tbuckley/cabot-search huggingface dataset:
Photodynamic therapy is more effective than imiquimod for actinic keratosis in organ transplant recipients: a randomized intraindividual controlled trial
Authors: K. Togsverd-Bo, C. Halldin, C. Sandberg, H. Gonzalez, A.M. Wennberg, S.S. Sørensen, H.C. Wulf, M. Hædersdal
Journal: British Journal of Dermatology (2017)

Actinic keratoses (AKs) in solid organ transplant recipients (OTRs) are difficult-to-treat premalignancies and comparison of topical therapies is therefore warranted.In an intraindividual study to compare the efficacy and safety of field treatment with methyl aminolaevulinate photodynamic therapy (MAL-PDT) and imiquimod (IMIQ) for AKs in OTRs.OTRs (n = 35) with 572 AKs (grade I-III) in two similar areas on the face, scalp, dorsal hands or forearms were included. All patients received one MAL-PDT and one IMIQ session (three applications per week for 4 weeks) in each study area according to randomization. Treatments were repeated after 2 months (IMIQ) and 3 months (PDT) in skin with incomplete AK response. Outcome measures were complete lesion response (CR), skin reactions, laboratory results and treatment preference.The majority of study areas received two treatment sessions (PDT n = 25 patients; IMIQ n = 29 patients). At 3 months after two treatments, skin treated with PDT achieved a higher rate of CR (AK I-III median 78%; range 50-100) compared with IMIQ-treated skin areas (median 61%, range 33-100; P < 0·001). Fewer emergent AKs were seen in PDT-treated skin vs. IMIQ-treated skin (0·7 vs. 1·5 AKs, P = 0·04). Patients developed more intense inflammatory skin reactions following PDT, which resolved more rapidly compared with IMIQ (median 10 days vs. 18 days, P < 0·01). Patient preference (P = 0·47) and cosmesis (P > 0·30) were similar for PDT and IMIQ.Compared with IMIQ, PDT treatment obtained a higher rate of AK clearance at 3-month follow-up and achieved shorter-lasting, but more intense, short-term skin reactions.
Impact of cytogenetic abnormalities in adults with Ph-negative B-cell precursor acute lymphoblastic leukemia
Authors: Marina Lafage-Pochitaloff, Laurence Baranger, Mathilde Hunault, Wendy Cuccuini, Christine Lefebvre, Audrey Bidet, Isabelle Tigaud, Virginie Eclache, Eric Delabesse, Chrystèle Bilhou-Nabéra, Christine Terré, Elise Chapiro, Nathalie Gachard, Marie-Joelle Mozziconacci, Geneviève Ameye, Sarah Porter, Nathalie Grardel, Marie C. Béné, Yves Chalandon, Carlos Graux, Françoise Huguet, Véronique Lhéritier, Norbert Ifrah, Hervé Dombret
Journal: Blood (2017)
プロモーター:プロモーターの型は集団によって多様であり,プロモーターの進化や発現ノイズに影響を及ぼす
Authors: Schor Ignacio E, Degner Jacob F, Harnett Dermot, Cannavo Enrico, Garfield David A, Furlong Eileen E M, Casale Francesco P, Birney Ewan, Stegle Oliver, Shim Heejung, Stephens Matthew
Journal: Nature Genetics (2017)
Patient-reported outcomes from a phase 3 study of baricitinib versus placebo or adalimumab in rheumatoid arthritis: secondary analyses from the RA-BEAM study
Authors: Edward C Keystone, Peter C Taylor, Yoshiya Tanaka, Carol Gaich, Amy M DeLozier, Anna Dudek, Jorge Velasco Zamora, Jose Arturo Covarrubias Cobos, Terence Rooney, Stephanie de Bono, Vipin Arora, Bruno Linetzky, Michael E Weinblatt
Journal: Annals of the Rheumatic Diseases (2017)

To assess the effect of baricitinib on patient-reported outcomes (PROs) in patients with active rheumatoid arthritis and an inadequate response to methotrexate (MTX).In this double-blind phase 3 study, patients were randomised 3:3:2 to placebo (n=488), baricitinib 4 mg once daily (n=487), or adalimumab 40 mg biweekly (n=330) with background MTX. PROs included the SF-36, EuroQol 5-D (EQ-5D) index scores and visual analogue scale, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient's Global Assessment of Disease Activity (PtGA), patient's assessment of pain and Work Productivity and Activity Impairment