tbuckley/cabot-search huggingface dataset:
Risk of myocardial infarction with use of selected non-steroidal anti-inflammatory drugs in patients with spondyloarthritis and osteoarthritis
Authors: Maureen Dubreuil, Qiong Louie-Gao, Christine E Peloquin, Hyon K Choi, Yuqing Zhang, Tuhina Neogi
Journal: Annals of the Rheumatic Diseases (2018)

Spondyloarthritis (SpA) is associated with an increased risk of myocardial infarction (MI) due to underlying inflammation and possibly due to medications such as certain non-steroidal anti-inflammatory drugs (NSAIDs). We sought to describe MI risk among patients with SpA who were prescribed NSAIDs, and to compare the pattern of risk in SpA with that in osteoarthritis (OA).Nested case-control studies were performed using The Health Improvement Network (THIN). Underlying cohorts included adults with incident SpA or OA who had >1 NSAID prescription and no history of MI. Within each cohort, we matched each MI case to four controls without MI. NSAID use was categorised as: (a) current (prescription date 0-180 days prior to index date), (b) recent (181-365 days) or (c) remote (>365 days). We performed conditional logistic regression to compare the odds of current or recent NSAID use relative to remote use of any NSAID, considering diclofenac and naproxen specifically.Within the SpA cohort of 8140 and the OA cohort of 244 339, there were 115 and 6287 MI cases, respectively. After adjustment, current diclofenac use in SpA was associated with an OR of 3.32 (95% CI 1.57 to 7.03) for MI. Naproxen was not associated with any increase (adjusted OR 1.19, 95% CI 0.53 to 2.68). A ratio of ORs for SpA/diclofenac relative to OA/diclofenac was 2.64 (95% CI 1.24 to 5.58).MI risk in SpA is increased among current users of diclofenac, but not naproxen. The MI risk with diclofenac in SpA appears to differ from that in OA.
Assessment of tumor hypoxia with radiolabeled metronidazole
Authors: Richard Mendez, David Yang, Cliff Chao, Ali Azhdarinia, Chang-Sok Oh, Mithu Chanda, Dong-Fang Yu, Edmund Kim
Journal: Cancer Research (2005)

3823  Introduction: This study was aimed to develop 99mTc- and 68Ga-labeled metronidazole (MN) using ethylenedicysteine (EC) as a chelator and evaluate their potential use to assess tumor hypoxia. 99mTc (6hr, 140 keV) is for SPECT and 68Ga (68 min, 511 keV) is for PET. Methods: EC-MN was labeled with 99mTc in the presence of tin (II) chloride. Labeling EC-MN with 68Ga was achieved by adding 68GaCl3 (2 mCi with 3.4 μg cold GaCl3). In vitro cellular uptakes of 99mTc- and 68Ga-EC-MN were obtained in various types of tumor cells at 0.5-4 hrs. Tissue distribution and PET imaging of 99mTc and 68Ga-EC-MN were evaluated in breast tumor-bearing rats at 0.5-4 hrs. Tumor oxygen tension was measured using an oxygen probe. In a pilot study, cancer patients were administered 30 mCi 99mTc-EC-MN and SPECT images were acquired at 3 hrs. Results: There were similar cellular uptakes (2-10%) between 99mTc- and 68Ga-EC-MN at 0.5-4 hrs. In vivo biodistribution of 99mTc- and 68Ga-EC-MN in breast tumor-bearing rats showed increased tumor-to-blood and tumor-to-muscle count density ratios as a function of time. Planar, SPECT and PET images confirmed that the tumors could be visualized clearly with 99mTc- and 68Ga-EC-MN. Oxygen tension in tumor tissue was determined to be 6-10 mmHg compared to 40-50 mmHg in normal muscle tissue. Conclusions: The results indicated that it is feasible to noninvasively use 99mTc- and 68Ga-EC-MN for the assessment of tumor hypoxia by PET or SPECT. These agents may be useful in selecting and evaluating cancer therapy.
Medico-Chirurgical Society: Tuesday, Feb. 9, 1841
Authors: B. C. Brodie
Journal: BMJ (1841)

