tbuckley/cabot-search huggingface dataset:
P113Levels of anti-elastin IgA antibodies are associated with high risk of atherosclerosis in diabetics with essential hypertension
Authors: A Nikolov, M Tsekova, A Blazhev
Journal: Cardiovascular Research (2018)

after, and 24h post cell delivery.In vitro bioluminescence signal was used to identify tissue samples containing GFP-Luc-MSCs.Myocardial tissue matrix metalloproteinase 2 (MMP2) (index of ischemic/oxidative stress) and CXCR4 receptor expression (index of homing signal) were measured in bioluminescence positive and negative myocardial areas one day post cell transfer.Biodistribution of the implanted cells was quantified by using Luciferase assay and confirmed by fluorescence immunochemistry.Global left ventricular ejection fraction (LVEF) was measured at baseline and one month post cell therapy using MRI.Results: AMF decreased immediately after intracoronary cell delivery, while no change in tissue perfusion was found in the IM group.Intracoronary delivery led to a significant increase in myocardial MMP2 expression and decreased expression of CXCR4.Fluorescence immunochemistry indicated a higher expression level of a variety of homing (tenascin and cadherin) and angiogenic factor (FGF-2 and VEGF) in the IM group.LVEF increase was also significantly higher in IM group at the 1-month follow up.Conclusions: Intracoronary stem cell delivery decreased AMF, increased myocardial expression of MMP2, and lead to reduced CXCR4 expression with enhanced biodistribution and diminished functional recovery post-infarction.
How Many GP Referrals to Dermatology Outpatients are Really Necessary?
Authors: M J Sladden, R A C Graham-Brown
Journal: Journal of the Royal Society of Medicine (1989)

In a survey of patients referred to the dermatology outpatients department of a British teaching hospital, 26% of referrals were considered unnecessary by a senior house officer with three months practical dermatological experience. We conclude that better undergraduate and postgraduate education in dermatology is essential. A period spent in dermatology should be included in all vocational training schemes for general practice.
Atrophic scar formation in patients with acne involves long-acting immune responses with plasma cells and alteration of sebaceous glands
Authors: I. Carlavan, B. Bertino, M. Rivier, P. Martel, V. Bourdes, M. Motte, S. Déret, P. Reiniche, C. Menigot, A. Khammari, B. Dreno, P. Fogel, J.J. Voegel
Journal: British Journal of Dermatology (2018)

Possible outcomes of acne lesions are atrophic scars, which may cause serious psychological distress. Current treatments for postacne scarring often require invasive procedures. Pathophysiological studies on acne scarring have only investigated the first week of papule life. To study the pathophysiology of atrophic scar formation to identify molecular and cellular pathways that can lead to new therapies for the prevention of acne scarring. Large‐scale gene expression profiling and immunohistochemistry analysis were performed on uninvolved skin and papules in both scar‐prone (SP) and non‐scar‐prone (NSP) patients with acne, at different time points. Gene expression and immunohistochemistry analyses showed a very similar immune response in 48‐h‐old papules in SP and NSP populations, characterized by elevated numbers of T cells, neutrophils and macrophages. However, the immune response only persisted in SP patients in 3‐week‐old papules, and was characterized by an important B‐cell infiltrate. Transient downmodulation of sebaceous gland markers related to lipid metabolism was observed in 48‐h‐old papules in NSP patients, followed by normalization after 3 weeks. In contrast, in SP patients a drastic reduction of these markers persisted in 3‐week‐old papules, suggesting an irreversible destruction of sebaceous gland structures after inflammatory remodelling in SP patients with acne. Long‐lived acne papules are characterized by a B‐cell infiltrate. A relationship exists between the duration and severity of inflammation and the alteration of sebaceous gland structures, leading to atrophic scar formation in acne.
Reply to Martelli <i>et al.</i>: eHealth in Cystic Fibrosis: Promising, but Proof of Concept Is Still Needed
Authors: Noah Lechtzin, Nicole Mayer-Hamblett, Umer Khan, Christopher H. Goss
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