Questionnaire-Rheumatoid Arthritis (WPAI-RA), and measures collected in electronic patient daily diaries: duration and severity of morning joint stiffness (MJS), Worst Ttiredness and Worst Joint Pain. The primary study endpoint was at week 12. Treatment comparisons were assessed with logistic regression for categorical measures or analysis of covariance for continuous variables.Compared with placebo and adalimumab, baricitinib showed statistically significant improvements (p≤0.05) in HAQ-DI, PtGA, pain, FACIT-F, SF-36 physical component score, EQ-5D index scores and WPAI-RA daily activity at week 12. Improvements were maintained for measures assessed to week 52. Statistically significant improvement in patient diary measures (MJS duration and severity), worst tiredness and worst joint pain were observed for baricitinib versus placebo and adalimumab at week 12 (p≤0.05).Baricitinib provided significantly greater improvement in most PROs compared with placebo and adalimumab, including physical function MJS, pain, fatigue and quality of life. Improvement was maintained to the end of the study (week 52).NCT01710358.
Lenalidomide (LEN) maintenance (MNTC) after high-dose melphalan and autologous stem cell transplant (ASCT) in multiple myeloma (MM): A meta-analysis (MA) of overall survival (OS).
Authors: Michel Attal, Antonio Palumbo, Sarah A. Holstein, Valerie Lauwers-Cances, Maria Teresa Petrucci, Paul G. Richardson, Cyrille Hulin, Patrizia Tosi, Kenneth Carl Anderson, Denis Caillot, Valeria Magarotto, Philippe Moreau, Gerald Marit, Zhinuan Yu, Philip L. McCarthy
Journal: Journal of Clinical Oncology (2016)

8001 Background: Several studies demonstrate that LEN MNTC post ASCT reduces the risk of disease progression or death in patients (pts) with MM by ≈ 50% (Attal NEJM 2012; McCarthy NEJM 2012; Palumbo NEJM 2014). However, these studies were not powered for OS. To assess the effect of LEN MNTC post ASCT on OS, an MA was conducted. Methods: A prospectively planned MA assessed the OS of LEN vs placebo/no MNTC (control; CTL) after ASCT. A search identified 17 randomized controlled trials (RCTs) using LEN post ASCT. 3 RCTs (IFM 2005-02, CALGB 100104 [Alliance], GIMEMA RV-209) met prespecified inclusion criteria (had pt-level data, a CTL arm, and achieved database lock for primary efficacy analysis of NDMM pts receiving LEN post ASCT). A March 2015 cutoff of the 3 RCTs enabled sufficient OS events to test treatment effect (HR = 0.78). Results: In the 3 RCTs, 1209 pts were randomized from 2005 to 2009 to receive LEN (n = 605) 10 mg/day on days 1-21/28 (GIMEMA) or 1-28/28 (IFM and CALGB) or CTL (n = 604). With a median follow-up of 6.6 yrs, 491 pts (41%) had died. Baseline characteristics were generally balanced in the pooled data. After induction and single (82%) or tandem (18%) ASCT, 55% of pts achieved a complete response (CR) or very good partial response (VGPR). Median OS for LEN vs CTL was not reached vs 86 mos (HR = 0.74; 95% CI, 0.62-0.89; log-rank P = .001), and 5-, 6-, and 7-yr OS were longer in LEN vs CTL group (71% vs 66%, 65% vs 58%, and 62% vs 50%, respectively). Fisher's combination test confirmed the significant OS benefit of the MA (P = .001). Pts who achieved ≤ PR post ASCT benefited from LEN (HR = 0.86; 95% CI, 0.65-1.15) as well as pts with CR/VGPR (HR = 0.70; 95% CI, 0.54-0.90). OS benefit was generally consistent across subgroups. Heterogeneity test showed significant difference across trials (P = .047). The potential impact of baseline/disease characteristics, as well as 2nd-line therapy (IFM and CALGB), on OS will be explored and presented. Second primary malignancy data will be presented. Conclusions: This large MA demonstrates that LEN MNTC significantly prolonged OS vs CTL post ASCT, including in pts who achieved CR, demonstrating benefit in pts in all response categories. Clinical trial information: NCT00430365; NCT00114101; NCT00551928.
