tbuckley/cabot-search huggingface dataset:
Nucleoside-modified mRNA encoding HSV-2 glycoproteins C, D, and E prevents clinical and subclinical genital herpes
Authors: Sita Awasthi, Lauren M. Hook, Norbert Pardi, Fushan Wang, Arpita Myles, Michael P. Cancro, Gary H. Cohen, Drew Weissman, Harvey M. Friedman
Journal: Science Immunology (2019)

The goals of a genital herpes vaccine are to prevent painful genital lesions and reduce or eliminate subclinical infection that risks transmission to partners and newborns. We evaluated a trivalent glycoprotein vaccine containing herpes simplex virus type 2 (HSV-2) entry molecule glycoprotein D (gD2) and two immune evasion molecules: glycoprotein C (gC2), which binds complement C3b, and glycoprotein E (gE2), which blocks immunoglobulin G (IgG) Fc activities. The trivalent vaccine was administered as baculovirus proteins with CpG and alum, or the identical amino acids were expressed using nucleoside-modified mRNA in lipid nanoparticles (LNPs). Both formulations completely prevented genital lesions in mice and guinea pigs. Differences emerged when evaluating subclinical infection. The trivalent protein vaccine prevented dorsal root ganglia infection, and day 2 and 4 vaginal cultures were negative in 23 of 30 (73%) mice compared with 63 of 64 (98%) in the mRNA group (P = 0.0012). In guinea pigs, 5 of 10 (50%) animals in the trivalent subunit protein group had vaginal shedding of HSV-2 DNA on 19 of 210 (9%) days compared with 2 of 10 (20%) animals in the mRNA group that shed HSV-2 DNA on 5 of 210 (2%) days (P = 0.0052). The trivalent mRNA vaccine was superior to trivalent proteins in stimulating ELISA IgG antibodies, neutralizing antibodies, antibodies that bind to crucial gD2 epitopes involved in entry and cell-to-cell spread, CD4+ T cell responses, and T follicular helper and germinal center B cell responses. The trivalent nucleoside-modified mRNA-LNP vaccine is a promising candidate for human trials.
African Women’s Preferences for HIV Prevention
Authors: Bridget Kuehn
Journal: JAMA (2019)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Prognostic role of VEGF, EGFR, COX-2, cERB-b2 and ER-alpha in stage 1 non-small cell lung cancers
Authors: C. Sadasiwan, S. Medendorp, R. Sreedhar, A. Raji, M. Blum, A. DeHoyas, J. Patel, A. Yeldandi
Journal: Journal of Clinical Oncology (2007)

7696 Introduction: Five-year survival rates for pathologic stage one NSCLC are between 57–67%. We looked at VEGF, EGFR, COX-2, cERB-b2 and ER-a in relationship to predicting recurrence. Methods: Tumors from 65 consecutive patients with stage I NSCLC were included. After marking representative areas on the slides, tissue microarrays were prepared and stained immunohistochemically using commercially available antibodies. The scoring was done by the pathologist and the principal investigator and is calculated as the product of staining intensity, the percentage of positively stained tumor cells and extent of membrane involvement. Results: 27 (42%) males/38 (58%) females. 75% stage IA/25% stage IB. Median smoking history was 40 pack-years (range 0–160pyr). 77% adenocarcinomas/23% squamous cell carcinomas. 19 (29%) patients had a recurrence of which 14 (74%) recurred locally and 5 (26.%) recurred at distant sites. The most common site of recurrence was the lung. Median time to recurrence was 30 months (range 4–97 mos). Scores for the molecular markers are reported in table 1 . Logistic regression of all the variables on multivariate analysis showed that VEGF scores predicted recurrence (p=0.021, Odds Ratio of 1.021). Scores of &gt;200 for VEGF were even more discriminatory. (p =0.034, Odds Ratio of 7.22). The rate of recurrence in this subgroup of patients was 39.5% as opposed to a rate of 14.8% among those with scores of less than 200. EGFR, COX-2, cERB-B2 and ER alpha were not found to be significant predictors of recurrence. Table 1 . Univariate analysis: Conclusion: VEGF scores predict risk of recurrence in stage I Non Small Cell Lung Cancers. We propose the use of high scores of VEGF, in Stage I Non Small Cell Carcinoma using immunohistochemistry to select those patients who are likely to recur. No significant financial relationships to disclose. [Table: see text]
A simplified blood culture sampling protocol for reducing contamination and costs: a randomized controlled trial
Authors: A. Lalezari, M.J. Cohen, O. Svinik, O. Tel-Zur, S. Sinvani, Y. Abed Al-Dayem, C. Block, A.E. Moses, Y. Oster, S. Salameh, J. Strahilevitz
Journal: Clinical Microbiology and Infection (2019)
Longterm Exercise-Derived Exosomal miR-342-5p
Authors: Zuoxu Hou, Xinghua Qin, Yuanyuan Hu, Xing Zhang, Guohua Li, Jie Wu, Jia Li, Jianding Sha, Jiangwei Chen, Jielai Xia, Lifeng Wang, Feng Gao
Journal: Circulation Research (2019)

