tbuckley/cabot-search huggingface dataset:
A phase I trial of panobinostat and epirubicin in solid tumors with a dose expansion in patients with sarcoma
Authors: S. Thomas, R. Aggarwal, T. Jahan, C. Ryan, T. Troung, A.M. Cripps, P. Raha, K.T. Thurn, S. Chen, J.A. Grabowsky, J. Park, J. Hwang, A. Daud, P.N. Munster
Journal: Annals of Oncology (2016)
BaitFisher: A Software Package for Multispecies Target DNA Enrichment Probe Design
Authors: Christoph Mayer, Manuela Sann, Alexander Donath, Martin Meixner, Lars Podsiadlowski, Ralph S. Peters, Malte Petersen, Karen Meusemann, Karsten Liere, Johann-Wolfgang Wägele, Bernhard Misof, Christoph Bleidorn, Michael Ohl, Oliver Niehuis
Journal: Molecular Biology and Evolution (2016)

Target DNA enrichment combined with high-throughput sequencing technologies is a powerful approach to probing a large number of loci in genomes of interest. However, software algorithms that explicitly consider nucleotide sequence information of target loci in multiple reference species for optimizing design of target enrichment baits to be applicable across a wide range of species have not been developed. Here we present an algorithm that infers target DNA enrichment baits from multiple nucleotide sequence alignments. By applying clustering methods and the combinatorial 1-center sequence optimization to bait design, we are able to minimize the total number of baits required to efficiently probe target loci in multiple species. Consequently, more loci can be probed across species with a given number of baits. Using transcript sequences of 24 apoid wasps (Hymenoptera: Crabronidae, Sphecidae) from the 1KITE project and the gene models of Nasonia vitripennis, we inferred 57,650, 120-bp-long baits for capturing 378 coding sequence sections of 282 genes in apoid wasps. Illumina reduced-representation library sequencing confirmed successful enrichment of the target DNA when applying these baits to DNA of various apoid wasps. The designed baits furthermore enriched a major fraction of the target DNA in distantly related Hymenoptera, such as Formicidae and Chalcidoidea, highlighting the baits' broad taxonomic applicability. The availability of baits with broad taxonomic applicability is of major interest in numerous disciplines, ranging from phylogenetics to biodiversity monitoring. We implemented our new approach in a software package, called BaitFisher, which is open source and freely available at https://github.com/cmayer/BaitFisher-package.git.
Clinical outcomes of rectal carcinoids: A single-institution experience.
Authors: Yue Jiang, Yufei Lu, Xiaoli Zheng, Leiming Guo, Xijuan Chen
Journal: Journal of Clinical Oncology (2014)

e14652 Background: The aim of our study was to summarize the clinical outcomes of patients with rectal carcinoids. Methods: From January 2003 to December 2013, 16 consecutive patients with biopsy-proven rectal carcinoids were enrolled at our institution, including 10 males and six females, with a medial age of 49 years old. The median tumor size was 12.3 mm. There were five lesions with the diameter ≥20 mm, eight with the diameter ≤10 mm, and three with the diameter of 10 mm-20 mm. All rectal lesions were located within 10 cm from the anal verge. There were nine patients undergoing transanal local excision, three anterior resection (Dixon), two abdominal operineal resection (APR), and two endoscopic submucosal dissection (ESD), in which two patients received post-operative chemotherapy or radiotherapy. The five-year overall survival (OS), recurrence-free survival (RFS) and cancer specific survival (CSS) were performed by Kaplan-Meier method. Results: All patients were followed up for a median of 45.4 months, and no one was lost to follow-up. The five-year OS, RFS and CSS were 85.2%, 93.8% and 90.9%, respectively. Conclusions: Rectal carcinoids usually have a favorable prognosis, while an adequate resection plays a key role in the management of rectal carcinoid tumors, and the extent of the surgical resection depends on tumor size, anticipated stage and the specific demands of patients.
Obsessive-compulsive disorders: a review of the literature
Authors: L Salzman, F H Thaler
Journal: American Journal of Psychiatry (1981)

The authors reviewed the studies on obsessive-compulsive disorders published from 1953 to 1978. They report on various theories of the etiology of the disorders and provide an overview of the studies based on these theories. The treatment modalities covered include behavioral modification, drug therapy psychotherapy, surgery, and experimental therapies. the authors conclude that, although the obsessive-compulsive disorders are widely present, there is a paucity of new data concerning their treatment. The evidence to date, however, suggests that psychotherapy is an essential ingredient in the treatment process. They recommended that further clinical studies be done to elucidate the etiology and treatment of these disorders.
Biologic Agents in the Management of Hodgkin Lymphoma
Authors: Armin Rashidi, Nancy L. Bartlett
Journal: Journal of the National Comprehensive Cancer Network (2015)

