tbuckley/cabot-search huggingface dataset:
A Panel of Novel Detection and Prognostic Methylated DNA Markers in Primary Non–Small Cell Lung Cancer and Serum DNA
Authors: Akira Ooki, Zahra Maleki, Jun-Chieh J. Tsay, Chandra Goparaju, Mariana Brait, Nitesh Turaga, Hae-Seong Nam, William N. Rom, Harvey I. Pass, David Sidransky, Rafael Guerrero-Preston, Mohammad Obaidul Hoque
Journal: Clinical Cancer Research (2017)

Purpose: To establish a novel panel of cancer-specific methylated genes for cancer detection and prognostic stratification of early-stage non-small cell lung cancer (NSCLC).Experimental Design: Identification of differentially methylated regions (DMR) was performed with bumphunter on "The Cancer Genome Atlas (TCGA)" dataset, and clinical utility was assessed using quantitative methylation-specific PCR assay in multiple sets of primary NSCLC and body fluids that included serum, pleural effusion, and ascites samples.Results: A methylation panel of 6 genes (CDO1, HOXA9, AJAP1, PTGDR, UNCX, and MARCH11) was selected from TCGA dataset. Promoter methylation of the gene panel was detected in 92.2% (83/90) of the training cohort with a specificity of 72.0% (18/25) and in 93.0% (40/43) of an independent cohort of stage IA primary NSCLC. In serum samples from the later 43 stage IA subjects and population-matched 42 control subjects, the gene panel yielded a sensitivity of 72.1% (31/41) and specificity of 71.4% (30/42). Similar diagnostic accuracy was observed in pleural effusion and ascites samples. A prognostic risk category based on the methylation status of CDO1, HOXA9, PTGDR, and AJAP1 refined the risk stratification for outcomes as an independent prognostic factor for an early-stage disease. Moreover, the paralog group for HOXA9, predominantly overexpressed in subjects with HOXA9 methylation, showed poor outcomes.Conclusions: Promoter methylation of a panel of 6 genes has potential for use as a biomarker for early cancer detection and to predict prognosis at the time of diagnosis. Clin Cancer Res; 23(22); 7141-52. ©2017 AACR.
Safety and Outcomes of the Transoral Endoscopic Thyroidectomy Vestibular Approach
Authors: Angkoon Anuwong, Khwannara Ketwong, Pornpeera Jitpratoom, Thanyawat Sasanakietkul, Quan-Yang Duh
Journal: JAMA Surgery (2017)

Natural orifice transluminal endoscopic surgery thyroidectomy is a novel approach to avoid surgical scars.To compare the safety and outcomes of the transoral endoscopic thyroidectomy vestibular approach (TOETVA) with those of open thyroidectomy (OT).This study retrospectively reviewed all TOETVA and OT operations performed from April 1, 2014, through August 31, 2016, at Police General Hospital, Bangkok, Thailand. All patients who underwent TOETVA and patients who underwent OT were included. Exclusion criteria were (1) previous neck surgery, (2) substernal goiter, (3) lymph node or distance metastasis, and (4) suspicious invasion to the adjacent organs. Propensity score matching was conducted to reduce selective bias.Operative time, blood loss, and complications related to thyroid surgery.Of the 425 patients who underwent transoral endoscopic thyroidectomy (mean age, 35.3 [12.1] years; age range, 16-81 years; 389 [92.2%] female), 422 successfully were treated with the TOETVA; 3 patients were converted to a conventional operation because of bleeding. Twenty-five patients (5.9%) had transient recurrent laryngeal nerve palsy, and 46 (10.9%) had transient hypoparathyroidism. None had permanent recurrent laryngeal nerve palsy or permanent hypoparathyroidism. Three patients (0.7%) had transient mental nerve injury; all cases resolved by 4 months. One patient developed postoperative hematoma treated by OT. Twenty patients (4.7%) had seroma treated by simple aspiration. Operative time was longer for the TOETVA compared with the OT group (100.8 [39.7] vs 79.4 [32.1] minutes, P = 1.61 × 10-10). The mean (SD) visual analog scale score for pain was lower in the TOETVA group (1.1 [1.2] vs 2.8 [1.2], P = 2.52 × 10-38). Estimated mean (SD) blood loss (36.9 [32.4] vs 37.6 [23.1] mL, P = .43) and rate of complications (45 of 216 [20.8%] vs 38 of 216 [17.6%], P = .41) were not significantly different in the TOETVA vs OT group.The TOETVA was performed as safely as OT, requires only conventional laparoscopic instruments, and avoids incisional scars; thus, the approach may be an option for select patients.
Association of Trial Registration With Reporting of Primary Outcomes in Protocols and Publications
Authors: An-Wen Chan, Annukka Pello, Jessica Kitchen, Anna Axentiev, Jorma I. Virtanen, Annie Liu, Elina Hemminki
Journal: JAMA (2017)

