tbuckley/cabot-search huggingface dataset:
Insulin Resistance and Metabolic Syndrome in Young Men With Acne
Authors: Mohit Nagpal, Dipankar De, Sanjeev Handa, Arnab Pal, Naresh Sachdeva
Journal: JAMA Dermatology (2015)

Robust evidence of the association of insulin resistance and metabolic syndrome with acne in male patients is lacking.To assess the prevalence of metabolic syndrome and insulin resistance in male patients 20 years or older with acne.We performed a cross-sectional study in 100 male patients with acne and 100 age-matched male controls without acne from a dermatology outpatient department of a tertiary care institute. Postadolescent patients were recruited only to negate the effects of physiologic insulin resistance that are seen at the time of puberty and adolescence. Twenty-five patients were included in each of the 4 individual severity groups according to the Global Acne Grading System and were age matched to 100 male controls without acne.Clinical examination, Global Acne Rating System, National Cholesterol Education Programme Adult Treatment Panel III (NCEP-ATP III), and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR).Metabolic syndrome was diagnosed as per the criteria of the modified NCEP-ATP III. Insulin resistance was assessed by the HOMA-IR. A HOMA-IR value greater than 2.5 was arbitrarily considered as insulin resistance.Prevalence of insulin resistance was significantly higher in cases (22%) compared with controls (11%) (P = .03). The prevalence of metabolic syndrome was comparable between cases (17%) and controls (9%) (P = .09). Prevalence of insulin resistance and metabolic syndrome did not differ significantly among the acne severity groups.Postadolescent male patients with acne more commonly have insulin resistance. This resistance may be a stage of prediabetes, and the patients may develop hyperinsulinemia or type 2 diabetes in the future. These patients should be followed up for a prolonged time to determine whether they develop conditions associated with insulin resistance.
Cancer testis antigen expression in triple negative breast cancer: Candidate targets for cancer immunotherapy?
Authors: Wouter Hendrickx, Mariam Al-Muftah, Julie Decock
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Breast cancer is a major health concern in Qatar with a younger age at diagnosis and projections of 60% increase in new cases. Triple negative breast cancer (TNBC) is associated with advanced disease at diagnosis and poorer outcome, and can be subclassified into 6 gene-expression-
Circulating exosomes carrying an immunosuppressive cargo may interfere with adoptive cell therapies in leukemia
Authors: Michael Boyiadzis, Chang-Sook Hong, Theresa L Whiteside
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Adoptive immunotherapy, including transfer of activated NK cells, is currently under active investigation for patients with refractory and relapsed acute myeloid leukemia (AML). However, a highly immunosuppressive microenvironment sustained in part by tumor-derived exosomes,
Overall survival with sunitinib versus interferon (IFN)-alfa as first-line treatment of metastatic renal cell carcinoma (mRCC)
Authors: R. A. Figlin, T. E. Hutson, P. Tomczak, M. D. Michaelson, R. M. Bukowski, S. Négrier, X. Huang, S. T. Kim, I. Chen, R. J. Motzer
Journal: Journal of Clinical Oncology (2008)

