tbuckley/cabot-search huggingface dataset:
Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine
Authors: Andrew J. Aguirre, Jonathan A. Nowak, Nicholas D. Camarda, Richard A. Moffitt, Arezou A. Ghazani, Mehlika Hazar-Rethinam, Srivatsan Raghavan, Jaegil Kim, Lauren K. Brais, Dorisanne Ragon, Marisa W. Welch, Emma Reilly, Devin McCabe, Lori Marini, Kristin Anderka, Karla Helvie, Nelly Oliver, Ana Babic, Annacarolina Da Silva, Brandon Nadres, Emily E. Van Seventer, Heather A. Shahzade, Joseph P. St. Pierre, Kelly P. Burke, Thomas Clancy, James M. Cleary, Leona A. Doyle, Kunal Jajoo, Nadine J. McCleary, Jeffrey A. Meyerhardt, Janet E. Murphy, Kimmie Ng, Anuj K. Patel, Kimberly Perez, Michael H. Rosenthal, Douglas A. Rubinson, Marvin Ryou, Geoffrey I. Shapiro, Ewa Sicinska, Stuart G. Silverman, Rebecca J. Nagy, Richard B. Lanman, Deborah Knoerzer, Dean J. Welsch, Matthew B. Yurgelun, Charles S. Fuchs, Levi A. Garraway, Gad Getz, Jason L. Hornick, Bruce E. Johnson, Matthew H. Kulke, Robert J. Mayer, Jeffrey W. Miller, Paul B. Shyn, David A. Tuveson, Nikhil Wagle, Jen Jen Yeh, William C. Hahn, Ryan B. Corcoran, Scott L. Carter, Brian M. Wolpin
Journal: Cancer Discovery (2018)

Clinically relevant subtypes exist for pancreatic ductal adenocarcinoma (PDAC), but molecular characterization is not yet standard in clinical care. We implemented a biopsy protocol to perform time-sensitive whole-exome sequencing and RNA sequencing for patients with advanced PDAC. Therapeutically relevant genomic alterations were identified in 48% (34/71) and pathogenic/likely pathogenic germline alterations in 18% (13/71) of patients. Overall, 30% (21/71) of enrolled patients experienced a change in clinical management as a result of genomic data. Twenty-six patients had germline and/or somatic alterations in DNA-damage repair genes, and 5 additional patients had mutational signatures of homologous recombination deficiency but no identified causal genomic alteration. Two patients had oncogenic in-frame BRAF deletions, and we report the first clinical evidence that this alteration confers sensitivity to MAPK pathway inhibition. Moreover, we identified tumor/stroma gene expression signatures with clinical relevance. Collectively, these data demonstrate the feasibility and value of real-time genomic characterization of advanced PDAC.Significance: Molecular analyses of metastatic PDAC tumors are challenging due to the heterogeneous cellular composition of biopsy specimens and rapid progression of the disease. Using an integrated multidisciplinary biopsy program, we demonstrate that real-time genomic characterization of advanced PDAC can identify clinically relevant alterations that inform management of this difficult disease. Cancer Discov; 8(9); 1096-111. ©2018 AACR.See related commentary by Collisson, p. 1062This article is highlighted in the In This Issue feature, p. 1047.
Retraction and Republication: Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. N Engl J Med 2013;368:1279-90.
Authors: Ramón Estruch, Emilio Ros, Jordi Salas-Salvadó, Maria-Isabel Covas, Dolores Corella, Fernando Arós, Enrique Gómez-Gracia, Valentina Ruiz-Gutiérrez, Miquel Fiol, José Lapetra, Rosa M Lamuela-Raventos, Lluís Serra-Majem, Xavier Pintó, Josep Basora, Miguel A Muñoz, José V Sorlí, J Alfredo Martínez, Miguel A Martínez-González
Journal: New England Journal of Medicine (2018)

To the Editor: Because of irregularities in the randomization procedures, we wish to retract the following article: Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. N Engl J Med 2013;368:1279-90. DOI: 10.1056/NEJMoa1200303.1 We have reanalyzed the data and have published a new report: Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. N Engl J Med. DOI: 10.1056/NEJMoa1800389.2 . . .