TIIE SOUTH LONDON DISPENSARY.MUCH difference of opinion exists in regard to the treatment of phlebitis, and much remains to be known, respect- ing its cause, nature, and consequences; all are agreed as to its danger.It is the object of the author of the paper to describe the disease, its phenomena during life, and the pathological appearances after death, as they occurred in an isolated case.The patient, about 60 years of age, the subject of piles and large varicose veins in both extremities, received a slight wound, probably from his razor, in the upper lip, which was followed by eniormous swelling of the part, but not much constitutional disturbance.At the end of fourteen days, the disease appeared to have finished its
THE EFFECT OF ROUTINE VIDEO-RECORDING ON COLONOSCOPY QUALITY INDICATORS: A MULTICENTER, CLUSTER RANDOMIZED CONTROLLED TRIAL
Authors: M Rupinska, P Wieszczy, R Franczyk, M Rupinski, J Reguła, MF Kaminski
Journal: Endoscopy (2018)

To assess the effect of routine video-recording (REC) on colonoscopy quality indicators: adenoma detection rate (ADR), and cecal intubation rate (CIR).
Financial Impact of Breast Cancer in Black Versus White Women
Authors: Stephanie B. Wheeler, Jennifer C. Spencer, Laura C. Pinheiro, Lisa A. Carey, Andrew F. Olshan, Katherine E. Reeder-Hayes
Journal: Journal of Clinical Oncology (2018)

Purpose Racial variation in the financial impact of cancer may contribute to observed differences in the use of guideline-recommended treatments. We describe racial differences with regard to the financial impact of breast cancer in a large population-based prospective cohort study. Methods The Carolina Breast Cancer Study oversampled black women and women younger than age 50 years with incident breast cancer in North Carolina from 2008 to 2013. Participants provided medical records and data regarding demographics, socioeconomic status, and financial impact of cancer at 5 and 25 months postdiagnosis. We report unadjusted and adjusted financial impact at 25 months postdiagnosis by race. Results The sample included 2,494 women who completed follow-up surveys (49% black, 51% white). Since diagnosis, 58% of black women reported any adverse financial impact of cancer ( v 39% of white women; P &lt; .001). In models adjusted for age, stage at diagnosis, and treatment received, black women were more likely to report adverse financial impact attributable to cancer (adjusted risk difference [aRD], +14 percentage points; P &lt; .001), including income loss (aRD, +10 percentage points; P &lt; .001), health care–related financial barriers (aRD, +10 percentage points; P &lt; .001), health care–related transportation barriers (aRD, +10 percentage points; P &lt; .001), job loss (aRD, 6 percentage points; P &lt; .001), and loss of health insurance (aRD, +3 percentage points; P &lt; .001). The effect of race was attenuated when socioeconomic factors were included but remained significant for job loss, transportation barriers, income loss, and overall financial impact. Conclusion Compared with white women, black women with breast cancer experience a significantly worse financial impact. Disproportionate financial strain may contribute to higher stress, lower treatment compliance, and worse outcomes by race. Policies that help to limit the effect of cancer-related financial strain are needed.
Early versus late parenteral nutrition in critically ill, term neonates: a preplanned secondary subgroup analysis of the PEPaNIC multicentre, randomised controlled trial
Authors: Esther van Puffelen, Ilse Vanhorebeek, Koen F M Joosten, Pieter J Wouters, Greet Van den Berghe, Sascha C A T Verbruggen
Journal: The Lancet Child & Adolescent Health (2018)
Acetyl-CoA Carboxylase Inhibitor GS-0976 for 12 Weeks Reduces Hepatic De Novo Lipogenesis and Steatosis in Patients With Nonalcoholic Steatohepatitis
Authors: Eric J. Lawitz, Angie Coste, Fred Poordad, Naim Alkhouri, Nicole Loo, Bryan J. McColgan, Jacqueline M. Tarrant, Tuan Nguyen, Ling Han, Chuhan Chung, Adrian S. Ray, John G. McHutchison, G. Mani Subramanian, Robert P. Myers, Michael S. Middleton, Claude Sirlin, Rohit Loomba, Edna Nyangau, Mark Fitch, Kelvin Li, Marc Hellerstein
Journal: Clinical Gastroenterology and Hepatology (2018)
Improving the global diagnosis and management of asthma in children
Authors: Warren Lenney, Andrew Bush, Dominic A Fitzgerald, Monica Fletcher, Anders Ostrem, Soren Pedersen, Stanley J Szefler, Heather J Zar
Journal: Thorax (2018)

