tbuckley/cabot-search huggingface dataset:
ENDOSCOPY AS THE ULTIMATE METHOD IN CASES OF DELAYED DIAGNOSIS OF CONGENITAL DUODENAL MEMBRANE IN CHILDREN
Authors: S Semeniv, D Voroniak, L Trembach, I Kolomoiets
Journal: Endoscopy (2019)

Congenital duodenal membrane (CDM) is anomaly characterized by luminal gastrointestinal obstruction and consists of a diaphragm with openings. Clinical presentation in such malformations occur from the first days of life, in some cases – much later, depends on the degree of the duodenum stenosis. The aim of our study is to describe the management and characterise endoscopic findings of patients with delayed presentation of CDM.
Benralizumab for the Prevention of COPD Exacerbations
Authors: Gerard J. Criner, Bartolome R. Celli, Christopher E. Brightling, Alvar Agusti, Alberto Papi, Dave Singh, Don D. Sin, Claus F. Vogelmeier, Frank C. Sciurba, Mona Bafadhel, Vibeke Backer, Motokazu Kato, Alejandra Ramírez-Venegas, Yu-Feng Wei, Leif Bjermer, Vivian H. Shih, Maria Jison, Sean O’Quinn, Natalya Makulova, Paul Newbold, Mitchell Goldman, Ubaldo J. Martin
Journal: New England Journal of Medicine (2019)

The efficacy and safety of benralizumab, an interleukin-5 receptor alpha–directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known.
Smoking and Multiple Sclerosis
Journal: BMJ (1964)

of medical opinion in India to withhold anti- coagulant therapy even in the acute stages of cardiac infarction.The rarity of pulmonary embolism in the East is linked with the comparative rarity of disorders of " hypercoagulability " of blood in general, and can be better understood only when the pathogenesis of these disorders is better known.At the present time, the role of genetic and environmental factors seems significant.-Iam, etc.,
Altered airway ciliary orientation in patients with X-linked retinitis pigmentosa
Authors: Gabrielle McCray, Paul Griffin, Paul Martinello, Robb de Iongh, Jonathan Ruddle, Phil Robinson
Journal: Thorax (2019)

Previous reports suggested links between respiratory ciliary dysfunction and primary ciliopathies such as X-linked retinitis pigmentosa (XLRP). To investigate if patients with XLRP have abnormal airway ciliary structure or function, we assessed respiratory ciliary beat pattern and ultrastructure, including ciliary orientation, in 12 patients with XLRP without respiratory disease and 10 control subjects. Patients with XLRP had normal ciliary ultrastructure but significantly (p=0.004) increased mean ciliary deviation (33.8°±9.4°) compared with normal subjects (14.8°±5.4°). Altered orientation was associated with impaired ciliary beat pattern in six patients with XLRP. These findings indicate that XLRP mutations, affecting non-motile cilia of the photoreceptors in the retina, can have effects on motile cilia in the respiratory tract. The observation of disrupted ciliary orientation in patients with XLRP is suggestive of a defect in planar cell polarity.
MicroRNA in combination with HER2-targeting drugs reduces breast cancer cell viability in vitro
Authors: L.G. Svartdal, M.R. Aure, S.-K. Leivonen, M.H. Haugen, V. Hongisto, V.N. Kristensen, G.M. Mælandsmo, K.K. Sahlberg
Journal: Annals of Oncology (2019)