The Suicide Fusion Gene YCD-YUPRT Induces High and Specifi c Cytotoxicity in Small Cell Lung Cancer Cell Lines and Tumor Growth Delay in Xenografts When Regulated from a Cancer-Specific Promoter
Authors: Camilla L. Christensen, Torben Gjetting, Thomas T. Poulsen, Hans S. Poulsen
Journal: Molecular Therapy (2009)
MET Exon 14 Alterations and New Resistance Mutations to Tyrosine Kinase Inhibitors: Risk of Inadequate Detection with Current Amplicon-Based NGS Panels
Authors: Brigitte Poirot, Ludovic Doucet, Shirine Benhenda, Jérôme Champ, Véronique Meignin, Jacqueline Lehmann-Che
Journal: Journal of Thoracic Oncology (2017)
Nonclinical toxicities associated with enzastaurin, a potent and specific inhibitor of protein kinase C (PKC), in dogs
Authors: Noel Horton, Rachel Reams, Gregory Ruppert
Journal: Cancer Research (2007)

266   Enzastaurin is being developed as a therapy in solid malignant tumors, alone or in combination with chemotherapy or radiation. Enzastaurin, an oral, targeted multi-kinase inhibitor, suppresses signaling through PKCs and the PI3K/AKT pathway to induce tumor cell apoptosis, reduce proliferation, and suppress tumor-induced angiogenesis. Enzastaurin has been studied in dogs in repeat-dose toxicity studies of up to 6 months duration. Enzastaurin-related effects identified in dogs include ocular cataracts and hepatobiliary toxicity in a 6-month study and prolongation of the QT interval in a 1-month study.  In a 6 month repeat dose study, non-reversible bilateral lenticular cataracts, identified following 13 weeks of daily oral dosing, were noted in dogs given 200/100 mg/kg. These dogs were orally administered 200 mg/kg daily for 24 days. Due to anorexia and body weight loss, dosing for this group was suspended, the dose was reduced to 100 mg/kg, and dosing was resumed on Day 33. The cataracts were first noted in the posterior capsular region, and, in some animals, progressed over the course of the study to the cortical and nuclear regions of the lens. By the end of the study, cataracts were observed in 5 of 7 males and 6 of 8 females given 200/100 mg/kg.  Hepatobiliary toxicity was noted after 4 weeks of dosing in dogs given 200 mg/kg and was characterized by increased aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma glutamyltransferase. The effects on liver enzyme activities for most of the high-dose dogs were partially to completely reversed following the reduction of the dose to 100 mg/kg. Important histomorphologic changes in the liver included chronic cholangiohepatitis. Hepatobiliary pigment, randomly distributed inflammation, and/or minimal biliary hyperplasia were also noted in this dose group.  At the end of a 1-month repeat dose study, prolongation of the QT interval (the time from the onset of ventricular depolarization [the Q wave] to completion of repolarization [the end of the T wave]) and of the QTc interval (QT interval corrected for heart rate) was noted at 60 mg/kg (the highest dose administered in this study). This finding was not replicated in dogs at higher administered doses (up to and including 200 mg/kg) and higher maximum plasma concentrations in the 6-month repeat-dose toxicity study.  In summary, toxicologically important findings in dogs were limited to irreversible hepatobiliary toxicity and cataracts in dogs given 200/100 mg enzastaurin/kg in a 6-month study and QT/QTc prolongation in dogs given 60 mg enzastaurin/kg in a 1-month study.
