tbuckley/cabot-search huggingface dataset:
Exosome-Mediated Small RNA Delivery: A Novel Therapeutic Approach for Inflammatory Lung Responses
Authors: Duo Zhang, Heedoo Lee, Xiaoyun Wang, Ashish Rai, Michael Groot, Yang Jin
Journal: Molecular Therapy (2018)

Exosomes (EXOs) are a type of extracellular nanovesicles released from living cells. Accumulating evidence suggests that EXOs are involved in the pathogenesis of human diseases, including lung conditions. In recent years, the potential of EXO-mediated drug delivery has gained increasing interest. In this report, we investigated whether inhaled EXOs serve as an efficient and practical delivery vehicle to activate or inhibit alveolar macrophages (AMs), subsequently modulating pulmonary immune responses. We first identified the recipient cells of the inhaled EXOs, which were labeled with PKH26. We found that only lung macrophages efficiently take up intratracheally instilled EXOs in vivo. Using modified calcium chloride-mediated transformation, we manipulated small RNA molecules in serum-derived EXOs, including siRNAs, microRNA (miRNA) mimics, and miRNA inhibitors. Via intratracheal instillation, we successfully delivered siRNA and miRNA mimics or inhibitors into lung macrophages using the serum-derived EXOs as vehicles. Furthermore, EXO siRNA or miRNA molecules are functional in modulating LPS-induced lung inflammation in vivo. Beneficially, serum-derived EXOs themselves do not trigger lung immune responses, adding more favorable features to serve as drug delivery agents. Collectively, we developed a novel protocol using serum-derived EXOs to deliver designated small RNA molecules into lung macrophages in vivo, potentially shedding light on future gene therapy of human lung diseases.
Prioritization and functional assessment of noncoding variants associated with complex diseases
Authors: Lin Zhou, Fangqing Zhao
Journal: Genome Medicine (2018)

Unraveling functional noncoding variants associated with complex diseases is still a great challenge. We present a novel algorithm, Prioritization And Functional Assessment (PAFA), that prioritizes and assesses the functionality of genetic variants by introducing population differentiation measures and recalibrating training variants. Comprehensive evaluations demonstrate that PAFA exhibits much higher sensitivity and specificity in prioritizing noncoding risk variants than existing methods. PAFA achieves improved performance in distinguishing both common and rare recurrent variants from non-recurrent variants by integrating multiple annotations and metrics. An integrated platform was developed, providing comprehensive functional annotations for noncoding variants by integrating functional genomic data, which can be accessed at http://159.226.67.237:8080/pafa .
Benign Thoracic Pain
Authors: F E Bruckner, S A Allard, N A Moussa
Journal: Journal of the Royal Society of Medicine (1987)

Seventy-three patients with mid-dorsal and/or unilateral chest pain seen consecutively in the rheumatology clinic by a single clinician over a three-year period were studied, after exclusion of visceral disease. The majority were young women. The pain was dull and continuous, was aggravated by coughing and sneezing and relieved by rest. There was frequently tenderness over the thoracic spine (T4-5) and an adjacent rib, and pain at extremes of thoracic spinal movement in one or two directions was invariable. Cutaneous hyperaesthesia in a radicular distribution was found in 16.4%, but there were no other neurological abnormalities. This clinical picture is probably the result of a thoracic disc prolapse, though confirmation by myelography was not thought to be ethically justified. The condition settled in most of the patients following manipulative treatment and advice on back care. No patient developed spinal cord compression. It is concluded that this is a common benign condition which deserves wider recognition.
Testosterone Prescribing in the United States, 2002-2016
Authors: Jacques Baillargeon, Yong-Fang Kuo, Jordan R. Westra, Randall J. Urban, James S. Goodwin
Journal: JAMA (2018)

J. Bradley Layton, PhD; Christoph R. Meier, PhD, MSc; Julie L. Sharpless, MD; Til Stürmer, MD, PhD; Susan S. Jick, DSc, MPH; M. Alan Brookhart, PhD
Preben: Pixantrone, Rituximab, Etoposide and Bendamustine, Spanish Experience in Diffuse Large B-Cell Lymphoma Treatment
Authors: Cristina Barrenetxea Lekue, Clara Alonso Caballero, Laura Hernández Vázquez, Belen Navarro Matilla, Fco Javier Capote Huelva, Dolores Caballero, Noelia Purroy Zuriguel, Irene Leal Martinez, Daniela Caballero Alvarez, Jose Antonio Marquez Navarro, Fernando Marco de Lucas
Journal: Blood (2017)
Nigel B Sprague
Authors: David Sprague
Journal: BMJ (2018)