Asthma is the most common chronic condition in children worldwide. It affects daytime activities, sleep and school attendance and causes anxiety to parents, families and other carers. The quality of asthma diagnosis and management globally still needs substantial improvement. From infancy to the teenage years, there are age-specific challenges, including both underdiagnosis and overdiagnosis with stigma-related barriers to treatment in some cultures and in adolescents. Guidelines are increasingly evidence based, but their impact on improving outcomes has been negligible in many parts of the world, often due to lack of implementation. New thinking is needed to enable substantial improvements in outcomes. The disease varies globally and plans will need to differ for individual countries or places where region-specific barriers prevent optimal care. A wide selection of educational activities is needed, including community-targeted initiatives, to engage with families. The Paediatric Asthma Project Plan has been initiated to strengthen diagnosis and management of asthma. This encompasses a vision for the next 10–15 years, building on the knowledge and experience from previous educational projects. It will take into account the educational needs of patients, carers and healthcare professionals as well as the accessibility and affordability of medication, particularly in low and middle-income countries where the prevalence of asthma is rising more rapidly. This overview presents a first step for those involved in the diagnosis and management of childhood asthma to strengthen care for children globally.
PTPN12/PTP-PEST Regulates Phosphorylation-Dependent Ubiquitination and Stability of Focal Adhesion Substrates in Invasive Glioblastoma Cells
Authors: Zhihua Chen, John E. Morales, Paola A. Guerrero, Huandong Sun, Joseph H. McCarty
Journal: Cancer Research (2018)

Abstract Glioblastoma (GBM) is an invasive brain cancer with tumor cells that disperse from the primary mass, escaping surgical resection and invariably giving rise to lethal recurrent lesions. Here we report that PTP-PEST, a cytoplasmic protein tyrosine phosphatase, controls GBM cell invasion by physically bridging the focal adhesion protein Crk-associated substrate (Cas) to valosin-containing protein (Vcp), an ATP-dependent protein segregase that selectively extracts ubiquitinated proteins from multiprotein complexes and targets them for degradation via the ubiquitin proteasome system. Both Cas and Vcp are substrates for PTP-PEST, with the phosphorylation status of tyrosine 805 (Y805) in Vcp impacting affinity for Cas in focal adhesions and controlling ubiquitination levels and protein stability. Perturbing PTP-PEST–mediated phosphorylation of Cas and Vcp led to alterations in GBM cell-invasive growth in vitro and in preclinical mouse models. Collectively, these data reveal a novel regulatory mechanism involving PTP-PEST, Vcp, and Cas that dynamically balances phosphorylation-dependent ubiquitination of key focal proteins involved in GBM cell invasion. Significance: PTP-PEST balances GBM cell growth and invasion by interacting with the ATP-dependent ubiquitin segregase Vcp/p97 and regulating phosphorylation and stability of the focal adhesion protein p130Cas. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/14/3809/F1.large.jpg. Cancer Res; 78(14); 3809–22. ©2018 AACR.
P508Massively parallel sequencing of patients affected with arrhythmogenic cardiomyopathy by a targeted gene panel identified a novel nonsense mutation in TP63 gene
Authors: G Poloni, M Calore, A Lorenzon, G Thiene, C Basso, D Corrado, B Bauce, A Rampazzo, M De Bortoli
Journal: Cardiovascular Research (2018)
The Detection of Uterine Leiomyoma (Fibroid) Calcifications on 18F-NaF PET/CT
Authors: Abdullah Al-Zaghal, Thomas J. Werner, Poul F. Høilund-Carlsen, Abass Alavi
Journal: Clinical Nuclear Medicine (2018)