Rationale: Exercise training, in addition to reducing cardiovascular risk factors, confers direct protection against myocardial ischemia/reperfusion injury and has been associated with improved heart attack survival in humans. However, the underlying mechanisms of exercise-afforded cardioprotection are still unclear. Objective: To investigate the role of exercise-derived circulating exosomes in cardioprotection and the molecular mechanisms involved. Methods and Results: Circulating exosomes were isolated from the plasma of volunteers with or without exercise training and rats subjected to 4-week swim exercise or sedentary littermates 24 hours after the last training session. Although the total circulating exosome level did not change significantly in exercised subjects 24 hours post-exercise compared with the sedentary control, the isolated plasma exosomes from exercised rats afforded remarkable protection against myocardial ischemia/reperfusion injury. miRNA sequencing combined with quantitative reverse transcription polymerase chain reaction validation identified 12 differentially expressed miRNAs from the circulating exosomes of exercised rats, among which miR-342-5p stood out as the most potent cardioprotective molecule. Importantly, the cardioprotective effects and the elevation of exosomal miR-342-5p were also observed in exercise-trained human volunteers. Moreover, inhibition of miR-342-5p significantly blunted the protective effects of exercise-derived circulating exosomes in hypoxia/reoxygenation cardiomyocytes; in vivo cardiac-specific inhibition of miR-342-5p through serotype 9 adeno-associated virus–mediated gene delivery attenuated exercise-afforded cardioprotection in myocardial ischemia/reperfusion rats. Mechanistically, miR-342-5p inhibited hypoxia/reoxygenation-induced cardiomyocyte apoptosis via targeting Caspase 9 and Jnk2 ; it also enhanced survival signaling (p-Akt) via targeting phosphatase gene Ppm1f . Of note, exercise training or laminar shear stress directly enhanced the synthesis of miR-342-5p in endothelial cells. Conclusions: Our findings reveal a novel endogenous cardioprotective mechanism that long-term exercise-derived circulating exosomes protect the heart against myocardial ischemia/reperfusion injury via exosomal miR-342-5p.
In US veterans, PPIs were linked to increased all-cause and some cause-specific mortality compared with H2-blockers
Authors: Ronald L. Koretz
Journal: Annals of Internal Medicine (2019)

Source Citation Xie Y, Bowe B, Yan Y, et al. Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: cohort study. BMJ. 2019;365:l1580. 31147311
Translational glycobiology: from bench to bedside
Authors: John Axford, Azita Alavi, Rick Cummings, Gordan Lauc, Ghislain Opdenakker, Celso Reis, Pauline Rudd
Journal: Journal of the Royal Society of Medicine (2019)

The importance of sugars to protein function is real and is of significant clinical relevance. Technology advances enable large population studies to be carried out, shedding light on individual sugar variation and variations with time. Three-dimensional mass spectroscopy on solid pathological specimens is going to open up a whole new world of pathology visualisation. The door is now open to exploit carbohydrate recognition in new therapeutics by identifying novel biomarkers in cancer to aid diagnosis, and also providing therapeutic targets for treatment. Glycan age correlates with biological age. This means we can map the reversal of biological age with exercise and diet.
Chromatin activity at GWAS loci identifies T cell states driving complex immune diseases
Authors: Blagoje Soskic, Eddie Cano-Gamez, Deborah J. Smyth, Wendy C. Rowan, Nikolina Nakic, Jorge Esparza-Gordillo, Lara Bossini-Castillo, David F. Tough, Christopher G. C. Larminie, Paola G. Bronson, David Willé, Gosia Trynka
Journal: Nature Genetics (2019)
Nucleos(t)ide analogues in patients with chronic hepatitis B: to stop or not to stop?
Authors: Jia-Horng Kao, Thomas Berg
Journal: Gut (2019)

