tbuckley/cabot-search huggingface dataset:
Retraction: Interleukin-12 Deficiency Is Permissive for Angiogenesis in UV Radiation-Induced Skin Tumors
Authors: Syed M. Meeran, Suchitra Katiyar, Craig A. Elmets, Santosh K. Katiyar
Journal: Cancer Research (2018)

This article (1) has been retracted at the request of the editors. Following a joint institutional investigation by the Birmingham VA Medical Center and the University of Alabama at Birmingham, the primary affiliations for several of the authors, it was determined that the images for both the wild-type and IL-12 knockout controls originated from the same source and are not from mice with different genotypes in Fig. 4. In addition, the same β-actin Western blot image was used to represent results from different experiments in Figs. 3D and 5B. The original research records related to the figures were not available during the review. Therefore, the institutions were not able to determine which of the published images are correct and recommended retraction; upon internal review, the editors agreed with this recommendation.A copy of this Retraction Notice was sent to the last known e-mail addresses for all four authors. One author (S. Katiyar) agreed to the retraction; two authors (S.M. Meeran and S.K. Katiyar) did not agree to the retraction; the remaining author (C.A. Elmets) did not respond.
Integration of palliative care consultation for patients with malignant bowel obstruction in gynecologic oncology: Qualitative approach to understand provider perspectives.
Authors: Claire Hoppenot, Julie Chor, Fay J. Hlubocky, Seiko Diane Yamada, Nita Karnik Lee
Journal: Journal of Clinical Oncology (2018)

116 Background: Gynecologic oncologists’ (GO) approaches to palliative care team (PCT) consultation for managing patients with malignant bowel obstruction (MBO) from recurrent gynecologic cancer remains unknown. Methods: GO practicing in a large metropolitan area underwent semi-structured interviews exploring their approaches to PCT involvement at the time of diagnosis of a MBO and factors leading to specific recommendations. Interviews were analyzed using theoretical and open coding qualitative analysis. Results: 15 GO completed interviews. They were in academic (93%), urban (67%) settings and at a range of timepoints in their career. GO expressed mixed feelings regarding PCT consultation for their patients with MBO. Many were comfortable managing symptoms (pain, nausea) and limited consultations to uncontrolled symptoms. Others involved PCT for ongoing support regardless of symptom severity. GO were less likely to involve PCT to help with goal-setting discussions. Many GO held a “the earlier the better” stance, preferring to involve PCT in the outpatient setting. At a high-risk decision-point, such as MBO, these physicians felt that PCT consultation was overdue. In this setting, most participants reserved PCT consultations only for patients who were not surgical candidates. Barriers to PCT consultation for women with MBO centered around GO concerns that involving another team fragments care. Participants feared involving PCT would complicate patients’ experiences by requiring additional appointments, suggesting potential abandonment from their GO, and including an additional, potentially conflicting, source of information. Many GO mentioned they chose gynecologic oncology for the continuity of care and leading role in a patient’s cancer care. Conclusions: Overall, GO expressed comfort involving PCT outside of critical decision-points, yet were reticent to involve PCT at the time of MBO due to concerns of requiring the patient to deal with another team. Early incorporation of the PCT through a standardized co-management system in a GO outpatient clinic may improve communication and reduce barriers to PCT involvement.
Determinants of responsiveness to herceptin in breast cancer cells.
Authors: Cynthia L. Gobbel, Rebecca K. Koziel, Kim E. Creek, Lucia Pirisi
Journal: Cancer Research (2004)