Uterine leiomyomas (fibroids) are the most common type of uterine neoplasms in premenopausal women. Leiomyomas are estrogen dependent and tend to atrophy and shrink in size after menopause. Dystrophic calcification, cystic changes, and necrosis are among the changes that indicate uterine fibroid involution. We are presenting a calcified uterine leiomyoma in a 61-year-old woman as incidentally detected on F-NaF PET/CT scanning. Many previous publications have reported the accumulation of F-NaF in soft tissue calcifications; these findings further set new directions in the evaluation of the metabolic activity of macrocalcification and microcalcification using molecular imaging probes.
Metreleptin-mediated improvements in insulin sensitivity are independent of food intake in humans with lipodystrophy
Authors: Rebecca J. Brown, Areli Valencia, Megan Startzell, Elaine Cochran, Peter J. Walter, H. Martin Garraffo, Hongyi Cai, Ahmed M. Gharib, Ronald Ouwerkerk, Amber B. Courville, Shanna Bernstein, Robert J. Brychta, Kong Y. Chen, Mary Walter, Sungyoung Auh, Phillip Gorden
Journal: Journal of Clinical Investigation (2018)

Recombinant leptin (metreleptin) ameliorates hyperphagia and metabolic abnormalities in leptin-deficient humans with lipodystrophy. We aimed to determine whether metreleptin improves glucose and lipid metabolism in humans when food intake is held constant.Patients with lipodystrophy were hospitalized for 19 days, with food intake held constant by a controlled diet in an inpatient metabolic ward. In a nonrandomized, crossover design, patients previously treated with metreleptin (n = 8) were continued on metreleptin for 5 days and then taken off metreleptin for the next 14 days (withdrawal cohort). This order was reversed in metreleptin-naive patients (n = 14), who were reevaluated after 6 months of metreleptin treatment on an ad libitum diet (initiation cohort). Outcome measurements included insulin sensitivity by hyperinsulinemic-euglycemic clamp, fasting glucose and triglyceride levels, lipolysis measured using isotopic tracers, and liver fat by magnetic resonance spectroscopy.With food intake constant, peripheral insulin sensitivity decreased by 41% after stopping metreleptin for 14 days (withdrawal cohort) and increased by 32% after treatment with metreleptin for 14 days (initiation cohort). In the initiation cohort only, metreleptin decreased fasting glucose by 11% and triglycerides by 41% and increased hepatic insulin sensitivity. Liver fat decreased from 21.8% to 18.7%. In the initiation cohort, changes in lipolysis were not independent of food intake, but after 6 months of metreleptin treatment on an ad libitum diet, lipolysis decreased by 30% (palmitate turnover) to 35% (glycerol turnover).Using lipodystrophy as a human model of leptin deficiency and replacement, we show that metreleptin improves insulin sensitivity and decreases hepatic and circulating triglycerides and that these improvements are independent of its effects on food intake.ClinicalTrials.gov NCT01778556FUNDING. This research was supported by the intramural research program of the NIDDK.
MicroRNA-210 overexpression promotes psoriasis-like inflammation by inducing Th1 and Th17 cell differentiation
Authors: Ruifang Wu, Jinrong Zeng, Jin Yuan, Xinjie Deng, Yi Huang, Lina Chen, Peng Zhang, Huan Feng, Zixin Liu, Zijun Wang, Xiaofei Gao, Haijing Wu, Honglin Wang, Yuwen Su, Ming Zhao, Qianjin Lu
Journal: Journal of Clinical Investigation (2018)

