tbuckley/cabot-search huggingface dataset:
MEDU-05. PROGNOSTIC IMPLICATION OF TERT PROMOTER MUTATION AND TP53 NUCLEAR STAINING IN ADULT MEDULLOBLASTOMA
Authors: Kay Ka-Wai Li, Zhi-feng Shi, Zhen-yu Zhang, Wei-wei Wang, Abudumijiti Aibaidula, Jingsong Wu, Ho-Keung Ng
Journal: Neuro-Oncology (2019)

Medulloblastoma (MB) only uncommonly occurs in adults and there were only few clinical-molecular studies. A total of 104 adult MBs were recruited. Molecular subgroups were determined by the NanoString platform. TERT promoter (TERTp) mutation, p53 status, and MYC/MYCN amplification were evaluated by Sanger sequencing, immunohistochemistry, and FISH respectively. Patients ranged between 19–63 years old. Nearly half of the adult MBs belonged to SHH (48.1%), and WNT, Group 3, and Group 4 tumors were found in 20.2%, 15.4%, and 16.3% respectively. TERTp mutation was identified in 23/92 (25%) cases. TERTp mutation was more often detected in SHH tumors, such that 78.3% of the mutation was identified in this subgroup. TP53 nuclear staining was detected in 33/104 (31.7%) tumors and was present in all molecular subgroups. MYC (2/94; 2.1%) and MYCN (3/94; 3.2%) amplifications were rarely detected and for the former, none in Group 3. We were able to study the survivals of 70 cases with the mean and median follow-up being 42.4 and 31.0 months respectively. Molecular subgroups, including WNT, did not impact on clinical outcome. Univariate analysis revealed that TERTp mutation was associated with a shorter progression-free survival (PFS; p=0.016), but the clinical significance was only maintained in the WNT tumors when subgrouped. Furthermore, patients with TP53 nuclear staining showed significantly shorter PFS (p=0.013) and overall survival (OS; p<0.001). When patients were stratified according to molecular subgroups, TP53 remained as strong predictor for PFS in Group 3 (p=0.004) and Group4 (p=0.018) tumors and OS in SHH (p=0.012) and Group 3 (p=0.046). Our study seems to suggest that SHH is not as over-represented in adult MB as previously reported, molecular subgroups may not be as strong prognostic indicators in adult MB as in pediatric patients and that TERTp mutation and TP53 are poor prognosticators across all subgroups.
Evolutionary Psychiatry. A new beginning
Authors: Ben Mills
Journal: BMJ (1999)

Routledge 1996; £15.99 (paperback)

ISBN 0 415 13840

Stevens and Price's opening gambit is that we have not one but three, evolutionary distinct, brains. If, like me, you've struggled in vain with neuroanatomy, this suggestion won't exactly bring tears of joy. But the idea is worth pursuing. The authors argue that at birth, there are, within the evolutionarily ancient parts of our brains, a number of “hard wired” behaviour routines, each of which, if acted out successfully, increases the chances of survival. Most of us know this already, …
Unilateral Asymptomatic Progressive Eruption of Hyperkeratotic Papules
Authors: Jaime Matarredona, Javier García-Abellán, Isabel Valencia Ramírez
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Prospective colonoscopic study to investigate risk of colorectal neoplasms in first-degree relatives of patients with non-advanced adenomas
Authors: Siew C Ng, Moe Htet Kyaw, Bing Yee Suen, Yee Kit Tse, Martin C S Wong, Aric J Hui, Hui Yee Tak, James Y W Lau, Joseph J Y Sung, Francis K L Chan
Journal: Gut (2019)