Nigel B Sprague entered Durham School in September 1936, where he discovered rowing. This passion remained with him for the rest of his life. In 1940 he became a medical student at Durham University (previously King's College, Newcastle), where he met his future wife, Daphne. While there he rowed for the university and the medics. After qualifying he did national service in the Royal Armey Medical Corps from 1946 to 1948 and was a peace keeper in Palestine as part of the Parachute Regiment. He was subsequently in the Territorial Army …
Is Heart Failure Inherited?
Authors: Christopher J. O’Donnell, Clyde W. Yancy, Elizabeth M. McNally
Journal: JAMA Cardiology (2018)

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 Cardiology 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 Cardiology journal
Abstract 1358: Reentry within the Working Myocardium is not the Sole Mechanisms by which Ventricular Fibrillation is Maintained
Authors: Li Li, Qi Jin, Jian Huang, William M Smith, Raymond E Ideker
Journal: Circulation (2007)

Background: For well over 50 years, it has been assumed that ventricular fibrillation (VF) is maintained solely by reentry in the working myocardium. This hypothesis has never been tested by recording VF with electrodes spaced sufficiently close together to map activation sequences in 3-dimensions. Methods and Results: We recorded for 10 min during VF from the region of insertion of the anterior papillary muscle in the left ventricle of 4 open-chest pigs. A 3-D transmural unipolar electrode array consisting of a 9×9 array of needles with 2-mm spacing and 6 electrodes 2 mm apart on each needle was used to record from the working myocardium. The numbers of wavefronts, foci and reentrant circuits per sec were counted. A focus was identified when a wavefront appeared de novo within the central portion of the mapped region, insuring that it did not arise from another wavefront nor propagate into the mapped region from outside it. While intramural reentry was present early but not late during VF in the mapped region, foci were numerous and increased as VF continued (Figure ). Conclusion: Intramural foci are present during VF in pigs and, as VF continues, increase in incidence while the incidence of reentry in working myocardium decreases. These results suggest that, particularly after the first 2 min of VF, mechanisms other than reentry in the working myocardium maintain VF. It remains to be determined if these mechanisms consist of abnormal automaticity, afterdepolarizations, or reentry in which Purkinje fibers form all or part of the circuit.
USE OF DOUBLE-LAYERED COVERED ESOPHAGEAL STENTS IN POST-SURGICAL ESOPHAGEAL LEAKS AND ESOPHAGEAL PERFORATIONS: OUR EXPERIENCE
Authors: P Sanz Segura, J Gotor Delso, P García Cámara, R Uribarrena Amezaga, E Sierra Moros, J Val Pérez, MT Soria San Teodoro
Journal: Endoscopy (2018)

Endoscopic placement of esophageal stents is a common procedure in the management of benign esophageal perforations and in the management of esophageal anastomotic leaks. One of their limitations is a high rate of stent migration. It is proposed the use of Double-layered Covered Nitinol Stent to solve this problem.
Experiencia de nuestro centro en el uso de cápsula endoscópica
Authors: F Valverde López, R Jiménez Rosales, MJ Rodríguez Sicilia, E Fernández Fernández, F Vadillo Calles, P Abellán Alfocea, EJ Ortega Suazo, E Redondo Cerezo, JG Martínez Cara
Journal: Endoscopy (2017)

La cápsula endoscópica supone el método no invasivo de elección para el estudio de la mucosa de intestino delgado, con especial importancia en la detección de sangrado de intestino delgado.
Abstract 78: Hippo Pathway and Dystrophin Glycoprotein Complex Regulate Cardiomyocyte Proliferation
Authors: Yuka Morikawa, Todd Heallen, John Leach, Yang Xiao, James Martin
Journal: Circulation Research (2017)