Immune imbalance of T lymphocyte subsets is a hallmark of psoriasis, but the molecular mechanisms underlying this aspect of psoriasis pathology are poorly understood. Here, we report that microRNA-210 (miR-210), a miR that is highly expressed in both psoriasis patients and mouse models, induces helper T (Th) 17 and Th1 cell differentiation but inhibits Th2 differentiation through repressing STAT6 and LYN expression, contributing to several aspects of the immune imbalance in psoriasis. Both miR-210 ablation in mice and inhibition of miR-210 by intradermal injection of antagomir-210 blocked the immune imbalance and the development of psoriasis-like inflammation in an imiquimod-induced or IL-23–induced psoriasis-like mouse model. We further showed that TGF-β and IL-23 enhance miR-210 expression by inducing HIF-1α, which recruits P300 and promotes histone H3 acetylation in the miR-210 promoter region. Our results reveal a crucial role for miR-210 in the immune imbalance of T lymphocyte subsets in psoriasis and suggest a potential therapeutic avenue.
TWO LITERS OF POLYETHYLENE GLYCOL (PEG) WITH 15 MG OF BISACODYL VERSUS 4 LITERS OF PEG FOR BOWEL PREPARATION TO COLONOSCOPY
Authors: A Elmekkaoui, M Oualgouh, A Zazour, W Khannoussi, G Kharrasse, Z Ismaili
Journal: Endoscopy (2018)

Comparing the tolerance, acceptability and efficacy of a protocol A based on 4L of PEG and a protocol B corresponding to 2L of PEG + 15 mg of Bisacodyl.
Change in bilirubin with obeticholic acid treatment in primary biliary cholangitis patients with high baseline bilirubin: a retrospective analysis of POISE, 201, and 202
Authors: G. Hirschfield, M. Shiffman, A. Pares, E.S. Malecha, R. Pencek, L. Macconell, D. Shapiro
Journal: Journal of Hepatology (2018)
Impact of Patient Age and Histological Type on Radioactive Iodine Avidity of Recurrent Lesions of Differentiated Thyroid Carcinoma
Authors: Kenichi Nakanishi, Toyone Kikumori, Noriyuki Miyajima, Yuko Takano, Sumiyo Noda, Dai Takeuchi, Shingo Iwano, Yasuhiro Kodera
Journal: Clinical Nuclear Medicine (2018)

Age is a prognostic factor for recurrent differentiated thyroid carcinoma (DTC) and may be related to radioactive iodine (RAI) nonavidity. Indications for molecular-targeted drugs (MTDs) are currently limited to RAI-refractory DTC. Demonstrating refractoriness to RAI, mainly indicated by RAI nonavidity, may be a barrier to the introduction of MTDs for elderly patients. The present study was conducted to evaluate the impact of age and histological type on the RAI avidity of recurrent lesions of DTC.Two hundred fifty-eight patients (189 patients with classic papillary thyroid carcinoma [cPTC], 8 patients with follicular variant of papillary thyroid carcinoma, and 61 patients with follicular thyroid carcinoma), who underwent their first RAI whole-body scanning for recurrent DTC at our institution between 2004 and 2013, were retrospectively studied. Radioactive iodine uptake was determined by visible uptake by metastatic lesion(s) in a diagnostic RAI-whole-body scan.The prevalence of RAI-avid lung metastases in cPTC indicated a significant, inverse correlation with age (<55 years, 36.2%; ≥55 years, 3%; P < 0.001). By contrast, for follicular thyroid carcinoma, the prevalence of RAI avidity was not influenced by age. Similar tendencies were observed for lymph node metastases.Radioactive iodine avidity by metastatic lesions of cPTC in elderly patients, especially those older than 55 years, was seldom demonstrated. Adherence to a strategy of restricting MTD administration after confirmation of RAI refractoriness should be revisited for elderly patients. A strategy of omitting RAI treatment should be taken into account when considering age and histological type.
Abstract 19423: ATF6 Serves a Novel Role as an Integrator of the Antioxidation and Adaptive ER Stress Responses in the Heart
Authors: Jung-Kang Jin, Khalid Azizi, Donna J Thuerauf, Erik A Blackwood, Asal G Fahem, Shirin Doroudgar, Christopher C Glembotski
Journal: Circulation (2016)

