tbuckley/cabot-search huggingface dataset:
Comparison of the 2017 and 2015 Global Initiative for Chronic Obstructive Lung Disease Reports. Impact on Grouping and Outcomes
Authors: Carlos Cabrera López, Ciro Casanova Macario, José María Marín Trigo, Juan P. de-Torres, Rebeca Sicilia Torres, Jesús María González, Francesca Polverino, Miguel Divo, Víctor Pinto Plata, Javier J. Zulueta, Bartolomé Celli
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) document has modified the grading system directing pharmacotherapy, but how this relates to the previous one from 2015 and to comorbidities, hospitalizations, and mortality risk is unknown.The aim of this study was to evaluate the changes in the GOLD groups from 2015 to 2017 and to assess the impact on severity, comorbidities, and mortality within each group.We prospectively enrolled and followed, for a mean of 5 years, 819 patients with chronic obstructive pulmonary disease (84% male) in clinics in Spain and the United States. We determined anthropometrics, lung function (FEV1%), dyspnea score (modified Medical Research Council scale), ambulatory and hospital exacerbations, and the body mass index, obstruction, dyspnea, and exercise capacity (BODE) and Charlson indexes. We classified patients by the 2015 and 2017 GOLD ABCD system, and compared the differential realignment of the same patients. We related the effect of the reclassification in BODE and Charlson distribution as well as chronic obstructive pulmonary disease and all-cause mortality between the two classifications.Compared with 2015, the 2017 grading decreased by half the proportion of patients in groups C and D (20.5% vs. 11.2% and 24.6% vs. 12.9%; P < 0.001). The distribution of Charlson also changed, whereas group D was higher than B in 2015, they become similar in the 2017 system. In 2017, the BODE index and risk of death were higher in B and D than in A and C. The mortality risk was better predicted by the 2015 than the 2017 system.Compared with 2015, the GOLD ABCD 2017 classification significantly shifts patients from grades C and D to categories A and B. The new grading system equalizes the Charlson comorbidity score in all groups and minimizes the differences in BODE between groups B and D, making the risk of death similar between them.
DINC 2.0: A New Protein–Peptide Docking Webserver Using an Incremental Approach
Authors: Dinler A. Antunes, Mark Moll, Didier Devaurs, Kyle R. Jackson, Gregory Lizée, Lydia E. Kavraki
Journal: Cancer Research (2017)

Abstract Molecular docking is a standard computational approach to predict binding modes of protein–ligand complexes by exploring alternative orientations and conformations of the ligand (i.e., by exploring ligand flexibility). Docking tools are largely used for virtual screening of small drug-like molecules, but their accuracy and efficiency greatly decays for ligands with more than 10 flexible bonds. This prevents a broader use of these tools to dock larger ligands, such as peptides, which are molecules of growing interest in cancer research. To overcome this limitation, our group has previously proposed a meta-docking strategy, called DINC, to predict binding modes of large ligands. By incrementally docking overlapping fragments of a ligand, DINC allowed predicting binding modes of peptide-based inhibitors of transcription factors involved in cancer. Here, we describe DINC 2.0, a revamped version of the DINC webserver with enhanced capabilities and a more user-friendly interface. DINC 2.0 allows docking ligands that were previously too challenging for DINC, such as peptides with more than 25 flexible bonds. The webserver is freely accessible at http://dinc.kavrakilab.org, together with additional documentation and video tutorials. Our team will provide continuous support for this tool and is working on extending its applicability to other challenging fields, such as personalized immunotherapy against cancer. Cancer Res; 77(21); e55–57. ©2017 AACR.