The advent of biologic approaches for the treatment of solid tumors and hematologic malignancies has been a major accomplishment in oncology and a rapidly growing field of clinical and translational research in cancer therapeutics. Classical Hodgkin lymphoma (HL) is no exception. Although the investigation of biologic therapies in HL started decades ago, it has only recently flourished, largely because of the development of new monoclonal antibody drug conjugates and checkpoint inhibitors. Biologic therapies represent a potent treatment option that have produced durable remissions even in patients who have had multiple relapses or with refractory disease. This article reviews 8 major classes of biologic approaches that have been investigated in HL: monoclonal antibodies, immunotoxins, antibody-drug conjugates, radioimmunotherapy, adoptive immunotherapy, immunomodulators, chimeric antigen receptor T cells, and checkpoint inhibitors. An armamentarium of biologic therapies for HL that are well tolerated and potentially more effective is expected to be available in the near future.
Abstract 933: Circulating biomarkers of B vitamins in relation to lung cancer risk in the Lung Cancer Cohort Consortium
Authors: Anouar Fanidi, David.C Muller, Ross Prentice, Albanes Demetrius, Jian-Min Yuan, Victoria Stevens, Stephanie J Weinstein, Mattias Johansson, Paul Brennan
Journal: Cancer Research (2015)

Abstract Background - B vitamins and factors related to one-carbon metabolism help to maintain DNA and regulate gene expression. Some epidemiological data suggest that factors related to the one-carbon metabolism are important in the pathogenesis of several cancers, including lung cancer. Methods - Within the NCI Cohort Consortium, we designed a prospective case-control study including a total of 5,546 case-control pairs nested within 20 prospective cohorts. Centralized biochemical analyses of all study participants were performed to measure circulating concentrations of vitamin B6, folate and methionine, which were subsequently evaluated in relation to lung cancer risk using conditional logistic regression models. Results - We observed an overall increased risk of lung cancer of 25% among study participants having a deficiency in circulating B6 concentrations compared to those with normal concentrations, the odds ratio (OR) being 1.23 95% confidence interval [CI] = 1.10 - 1.38. This association was primarily evident seen among men (OR 1.38 95% CI 1.20 - 1.60), but not among women (OR 1.03 95% CI 0.85-1.24), as well as for ever ever smokers (OR 1.32 95% CI 1.10 - 1.60). Subgroup analyses by histological sub-site indicated particularly strong association for squamous cell carcinoma type, with about 50% risk increase overall when comparing subjects with vitamin B6 deficiency to normal levels. No association was evident for methionine. Detailed results will be presented at the conference. Conclusion - Our results are compatible with the hypothesis that vitamin B6 deficiency is associated with increased lung cancer risk, although the risk increase appears to be moderate. Citation Format: Anouar Fanidi, David.C Muller, Ross Prentice, Albanes Demetrius, Jian-Min Yuan, Victoria Stevens, Stephanie J Weinstein, Mattias Johansson, Paul Brennan, Lung Cancer Cohort Consortium (LC3). Circulating biomarkers of B vitamins in relation to lung cancer risk in the Lung Cancer Cohort Consortium. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 933. doi:10.1158/1538-7445.AM2015-933
Central nervous system (CNS) metastases (mets) in HER2+ metastatic breast cancer (MBC) patients (pts): Patterns of relapse and impact on survival
Authors: S. Verma, J. S. Azzi, L. A. Vandermeer, J. N. Spaans
Journal: Journal of Clinical Oncology (2007)