5024 Background: In a randomized, phase III trial, sunitinib demonstrated statistically significant improvement in progression-free survival (PFS) and objective response rate (ORR) compared to IFN-alfa as first-line therapy in mRCC patients (pts) (P<0.001) [Motzer et al. NEJM 2007;356:115], establishing sunitinib as a new reference standard of care. At the time of last analysis, survival data were not mature. Median overall survival (OS) had not been reached in both treatment groups (HR=0.65; P=0.0219). Methods: Pts with mRCC were randomized 1:1 to receive sunitinib 50 mg orally once daily in 6-wk cycles (4 wks on treatment, 2 wks off) or IFN-alfa (9 MU subcutaneously thrice weekly). The primary endpoint was PFS. Secondary endpoints included ORR, safety and OS. For survival analysis, 390 events are required for a 2-sided, unstratified log-rank test with an overall 2-sided significance level of 0.05 and power of 0.85. Patients were followed for survival and post-study cancer treatment information was collected. The influence of baseline clinical features and previously identified prognostic factors on treatment effect will be analyzed with the use of a Cox proportional hazards model. Results: 750 pts were randomized to study treatment, 375 pts in each arm. Median duration of treatment was 11 mos (range: <1–39) for sunitinib vs 4 mos (range: <1–37) for IFN-alfa. 72 pts on sunitinib (including pts who crossed over from IFN-alfa) and 7 pts on IFN-alfa continue on the study. The updated ORR is 47% (95% CI: 42, 52) for sunitinib vs 12% (95% CI: 9, 16) for IFN-alfa (P<0.000001), including 11 complete responses for sunitinib and 4 for IFN-alfa. Median PFS remains the same as reported previously (11 mos vs 5 mos [P<0.000001]). The most common grade 3/4 treatment-related AEs for the sunitinib group are hypertension (12%), fatigue (11%), diarrhea and hand-foot syndrome (both 8%), and, for IFN-alfa, fatigue (13%) and anorexia (2%). No new unexpected grade 3/4 treatment-related AEs have been observed. Events are sufficient for final OS analysis. Conclusions: Sunitinib remains a reference standard for the first-line treatment of mRCC, with significantly superior efficacy over IFN-alfa. Final survival analysis will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Bayer, Genentech, Novartis, Pfizer, Wyeth Pfizer Bayer, Genentech, Novartis, Pfizer, Wyeth Bayer, Genentech, Pfizer, Wyeth
Abstract 19526: Pathological Vascular Remodeling in Pulmonary Hypertension: A Role for Perturbed Matrix Cross-Linking?
Authors: Alexander H Nave, Nikolaus Kneidinger, Grazyna Kwapiszewska, Werner Seeger, Rory E Morty
Journal: Circulation (2010)

Introduction: Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling and arterial stiffness. We hypothesize that excessive cross-linking of the vascular matrix, as a conseque...
P-062 Baseline neutrophil-lymphocyte ratio as a prognostic factor for patients with resectable gastric cancer undergoing adjuvant chemotherapy
Authors: M.M. Laterza, A. Petrillo, J. Ventriglia, B. Savastano, A. Diana, G. Tirino, E. Martinelli, M. Orditura, F. Ciardiello, F. de Vita
Journal: Annals of Oncology (2015)
Politics, medical journals, the medical profession and the Israel lobby
Authors: J. S. Yudkin, J. Leaning
Journal: BMJ (2015)

Criticism of the Israeli government does not necessarily equate with antisemitism 

In April, Reed Elsevier, publishers of the Lancet , received a complaint written by Professor Mark Pepys and signed by 396 physicians and scientists, including five Nobel Laureates.1 They protested that the Lancet was being used for political purposes and for “publication of deliberately false material which deepens polarization between Israelis and Palestinians.” 

The most recent example of what was termed this “political vendetta” was the July publication, during the latest Israeli assault on Gaza, of an “Open letter for the people in Gaza.”2 They wrote that the letter “contains false assertions and unverifiable dishonest ‘facts,’ many of them libellous,” and that its authors had failed to declare possible conflicts of interest. The complaint insisted that the July letter be retracted (disagreeing with the Lancet ombudsman’s decision3) and that it contravened the code of the Committee on Publication Ethics (disagreeing with a former chair of the committee4). It asked for the support of all scientists and clinicians “on whom they [Reed Elsevier] depend for their business,” adding “none of us is under any obligation to submit and review material for publication in their journals or to serve on their editorial or advisory boards.” 

