tbuckley/cabot-search huggingface dataset:
Methylation panel is a diagnostic biomarker for Barrett’s oesophagus in endoscopic biopsies and non-endoscopic cytology specimens
Authors: Hamza Chettouh, Oliver Mowforth, Núria Galeano-Dalmau, Navya Bezawada, Caryn Ross-Innes, Shona MacRae, Irene Debiram-Beecham, Maria O’Donovan, Rebecca C Fitzgerald
Journal: Gut (2017)

Objective Barrett’s oesophagus is a premalignant condition that occurs in the context of gastro-oesophageal reflux. However, most Barrett’s cases are undiagnosed because of reliance on endoscopy. We have developed a non-endoscopic tool: the Cytosponge, which when combined with trefoil factor 3 immunohistochemistry, can diagnose Barrett’s oesophagus. We investigated whether a quantitative methylation test that is not reliant on histopathological analysis could be used to diagnose Barrett’s oesophagus. Design Differentially methylated genes between Barrett’s and normal squamous oesophageal biopsies were identified from whole methylome data and confirmed using MethyLight PCR in biopsy samples of squamous oesophagus, gastric cardia and Barrett’s oesophagus. Selected genes were then tested on Cytosponge BEST2 trial samples comprising a pilot cohort (n=20 cases, n=10 controls) and a validation cohort (n=149 cases, n=129 controls). Results Eighteen genes were differentially methylated in patients with Barrett’soesophagus compared with squamous controls. Hypermethylation of TFPI2 , TWIST1 , ZNF345 and ZNF569 was confirmed in Barrett’s biopsies compared with biopsies from squamous oesophagus and gastric cardia (p&lt;0.05). When tested in Cytosponge samples, these four genes were hypermethylated in patients with Barrett’s oesophagus compared with patients with reflux symptoms (p&lt;0.001). The optimum biomarker to diagnose Barrett’s oesophagus was TFPI2 with a sensitivity and specificity of 82.2% and 95.7%, respectively. Conclusion TFPI2 , TWIST1 , ZNF345 and ZNF569 methylation have promise as diagnostic biomarkers for Barrett’s oesophagus when used in combination with a simple and cost effective non-endoscopic cell collection device.
Mitochondrial Reactive Oxygen Species in Lipotoxic Hearts Induce Post-Translational Modifications of AKAP121, DRP1, and OPA1 That Promote Mitochondrial Fission
Authors: Kensuke Tsushima, Heiko Bugger, Adam R. Wende, Jamie Soto, Gregory A. Jenson, Austin R. Tor, Rose McGlauflin, Helena C. Kenny, Yuan Zhang, Rhonda Souvenir, Xiao X. Hu, Crystal L. Sloan, Renata O. Pereira, Vitor A. Lira, Kenneth W. Spitzer, Terry L. Sharp, Kooresh I. Shoghi, Genevieve C. Sparagna, Eva A. Rog-Zielinska, Peter Kohl, Oleh Khalimonchuk, Jean E. Schaffer, E. Dale Abel
Journal: Circulation Research (2017)

Cardiac lipotoxicity, characterized by increased uptake, oxidation, and accumulation of lipid intermediates, contributes to cardiac dysfunction in obesity and diabetes mellitus. However, mechanisms linking lipid overload and mitochondrial dysfunction are incompletely understood.To elucidate the mechanisms for mitochondrial adaptations to lipid overload in postnatal hearts in vivo.Using a transgenic mouse model of cardiac lipotoxicity overexpressing ACSL1 (long-chain acyl-CoA synthetase 1) in cardiomyocytes, we show that modestly increased myocardial fatty acid uptake leads to mitochondrial structural remodeling with significant reduction in minimum diameter. This is associated with increased palmitoyl-carnitine oxidation and increased reactive oxygen species (ROS) generation in isolated mitochondria. Mitochondrial morphological changes and elevated ROS generation are also observed in palmitate-treated neonatal rat ventricular cardiomyocytes. Palmitate exposure to neonatal rat ventricular cardiomyocytes initially activates mitochondrial respiration, coupled with increased mitochondrial polarization and ATP synthesis. However, long-term exposure to palmitate (>8 hours) enhances ROS generation, which is accompanied by loss of the mitochondrial reticulum and a pattern suggesting increased mitochondrial fission. Mechanistically, lipid-induced changes in mitochondrial redox status increased mitochondrial fission by increased ubiquitination of AKAP121 (A-kinase anchor protein 121) leading to reduced phosphorylation of DRP1 (dynamin-related protein 1) at Ser637 and altered proteolytic processing of OPA1 (optic atrophy 1). Scavenging mitochondrial ROS restored mitochondrial morphology in vivo and in vitro.Our results reveal a molecular mechanism by which lipid overload-induced mitochondrial ROS generation causes mitochondrial dysfunction by inducing post-translational modifications of mitochondrial proteins that regulate mitochondrial dynamics. These findings provide a novel mechanism for mitochondrial dysfunction in lipotoxic cardiomyopathy.
Tuberculose dans une prison du Yorkshire: rapport de cas
Authors: S Ahmed, Autilia Newton, T Allison
Journal: Eurosurveillance (2007)