Zika, Chikungunya, and Other Emerging Vector-Borne Viral Diseases
Authors: Scott C. Weaver, Caroline Charlier, Nikos Vasilakis, Marc Lecuit
Journal: Annual Review of Medicine (2017)

Arthropod-borne viruses (arboviruses) have a long history of emerging to infect humans, but during recent decades, they have been spreading more widely and affecting larger populations. This is due to several factors, including increased air travel and uncontrolled mosquito vector populations. Emergence can involve simple spillover from enzootic (wildlife) cycles, as in the case of West Nile virus accompanying geographic expansion into the Americas; secondary amplification in domesticated animals, as seen with Japanese encephalitis, Venezuelan equine encephalitis, and Rift Valley fever viruses; and urbanization, in which humans become the amplification hosts and peridomestic mosquitoes, mainly Aedes aegypti, mediate human-to-human transmission. Dengue, yellow fever, chikungunya, and Zika viruses have undergone such urban emergence. We focus mainly on the latter two, which are recent arrivals in the Western Hemisphere. We also discuss a few other viruses with the potential to emerge through all of these mechanisms.
Intérêt et limites de la fonction algorythmique de repérage de la présence de lésions hémorragiques (SBI) au cours de l’examen de l’intestin grêle par vidéocapsule M2A
Authors: PN D’Haluin, G Gay, B Filoche, JC Saurin, MG Lapalus, S Sacher-Huvelin, E Ben Soussan, D Heresbach
Journal: Endoscopy (2004)

Introduction: L’exploration des hémorragies digestives obscures, occultes (HOO) ou patentes (HOP) repose actuellement sur l’examen endoscopique de l’intestin grêle par vidéocapsule apportant un gain diagnostique de l’ordre de 40% par rapport à l’entéroscopie poussée. Afin de proposer une aide au diagnostic, le logiciel de lecture des examens par vidéocapsule M2A a été doté d’un système de détection des signes rouges ou SBI (Suspected Blood Indicator) utilisant la longueur d’onde spécifique du sang frais. L'objectif de notre enquête était d’évaluer l’intérêt du système SBI dans le cadre des HOO et HOP de l’intestin grêle. Patients et Méthodes: Il s’agit d’une enquête rétrospective multi centrique (janvier – août 2003) d’utilisation du système SBI lors de l’exploration par vidéocapsule. La lecture des examens était réalisée par un opérateur dans chaque centre et les lésions visualisées du pylore à la valvule iléo caecale ont été classées en fonction de leur imputabilité (P0 nulle, P1 incertaine et P2 certaine) puis le nombre de traits rouges visualisés par le système SBI a été comptabilisé. L’analyse a été réalisée par patient puis par trait rouge en les classant en Vrai Positif (trait rouge en regard de lésions P1 ou P2 visualisées par l’opérateur), Vrai Négatif (absence de trait rouge et absence de lésion ou lésion P0 visualisée par l’opérateur), Faux Positif (trait rouge sans lésion P1 ou P2 visualisée par l’opérateur en regard de traits même s’il existe une lésion P1 ou P2 sur l’intestin grêle à distance du repérage par le SBI) et Faux Négatif (absence de trait rouge en regard de lésions P1 ou P2 visualisées par l’opérateur). Résultats: 176 patients ont été explorés pour HOO (n = 130) ou HOP (n = 46); 18 patients ont été exclus en raison d’une cause gastrique (n = 14) ou colique (n = 4) (identifiée par le SBI respectivement dans 5/14 et 3/4 cas). Parmi les 158 patients inclus, 65 patients présentaient des lésions P1 (n = 14) et/ou P2 (n = 51) de l’intestin grêle et 93 patients pas de lésion (n = 64) ou des lésions P0 (n = 29). Le système SBI a indiqué 217 traits rouges: 161 traits correspondaient à des lésions P2 ou P1 et 56 à des lésions P0 ou à l’absence de lésion. Le système SBI avait une Sensibilité, une Spécificité, une Valeur Prédictive Positive et une Valeur Prédictive Négative exprimées par patient, respectivement de 44,6%, 78,5%, 59,2% et 67,0% pour le diagnostic de lésions P1 et/ou P2 alors que la sensibilité et la Valeur Prédictive Positive étaient respectivement de 77,0% et 74,2% pour la présence d’une lésion P1 et/ou P2 en regard d’un trait rouge. Conclusion: Le système SBI ne permet pas de s’affranchir d’une analyse visuelle pour le diagnostic de lésions de l’intestin grêle à l’origine des HOO et HOP.
