nelson, Stephen R. Plymate, Anna C. Groner, Myles Brown
Journal: Cancer Cell (2019)
The Histone Methyltransferase SETDB1 Controls T Helper Cell Lineage Integrity by Repressing Endogenous Retroviruses
Authors: Véronique Adoue, Bénédicte Binet, Agathe Malbec, Joanna Fourquet, Paola Romagnoli, Joost P.M. van Meerwijk, Sebastian Amigorena, Olivier P. Joffre
Journal: Immunity (2019)
Risk of Post-Transplant Lymphoproliferative Disorders (PTLD) in Solid Organ Transplantation Patients with EBV Viremia
Authors: Yazeed Sawalha, John McMichael, Lisa Rybicki, Tamara A. Sussman, Alex V. Mejia Garcia, Robert M. Dean, Brad Pohlman, Brian T. Hill, Deepa Jagadeesh
Journal: Blood (2018)
Clinical and functional analysis of SOX9 in colorectal cancer.
Authors: Erik Lizarraga, Erika Ruiz Garcia, Cesar Lopez-Camarillo, Abelardo Meneses, Horacio Astudillo, Edith Araceli Fernandez Figueroa, Leonardo Lino-Silva, Mariana Melisa Avendaño-Félix, Maryelv Parra-Niebla, Mercedes Bermúdez-Cortés, Rosalío Ramos-Payán, Erik Silva-Benítez, José Geovanni Romero-Quintana, Elsa Maribel Aguilar-Medina
Journal: Journal of Clinical Oncology (2019)

519 Background: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. CRC develops within the intestinal epithelium, which is constantly self-renewing, developmental genes could promote the initiation and progression of cancer. SOX9 transcription factor is expressed especially in intestinal stem cells and in Paneth cells, thus alterations in expression could greatly promote neoplasia. However, the clinical significance and functional role of SOX9 in CRC remains unclear. The aim of this study is to investigate the association of SOX9 expression with relapse in CRC patients and initiate functional studies by evaluating the effects of silencing SOX9 in stem cells properties such as colonospheres formation in HCT116 CRC cells. Methods: 97 FFPE biopsies from CRC patients in stage I (N = 34) and stage II (N = 63) were analyzed. Immunoreactivity of SOX9 was classified as low and high expression groups based on the percentage of positive nucleus and tissue staining intensity. SOX9 silencing was achieved using a specific siRNA and Lipofectamine-RNAiMax and confirmed by qPCR 24 h postransfection. 40,000 HCT116 and HCT116-siSOX9 cells were seeded under adherent and ultra-low attachment conditions for tumorigenesis assays. After 72 h colonospheres were seeded and quantified. ROC analysis was used to assess the clinical correlation of SOX9 with relapse. Experimental data were expressed as means and differences tested by t-Student. Results: Data showed that 12.3% of patients relapsed. Interestingly, all of them showed lower SOX9 expression (p ≤ 0.05), regardless of their relapse free survival. In functional analysis, SOX9-deficient HCT116 cells formed smaller and less-compacted spheroid when compared to non-transfected HCT116 (p ≤ 0.05). Nonetheless, cell proliferation and migration under adherent condition were similar between the groups. Conclusions: This study did not find association between SOX9 expression and relapse. So far, in vitro assays results suggest that silencing of SOX9 inhibits colonospheres formation in HCT116 cells. Further investigation will be performed in order to evaluate the functional importance of SOX9 in chemotherapy response.
Impact of sarcopenia on outcomes in patients with rectal carcinoma treated with trimodality therapy.
Authors: Maria Luisa Sandoval, Zhigang Yuan, G. Daniel Grass, Seth Felder, Julian Sanchez, Sophie Dessureault, Iman Imanirad, Richard D. Kim, Sarah E. Hoffe, Jessica Frakes
Journal: Journal of Clinical Oncology (2019)