Chronic HBV infection is a treatable but not curable disease. Long-term treatment with potent and safe nucleos(t)ide analogues (NA) with a high genetic barrier to drug resistance helps to reduce cirrhosis, hepatocellular carcinoma and liver-related mortality by profound viral suppression.1 Nevertheless, several controversial issues of chronic hepatitis B (CHB) management still exist and deserve further studies, including the selection of best candidates for a finite approach of NA therapy (box 1).

Box 1 
### Controversial issues and unmet needs of chronic hepatitis B management

International practising guidelines recommend that NA therapy should continue until HBsAg loss, at least in patients with HBeAg-negative CHB. However, a finite NA therapy has been practised in resource-limited regions, especially in Asia. The recent European Association for the Study of the Liver (EASL) guideline suggested NA may be stopped in HBeAg-positive non-cirrhotic patients who achieve HBeAg seroconversion with undetectable HBV DNA for at least 12 months, or in HBeAg-negative non-cirrhotic patients with persistent virological remission for >/=3 years.2 The pros of stopping NA are a finite treatment duration, with improved adherence, reduced costs and minimisation of renal and bone toxicity. The cons are the risk of reactivation of suppressed HBV, resulting in an unpredictable worsening of disease and possible development of severe hepatitis or even acute-on-chronic liver failure. The off-therapy relapse is common and up …
Evidence that tissue resident human enthesis γδT-cells can produce IL-17A independently of IL-23R transcript expression
Authors: Richard James Cuthbert, Abdulla Watad, Evangelos M Fragkakis, Robert Dunsmuir, Peter Loughenbury, Almas Khan, Peter A Millner, Adam Davison, Helena Marzo-Ortega, Darren Newton, Charlie Bridgewood, Dennis G McGonagle
Journal: Annals of the Rheumatic Diseases (2019)

Objectives Murine models of interleukin (IL)-23-driven spondyloarthritis (SpA) have demonstrated entheseal accumulation of γδT-cells which were responsible for the majority of local IL-17A production. However, IL-23 blockers are ineffective in axial inflammation in man. This study investigated γδT-cell subsets in the normal human enthesis to explore the biology of the IL-23/17 axis. Methods Human spinous processes entheseal soft tissue (EST) and peri-entheseal bone (PEB) were harvested during elective orthopaedic procedures. Entheseal γδT-cells were evaluated using immunohistochemistry and isolated and characterised using flow cytometry. RNA was isolated from γδT-cell subsets and analysed by qPCR. Entheseal γδT-cells were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, anti-CD3/28 or IL-23 and IL-17A production was measured by high-sensitivity ELISA and qPCR. Results Entheseal γδT-cells were confirmed immunohistochemically with Vδ1 and Vδ2 subsets that are cytometrically defined. Transcript profiles of both cell populations suggested tissue residency and immunomodulatory status. Entheseal Vδ2 cells expressed high relative abundance of IL-23/17-associated transcripts including IL-23R, RORC and CCR6, whereas the Vδ1 subset almost completely lacked detectable IL-23R transcript. Following PMA stimulation IL-17A was detectable in both Vδ1 and Vδ2 subsets, and following CD3/CD28 stimulation both subsets showed IL-17A and IL-17F transcripts with neither transcript being detectable in the Vδ1 subset following IL-23 stimulation. Conclusion Spinal entheseal Vδ1 and Vδ2 subsets are tissue resident cells with inducible IL-17A production with evidence that the Vδ1 subset does so independently of IL-23R expression.
A National Survey of Marijuana Use Among US Adults With Medical Conditions, 2016-2017
Authors: Hongying Dai, Kimber P. Richter
Journal: JAMA Network Open (2019)

