tbuckley/cabot-search huggingface dataset:
Inactivation of Hippo Pathway Is Significantly Associated with Poor Prognosis in Hepatocellular Carcinoma
Authors: Bo Hwa Sohn, Jae-Jun Shim, Sang-Bae Kim, Kyu Yun Jang, Soo Mi Kim, Ji Hoon Kim, Jun Eul Hwang, Hee-Jin Jang, Hyun-Sung Lee, Sang-Cheol Kim, Woojin Jeong, Sung Soo Kim, Eun Sung Park, Jeonghoon Heo, Yoon Jun Kim, Dae-Ghon Kim, Sun-Hee Leem, Ahmed Kaseb, Manal M. Hassan, Minse Cha, In-Sun Chu, Randy L. Johnson, Yun-Yong Park, Ju-Seog Lee
Journal: Clinical Cancer Research (2015)

Abstract Purpose: The Hippo pathway is a tumor suppressor in the liver. However, the clinical significance of Hippo pathway inactivation in HCC is not clearly defined. We analyzed genomic data from human and mouse tissues to determine clinical relevance of Hippo pathway inactivation in HCC. Experimental Design: We analyzed gene expression data from Mst1/2−/− and Sav1−/− mice and identified a 610-gene expression signature reflecting Hippo pathway inactivation in the liver [silence of Hippo (SOH) signature]. By integrating gene expression data from mouse models with those from human HCC tissues, we developed a prediction model that could identify HCC patients with an inactivated Hippo pathway and used it to test its significance in HCC patients, via univariate and multivariate Cox analyses. Results: HCC patients (National Cancer Institute cohort, n = 113) with the SOH signature had a significantly poorer prognosis than those without the SOH signature [P &amp;lt; 0.001 for overall survival (OS)]. The significant association of the signature with poor prognosis was further validated in the Korean (n = 100, P = 0.006 for OS) and Fudan University cohorts (n = 242, P = 0.001 for OS). On multivariate analysis, the signature was an independent predictor of recurrence-free survival (HR, 1.6; 95% confidence interval, 1.12–2.28: P = 0.008). We also demonstrated significant concordance between the SOH HCC subtype and the hepatic stem cell HCC subtype that had been identified in a previous study (P &amp;lt; 0.001). Conclusions: Inactivation of the Hippo pathway in HCC is significantly associated with poor prognosis. Clin Cancer Res; 22(5); 1256–64. ©2015 AACR.
Impaired efferocytosis in human chronic granulomatous disease is reversed by pioglitazone treatment
Authors: Ruby F. Fernandez-Boyanapalli, Emilia Liana Falcone, Christa S. Zerbe, Beatriz E. Marciano, S. Courtney Frasch, Peter M. Henson, Steven M. Holland, Donna L. Bratton
Journal: Journal of Allergy and Clinical Immunology (2015)
Neuronal Mechanisms of Visual Categorization: An Abstract View on Decision Making
Authors: David J. Freedman, John A. Assad
Journal: Annual Review of Neuroscience (2016)

Categorization is our ability to flexibly assign sensory stimuli into discrete, behaviorally relevant groupings. Categorical decisions can be used to study decision making more generally by dissociating category identity of stimuli from the actions subjects use to signal their decisions. Here we discuss the evidence for such abstract categorical encoding in the primate brain and consider the relationship with other perceptual decision paradigms. Recent work on visual categorization has examined neuronal activity across a hierarchically organized network of cortical areas in monkeys trained to group visual stimuli into arbitrary categories. This has revealed a transformation of visual-feature encoding in early visual cortical areas into more flexible categorical representations in downstream parietal and prefrontal areas. These neuronal category representations are encoded as abstract internal cognitive states because they are not rigidly linked with either specific sensory stimuli or the actions that the monkeys use to signal their categorical choices.
The incidence of tuberculosis in patients taking anti TNF alpha therapy
Authors: Coskun Dogan, Nesrin Kiral, Sevda Cömert, Ali Fidan, Banu Salepci, Benan Caglayan
Journal: European Respiratory Journal (2011)

Aim: The aim of study is to investigate the incidence of tuberculosis during the treatment in patients taking anti-tumor necrosis factor alpha (anti TNF-α).

Material/Method: The patients with rheumotoid arthritis,ankylosing spondylitis,jeuvenil rheumotoid arthritis or psoriatic arthiritis who were planned to treat with anti TNF-α or taking anti TNF-α therapy and sent to our pulmonary diseases outpatient clinic between July 2007-February 2010 were included in this study.PPD tests and chest X-rays were evaluated.Chest x-rays were examined for tuberculous sequelea and the patients suspicious for tuberculous sequelea were asked for contact with a tuberculosis case,physical examinations were done and their sputum was examined for acid-fast bacilli.