The risk associated with a family history of non-advanced adenoma (non-AA) is unknown. We determined the prevalence of colorectal neoplasms in subjects who have a first-degree relative (FDR) with non-AA compared with subjects who do not have an FDR with adenomas.In a blinded, cross-sectional study, consecutive subjects with newly diagnosed non-AA were identified from our colonoscopy database. 414 FDRs of subjects with non-AA (known as exposed FDRs; mean age 55.0±8.1 years) and 414 age and sex-matched FDRs of subjects with normal findings from colonoscopy (known as unexposed FDRs; mean age 55.2±7.8 years) underwent a colonoscopy from November 2015 to June 2018. One FDR per family was recruited. FDRs with a family history of colorectal cancer were excluded. The primary outcome was prevalence of advanced adenoma (AA). Secondary outcomes included prevalence of all adenomas and cancer.The prevalence of AA was 3.9% in exposed FDRs and 2.4% in unexposed FDRs (matched OR (mOR)=1.67; 95% CI 0.72 to 3.91; p=0.238 adjusted for proband sex and proband age). Exposed FDRs had a higher prevalence of any adenomas (29.2% vs 18.6%; mOR=1.87; 95% CI 1.32 to 2.66; p<0.001) and non-AA (25.4% vs 16.2%; mOR=1.91; 95% CI 1.32 to 2.76; p=0.001). A higher proportion of exposed FDRs than unexposed FDRs (4.3% vs 2.2%; adjusted mOR=2.44; 95% CI 1.01 to 5.86; p=0.047) had multiple adenomas. No cancer was detected in both groups.A positive family history of non-AA does not significantly increase the risk of clinically important colorectal neoplasia. The data support current guidelines which do not advocate earlier screening in individuals with a family history of non-AA.NCT0252172.
QI falters after trial fails to reduce mortality after abdominal surgery
Authors: Nigel Hawkes
Journal: BMJ (2019)

A quality improvement (QI) programme aimed at reducing mortality after emergency abdominal surgery had no effect, a large randomised trial in the NHS has shown.1

Just as many patients died in the hospitals implementing the quality improvements as in those providing usual care, the EPOCH (enhanced perioperative care for high risk patients) trial showed. The result casts a cloud over efforts to improve outcomes in healthcare by using the formal and systematic methods known as QI.

Rupert Pearse, professor and consultant in intensive care at Queen Mary University of London and senior author, said: “QI programmes are not a quick and easy solution to improving …
Abstract 9916: Evaluation of the Best Cut-off Value of Ischemia in Instantaneous Wave-Free Ratio in Patients With Aortic Valve Stenosis
Authors: Hiroyuki Arashi, Junichi Yamaguchi, Tonre Ri, Eiji Shibahashi, Ryosuke Itani, Kensuke Shimazaki, Hisao Otsuki, Shintarou Haruki, Masashi Nakao, Kazuho Kamishima, Kentaro Jujo, Yuichiro Minami, Nobuhisa Hagiwara
Journal: Circulation (2015)