Abstract 15224: Importance of Beta Blocker Subtype for the Risk of Perioperative Adverse Events in Patients Without Heart Failure and Myocardial Infarction
Authors: Mads E Jørgensen, Gunnar H Gislason, Christian Torp-Pedersen, Mark Hlatky, C harlotte Andersson
Journal: Circulation (2015)

Objective: Beta blocker therapy in patients undergoing surgery is being revisited. Previous studies have demonstrated increased risks of perioperative adverse outcomes associated with beta blocker therapy, but whether some beta blocker subtypes may be superior to others remains unknown. Methods: Using nationwide Danish registries we included all non-cardiac surgeries in patients without heart failure or myocardial infarction in 2005-2011. Patients were grouped according to beta blocker use prior to surgery. Risks of 30-day MACE (major adverse cardiovascular events; non-fatal myocardial infarction, non-fatal stroke or cardiovascular death) were estimated using logistic regression models adjusted for gender, age, body mass index, pharmacotherapy, comorbidities, type of surgery and surgery risk. Results: We included 607,338 patients in the study. Patients on beta blockers (n=50,480) were older with similar gender distribution (mean age 66 years [sd=12.9], 45%male) compared with patients not on beta blockers (n=556,858) (mean age 52 years [sd=17.6], 44%male). Patients on beta blockers had more comorbidities and received more pharmacotherapy (all p&lt;0.001). Unadjusted absolute risks of MACE were increased with all beta blocker subtypes (range 1.7% for propranolol to 4.2% for sotalol) compared with untreated patients (0.8%). Odds ratios for the risk of 30-day MACE are shown in the Figure Conclusion: Patients without chronic heart failure and prior myocardial infarction were at increased risk of 30-day perioperative MACE when treated with beta blockers, with the exception of bisoprolol. Patients treated with carvedilol seemed to be at especially high risk.
miR34a/GOLPH3 Axis abrogates Urothelial Bladder Cancer Chemoresistance via Reduced Cancer Stemness
Authors: Qing Zhang, Junlong Zhuang, Yongming Deng, Lin Yang, Wenmin Cao, Wei Chen, Tingsheng Lin, Xiaoyu Lv, Hang Yu, Yanshi Xue, Hongqian Guo
Journal: Theranostics (2017)

Rationale: Chemoresistance and subsequent recurrence of human urothelial bladder cancer (UBC) is partially driven by a subpopulation of tumor initiating cells, namely cancer stem cells (CSCs). However, the underlying molecular mechanism in chemotherapy-induced CSCs enrichment and following chemoresistance and recurrence remains largely unclear. Methods: Gemcitabine and cisplatin (GC) chemoresistant cell lines (T24 GC 3rd and 5637 GC 3rd cells) and the chemo-sensitive UBC cell lines T24 and 5637 were established in vivo for the investigation of acquired resistance mechanisms. The role of miR34a/GOLPH3 axis in regulating UBC chemoresistance and recurrence was evaluated in cell and animal models. The expression levels of miR34a/GOLPH3 axis and CSCs markers were assayed in specimens of UBC. The association of GOLPH3 with clinicopathologic features and prognosis was analysed. Results: RT-PCR and western blotting confirmed that the expression levels of miR34a were decreased and GOLPH3 were increased in GC chemoresistant UBC cell lines. Downregulation of miR34a resulted in the overexpression of GOLPH3, which is a target gene of miR34a confirmed by luciferase experiment. The ectopic expression of miR34a decreased the stem cell properties of chemoresistant UBC cells and re-sensitized these cells to GC treatment in vitro and in vivo. Moreover, miR34a/GOLPH3 axis has obvious clinical relevance with prognosis and recurrence in human UBC patients with standard GC chemotherapy. Conclusion: Our results suggest that miR34a/GOLPH3 axis exert key role in CSCs involved UBC drug resistance and recurrence and warrant further development as a promising therapeutic approach in treating drug-resistant UBC.