<h3>Importance</h3> The number of states legalizing marijuana for medical and recreational use is increasing. Little is known regarding how or why adults with medical conditions use it. <h3>Objectives</h3> To report the prevalence and patterns of marijuana use among adults with and without medical conditions, overall and by sociodemographic group, and to further examine the associations between current marijuana use and the types and number of medical conditions. <h3>Design, Setting, and Participants</h3> This survey study used a probability sample of US adults aged 18 years and older from the 2016 and 2017 Behavioral Risk Factor Surveillance System, a telephone-administered survey that collects data from a representative sample of US adult residents across the states regarding health-related risk behaviors, chronic health conditions, and use of preventive services. <h3>Main Outcomes and Measures</h3> Current (past month) and daily (≥20 days in the last 30 days) marijuana use. <h3>Results</h3> The study sample included 169 036 participants (95 780 female [weighted percentage, 52.0%]). Adults with medical conditions had higher odds of reporting current marijuana use than those without medical conditions (age 18-34 years: adjusted odds ratio, 1.8 [95% CI, 1.5-2.1]; age 35-54 years: adjusted odds ratio, 1.4 [95% CI, 1.2-1.7]; age ≥55 years: adjusted odds ratio, 1.6 [95% CI, 1.3-2.0]), especially among those with asthma, chronic obstructive pulmonary disease, arthritis, cancer, and depression. Among those with medical conditions, the prevalence of marijuana use decreased with increasing age, ranging from 25.2% (95% CI, 22.0%-28.3%) for those aged 18 to 24 years to 2.4% (95% CI, 2.0%-2.8%) for those aged 65 years or older for current marijuana use and from 11.2% (95% CI, 8.7%-13.6%) to 0.9% (95% CI, 0.7%-1.2%), respectively, for daily marijuana use. Most adults who used marijuana (77.5%; 95% CI, 74.7%-80.3%), either with or without medical conditions, reported smoking as their primary method of administration. Adults with medical conditions were more likely than those without medical conditions to report using marijuana for medical reasons (45.5% [95% CI, 41.1%-49.8%] vs 21.8% [95% CI, 17.8%-25.7%]; difference, 23.7% [95% CI, 17.8%-29.6%]) and less likely to report using marijuana for recreational purposes (36.2% [95% CI, 32.1%-40.3%] vs 57.7% [95% CI, 52.6%-62.9%]; difference, −21.5% [95% CI, −28.1% to 14.9%]). <h3>Conclusions and Relevance</h3> This study found that marijuana use was more common among adults with medical conditions than those without such conditions. Notably, 11.2% of young adults with medical conditions reported using marijuana on a daily basis. Clinicians should screen for marijuana use among patients, understand why and how patients are using marijuana, and work with patients to optimize outcomes and reduce marijuana-associated risks.
The Key Combined Value of Multiparametric Magnetic Resonance Imaging, and Magnetic Resonance Imaging–targeted and Concomitant Systematic Biopsies for the Prediction of Adverse Pathological Features in Prostate Cancer Patients Undergoing Radical Prostatectomy
Authors: Giorgio Gandaglia, Guillaume Ploussard, Massimo Valerio, Agostino Mattei, Cristian Fiori, Mathieu Roumiguié, Nicola Fossati, Armando Stabile, Jean-Baptiste Beauval, Bernard Malavaud, Simone Scuderi, Francesco Barletta, Marco Moschini, Stefania Zamboni, Arnas Rakauskas, Zhe Tian, Pierre I. Karakiewicz, Francesco De Cobelli, Francesco Porpiglia, Francesco Montorsi, Alberto Briganti
Journal: European Urology (2019)
The Tumor Suppressor Interferon Regulatory Factor 2 Binding Protein 2 Regulates Hippo Pathway in Liver Cancer by a Feedback Loop in Mice
Authors: Xue Feng, Tiantian Lu, Jinhui Li, Ruizeng Yang, Liqiao Hu, Yi Ye, Feifei Mao, Lingli He, Jinjin Xu, Zuoyun Wang, Yingbin Liu, Yonglong Zhang, Hongbin Ji, Yun Zhao, Shuqun Cheng, Wei Tian, Lei Zhang
Journal: Hepatology (2019)