Downregulation of CXCR4 by E1A
Authors: Xiaoyun Cheng, Yan M. Li, Yong Pan, Yong Liao, Mien-Chie Hung
Journal: Cancer Research (2005)

5656   The adenovirus type 5 E1A proteins have multiple antitumor effects on tumor cells, including reversion of transformation, induction of apoptosis and inhibition of metastasis, which have been used in the clinical trial since 1995. Although the functionality of E1A as a tumor suppressor has been extensively studied, its role in inhibition of tumor progression is still not being completely understood, especially its role in inhibition of metastasis. Recently, it was suggested that CXCR4 is involved in the targeted metastasis of breast cancer to lung, of prostate cancer to the bone marrow and of colon cancer to the liver. Here we show that E1A can inhibit the CXCR4 expression by FACS analysis and immunofluorescent staining. Further more E1A inhibits invasive activity induced by CXCR4  in vitro.  Finally we found that E1A can suppress CXCR4 transcriptional activity by inhibiting HIF regulation element on the CXCR4 promoter. These results provide the possible mechanism that E1A can function as a tumor suppressor by repressing CXCR4 mediated metastasis.
FRI0079 Adiponectin level, insulin resistance, endothelial dysfunction in females with rheumatoid arthritis and comorbid hypertension
Authors: O. Sirenko, O. Kuryata, T. Lysunets
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> <i>Rheumatoid arthritis (RA) associates with accelerated atherosclerosis and high cardiovascular mortality. Cardiovascular risk assessment in RA pts with comorbid hypertension (HT) is do not fully reflected by traditional risk scales, thus additional factors searching is required.</i> <h3>Objectives</h3> We aimed to estimate the adiponectin level, insulin resistance, endothelial function in RA females with comorbid HT and its relationship with subclinical manifestations of atherosclerosis. <h3>Methods</h3> The study included 82 RA females with low disease activity and comorbid HT (mean age of 54.6 [49.7; 62.5] years) and 40 HT females without RA (control group). All pts received stable therapy of RA more than 6 months. Pts with coronary artery disease were excluded. The risk of fatal cardiovascular disease was calculated using mSCORE. RA disese activity was measured using DAS28 scale. Carotid ultrasound detection and endothelial-dependent flow mediated vasodilatation (EDVD) by Celermajer method were performed. The levels of adiponectin, insulin were measured using ELISA kit test, insulin resistance was estimated using HOMA2 index. <h3>Results</h3> Endothelial dysfunction was established in the majority of main group patients – 61 (74.4%), insulin resistance – in 70 (85.4%), elevated levels of adiponectin – in 35 (42.7%). Hypertensive females with RA had significantly higher adiponectin, insulin, insulin resistance levels compare to control (p&lt;0.05). <i>Subclinical manifestations of atherosclerosis were established in</i> 64 (78.0%) <i>HT females with RA and</i> 10 (50%) <i>control group pts. While the median cardiovascular risk level was</i> 4.2 [2.7; 6.5]% match<i>ed by mSCORE.</i> The presence of atherosclerotic plaques in HT females with RA was associated with age (OR=1.242, p=0.004, 95% CI 1.007–1.78), glucocorticosteroid therapy &gt;3 months (OR=1.56, p=0.001, 95% CI 1.22–2.45), endothelial dysfunction (OR=3.584, p=0.001, 95% CI 1.71–4.723), insulin resistance (OR=1.684, p=0.011, 95% CI 1.22–2.74), abnormal adiponectin level (OR=1.71, p=0.028, 95% CI 1.17–2.43).<i> AUROC index for prognostic role of adiponectin and HOMA2 in subclinical atherosclerosis develop were 0.79 (95% CI 0.64–0.95</i>; p<i>&lt;0.05) and 0.76 (95% CI 0.61–0.92</i>; p<i>&lt;0.05) respectively, that indicate a good quality of diagnostic models.</i> <h3>Conclusions</h3> Hypertensive females with rheumatoid arthritis are characterised by higher frequency of insulin resistance, endothelial dysfunction, adiponectin level changes which associates with subclinical atherosclerosis manifestations. <h3>Disclosure of Interest</h3> None declared
Study of penetration mechanism of labrasol on rabbit cornea by Ussing chamber, RT-PCR assay, Western blot and immunohistochemistry
Authors: Pan Guo, Nan Li, Lili Fan, Jun Lu, Boying Liu, Bing Zhang, Yumei Wu, Zhidong Liu, Jiawei Li, Jiaxin Pi, Dongli Qi
Journal: Asian Journal of Pharmaceutical Sciences (2018)

Labrasol, as a non-ionic surfactant, can enhance the permeation and absorption of drugs, and is extensively used in topical, transdermal, and oral pharmaceutical preparations as an emulsifier and absorption enhancer. Recent studies in our laboratory have indicated that labrasol has a strong absorption enhancing effect on different types of drugs in vitro and in vivo. This study was performed to further elucidate the action mechanism of labrasol on the corneal penetration. In this research, the fluorescein sodium, a marker of passive paracellular transport of tight junction, was selected as the model drug to assess the effect of labrasol on in vitro corneal permeability. To investigate the continuous and real-time influence of labrasol on the membrane permeability and integrity, the Ussing chamber system was applied to monitor the electrophysiological parameters. And, furthermore, we elucidated the effect of labrasol on excised cornea at the molecular level by application of RT-PCR, Western blot, and immunohistochemical staining. The results indicated that labrasol obviously enhance the transcorneal permeability of fluorescein sodium, and the enhancement was realized by interacting with and down-regulating the associated proteins, such as F-actin, claudin-1 and β-catenin, which were contributed to cell-cell connections, respectively.