687 Background: Sarcopenia has been identified as a negative prognostic factor in several gastrointestinal malignancies. We sought to evaluate whether total psoas area (TPA) was predictive of grade ≥ 3 toxicity, recurrence and overall survival in patients with rectal carcinoma who received tri-modality therapy. Methods: After IRB approval, a retrospective analysis of 112 patients with biopsy-proven rectal cancer treated with neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy was performed. The L4 vertebra was identified on pre-treatment axial CT and the bilateral psoas muscles were manually contoured to determine the skeletal muscle index, which was normalized by height. Sarcopenia was defined as TPA less than the median of the cohort. (&lt; 1463 mm 3 /m). Acute toxicity was defined as within 3 months of radiation based on Common Terminology Criteria for Adverse Events version 4. Chi-square was used to assess differences between groups. Time to event analysis was estimated by Kaplan-Meier methods followed by log rank comparison. Predictor variables for outcomes were assessed with Cox regression. Results: Median follow-up was 31 months. Female gender was strongly associated with being sarcopenic (P &lt; 0.001) otherwise no other differences in clinical or treatment characteristics were found. 20 patients (17.8%) developed recurrence (95% distant). Patients with sarcopenia had a decreased risk of recurrence (P = 0.048) as well as a longer time to recurrence from radiation (50 vs. 21.4 months, P = 0.006) and surgery (47.2 vs. 17.9 months, P = 0.006). Gender was not associated with risk of recurrence (p = 0.131). On multivariable analysis, absence of sarcopenia was predictive of time to recurrence following radiation (HR 4.7, 95% CI: 1.2-18.8; P = 0.03). The presence of sarcopenia was not associated with overall survival (P = 0.12) or grade ≥ 3 acute toxicity (P = 0.242). Conclusions: In our cohort, patients with sarcopenia appear to have better tumor control when compared to patients without sarcopenia independent of gender, suggesting this may be a predictor of treatment response. However, sarcopenia was not associated with overall survival or probability of having grade ≥ 3 acute toxicity.
Myelofibrosis Is Initiated and Sustained By Rare Multipotent Stem Cells
Authors: Jessie J.F. Medeiros, Amanda Mitchell, Aaron Trotman-Grant, Tristan Woo, Jenny M. Ho, Andrea Arruda, Mark D. Minden, John E. Dick, Vikas Gupta, Liran I. Shlush
Journal: Blood (2018)
Multidisciplinary, evidence-based consensus guidelines for human papillomavirus (HPV) vaccination in high-risk populations, Spain, 2016
Authors: Xavier Martínez-Gómez, Adrian Curran, Magda Campins, Laia Alemany, José Ángel Rodrigo-Pendás, Natalia Borruel, Xavier Castellsagué, Cristina Díaz-de-Heredia, Fernando A Moraga-Llop, Marta del Pino, Aureli Torné
Journal: Eurosurveillance (2019)

Although human papillomavirus (HPV) routine vaccination programmes have been implemented around the world and recommendations have been expanded to include other high-risk individuals, current recommendations often differ between countries in Europe, as well as worldwide.
Abstract 18874: A microRNA Signature of Tobacco Exposure
Authors: Christine Willinger, Jian Rong, Tianxiao Huan, Kahraman Tanriverdi, Paul Courchesne, Josée Dupuis, George O’Connor, Jane Freedman, Martin G Larson, Daniel Levy
Journal: Circulation (2014)