This study characterizes discrepancies between primary outcomes specified in trial protocols, registrations, and publications, and the association between prospective registration and consistency of published outcomes.
A population-based approach to assess the heritability and distribution of renal handling of electrolytes
Authors: Flore Moulin, Belen Ponte, Menno Pruijm, Daniel Ackermann, Yassine Bouatou, Idris Guessous, Georg Ehret, Olivier Bonny, Antoinette Pechère-Bertschi, Jan A. Staessen, Fred Paccaud, Pierre-Yves Martin, Michel Burnier, Bruno Vogt, Olivier Devuyst, Murielle Bochud
Journal: Kidney International (2017)
CMR T1 Mapping at 3T Characterizes the Extent of Acute Ischemic Myocardial Injury: Comparison to Standard Techniques
Authors: E Dall'Armellina, S Piechnik, V Ferreira, T D Karamitsos, J M Francis, F Cuculi, C Forfar, B D Prendergast, A P Banning, K M Channon, R K Kharbanda, Robson, R P Choudhury, S Neubauer
Journal: Circulation (2011)
Abstract P058: Necessity of mTOR Inhibition and Autophagy Induction for Maintaining Cardiac Homeostasis During Caloric Restriction
Authors: Kai Chen, Derek Timm, Tyler Jepperson, Xianmin Xu, Satoru Kobayashi, Qiangrong Liang
Journal: Circulation Research (2011)

Caloric restriction (CR) is a robust dietary intervention known to delay age-related heart disease. CR is able to antagonize cardiac remodeling in animal and human under various pathological conditions. However, the direct effect of CR on the heart at basal physiological state is not well characterized. In this study, we examined the impact of CR on cardiac homeostasis and explored the signaling mechanisms that mediate the cardiac effect of CR. Male C57BL/6J mice underwent 20% CR, i.e. 20% less food than ad libitum (AL), for 2 weeks and 40% CR for another 2 weeks. This CR regimen caused a roughly 20% decrease in heart weight and myocyte cross-sectional area. CR diminished the activity of the mammalian target of rapamycin ( mTOR) and accelerated autophagic flux. To determine the functional role of mTOR inhibition in CR-induced heart size reduction, we used transgenic mice that express a constitutively active mTOR (mTORca) in the heart. CR did not inhibit cardiac mTOR signaling in mTORca mice as it did in wild type (WT) mice. As a result, the ability of CR to reduce heart size in WT mice was severely impaired in mTORca mice. Specifically, CR reduced the heart weight by 23.1% in WT mice (p&lt;0.01 vs AL), but only tended to reduce it in mTORca mice (13.1%, p&gt;0.05 vs AL). Strikingly, when animals were treated with the mTOR inhibitor rapamycin, CR decreased heart weight in both WT and mTORca mice to the same extent, strongly suggesting that mTOR inhibition is required for CR to exert its cardiac effect. Autophagy is a cellular degradation pathway that may contribute to CR-induced heart size reduction. Surprisingly, CR can still decrease heart weight in 2 different autophagy-deficient mouse models, namely, beclin 1 heterozygous knockout mice and ATG16L1 hypomorphic mice. Nonetheless, cardiac function in these mice was markedly deteriorated during CR as indicated by decreased fractional shortening (Beclin 1+−: AL 37.9±2.8 vs CR 29.6±2.1, p&lt;0.01; ATG16L1-HM: AL 36.8±1.8 vs CR 30.1±2.1, p&lt;0.05). This was accompanied by increased oxidative injury, suggesting that autophagy is indispensible for a normal cardiac function during CR. In conclusion, both mTOR inhibition and autophagy induction are essential for maintaining cardiac homeostasis in response to CR-triggered mild stress.
Analysis of the Early Clonal Dynamics in Ibrutinib-Treated Chronic Lymphocytic Leukemia
Authors: Valeria Spina, Fary Diop, Alessio Bruscaggin, Lorenzo De Paoli, Chiara Favini, Anastasios Stathis, Bernhard Gerber, Lydia Scarfò, Antonella Zucchetto, Clara Deambrogi, Daniela Clerici, Martina di Trani, Andrea Rinaldi, Pietro Bulian, Carmelo Carlo Stella, Francesco Zaja, Paolo Ghia, Michael Gregor, Jakob Passweg, Luca Laurenti, Emanuele Zucca, Franco Cavalli, Francesco Bertoni, Valter Gattei, Marco Montillo, Alessandra Tedeschi, Georg Stüssi, Gianluca Gaidano, Davide Rossi
Journal: Blood (2016)
Abstract 373: Spatial Expression Analysis of the Ischemic Heart Identifies Novel Factors Involved in Cardiac Remodeling and Disease
Authors: Gregory Lacraz, Jan Philipp Junker, Koen Scholman, Danielle Versteeg, Alexander van Oudenaarden, Eva van Rooij
Journal: Circulation Research (2015)