Background: Human epidermal growth factor receptor 2 positive (HER2+) breast cancer is an aggressive cancer form due to regulation and initiation of intracellular signaling pathways that promote cell survival and proliferation. Although HER2-targeted therapy, like trastuzumab and lapatinib, has improved outcome for HER2+ breast cancer patients, not all patients respond to treatment. We hypothesize that HER2+ breast cancer cells with poor response to targeted treatment can be sensitized by combining microRNAs (miRNAs) with traditional targeted therapy. Methods: Two HER2+ cell lines with poor response to trastuzumab and lapatinib, KPL4 and SUM190, were transfected with a panel of 810 miRNA mimics and 816 inhibitors. The cells were treated with the miRNAs alone and in combination with trastuzumab and/or lapatinib. Viability was measured after incubation for 72 hours. In addition, cell lysates were prepared and protein expression of cPARP, KI67, AKT, pAKT, ERK, pERK, HER2, pHER2-Y1222 and pHER2-Y877 were measured using a lysate microarray. Based on the findings, 17 miRNAs were chosen for further validation. Results: Of the 17 miRNAs validated from the screen, eight miRNAs show a sensitization effect and significantly improve the effect of trastuzumab and lapatinib in vitro. The cell viability is reduced with 14-83 % by the miRNAs alone compared to negative control; 14-76 % compared to trastuzumab; 18-69 % compared to lapatinib; and 13-59 % compared to the two drugs in combination. The protein lysate arrays show that some of the miRNAs affect the protein expression levels, and this will be further explored. Conclusions: Eight miRNAs in combination with the HER2-targeting drugs trastuzumab and lapatinib reduce breast cancer cell viability in vitro. This implies the potential of miRNAs as a combinatorial therapeutic together with targeted drugs to improve the effect for poor-responding HER2+ breast cancer patients. Legal entity responsible for the study: Research Unit, Vestre Viken HF. Funding: South-Eastern Norway Regional Health Authority. Disclosure: All authors have declared no conflicts of interest.
Long non-coding RNA PART1 contributes to cell proliferation and stem cell maintenance in triple-negative breast cancer
Authors: B.M. Cruickshank, D. Vidovic, M.L. Dahn, M. Sultan, P. Marcato
Journal: Annals of Oncology (2019)

Background: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype lacking targeted therapy options. Novel therapies which also target chemotherapy-resistant cancer stem cells (CSCs) within tumors would lead to improved outcomes for TNBC patients. Breast CSCs can be defined by increased aldehyde dehydrogenase (ALDH) enzymatic activity. Recent evidence suggests that long non-coding RNAs (lncRNAs) contribute to CSC maintenance and are potential novel therapeutic targets. Methods: To discover novel therapeutic targets for TNBC and CSCs we screened lncRNAs that are most enriched in TNBCs and breast CSCs for oncogenic activity. We used quantitative polymerase chain reaction (QPCR), cellular fractionization, flow cytometry, antisense oligonucleotides and mammosphere formation assays to assess lncRNA function and targetability in TNBC cell lines and a patient-derived xenograft. Results: We identified prostate androgen regulated transcript 1(PART1) as enriched in both TNBCs and CSCs. PART1 is also associated with worse patient outcomes among basal-like breast cancer patients. Knockdown of PART1 decreased cell proliferation of TNBC cell lines HCC1806 and HCC1395, and reduced tumor growth of HCC1806 cells. Cellular fractionization revealed that PART1 is predominately located in the cytoplasm, consistent with potential function as a miRNA sponge. Targeting PART1 with antisense oligonucleotides in a PDX and in the HCC1806 cell line resulted in a decrease in mammosphere forming potential. This suggests that PART1 may contribute to CSC maintenance and could be targeted to reduce CSC numbers in tumors. Conclusions: PART1 is of interest as a novel therapeutic target for TNBCs and CSCs. Further analysis will focus on investigating its potential function as a miRNA sponge in breast cancer. Legal entity responsible for the study: The authors. Funding: Canadian Institutes of Health Research Dalhousie University (Killam Award) Cancer Research Trainee Program. Disclosure: All authors have declared no conflicts of interest.
Клініко-анамнестичні особливості стеатозу печінки у дітей
Authors: N.Yu. Zavgorodnia, O.Yu. Lukianenko, V.B. Yagmur, I.Yu. Skyrda, O.P. Petishko
Journal: GASTROENTEROLOGY (2020)