We thank Dr. Martelli and colleagues for their interest in our study of home symptom and spirometric monitoring for individuals with cystic fibrosis (CF), termed the eICE (Early Intervention in Cystic Fibrosis Exacerbation) study (1).A study of this nature is complicated and poses many challenges that are not encountered in a typical drug trial.Blinding is certainly one aspect that we debated when designing our study, but as Dr. Martelli and colleagues noted, we did not believe it would be ethical to have patients perform home monitoring without study personnel acting on the results.Their letter raises concerns that certain study design factors may have biased the study toward a negative result.We agree with many of the issues raised in the letter, but they are primarily related to study conduct, which in many cases is beyond the control of investigators, rather than design.For example, the authors note that the population had relatively mild disease.The study entry criteria were much broader than those used in many CF trials and included patients with FEV 1 as low as 25% predicted.Also, as we note in our paper, the study population was very similar to the general CF population in the United States.Martelli and colleagues note that adherence with the study intervention was suboptimal.We concur, but supplemental analyses failed to demonstrate any differences in outcomes, whether or not individuals were adherent with the intervention.They also suggest that some alarms in the early-intervention arm may have been due to poor spirometry technique rather than pulmonary exacerbations.Although this is possible, patients with CF are generally very experienced in performing spirometry, and we have pilot data for individuals with CF that demonstrate good agreement between home spirometry and spirometry performed in a pulmonary function testing lab (2).We agree with Martelli and colleagues that differential loss to follow-up was problematic.More subjects in the early-intervention arm dropped out than in the usual-care arm.This may have been due to challenges with the technology we used for the study and the burden it placed on patients.Nevertheless, we performed several different sensitivity analyses and did not see differences in outcomes if we excluded subjects who withdrew early, or if we compared outcomes at the time subjects withdrew.Contrary to the author's viewpoint, we did not use the last observation carried forward approach for missing data.Rather, our primary analysis of the
434Effect of preventive heart failure treatment in mice with arrhythmogenic right ventricular cardiomyopathy type 5 due to mutation in TMEM43
Authors: F Dominguez Rodriguez, L Padron-Barthe, M Villalba-Orero, M Lopez-Olaneta, J Larrasa-Alonso, P Ortiz-Sanchez, E Bello-Arroyo, P Garcia-Pavia, E Lara-Pezzi
Journal: Cardiovascular Research (2018)

BMPF, SymAtrial
The liver-specific deletion of the respiratory chain inhibitor MCJ attenuates NAFLD progression by enhancing hepatic betaoxidation
Authors: L. Barbier-Torres, T.C. Delgado, P. Iruzubieta, D.F. Ramos, V.G. de Juan, M. Varela-Rey, P.F. Tussy, I. Zubiete-Franco, J. Simón, F.L. Otsoa, D.M. Congregado, B.G. Santos, X. Buqué, J. Crespo, S.C. Lu, J. Matos, P. Aspichueta, J. Anguita, M. Rincón, M.L. Martínez-Chantar
Journal: Journal of Hepatology (2018)
Multidisciplinary Support Program for patients with addictions and suspected chronic hepatitis C (MSPADIC-C) to improve their evaluation and access to antiviral treatment
Authors: M. Puigvehí, F. Fonseca, E. González-Colominas, D. Giménez, A. Viu, R. Fernández, J. Tirado, L. Badenas, P. Samos, S. Jornalé, G. Vallecillo, C. Castillo, N. Cañete, T. Broquetas, M.G. Retortillo, S. Coll, R.S. Lamoglia, M. Torrens, J.A. Carrión
Journal: Journal of Hepatology (2018)
The BMJ Awards: mental health service for doctors wins 2018 award
Authors: Abi Rimmer
Journal: BMJ (2018)

The practitioner health service was one of 15 winners at the 2018 BMJ Awards. The service won the Mental Health Team of the Year award for its work, through the NHS Practitioner Health Programme, with doctors who experience stress, mental illness, or addiction.