Background: Instantaneous wave-free ratio (iFR) is a vasodilator free index calculated using trans-lesional pressure ratio during a specific period of diastole that is called “wave-free period”, and reported to have a good correlation with fractional flow reserve (FFR). In patients with severe aortic valve stenosis (AS), evaluation of intermediate coronary stenosis by FFR using vasodilators is thought to be a contraindication in some situations. Moreover, previous studies reported unique coronary flow pattern during diastolic phase in patients with AS. To date, there is no report claiming the correlation of iFR and FFR in this population. The purpose of the present study was to examine the clinical value of iFR in patients with AS. Method and Results: We examined consecutive 154 patients (with 214 stenosis) whose iFR and FFR were measured simultaneously. The mean age of AS patients (n=10, mean aortic valve area: 0.75 ± 0.42cm2) was higher than non-AS patients (n=144). Other patients’ characteristics are shown in Table 1. The mean iFR value in AS patients was significantly lower than that of non-AS patients, despite no significant difference was observed in the mean FFR value and % diameter stenosis (Table 2). iFR showed a good correlation with FFR in AS patients (Figure 1) and the best cut-off value of iFR in receiver operator curve analysis to predict FFR ≤ 0.8 was 0.73 in AS patients (AUC 0.84, sensitivity 0.8, specificity 0.86, p=0.016; Figure 2), whereas, 0.90 in non-AS patients. Conclusion: The present study demonstrated the good correlation between iFR and FFR in AS patients. Besides, the value below 0.73 of iFR was thought to be a predictor of myocardial ischemia in AS patients, which was lower than standard predictive range of ischemia in iFR. Vasodilator-free assessment by iFR may have potential benefits in evaluating intermediate coronary stenosis in patients with AS.
Targeted point-of-care testing compared with syndromic management of urogenital infections in women (WISH): a cross-sectional screening and diagnostic accuracy study
Authors: Marijn C Verwijs, Stephen K Agaba, Jean-Claude Sumanyi, Marie Michele Umulisa, Lambert Mwambarangwe, Viateur Musengamana, Mireille Uwineza, Vicky Cuylaerts, Tania Crucitti, Vicky Jespers, Janneke H H M van de Wijgert
Journal: The Lancet Infectious Diseases (2019)
Abstract 15290: Proteomic Profiling of Left Ventricular Mass Index and Incident Heart Failure: Insights From the Jackson Heart Study
Authors: Daniel H Katz, Usman Tahir, Matthew Herzig, Thomas J Wang, Debby Ngo, Michael E Hall, Adolfo Correa, James G Wilson, Robert E Gerszten
Journal: Circulation (2018)

Background: Increased left ventricular mass index (LVMI) is associated with adverse cardiovascular events including heart failure (HF). Both increased LVMI and HF disproportionally affect African A...
Association between Outdoor Air Pollution and Childhood Leukemia: A Systematic Review and Dose–Response Meta-Analysis
Authors: Tommaso Filippini, Elizabeth E. Hatch, Kenneth J. Rothman, Julia E. Heck, Andrew S. Park, Alessio Crippa, Nicola Orsini, Marco Vinceti
Journal: Environmental Health Perspectives (2019)

Background: A causal link between outdoor air pollution and childhood leukemia has been proposed, but some older studies suffer from methodological drawbacks. To the best of our knowledge, no systematic reviews have summarized the most recently published evidence and no analyses have examined the dose–response relation. Objective: We investigated the extent to which outdoor air pollution, especially as resulting from traffic-related contaminants, affects the risk of childhood leukemia. Methods: We searched all case–control and cohort studies that have investigated the risk of childhood leukemia in relation to exposure either to motorized traffic and related contaminants, based on various traffic-related metrics (number of vehicles in the closest roads, road density, and distance from major roads), or to measured or modeled levels of air contaminants such as benzene, nitrogen dioxide, 1,3-butadiene, and particulate matter. We carried out a meta-analysis of all eligible studies, including nine studies published since the last systematic review and, when possible, we fit a dose–response curve using a restricted cubic spline regression model. Results: We found 29 studies eligible to be included in our review. In the dose–response analysis, we found little association between disease risk and traffic indicators near the child's residence for most of the exposure range, with an indication of a possible excess risk only at the highest levels. In contrast, benzene exposure was positively and approximately linearly associated with risk of childhood leukemia, particularly for acute myeloid leukemia, among children under 6 y of age, and when exposure assessment at the time of diagnosis was used. Exposure to nitrogen dioxide showed little association with leukemia risk except at the highest levels. Discussion: Overall, the epidemiologic literature appears to support an association between benzene and childhood leukemia risk, with no indication of any threshold effect. A role for other measured and unmeasured pollutants from motorized traffic is also possible. https://doi.org/10.1289/EHP4381
Reprogramming identifies functionally distinct stages of clonal evolution in myelodysplastic syndromes
Authors: Jasper Hsu, Andreea Reilly, Brian J. Hayes, Courtnee A. Clough, Eric Q. Konnick, Beverly Torok-Storb, Suleyman Gulsuner, David Wu, Pamela S. Becker, Siobán B. Keel, Janis L. Abkowitz, Sergei Doulatov
Journal: Blood (2019)
CLINICAL CONSEQUENCES OF NON-ADHERENCE IN SURVEILLANCE OF BARRETT'S ESOPHAGUS: A MULTICENTER PROSPECTIVE COHORT STUDY
Authors: CAM Roumans, RD van der Bogt, D Nieboer, EW Steyerberg, D Rizopoulos, I Lansdorp-Vogelaar, K Biermann, MJ Bruno, MCW Spaander
Journal: Endoscopy (2019)