An email chain soliciting support for this complaint was more explicit.5 In it Pepys accused the July letter of “viciously attacking Israel with blood libels echoing those used for a thousand years to …
Cooperative role of lymphotoxin β receptor and tumor necrosis factor receptor p55 in murine liver regeneration
Authors: Ursula R. Sorg, Kristina Behnke, Daniel Degrandi, Maria Reich, Verena Keitel, Diran Herebian, René Deenen, Marc Beyer, Joachim L. Schultze, Karl Köhrer, Helmut E. Gabbert, Ertan Mayatepek, Dieter Häussinger, Klaus Pfeffer
Journal: Journal of Hepatology (2015)
Impact of INT-0116 Trial on adjuvant treatment of gastric cancer
Authors: C. Gemici, A. Mayadagli, T. Salepci, F. Tugrul, C. Parlak, M. Gumus
Journal: Journal of Clinical Oncology (2004)

4253 Background: Gastric cancer has a bad prognosis. Even for patients who have undergone potentially curative resection, the rate of locoregional and distant recurrance is very high. Thus improvement of the survival in this disease relies on the development of effective adjuvant treatments. The most commonly applied adjuvant treatments after surgery are chemotherapy, radiotherapy and chemoradiotherapy which has gained popularity recently after INT-0116 study. Method: With an aim to determine which type of adjuvant treatment is applied most frequently and how INT-0116 study has changed this practice, we retrospectively analyzed the data on 289 resected gastric cancer patients referred to our center since 1998. Results: Adjuvant treatment is a common practice in our center. Most of the patients after surgical resection receive some form of adjuvant treatment. While most frequently delivered adjuvant treatment was chemotherapy until 2002, there is progressive decline in chemotherapy application with progressive increase in chemoradiotherapy application. This change in the adjuvant treatment approach is the result of INT-0116 study. Actually adjuvant chemoradiotherapy represents the standart of care in our center nowadays. Conclusions: Different adjuvant treatment approaches have been proposed and evaluated in clinical trials in an attempt to improve post-surgical results of gastric cancer. Chemotherapy is the most commonly studied approach with many randomized trials and two meta-analysis. Although the benefit from chemotherapy is small, most centers as ours accepted this small benefit to consider chemotherapy as the standart adjuvant treatment due to poor prognosis of this disease. However with the first results of the INT-0116 study, adjuvant chemoradiotherapy has gained popularity worldwide and replaced chemotherapy. This represents a major change in treatment of gastric cancer. No significant financial relationships to disclose.
A plethora of mechanisms in the HERG-related long QT syndrome Genetics meets electrophysiology
Authors: D Roden
Journal: Cardiovascular Research (1999)

See article by Nakajima et al. [15] (pages 283–293) in this issue. 

The ether a-go-go-related gene ( eag ) was cloned from a Drosophila mutant displaying a dance-like movement disorder on exposure to ether [1]. Homologs of eag have been cloned in mouse and rat, but not (at least yet) in human. However, a related gene, the human ether a-go-go-related gene ( HERG ) was cloned from a human hippocampal cDNA library in 1994 [2]. The function of HERG was initially obscure, but came to dramatic attention in early 1995 when Keating et al. [3] identified mutations in HERG linked to one form of the congenital long QT syndrome (LQT2), and shortly thereafter HERG was identified as the α-subunit encoding the rapid component of delayed rectifier ( I Kr) [4,5]. Thus, HERG rapidly became of interest not only to geneticists interested in LQTS, but also to cardiac physiologists and pharmacologists interested in studying I Kr and its block by drugs.

Studies from multiple laboratories have now made it clear that the vast majority of drugs associated with Torsades de Pointes are also I Kr blockers [6–14]. This finding, in turn, can go a long way in explaining the similarities between the congenital and drug-induced forms of the long QT syndrome, and may have important implications for drug development. Quite independent of the long QT syndrome, the availability of a cDNA encoding the structural subunit underlying I Kr has provided a crucial reagent for biophysicists studying the normal physiology, and the pathophysiology, of the channel. Therefore, mutagenesis of HERG is proceeding along two complementary lines: directed by physiology (often targeting residues or domains known to be important in other voltage-gated channels) or by clinical genetics, as new mutations are identified and characterized in patients with LQT2. The two approaches together are developing … 