The programme was first launched in 2008 by Clare Gerada, its medical director, as a mental health and addiction service for London doctors. In 2016 the service was expanded to include a health and wellbeing service for all trainees in London and the south east, and in 2017 it was extended to all GPs and trainees in England.

Competition for this year’s BMJ Awards—now in their 10th year—was fierce, with 250 entries across 15 categories, including cancer care, …
Genome-wide association analysis identifies a meningioma risk locus at 11p15.5
Authors: Elizabeth B Claus, Alex J Cornish, Peter Broderick, Joellen M Schildkraut, Sara E Dobbins, Amy Holroyd, Lisa Calvocoressi, Lingeng Lu, Helen M Hansen, Ivan Smirnov, Kyle M Walsh, Johannes Schramm, Per Hoffmann, Markus M Nöthen, Karl-Heinz Jöckel, Anthony Swerdlow, Signe Benzon Larsen, Christoffer Johansen, Matthias Simon, Melissa Bondy, Margaret Wrensch, Richard S Houlston, Joseph L Wiemels
Journal: Neuro-Oncology (2018)

Abstract Background Meningiomas are adult brain tumors originating in the meningeal coverings of the brain and spinal cord, with significant heritable basis. Genome-wide association studies (GWAS) have previously identified only a single risk locus for meningioma, at 10p12.31. Methods To identify a susceptibility locus for meningioma, we conducted a meta-analysis of 2 GWAS, imputed using a merged reference panel from the 1000 Genomes Project and UK10K data, with validation in 2 independent sample series totaling 2138 cases and 12081 controls. Results We identified a new susceptibility locus for meningioma at 11p15.5 (rs2686876, odds ratio = 1.44, P = 9.86 × 10–9). A number of genes localize to the region of linkage disequilibrium encompassing rs2686876, including RIC8A, which plays a central role in the development of neural crest-derived structures, such as the meninges. Conclusions This finding advances our understanding of the genetic basis of meningioma development and provides additional support for a polygenic model of meningioma.
Fatal Intracranial Hemorrhage Due to Thrombocytopenia in a Patient With Castration-Resistant Prostate Cancer Showing Extensive Bone Uptake of Injected 223Ra Dichloride
Authors: Tadaki Nakahara, Yoshiki Owaki, Takeo Kosaka, Junichi Fukada, Akira Ichimura, Masahiro Jinzaki
Journal: Clinical Nuclear Medicine (2018)

A 64-year-old man with castration-resistant prostate cancer received Ra injection to treat bone metastases. The patient underwent a Ra SPECT scan after the first Ra injection in which there was increased uptake all over the spine. Spine-to-background activity ratio in the patient was approximately three times greater than normal spine-to-background activity ratios in Ra SPECT obtained from the other patients. Eight days after the fifth injection, the patient exhibited a very poor neurologic examination and died of intracranial hemorrhage due to severe thrombocytopenia (platelet counts, 23,000/mm). The extensive radiation to the spine may have enhanced myelophthisic process in this case.
First line treatment of aplastic anemia with thymoglobuline in Europe and Asia: Outcome of 955 patients treated 2001‐2012
Authors: Andrea Bacigalupo, Rosi Oneto, Hubert Schrezenmeier, Britta Hochsmann, Carlo Dufour, Seiji Kojima, Xiaofan Zhu, Xiaojuan Chen, Surapol Issaragrisil, Suporn Chuncharunee, Dae Chul Jeong, Sabrina Giammarco, Maria Teresa Van Lint, Yizhou Zheng, Carlos Vallejo
Journal: American Journal of Hematology (2018)