3506  The overall goal of our studies is to investigate the molecular basis of malignancy in breast cancer cells. Breast cancer is a devastating disease, which claims approximately 43,000 lives in the United States alone. About 25% of breast tumors overexpress ErbB2, a member of the epidermal growth factor receptor (EGFR) family, which is an independent predictor of poor prognosis. Herceptin, a monoclonal anti-ErbB2 antibody, is routinely used in the treatment of ErbB2-overexpressing metastatic breast cancer, both alone and in combination with various chemotherapeutic agents. However, approximately 50% of patients treated with Herceptin are unresponsive to treatment. The mechanism of action of Herceptin is not fully understood, nor are the reasons for treatment failure. Previous studies in our laboratory have identified an interaction between ErbB2 and two novel alternatively spliced variants of the transforming growth factor alpha (TGF-α) precursor, variants I (VaI) and II (VaII). Interestingly, in CHO cells expressing TGF-α VaII, phosphorylation of ErbB2 was observed in the absence of serum, suggesting that this interaction may lead to activation of ErbB2. Therefore, we investigated the ability of TGF-α VaII to modify the responsiveness of ErbB2-positive breast cancer cells to the growth inhibitory effects of Herceptin. The breast cancer cell lines SKBr3, MDA453, T47D, MCF7, MDA231, and MDA468 were characterized for their responsiveness to Herceptin by [3H]thymidine uptake, and for their levels of ErbB2, phospho-ErbB2, EGFR, ErbB3, and ErbB4 by western blot analysis. Additionally, the levels of TGF-α wild-type (WT) and VaII mRNA were determined by real-time RT/PCR. Interestingly, an inverse correlation was found between TGF-α WT and VaII mRNA levels and Herceptin sensitivity. When TGF-α WT, VaI, and VaII were overexpressed in MCF7 cells, which express low but detectable levels of ErbB2 and show a modest growth inhibition by Herceptin, overexpression of VaII, but not WT or VaI, reversed their growth response to Herceptin; in fact, the cells were growth stimulated by Herceptin. Immunofluorescence data indicate that exogenously expressed TGF-α VaII colocalizes with ErbB2 in MCF7 and SKBr3 cells. The ErbB2-overexpressing, Herceptin-sensitive breast cancer cell lines (SKBr3, MDA453 and T47D) either would not express, or would not tolerate stable overexpression of exogenous TGF-α WT or Variants. The results of these studies indicate that expression of TGF-α precursors may play a role in the responsiveness of breast cancer cells to the growth inhibitory effects of Herceptin. We are currently developing an inducible system for overexpression of TGF-α precursors in these cell lines. We will then investigate the effects of TGF-α WT and Variant precursors on growth inhibition by Herceptin, binding of Herceptin to ErbB2, and internalization and trafficking of ErbB2 in the above described cell lines.
Abstract 1: <i>Sprr2b</i> Drives Proliferation of Cardiac Fibroblasts by Relieving p53-mediated Cell Cycle Inhibition
Authors: Ryan M Burke, Janet K Lighthouse, Pearl J Quijada, Ronald Dirkx, Michael A Trembley, Eric M Small
Journal: Circulation Research (2017)

Pathological cardiac remodeling is initially a compensatory attempt to increase cardiac output, but ultimately leads to the development of fibrosis, a form of scarring that contributes to heart failure (HF). In contrast, physiological cardiac remodeling in response to exercise is not associated with the development of fibrosis and typically remains compensatory. Understanding how cardiac fibroblasts (CF), the primary source of extracellular matrix in the heart, respond to pathological and physiological cues might lead to novel approaches to limit the maladaptive effects of pathological cardiac remodeling. We performed RNA sequencing to define genes that are differentially regulated in CF during physiological (swimming) or pathological (pressure overload) remodeling. This study revealed that cardiac expression of the s mall pr oline r ich 2b ( Sprr2b) gene is restricted to CFs and is significantly elevated in disease and lost in exercise. We demonstrate that SPRR2B drives CF proliferation, but not myofibroblast differentiation, in response to pathological cues. SPRR2B facilitates an interaction between MDM2 and USP7, a nuclear deubiquitinase that leads to proteasomal degradation of p53. SPRR2B-USP7-MDM2 complex formation and p53 degradation is at least partially dependent upon phosphorylation of SPRR2B by Src-family NRTKs. SPRR2B thus relieves p53-mediated constraints on cell cycle progression in response to Src-dependent signaling, leading to CF accumulation. Importantly, SPRR2B expression is elevated in cardiac tissue from human HF patients relative to individuals without heart disease and positively correlates with a proliferative, activated gene expression profile in HF patient CF. Treatment of human HF fibroblasts with IGF-1/H 2 O 2 to mimic physiological cues significantly abrogated SPRR2B expression and increased expression of p53-dependent cell cycle checkpoint genes, which correlated with a less activated phenotype. Taken together, this study defines a unique tissue-specific role of Sprr2b in driving pathological CF cell cycle progression that may underlie the development of cardiac fibrosis.
Abstract 17008: Dipeptidyl peptidase-4 Inhibitor Ameliorates Stress-induced Glucose Metabolism Disorder and Prothrombotic State
Authors: Kyosuke Takeshita, Maimaiti Yisireyili, Toyoaki Murohara
Journal: Circulation (2015)