Regeneration of mammalian heart is limited due to the extremely low renewal rate of cardiomyocytes and their inability to reenter the cell cycle. The Hippo pathway controls heart size during development and represses postnatal heart regeneration by repressing cardiomyocyte proliferation. Our approach for activating adult heart regeneration is to uncover the mechanisms responsible for repression of cardiomyocyte proliferation. We have previously found that deletion of Salv, a modulator of the Hippo pathway, results in myocardial damage repair in postnatal and adult hearts. Deletion of Salv results in activation of the transcription factor, Yap, which positively regulates cytoskeleton and cell cycle genes. We also found that the components of dystrophin glycoprotein complex (DGC) are the target of Yap and DGC regulates heart regeneration. The dystrophin glycoprotein complex (DGC) is essential for muscle maintenance by anchoring the cytoskeleton and extracellular matrix. Disruption of the DGC results in muscular dystrophies, including Duchenne muscular dystrophy, resulting in both skeletal and cardiac myopathies. To explore the connection between DGC and the Hippo pathway, we conditionally deleted Salv in the mdx background, a mouse model of muscular dystrophy. We found that simultaneous disruption of the DGC and the Hippo pathway leads an increased cardiomyocyte proliferation after heart damage. This is associated with increased activity of Yap, suggesting DGC negatively regulate Yap to repress proliferation. We also found that one of the components DGC, dystroglycan directly binds Yap and anchors to the membrane. Our findings provide new insights into the mechanisms leading to heart repair through proliferation of endogenous cardiomyocytes.
Forestalling BRAF-Inhibitor Resistance in a Shocking Way
Authors: Ryan J. Sullivan
Journal: Clinical Cancer Research (2018)

Targeting BRAF in BRAF-mutant melanoma is highly effective, but most patients develop resistance. HSP90 has been implicated and identified as a therapeutic target. Ultimately, early-stage clinical investigation will be necessary to provide proof of principle of this approach and if appropriate randomized trials to confirm promising findings. Clin Cancer Res; 24(22); 5496-8. ©2018 AACRSee related article by Eroglu et al., p. 5516.
Efficient Gene Transfer to Kidney Mesenchymal Cells Using a Synthetic Adeno-Associated Viral Vector
Authors: Yoichiro Ikeda, Zhao Sun, Xiao Ru, Luk H. Vandenberghe, Benjamin D. Humphreys
Journal: Journal of the American Society of Nephrology (2018)

After injury, mesenchymal progenitors in the kidney interstitium differentiate into myofibroblasts, cells that have a critical role in kidney fibrogenesis. The ability to deliver genetic material to myofibroblast progenitors could allow new therapeutic approaches to treat kidney fibrosis. Preclinical and clinical studies show that adeno-associated viruses (AAVs) efficiently and safely transduce various tissue targets
New Ebola Outbreak in Africa Is a Major Test for the WHO
Authors: Lawrence O. Gostin
Journal: JAMA (2018)

On May 8, the Democratic Republic of Congo (DRC) notified the World Health Organization (WHO) of a confirmed outbreak of Ebola in Bikoro, on the shores of Lake Tumba in Equateur Province. Ebola in the DRC is not unexpected. The first-ever identified Ebola outbreak occurred in the DRC — then Zaire — in 1976. This is the ninth of DRC’s outbreaks, which until now have been confined mainly to rural areas. With high fatality rates, earlier outbreaks quickly burned out due to the natural firewall of remoteness. Bikoro and a nearby village, Ikoko-Impenge, are rural, but on May 16, the WHO confirmed spread to Mbandaka, home to 1.2 million people. Peter Salama, MD, MPH, head of the WHO’s Emergencies Program, called urban spread a game changer that could spill over porous borders. Lake Tumba flows to the Congo River, connecting 2 capital cities (Kinshasa, DRC, and Brazzaville, Republic of the Congo) along the waterway. The WHO warned that 9 neighboring countries, including the Central African Republic, are at high risk.
Abstract 16256: Cardiac Magnetic Resonance Imaging of Myocardial Scar and EntropyX of Cardiac Repolarization Independently Predict Appropriate Shock and Cardiac Death in Primary Prevention ICD Recipients
Authors: Deeptankar DeMazumder, Brian O’Rourke, Gordon F Tomaselli, Steven R Jones, Katherine C Wu
Journal: Circulation (2016)