Results: Two hundred and twenty patients were included in the study.Anti TNF-α therapy was given the first time in 168 patients.Fifty two patients were already taking anti TNF-α therapy and directed to our outpatient clinic for follow-up.One hundred seventy nine patients were followed up regularly,41 patients did not continue follow-up and were excluded.Median follow-up period was 17 months (max: 31; min: 3 months). Two patients were diagnosed as tuberculosis during antiTNF-α therapy.

Conclusion: According to the data of ministry of health,the incidence of tuberculosis is 0.0026% in our country.In our study it is estabilished as 1.1%.When compared with the community,the incidence of tuberculosis is increased with antiTNF-α therapy.The blockade of TNF which one of the fundamental cytokins in human defense system leads to an increase in tuberculosis infection.The patients who were planned to treat with anti TNF-α should be monitored closely for tuberculosis during the treatment.
Abstract 16295: Human Epicardial Bipolar Electrograms Prolong and Reduce in Amplitude Prior to Induction of Peri-Operative Atrial Fibrillation and Are Related to Sites of High Electrogram Dominant Frequency in Sinus Rhythm
Authors: Junaid Zaman, Leanne Harling, Thanos Athanasiou, Nicholas S Peters
Journal: Circulation (2014)

Background: The exact trigger/substrate interactions leading to post-operative AF are unknown. Sites of high DF in sinus rhythm are proposed to harbor ‘fibrillar myocardium’ or ‘AF nests’. We studied AF inducibility related to putative upstream substrate changes by characterising epicardial electrograms (EGM) in both time and frequency domains. Method: AF naïve patients (n=14) undergoing coronary artery bypass grafting (CABG) had bipolar electrograms recorded from the lateral right atria (RA) wall with a high density spiral catheter, sampled at 1kHz. RA burst pacing at cycle lengths (CL) of 200, 500 and 1000ms was performed with any episodes of AF &gt; 30s recorded. Electrograms were analysed using an average of 5 consecutive beats for duration, peak to peak amplitude, dominant frequency (DF) and activation time at all bipole pairs during every pacing drive train (total EGMs analysed 3430). Results: Bipolar EGM duration was significantly longer during AF (mean = 76.64ms, SD = 29.35ms) than all other CLs or NSR (p&lt;0.0001). There was no difference between CLs but a trend to longer EGM at 200ms CL. EGM amplitude was significantly smaller during AF (mean = 0.85mV, SD = 0.51mv) vs. 500ms CL and NSR (p&lt;0.0001) and at 200ms vs. 500ms CL (p&lt;0.05) and NSR (p&lt;0.0001). The EGM DF was significantly lower in AF (mean = 75.87Hz, SD = 23.63Hz) vs NSR (mean = 89.33Hz, SD = 25.99Hz) (p&lt;0.05) but not vs. pacing CLs. Activation time was significantly prolonged at 200ms CL (mean = 29.41ms, SD = 16.23ms) vs AF and NSR (p&lt;0.001 and 0.05 respectively). Conclusions: Human bipolar EGMs prolong and reduce in amplitude in induced peri-operative AF than in NSR or pacing. Atrial activation slows at 200ms CL, prior to initiation of AF. These changes are accompanied by high DF sites in NSR which may reveal underlying ‘AF nests’ even in non-remodelled atria. These novel peri-operative electrophysiological findings suggest upstream substrate changes which may predispose patients to post-operative AF.
The Cytochrome bd Oxidase ofPorphyromonas gingivalis Contributes toOxidative Stress Resistance and DioxygenTolerance
Authors: Julia Leclerc, Eric Rosenfeld, Mathieu Trainini, Benedicte Martin, Vincent Meuric, Martine Bonnaure-Mallet, Christine Baysse
Journal: PLoS Medicine (2015)

