tbuckley/cabot-search huggingface dataset:
Abstract 13300: The Risk of Incident Hypertension According to the Metabolic Health and Obesity: Definition of Metabolic Health Does Not Matter
Authors: Yu Mi Kang, Chang Hee Jung, Jung Eun Jang, JenieYoonoo Hwang, Eun Hee Kim, Joong-Yeol Park, Hong-Kyu Kim, Woo Je Lee
Journal: Circulation (2015)

Background: Obesity is considered to be an important risk factor for hypertension. The metabolically healthy obese (MHO) phenotype refers to obese individuals with a favorable metabolic profile. Its prognostic value remains controversial and may partly depend on differences in defining methods. We examined the risk of MHO phenotype with incident hypertension in a Korean population using four representative criteria to define metabolic health status. Design and methods: The study population comprised of 31,033 Koreans without hypertension. Participants were stratified by body mass index (BMI) (cut-off value, 25.0 kg/m2) and metabolic health state, according to four defining methods; Adult Treatment Panel (ATP)-III criteria, Wildman criteria, Karelis criteria, and Homeostasis Model Assessment (HOMA) criteria. Results: Over the median follow-up period of 35.0 months (range, 4.5-81.4 months), 4,589 of the 31,033 individuals (14.8%) developed incident hypertension. Compared with the metabolically healthy nonobese (MHNO) group, the MHO group showed increased risk of incident hypertension with a multivariate-adjusted hazard ratio (HR) of 1.42 (95% confidence interval [CI], 1.30-1.54), 1.43 (95% CI 1.31-1.57), 1.41 (95% CI 1.27-1.56), and 1.33 (95% CI 1.23-1.45), when defined by ATP-III criteria, Wildman criteria, Karelis criteria, and HOMA criteria, respectively. Metabolically unhealthy obese (MUO) individuals were at the highest risk of incident hypertension. Conclusions: MHO subjects showed a substantially higher risk of incident hypertension regardless of the definition for metabolic health. Thus, it is important to consider both metabolic health and obesity when evaluating risk of hypertension.
Ethical Management of Diagnostic Uncertainty: Response to Open Peer Commentaries on “Why Bioethics Should Be Concerned With Medically Unexplained Symptoms”
Authors: Diane O’Leary
Journal: The American Journal of Bioethics (2018)

(2018). Ethical Management of Diagnostic Uncertainty: Response to Open Peer Commentaries on "Why Bioethics Should Be Concerned With Medically Unexplained Symptoms". The American Journal of Bioethics: Vol. 18, No. 8, pp. W6-W11.
An extracellular matrix fragment drives epithelial remodeling and airway hyperresponsiveness
Authors: Dhiren F. Patel, Teresa Peiró, Amelia Shoemark, Samia Akthar, Simone A. Walker, Aleksander M. Grabiec, Patricia L. Jackson, Tracy Hussell, Amit Gaggar, Xin Xu, Jennifer L. Trevor, Jindong Li, Chad Steele, Gael Tavernier, J. Edwin Blalock, Robert M. Niven, Lisa G. Gregory, Angela Simpson, Clare M. Lloyd, Robert J. Snelgrove
Journal: Science Translational Medicine (2018)

It is anticipated that bioactive fragments of the extracellular matrix (matrikines) can influence the development and progression of chronic diseases. The enzyme leukotriene A4 hydrolase (LTA4H) mediates opposing proinflammatory and anti-inflammatory activities, through the generation of leukotriene B4 (LTB4) and degradation of proneutrophilic matrikine Pro-Gly-Pro (PGP), respectively. We show that abrogation of LTB4 signaling ameliorated inflammation and airway hyperresponsiveness (AHR) in a murine asthma model, yet global loss of LTA4H exacerbated AHR, despite the absence of LTB4 This exacerbated AHR was attributable to a neutrophil-independent capacity of PGP to promote pathological airway epithelial remodeling. Thus, we demonstrate a disconnect between airway inflammation and AHR and the ability of a matrikine to promote an epithelial remodeling phenotype that negatively affects lung function. Subsequently, we show that substantial quantities of PGP are detectable in the sputum of moderate-severe asthmatics in two distinct cohorts of patients. These studies have implications for our understanding of remodeling phenotypes in asthma and may rationalize the failure of LTA4H inhibitors in the clinic.
New York University medical school gives students free tuition
Authors: Janice Hopkins Tanne
Journal: BMJ (2018)

New York University (NYU) announced on 16 August that it will offer free tuition to all current and future medical students.