PS04.01 ADAURA: PhIII, Double-Blind, Randomized Study of Osimertinib vs Placebo in EGFR Mutation-Positive NSCLC Post-Tumor Resection
Authors: R.S. Herbst, Y. Wu, H. Mann, Y. Rukazenkov, M. Marotti, M. Tsuboi
Journal: Journal of Thoracic Oncology (2017)
Capecitabine versus S-1 as adjuvant chemotherapy for patients with stage III colorectal cancer (JCOG0910): an open-label, non-inferiority, randomised, phase 3, multicentre trial
Authors: Tetsuya Hamaguchi, Yasuhiro Shimada, Junki Mizusawa, Yusuke Kinugasa, Yukihide Kanemitsu, Masayuki Ohue, Shoichi Fujii, Nobuhiro Takiguchi, Toshimasa Yatsuoka, Yasumasa Takii, Hitoshi Ojima, Hiroyuki Masuko, Yoshiro Kubo, Hideyuki Mishima, Takashi Yamaguchi, Hiroyuki Bando, Toshihiko Sato, Takeshi Kato, Kenichi Nakamura, Haruhiko Fukuda, Yoshihiro Moriya
Journal: The Lancet. Gastroenterology & hepatology (2017)
OA03.05 Tocilizumab for the Management of Immune Mediated Adverse Events Secondary to PD-1 Blockade: Overall Survival Analysis
Authors: C.R.G. Stroud, A. Hegde, A.R. Naqash, C. Cherry, T. Parent, J. Hardin, P.R. Walker
Journal: Journal of Thoracic Oncology (2017)
Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Focused Update
Authors: Ian Krop, Nofisat Ismaila, Fabrice Andre, Robert C. Bast, William Barlow, Deborah E. Collyar, M. Elizabeth Hammond, Nicole M. Kuderer, Minetta C. Liu, Robert G. Mennel, Catherine Van Poznak, Antonio C. Wolff, Vered Stearns
Journal: Journal of Clinical Oncology (2017)

Purpose This focused update addresses the use of MammaPrint (Agendia, Irvine, CA) to guide decisions on the use of adjuvant systemic therapy. Methods ASCO uses a signals approach to facilitate guideline updates. For this focused update, the publication of the phase III randomized MINDACT (Microarray in Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy) study to evaluate the MammaPrint assay in 6,693 women with early-stage breast cancer provided a signal. An expert panel reviewed the results of the MINDACT study along with other published literature on the MammaPrint assay to assess for evidence of clinical utility. Recommendations If a patient has hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-negative breast cancer, the MammaPrint assay may be used in those with high clinical risk to inform decisions on withholding adjuvant systemic chemotherapy due to its ability to identify a good-prognosis population with potentially limited chemotherapy benefit. Women in the low clinical risk category did not benefit from chemotherapy regardless of genomic MammaPrint risk group. Therefore, the MammaPrint assay does not have clinical utility in such patients. If a patient has hormone receptor-positive, HER2-negative, node-positive breast cancer, the MammaPrint assay may be used in patients with one to three positive nodes and a high clinical risk to inform decisions on withholding adjuvant systemic chemotherapy. However, such patients should be informed that a benefit from chemotherapy cannot be excluded, particularly in patients with greater than one involved lymph node. The clinician should not use the MammaPrint assay to guide decisions on adjuvant systemic therapy in patients with hormone receptor-positive, HER2-negative, node-positive breast cancer at low clinical risk, nor any patient with HER2-positive or triple-negative breast cancer, because of the lack of definitive data in these populations. Additional information can be found at www.asco.org/breast-cancer-guidelines and www.asco.org/guidelineswiki .