En 2005, on a denombre 8,8 millions de nouveaux cas de tuberculose (TB) dans le monde et 1,6 million de deces. Les taux d’incidence en Europe occidentale allaient de 4 a 10 pour 100 000 en 2001 mais la tuberculose constitue encore un defi considerable dans cette region, notamment en raison des retards dans le diagnostic et la prise en charge.
Triaging in the face of terror
Authors: Chris B Yates
Journal: BMJ (2017)

Gulland describes how doctors rose to the challenge of the recent terror attacks in the UK.1 Before (and as the direct trigger for) becoming a junior doctor, I was deployed to Afghanistan with the British army and witnessed first hand the effect of mass casualty events and the importance of rapid triage in those first crucial moments.

Accurate triaging of patients into categories T1-3 (not dissimilar to the paramedic “priority” …
Investigation of the mechanism of action of Campath (Alemtuzumab)
Authors: William M. Siders, Jacqueline Shields, Andrea Sullivan, Carrie Johnson, Paula Boutin, Tri-Hung Nguyen, Srinivas Shankara, Bruce Roberts, Johanne Kaplan
Journal: Cancer Research (2006)

643  Campath (Alemtuzumab) is a recombinant humanized IgG1 monoclonal antibody directed against the 28 kD cell surface glycoprotein CD52 which is expressed on the surface of normal and malignant B and T lymphocytes as well as on NK cells, monocytes, macrophages, and tissues of the male reproductive system. Currently, Campath is indicated for the treatment of B-cell chronic lymphocytic leukemia (B-CLL) in patients who have been treated with alkylating agents and who have failed fludarabine therapy. The mechanism(s) by which Campath depletes malignant lymphocytes in vivo is not clearly defined. In order to better understand the mechanism of action of Campath, several cell lines were screened in vitro for their susceptibility to Campath-mediated lysis in both antibody dependent cell-mediated cytotoxicity (ADCC) and complement mediated cytotoxicity (CMC) assays. The results indicated that cell lines such as BL31, B104, MC-CAR, and Raji which express moderate to high levels of CD52 are sensitive to both ADCC and CMC mediated lysis. In addition, the degree of lysis correlated overall with the level of CD52 expression on the cell surface. To evaluate the activity of Campath in vivo, xenogeneic tumor studies were performed to determine whether treatment with the antibody could cause the regression of established subcutaneous tumors. SCID mice were injected with a lethal dose of CD52 positive B-cell MC/CAR tumor cells and tumors were allowed to grow to an average size of 3x3 mm2. Mice were then treated with either 1 or 10 mg/kg Campath or a control antibody twice weekly. Treatment with either vehicle or control antibody had no significant impact on the progression of the tumors. In contrast, administration of Campath resulted in 100 % regression of the tumors with a concomitant increase in survival (P=0.003). Once tumor regression was complete, treatment with Campath was discontinued. No tumor regrowth was observed, suggesting that treatment with Campath resulted in complete eradication of MC/CAR tumor cells. This xenograft model is now being used to investigate the role of CMC and ADCC in Campath-mediated elimination of tumor cells in vivo.
Hospital doctors call for inquiry into future of NHS as patient care deteriorates
Authors: Zosia Kmietowicz
Journal: BMJ (2017)

A body representing hospital consultants has called for an independent inquiry into the NHS’s future after a survey found that half of trust finance directors (41 of 85) said that patient care in their area had deteriorated over the past year.