Guideline recommendations for surveillance of Barrett's esophagus (BE) aim to reduce heterogeneity and to improve quality of care. We aimed to estimate the clinical consequences of non-adherence on (1) the endoscopic resectability of esophageal adenocarcinoma (EAC), (2) mortality due to EAC, and (3) the risk of misdiagnosis of grade of dysplasia.
TMOD-03. GAINING A MECHANISTIC UNDERSTANDING OF THERAPY EVASION FROM DUAL MAPK PATHWAY INHIBITION IN A SYNGENEIC BRAFV600E MUTANT CDKN2A DELETED MOUSE MODEL TO PREEMPT RESISTANCE IN PATIENTS WITH BRAFV600E MUTANT PEDIATRIC GLIOMA
Authors: Wei Wang, Stefan Grossauer, Katharina Koeck, Erin Simonds, Edbert Lu, Gabriele Bergers, William Weiss, Claudia Petritsch
Journal: Neuro-Oncology (2019)

Pediatric patients with gliomas expressing the constitutively active BRAFV600E-mutant kinase are candidates for clinical trials for small molecule inhibitors specific for BRAFV600E (BRAFi) and MEK (MEKi) (Grossauer et al; Oncotarget 2016, 15:75839). Clinical results from combined BRAF and MEK inhibition (BRAFi+ MEKi) showed promising results with overall response rate of 43% in patients with recurrent high-grade gliomas and younger than 40 years. We previously observed that BRAFi increases intratumoral heterogeneity brought on by glioma stem cells in BRAFV600E-mutant glioblastoma xenografts (Lerner et al; Cancer Res 2015, 75:5355). These data point at glioma stem cells as a culprit in therapy resistance to molecular targeted therapy. Here, we aimed to understand the mechanisms of therapy evasion by studying changes in glioma stem cells and the tumor immune microenvironment in response to dual BRAFi + MEKi our syngeneic, BRAFV600E-mutant CDKN2A-deleted orthotopic mouse model (Grossauer et al; Oncotarget 2016, 15:75839). We found that while BRAFi increases the frequency of glioma stem cells, dual BRAFi+MEKi reduced glioma stem cells frequency, and failed to completely eliminate these malignant cells. BRAFi altered the tumor microenvironment, by increasing the frequency of proliferative cells that express a checkpoint inhibitor molecule. Analyses are ongoing of mechanisms of adaptation by cancer stem cells and of potential immunomodulatory effects of BRAFi + MEKi by single-cell mass spectrometry (CyTOF). Results from these analyses are expected to reveal changes in the tumor stem cell compartment and its immune microenvironment that will inform about mechanisms of therapy evasion to dual MAPK pathway inhibition. Our preclinical studies indicate a survival benefit of combined immune checkpoint inhibition and dual BRAFi + MEKi for animal subjects carrying orthotopic BRAFV600E mutant gliomas. Completion of these studies will bring us one step closer to overcome therapy resistance in patients with BRAFV600E-mutant CDKN2A-deleted glioma.
Inpatient dermatology: a paradigm shift in the management of skin disease in the hospital
Authors: L. C. Strowd
Journal: British Journal of Dermatology (2019)