Abstract The aim of this study was to assess the outcome of patients with aplastic anemia (AA), receiving rabbit anti‐thymocyte globulin (Thymoglobulin, SANOFI) and cyclosporin, as first line treatment. Eligible were 955 patients with AA, treated first line with Thymoglobulin, between 2001 and 2008 ( n = 492), or between 2009 and 2012 ( n = 463). The median age of the patients was 21 years (range 1‐84). Mortality within 90 days was 5.7% and 2.4%, respectively in the two time periods ( P = .007).The actuarial 10‐year survival for the entire population was 70%; transplant free survival was 64%. Predictors of survival in multivariate analysis, were severity of the disease, patients age and the interval between diagnosis and treatment. Survival was 87% vs 61% for responders at 6 months versus nonresponders ( P &lt; .0001). The 10‐year survival of nonresponders at 6 months, undergoing a subsequent transplant ( n = 110), was 64%, vs 60% for patient not transplantated ( n = 266) ( P = .1). The cumulative incidence of response was 37%, 52%, 65% respectively, at 90, 180, and 365 days. In multivariate analysis, negative predictors of response at 6 months, were older age, longer interval diagnosis treatment, and greater severity of the disease. In conclusion, early mortality is low after first line treatment of AA with Thymoglobulin, and has been further reduced after year 2008. Patients age, together with interval diagnosis—treament and severity of the disease, remain strong predictors of response and survival.
Integrative molecular classification of extrahepatic cholangiocarcinoma
Authors: R. Montal, W.Q. Leow, C. Montironi, L. Bassaganyas, A. Moeini, D. Sia, R. Pinyol, L. Cabellos, J. Peix, M. Maeda, P. Tabrizian, B. Minguez, T. Pawlik, I. Labgaa, L. Roberts, M. Sole, M.I. Fiel, S. Thung, S. Roayaie, A. Villanueva, M. Schwartz, J.M. Llovet
Journal: Journal of Hepatology (2018)
Dose response and safety of the daily, oral RIG-I agonist Inarigivir (SB 9200) in treatment naïve patients with chronic hepatitis B: results from the 25mg and 50mg cohorts in the ACHIEVE trial
Authors: M.-F. Yuen, M. Elkashab, C.-Y. Chen, C. Coffin, S. Fung, S. Greenbloom, J.W. Jang, R.W.-J. Jeng, D.J. Kim, Y.J. Kim, W. Kim, K.S. Lee, Y.-S. Lim, A. Ramji, R. Iyer, C. Macfarlane, K. Jackson, S. Locarnini, N. Afdhal, H. Chan
Journal: Journal of Hepatology (2018)
Involvement of the CREB-E2F2-PPAR axis in non-alcoholic fatty liver disease development and progression to hepatocarcinoma
Authors: D.M. Congregado, I. Aurrekoetxea, B.G. Santos, D.S. de Urturi, M. Núnez, J.L.G. Rodriguez, F. Gonzalez-Romero, L.F. Ares, A. Iglesias, I. Bernales, P. Iruzubieta, V.G. de Juan, M. Varela-Rey, G.E. Olartekoetxea, L.M. González, S. Gaztambide, L.A.C. González, J. Crespo, M.L. Martinez-Chantar, X. Buque, A. Zubiaga, P. Aspichueta
Journal: Journal of Hepatology (2018)
Abstract 10390: Impact of Diabetes Mellitus on the Prognosis of Patients With Heart Failure and Preserved Left Ventricle Ejection Fraction: Insights From the TOPCAT Study
Authors: Thao Huynh, Brian Harty, Susan Assmann, Eileen O'Meara, Inder Anand, Jerome Fleg, Brian Claggett, Bertram Pitt, Jean Rouleau
Journal: Circulation (2015)