Introduction: Psychological stress evokes lipolytic release of free fatty acid (FFA) and low-grade inflammation in visceral adipose tissue, mediated by increased adipokine secretion, and contributes to glucose metabolism disorder and prothrombotic state via production of coagulation factors (plasminogen activation inhibitor-1 [PAI-1] and tissue factor [TF]) in white adipose tissue (WAT). Hypothesis: As accumulating evidence suggests anti-inflammatory potential of dipeptidyl peptidase-4 (DPP4) inhibitors, we investigated the effects of alogliptin on stress-induced adipose tissue inflammation, insulin resistance and prothrombotic state. Methods: Mice were subjected to 2-week intermittent restraint stress and orally treated with vehicle, 15 or 45 mg/kg/day alogliptin. Plasma lipids, expression of GLP-1, DPP4 activity, 8OHdG (an oxidant stress marker), monocyte/macrophage markers (CD11b, CD68, and F4/80), proinflammatory cytokines (monocyte chemoattractant protein-1, tumor necrosis factor-α, and interleukin-6), adiponectin, and coagulation factors (PAI-1 and TF) in blood and inguinal WAT was determined using immunohistochemistry, enzyme-linked immunosorbent assay, and RT-PCR, respectively. Glucose metabolism was assessed by glucose tolerance tests (GTTs) and insulin tolerance tests (ITT), and expression of insulin receptor substrate-1 (IRS-1) and glucose transporter 4 (GLUT4) in WAT. Results: The stress procedure increased FFA release, 8OHdG-positive cells and monocyte accumulation in WAT, proinflammatory cytokine, and reduced adiponectin and GLP-1, followed by DPP4 activation in plasma. The stress-induced adipose inflammation increased PAI-1 and TF, and worsened insulin sensitivity and decreased IRS-1 and GLUT4 in WAT. The alogliptin administration suppressed stress-induced FFA release, oxidant stress production, adipose inflammation, procoagulant state in a dose dependent manner, and restored glucose metabolism in GTT and ITT. Conclusions: The results indicate that alogliptin improves stress-induced prothrombotic state, and glucose metabolism disorder. Our results suggests that alogliptin exerts additive benefits for cardiovascular complication in diabetes patients with mental stress.
Tackling the primary care access challenge in South Asia
Authors: Amit Sengupta, Shehla Zaidi, T Sundararaman, Sharad Onta, Manuj C Weerasinghe
Journal: BMJ (2018)

Increased public financing for primary care and medical education as well as regulation of private services are vital to tackle the primary care crisis in South Asia, argue <b>Amit Sengupta and colleagues</b>
Abstract 17783: Improved Aortic Valve Area Calculation Using a Novel Biplane Echo Continuity Equation
Authors: Thorsten M Leucker, Edward P Shapiro
Journal: Circulation (2015)

The aim of this study was to improve the accuracy of transthoracic echo- cardiographic (TTE) assessment of the aortic valve area (AVA) in patients with aortic stenosis (AS). The traditional continuity equation (CE) for determining AVA requires a measurement of left ventricular outflow tract (LVOT) area, which is calculated from a linear LVOT dimension using the parasternal long axis view, assuming circular geometry. However, routine use of multidetector computed tomography (MDCT) in patients undergoing evaluation for transcatheter aortic valve replacement (TAVR) has shown that the LVOT is elliptical rather than round. Assumption of circular geometry may introduce inaccuracies into AVA assessment. A total of 61 patients (76 ± 11 years of age, 61% men) with isolated calcific AS (mean gradient 42 ± 9 mm Hg; ejection fraction 56 ± 11%) underwent Doppler TTE as part of pre TAVR or aortic valvuloplasty evaluation. AVA was calculated by TTE using two near- perpendicular planes (parasternal long axis and apical five chamber view) to evaluate the LVOT. A modified CE was used to calculate AVA (cm2) = (π((D1 x D2)/4)x LVOT VTI)/(AV VTI) in order to account for the elliptical rather than round shape of the LVOT. AVA measurements from the traditional and modified CE were compared to invasive AVA assessment. Biplane (Figure, Panel B+D) vs. traditional single plane (Panel A+C) TTE measurement of the LVOT yielded a significantly improved positive correlation between TTE and invasive AVA assessment (r2=0.861 vs. 0.296) and a markedly reduced mean error (0.07 cm2 vs. 0.18 cm2), p&lt;0.001. Utilizing the proposed modified continuity equation greatly improves the accuracy of TTE guided AVA measurements. This simple calculation can be performed using standard TTE without additional costly equipment (ie, biplane transducers), without additional echo views (ie, more sonographer time), and without the need to subject patients to further invasive or non- invasive testing (ie, TEE or MDCT).
Abstract 19868: A Novel Chest Compression Depth Estimation Algorithm Based on a Smartwatch for High-Quality Cardiopulmonary Resuscitation
Authors: Tsung-Chien Lu, Yi Chen, Te-Wei Ho, Yao-Ting Chang, Yi-Ting Lee, Yu-Siang Wang, Yen-Pin Chen, Chia-Ming Fu, Wen-Chu Chiang, Matthew Huei-Ming Ma, Cheng-Chung Fang, Feipei Lai, Anne M Turner
Journal: Circulation (2017)