1017 Background: Several studies have documented an increase in the incidence of CNS mets in HER2+ MBC pts (Bendell, 2003; Heinrich, 2003). Of interest is whether there are any specific patterns of CNS metastasis and if they have an impact on survival. Methods: This retrospective study included 100 HER2+ MBC pts who received trastuzumab with or without chemotherapy for their disease between Jan 1/00 and Jan 1/05. Pts were selected for the presence (n=50) or absence (n=50) of CNS mets. Demographics, location of mets and timeline-related variables (survival) were compared. Results: In 50 MBC pts with CNS mets, the most common site was the cerebellum (82%); and symptoms were related to increased intracranial pressure, primarily as a result of disease-related cerebral edema (73%). Compared to 50 pts without CNS mets, there was no statistically significant difference in overall survival from the time of initial diagnosis of breast cancer. Of interest, pts with CNS mets lived longer (61.3 months) than pts without CNS mets (47.1 months). However, survival after disease progression or recurrence significantly favoured patients with CNS mets (36.8 months v. 22.0 months respectively; p=0.02). Causes of death in both cohorts were also examined. Conclusions: In our observation, CNS mets did not have an adverse effect on overall survival. In fact, pts who developed CNS mets lived longer than those pts without CNS mets. This may in part be due to more aggressive management of CNS mets, or lack of extracranial progression. No significant financial relationships to disclose.
Phase IIa trial of chimeric antigen receptor modified T cells directed against CD19 (CTL019) in patients with relapsed or refractory CD19+ lymphomas.
Authors: Stephen J. Schuster, Jakub Svoboda, Sunita Nasta, David L. Porter, Anthony Mato, Gaurav D. Shah, Daniel Jeffrey Landsburg, Elise A Chong, Simon F. Lacey, Jan J. Melenhorst, Anne Chew, Jens Hasskarl, Nirav Niranjan Shah, Mariusz A. Wasik, Katherine Marcucci, Zhaohui Zheng, Bruce Levine, Carl H. June
Journal: Journal of Clinical Oncology (2015)

8516 Background: Autologous T cells expressing a chimeric antigen receptor with an external anti-CD19 single chain antibody domain and CD3ζ and 4-1BB signaling domains (CTL019 cells) mediate anti-tumor effects in patients (pts) with relapsed/refractory (r/r) CD19+ leukemias. We are conducting a phase IIa clinical trial of CTL019 cells in r/r CD19+ non-Hodgkin lymphomas. Methods: Eligible pts have CD19+ follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL), or mantle cell lymphoma (MCL) with anticipated survival less than 2 years. After collection of peripheral blood leukocytes, pts receive lymphodepleting chemotherapy based on histology and past therapies. One to 4 days after chemotherapy, pts receive 5 x 108CTL019 cells intravenously. Blood and marrow samples are collected for correlative studies. Response assessment is 3 months (mo) after infusion. Enrollment began February 2014; data reported are through January 2015. Results: Twenty-nine pts (19 DLBCL; 8 FL; 2 MCL) have enrolled. Median age is 56 (range: 25-77), male:female ratio 17:12, median prior therapies 4 (range: 1-8), and pts with prior ASCT 9 (31%). At enrollment, stages were: IV, 16 pts (55%); III, 5 pts (17%); II, 6 pts (21%); IE, 2 pts (7%); LDH was increased in 20 pts (69%). Eight pts are not evaluable for response (DLBCL 7; FL 1): 3 pts removed from study before T cell infusion due to progressive disease; 1 pt withdrew consent; 3 pts had inadequate T cell expansion; 1 pt received < protocol-specified cell dose. Twenty pts received CTL019 per protocol dose (12 DLBCL; 7 FL; 1 MCL). Pre-infusion chemotherapy regimens were EPOCH (2); cyclophosphamide (9); radiation + cyclophosphamide (2); bendamustine (6); cyclophosphamide-fludarabine (1). Cytokine release syndrome occurred in 15 pts (13 grade 2; 2 grade 3); neurologic toxicity in 3 pts: transient delirium (1 grade 2, 1 grade 3) and 1 possibly related, grade 5 encephalopathy. For 18 pts evaluable for response at 3 mo (12 DLBCL; 6 FL), overall response rate is 67% (DLBCL 50%; FL 100%). At median follow up 6 mo, progression-free survival for evaluable pts is 59% (DLBCL 37%; FL 100%). Conclusions: CTL019 cells induce durable responses in pts with r/r DLBCL and FL with acceptable toxicity. Clinical trial information: NCT02030834.
Prevalence and Responsiveness to Treatment of Lung Abnormalities on Chest Computed Tomography in Patients With Microscopic Polyangiitis: A Multicenter, Longitudinal, Retrospective Study of One Hundred Fifty Consecutive Hospital‐Based Japanese Patients
Authors: Mieko Yamagata, Kei Ikeda, Kenji Tsushima, Ken Iesato, Mitsuhiro Abe, Takashi Ito, Daisuke Kashiwakuma, Shin‐ichiro Kagami, Itsuo Iwamoto, Daiki Nakagomi, Takao Sugiyama, Yuichiro Maruyama, Shunsuke Furuta, David Jayne, Takashi Uno, Koichiro Tatsumi, Hiroshi Nakajima
Journal: Arthritis & Rheumatology (2015)