Стаття присвячена вивченню клініко-анамнестичних особливостей стеатозу печінки у дітей. Наведені результати порівняльного аналізу даних обстеження хворих з ознаками стеатозу печінки та хворих без стеатозу. Визначення наявності й ступеня стеатозу печінки проведено за допомогою апарата FibroScan-502-touch з дослідженням контрольованого параметра ультразвукового затухання (САР). Виявлено особливості способу життя й харчування дітей із стеатозом печінки: гіподинамічний спосіб життя, переважання звичок швидкого харчування, вживання недостатньої добової кількості рідини. Встановлено, що стеатоз печінки тісно асоційований з ожирінням і гіпоталамічними розладами, підвищенням артеріального тиску та рівнів атерогенних ліпідів сироватки крові.
Abstract 19425: A Small Molecule Enforcing MEF2 Deacetylation Prevents and Reverses Hypertrophy and Normalizes Cardiac Function in Multiple Stress Models
Authors: Jian Qin Wei, Shaurya Joshi, Yan Gao, Lin Chen, Nanette H Bishopric
Journal: Circulation (2015)

Background: Cardiac hypertrophy leads to progressive cardiac dysfunction, and is an independent risk factor for death. Myocyte enhancer factor 2 (MEF2) is silenced by interaction with class IIa histone deacetylases and activated by p300 acetyltransferase during hypertrophy. Hypothesis: Targeting the co-regulatory site on MEF2 will prevent and reverse hypertrophy and associated cardiac dysfunction. Methods: Transverse aortic coarctation (TAC) and swimming stress models were used to initiate cardiac hypertrophy in male C57Bl/6 mice. Mice swam for 3 hours twice daily; control mice were immersed briefly. 8MI was administered by daily IP injection at a dose of 40 mg/kg beginning either at the time of intervention (TAC, swimming stress) or 4 weeks afterward (TAC) and continued for 4 weeks. N ≥ 5 per group. RT-PCR, immunohistochemistry, and echocardiography were used to assess cardiac structure and function. Neonatal rat ventricular myocytes (NRVM) were treated with 8MI, the histone deacetylase inhibitors MC1568 (class IIa-selective) or trichostatin A (nonselective, TSA). Results: Both TAC and forced swimming induced pathological hypertrophy with deterioration in systolic function in mice receiving DMSO (p&lt;0.001 for both). 4 weeks after TAC or the initiation of swimming, 8MI-treated animals had myocardial mass and function similar to those of sham-operated or immersed-control mice. After 8MI treatment was stopped at 4 weeks, hypertrophy developed in mice that continued to swim, similar to DMSO-treated animals. In mice with established hypertrophy 4 weeks after TAC, treatment with 8MI, but not DMSO, reversed systolic dysfunction (n=5 per group, p=0.0018) and reduced myocardial wall thickness to near that of sham-operated animals. No evidence of systemic toxicity was seen. Mechanistically, 8MI, but not MC1568, promoted HDAC4 nuclear retention and maintained MEF2 in a deacetylated state, and unlike TSA, prevented EP300 accumulation. Conclusions: Pharmacological targeting of MEF acetylation in vivo prevents and reverses stress-associated hypertrophy in multiple models. Reversal of hypertrophy by this means improves systolic function and does not prevent successful adaptation to increased cardiac work.
ENDOSCOPIC RESECTION OF SMALL COLORECTAL POLYPS: WHAT IS THE OPTIMAL TECHNIQUE?
Authors: D Trad, H Jlassi, K Lassoued, M Sabbah, N Bibani, H Elloumi, A Ouakaa, D Gargouri
Journal: Endoscopy (2019)

More than 70% of the polyps detected during colonoscopies are small (1 – 10 mm). The optimal technique of their complete resection is a subject of concern for endoscopists.
ER pathway activity score as a predictive biomarker to improve stratification for neoadjuvant endocrine therapy
Authors: D. Keizer, M.A. Inda, D. Clout, A. van de Stolpe, A. Fernando, C. Martinez-Perez, J.M. Dixon, A.H. Sims, A.K. Turnbull
Journal: Annals of Oncology (2019)