BACKGROUND: Smoking is a cardinal risk factor for cardiovascular disease, and microRNAs (miRNAs) are key regulators of gene expression that may be involved in the development of smoking-related diseases. We sought to unravel the relationship between miRNAs and smoking by describing a miRNA signature of tobacco exposure and relating these results to the expression of smoking-associated genes. METHODS: Expression profiling of 333 miRNAs was conducted on whole blood RNA from 5,728 Framingham Heart Study participant samples using TaqMan assays and high-throughput qRT-PCR. Smoking status was classified as current, former, or never. The association of miRNA expression with smoking status was tested using general linear models, and significant miRNAs were analyzed in pairwise comparisons. Smoking-related mRNA expression associations were identified from gene expression profiling of the same RNA samples with the Affymetrix Human Exon Array ST v1.0. MiRNA-mRNA coexpression was analyzed using linear mixed effects models. RESULTS: Seven miRNAs were associated with smoking status: miR-1180, miR-181a2-3p, miR-423-5p, miR-25-5p, miR-1285-3p, miR-342-5p, and miR-744-3p (Table 1). 1,626 gene transcripts were coexpressed with one or more smoking-related miRNAs. Gene ontology enrichment analysis implicated the coexpressed genes in multiple biological processes, e.g., the ubiquitin cycle, intracellular transport, and DNA metabolism. Four genes were coexpressed with all seven smoking-associated miRNAs; most notable were TMEM56 , reported to be associated with coronary heart disease, and DOCK8 , which has been linked to lung cancer in vitro . CONCLUSIONS: We identified a novel miRNA signature of tobacco exposure featuring decreased expression of miRNAs in smokers. Our coexpression results implicate these miRNAs in smoking-related diseases and suggest broad regulatory effects on protein synthesis and turnover. TABLE 1. miRNA Associations with Smoking Status
Sequencing of different targeted therapies in management of KRAS wild-type metastatic colorectal cancer: A meta-analysis.
Authors: Jin Li, Gong Chen, Weijia Fang, Yongsong Tang
Journal: Journal of Clinical Oncology (2019)

679 Background: First-line (1L) antiendothelial growth factor receptor (anti-EGFR) is considered suitable in metastatic colorectal cancer (mCRC) patients. As no treatment guidelines recommend target therapy sequence in mCRC, this meta-analysis determined the optimal sequence of targeted therapies in patients with KRAS wild type (WT) mCRC. Methods: PICO framework was used to retrieve relevant studies from PubMed, Embase, Cochrane Library and Google Scholar. mCRC patients treated with 1L anti-EGFR and second-line (2L) anti -VEGF were compared with 1L anti-VEGF and 2L anti-EGFR treatment (gp. A). Patients treated with 1L anti-VEGF and 2L anti-EGFR treatment were compared with anti-VEGF in 1L and 2L (gp. B). We also compared 2L and 3L anti-EGFR therapies (gp. C). Primary and secondary outcomes of overall survival (OS) and progression free survival (PFS) were presented as hazard ratio (HR) and 95% confidence intervals (95% CIs). Objective response rate (ORR) was evaluated in terms of relative risk (RR) and 95% CI. P &lt; 0.05 was considered statistically significant. Results: We identified nine studies for this analysis including 1478 KRAS WT mCRC patients. In gp. p A (three studies; two retrospective and one post-hoc analysis; 450 patients), 1L anti-EGFR and 2L anti-VEGF treatment had a significantly higher OS (HR 0.83, 95% CI 0.53-1.32; p = 0.0022) and PFS (HR 0.85, 95% CI 0.76- 0.96; p = 0.0081) than 1L anti-VEGF and 2L anti-EGFR. Comparison in gp. B (n = 3 RCTs involving 431 mCRC KRAS WT patients) showed no significant difference in OS (HR 0.95, 95% CI 0.70- 1.29; p = 0.6897; I 2 = 42.69%) and PFS (HR 1.43, 95% CI 0.83- 2.47; p = 0.1962; I 2 = 81.55%) between the two lines of treatment. ORR was higher with anti-VEGF in both 1L and 2L in gp. B (RR 3.58, 95% CI 0.72- 17.85; p = 0.1191). In gp. C, indirect comparison showed similar OS with 3L and 2L anti-EGFR therapies ((3L and 2L: n = 2 studies each; HR 0.86. 95% CI 0.71-1.04; HR 0.78, 95% CI 0.51-1.20; 2L vs. 3L; p = 0.06). Conclusions: Patients with KRAS WT mCRC achieved maximum benefit with 1L anti-EGFR and 2L anti-VEGF than with 1L anti-VEGF and 2L anti-EGFR or 1L and 2L anti-VEGF. Hence, it is suggested to initiate the therapy with 1L anti-EGFR to derive the maximum clinical benefit.
Carfilzomib Induces Acute Endothelial Dysfunction Which Correlates with the Occurrence of Cardiovascular Events
Authors: Efstathios Kastritis, Aggeliki Laina, Maria Gavriatopoulou, Georgios Georgiopoulos, Evangelos Eleutherakis-Papaiakovou, Fotiou Despina, Nikolaos Kanellias, Ioanna Dialoupi, Nikolaos Makris, Efstathios Manios, Magdalini Migkou, Dimitrios C. Ziogas, Maria Roussou, Aristea-Maria Papanota, Eleni-Dimitra Papanagnou, Evangelos Terpos, Ioannis P. Trougakos, Kimon Stamatelopoulos, Meletios A Dimopoulos
Journal: Blood (2018)
Precision medicine: discovering clinically relevant and mechanistically anchored disease subgroups at scale
Authors: Antony Rosen, Scott L. Zeger
Journal: Journal of Clinical Investigation (2019)