Obesity Prevalence Among Adults Living in Metropolitan and Nonmetropolitan Counties — United States, 2016
Authors: Elizabeth A. Lundeen, Sohyun Park, Liping Pan, Terry O’Toole, Kevin Matthews, Heidi M. Blanck
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Approximately 46 million persons (14%) in the United States live in nonmetropolitan counties.* Compared with metropolitan residents, nonmetropolitan residents have a higher prevalence of obesity-associated chronic diseases such as diabetes (1), coronary heart disease (1), and arthritis (2). The 2005-2008 National Health and Nutrition Examination Survey (NHANES) found a significantly higher obesity prevalence among adults in nonmetropolitan (39.6%) than in metropolitan (33.4%) counties (3). However, this difference has not been examined by state. Therefore, CDC examined state-level 2016 Behavioral Risk Factor Surveillance System (BRFSS) data and found that the prevalence of obesity (body mass index [BMI] ≥30 kg/m2) was 34.2% among U.S. adults living in nonmetropolitan counties and 28.7% among those living in metropolitan counties (p<0.001). Obesity prevalence was significantly higher among nonmetropolitan county residents than among metropolitan county residents in all U.S. Census regions, with the largest absolute difference in the South (5.6 percentage points) and Northeast (5.4 percentage points). In 24 of 47 states, obesity prevalence was significantly higher among persons in nonmetropolitan counties than among those in metropolitan counties; only in Wyoming was obesity prevalence higher among metropolitan county residents than among nonmetropolitan county residents. Both metropolitan and nonmetropolitan counties can address obesity through a variety of policy and environmental strategies to increase access to healthier foods and opportunities for physical activity (4).
Lorna Creighton Kinloch
Authors: Tom Kinloch
Journal: BMJ (2018)

Lorna Creighton Kinloch was born in Greenock, Scotland, the older of two daughters of a colonial medical officer and general practitioner. After qualifying she initially worked in Glasgow and Scunthorpe. Between 1953 and 1955 she lived in Moscow during very interesting times, early in the cold war. Her husband, Peter, was …
Postprandial Oxidative Metabolism of Human Brown Fat Indicates Thermogenesis
Authors: Mueez U Din, Teemu Saari, Juho Raiko, Nobu Kudomi, Stefanie F. Maurer, Minna Lahesmaa, Tobias Fromme, Ez-Zoubir Amri, Martin Klingenspor, Olof Solin, Pirjo Nuutila, Kirsi A. Virtanen
Journal: Cell Metabolism (2018)
AB1051 Brucellosis in rheumatology: a study of 27 cases in tunisia
Authors: K. Saadaoui, H. Sahli, S. Rekik, H. Ajlani, M. Mariem, T. Aissaoui, S. Boussaid, E. Cheour, M. Elleuch
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Brucellosis is an endemic zoonosis in the Mediterranean basin. The osteo articular localization, although rare, remains redoubtable. <h3>Objectives</h3> The aim of our work is to study the characteristics of osteoarticular brucellosis in Tunisia. <h3>Methods</h3> This is a descriptive retrospective study including 27 cases of osteoarticular brucellosis, collected in a rheumatology department over a period of 12 years (2006–2017) <h3>Results</h3> The Sex Ratio Female/male was 1.07 with an average age of 50.9 years.<sup>15–76</sup> Diagnosis delay was 5.9 months [0.3–13]. The diagnosis of spondylodiscitis was retained in 23 patients (85.2%) and sacroiliitis in 4 cases (14.8%). Spinal or sacroiliac pain was found in all patients. Fever was present in 22 patients, sweat in 11 patients, loss of weight or appetite were respectively found in 16 and 12 patients. Eleven patient reported fatigue. Laboratory examination found high erythrocyte sedimentation rate in 23 patients with an average of 69.4 mm.