The quarterly monitoring report from the think tank the King’s Fund1 found that just 6% (5 of 85) of finance directors thought that patient care in their area had improved. Of 233 NHS trust finance directors in England, 85 completed the survey (response rate 36%).

The report authors said that the NHS was heading into winter on …
What is precision medicine?
Authors: Inke R. König, Oliver Fuchs, Gesine Hansen, Erika von Mutius, Matthias V. Kopp
Journal: European Respiratory Journal (2017)

The term "precision medicine" has become very popular over recent years, fuelled by scientific as well as political perspectives. Despite its popularity, its exact meaning, and how it is different from other popular terms such as "stratified medicine", "targeted therapy" or "deep phenotyping" remains unclear. Commonly applied definitions focus on the stratification of patients, sometimes referred to as a novel taxonomy, and this is derived using large-scale data including clinical, lifestyle, genetic and further biomarker information, thus going beyond the classical "signs-and-symptoms" approach.While these aspects are relevant, this description leaves open a number of questions. For example, when does precision medicine begin? In which way does the stratification of patients translate into better healthcare? And can precision medicine be viewed as the end-point of a novel stratification of patients, as implied, or is it rather a greater whole?To clarify this, the aim of this paper is to provide a more comprehensive definition that focuses on precision medicine as a process. It will be shown that this proposed framework incorporates the derivation of novel taxonomies and their role in healthcare as part of the cycle, but also covers related terms.
TCT-218 The ‘SYNTAX Score derivatives’ to predict clinical outcomes after percutaneous coronary intervention with Everolimus-eluting stents for Left main/three vessel disease patients
Authors: Jeehoon Kang, Jung-Kyu Han, Chee Hae Kim, Min-Gyu Kong, Jiesuck Park, Han-Mo Yang, Kyung Woo (KW) Park, Hyun-Jae Kang, Bon-Kwon Koo, Hyo-Soo Kim
Journal: Journal of the American College of Cardiology (2017)
La gripe bajo estricta vigilancia
Authors: M. S. Vilayleck
Journal: Eurosurveillance (2002)

Durante los meses de julio y agosto de 2002 se produjo una importante epidemia de gripe en Madagascar. El marcado aumento del numero de casos en un periodo corto de tiempo indujo a las autoridades sanitarias a sospechar la aparicion de una nueva cepa muy virulenta del virus gripal. Esto desencadeno una reaccion internacional inmediata y un equipo internacional de la OMS colaboro con las autoridades sanitarias locales en la investigacion y el control de la epidemia. Afortunadamente, la investigacion preliminar descubrio que la cepa virica implicada era conocida, tipo A/Panama/2007/99, en circulacion por todo el mundo desde hace varios anos.
Gastric Banding Surgery versus Continuous Positive Airway Pressure for Obstructive Sleep Apnea: A Randomized Controlled Trial
Authors: Jessie P. Bakker, Ali Tavakkoli, Michael Rueschman, Wei Wang, Robert Andrews, Atul Malhotra, Robert L. Owens, Amit Anand, Katherine A. Dudley, Sanjay R. Patel
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

We performed a randomized trial of continuous positive airway pressure (CPAP) versus laparoscopic gastric banding (LGB) for patients with severe obstructive sleep apnea (OSA), hypothesizing that residual disease (effective apnea-hypopnea index [AHI]) (1-3) and Epworth Sleepiness Scale (ESS) scores would be significantly lower with LGB compared with CPAP at 9 and 18 months.Approval was obtained from the institutional review boards at Brigham and Women's Hospital and Beth Israel Deaconess Medical Center.The protocol was registered at clinicaltrials.gov(NCT01187771).All participants gave written informed consent.The inclusion criteria were age 18-65 years, body mass index (BMI) 35-45 kg/m 2 , severe OSA (AHI > 30 events/h [level 1 study] or AHI > 20 events/h [level 3 study]), and at least one OSA symptom.The exclusion criteria were prior CPAP or bariatric surgery, hypoventilation syndrome, increased perioperative risk, drowsy driving, non-English fluency, or any unstable medical condition.Suitability for both treatments, as well as the equipoise of each patient, was established by a sleep specialist and bariatrician before consent was obtained.Patients underwent attended polysomnography using the Compumedics E-Series at baseline, 9 months, and 18 months.Randomization was stratified by recruitment clinic, baseline BMI (35-40 or 40-45 kg/m 2 ), and sex.Sequences had block sizes of two and four, with a 50% chance of choosing either one.
Response by Choi et al to Letters Regarding Article, “Dipeptidyl Peptidase-4 Induces Aortic Valve Calcification by Inhibiting Insulin-Like Growth Factor-1 Signaling in Valvular Interstitial Cells”
Authors: Bongkun Choi, Sahmin Lee, Eun-Ju Chang, Jae-Kwan Song
Journal: Circulation (2017)
Colon inflammatory fibroid polyp in a patient with von Recklinghausen’s disease: endoscopic aspect with narrow-band imaging and magnification
Authors: Julie Benard, Jérôme Rivory, Florian Rostain, Céline Montuclard, Valérie Hervieu, Thierry Ponchon, Mathieu Pioche
Journal: Endoscopy (2017)