SAT0004 New autoantigen (JKTBP) part of stress granules closes the sensitivity gap in rheumatoid arthritis
Authors: B Marklein, M Jenning, K Muenzer, G Burmester, K Skriner
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis triggers the formation of prion-like stress granules. To investigate which members of the heterogeneous nuclear ribonucleoprotein (hnRNP)-family, components of functionally important subcellular particles are targeted by autoantibodies from RA and other systemic rheumatic diseases. <h3>Methods</h3> Using a protein macroarray we identified JKTBP in humans and animal models of inflammatory rheumatic diseases. Bacterially expressed recombinant JKDBP proteins were used to confirm the obtained data. Epitope, TLR7/9 and MyD88 dependency was determined by ELISA. JKTBP expression in cultivated cells and synovial tissue was analysed by indirect immunofluorescence, immunoblot and immunohistochemistry. <h3>Results</h3> Anti-JKTBP autoantibodies were detected in 46% of the patients with systemic lupus erythematosus (n=103), in 20–30% of the patients with rheumatoid arthritis (n=286), in 10% of the patients with mixed connective tissue disease (n=20) or spondyloathropathy (n=20), and in &lt;10% of patients with other autoimmune disorders (n=382). Sera positive to JKTBP as well as hnRNP-B1, revealed nearly two thirds of the RF IgM/ CCP2-seronegative patients as early RA patients. Combining sensitivities to all autoantigens tested (JKTBP, AUF1, hnRNP-B1), it was possible to identify 92% of the early RA patients (n=91). In the MRL/lpr mouse model of SLE, mice deficient of MyD88 or TLR7/9 lacked anti-JKTBP autoantibodies, whereas mice deficient of SIGIRR/TIR8 showed enhanced anti-JKTBP autoantibody production. These results show that autoantibody generation against JKTBP, AUF1, hnRNP-B1 is dependent on TLR 7 and TLR9 like rheumatoid factor different to TLR 7 dependent generation of snRNPs. For all tested autoantigens either their titter or generation are dependent on the activation of innate immunity genes MyD88 and SIGIRR/TIR8 gene. In localization, experiments anti-JKTBP autoantibodies specifically stained stress granules (SG) in the cytoplasm. Immunohistochemical studies revealed JKTBP to be highly expressed in SG in the cytoplasm of RA synovial tissue different from OA and normal control tissue <h3>Conclusions</h3> These data identify SG as targeted particle in RA and JKTBP as a novel autoantigen in RA, SLE patients and mouse models of inflammatory rheumatic diseases. In combination with the hnRNPs AUF1 and hnRNP-B1, JKTBP autoantibodies close the sensitivity gap in RA left by rheumatoid factor and anti-CCP2 antibodies. <h3>Disclosure of Interest</h3> None declared
Abstract 10868: Prognostic Value of Fragmented QRS Localization for Myocardial Ischemia and Left Ventricular Dyssynchrony: Analysis Using Semiconductor Single Photon Emission Computed Tomography
Authors: Masato Shimizu, Hiroyuki Fujii, Noriyoshi Yamawake, Mitsuhiro Nishizaki
Journal: Circulation (2015)

Introduction: Fragmented QRS (fQRS) in 12-lead electrocardiography is reported to be a predictor of cardiac prognosis in ischemic heart disease. In contrast, certain studies have reported that fQRS is associated with cardiac resynchronization therapy response. However, few studies have evaluated the diagnostic performance of local fQRS using semiconductor single photon emission computed tomography (SPECT). Hypothesis: fQRS is a powerful indicator of anterior myocardial ischemia and left ventricular (LV) dyssynchrony. Methods: A total of 740 consecutive sinus rhythm patients with various cardiac diseases underwent SPECT with adenosine stress. The local fQRS was classified into I/aVL/V5-6 (lateral), II/III/aVF (inferior), and V1-4 (anterior). Cases with wide QRS (&gt;120ms), obvious right bundle branch block, and where fQRS existed in multi-classes were excluded. A 17-segment model of myocardial perfusion SPECT was divided into 3 areas: anterior, inferior, and lateral. Each summed score at rest (SRS), under stress (SSS), and the difference (SDS) was calculated. Results: fQRS was present in 82 cases (lateral, 13; anterior, 15; inferior, 54) and analysis of variance showed that anterior SSS was significantly higher in anterior fQRS cases (p=0.012). Histogram bandwidth of LV contraction onset - a known dyssynchrony parameter - was significantly higher in lateral fQRS cases (p135 degrees and SD&gt;43 degree, lateral fQRS had a high OR (7.91) with significant 95%CI (2.32-27.0) for indicating the condition. Conclusions: fQRS in anterior leads is a significant indicator of anterior wall ischemia; and fQRS in lateral leads is a significant indicator of LV dyssynchrony.
