tbuckley/cabot-search huggingface dataset:
Patients' perception about difficulty of treatment with trifluridine/tipiracil and pharmaceutical care: Effectiveness and safety.
Authors: Marca Diaz, Alberto Llorente, Manuel Touris, Yolanda Vidal, Alicia Mosquera, Elena Lopez, Maria Francisca Vazquez, Bibiana Sanchez, Goretti Duran, Cristina Gonzalez-Anleo, Anais Garcia, Rafael Lopez, Maria J. Lamas, Beatriz Bernardez
Journal: Journal of Clinical Oncology (2017)

e18249 Background: Trifluridine/tipiracil (TAS) is a new alternative in metastatic colorectal cancer patients (pts) previously treated with fluoropyrimidines, oxaliplatin and irinotecan. Objective:to analyze patients` perception about difficulty of dosage regimen with TAS, the effectiveness and safety. Methods: Retrospective observational study, including pts treated with TAS during expanded access in Spain. Oncology pharmacists, as integral part of cancer team, provide direct patient care medication therapy review, pharmacotherapy management, disease management, medication safety, dispense the medication and other clinical support that may lead to improved quality and clinical outcomes for cancer patient at the beginning of treatment with TAS. About perception we applied a survey with a numeric rating scale (0-10 integers) with 3 questions: difficulty of dosage at the beginning, at the end of 3 rd cycle, and the relevance of the information provided by the oncology pharmacist. Variables studied: sex, age, KRAS status, treatment line, ECOG performance status (PS), dose reduction, previous chemotherapy and adverse events (AE) classified according to CTCAE v4.0. Effectiveness variable: progression-free survival (PFS). Results: 12 pts (10 men; 7 mutated KRAS) were included; median age 60.5 years (range 52-81). TAS line: 3 rd line (4), ≥ 4th (8). PS 1 in 10 patients; 2 pts PS 2. Dose reduction was necessary in 41.7% pts. Currently 5 pts are still alive and in the survey they scored the dosage regimen with ≤5 points at the beginning and the same after 3 cycles. The relevance of, information provided by the oncology pharmacist was evaluated with 10 points. Effectiveness: median PFS 3.1 months (0.5-8.3), 2 pts continue on treatment ( medianfollow-up 8.1 months). Overall survival is not evaluable. Grade 3/4 hemotologic toxicities were most common (anemia 8,3%, neutropenia 25%). Conclusions: The perceived dosage difficulty is low, contrary to expectations. It is important to emphasize the evaluation of the information provided by the oncological pharmacist. Our study supports an effectiviness similar than the efficacy. Hematological is the most important and common toxicity.
Pathway discovery using transcriptomic profiles in adult-onset severe asthma
Authors: Pieter-Paul Hekking, Matt J. Loza, Stelios Pavlidis, Bertrand de Meulder, Diane Lefaudeux, Fred Baribaud, Charles Auffray, Ariane H. Wagener, Paul Brinkman, Rene Lutter, Aruna T. Bansal, Ana R. Sousa, Steve A. Bates, Yannis Pandis, Louise J. Fleming, Dominique E. Shaw, Stephen J. Fowler, Y. Guo, Andrea Meiser, Kai Sun, Julie Corfield, Peter H. Howarth, Elisabeth H. Bel, Ian M. Adcock, Kian Fan Chung, Ratko Djukanovic, Peter J. Sterk, I.M. Adcock, H. Ahmed, C. Auffray, P. Bakke, A.T. Bansal, F. Baribaud, S. Bates, E.H. Bel, J. Bigler, H. Bisgaard, M.J. Boedigheimer, K. Bønnelykke, J. Brandsma, P. Brinkman, E. Bucchioni, D. Burg, A. Bush, M. Caruso, A. Chaiboonchoe, P. Chanez, F.K. Chung, C.H. Compton, J. Corfield, A. D'Amico, S.E. Dahlen, B. De Meulder, R. Djukanovic, V.J. Erpenbeck, D. Erzen, K. Fichtner, N. Fitch, L.J. Fleming, E. Formaggio, S.J. Fowler, U. Frey, M. Gahlemann, T. Geiser, Y. Guo, S. Hashimoto, J. Haughney, G. Hedlin, P.W. Hekking, T. Higenbottam, J.M. Hohlfeld, C. Holweg, I. Horváth, P. Howarth, A.J. James, R. Knowles, N. Krug, D. Lefaudeux, M.J. Loza, R. Lutter, A. Manta, S. Masefield, J.G. Matthews, A. Mazein, A. Meiser, R.J.M. Middelveld, M. Miralpeix, N. Mores, C.S. Murray, J. Musial, D. Myles, L. Pahus, I. Pandis, S. Pavlidis, P. Powel, G. Praticò, M Puig Valls, N. Rao, J. Riley, A. Roberts, G. Roberts, A. Rowe, T. Sandström, W. Seibold, A. Selby, D.E. Shaw, R. Sigmund, F. Singer, P.J. Skipp, A.R. Sousa, P.J. Sterk, K. Sun, B. Thornton, W.M. van Aalderen, M. van Geest, J. Vestbo, N.H. Vissing, A.H. Wagener, S.S. Wagers, Z. Weiszhart, C.E. Wheelock, S.J. Wilson
Journal: Journal of Allergy and Clinical Immunology (2017)
Epidermal E-Cadherin Dependent β-Catenin Pathway Is Phytochemical Inducible and Accelerates Anagen Hair Cycling
Authors: Noha S. Ahmed, Subhadip Ghatak, Mohamed S. El Masry, Surya C. Gnyawali, Sashwati Roy, Mohamed Amer, Helen Everts, Chandan K. Sen, Savita Khanna
Journal: Molecular Therapy (2017)