Introduction:  Independent of left-ventricular ejection fraction (LVEF) and other conventional risk factors, LV scar characterization by cardiac magnetic resonance imaging (cMRI) predicts adverse events in primary prevention ICD recipients. Similarly, reduced repetition of fluctuation patterns underlying the variability of cardiac repolarization, quantified by the novel nonlinear parameter EntropyX QT , predicts adverse events. Because cMRI characteristics and EntropyX QT  are distinct measures, we hypothesized they have independent and incremental prognostic value for potentially lethal ventricular tachyarrhythmias and cardiac mortality.   Methods:  In 220 consecutive cardiomyopathy patients in normal sinus rhythm and receiving optimal medical therapy at time of ICD implantation (baseline), we quantified the amount of heterogeneous myocardial tissue (gray zone), dense core, and total scar on cMRI with late gadolinium enhancement, and EntropyX QT  from 5-min ECGs. The primary endpoint was appropriate ICD shock or cardiac deaths not aborted by ICD.   Results:  Over 4.4±2.8 years, 68 patients experienced appropriate ICD shocks (N=46) or died (N=22). In multivariate analysis, adjusted hazard ratios comparing the 3rd to the 1st tertile of EntropyX QT  and cMRI characteristics were 2.93 (95% CI 1.51-5.70) and 1.96 (1.03-3.69), respectively, regardless of demographics, medical history, ischemic or non-ischemic cardiomyopathy, and absence or presence of other risk factors. Addition of EntropyX QT  to a model comprised of LVEF and cMRI characteristics improved the ROC curve area from 60.6±4.5% to 68.3±4.2% (p=0.032) and continuous net reclassification by 49.8% (20.5-85.0). Similar improvements in prognostic discrimination were observed when EntropyX QT  was added to conventional risk predictors.   Conclusions:  EntropyX QT , a novel, inexpensive and easily measured parameter, expands on simpler concepts of repolarization variability and increases the prognostic value of cMRI, above and beyond other risk predictors. This robust and non-invasive personalized approach for risk stratification may be used to better identify those who would and would not benefit from ICD implantation.
Sporadic cases of chikungunya, Réunion Island, August 2009
Authors: E D’Ortenzio, M Grandadam, E Balleydier, J S Dehecq, M C Jaffar-Bandjee, A Michault, S F Andriamandimby, J M Reynes, L Filleul
Journal: Eurosurveillance (2009)

On 28 August 2009, French authorities reported five cases of chikungunya fever on Réunion Island: three confirmed, one probable, and one suspected case under investigation. All three confirmed patients presented with an acute febrile syndrome, arthralgia, myalgia and cutaneaous rash. All live in the same area on the western side of the island.
INUSUAL CAUSE OF UPPER GASTROINTESTINAL BLEEDING: METASTASIC RENAL ANGIOSARCOMA
Authors: AR Guerra Romero, JA Ferrer Rosique, JL Perez Calle, M Gonzalez Fernández, ML Gutierrez, C Fernandez
Journal: Endoscopy (2018)

Metastatic gastric tumours have low prevalence, 0.7% in autopsy, usually the primary neoplasms comes from breast, lungs and melanoma. (8 – 10) Some cases had been described of Kidney metastases, most of them coming from renal adenocarcinoma. Renal Angiosarcoma (AS) with gastric metastasis is not usual, therefore we decided to bring this clinical case.
Serum and glucocorticoid inducible protein kinases (SGKs): a potential target for cancer intervention
Authors: Rajesh Basnet, Grace Qun Gong, Chenyao Li, Ming-Wei Wang
Journal: Acta Pharmaceutica Sinica B (2018)

The serum and glucocorticoid inducible protein kinase (SGK) family members share similar structure, substrate specificity and function with AKT and signal downstream of the phosphatidylinositol 3-kinase (PI3K) signalling pathway. They regulate a range of fundamental cellular processes such as cell proliferation and survival, thereby playing an important role in cancer development. This perspective intends to give an overview on the involvement of SGKs (particularly SGK3) in cancer progression, and compares the actions of SGK3 and AKT in cell cycle regulation, oncogenic signalling, and the potential as a therapeutic target for cancer.
EUS GUIDED CONTINUOUS CATHETER THROMBOLYSIS OF PORTAL VENOUS SYSTEM
Authors: P Somani, M Sharma
Journal: Endoscopy (2018)

Portal vein thrombosis (PVT) is an unusual thrombotic condition associated with significant morbidity and mortality. Treatment of PVT currently ranges from observation to anticoagulation or thrombolytic therapy. Thrombolytic therapy can be considered in those with thrombus extension or worsening pain while on therapeutic anticoagulation. It is usually performed under fluoroscopy by interventional radiologist.
Serum androgen levels are positively correlated with athletic performance and competition results in elite female athletes
Authors: Stéphane Bermon, Angelica Lindén Hirschberg, Jan Kowalski, Emma Eklund
Journal: British Journal of Sports Medicine (2018)

We thank our colleagues for their constructive comments that relate to our two articles in the July 2017 issue of BJSM .1 2 