CATASTROPHIC INJURY INCIDENCE RATES IN SOUTH AFRICAN RUGBY UNION: ARE THERE REGIONAL DIFFERENCES?
Authors: Marelise Badenhorst, Evert Verhagen, Willem van Mechelen, Mike Lambert, Wayne Viljoen, Clint Readhead, Gail Baerecke, James Brown
Journal: British Journal of Sports Medicine (2017)

Background South Africa has 14 Provincial Rugby regions ('Unions'). Although rugby-related catastrophic injuries have been reported at 2.0 per 100 000 players per year, the comparative risk between each of these SA Unions has not yet been quantified. Understanding the difference in injury risk between Unions is important for potential intervention modifications. Objective The objective of this study was to compare the catastrophic injury incidence rates between the 14 SA Unions. Design A prospective, population-based study was conducted across all SA Unions between 2008–2014. Setting The number of verified players (males and females; under-seven age group to adult; amateur and professional) in each Union was obtained from SA Rugby's 2013 Census. Patients (or Participants) Catastrophic injuries were analysed using BokSmart's serious injury database. Interventions (or Assessment of Risk Factors) Union-specific injury incidence rates with 95% Confidence Intervals were calculated. Catastrophic injuries (Acute Spinal Cord Injuries (ASCI) and Traumatic Brain Injuries (TBI)) within Unions were compared statistically using a Poisson regression with Incidence Rate Ratios (IRR) and a 95% level of confidence (p&lt;0.05). Results Catastrophic injury incidence rates per Union ranged from 1.8 per 100 000 players (95% CI: 0.0 to 6.5) to 7.9 (95%CI: 0.0 to 28.5). The Union with the highest incidence rate of permanent outcome ASCIs was reported at 7.1 per 100 000 players (95% CI: 0.0 to 17.6). Compared to this Union, five (n=5/14, 36%) of the Unions had significantly lower injury incidence rates of ASCI. Conclusions Regional differences in catastrophic injury incidence rates exist in SA and interventions should be tailored accordingly. Future studies should investigate the underlying reasons contributing to these regional differences.
Patient Consent: Defining Control of Genetic Information
Authors: Susan Jenks
Journal: JNCI Journal of the National Cancer Institute (2017)

month and their diabetes drug the next month, "which of course doesn't work and creates crises and emergencies and results in hospital admissions.It's heartbreaking."The oncologists and researchers heading up Vi3C have been involved in other efforts to increase value in cancer care.Lichter, for example, served as CEO of ASCO from 2006 to 2016.During that time, ASCO established a Value in Cancer Care Task Force, published a value framework (doi:10.1200/JCO.2015.61.6706), and encouraged oncologists to discuss cost of care with their patients.Vi3C received initial backing from the Laura and John Arnold Foundation.Hortobagyi is coleading the effort to glean from oncologists a list of ideas for the consortium's initial clinical trials.From that list, the consortium will select trials that with the most potential impact.Then, they will look for support to fund them.The goal, Lichter said, is to begin enrolling patients in their first two studies in the spring of 2018.Those studies will each probably enroll about 300-400 participants, and they could take place in the U.S. or internationally."We are not saying giving a lower dose less frequently is the right thing to do in every case," Lichter said, "but we hope we can illustrate this is an extremely viable alternative for a variety of reasons.This is probably the most practical idea of how to increase the value of cancer care."Saltz added, "We are trying to be constructive and make patient care more affordable in a way that will not compromise patient outcomes.A drug can't help patients if patients can't get the drug."