Introduction: High-quality cardiopulmonary resuscitation (CPR) is a key factor to cardiac arrest survival. Accurate monitoring and real-time feedback are emphasized to improve CPR quality. The purp...
Sorafenib As Maintenance Therapy Post Allogeneic Stem Cell Transplantation for FLT3-ITD Positive AML: Results from the Randomized, Double-Blind, Placebo-Controlled Multicentre Sormain Trial
Authors: Andreas Burchert, Gesine Bug, Jürgen Finke, Matthias Stelljes, Christoph Rollig, Ralph Wäsch, Martin Bornhäuser, Tobias Berg, Fabian Lang, Gerhard Ehninger, Hubert Serve, Robert Zeiser, Eva-Maria Wagner, Nicolaus Kroeger, Christine Wolschke, Michael Schleuning, Ahmet Elmaagacli, Katharina S. Götze, Christoph Schmid, Edgar Jost, Dominik Wolf, Alexandra Böhm, Christian Thiede, Torsten Haferlach, Wolfgang Bethge, Susanne Harnisch, Michael Wittenberg, Susanne Rospleszcz, Andreas Neubauer, Markus Brugger, Konstantin Strauch, Carmen Schade-Brittinger, Stephan K Metzelder
Journal: Blood (2018)
Gallbladder Metastasis From Conjunctival Melanoma
Authors: Thibaut Cassou-Mounat, Marie Luporsi, Virginie Huchet, Nina Jehanno
Journal: Clinical Nuclear Medicine (2018)

Malignant conjunctival melanoma is a rare tumor. A 46-year-old woman with a history of locally recurrent left conjunctival melanoma was followed by F-FDG PET/CT. Four years after the local recurrence treated by orbital exenteration, the follow-up PET/CT scan showed an incidental intense FDG uptake mass infiltrating the gallbladder associated with a low uptake of an infracentimetric pulmonary nodule. The patient was completely asymptomatic with no sign of local recurrence. Laparoscopic cholecystectomy was performed, and histopathologic findings were consistent with gallbladder metastasis of melanoma. After almost 2 years of immunotherapy, the patient is still in complete response.
Evolution of efficacious pangenotypic hepatitis C virus therapies
Authors: Muhammad Usman Ashraf, Kanzal Iman, Muhammad Farhan Khalid, Hafiz Muhammad Salman, Talha Shafi, Momal Rafi, Nida Javaid, Rashid Hussain, Fayyaz Ahmad, Syed Shahzad‐Ul‐Hussan, Shaper Mirza, Muhammad Shafiq, Samia Afzal, Sadia Hamera, Saima Anwar, Romena Qazi, Muhammad Idrees, Sohail A. Qureshi, Safee Ullah Chaudhary
Journal: Medicinal Research Reviews (2018)

Hepatitis C compromises the quality of life of more than 350 million individuals worldwide. Over the last decade, therapeutic regimens for treating hepatitis C virus (HCV) infections have undergone rapid advancements. Initially, structure-based drug design was used to develop molecules that inhibit viral enzymes. Subsequently, establishment of cell-based replicon systems enabled investigations into various stages of HCV life cycle including its entry, replication, translation, and assembly, as well as role of host proteins. Collectively, these approaches have facilitated identification of important molecules that are deemed essential for HCV life cycle. The expanded set of putative virus and host-encoded targets has brought us one step closer to developing robust strategies for efficacious, pangenotypic, and well-tolerated medicines against HCV. Herein, we provide an overview of the development of various classes of virus and host-directed therapies that are currently in use along with others that are undergoing clinical evaluation.
Untreated Bleeds May Be Historically Under-Reported and More Prevalent in People with Hemophilia A with Inhibitors: An Examination of Bleed Data from a Prospective, Non-Interventional Study
Authors: Michael U. Callaghan, Elina Asikanius, Michaela Lehle, Johannes Oldenburg, Johnny Mahlangu, Marianne Uguen, Sammy Chebon, Rebecca Kruse-Jarres, Victor Jimenez-Yuste, Midori Shima, Peter Trask, Christine L. Kempton, Craig M. Kessler, Gallia G. Levy, Elena Santagostino
Journal: Blood (2018)
Evaluation of the effectiveness of a new medical device containing verbascoside, polyvinylpyrrolidone, and hyaluronic acid in prevention and treatment of mucositis in patients with cancer.
Authors: Olga Nigro
Journal: Journal of Clinical Oncology (2018)