Background: Endocrine therapy for breast cancer patients is currently determined based on positive estrogen receptor alpha (ER) staining measured by immunohistochemistry. However, not all selected patients will respond to this therapy, suggesting that ER staining is not an optimal predictor for therapy response. We previously described a new method to measure functional signal transduction pathways based on a Bayesian inference from measurements of mRNA levels (microarray, qPCR) of the specific ER pathway related target genes. Initial evaluation suggested that ER pathway activity score of the primary biopsy is related to clinical response. In this study, this association is confirmed together with the observation that only the ER pathway activity is targeted by endocrine therapy, making this pathway activity score a possible candidate for response prediction to this therapy. Methods: The Edinburgh Breast Cancer Unit collected pre-treatment biopsies of 29 post-menopausal patients with primary localized ER-positive breast cancer. Patients received neo-adjuvant letrozole treatment and clinical outcome was assessed at 3 months follow-up based on 3D ultrasound measurements (single clinician) and translated into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Archival RNA from fresh frozen (FF) biopsy samples was used to measure gene expression of target genes from several pathways (ER, AR, FOXO, HH, TGFb and Wnt) using RT-qPCR. Pathway activity scores were computed and expressed on a 0-100 scale. Results: A high ER pathway activity score was correlated with a higher decrease in tumour size (Pearson 0.4; p = 0.02), and low ER pathway score was clearly associated with PD (ER score of 20.2 in PD vs 43.8 in non-PD, two-sided t-test p = 0.03) with an AUC of 0.84 (CI 95% 0.63-1). Similar results were obtained by comparing CR/PR vs SD/PD. Other measured pathway activities did not correlate to clinical response confirming the ER pathway as primary target for endocrine therapy. Conclusions: This study confirms the potential use of ER pathway activity score from a primary biopsy of ER-positive breast cancer patients as an improved biomarker in the prediction of neoadjuvant endocrine therapy response. Legal entity responsible for the study: Philips Electronics Nederland B.V., acting through its HealthWorks Molecular Pathway Dx. Funding: Has not received any funding. Disclosure: D. Keizer, M.A. Inda, D. Clout A. van de Stolpe: Employee: Philips Reasearch. All other authors have declared no conflicts of interest.
Molecular pathways regulated by areca nut in the etiopathogenesis of oral submucous fibrosis
Authors: Paturu Kondaiah, Ila Pant, Imran Khan
Journal: Periodontology 2000 (2019)

Many oral mucosal lesions are due to substance abuse, such as tobacco and areca nut, amongst others. There is considerable evidence that oral lesions/disorders such as some leukoplakias, most erythroplakias, and submucous fibrosis have malignant potential, with a conversion rate of 5%-10% over a 10-year period. There have been several reports on possible biomarkers that predict malignant conversion of the oral lesions associated with these disorders. Management of these is mostly surgical removal of the lesion followed by observation, and in some cases treatment by antioxidants and anti-inflammatory agents. Oral submucous fibrosis is due to excessive deposition of extracellular matrix in the connective tissue plus, particularly, collagens. The deposition of collagen leads to stiffness of the affected regions and results in difficulty in mouth opening. Areca nut chewing is proposed as the most probable etiological factor in the manifestation of oral submucous fibrosis. Several studies suggest involvement of proinflammatory cytokines, dysregulated by areca nut, in the development of the disease. Amongst these, transforming growth factor-β is in the forefront, which is also shown to be involved in fibrosis of other organs. This review addresses the molecular mechanisms involved in oral submucous fibrosis development and provides a model for the regulation of transforming growth factor-β by areca nut. It provides an exemplar of the role of modern molecular techniques in the study of oral disease.
Abstract A22: The histone demethylase KDM3A in Ewing sarcoma metastasis
Authors: Marybeth Sechler, Janet Parrish, Paul Jedlicka
Journal: Cancer Research (2016)