To determine the prevalence of lung abnormalities on chest computed tomography (CT) in patients with microscopic polyangiitis (MPA), to assess the responsiveness of such abnormalities to initial treatment, and to assess associations between these abnormalities and patient and disease characteristics and mortality.We retrospectively identified 167 consecutive hospital-based patients with MPA in 3 hospitals in Japan. We longitudinally collected clinical information for 150 of these patients, for whom CT images obtained before treatment were available. We then determined the presence of 22 imaging components of lung abnormalities in these patients.The vast majority of patients (97%) had at least 1 lung abnormality on chest CT images, including interstitial lung lesions (66%), airway lesions (66%), pleural lesions (53%), and emphysematous lesions (37%). In multivariate analyses, ground-glass opacity was associated with the Birmingham Vasculitis Activity Score, whereas 3 of 4 airway lesions were associated with myeloperoxidase-antineutrophil cytoplasmic antibodies. Latent class analysis identified a distinct group of patients with airway-predominant lung lesions. Airway lesions such as bronchiolitis and bronchovascular bundle thickening were among the components that showed improvement within 3 months of the initial treatment. An idiopathic pulmonary fibrosis pattern was the only chest CT variable that was independently associated with shorter survival.Abnormalities in a wide range of anatomic areas, including the whole airway, can be identified in the lungs of patients with MPA before treatment. The prevalence, clustering patterns, and responsiveness to treatment of individual lung abnormalities provide groundwork for informing future studies to understand the pathophysiology of MPA.
Activity of combined therapy with bevacizumab (BV) and paclitaxel (P) in HER2/neu negative patients with widely disseminated metastatic breast cancer (WDMBC).
Authors: I. I. Schnirer, M. A. Cohen, M. Zilberman, S. Yeganah, M. G. Edelson
Journal: Journal of Clinical Oncology (2010)

e11521 Background: BV is a targeting vascular endothelial growth factor that is used in combination with chemotherapy (CTX) in a variety of advanced metastatic cancers. Methods: We used P as the standard upfront CTX along with BV to treat 10 patients aged 33-60 (mean age 44.2.) 100% Her2 /Neu negative ; 30% triple negative with WDMBC. (Metastatic sites listed in Table.) Treatment regime was P (175 mg/m2) and BV (15 mg/kg) every 3 weeks. The patients were followed for overall survival (OS); response rate (RR); and progression-free survival (PFS) over a 28-month period. Evaluation was via MRI, PET CT and spinal tap. Results: 2 patients (20%) achieved complete remission; 6 (60%) achieved partial remission; and 1 (10%) has stable disease. 2 (20%) died. OS was 80%. Median survival time was 9 months. Median number of cycles given was 13. Median time between starting treatment and documented remission was 5 months. Skin lesions disappeared after a median of 5 cycles. One patient with meningeal and brain metastases achieved CR after 10 cycles and remained disease free for 8 months without any radiation therapy to the meninges or brain. Side effects included mild neuropathy (80%), hematological toxicities (60%), and transient ischemic attack (10%). Performance status of the 8 surviving patients is 0. Conclusions: Patients with WDMBC receiving P and BV can experience disease regression and disappearance of metastases including meningeal and brain lesions. There are few reports in the literature documenting complete remission of meningeal and metastatic brain lesions without radiotherapy. Our promising results suggest that this combined therapy be evaluated in larger patient numbers to determine whether this regime might alleviate the need for radiotherapy to the meninges and brain in WDMBC patients. Site of metastases Bone Lung Liver Skin Brain Adrenal Meninges No. of patients 9 7 3 3 2 2 1 No significant financial relationships to disclose.
Abstract 11800: Whole Exome Sequencing in a Large Pedigree With DCM Identifies a Novel Mutation in RBM20
Authors: Tomas Robyns, Johan Van Cleemput, Rik Willems, Shalini Jhangiani, Donna Muzny, Richard Gibbs, James R Lupski, Jeroen Breckpot, Koenraad Devriendt, Gert Matthijs, Anniek Corveleyn
Journal: Circulation (2015)