Drs Finlay and Anstey recently published a timely editorial on the obstacles facing inpatient dermatology in the U.K., obstacles which echo throughout the global dermatology community. In their editorial they outlined the reduction in inpatient treatment for dermatological disease and the lack of literature focused on the economic impact of inpatient dermatological care.1 The shrinking numbers of inpatient dermatological services in the U.K. is a trend previously observed in the U.S.A., as evidenced by nationwide survey results published by Kirsner et al. in 1999.2 This paper suggested the rise of diagnosis‐related groups (DRGs) and subsequent correlation to insurance payments to hospital systems negatively affected by the coverage and reimbursement for inpatient dermatological care. Survey data from 71 different academic dermatology programmes nationwide supported this theory, with the majority of programmes citing DRGs and insurance issues as factors leading to reduced inpatient admissions. A second disturbing trend elucidated in this study was the shift in primary responsibility of inpatient dermatology patients to nondermatologists.2
Endoscopic Ultrasound Placement of Preloaded Fiducial Markers Shortens Procedure Time Compared to Back-Loaded Markers
Authors: Jorge D. Machicado, Joshua C. Obuch, Karyn A. Goodman, Tracey E. Schefter, Jessica Frakes, Sarah Hoffe, Kutjim Latifi, Violette C. Simon, Tess Santangelo, Eze Ezekwe, Steven A. Edmundowicz, Brian C. Brauer, Raj J. Shah, Hazem T. Hammad, Mihir S. Wagh, Augustin Attwell, Samuel Han, Jason Klapman, Sachin Wani
Journal: Clinical Gastroenterology and Hepatology (2019)
Neural respiratory drive predicts long-term outcome following admission for exacerbation of COPD: a post hoc analysis
Authors: Maxime Patout, Leonor Meira, Rebecca D’Cruz, Elodie Lhuillier, Georgios Kaltsakas, Gill Arbane, Eui-Sik Suh, Nicholas Hart, Patrick Brian Murphy
Journal: Thorax (2019)

Neural respiratory drive (NRD), as reflected by change in parasternal muscle electromyogram (EMGpara), predicts clinical deterioration and safe discharge in patients admitted to hospital with an acute exacerbation of COPD (AECOPD). The clinical utility of NRD to predict the long-term outcome of patients following hospital admission with an AECOPD is unknown. We undertook a post hoc analysis of a previously published prospective observational cohort study measuring NRD in 120 patients with AECOPD. Sixty-nine (57.5%) patients died during follow-up (median 3.6 years). Respiratory failure was the most common cause of death (n=29; 42%). In multivariate analysis, factors independently associated with an increased mortality included NRD (HR 2.14, 95% CI 1.29 to 3.54, p=0.003), age (HR 2.03, 95% CI 1.23 to 3.34, p=0.006), PaCO 2 at admission (HR 1.83, 95% CI 1.06 to 3.06, p=0.022) and long-term oxygen use (HR 2.98, 95% CI 1.47 to 6.03, p=0.002). NRD at hospital discharge could be measured in order to assess efficacy of interventions targeted to optimise COPD and reduce mortality following an AECOPD. Original clinicaltrial.gov number: NCT01361451
228. Relaxin Expression from Tumor-Targeting Adenoviruses and Its Intratumoral Spread, Apoptosis Induction, and Efficacy
Journal: Molecular Therapy (2007)