Porphyromonas gingivalis is an etiologic agent of periodontal disease in humans. The disease
is associated with the formation of a mixed oral biofilm which is exposed to oxygen
and environmental stress, such as oxidative stress. To investigate possible roles for cytochrome
bd oxidase in the growth and persistence of this anaerobic bacterium inside the oral
biofilm, mutant strains deficient in cytochrome bd oxidase activity were characterized. This
study demonstrated that the cytochrome bd oxidase of Porphyromonas gingivalis, encoded
by cydAB, was able to catalyse O2 consumption and was involved in peroxide and superoxide
resistance, and dioxygen tolerance.
Introduction
Porphyromonas gingivalis is a gram negative anaerobe populating the oral cavity. P. gingivalis
resides in the dental plaque and it is a main contributor to periodontal diseases. The oral biofilm
is a model of microbial multicellularity and multicellular behaviour ranging from commensal
microbiome to virulent infection. The accumulated body of studies of bacterial
pathogens in periodontal acute and chronic infections have designated P. gingivalis, Tannerella
forsythia and Treponema denticola (also called “the red complex”) as the tripartite cornerstone
of the community in its pathogenic state, as recently confirmed by metagenomic microbiome
analysis [1]. Not only do they produce proteases, toxins and inflammatory compounds that
attack host tissue, but they can shape the whole behaviour of the community [2]. Nevertheless,
the physiological properties of each individual of the red complex are not fully understood. In
this respect, P. gingivalis remains a puzzling organism. Although it is non-motile, and possesses
a rather undersized armament for adaptive responses compared to most ubiquitous organisms,
P. gingivalis sustains the infection disease by surviving in the unfavourable environment of the
oral cavity and periodontal pockets, and by invading host tissues. For example, the P. gingivalis
PLOS ONE
Mayo Clinic/Renal Pathology Society Consensus Report on Pathologic Classification, Diagnosis, and Reporting of GN
Authors: Sanjeev Sethi, Mark Haas, Glen S. Markowitz, Vivette D. D’Agati, Helmut G. Rennke, J. Charles Jennette, Ingeborg M. Bajema, Charles E. Alpers, Anthony Chang, Lynn D. Cornell, Fernando G. Cosio, Agnes B. Fogo, Richard J. Glassock, Sundaram Hariharan, Neeraja Kambham, Donna J. Lager, Nelson Leung, Michael Mengel, Karl A. Nath, Ian S. Roberts, Brad H. Rovin, Surya V. Seshan, Richard J.H. Smith, Patrick D. Walker, Christopher G. Winearls, Gerald B. Appel, Mariam P. Alexander, Daniel C. Cattran, Carmen Avila Casado, H. Terence Cook, An S. De Vriese, Jai Radhakrishnan, Lorraine C. Racusen, Pierre Ronco, Fernando C. Fervenza
Journal: Journal of the American Society of Nephrology (2015)

Renal pathologists and nephrologists met on February 20, 2015 to establish an etiology/pathogenesis-based system for classification and diagnosis of GN, with a major aim of standardizing the kidney biopsy report of GN. On the basis of etiology/pathogenesis, GN is classified into the following five pathogenic types, each with specific disease entities: immune-complex GN, pauci-immune GN, antiglomerular basement membrane GN, monoclonal Ig GN, and C3 glomerulopathy. The pathogenesis-based classification forms the basis of the kidney biopsy report. To standardize the report, the diagnosis consists of a primary diagnosis and a secondary diagnosis. The primary diagnosis should include the disease entity/pathogenic type (if disease entity is not known) followed in order by pattern of injury (mixed patterns may be present); score/grade/class for disease entities, such as IgA nephropathy, lupus nephritis, and ANCA GN; and additional features as detailed herein. A pattern diagnosis as the sole primary diagnosis is not recommended. Secondary diagnoses should be reported separately and include coexisting lesions that do not form the primary diagnosis. Guidelines for the report format, light microscopy, immunofluorescence microscopy, electron microscopy, and ancillary studies are also provided. In summary, this consensus report emphasizes a pathogenesis-based classification of GN and provides guidelines for the standardized reporting of GN.
Old age, left bundle branch block and acute myocardial infarction: a vexing and lethal combination∗∗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: Gottlieb C Friesinger, Raphael F Smith
Journal: Journal of the American College of Cardiology (2000)
The tryptophan metabolism enzyme L-kynureninase is a novel inflammatory factor in psoriasis and other inflammatory diseases
Authors: Jamie L. Harden, Steven M. Lewis, Samantha R. Lish, Mayte Suárez-Fariñas, Daniel Gareau, Tim Lentini, Leanne M. Johnson-Huang, James G. Krueger, Michelle A. Lowes
Journal: Journal of Allergy and Clinical Immunology (2015)
Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial
Authors: Roy S Herbst, Paul Baas, Dong-Wan Kim, Enriqueta Felip, José L Pérez-Gracia, Ji-Youn Han, Julian Molina, Joo-Hang Kim, Catherine Dubos Arvis, Myung-Ju Ahn, Margarita Majem, Mary J Fidler, Gilberto de Castro, Marcelo Garrido, Gregory M Lubiniecki, Yue Shentu, Ellie Im, Marisa Dolled-Filhart, Edward B Garon
Journal: The Lancet (2015)
Curcumin Add-on Therapy for Remission Induction in Mild-moderate Active Ulcerative Colitis: A Multi-center, Randomized, Placebo-Controlled Trial
Authors: N. Salomon, A. Lang, U. Kopylov, A. Lahat, O. Har-Noy, J. Wu, J. Ching, P.K. Cheong, B. Avidan, D. Gamus, J. Kaimaklotis, A. Eliakim, S.C. Ng, S. Ben-Horin
Journal: Clinical Gastroenterology and Hepatology (2015)
Early clinical sequelae of Ebola virus disease in Sierra Leone: a cross-sectional study
Authors: John G Mattia, Mathew J Vandy, Joyce C Chang, Devin E Platt, Kerry Dierberg, Daniel G Bausch, Tim Brooks, Sampha Conteh, Ian Crozier, Robert A Fowler, Amadu P Kamara, Cindy Kang, Srividya Mahadevan, Yealie Mansaray, Lauren Marcell, Gillian McKay, Tim O'Dempsey, Victoria Parris, Ruxandra Pinto, Audrey Rangel, Alex P Salam, Jessica Shantha, Vanessa Wolfman, Steven Yeh, Adrienne K Chan, Sharmistha Mishra
Journal: The Lancet Infectious Diseases (2015)
Genome‐Wide DNA Methylation Study Identifies Significant Epigenomic Changes in Osteoarthritic Subchondral Bone and Similarity to Overlying Cartilage
Authors: Matlock A. Jeffries, Madison Donica, Lyle W. Baker, Michael E. Stevenson, Anand C. Annan, Mary Beth Humphrey, Judith A. James, Amr H. Sawalha
Journal: Arthritis & Rheumatology (2015)