In small skin abscesses, clindamycin or trimethoprim–sulfamethoxazole after incision and drainage increased cures
Authors: Christopher A. Feddock
Journal: Annals of Internal Medicine (2017)

ACP Journal Club17 October 2017In small skin abscesses, clindamycin or trimethoprim–sulfamethoxazole after incision and drainage increased curesChristopher A. Feddock, MDChristopher A. Feddock, MDUniversity of Kentucky College of Medicine, Lexington, Kentucky, USA (C.A.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2017-167-8-039 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationDaum RS, Miller LG, Immergluck L, et al; DMID 07-0051 Team. A placebo-controlled trial of antibiotics for smaller skin abscesses. N Engl J Med. 2017;376:2545-55. https://pubmed.ncbi.nlm.nih.gov/28657870Clinical Impact RatingsGIM/FP/GP: Infectious Disease: References1 Stevens DL, Bisno AL, Chambers HF, et al; Infectious Diseases Society of America. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59:e10-52. [PMID: 24973422] Google Scholar2 Talan DA, Mower WR, Krishnadasan A, et al. Trimethoprim–sulfamethoxazole versus placebo for uncomplicated skin abscess. N Engl J Med. 2016;374:823-32. [PMID: 26962903] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Kentucky College of Medicine, Lexington, Kentucky, USA (C.A.F.)This article was published at Annals.org on 3 October 2017. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 17 October 2017Volume 167, Issue 8Page: JC39KeywordsAbscessesAntibioticsChildrenClindamycinInfectious diseasesSkin abscessesSkin infectionsStaphylococcal infectionSurgerySystemic inflammatory response syndrome ePublished: 17 October 2017 Issue Published: 17 October 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Crash-test dummy and pendulum impact tests of ice hockey boards: greater displacement does not reduce impact
Authors: Kai-Uwe Schmitt, Markus H Muser, Hansjuerg Thueler, Othmar Bruegger
Journal: British Journal of Sports Medicine (2017)

One injury mechanism in ice hockey is impact with the boards. We investigated whether more flexible hockey boards would provide less biomechanical loading on impact than did existing (reference) boards.We conducted impact tests with a dynamic pendulum (mass 60 kg) and with crash test dummies (ES-2 dummy, 4.76 m/s impact speed). Outcomes were biomechanical loading experienced by a player in terms of head acceleration, impact force to the shoulder, spine, abdomen and pelvis as well as compression of the thorax.The more flexible board designs featured substantial displacement at impact. Some so-called flexible boards were displaced four times more than the reference board. The new boards possessed less stiffness and up to 90 kg less effective mass, reducing the portion of the board mass a player experienced on impact, compared with boards with a conventional design. Flexible boards resulted in a similar or reduced loading for all body regions, apart from the shoulder. The displacement of a board system did not correlate directly with the biomechanical loading.Flexible board systems can reduce the loading of a player on impact. However, we found no correlation between the displacement and the biomechanical loading; accordingly, displacement alone was insufficient to characterise the overall loading of a player and thus the risk of injury associated with board impact. Ideally, the performance of boards is assessed on the basis of parameters that show a good correlation to injury risk.
Severe submucosal fibrosis – the “Achilles’ heel” of peroral endoscopic myotomy
Authors: Zaheer Nabi, D. Reddy, Mohan Ramchandani
Journal: Endoscopy (2017)

We read with great interest the article by Zhou et al. entitled "Submucosal fibrosis in achalasia patients is a rare cause of aborted peroral endoscopic myotomy procedures" [1]. This was a retrospective analysis of a large cohort of patients (n = 1693) in which the authors assessed the factors responsible for premature termination of peroral endoscopic myotomy (POEM) procedures. The authors concluded that severe submucosal fibrosis was the major factor leading to technical failure. We applaud the authors for their efforts in extracting enlightening information with regard to the prediction of submucosal fibrosis.