<sup>10–120</sup> CRP was elevated in 26 patients with an average of 59.6 mg/L [3.3–237], the WBC average was 9451 elements/ml [5550–14 000]. Wright serology was positive in all cases, Rose Bengal was positive in 15 cases, and IFI was positive in 3 cases. Brucella melitensis was isolated in blood cultures in 3 cases. Standard X Rays showed disk involvement in 21 patients, vertebral lesions in 20 cases and sacroiliitis in 4 patients. Sectional imaging (MRI or CT) was performed for all patients confirming standard X rays data and showing abscess in 13 patients and epiduritis in 7 patients. The most affected spinal segment was the lumbar one (13 cases), cervical localization was found in 5 cases and thoracic in only 1 case. The spondylitis was multifocal in 2 cases. Spinal disc biopsy was performed in only 4 cases, neither anatomopathologic nor bacteriological examination were conclusive. The treatment was based on the cycline and rifampicin combination for an average duration of 4.5 months.<sup>3–9</sup> The evolution was favourable in the majority of the cases with a relapse in only 2 cases. <h3>Conclusions</h3> Osteoarticular brucellosis is a focal form of brucellosis, the most frequent location is spinal and whose adequate treatment allows a favourable evolution. <h3>Disclosure of Interest</h3> None declared
Abstract 20227: Global Myocardial Injury as a New Criterion Independent of Infarct Size and Area-at-risk
Authors: Steven E Johnson, Daniel C Lee, Brandon C Benefield, Thomas A Holly, Rishi Arora, Wei Fang, Jeffrey J Goldberger, Ming Zhao
Journal: Circulation (2014)

Introduction: In acute coronary syndromes, the extent of myocardial injury can be substantially greater than the infarct zone. Existing imaging methods identify the infarct zone but do not assess “global myocardial injury” (GMI), which measures the total area of myocardium that sustained injuries including and beyond the infarct zone per se. Hypothesis: GMI can be detected based on changes in cellular membrane organization as a surrogate marker, using Tc-99m-duramycin. Methods: Balloon angioplasty was used for coronary occlusion in a pig model of myocardial ischemia and reperfusion (n = 9). Tc-99m-duramycin scans were acquired on a SPECT/CT scanner on day 1. On day 2, the infarct zone was assessed with Tc-99m-tetrofosmin. In an open-chest pig model of myocardial ischemia/reperfusion (n = 4) we used Evans Blue dye to facilitate the measurement of area-at-risk (AAR). Tc-99m-duramycin uptake was measured by gamma counting after tetrazolium (TTC) staining and physically dissecting the AAR, infarct zone and the noninfarcted-but-ischemically-damaged tissues. Histopathology was used to document cellular damages. Results: Quantitatively, Tc-99m-duramycin uptake delineated an area of myocardium that included but was substantially more extensive than the infarct zone. Under the current experimental condition, this area accounted for 81.0 ± 9.6% of the AAR, whereas the infarct zone was 25.5 ± 14.0% of the AAR. This was consistent with in vivo imaging, where the size of Tc-99m-duramycin positive tissue was visually larger than the perfusion defect in the Tc-99m-tetrofosmin scan. By histopathology, the noninfarcted-but-ischemically-damaged tissues contained features associated with cellular damages, and a heterogeneous mix of viable and dead cells. Conclusions: Tc-99m-duramycin has significant uptake in infarcted as well as noninfarcted-but-ischemically-damaged myocardium, thus reflecting global myocardial injury. The data support GMI as a new criterion independent of infarct size and AAR. The noninfarcted-but-ischemically-damaged myocardium is pathologically heterogeneous, thus a potential substrate for ventricular arrhythmias. The ability to detect such tissues may have important diagnostic and prognostic value.