Introduction:  Secreted and membrane proteins are synthesized and folded in the endoplasmic reticulum (ER). We previously showed that myocardial ischemia increases ER protein misfolding and activates the ER stress response, which is initially adaptive, fostering myocyte survival. However, if left unresolved, the ER stress response is maladaptive leading to myocyte death. ATF6 is an ER-transmembrane protein that senses misfolded proteins in the ER, and then becomes a transcription factor that induces ER stress response genes encoding ER proteins that adaptively restore ER protein folding. We previously showed that compared to non-transgenic mice, the hearts of ATF6 transgenic mice had better function and less damage upon ischemia/reperfusion (I/R); however, the mechanism of these protective effects is not known.   Methods:  Here, PCR gene array results showed that in cardiac myocytes, ATF6 induces genes encoding antioxidant proteins residing outside the ER, one of which is catalase. Thus, we explored the functions of ATF6-mediated catalase induction in the oxidative stress response during I/R in cardiac myocytes,  in vitro  and  in vivo .   Results:  In vitro,  overexpression of ATF6 in neonatal rat ventricular myocytes (NRVMs) induced protective ER stress response genes, while reducing reactive oxygen species (ROS), and necrotic cell death in cells treated with H 2 O 2  or simulated I/R (sI/R); ATF6 knockdown had the opposite effects. Catalase knockdown in NRVMs increased ROS, and necrotic cell death in cells treated with sI/R. ATF6 bound to putative ER stress response elements in the catalase gene and activated the catalase promoter. Mutation of these elements ablated ATF6 binding and ATF6-mediated catalase promoter activation.  In vivo,  compared to wild type, ATF6 knockout mouse hearts exhibited decreased catalase expression, reduced function and greater damage in response to myocardial infarction or I/R.   Conclusions:  This is the first demonstration in any cell type that ATF6 is critical for the adaptive oxidative stress response and the adaptive ER stress response, and describes a novel mechanism of ATF6-mediated protection of the heart from ischemic damage.
Late mortality after autologous blood or marrow transplantation in childhood: a Blood or Marrow Transplant Survivor Study-2 report
Authors: Anna Sällfors Holmqvist, Yanjun Chen, Jessica Wu, Kevin Battles, Ravi Bhatia, Liton Francisco, Lindsey Hageman, Michelle Kung, Emily Ness, Mariel Parman, Donna Salzman, Jeanette Falck Winther, Joseph Rosenthal, Stephen J. Forman, Daniel J. Weisdorf, Mukta Arora, Saro H. Armenian, Smita Bhatia
Journal: Blood (2018)
γδ T cells producing interleukin-17A regulate adipose regulatory T cell homeostasis and thermogenesis
Authors: Ayano C. Kohlgruber, Shani T. Gal-Oz, Nelson M. LaMarche, Moto Shimazaki, Danielle Duquette, Hui-Fern Koay, Hung N. Nguyen, Amir I. Mina, Tyler Paras, Ali Tavakkoli, Ulrich von Andrian, Adam P. Uldrich, Dale I. Godfrey, Alexander S. Banks, Tal Shay, Michael B. Brenner, Lydia Lynch
Journal: Nature Immunology (2018)
The contribution of injecting drug use to Hepatitis C virus transmission globally, regionally, and at country level: a modelling study
Authors: A. Trickey, H. Fraser, A.G. Lim, J. Walker, A. Peacock, S. Colledge, J. Leung, J. Grebely, S. Larney, L. Degenhardt, M. Hickman, P. Vickerman
Journal: Journal of Hepatology (2018)