Abstract 1088: Prevention of Connexin 43 (Cx43) Dephosphorylation is Associated with Reduced Ventricular Tachycardia in Cardiac-Specific Angiotensin Converting Enzyme (ACE) Overexpression Mice
Authors: Shahriar Iravanian, Hong D Xiao, Emily A Witham, Kenneth E Bernstein, Samuel Dudley
Journal: Circulation (2007)

Introduction: Connexin 43 (Cx43) is a major component of the ventricular gap junctional complex, which provides a low resistance pathway for electrical conduction between myocytes. Reduction of Cx43 amount of phosphorylation has been implicated in the pathogenesis of ventricular tachycardia (VT) and fibrillation. Cardiac-specific angiotensin converting enzyme overexpression mice (ACE 8/8) have slow conduction, show conduction blocks, are prone to VT and sudden death, and show profound reductions in Cx43 levels and phosphorylation. Therefore, we hypothesized that reversal of Cx43 changes, by preventing the renin-angiotensin system (RAS) activation, would reduce the arrhythmic risk in these animals. Methods: Prevention of RAS activation was accomplished by one of three methods: ACE 8/8 receiving an ACE inhibitor (captopril), ACE 8/8 mice treated with a specific angiotensin receptor type-1 blocker (losartan), and ACE 8/8 mice crossed with homozygote angiotensinogen null mice. Pooled results were compared to untreated ACE 8/8 littermates. Surface electrocardiography and invasive electrophysiological study with programmed ventricular stimulation were performed on ten-week old mice, and the hearts were extracted for immunoblotting. Results: VT was induced in 10 out of 12 untreated ACE 8/8 mice, but only in 3 out of 11 treated mice (p&lt;0.02). Total Cx43 was not changed significantly in treated animals as compared to controls, but the ratio (P/NP) of phosphorylated Cx43 (bands P1 and P2 in immunoblot) to non-phosphorylated Cx43 (band P0) showed a trend toward increase in the treatment group (0.78±0.18 vs. 1.25±0.19; P=0.09). Dividing the mice into two groups, high-risk (inducible and/or spontaneous VT) versus low-risk (no VT), we observed a significant difference in P/NP ratio (0.75±0.12 in high-risk mice vs. 1.78±0.32 in low-risk, p&lt;0.01). Discussion: Unexpectedly, disruption of RAS signaling did not increase total Cx43 levels in ACE 8/8 mice. On the other hand, the treatments increased phospho-Cx43, suggesting that RAS controls Cx43 phosphorylation but not total amount. Even in the presence of significantly depressed levels of Cx43, small changes in Cx43 phosphorylation were associated with a significant reduction in VT inducibility.
TCT-438 Impact of concomitant coronary artery disease on risk for short-term MACCE in patients after TAVR
Authors: Birgit Vogel, Usman Baber, Melissa Aquino, Samantha Sartori, Jaya Chandrasekhar, Serdar Farhan, Sabato Sorrentino, Jason Kovacic, Zhen Ge, Joseph Sweeny, Samaneh Rabieihashemi, Abdul Qadeer, Srushti Shah, Pooja Vijay, Nitin Barman, Pedro Moreno, George Dangas, Roxana Mehran, Annapoorna Kini, Samin Sharma
Journal: Journal of the American College of Cardiology (2017)
A 52-Year-Old Man With Unheralded Syncope
Authors: Rishi K. Wadhera, Garrick C. Stewart, Patrick T. O’Gara
Journal: JAMA Cardiology (2017)

A 52-year-old man with mild asthma who experienced an episode of unheralded syncope while walking has sinus bradycardia and first-degree atrioventricular, left posterior fascicle, and right bundle branch blocks on electrocardiography. What is your diagnosis?