* Corresponding author. Division of Clinical Pharmacology, 532 Medical Research Building I, Vanderbilt University School of Medicine, 23d Ave. South at Pierce Avenue, Nashville, TN 37232-6602, USA. Tel.: +1-615-322-0067; fax: +1-615-343-4522 dan.roden{at}mcmail.vanderbilt.edu
<i>Le Discret (The Silence)</i>
Authors: Carrie A. Butt
Journal: JAMA (2015)

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Pretreatment of tumor cells with an aromatase inhibitor increases sensitivity to human monocyte-mediated, antibody-dependent cellular cytotoxicity
Authors: Donald P. Braun, Keith A. Crist, Fehr Shaheen, Edgar D. Staren, Joanne Parker
Journal: Cancer Research (2005)

5312   Recent results from a Phase III clinical trial of the breast cancer vaccine, Theratope®, which contains the carbohydrate determinant, STn, revealed that vaccinated patients treated concomitantly with hormone therapy survived significantly longer than patients treated with hormone therapy + a control vaccine lacking the STn epitope. The objective of this study was to investigate mechanisms to explain the apparent collaboration between anti-hormone treatment and vaccination observed in vivo in patients. Human peripheral blood mononuclear cells (PBMC) were activated in vitro with gamma interferon + lipopolysaccharide (IFN/LPS) and tested for the capacity of the monocyte (PBM) and lymphocyte (PBL) fractions to mediate cytolysis of STn-positive tumor cell lines in the presence and absence of monoclonal anti-STn antibodies (STn mAb). OvCar3 cells (ER+/STn+) cultured in medium were sensitive to lysis by activated PBM from normal donors (mean % cytolysis +/− SD = 54.6+/−11%); this level of cytolysis was not enhanced by treatment of the target cells with STn mAb (55.0 +/− 12%, n.s). OvCar3 cells treated with an I:C 50 concentration of the aromatase inhibitor (AI), formestane, exhibited decreased sensitivity to PBM-mediated cytolysis in the absence of STn mAb (44.8 +/− 12%, p=0.07 compared to media-cultured cells) but significantly increased sensitivity to cytolysis in the presence of STn mAb (64.8 +/− 8%; p=0.003 compared to formestane-treated cells in the absence of STn mAb and p=0.02 compared to media-cultured cells in the presence of STn mAb). The additive effects of formestane pretreatment and STn mAb treatment were not attributable to increased binding of STn mAbs as measured in cell-based ELISA or to Ab-mediated tumor cell cytostasis as measured in MTT assays. Additional experiements with MCF7 cells (ER+/STn-) and DU4475 cells (ER-/STn+) revealed that collaboration between AI pretreament and PBM-mediated ADCC appeared to require both estrogen sensitivity and STn positivity on the part of the target tumor cells. Although tumor cells were also sensitive to in vitro cytolysis by PBL from the same donors (mean % cytolysis +/− SD = 31.9 +/−4%) neither STn mAb treatment alone (30.2 +/− 4%); formestane pretreatment alone (28.8 +/− 3%); nor formestane pretreatment + STn mAb treatment (26.3 +/− 8%) significantly affected the level of tumor cytolysis. These results demonstrate that tumor cells which survive treatment with an AI exhibit increased sensitivity to human monocyte-mediated, antibody dependent cellular cytotoxicity. The capacity of an AI to “sensitize” tumor cells to this form of anti-tumor immunity represents a heretofore, undescribed mechanism whereby a hormone-based cytostatic/cytotoxic treatment may collaborate with antigen-specific tumor immunity to produce improved tumor control in vivo in patients.
Antidepressant augmentation with metyrapone for treatment-resistant depression (the ADD study): a double-blind, randomised, placebo-controlled trial
Authors: R Hamish McAllister-Williams, Ian M Anderson, Andreas Finkelmeyer, Peter Gallagher, Heinz C R Grunze, Peter M Haddad, Tom Hughes, Adrian J Lloyd, Chrysovalanto Mamasoula, Elaine McColl, Simon Pearce, Najma Siddiqi, Baxi N P Sinha, Nick Steen, June Wainwright, Fiona H Winter, I Nicol Ferrier, Stuart Watson
Journal: The Lancet Psychiatry (2015)
Outcome of surgery versus radiotherapy after induction treatment in patients with N2 disease: systematic review and meta-analysis of randomised trials
Authors: P J McElnay, A Choong, E Jordan, F Song, E Lim
Journal: Thorax (2015)