To perform a genome-wide DNA methylation study to identify differential DNA methylation patterns in subchondral bone underlying eroded and intact cartilage from patients with hip osteoarthritis (OA) and to compare these with DNA methylation patterns in overlying cartilage.Genome-wide DNA methylation profiling using Illumina HumanMethylation 450 arrays was performed on eroded and intact cartilage and subchondral bone from within the same joint of 12 patients undergoing hip arthroplasty. Genes with differentially methylated CpG sites were analyzed to identify shared pathways, upstream regulators, and overrepresented gene ontologies, and these patterns were compared with those of the overlying cartilage. Histopathology was graded by modified Mankin score and assessed for correlation with DNA methylation.We identified 7,316 differentially methylated CpG sites in subchondral bone underlying eroded cartilage, most of which (∼75%) were hypomethylated, and 1,397 sites in overlying eroded cartilage, 126 of which were shared. Samples clustered into 3 groups with distinct histopathologic scores. We observed differential DNA methylation of genes including the RNA interference-processing gene AGO2, the growth factor TGFB3, the OA suppressor NFATC1, and the epigenetic effector HDAC4. Among known susceptibility genes in OA, 32 were differentially methylated in subchondral bone, 8 were differentially methylated in cartilage, and 5 were shared. Upstream regulator analysis using differentially methylated genes in OA subchondral bone showed a strong transforming growth factor β1 signature (P = 1 × 10(-40) ) and a tumor necrosis factor family signature (P = 3.2 × 10(-28) ), among others.Our data suggest the presence of an epigenetic phenotype associated with eroded OA subchondral bone that is similar to that of overlying eroded OA cartilage.
Novel protein markers identified by tissue fraction technique comparing estrogen receptor negative- against positive-breast cancer cells and tissues
Authors: Bae Ji-Yeon, Dong Hyun Kim, Wonshik Han, Cheolju Lee, Dong-Young Noh
Journal: Cancer Research (2007)