The prevalence of gastrointestinal involvement in von Recklinghausen’s disease is frequent (11 % – 25 %) [1] with different types of neurofibroma and juvenile-like polyps [2]. However, the association of von Recklinghausen’s disease with inflammatory fibroid polyps has been only rarely described [3]. We report here the case of a 39-year-old woman with past history of type 1 neurofibromatosis who was referred for hematochezia.
Transcriptomic analysis uncovers novel synergistic mechanisms in combination therapy for lupus nephritis
Authors: Jia Fu, Zichen Wang, Kyung Lee, Chengguo Wei, Zhengzhao Liu, Mingchao Zhang, Minlin Zhou, Minchao Cai, Weijia Zhang, Peter Y. Chuang, Avi Ma’ayan, John Cijiang He, Zhihong Liu
Journal: Kidney International (2017)
Validation of urinary HE4 as a biomarker for ovarian cancer.
Authors: Zhong-Qian Li, Christian Fermer, Rachel R. Radwan, Maria Hellman, Kuanglin He, Katherine L. Falcone, Savitha S. Raju, Maryellen Fegely, Zivjena Vucetic, Diana L. Dickson, Timothy R. Kettlety, Richard G. Moore, Grady Barnes
Journal: Journal of Clinical Oncology (2013)

5563 Background: Urinary HE4 has been reported as a promising biomarker for ovarian cancer (OC). In the current study, a large validation was performed to evaluate urinary HE4 as a biomarker for the stratification of OC from benign pelvic masses. Methods: Normalized HE4 was obtained from the ratio of HE4 (pmol/L measured with HE4 EIA) and creatinine (mg/dL measured with a Jaffe Reaction) in single-point urine samples from female subjects with a pelvic mass (N = 809). The samples were from one case-control prospective study (Moore RG, 2008) and two prospective clinical trials (NCT00315692 and NCT00987649). R Package was used to randomly distribute the subjects into the Training and Testing Sets. Analyze-it was used to analyze the clinical performance. Results: Medians of Normalized HE4, sensitivities (SN) and likelihood ratios (LR) (+) of Normalized HE4 at two levels of specificity (SP) are presented in the Table. Conclusions: Urinary HE4 normalized with urinary creatinine appears to be a valid biomarker for the stratification of OC from a benign pelvic mass. [Table: see text]
All Thiopurines Are Equal but Some Thiopurines Are More Equal Than Others
Authors: Berrie Meijer, Nanne K. H. de Boer
Journal: JAMA Oncology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Abstract 20407: Acute Leukemia is Associated With Cardiac Dysfunction Before Chemotherapy
Authors: Bruna M Assuncao, Timothy C Tan, Kai-Hung Cheng, Evin Yucel, Mark D Handschumacher, Marielle Scherrer-Crosbie
Journal: Circulation (2016)

Background: Patients with acute leukemia (AL) develop a higher rate of congestive heart failure than patients with other cancers. Acute leukemia may predispose to cardiac dysfunction prior to chemo...
Carcinogenicity of benzene
Authors: Dana Loomis, Kathryn Z Guyton, Yann Grosse, Fatiha El Ghissassi, Véronique Bouvard, Lamia Benbrahim-Tallaa, Neela Guha, Nadia Vilahur, Heidi Mattock, Kurt Straif
Journal: The Lancet Oncology (2017)
Association of Autoimmune Connective Tissue Disease With Abdominoplasty Outcomes
Authors: Gustavo A. Rubio, Leela S. Mundra, Seth R. Thaller
Journal: JAMA Surgery (2017)