The medical school, ranked among the top 10 in the United States, has an incoming class of 93 students and has 350 students already in the school. The free tuition was a surprise announcement at the annual “white coat ceremony,” where new students are presented with a white lab coat to mark the start of their medical training.

The decision was made because the rising cost of medical education is burdening most medical students with heavy debts, the …
Expression of HAVcR-1/TIM-1 (Hepatitis A virus cellular receptor) in human prostate cancer and its potential role in invasiveness of prostate cancer cells
Authors: G. M. Harrison, Gaynor Davies, Tracey A. Martin, Malcolm D. Mason, Wen G. Jiang
Journal: Cancer Research (2005)

5655  Background. Hepatitis A virus (HAV) cellular receptor HAVcR1, also known as KIM-1 and TIM-1, is the cellular receptor for the hepatotropic picornavirus that causes acute hepatitis-A in humans. HAVcR-1 is a class I integral membrane glycoprotein with an extracellular domain containing an N-terminal cysteine-rich region, followed by a extended O-glycosylated threonine-, serine-, and proline-rich region and makes it accessible for interactions with extracellular molecules. Although HAVcr-1 is expressed in every human organ, the natural function of havcr-1 remains unknown. In the current study, we examined the expression of HAVcr-1 in both normal and tumour prostate tissues/cells and examined its role in cancer cells functions. Methods. A total of 9 human prostate cancer cell lines were used. HAVcR1 protein in human prostate tissues was visualised using immunohistochemistry and mRNA transcript by RT-PCR. The staining intensity was quantified using a computer image analysis package. A hammerhead ribozyme transgene that specifically targeted human HAVcR-1 was constructed and used to knockout the HAVcR-1 transcript from invasive prostate cancer cells. In vitro invasiveness and motility of the cells were assayed using a Matrigel invasion assay and a Cytodex carrier assay. Statistical analysis was using t test. Results. Immunohistochemistry staining of prostate normal and tumour sections showed a distinct staining pattern of HAVcR1 in prostate tissues. Normal prostate epithelial cells displayed a weak to moderate staining of HAVcR1 in the cytoplasm. Malignant cells in tumour tissues however, showed significantly increased staining in the cytosol (staining intensity 0.16±0.05 in normal and 0.23±0.07 in tumour cells, p=0.0006). All the prostate cancer cells expressed HAVcR1 transcript, irrespective of their invasive potential. Using an in vitro invasion assay, we showed that when HAVcR1 expression was knocked out in PC-3 cells, the cells significantly reduced its invasive potential, compared with the wild-type PC-3 cells (p
Inconsistent Reporting of Potential Conflicts of Interest
Authors: Vinay Prasad
Journal: JAMA Oncology (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 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
Pregnancy in idiopathic non-cirrhotic portal hypertension: A multicentric study on maternal and fetal management and outcome
Authors: Filipe Andrade, Akash Shukla, Christophe Bureau, Marco Senzolo, Louis D'Alteroche, Alexandra Heurgué, Juan-Carlos Garcia-Pagan, Fanny Turon, Frédéric Oberti, Dhiraj Tripathi, Olivier Roux, Pierre-François Ceccaldi, Emmanuelle de Raucourt, Audrey Payancé, Dominique Valla, Aurélie Plessier, Pierre-Emmanuel Rautou
Journal: Journal of Hepatology (2018)
Efficacy of Resistance Exercise Training With Depressive Symptoms—Reply
Authors: Brett R. Gordon, Mark Lyons, Matthew P. Herring
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Abstract 20003: A 15-year Analysis and Descriptive Study of the Incidence, Clinical Characteristics, Management, and Outcomes of Lower Limb Ischemia in Type A and Type B Aortic Dissection Patients: Insights From the International Registry of Acute Aortic Dissection
Authors: Susan Alaei, Thoralf M Sundt, Udo Sechtem, Truls Myrmel, Marco Di Eusanio, Thomas G Gleason, Anil Bhan, Linda Pape, Takeyoshi Ota, Brett Reece, Eva Kline-Rogers, Daniel G Montgomery, Christoph A Nienaber, Eric M Isselbacher, Kim A Eagle
Journal: Circulation (2015)