Background: The impact of diabetes mellitus (DM) for patients with heart failure and preserved left ventricle ejection fraction (HFpEF) remains unclear. We aimed to determine the impact of DM on the prognosis of patients with DM and HFpEF enrolled in the TOPCAT trial. Methods: We classified TOPCAT patients into three groups: insulin-dependent DM (IDDM), non-insulin dependent DM (NIDDM) and non-DM. We investigated the occurrence of a major adverse cardiovascular event (MACE), defined as CV mortality, hospitalization for HF, non-fatal myocardial infarction (MI), non-fatal non-hemorrhagic stroke, or aborted cardiac arrest. Secondary outcomes included the individual components of MACE and all-cause mortality. We used multivariate Cox proportional hazards regression models to evaluate the independent associations of DM on time to MACE. Results: There were 1,134 DM patients (439 IDDM and 695 NIDDM) and 2,307 non-DM patients. The IDDM patients were younger and more likely to be male, non-white, and from the Americas. Despite having the highest median left ventricle’s ejection fraction (LVEF) (58%) compared to NIDDM and non-DM patients (57% and 56%, respectively, p=0.007), they were more symptomatic. Forty-eight percent of IDDM patients were of New York Heart Association (NYHA) III/IV functional classes compared to 36% of NIDDM and 29% of non-DM patients (p&lt;0.001). IDDM patients had significantly increased risks for MACE, CV mortality, MI, HF hospitalization, and all-cause mortality when compared to non-DM patients (p-values&lt;0.01). NIDDM patients had similar risks for MACE and the secondary outcomes as the non-DM patients. The effect of diabetes on outcomes was similar between regions. Conclusion: Among HFpEF patients, IDDM but not NIDDM was independently associated with increased risks of MACEs. Future research is needed to evaluate whether optimal medications and lifestyle interventions may reduce MACE in these high-risk patients.
Rheb requires a farnesyl or geranylgeranyl to bind to mTOR: implications for FTI antitumor activity
Authors: De-an Wang, Andrew Hamilton, Said Sebti
Journal: Cancer Research (2007)

5639   Farnesyltransferase inhibitors (FTIs) are potent inhibitors of tumor cell growth and survival and are presently undergoing human clinical trials. Yet the mechanism of action of FTIs is ill understood mainly because the critical FTase substrates for FTIs are not known. Here we demonstrate that a farnesyl or geranylgeranyl group is required for Rheb to bind mTOR. Furthermore, an exclusively geranylgeranylated form of Rheb, Rheb-GG, that we made co-localized with mTOR and was as effective as Rheb-F at activating the downstream effector of mTOR, S6 kinase. Importantly, Rheb-GG rescued human cancer cells from FTI inhibition of S6 kinase, inhibition of anchorage-dependent and -independent tumor cell growth and induction of apoptosis. Taken together these results suggest that inhibition of Rheb farnesylation by FTIs is required for their ability to inhibit tumor growth and survival.
Creating Entrustable Professional Activities to Assess Internal Medicine Residents in Training
Authors: David R. Taylor, Yoon Soo Park, Christopher A. Smith, Jolanta Karpinski, William Coke, Ara Tekian
Journal: Annals of Internal Medicine (2018)

Competency-based medical education has not advanced residency training as much as many observers expected. Some medical educators now advocate reorienting competency-based approaches to focus on a resident's ability to do authentic clinical work.To develop descriptions of clinical work for which internal medicine residents must gain proficiency to deliver meaningful patient care (for example, "Admit and manage a medical inpatient with a new acute problem").A modified Delphi process involving clinical experts followed by a conference of educational experts.The Royal College of Physicians and Surgeons of Canada.In phase 1 of the project, members of the Specialty Committee for Internal Medicine participated in a modified Delphi process to identify activities in internal medicine that represent the scope of the specialty. In phase 2 of the project, 5 experts who were scholars and leaders in competency-based medical education reviewed the results.Phase 1 identified important activities, revised descriptions to improve accuracy and avoid overlap, and assigned activities to stages of training. Phase 2 compared proposed activity descriptions with published guidelines for their development and application in medical education.The project identified 29 activities that qualify as entrustable professional activities. The project also produced a detailed description of each activity and guidelines for using them to assess residents.These activities reflect the practice patterns of the developers and may not fully represent internal medicine practice in Canada.Identification of these activities is expected to facilitate modification of training and assessment programs for medical residents so that programs focus less on isolated skills and more on integrated tasks.Southeastern Ontario Academic Medical Organization Endowed Scholarship and Education Fund and Queen's University Department of Medicine Innovation Fund.
Saturated fat is more metabolically harmful for the human liver than polyunsaturated fat or simple sugars
Authors: P. Luukkonen, S. Sadevirta, Y. Zhou, A. Ali, L. Ahonen, S. Lallukka, M. Gaggini, C. Jian, A. Hakkarainen, N. Lundbom, H. Gylling, A. Salonen, M. Orešič, T. Hyötyläinen, A. Gastaldelli, M. Orho-Melander, A. Rissanen, L. Hodson, H. Yki-Järvinen
Journal: Journal of Hepatology (2018)
Safety of panitumumab-IRDye800CW and cetuximab-IRDye800CW for fluorescence-guided surgical navigation in head and neck cancers
Authors: Rebecca W. Gao, Nutte Teraphongphom, Esther de Boer, Nynke S. van den Berg, Vasu Divi, Michael J. Kaplan, Nicholas J. Oberhelman, Steven S. Hong, Elissa Capes, A. Dimitrios Colevas, Jason M. Warram, Eben L. Rosenthal
Journal: Theranostics (2018)