Background and hypothesis: Familial dilated cardiomyopathy (DCM) is genetically heterogeneous and is associated with mutations in at least 30 different genes. None of these genes have an expected diagnostic yield of more than 10% complicating genetic diagnosis. Whole exome sequencing (WES) is a powerful alternative for the identification of the causal gene, however variant interpretation remains challenging. We performed WES in a large family with autosomal dominant DCM complicated by end stage heart failure and ventricular arrhythmias. The index of this family was evaluated previously by means of targeted gene panel analysis including 28 genes, but no causal mutation was found. Methods and results: WES was applied on 2 affected cousins. First, shared heterozygous variants (single nucleotide variants, small insertions and deletions) located inside the exon or at the exon/intron boundary were selected. Synonymous variants were excluded, except if they were located at the exon/intron boundaries. Variants with a minor allele frequency of &gt;0.1% in publically available exome databases (1000 Genomes and ESP) were excluded. Furthermore, variants that were present in an in-house exome cohort performed for other disease entities were also excluded since these probably represent local SNV’s. The remaining 19 variants were evaluated using a comprehensive scoring system that includes different in-silico analysis tools, orthologous and paralogous conservation and population frequencies. Subsequently Sanger sequencing was performed for 10 variants that were classified as likely pathogenic (N=1) or variants of unknown significance (N=9) according to the scoring system in order to confirm the presence of the variant and to evaluate co-segregation. Only one variant in exon 9 of the RBM20 gene (c.2714T&gt;A, p.Met950Lys, NM_001334363) showed full co-segregation in the 7 affected family members resulting in a maximum 2-point LOD score of 2.1 and suggesting this as the pathogenic mutation responsible for the phenotype. Recently mutations in RBM20 have been linked to dilated cardiomyopathy caused by defective splicing of the giant sarcomeric protein titin. Conclusions: We report the identification of a novel mutation in RBM20 by WES in a large pedigree with DCM.
Delayed access to clinical audit data has risks for patient care
Authors: Kevin Stewart, Rhona Buckingham, Finbarr Martin
Journal: BMJ (2015)

Researchers are not the only group to experience constraints with the Health and Social Care Information Centre (HCSIC). Many of those who lead national clinical audits and databases have had the same experiences as Filippon when trying to access anonymised data.1 Despite the best efforts of some within the HSCIC, delays, duplication, and increasing complexity of the process are common.

This is unfortunately more …
Initial dual oral combination therapy in pulmonary arterial hypertension
Authors: Olivier Sitbon, Caroline Sattler, Laurent Bertoletti, Laurent Savale, Vincent Cottin, Xavier Jaïs, Pascal De Groote, Ari Chaouat, Céline Chabannes, Emmanuel Bergot, Hélène Bouvaist, Claire Dauphin, Arnaud Bourdin, Fabrice Bauer, David Montani, Marc Humbert, Gérald Simonneau
Journal: European Respiratory Journal (2016)

Treatment for pulmonary arterial hypertension (PAH) has been underpinned by single-agent therapy to which concomitant drugs are added sequentially when pre-defined treatment goals are not met.This retrospective analysis of real-world clinical data in 97 patients with newly diagnosed PAH (86% in New York Heart Association functional class III-IV) explored initial dual oral combination treatment with bosentan plus sildenafil (n=61), bosentan plus tadalafil (n=17), ambrisentan plus tadalafil (n=11) or ambrisentan plus sildenafil (n=8).All regimens were associated with significant improvements in functional class, exercise capacity, dyspnoea and haemodynamic indices after 4 months of therapy. Over a median follow-up period of 30 months, 75 (82%) patients were still alive, 53 (71%) of whom received only dual oral combination therapy. Overall survival rates were 97%, 94% and 83% at 1, 2 and 3 years, respectively, and 96%, 94% and 84%, respectively, for the patients with idiopathic PAH, heritable PAH and anorexigen-induced PAH. Expected survival rates calculated from the French equation for the latter were 86%, 75% and 66% at 1, 2 and 3 years, respectively.Initial combination of oral PAH-targeted medications may offer clinical benefits, especially in PAH patients with severe haemodynamic impairment.
An outbreak of Norwalk-like viral gastroenteritis in holidaymakers travelling to Andorra, January–February 2002
Authors: B Pedalino, E Feely, P McKeown, B Foley, B Smyth, A Moren
Journal: Eurosurveillance (2003)

A retrospective cohort study was conducted to investigate an outbreak of Norwalk-like viral gastroenteritidis that occurred in Irish holidaymakers visiting Andorra, in January-February 2002. Preliminary results showed the risk exposure was higher for tourists who stayed in Soldeu and consumed ice cubes in their drinks (OR = 2.5, 95% CI [1.3-4.6)], after logistic regression and adjusting for sex and water consumption).