A novel genetic and morphologic phenotype of ARID2-mediated myelodysplasia
Authors: H Sakai, N Hosono, H Nakazawa, B Przychodzen, C Polprasert, H E Carraway, M A Sekeres, T Radivoyevitch, K Yoshida, M Sanada, T Yoshizato, K Kataoka, M M Nakagawa, H Ueno, Y Nannya, A Kon, Y Shiozawa, J Takeda, Y Shiraishi, K Chiba, S Miyano, J Singh, R A Padgett, S Ogawa, J P Maciejewski, H Makishima
Journal: Leukemia (2017)
Prospective Feasibility Trial for Genomics-Informed Treatment in Recurrent and Progressive Glioblastoma
Authors: Sara A. Byron, Nhan L. Tran, Rebecca F. Halperin, Joanna J. Phillips, John G. Kuhn, John F. de Groot, Howard Colman, Keith L. Ligon, Patrick Y. Wen, Timothy F. Cloughesy, Ingo K. Mellinghoff, Nicholas A. Butowski, Jennie W. Taylor, Jennifer L. Clarke, Susan M. Chang, Mitchel S. Berger, Annette M. Molinaro, Gerald M. Maggiora, Sen Peng, Sara Nasser, Winnie S. Liang, Jeffrey M. Trent, Michael E. Berens, John D. Carpten, David W. Craig, Michael D. Prados
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Glioblastoma is an aggressive and molecularly heterogeneous cancer with few effective treatment options. We hypothesized that next-generation sequencing can be used to guide treatment recommendations within a clinically acceptable time frame following surgery for patients with recurrent glioblastoma. Experimental Design: We conducted a prospective genomics-informed feasibility trial in adults with recurrent and progressive glioblastoma. Following surgical resection, genome-wide tumor/normal exome sequencing and tumor RNA sequencing were performed to identify molecular targets for potential matched therapy. A multidisciplinary molecular tumor board issued treatment recommendations based on the genomic results, blood–brain barrier penetration of the indicated therapies, drug–drug interactions, and drug safety profiles. Feasibility of generating genomics-informed treatment recommendations within 35 days of surgery was assessed. Results: Of the 20 patients enrolled in the study, 16 patients had sufficient tumor tissue for analysis. Exome sequencing was completed for all patients, and RNA sequencing was completed for 14 patients. Treatment recommendations were provided within the study's feasibility time frame for 15 of 16 (94%) patients. Seven patients received treatment based on the tumor board recommendations. Two patients reached 12-month progression-free survival, both adhering to treatments based on the molecular profiling results. One patient remained on treatment and progression free 21 months after surgery, 3 times longer than the patient's previous time to progression. Analysis of matched nonenhancing tissue from 12 patients revealed overlapping as well as novel putatively actionable genomic alterations. Conclusions: Use of genome-wide molecular profiling is feasible and can be informative for guiding real-time, central nervous system–penetrant, genomics-informed treatment recommendations for patients with recurrent glioblastoma. Clin Cancer Res; 24(2); 295–305. ©2017 AACR. See related commentary by Wick and Kessler, p. 256
Analysis of patients with malignant tumor diagnosed at the department of G.I.M. in our hospital over the past five years
Authors: Junya Makiyama, Yasumori Izumi, Hideaki Kitanosono, Jun Nakashima, Seiji Doi, Akira Saeki, Seiji Nagashima, Shinichiro Yoshida
Journal: Annals of Oncology (2017)
Enhanced antitumor efficacy of biocompatible magnetosomes for the magnetic hyperthermia treatment of glioblastoma
Authors: Raphaël Le Fèvre, Mickaël Durand-Dubief, Imène Chebbi, Chalani Mandawala, France Lagroix, Jean-Pierre Valet, Ahmed Idbaih, Clovis Adam, Jean-Yves Delattre, Charlotte Schmitt, Caroline Maake, François Guyot, Edouard Alphandéry
Journal: Theranostics (2017)

In this study, biologically synthesized iron oxide nanoparticles, called magnetosomes, are made fully biocompatible by removing potentially toxic organic bacterial residues such as endotoxins at magnetosome mineral core surfaces and by coating such surface with poly-L-lysine, leading to magnetosomes-poly-L-lysine (M-PLL). M-PLL antitumor efficacy is compared with that of chemically synthesized iron oxide nanoparticles (IONPs) currently used for magnetic hyperthermia. M-PLL and IONPs are tested for the treatment of glioblastoma, a dreadful cancer, in which intratumor nanoparticle administration is clinically relevant, using a mouse allograft model of murine glioma (GL-261 cell line). A magnetic hyperthermia treatment protocol is proposed, in which 25 µg in iron of nanoparticles per mm