Purpose: To demonstrate the safety and feasibility of leveraging therapeutic antibodies for surgical imaging. Procedures: We conducted two phase I trials for anti-epidermal growth factor receptor antibodies cetuximab-IRDye800CW (n=12) and panitumumab-IRDye800CW (n=15). Adults with biopsy-confirmed head and neck squamous cell carcinoma scheduled for standard-of-care surgery were eligible. For cetuximab-IRDye800CW, cohort 1 was intravenously infused with 2.5 mg/m2, cohort 2 received 25 mg/m2, and cohort 3 received 62.5 mg/m2. For panitumumab-IRDye800CW, cohorts received 0.06 mg/kg, 0.5 mg/kg, and 1 mg/kg, respectively. Electrocardiograms and blood samples were obtained, and patients were followed for 30 days post-study drug infusion. Results: Both fluorescently labeled antibodies had similar pharmacodynamic properties and minimal toxicities. Two infusion reactions occurred with cetuximab and none with panitumumab. There were no grade 2 or higher toxicities attributable to cetuximab-IRDye800CW or panitumumab-IRDye800CW; fifteen grade 1 adverse events occurred with cetuximab-IRDye800CW, and one grade 1 occurred with panitumumab-IRDye800CW. There were no significant differences in QTc prolongation between the two trials (p=0.8). Conclusions: Panitumumab-IRDye800CW and cetuximab-IRDye800CW have toxicity and pharmacodynamic profiles that match the parent compound, suggesting that other therapeutic antibodies may be repurposed as imaging agents with limited preclinical toxicology data.
Abstract 13731: The Association of High-Sensitivity Cardiac Troponin T and Natriuretic Peptide With Incident End-Stage Renal Disease: the Atherosclerosis Risk in Communities Study
Authors: Yuhree Kim, Kunihiro Matsushita, Yingying Sang, Morgan Grams, Hicham Skali, Amil M Shah, Ron C Hoogeveen, Scott D Solomon, Christie M Ballantyne, Josef Coresh
Journal: Circulation (2013)

Introduction: Although there are abundant data supporting kidney dysfunction as a predictor of cardiac disease, epidemiological data for cardiac dysfunction predating kidney dysfunction are sparse,...
Cholangioscopy and electrohydraulic lithotripsy in the management of fistulated pancreatic duct stones
Authors: George Goodchild, Sanjay Sivalokanathan, George Webster
Journal: Endoscopy (2018)

An 80-year-old man with a history of alcohol-induced chronic calcific pancreatitis presented with new pain and obstructive jaundice. The computed tomography (CT) scan confirmed features of chronic pancreatitis and showed a heavily calcified stone within the bile duct and associated dilatation ([Fig. 1]). Endoscopic retrograde cholangiopancreatography (ERCP) demonstrated dense calcified stones within the extrahepatic bile ducts ([Fig. 2]).