Abstract This study aims to explore the roles and mechanisms of new candidates for therapeutic targeting in Ewing Sarcoma. Ewing Sarcoma is an aggressive pediatric malignancy of the bone and soft tissue, driven by EWS/Ets oncogenic fusions and characterized by high propensity for metastasis and poor clinical outcomes. We have identified the histone demethylase KDM3A as a novel tumor and metastasis promoter downstream of EWS/Fli1, the most common driver in this disease. Moreover, we have identified the cell surface protein, Melanoma Cell Adhesion Molecule (MCAM), as a potential important mediator of KDM3A action. Our data show that both KDM3A and MCAM depletion can inhibit growth and metastatic phenotypes. Additionally we explore the regulation of MCAM, showing that KDM3A may upregulate MCAM expression both through a direct as well as an indirect mechanism via the Ets1 transcription factor. Since both KDM3A and MCAM are pharmacologically targetable, understanding of this pathway could provide at least two new therapeutic targets in Ewing Sarcoma, and, importantly alternatives to drugging of EWS/Ets fusions, which to date has proven very difficult. Citation Format: Marybeth Sechler, Janet Parrish, Paul Jedlicka. The histone demethylase KDM3A in Ewing sarcoma metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr A22.
Financial Toxicity of Acute Cardiovascular Disease in India
Authors: Khurram Nasir, Rohan Khera
Journal: JAMA Network Open (2019)

Padinhare P. Mohanan, MD, DM; Mark D. Huffman, MD, MPH; Abigail S. Baldridge, MS; Raji Devarajan, MS; Dimple Kondal, PhD; Lihui Zhao, PhD; Mumtaj Ali, MCA; Johny Joseph, MD, DM; Koshy Eapen, MD, DM; Mangalath N. Krishnan, MD, DM; Jaideep Menon, MD, DM; Manoj Thomas, MD, DM; Donald M. Lloyd-Jones, MD, ScM; Sivadasanpillai Harikrishnan, MD, DM; Dorairaj Prabhakaran, MD, DM, MSc; for the ACS QUIK Investigators
Abstract 11015: Impact of Residual Risks After Achievement of Appropriate Low-Density Lipoprotein Cholesterol Lowering Management in Secondary Prevention of Japanese Patients
Authors: Akihiro Endo, Taiji Okada, Hirotomo Sato, Yuzo Kagawa, Yusuke Morita, Misun Pak, Takeshi Ouchi, Nobuhide Watanabe, Kazuto Yamaguchi, Hiroyuki Yoshitomi, Kazuaki Tanabe
Journal: Circulation (2018)

Introduction: In secondary prevention of ischemic heart disease, target value of LDL-C <100mg/dl with using statins is recommended as standard management in Japanese guideline. Hypothesis: We asses...
LEARNING CURVE FOR COLORECTAL ESD
Authors: K Khalin, M Agapov, L Zvereva, E Ryzhkov
Journal: Endoscopy (2019)

The results of the first 170 ESD for colorectal tumors from 09.2007 till 09.2018 have been analyzed. ESD speed, number of complications, rate of en-block resections and snare assistances have been evaluated. All patients were divided into two groups (85 patients each). Age – 61.8 ± 0.73 years, (F – 94, M – 76).
Abstract 19492: Cardiac CTRP9 Regulates Endoplasmic Reticulum Calreticulin Retrotranslocation to Protect Against Myocardial Ischemia/Reperfusion Injury
Authors: Dajun Zhao, Yang Sun, Zhigang Qin, Wenhao Chen, Yanzhen Tan, Pan Feng, Dinghua Yi, Wei Yi
Journal: Circulation (2017)