Abdominoplasty is generally associated with favorable outcomes and high levels of patient satisfaction.Nonetheless, abdominoplasties have one of the highest complication rates among aesthetic procedures. 1 Patient selection and risk stratification is paramount to preventing postoperative complications.Patients with autoimmune connective tissue diseases (CTDs) may have associated systemic and soft tissue manifestations that increase their risk of complications. 2 To date, the association of CTDs with abdominoplasty outcomes has not been reported.The purpose of this study was to evaluate whether patients with autoimmune CTDs undergoing abdominoplasties are at an increased risk of complications.
Accuracy of Prehospital Triage in Selecting Severely Injured Trauma Patients
Authors: Frank J. Voskens, Eveline A. J. van Rein, Rogier van der Sluijs, Roderick M. Houwert, Robert Anton Lichtveld, Egbert J. Verleisdonk, Michiel Segers, Ger van Olden, Marcel Dijkgraaf, Luke P. H. Leenen, Mark van Heijl
Journal: JAMA Surgery (2017)

A major component of trauma care is adequate prehospital triage. To optimize the prehospital triage system, it is essential to gain insight in the quality of prehospital triage of the entire trauma system.To prospectively evaluate the quality of the field triage system to identify severely injured adult trauma patients.Prehospital and hospital data of all adult trauma patients during 2012 to 2014 transported with the highest priority by emergency medical services professionals to 10 hospitals in Central Netherlands were prospectively collected. Prehospital data collected by the emergency medical services professionals were matched to hospital data collected in the trauma registry. An Injury Severity Score of 16 or more was used to determine severe injury.The quality and diagnostic accuracy of the field triage protocol and compliance of emergency medical services professionals to the protocol.A total of 4950 trauma patients were evaluated of which 436 (8.8%) patients were severely injured. The undertriage rate based on actual destination facility was 21.6% (95% CI, 18.0-25.7) with an overtriage rate of 30.6% (95% CI, 29.3-32.0). Analysis of the protocol itself, regardless of destination facility, resulted in an undertriage of 63.8% (95% CI, 59.2-68.1) and overtriage of 7.4% (95% CI, 6.7-8.2). The compliance to the field triage trauma protocol was 73% for patients with a level 1 indication.More than 20% of the patients with severe injuries were not transported to a level I trauma center. These patients are at risk for preventable morbidity and mortality. This finding indicates the need for improvement of the prehospital triage protocol.
Modelling the process of falling behind and its psychophysiological consequences
Authors: Andreas Venhorst, Dominic Micklewright, Timothy D Noakes
Journal: British Journal of Sports Medicine (2017)

A preceding article investigated the psychophysiological responses to falling behind a performance matched opponent. The following temporally linked cause-effect relationships were hypothesised: falling behind precedes deterioration in valence, deterioration in valence precedes development of an action crisis, experience of an action crisis precedes psychoneuroendocrinological distress response and non-adaptive distress response reduces conduciveness to high performance, thereby preceding performance decrement.In this article, we applied structural equation modelling to test the extent to which the observed data fit the hypothesised cause-effect relationships. A five-step procedure was applied to model the interrelationships between the major study variables in the hypothesised temporal order.Significant linear relationships were found between all hypothesised predictor and outcome variable pairs (p<0.024). The dynamic change in valence was a significant mediator (p=0.011) as it explained 35% of the relationship between falling behind and action crisis. All hypothesised cause-effect relationships continued to be significant after controlling for performance, descriptor, training and perceived strain variables. The observed data fitted the hypothesised structural model well with excellent model fit indices throughout.We applied, tested and confirmed the hypothesised debilitative psychophysiological processes that unfold in response to falling behind a performance matched opponent. The main findings were: deterioration in valence mediated the relationship between falling behind and action crisis, the mindset shift associated with an action crisis predicted increased blood cortisol concentrations and non-adaptive blood cortisol concentrations predicted performance decrement. The findings point towards the crucial role of affective and cognitive modifiers in centrally regulated and goal-directed exercise behaviour.
TCT-647 Impella CP Use in Acute Myocardial Infarction Complicated by Cardiogenic Shock: A community Hospital Experience
Authors: Murad Abdelsalam, Augustine George, Brett Milford, Rudin Gjeka, Nishtha Sareen, Abdul Halabi, Michele De Gregorio, Kiritkumar Patel
Journal: Journal of the American College of Cardiology (2017)