Background: This study assessed the incidence of lower limb ischemia as well as trends in management and outcomes while examining acute aortic dissection patients over a period of 15 years. Additionally, differences in clinical presentation, interventions performed, and mortality between patients with and without lower limb ischemia were investigated. Methods: Lower limb ischemia (LLI) was evaluated among 3812 patients enrolled in the International Registry of Acute Aortic Dissection over a 15-year period that was separated into three 5-year intervals: 1996-2001, 2002-2007, and 2008-2012. The cohort was then divided by dissection type and presence or absence of LLI. Results: Type A patients presenting with limb ischemia (N=280, 11.4%) were much more likely to have atherosclerosis (p=0.021) and to present with back, abdominal and leg pain versus chest pain (p&lt;0.001 unless noted). Other symptoms of malperfusion, including ischemic spinal cord damage (p&lt;0.001) and coma/altered consciousness (p=0.006) were more common in patients presenting with LLI. Surgery was less commonly performed in Type A LLI patients (79.3% vs 86.1%, p=0.002), a difference that did not change over time (p=0.453, trend p=0.479). Additionally, overall mortality was higher in LLI patients (37.5% vs 22.9%, p&lt;0.001) and did not show improvement among the LLI cohort over time. Type B patients with LLI (N=102, 7.5%) were more likely to be current smokers (p=0.028), to present febrile (p=0.022), and to have leg pain (p&lt;0.001). As with Type A, ischemic spinal cord damage was more common in the LLI cohort (p&lt;0.001). Patients with LLI were much more likely to be managed with endovascular therapy (19.6% vs 50.0%, p&lt;0.001) than with medication alone (66.5% vs 29.4%, p&lt;0.001), with endovascular repair increasing in LLI patients over time (p=0.008, trend p=0.002). Again, overall mortality was higher in the LLI cohort (24.5% vs 9.7%, p&lt;0.001) and did not change over time. Conclusions: Although Type B patients with LLI received more endovascular procedures in later years, overall mortality did not improve. Increased complications and higher mortality in the LLI cohort suggests a need for better monitoring and increased implementation of interventions in this population.
Dependency on the TYK2/STAT1/MCL1 axis in anaplastic large cell lymphoma
Authors: Nicole Prutsch, Elisabeth Gurnhofer, Tobias Suske, Huan Chang Liang, Michaela Schlederer, Simone Roos, Lawren C. Wu, Ingrid Simonitsch-Klupp, Andrea Alvarez-Hernandez, Christoph Kornauth, Dario A. Leone, Jasmin Svinka, Robert Eferl, Tanja Limberger, Astrid Aufinger, Nitesh Shirsath, Peter Wolf, Thomas Hielscher, Christina Sternberg, Fritz Aberger, Johannes Schmoellerl, Dagmar Stoiber, Birgit Strobl, Ulrich Jäger, Philipp B. Staber, Florian Grebien, Richard Moriggl, Mathias Müller, Giorgio G. Inghirami, Takaomi Sanda, A. Thomas Look, Suzanne D. Turner, Lukas Kenner, Olaf Merkel
Journal: Leukemia (2018)