The main criticisms expressed about the data used and our statistical analysis were (1) our ‘concentration’ on free testosterone (fT) rather than total testosterone (T)3 (presumably because the T results were only presented in the Internet version of the paper), (2) the fact that 17.3% of the athletes were sampled at both World Championships (Daegu and Moscow),3 (3) the fact that no correlation analysis was performed other than comparison of fT or T tertiles,3 (4) the absence of statistical comparison between a group with high T levels and a group with normal T levels4 and (5) the lack of adjustment for multiple comparisons (suggesting that the significant differences observed in our study could have happened by chance).5 

Taking this last criticism first, we note that we presented an exploratory study, without no attempt to claim confirmatory results. In fact, the exploratory evidence presented in the study is strong, and correction for multiplicity may be too conservative. But we agree that the results should be put into context. At the type 1 error level of 0.05, we could expect 1 of 20 hypotheses tested to be significant merely by chance, that is, p <0.05. In this study, we have observed significant correlations at the 0.05 level in five events, out of 21 events in total. Therefore, it is very unlikely that all these findings are caused by chance. Moreover, the five flagged events were showing similar findings in both fT and T, which indicates that the evidence and findings are robust.

Franklin et al report that, using Fisher’s combination test, they were unable to reject the hypothesis that the p values calculated from the …
Influencia de la inmersión de la pinza de biopsia en formaldehído en el resultado del test rápido de ureasa Clo-test®
Authors: E Borobio Aguilar, A Esparza Nieva, MP Ortiz Lana, C Echeverria Pérez, A Cebrián García, R Irisarri Garde, MR Vidarte García, R Rojas Zuasti, C Alonso Ganuza, E Aróstegui Iturralde
Journal: Endoscopy (2017)

El test rápido de ureasa Clo-test® (Campylobacter-like organism test, Kimberly-Clark Ballard Medical Products, Roswell, GA, USA) es un método invasivo para la detección de Helicobacter pylori (HP) en las biopsias gástricas. Existe controversia en cuanto a la aparición de falsos negativos de Clo-test® si previamente la pinza de biopsia se ha sumergido en formaldehído al 10% al remitir las muestras para estudio histológico. Para evitar estos falsos negativos, clásicamente se ha lavado la pinza de biopsia con agua.
Skin cancer: smartphone diagnostic apps may offer false reassurance, warn dermatologists
Authors: Jacqui Wise
Journal: BMJ (2018)

Some smartphone apps designed to diagnose skin cancer may give patients false reassurance because the apps may not recognise rare or unusual cancers or may not pick up on all red flag symptoms, dermatologists have warned.

The number of apps for diagnosing skin cancer has grown hugely, but researchers say that they vary in quality and that some have not been tested properly to show that they work and are safe.

Researchers from the University of Birmingham’s College of Medical and Dental Sciences reviewed the available medical literature on skin cancer apps and presented their findings at the British Association of Dermatologists’ …
糖尿病与降脂治疗：研究现状——现确信他汀类药物可减少2型糖尿病患者的心血管危险
Authors: John, Reckless, 杜昕（译）
Journal: BMJ (2006)

中青年发病和死亡多由心血管疾病引起，吸烟、高血压和血脂异常是导致心血管疾病的主要原因，而这些危险因素都是可以控制的。糖尿病与心血管风险直接相关，糖尿病患者的心血管疾病风险与无糖尿病而有心肌梗死病史的患者相同。由于多数2型糖尿病患者10年内患心血管疾病的绝对危险≥20％，指南推荐采取积极措施来干预糖尿病患者的危险因素，包括他汀类药物治疗，使血清低密度脂蛋白胆固醇（LDL-C）水平降低至2mmol／L以下。本期杂志发表了Costa等对降脂治疗临床试验汇总分析的结果（见第291页），这些临床试验评价了降脂治疗在糖尿病和非糖尿病患者冠心病一级预防和二级预防中的作用。
Varices gástricas: Factores pronósticos y tratamiento
Authors: A Sanahuja, J Tosca, C Suria, C Montón, J Ballester, R Villagrasa, A Peña, I Pascual, MÁ Serra, F Mora
Journal: Endoscopy (2017)

Las varices gástricas (VG) derivan de la formación de shunts porto-sistémicos debidos a hipertensión portal (HTP). Los estudios sobre el riesgo de sangrado y su tratamiento son heterogéneos, de reducida muestra y no proporcionan resultados concluyentes.