606    Background:  It is known that the biology and clinical features of breast cancers were very different according to hormone receptor expression. Recent gene expression profiling studies identified estrogen receptor (ER) expression as a fundamental classifier of breast cancers. Our purpose is to compare the proteomic profiles of hormone receptor positive vs. negative breast cancer cells and tissues, respectively.   Material and Methods:  MCF-7 and MDA-MB-231 harvested with scrapper. After sonication and centrifuge, urea lysis buffer were used. Three pairs of ER+ and ER- snap frozen human breast cancer tissue samples were obtained during operation. ER+ and ER- patients were matched by age and tumor stage. Tissue samples were homogenized and sonicated and then membrane fraction was isolated from the supernatant. 2-D difference in gel electrophoresis (2-D DIGE) and tandem mass spectrometry were used to investigate differentially expressed proteins.   Results:  A total of  57 identified proteins showed significantly different level of expression between MCF-7 and MDA-MB-231 cells. In MDA-MB-231, 33 proteins such as, tropomyosin 4, Glyoxalase I, Brevin, Stratifin, and annexin A5, were increased and 24 proteins such as, Cytokeratin 8, 18, and 19, G6PD, and Peroxiredoxin 2 were decreased compared with MCF-7 more than two-fold. In tissues, a total of 12 significant proteins were identified. Among membrane fraction, 6 proteins showed increased and 6 proteins showed decreased expression in ER- cancers compared to ER+ cancers. In cytosol fraction, another 12 proteins different between ER- and + cancers were identified. A total of 55 proteins in whole proteome samples were identified to show significantly different level of expression between normal and cancer. 41 proteins, such as Alpha enolase, malate dehydrogenase, and heat shock 27 kDa protein, were increased, and 14 proteins, such as serotransferrin precursor, fatty acid-binding protein, and retinal dehydrogenase 1, were decreased in cancer samples compared to normal samples. In the analysis of fraction samples, 8 and 12 differentially expressed proteins were identified in membrane fraction and cytosolic fraction, respectively. A total of 55 proteins in whole proteome samples were identified to show significantly different level of expression between normal and cancer. In the analysis of fraction samples, 8 and 12 differentially expressed proteins were identified in membrane fraction and cytosolic fraction, respectively.  Conclusion:  We found several novel protein markers that can differentiate ER+ and ER- breast cancer cells and tissues. It could be due to the narrow pH range of our experiment and posttranscriptional change. The proteins are under validation with conventional methods.
Experience and outcomes of nipple-sparing mastectomy following reduction mammoplasty.
Authors: Michael Alperovich, Keith M. Blechman, Fares Samra, Richard Shapiro, Deborah M. Axelrod, Mihye Choi, Nolan S. Karp, Amber Azniv Guth
Journal: Journal of Clinical Oncology (2012)

193 Background: Breast cancer resection strives for less radical approaches that offer superior aesthetic results without compromising oncologic safety. Nipple-sparing mastectomy (NSM) has gained popularity, but usually has been offered to smaller breasted and minimally ptotic women without history of extensive breast surgery. We present a series of nine nipple-sparing mastectomies following reduction mammoplasty. Methods: Charts of patients who underwent NSM following reduction mammoplasty at the NYU Medical Center from 2006 through 2011 were reviewed. Outcomes measured include post-operative complications, breast cancer recurrence, presence of cancer in the nipple-areolar complex, and nipple-areolar complex viability. Results: In total, the records of 235 (145 prophylactic, 90 therapeutic) NSM patients at NYU Medical Center were reviewed. Six patients for a total of 9 breasts had NSM following reduction mammoplasty. This subset of patients had a mean age of 46.2, mean BMI of 25.1, no history of diabetes and 1 smoker. Seven of 9 breasts were therapeutic resections and 2 of 9 were prophylactic. Time elapsed between reduction mammoplasty and NSM ranged from 33 days to 11 years. The majority of resections were in Stage 0 patients (6/9) with 1/9 in Stage I and 2/9 in Stage IIA. In all cases, prior reduction mammoplasty incisions were utilized for NSM. Eight patients were reconstructed immediately with tissue expanders, and 1 patient had a latissimus dorsi flap with immediate implant. Complications included 1 hematoma requiring evacuation and 1 displaced implant requiring revision. There were no positive subareolar biopsies and 100% nipple viability. Mean follow-up time was 9.4 months. Conclusions: Our experience demonstrates that NSM can be offered following reduction mammoplasty with comparable reconstructive outcomes to NSM alone. Reduction mammoplasty followed by NSM has potential as a reconstructive tool in prophylactic cases unsuited for primary NSM.
Why don't people exercise, even a little?
Authors: D. Kamerow
Journal: BMJ (2015)

There must be something we can do about it



Everyone knows that exercise is good for you. Physical inactivity is estimated to cause 3.2 million deaths a year globally, making it number four on the list of risk factors.1 In the United States, inactivity combined with poor diet is second only to smoking as a risk factor for death.2 There is much evidence showing that regular exercise is one of the most important things you can do for your health, better than any pill that we have.

Brief digression for a small rant: why do experts insist on the term “physical activity,” which sounds clinical and scientific, instead of “exercise,” which only sounds arduous and undesirable? (I guess I answered my own question.)

Anyway, physical activity is defined as anything that gets the skeletal muscles moving and that expends energy. The list of benefits of regular physical activity grows each year and includes decreased risk of heart disease, diabetes, some cancers, and depression and dementia, along with help with weight control, bone strength, and, for elderly …