TYK2 is a member of the JAK family of tyrosine kinases that is involved in chromosomal translocation-induced fusion proteins found in anaplastic large cell lymphomas (ALCL) that lack rearrangements activating the anaplastic lymphoma kinase (ALK). Here we demonstrate that TYK2 is highly expressed in all cases of human ALCL, and that in a mouse model of NPM-ALK-induced lymphoma, genetic disruption of Tyk2 delays the onset of tumors and prolongs survival of the mice. Lymphomas in this model lacking Tyk2 have reduced STAT1 and STAT3 phosphorylation and reduced expression of Mcl1, a pro-survival member of the BCL2 family. These findings in mice are mirrored in human ALCL cell lines, in which TYK2 is activated by autocrine production of IL-10 and IL-22 and by interaction with specific receptors expressed by the cells. Activated TYK2 leads to STAT1 and STAT3 phosphorylation, activated expression of MCL1 and aberrant ALCL cell survival. Moreover, TYK2 inhibitors are able to induce apoptosis in ALCL cells, regardless of the presence or absence of an ALK-fusion. Thus, TYK2 is a dependency that is required for ALCL cell survival through activation of MCL1 expression. TYK2 represents an attractive drug target due to its essential enzymatic domain, and TYK2-specific inhibitors show promise as novel targeted inhibitors for ALCL.
Topotecan (T) + Pazopanib (P) in platinum-resistant or intermediate-sensitive ovarian cancer: a phase I/II single-arm multicentre trial of the North-Eastern German Society of Gynaecologic Oncology: TOPAZ.
Authors: Radoslav Chekerov, Ulrich Canzler, Hans-Georg Strauss, Volkmar Müller, Nikolaus de Gregorio, Ulrich Hacker, Tanja Neunhoeffer, Rolf Richter, Elena Ioana Braicu, Guelhan Inci, Klaus Pietzner, Isil Yalcinkaya, Antje Kristina Belau, Ekkehard von Abel, Pauline Wimberger, Jalid Sehouli
Journal: Journal of Clinical Oncology (2018)

e17553 Background: Pazopanib(P), an oral multi TK-inhibitor was combined with topoisomerase inhibitor topotecan (T) given in a weekly schedule in patients with first or second recurrence of ovarian cancer. Methods: Eligible patients had resistant of intermediate-sensitive recurrence (progression ≤ 12 mo after ≥ 4 platinum cycles) and ≤ 2 prior chemotherapy lines. In a dose-escalation step a maximal tolerable dose (MTD) of 400mg pazopanib daily was selected for combination with topotecan. The phase-II-trial registered patients to weekly topotecan 4 mg/m² (day 1,8,15, 28 day cycle) and pazopanib 400 mg/daily, for 6 chemotherapy cycles and in case of CR, PR or SD maintenance with pazopanib untill progression. The number of treatment lines was stratified. The primary objective was dose-limiting toxicity (part I) and PFS (part II). Secondary endpoints include OAS, objective response, safety. Results: Inside the 60 eligible patients of the ITT cohort with median age 55 (30-76 years), 19 pts were in second and 41 in third line. 65.7% of the patients received 6 cycles chemotherapy. Addition of P to T induced additional toxicity where grade 3/4 haematological reactions were most common and a main reason for dose reduction of pazopanib (43.3%). After a median follow-up of 8 months (range 1.2-53.8) the objective response rate was 5% with SD of 31.7%. TP does not improved significantly PFS with a median of 3.52 months (95% CI 2.21-4.82) and OS of 8.94 months (95%CI of 5.03-12.85). Conclusions: Addition of the multi TK-inhibitor pazopanib into the palliative treatment of recurrent ovarian cancer patients failed to demonstrate a clinical significant effect on survival. Clinical trial information: NCT01600573.
Abstract 15408: Long-term Antithrombotic Management Patterns After Acute Coronary Syndromes: 2-[[Unsupported Character - Codename ­]]years Follow-up in the EPICOR Asia Study
Authors: Yong Huo, Stephen W Lee, Jitendra P Sawhney, Hyo-Soo Kim, Rungroj Krittayaphong, Stuart J Pocock, Vo T Nhan, Chee Tang Chin, Xiaoning Han, Ana Vega, Yohji Itoh, Tiong K Ong
Journal: Circulation (2015)

Introduction: Guidelines recommend dual-antiplatelet therapy (DAPT) for 12 months in patients with acute coronary syndromes (ACS). Information on patterns and duration of DAPT use after hospital di...
Abstract 13974: Association Between Carotid Plaque and Presence, Extent and Severity of Coronary Atherosclerosis and Long-term Clinical Outcome in Asymptomatic Type 2 Diabetic Patients: Evaluation by Coronary CT Angiography
Authors: Jin Jin Kim, Young Choi, Kwan Yong Lee, Young Soo Lee, Ha-Wook Park, Tae-Hoon Kim, Yoon Seok Koh, Hun Jun Park, Pum Joon Kim, Wook Sung Chung, Ki-Bae Seung, Byung-Hee Hwang, Dong-Bin Kim, Sung-Won Jang, Eun Ho Choo, Ik Jun Choi, Sungmin Lim, Sang-Hyun Ihm, Chan Jun Kim, Donggyu Moon, Kiyuk Chang
Journal: Circulation (2015)