Cardiac ischemic injury is associated with expressional changes in a broad range of coding and non-coding genes. While genome-wide expression techniques like RNA sequencing, give valuable information about the transcriptional activity of genes, spatial clues are lost. Here, we use a novel method (TomoSEQ) based on traditional histological techniques with low-input RNA sequencing to generate a spatial gene expression atlas for the infarcted heart. Transcriptome profiling of 50 consecutive sections from hearts exposed to ischemia reperfusion or sham surgery, allowed us to trace differential gene regulation throughout the infarct, borderzone and remote area. Fourteen days post-injury, we clearly observed differential expression curves specific for genes known to be relevant for cardiac function and disease, like Nppa (remodeling/hypertrophy), Col3a1 (fibrosis) and Atp2a2 (calcium handling), with the first two being more abundantly expressed in the infarct, and the latter more dominant towards the remote. Interestingly, the exact spatial information on these 3 reference genes enabled us to identify a set of genes that show an identical regulation, potentially linking these transcripts to the aforementioned biological function of the reference genes. The validity of using this method to identify genes that are expressionally linked was underscored by the observation that the correlation between the expression level of the Nppa , Col3a1 , Atp2a2 and the newly identified genes could be confirmed in human cardiac tissue samples from patients suffering from ischemic heart disease. We next used an in silico approach to identify common transcription factors among the co-regulated genes. TomoSEQ analysis revealed a strong spatial correlation between these identified transcription factors and their target genes. This provides further support for our methodology, but also provides an opportunity to identify novel transcription factors relevant for cardiac function and disease. Our study shows the power of spatial transcriptome profiling throughout the infarcted heart by giving local clues on changes in gene expression and allowing for the identification of novel genes and key transcription factors that could be relevant for cardiac repair upon injury.
A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (TRANSFORM)
Authors: Samuel V. Kemp, Dirk-Jan Slebos, Alan Kirk, Malgorzata Kornaszewska, Kris Carron, Lars Ek, Gustav Broman, Gunnar Hillerdal, Herve Mal, Christophe Pison, Amandine Briault, Nicola Downer, Kaid Darwiche, Jagan Rao, Ralf-Harto Hübner, Christof Ruwwe-Glosenkamp, Valéry Trosini-Desert, Ralf Eberhardt, Felix J. Herth, Eric Derom, Thomas Malfait, Pallav L. Shah, Justin L. Garner, Nick H. ten Hacken, Hazem Fallouh, Sylvie Leroy, Charles H. Marquette
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Single-center randomized controlled trials of the Zephyr endobronchial valve (EBV) treatment have demonstrated benefit in severe heterogeneous emphysema. This is the first multicenter study evaluating this treatment approach.Objectives: To evaluate the efficacy and safety of Zephyr EBVs in patients with heterogeneous emphysema and absence of collateral ventilation.Methods: This was a prospective, multicenter 2:1 randomized controlled trial of EBVs plus standard of care or standard of care alone (SoC). Primary outcome at 3 months post-procedure was the percentage of subjects with FEV1 improvement from baseline of 12% or greater. Changes in FEV1, residual volume, 6-minute-walk distance, St. George’s Respiratory Questionnaire score, and modified Medical Research Council score were assessed at 3 and 6 months, and target lobe volume reduction on chest computed tomography at 3 months.Measurements and Main Results: Ninety seven subjects were randomized to EBV (n = 65) or SoC (n = 32). At 3 months, 55.4% of EBV and 6.5% of SoC subjects had an FEV1 improvement of 12% or more (P < 0.001). Improvements were maintained at 6 months: EBV 56.3% versus SoC 3.2% (P < 0.001), with a mean ± SD change in FEV1 at 6 months of 20.7 ± 29.6% and −8.6 ± 13.0%, respectively. A total of 89.8% of EBV subjects had target lobe volume reduction greater than or equal to 350 ml, mean 1.09 ± 0.62 L (P < 0.001). Between-group differences for changes at 6 months were statistically and clinically significant: ΔEBV–SoC for residual volume, −700 ml; 6-minute-walk distance, +78.7 m; St. George’s Respiratory Questionnaire score, −6.5 points; modified Medical Research Council dyspnea score, −0.6 points; and BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index, −1.8 points (all P < 0.05). Pneumothorax was the most common adverse event, occurring in 19 of 65 (29.2%) of EBV subjects.Conclusions: EBV treatment in hyperinflated patients with heterogeneous emphysema without collateral ventilation resulted in clinically meaningful benefits in lung function, dyspnea, exercise tolerance, and quality of life, with an acceptable safety profile.Clinical trial registered with www.clinicaltrials.gov (NCT02022683).
THU0608 Association between allopurinol dose-titration and serum uric acid levels in gout patients: us electronic health record data
Authors: A-C Fu, DC Taylor, DS Reasner
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Allopurinol is a first-line urate lowering therapy for patients with gout. The American College of Rheumatology guidelines recommend allopurinol dose-titration to maintain serum uric acid (sUA) levels &lt;6 mg/dl. <h3>Objectives</h3> To understand allopurinol dose-titration relative to sUA levels. <h3>Methods</h3> This retrospective study used the de-identified Humedica electronic medical record database. The study included all sUA and allopurinol records among gout patients (ICD-9-CM: 274.xx) ≥18 years old with first gout diagnosis in 2007 – 2015. An episode was defined as an allopurinol initial dose (ID) prior to (closest) and titrated dose (TD) after (within 30 days) an sUA test. Dose-titration was categorized as an episode with a dose-change (up-titration: ID &lt; TD; down-titration: ID &gt; TD), or no-dose-change (ID = TD). For multiple different doses recorded on the same prescription date, the sum of doses was taken as daily dosage. Episodes were considered uncontrolled when sUA ≥6 mg/dl. Descriptive episode-level analyses were performed. <h3>Results</h3> Within 64,609 episodes, 57% of episodes were uncontrolled (sUA: 6 to &lt;8 mg/dl: 38%; 8 to &lt;10 mg/dl: 15%; ≥10mg/dl: 4%). Seventy-one percent of uncontrolled episodes were no-dose-change, 21% were up-titrated, and 7% were down-titrated. Within no-dose-change episodes, 51% were uncontrolled and lower doses corresponded to higher percentages of uncontrolled episodes (&lt;100mg/day: 88%; 100mg/day: 70%; &gt;100, &lt;300 mg/day: 49%; 300mg/day: 38%; &gt;300mg/day: 36%). Seventy-eight percent of dose-change episodes were uncontrolled, of which 100 to 300 mg/day (39%) was the most frequent dose titration. Overall, the most frequent TD was 300 mg/day (52%) followed by 100mg/day (36%), &gt;100 – &lt;300mg/day (8%), &gt;300mg/day (3%), and &lt;100mg/day (&lt;1%). <h3>Conclusions</h3> Allopurinol dose is not generally titrated regardless of sUA control. This pattern suggests a need for active management of patients with gout with uncontrolled sUA including consideration of new treatment options in addition to allopurinol. <h3>References</h3> Juraschek SP et al. Gout, urate-lowering therapy, and uric acid levels among adults in the United States. Arthritis Care Res (Hoboken). 2015 Apr;67(4):588–92. Khanna D et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). 2012 Oct;64(10):1431–46. <h3>Acknowledgements</h3> This study was funded by Ironwood Pharmaceuticals. <h3>Disclosure of Interest</h3> A.-C. Fu Employee of: Employee of Ironwood Pharmaceuticals, D. Taylor Employee of: Employee of Ironwood Pharmaceuticals, D. Reasner Employee of: Employee of Ironwood Pharmaceuticals
Meta-Epidemiology of Testosterone’s Risks and Benefits—Will We Ever Know the Answer?—Reply
Authors: Peter J. Snyder, Susan S. Ellenberg
Journal: JAMA Internal Medicine (2017)