Background: Cardiokines are a group of heart produced-secretomes that maintain cardiac function and modulate pathologic remodeling. CTRP9 is a newly identified cardiokine. However, the biological function of cardiac generated CTRP9 remains unclear. Methods and Results: Mice were subjected to myocardial ischemia/reperfusion (MI/R) and gene interfering methods were used. Compare to vehicle, inhibition of cardiac CTRP9 via intra-myocardial siRNA injection significantly reduced left ventricular ejection fraction (LVEF, 28.6%, P<0.01), augmented infarct size (P<0.05) and increased apoptosis post-MI/R (P<0.05). In contrast, overexpression of CTRP9 via lentivirus reversely improved MI/R-induced cardiac dysfunction and apoptosis (P<0.05, respectively). Notably, cardiac CTRP9 overexpression up-regulated endoplasmic reticulum (ER) protein calreticulin (CRT) expression (P<0.01). Co-IP results demonstrated that cardiac CTRP9 interacted with CRT and confocal images revealed that CTRP9 colocalized with CRT in the cytop...
Re: Maud Rijnders, Astrid A.M. van der Veldt, Tahlita C.M. Zuiverloon, et al. PD-L1 Antibody Comparison in Urothelial Carcinoma. Eur Urol 2019;75:538–40
Authors: Thomas Gevaert, Markus Eckstein, Rodolfo Montironi, Antonio Lopez-Beltran
Journal: European Urology (2019)
Polypes gastriques hyperplasiques: à propos de 63 cas
Authors: M Yakoubi, M Medhioub, O Gharbi, L Hamzaoui, A Khsiba, M Mahmoudi, MM Azouz
Journal: Endoscopy (2019)

Les polypes hyerplasiques sont parmi les polypes gastriques les plus fréquents. La présence à l'examen histologique de foyer de dysplasie est une situation rare mais dont la fréquence est diversement appréciée dans la littérature, allant de 1 à 20%. De plus, l'attitude vis-à-vis de ces polypes n'est pas consensuelle et leur prise en charge reste discutable jusqu'à ce jour.
Derivation and External Validation of a Scoring System for Predicting Fracture Risk After Ischemic Stroke in a Canadian Cohort
Authors: Eric E. Smith, Jiming Fang, Shabbir M. Alibhai, Peter Cram, Angela M. Cheung, Leanne K. Casaubon, Eshita Kapoor, Peter C. Austin, Moira K. Kapral
Journal: JAMA Neurology (2019)

The risk for low-trauma fracture is increased by more than 30% after ischemic stroke, but existing fracture risk scores do not account for history of stroke as a high-risk condition.To derive a risk score to predict the probability of fracture within 1 year after ischemic stroke and validate it in a separate cohort.Prognostic study of a cohort from the Ontario Stroke Registry, a population-based sample of adults in Ontario, Canada, who were hospitalized with ischemic stroke from July 1, 2003, to March 31, 2012, with 1 year of follow-up. A population-based validation cohort consisted of a sample of 13 698 consecutive stroke admissions captured across 5 years: April 2002 to March 2003, April 2004 to March 2005, April 2008 to March 2009, April 2010 to March 2011, and April 2012 to March 2013.Predictor variables were selected based on biological plausibility and association with fracture risk. Age, sex, and modified Rankin score were abstracted from the medical records part of the Ontario Stroke Audit, and other characteristics were abstracted from administrative health data.Incidence of low-trauma fracture within 1 year of discharge, based on administrative health data.The Fracture Risk after Ischemic Stroke (FRAC-Stroke) Score was derived in 20 435 patients hospitalized for ischemic stroke (mean [SD] age, 71.6 [14.0] years; 9564 [46.8%] women) from the Ontario Stroke Registry discharged from July 1, 2003, to March 31, 2012, using Fine-Gray competing risk regression. Low-trauma fracture occurred within 1 year of discharge in 741 of the 20 435 patients (3.6%) in the derivation cohort. Age, discharge modified Rankin score (mRS), and history of rheumatoid arthritis, osteoporosis, falls, and previous fracture were associated with the cumulative incidence of low trauma fracture in the derivation cohort. Model discrimination in the validation cohort (n = 13 698) was good (C statistic, 0.70). Discharge mRS was an important discriminator of risk (relative integrated discrimination improvement, 8.7%), with highest risk in patients with mRS 3 and 4 but lowest in bedbound patients (mRS 5). From the lowest to the highest FRAC-Stroke quintile, the cumulative incidence of 1-year low-trauma fracture increased from 1.3% to 9.0% in the validation cohort. Predicted and observed rates of fracture were similar in the external validation cohort. Analysis was conducted from July 2016 to January 2019.The FRAC-Stroke score allows the clinician to identify ischemic stroke survivors at higher risk of low-trauma fracture within 1 year of hospital discharge. This information might be used to select patients for interventions to prevent fractures.