Objective Chemoradiotherapy is often considered the ‘standard of care’ for patients with N2 disease. The aim was to evaluate survival outcomes of patients with N2 disease in multimodality trials of chemotherapy, radiotherapy and surgery. Methods Systematic review and meta-analyses (random and fixed effects) were performed. Searches of Medline and Embase (1980–2013) were conducted. Abstracts from thoracic scientific meetings were searched. Reference lists of all relevant studies were reviewed. All studies of patients with N2 disease who received induction chemotherapy or chemoradiotherapy and randomised to surgery or radiotherapy were included. No language restrictions were imposed. The main outcome was overall survival. Results 805 publications were identified. 519 and 281 were excluded because they were not primary results from randomised trials (or did not include N2 disease) or did not compare surgery with radiotherapy, respectively. The final six trials consisted of 868 patients. In four trials, patients received induction chemotherapy and in two trials patients received induction chemoradiotherapy. The HR comparing patients randomised to surgery after chemotherapy was 1.01 (95% CI 0.82 to 1.23; p=0.954) whereas for patients randomised to surgery after chemoradiotherapy was 0.87 (0.74 to 1.02; p=0.078). The overall HR of all pooled trials was 0.92 (0.81 to 1.04; p=0.179). Conclusions In trials where patients received surgery as part of bimodality (with chemotherapy) or trimodality (with chemoradiotherapy) treatment, overall survival was not significantly better than radiotherapy (with chemotherapy) or combination chemoradiotherapy alone.
The Human Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF ) Receptor Exists as a Preformed Receptor Complex That Can Be Activated by GM-CSF, Interleukin-3, or Interleukin-5
Authors: Joanna M. Woodcock, Barbara J. McClure, Frank C. Stomski, Michael J. Elliott, Christopher J. Bagley, Angel F. Lopez
Journal: Blood (1997)
Building Momentum: Taking on the Real “Issues” of <i>Diabetes Care</i>!
Authors: William T. Cefalu, Andrew J.M. Boulton, William V. Tamborlane, Robert G. Moses, Derek LeRoith, Eddie L. Greene, Frank B. Hu, George Bakris, Judith Wylie-Rosett, Julio Rosenstock, Katie Weinger, Lawrence Blonde, Mary de Groot, Matthew C. Riddle, Sherita Hill Golden, Stephen S. Rich, David D’Alessio, Lyn Reynolds
Journal: Diabetes Care (2015)

As the saying goes, time flies when you are having fun! So, our editorial team was surprised to find that with this issue of Diabetes Care we are celebrating our fourth year guiding the scientific aspects of Diabetes Care . It seems like just yesterday that we were introducing the team and our vision for the direction of the journal. We saw immediately that we had “issues” to address—we could easily fail to keep pace with the rapid advances in our field unless we introduced changes in our format and tactics. By this time you are very familiar with many of the changes we have put in place as we have been diligent in updating you in both the July and January issues (1,2). Thus, with this commentary, we will not review details previously provided. We will, however, focus on two initiatives that continue to grow and flourish and have exceeded our expectations. We are referring to the Diabetes Care Symposia that we coordinate and our special monthly thematic issues.

Our Diabetes Care Symposium, held each year during the American Diabetes Association’s (ADA’s) Scientific Sessions, has become our editorial team’s signature event. In June 2015, we held our fourth annual symposium, which consisted of two 1-h sessions and a selected overarching theme. The first segment—in a format used for the past 2 years—was entitled “Best of Diabetes Care .” This provided brief overviews of several articles felt by the associate editors to be some of the most noteworthy original research reports published in Diabetes Care during the past year, and it has received rave reviews. The second segment of this year’s program had presentations from four selected original …