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最適化された角膜移植片組成と安定性のためのセルフリフティング自動生成組織等価(SLATEs)の3次元構造の制御【Powered by NICT】
Authors: M Gouveia Ricardo, Gonzalez-Andrades Elena, C Cardona Juan, Gonzalez-Gallardo Carmen, M Ionescu Ana, Garzon Ingrid, Alaminos Miguel, Gonzalez-Andrades Miguel, J Connon Che
Journal: Biomaterials (2017)
Youth tobacco surveillance United States, 1998-1999
Authors: Cheryl Healton, Cheri Ahern, Scott M. Batchelor, Curtis J. Blanton, Marcella Law, Clifton M. Loo, Eric S. Pevzner, Heather A. Ryan, Stephanie A. Stolfus, Mark Tabladillo, Charles Warren, Leah R. Zinner, Michael P. Eriksen, Peter Messeri, Jennifer Reynolds, Charles Stokes, James R. Gross, Kathryn Flint, William H. Robb
Journal: MMWR Morbidity and Mortality Weekly Report (2000)
Letter to the Editor: Surveillance of mcr-1 and mcr-2 genes in Carbapenem-resistant Klebsiella pneumoniae strains from an Italian Hospital
Authors: Carolina Venditti, Carla Nisii, Silvia D’Arezzo, Antonella Vulcano, Antonino Di Caro
Journal: Eurosurveillance (2017)