Introduction: We investigated the association between carotid plaque and the presence, extent and severity coronary atherosclerosis using coronary computed tomography angiography (CCTA) and long-term clinical outcome in asymptomatic type 2 diabetic patients. Methods: We consecutively enrolled 788 asymptomatic type 2 diabetic patients without known coronary artery disease (CAD) who underwent CCTA and carotid ultrasound. The presence of carotid plaque was defined as a focal increase in thickness of 1.5 mm or 50% of the surrounding IMT value. We compared the prevalence, extent and severity of coronary atherosclerosis, including coronary artery calcium score (CACS), atheroma burden obstructive score (ABOS), segment involvement score (SIS), and segment stenosis score (SSS) between groups. All-cause mortality during 5 years follow-up was also compared. Results: Higher rates of obstructive CAD (p&lt;0.001) and multi-vessel disease (p&lt;0.005) were noted for patients with carotid plaque. Patients with carotid plaque showed greater degree of CACS, ABOS, SIS, and SSS (p&lt;0.001 for all) on CCTA scans, and had a higher risk of all-cause mortality (p=0.025). The presence of carotid plaque was associated with an increased risk of significant coronary stenosis, independent of conventional cardiovascular risk factors (odds ratio 2.102, confidence interval 1.454-3.039, p&lt;0.001). Conclusions: The presence of carotid plaque is associated with the increased prevalence, extent and severity of coronary atherosclerosis on CCTA and the risk of all-cause mortality. Moreover, carotid plaque was an independent predictor for significant coronary stenosis in asymptomatic type 2 diabetic patients.
Abstract #5324: Loss of NF1 contributes to the progression of epithelial ovarian cancer
Authors: Jason Hurt, Debra Richardson, Audrey Papp, David Cohn, Jeffrey Fowler, Wolfgang Sadee
Journal: Cancer Research (2009)

Objective: Genetic alterations of  BRCA1  and  P53,  both located on chromosome 17, are common in many gynecologic cancers. Mutations in  NF1 , also located on chromosome 17, have been implicated in the development of neurologic and hematologic cancers but to date, research has not focused on the role of  NF1  in gynecologic cancers. We aimed to determine if the loss or partial loss of  NF1  is an initiating event in the development of epithelial ovarian cancer (EOC), in comparison to  BRCA1  and  P53 . Materials and Methods: Loss of heterozygosity (LOH) for  NF1, BRCA1 , and  P53 , all located on chromosome 17, was analyzed in tumors from 64 primary EOC tumors with SNaPshot primer extension. LOH was defined by allelic ratios >1.5. mRNA expression of these three genes was also measured with RT-PCR, to determine whether LOH is linked to a drastic downregulation of mRNA expression. Results: Seven SNPs were evaluated as markers for quantitation of LOH. LOH was demonstrated in 45% (21/47) of samples analyzed for SNP rs2592999, 18% (5/28) in rs7505, and 65% (14/21) for rs1801052 of  NF1 . Sixty six percent (17/26) demonstrated LOH for rs799917, 14% (3/21) for rs16492, zero for rs4986857 of  BRCA1  samples and 62% (16/26) of samples analyzed for rs1042522 of  P53 . Total mRNA expression was measured using RT-PCR. There was reduction in mRNA production in 59% of samples for  P53  and 64% for  NF1 . For those samples with LOH, there was a corresponding decrease in mRNA production in 12% of  NF1  samples and 8% of  P53 .  BRCA1  expression was too low to quantitate accurately. LOH of all three genes was demonstrated in 6% of samples. Conclusion: Substantial LOH observed with each of the three genes implies a possible role in early tumor development. No relationship in the extent of LOH between  NF1 ,  P53,  and  BRCA1  was demonstrated, suggesting independent deletion events that do not affect the entire chromosome. While LOH occurred in a large portion of samples analyzed, a corresponding large decrease in mRNA occurred in only ~10% of the tissues for  NF1  and  P53 , arguing against a frequent silencing of the remaining allele as a driving force of tumor progression in EOC. These results suggest that loss of  NF1  or  P53  does not serve as a primary initiating event in the development of ovarian cancer, but the high frequency of LOH supports a role in tumor progression.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5324.