American medicine is on the precipice of dramatic change, forced by disruptive technologies in measurement, computation, and communication.This change is inevitable, because society can no longer afford the nearly $1 trillion in annual waste, a major fraction of which is caused by poorly informed medical decisions and misaligned incentives.In America, if top-down solutions remain stalled, the needed change can only occur through better health decisions based on more valid measurements and analyses that improve medical decisions and the health of individuals and populations.In our view, precision medicine, by this or any other name, is the science-based application of modern measurement and analysis to improve each health decision.Precision medicine must define clinically relevant and mechanistically anchored health and disease subgroups for which optimal strategies can be followed (when known) and discovered (when not).Precision medicine is the scientific framework of the learning health system that can bring informed innovations to clinical practice (1).As such, precision medicine has the potential to exploit the technology revolutions (2), as most other industries are doing, to improve the health of Americans at more affordable costs.
Temozolomide in grade III neuroendocrine neoplasms (G3 NENs): A multicenter retrospective review.
Authors: David Chan, Emily K. Bergsland, Jennifer A. Chan, Rujuta Gadgil, Thorvardur Ragnar Halfdanarson, Kathleen Hornbacker, Virginia Kelly, Pamela L. Kunz, Patrick Walsh McGarrah, Nitya Prabhakar Raj, Diane Lauren Reidy, Alia Thawer, Julia Whitman, Linda Wu, Simron Singh
Journal: Journal of Clinical Oncology (2019)

321 Background: G3 NENs are aggressive, and optimal systemic treatment is unclear. Temozolomide (TEM)-based regimens have been used to treat grade 1-2 NETs, but their efficacy in G3 NENs (Ki-67 &gt; 20%) remains undetermined. Aims: To assess the clinical efficacy of TEM-containing regimens in advanced grade III gastroenteropancreatic NENs (GEPNENs). Methods: A multicentre retrospective review (2008-2017) of patients with metastatic/unresectable G3 GEPNENs who received a TEM-containing regimen. The primary endpoint was time to treatment failure (TTF). Radiologic response was extracted from local reports without formal RECIST criteria. Results: 118 patients in six centers were included (median age 55, 65% male, 15% functional, 75% pancreatic NEN). 57% were well-differentiated, 35% poorly-differentiated, and 18% unknown based on local pathology reports. The regimen used was CAPTEM in 93% and TEM in 7%. Best radiological responses were: complete response (1%), partial response (39%), stable disease (22%), progressive disease (31%), unknown (7%) not by RECIST. Median TTF was 150 days and median overall survival (OS) 18.0 months. Fifteen patients (14%) required dose reductions/discontinuation due to adverse events. TTF was shorter for patients on TEM alone (p = 0.02, Table 1). Well-differentiated NENs had better response rate (52% vs 26%, p = 0.02) and overall survival (30.1 vs 12.0 mo, p = 0.008) compared to poorly-differentiated NEN. Conclusions: This is the largest TEM treatment series in G3 NEN, involving collaboration of several major North American NET centers. 40% of patients showed some degree of response, and treatment was generally well-tolerated. TEM-based regimens should be considered a viable treatment option in this setting. Prospective confirmatory trials (such as EA2142) may face difficulties in accrual due to disease rarity. [Table: see text]
Collaborative ISL1/GATA3 interaction in controlling neuroblastoma oncogenic pathways overlapping with but distinct from MYCN
Authors: Qitong Zhang, Qingquan Zhang, Xue Jiang, Youqiong Ye, Huimin Liao, Fugui Zhu, Jie Yan, Lina Luo, Li Tian, Cizhong Jiang, Yihan Chen, Xingqun Liang, Yunfu Sun
Journal: Theranostics (2019)