Background  The use of oncolytic adenoviruses as cancer gene therapy is limited by their uneven penetration and distribution in tumors. We investigated whether the expression of the cell matrix-degradative protein relaxin by adenovirus could improve adenovirus distribution and penetration in tumors.  Methods  We generated relaxin-expressing, replication-incompetent (dl-lacZ-RLX) and -competent (Ad-deltaE1B-RLX) adenoviruses by inserting a relaxin gene into the E3 adenoviral region. Controls were parental adenoviruses (dl-lacZ and Ad-deltaE1B) and phosphate-buffered saline (PBS) (vehicle). Replication-incompetent viruses, which do not lyse cells, were used to assess transduction efficiency. Viral spread in tumor spheroids, made by dissecting tumor tissue into homogeneous fragments, was assessed by reporter gene (i.e., lacZ) expression. Tumor growth inhibition was assessed by injecting adenoviruses into xenograft tumors in athymic mice (n = 8 or 9). Overall survival was assessed by the Kaplan-Meier method. Extracellular matrix was examined with Masson's trichrome staining. Therapeutic efficacy was evaluated by assessing spontaneous pulmonary metastasis in the B16BL6 melanoma mouse model and growth inhibition of orthotopically implanted hepatoma (n = 4-6). All statistical tests were two-sided.  Results  In tumor spheroids and established solid tumors in vivo, transduction with dl-lacZ-RLX, compared with parental virus or vehicle, elicited higher transduction efficiency and viral spread throughout the tumor mass. Infection with Ad-deltaE1B-RLX, compared with parental virus, elicited greater viral persistence and spread, leading to increased survival (e.g., 100%, 95% confidence interval [CI] = 63.1% to 100%, for C33A tumor-bearing mice treated with Ad-deltaE1B-RLX, and 50%, 95% CI = 15.7% to 84.3%, for C33A tumor-bearing mice treated with Ad-deltaE1B). Infection with Ad-deltaE1B-RLX substantially decreased the collagen content of tumor tissue but not of adjacent normal tissue, compared with noninfected tissues. Intratumoral injection of Ad-deltaE1B-RLX inhibited the formation of lung metastases in mice (PBS = 268 mg of metastatic tumor per mouse and Ad-deltaE1B-RLX = 10 mg; difference = 258 mg, 95% CI = 94 to 426; P = .003, Mann-Whitney test). Systemic treatment with Ad-deltaE1B-RLX completely inhibited the growth of Hep1 hepatocellular carcinomas (PBS = 20.2 mg of tumor per mouse and Ad-deltaE1B-RLX = 0 mg; difference = 20.2 mg, 95% CI = 3.7 to 36.7; P = .004, Mann-Whitney test).  Conclusion  Extracellular matrix degradation by relaxin expressed by adenoviruses increased viral distribution and tumor penetration, inhibited tumor growth and metastasis, and increased survival of mice.
microRNA-21-5p dysregulation in exosomes derived from heart failure patients impairs regenerative potential
Authors: Li Qiao, Shiqi Hu, Suyun Liu, Hui Zhang, Hong Ma, Ke Huang, Zhenhua Li, Teng Su, Adam Vandergriff, Junnan Tang, Tyler Allen, Phuong-Uyen Dinh, Jhon Cores, Qi Yin, Yongjun Li, Ke Cheng
Journal: Journal of Clinical Investigation (2019)

Exosomes, as functional paracrine units of therapeutic cells, can partially reproduce the reparative properties of their parental cells. The constitution of exosomes, as well as their biological activity, largely depends on the cells that secrete them. We isolated exosomes from explant-derived cardiac stromal cells from patients with heart failure (FEXO) or from normal donor hearts (NEXO) and compared their regenerative activities in vitro and in vivo. Patients in the FEXO group exhibited an impaired ability to promote endothelial tube formation and cardiomyocyte proliferation in vitro. Intramyocardial injection of NEXO resulted in structural and functional improvements in a murine model of acute myocardial infarction. In contrast, FEXO therapy exacerbated cardiac function and left ventricular remodeling. microRNA array and PCR analysis revealed dysregulation of miR-21-5p in FEXO. Restoring miR-21-5p expression rescued FEXO's reparative function, whereas blunting miR-21-5p expression in NEXO diminished its therapeutic benefits. Further mechanistic studies revealed that miR-21-5p augmented Akt kinase activity through the inhibition of phosphatase and tensin homolog. Taken together, the heart failure pathological condition altered the miR cargos of cardiac-derived exosomes and impaired their regenerative activities. miR-21-5p contributes to exosome-mediated heart repair by enhancing angiogenesis and cardiomyocyte survival through the phosphatase and tensin homolog/Akt pathway.