AB0254 The impact of the patient global assessment variation on the das 28 value
Authors: K. ben abdelghani, M. boudokhane, M. chammakhi, A. fazaa, K. ouenniche, S. kassab, S. chekili, A. laatar
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is the most frequent chronic inflammatory rheumatism. The DAS 28 is a disease activity measure method used to assess RA activity. It is a composite score taking into account 4 items: the number of swollen joints/28, the number of tender joints/28, the erythrocyte sedimentation rate (ESR) or C reactive protein (CRP) rate, the patient global assessment (PGA) indicated on a 0–10 cm visual analogue scale (VAS) with 'not active at all' and 'extremely active' as anchors. The DAS28 determination is very important since it guides the therapeutic decision. <h3>Objectives</h3> The aim of this study was to determine the different ways of asking about the PGA and to assess the impact of its value variation on the calculation of the DAS 28. <h3>Methods</h3> In order to determine how to evaluate the GPA, a questionnaire including 4 propositions was asked to a cohort of Tunisian rheumatologists: how do you assess your health status this past week? what is the degree of the disease impact in your life this last week? what is the degree of the disease activity this last week? other Then, a DAS 28 calculation was proceeded according to the different choices of GPA question method for 10 Tunisian patients. <h3>Results</h3> The questionnaire was proposed to 37 rheumatologists, 15 working in the private sector and 22 in the public sector. These latter were 9 assistants, 3 professors, 5 specialist doctors and 5 associate professors. The first, second, third and fourth propositions were respectively chosen by 2, 14, 19 and 2 physicians. Subsequently DAS 28 was calculated. In the table 1 below, the variation of the DAS 28 value according to the choice of the PGA method is shown: <h3>Conclusions</h3> The GPA question is a subjective item taken into account for the calculation of the DAS 28. Despite the different ways of asking about it, our study showed that this factor have no real impact on the DAS28 value variation since it doesn't exceed 0.6. DAS28 remains a reliable tool in the clinical practice. <h3>Disclosure of Interest</h3> None declared
How We Measure Surgical Trainee Performance Matters—Reply
Authors: Aimee K. Gardner, Brian J. Dunkin
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Body-mass index, blood pressure, and cause-specific mortality in India: a prospective cohort study of 500 810 adults
Authors: Vendhan Gajalakshmi, Ben Lacey, Vendhan Kanimozhi, Paul Sherliker, Richard Peto, Sarah Lewington
Journal: The Lancet Global Health (2018)

The association between cause-specific mortality and body-mass index (BMI) has been studied mainly in high-income countries. We investigated the relations between BMI, systolic blood pressure, and mortality in India.
Association of Viral Suppression With Lower AIDS-Defining and Non–AIDS-Defining Cancer Incidence in HIV-Infected Veterans
Authors: Lesley S. Park, Janet P. Tate, Keith Sigel, Sheldon T. Brown, Kristina Crothers, Cynthia Gibert, Matthew Bidwell Goetz, David Rimland, Maria C. Rodriguez-Barradas, Roger J. Bedimo, Amy C. Justice, Robert Dubrow
Journal: Annals of Internal Medicine (2018)

Viral suppression is a primary marker of HIV treatment success. Persons with HIV are at increased risk for AIDS-defining cancer (ADC) and several types of non-AIDS-defining cancer (NADC), some of which are caused by oncogenic viruses.To determine whether viral suppression is associated with decreased cancer risk.Prospective cohort.Department of Veterans Affairs.HIV-positive veterans (n = 42 441) and demographically matched uninfected veterans (n = 104 712) from 1999 to 2015.Standardized cancer incidence rates and Poisson regression rate ratios (RRs; HIV-positive vs. uninfected persons) by viral suppression status (unsuppressed: person-time with HIV RNA levels ≥500 copies/mL; early suppression: initial 2 years with HIV RNA levels <500 copies/mL; long-term suppression: person-time after early suppression with HIV RNA levels <500 copies/mL).Cancer incidence for HIV-positive versus uninfected persons was highest for unsuppressed persons (RR, 2.35 [95% CI, 2.19 to 2.51]), lower among persons with early suppression (RR, 1.99 [CI, 1.87 to 2.12]), and lowest among persons with long-term suppression (RR, 1.52 [CI, 1.44 to 1.61]). This trend was strongest for ADC (unsuppressed: RR, 22.73 [CI, 19.01 to 27.19]; early suppression: RR, 9.48 [CI, 7.78 to 11.55]; long-term suppression: RR, 2.22 [CI, 1.69 to 2.93]), much weaker for NADC caused by viruses (unsuppressed: RR, 3.82 [CI, 3.24 to 4.49]; early suppression: RR, 3.42 [CI, 2.95 to 3.97]; long-term suppression: RR, 3.17 [CI, 2.78 to 3.62]), and absent for NADC not caused by viruses.Lower viral suppression thresholds, duration of long-term suppression, and effects of CD4+ and CD8+ T-cell counts were not thoroughly evaluated.Antiretroviral therapy resulting in long-term viral suppression may contribute to cancer prevention, to a greater degree for ADC than for NADC. Patients with long-term viral suppression still had excess cancer risk.National Cancer Institute and National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health.
Magnetic Resonance vs Transient Elastography Analysis of Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review and Pooled Analysis of Individual Participants
Authors: Cynthia Hsu, Cyrielle Caussy, Kento Imajo, Jun Chen, Siddharth Singh, Kellee Kaulback, Minh-Da Le, Jonathan Hooker, Xin Tu, Ricki Bettencourt, Meng Yin, Claude B. Sirlin, Richard L. Ehman, Atsushi Nakajima, Rohit Loomba
Journal: Clinical Gastroenterology and Hepatology (2018)