Preview this article: Letter to the Editor: Surveillance of mcr-1 and mcr-2 genes in Carbapenem-resistant Klebsiella pneumoniae strains from an Italian Hospital, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/22/35/eurosurv-22-35-4-1.gif
Persistence of Pancreatic Insulin mRNA Expression and Proinsulin Protein in Type 1 Diabetes Pancreata
Authors: Clive Wasserfall, Harry S. Nick, Martha Campbell-Thompson, Dawn Beachy, Leena Haataja, Irina Kusmartseva, Amanda Posgai, Maria Beery, Christopher Rhodes, Ezio Bonifacio, Peter Arvan, Mark Atkinson
Journal: Cell Metabolism (2017)
Novel Junction-specific and Quantifiable In Situ Detection of AR-V7 and its Clinical Correlates in Metastatic Castration-resistant Prostate Cancer
Authors: Yezi Zhu, Adam Sharp, Courtney M. Anderson, John L. Silberstein, Maritza Taylor, Changxue Lu, Pei Zhao, Angelo M. De Marzo, Emmanuel S. Antonarakis, Mindy Wang, Xingyong Wu, Yuling Luo, Nan Su, Daniel Nava Rodrigues, Ines Figueiredo, Jonathan Welti, Emily Park, Xiao-Jun Ma, Ilsa Coleman, Colm Morrissey, Stephen R. Plymate, Peter S. Nelson, Johann S. de Bono, Jun Luo
Journal: European Urology (2017)
Acute pulmonary embolism and multiple pulmonary nodules mimicking metastatic disease
Authors: Karina Brüstle, Katharina Zachariassen, Bart Vrugt, Thomas Frauenfelder, Walter Weder, Daniel Franzen
Journal: Thorax (2017)

A 62-year-old patient with a history of traumatic splenectomy after a paragliding accident and chronic hepatitis C presented to the emergency department with worsening dyspnoea and unintended weight loss of 8 kg in 2 months. He was a lifelong non-smoker and consumes alcohol on rare occasions. He also reported recent travels to Asia and South America for business affairs. On clinical examination, the patient was normotensive with a respiratory rate of 25/min. Lung auscultation and the remainder of the physical examination were uneventful. Laboratory parameters showed increased inflammatory parameters (leucocyte count 14.7 g/L, C reactive protein 87 mg/L), absolute eosinophilia (4.73 g/L) and elevated IgE levels (5170 kU/L). A CT scan revealed acute segmental pulmonary embolism and multiple irregular pulmonary nodules (figure 1A). A bronchoscopy showed no airway abnormalities such as inflammation or tumour protrusion; however, bronchoalveolar lavage revealed eosinophilia.



Figure 1 
(A) CT thorax showing multiple irregular pulmonaly nodules. (B) H&E staining: multifocal echinococcal cysts and granulomas forming an interface with adjacent alveolar tissue. (C) H&E staining: detail showing cyst wall and pallisading histiocytes. (D) EM2 antigen staining: identifying echinococcus multilocularis.



The radiological appearance mimicked metastatic disease. With multiple nodules, unintentional weight loss and a history of chronic hepatitis C, metastatic disease from hepatocellular carcinoma or progressive lung carcinoma was suspected. Furthermore, the initial workup showed a partly calcified liver lesion in the right lobe measuring 9×10 cm. A subsequent sonogram showed mild liver enlargement with homogenous parenchyma and an inhomogeneous, round liver lesion in segments V–VII. The corresponding CT showed a cystic lesion with scattered calcifications in the wall. With an extensive tropical travel history, common parasites as well as zoonotic diseases and fungal infection were included in the differential diagnoses.

At the time of initial workup, a parasitic disease was included in the differential. …