The conserved Hippo pathway regulates organ size, tissue homeostasis, and tumorigenesis. Interferon regulatory factor 2 binding protein 2 (IRF2BP2) was originally identified as a transcriptional corepressor. However, the association between IRF2BP2 and the Hippo pathway remains largely unknown. In addition, the biological function and regulation mechanism of IRF2BP2 in liver cancer are poorly understood.In this study, we uncovered the clinical significance of IRF2BP2 in suppressing hepatocellular carcinogenesis. We showed that IRF2BP2, a direct target repressed by the Yes-associated protein (YAP)/TEA domain transcription factor 4 (TEAD4) transcriptional complex, inhibited YAP activity through a feedback loop. IRF2BP2 stabilized vestigial-like family member 4 (VGLL4) and further enhanced VGLL4's inhibitory function on YAP. Moreover, liver-specific IRF2BP2 overexpression suppressed tumor formation induced by Hippo pathway inactivation.These results revealed the important role of IRF2BP2 in repressing liver cancer progression and highlighted a feedback loop underlying the Hippo pathway in organ-size control and tumorigenesis.
One-Stage Off-Pump Transapical Mitral Valve Repair and Aortic Valve Replacement
Authors: GinoGerosa, AugustoD’Onofrio, EricaManzan, LauraBesola, EleonoraBizzotto, FabioZucchetta, GiuseppeTarantini, DemetrioPittarello, AndreaColli
Journal: Circulation (2015)
Ruxolitinib in adult patients with secondary haemophagocytic lymphohistiocytosis: an open-label, single-centre, pilot trial
Authors: Asra Ahmed, Samuel A Merrill, Fares Alsawah, Paula Bockenstedt, Erica Campagnaro, Sumana Devata, Scott D Gitlin, Mark Kaminski, Alice Cusick, Tycel Phillips, Suman Sood, Moshe Talpaz, Albert Quiery, Philip S Boonstra, Ryan A Wilcox
Journal: The Lancet Haematology (2019)
Mortality rate after pneumatic dilatation for achalasia: authors’ reply
Authors: Philip R Harvey, Prashant Patel, Nigel J Trudgill
Journal: Gut (2019)

We thank Drs Van Hoeij and Bredenoord for their interest in our article.1 2 Their letter focuses on the observed mortality and perforation rates following pneumatic dilatation (PD) for achalasia.

It is important to recognise that, unlike the randomised controlled trial3 and systematic review4 quoted by Drs Van Hoeij and Bredenoord, our study was based on unselected subjects with achalasia receiving standard clinical care throughout England.2 Our study therefore contained much older subjects with more comorbidity, as …
Mission (nearly) impossible: ERCP using an oblique cap with suction cannulation in a diffusely strictured duodenal stump after Billroth II with Braun enteroenterostomy
Authors: Vincent Zimmer
Journal: Endoscopy (2019)

This is a unique clinical report of an 82-year-old man with cholangitis post distal gastrectomy for treatment of ulcer disease > 35 years ago, with no operative report available.
Cardiac Arrest and Cardiopulmonary Resuscitation Outcome Reports: Update of the Utstein Resuscitation Registry Template for In-Hospital Cardiac Arrest: A Consensus Report From a Task Force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian and New Zealand Council on Resuscitation, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Southern Africa, Resuscitation Council of …
Authors: Jerry P. Nolan, Robert A. Berg, Lars W. Andersen, Farhan Bhanji, Paul S. Chan, Michael W. Donnino, Swee Han Lim, Matthew Huei-Ming Ma, Vinay M. Nadkarni, Monique A. Starks, Gavin D. Perkins, Peter T. Morley, Jasmeet Soar
Journal: Circulation (2019)

Utstein-style reporting templates provide a structured framework with which to compare systems of care for cardiac arrest. The 2004 Utstein reporting template encompassed both out-of-hospital and in-hospital cardiac arrest. A 2015 update of the Utstein template focused on out-of-hospital cardiac arrest, which makes this update of the in-hospital template timely. Representatives of the International Liaison Committee on Resuscitation developed an updated in-hospital Utstein reporting template iteratively by meeting face-to-face, by teleconference, and by online surveys between 2013 and 2018. Data elements were grouped by hospital factors, patient variables, pre-event factors, cardiac arrest and postresuscitation processes, and outcomes. Elements were classified as core or supplemental by use of a modified Delphi process. Variables were described as core if they were considered essential. Core variables should enable reasonable comparisons between systems and are considered essential for quality improvement programs. Together with core variables, supplementary variables are considered useful for research.