206 Background: Mucosal injury is the consequence of biologic events coupled with the influence of the oral environment and microbiome. Oral mucositis is one of the most common toxicities of chemoradiation therapies. Incidence and severity varies by chemoradiation regimens, radiation fıelds, and tumor site. The influence of mucositis on quality of life is greater among patients than the medical literature would suggest. Lack of experience in evaluating treatment toxicities is a daily problem in cancer patients. The aim of this study was to assess the efficacy of verbascoside’s (mucosyte) oral solution on mucositis in cancer patients. Methods: Fourty-five patients with different grade mucositis treated with mucosyte (ranging from 1-2 to 6-7 rinses/day, according to the guidelines) were evaluated from October 2017 to June 2018. Patients were monitored every week until complete remission. Results: Of 45 patients enrolled, 5 had G1 oral mucositis at baseline, 21 had G2, 13 had G3 and 3 had G4. Three patients had G0 oral mucositis at baseline. Median age was 66.8 years. Six patients were treated with carboplatin/paclitaxel, and six with cisplatin/pemetrexed for non-small cell lung cancer; nine patients were treated with paclitaxel, six with adriamycin/cyclophosphamide, and two with eribulin for breast cancer; four patients were treated with FOLFOX for intestinal adenocarcinoma; three patients were treated with nab-paclitaxel/gemcitabine for pancreatic cancer; five patients were treated with cisplatin/cetuximab, and four with cisplatin/cetuximab plus radiotherapy for squamous-cell head and neck cancer. All patients reached complete remission in a median time of 14.9 days (10-24 days). Conclusions: Mucosyte treatment was able to rapidly shorten G3/4 oral mucositis to G1/2, and to never happen mucositis in G0 at baseline. Thus, we suggest that mucosyte can be effective both in prevention and treatment of mucositis.
AB0117 Association of vitamin d deficiency with crp/acpa positivity in algerian patients with rheumatoid arthritis
Authors: I. Allam, R. Djidjik
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Vitamin D (VD) is a steroid hormone belonging to the class of secosteroids with myriad immune functions and seems to be involved in the development and severity of rheumatoid arthritis (RA).<sup>1–3</sup> <h3>Objectives</h3> The aim of this study was to estimate the prevalence of vitamin D deficiency in patients with rheumatoid arthritis as compared to healthy controls and to analyse the association between levels of vitamin D and CRP(C-reactive protein)/ACPA (anti citrullinated protein antibodies) positivity. <h3>Methods</h3> Serum 25(OH)D levels were measured in 115 RA patients and 104 age- and gender-matched healthy controls using the chemiluminescent immunoassay method (CLIA). CRP (mg/dl) was measured by the nephelometric method and ACPA antibodies were evaluated using enzymatic linked immuno-assay (ELISA). <h3>Results</h3> There was no statistically significant difference between levels of 25(OH)D in RA (25.08±9.22 ng/ml) and healthy controls (15.62±5.34 ng/ml). The vitamin D deficiency (&lt;10 ng/ml) was found in 10% of RA patients, while 60% were insufficient (&lt;20 ng/ml). Low 25-OHD levels were negatively associated with CRP (23 ng/ml vs 29 ng/ml; p=0,023) and ACPA positivity (23 ng/ml vs 28 ng/ml; p=0, 03). <h3>Conclusions</h3> The 25(OH) D levels are inversely related to CRP and ACPA values in Algerian RA patients. <h3>References</h3> [1] Lee YH, Bae SC. Vitamin D level in rheumatoid arthritis and its correlation with the disease activity: a meta-analysis. Clin Exp Rheumatol. 2016Sep–Oct;34(5):827–833. [2] Bragazzi NL, Watad A, Neumann SG, et al.Vitamin D and rheumatoid arthritis: an ongoing mystery. Curr Opin Rheumatol2017Jul;29(4):378–388. [3] Ishikawa LLW, Colavite PM, Fraga-Silva TFC, et al. Vitamin D Deficiency and Rheumatoid Arthritis. Clin Rev Allergy Immunol2017Jun;52(3):373–388. <h3>Disclosure of Interest</h3> None declared