Background: Transcription factor ISL1 plays a critical role in sympathetic neurogenesis.Expression of ISL1 has been associated with neuroblastoma, a pediatric tumor derived from sympatho-adrenal progenitors, however the role of ISL1 in neuroblastoma remains unexplored.Method: Here, we knocked down ISL1 (KD) in SH-SY5Y neuroblastoma cells and performed RNA-seq and ISL1 ChIP-seq analyses.Results: Analyses of these data revealed that ISL1 acts upstream of multiple oncogenic genes and pathways essential for neuroblastoma proliferation and differentiation, including LMO1 and LIN28B.ISL1 promotes expression of a number of cell cycle associated genes, but represses differentiation associated genes including RA receptors and the downstream target genes EPAS1 and CDKN1A.Consequently, Knockdown of ISL1 inhibits neuroblastoma cell proliferation and migration in vitro and impedes tumor growth in vivo, and enhances neuronal differentiation by RA treatment.Furthermore, genome-wide mapping revealed a substantial co-occupancy of binding regions by ISL1 and GATA3, and ISL1 physically interacts with GATA3, and together they synergistically regulate the aforementioned oncogenic pathways.In addition, analyses of the roles of ISL1 and MYCN in MYCN-amplified and MYCN non-amplified neuroblastoma cells revealed an epistatic relationship between ISL1 and MYCN.ISL1 and MYCN function in parallel to regulate common yet distinct oncogenic pathways in neuroblastoma. Conclusion:Our study has demonstrated that ISL1 plays an essential role in neuroblastoma regulatory networks and may serve as a potential therapeutic target in neuroblastoma.
Dynamics of circulating TNF during adalimumab treatment using a drug-tolerant TNF assay
Authors: Lea C. Berkhout, Merel J. l’Ami, Jill Ruwaard, Margreet H. Hart, Pleuni Ooijevaar-de Heer, Karien Bloem, Michael T. Nurmohamed, Ronald F. van Vollenhoven, Maarten Boers, Daniel F. Alvarez, Catherine H. Smith, Gerrit J. Wolbink, Theo Rispens
Journal: Science Translational Medicine (2019)

TNF concentrations stabilize in patients with rheumatoid arthritis during long-term adalimumab therapy and are associated with antidrug antibodies.
p53 Functional Assessment and Correlation with 17p Deletion and/or TP53 Mutation Status: Final Report of the ICLL001 Bomp Trial
Authors: Magali Le Garff-Tavernier, Claire Quiney, Lauren Veronese, Florence Nguyen-Khac, Pauline Robbe, Patricia Combes, Marie-Sarah Dilhuydy, Pierre Feugier, Beatrice Mahe, Laurence Sanhes, Alain Jacques Delmer, Loic Ysebaert, Malgorzata Truchan-Graczyk, Brigitte Dreyfus, Choquet Sylvain, Thérèse Aurran, Emmanuelle Ferrant, Caroline Dartigeas, Stéphane Leprêtre, Gian Matteo Pica, Frederic Davi, Bruno Pereira, Roselyne Delepine, Anna Schuh, Romain Guieze, Jacques-Olivier Bay, Véronique Leblond, Helene Merle-Beral, Sophie de Guibert, Olivier Tournilhac
Journal: Blood (2018)