Unlike the epidermis, which regenerates continually, hair follicles anchored in the subcutis periodically regenerate by spontaneous repetitive cycles of growth (anagen), degeneration (catagen), and rest (telogen). The loss of hair follicles in response to injuries or pathologies such as alopecia endangers certain inherent functions of the skin. Thus, it is of interest to understand mechanisms underlying follicular regeneration in adults. In this work, a phytochemical rich in the natural vitamin E tocotrienol (TRF) served as a productive tool to unveil a novel epidermal pathway of hair follicular regeneration. Topical TRF application markedly induced epidermal hair follicle development akin to that during fetal skin development. This was observed in the skin of healthy as well as diabetic mice, which are known to be resistant to anagen hair cycling. TRF suppressed epidermal E-cadherin followed by 4-fold induction of β-catenin and its nuclear translocation. Nuclear β-catenin interacted with Tcf3. Such sequestration of Tcf3 from its otherwise known function to repress pluripotent factors induced the plasticity factors Oct4, Sox9, Klf4, c-Myc, and Nanog. Pharmacological inhibition of β-catenin arrested anagen hair cycling by TRF. This work reports epidermal E-cadherin/β-catenin as a novel pathway capable of inducing developmental folliculogenesis in the adult skin.
Beware the ‘luck’ capstone
Authors: Sheree Bekker, Lauren V Fortington, Evert ALM Verhagen, Caroline F Finch
Journal: British Journal of Sports Medicine (2017)

The recent BJSM educational review describing an ‘injury prevention pyramid for elite sports teams’, which has been widely promoted through social media, suggests that bad ‘luck’ plays a definitive role in injury occurrence, depicting its notable role as the capstone.1 This is in direct contrast to the rich theoretical and empirical history of injury prevention research, which refutes the concept of bad ‘luck’ in sports injury causation entirely.

In positioning ‘luck’ as the capstone of their injury …
FRI0699 Determinants of 12-months persistence in ankylosing spondylitis patients initiating subcutaneous tnf-alpha inhibitors
Authors: B Fautrel, M Belhassen, C Hudry, M-C Woronoff, N Gouyette, A Clément, E Van Ganse, F Tubach
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Biotherapies such as subcutaneous tumour necrosis factor-alpha inhibitors (SC-TNFis) have transformed the management of inflammatory joint diseases such as ankylosing spondylitis (AS). The assessment of SC- TNFis persistence and its determinants is needed. <h3>Objectives</h3> The objective of this study was to describe treatment persistence in real-world settings, and identify the determinants of persistence among AS patients initiating treatment with an SC-TNFi. <h3>Methods</h3> The French national health insurance scheme database lists all outpatient and inpatient healthcare consumption for individuals covered by the general health insurance scheme. Using French claims data, AS was diagnosed using Long Term Disease status and hospital admission, based on ICD-10 codes. Patients were then identified through prescription filled for adalimumab (ADA), etanercept (ETA), certolizumab pegol (CZP) and golimumab (GLM) between 2012/07/01 and 2013/12/31. A patient was considered as non-persistent in the event of a prolonged interruption of the therapy lasting 91 days or more. Persistence was estimated with Kaplan Meier analysis. Determinants of persistence in the 12 months before initiation were identified using Cox models. <h3>Results</h3> A total of 9,098 patients with AS were identified. In the descriptive analyses of the 12 months persistence, differences were observed for AS patients, with raw/non-adjusted persistence rates of 33.2% for CZP, 49.3% for ETA, 52.4% for ADA and 54.5% for GLM. Results of the Cox model are presented, including hazard ratio for biotherapy, adjusted on sex, age, socio-economic status, and criteria on disease severity. The variables biotherapy, socio-economic status and hospital admission for IRMD did not meet the proportionality hypothesis of risks, and were corrected by the addition of a variable integrating the interaction with time. <h3>Conclusions</h3> Non-persistent patients were more likely female, with deprived socio-economic status, multiple comorbid conditions, and multiple line of biotherapy. Age, hospital admission for IRMD and treatment with GLM (compared to CZP, ETA and ADA) decreased the risk of non-persistence. Further analyses are needed to assess the impact of non-persistence. <h3>Disclosure of Interest</h3> B. Fautrel Grant/research support from: AbbVie, MSD, Pfizer, Consultant for: AbbVie, Biogen, BMS, Celgène, Hospira, Janssen, Lilly, MSD, NORDIC Pharma, Pfizer, Roche, SOBI, UCB, M. Belhassen Employee of: PELyon, C. Hudry Consultant for: ABBVIE, MSD, BMS, PFIZER, ROCHE, CELGENE, NOVARTIS, BIOGEN, UCB, SANDOZ, AMGEN., Employee of: COCHIN Hospital, M.-C. Woronoff: None declared, N. Gouyette Employee of: MSD France, A. Clément Employee of: MSD France, E. Van Ganse Consultant for: PELyon; ALK ABELLO; AstraZeneca; Bayer; BMS; BIF; GSK; IMS; LASER; MSD, F. Tubach: None declared
The Selinexor in Advanced Liposarcoma (SEAL) study: A phase 2/3, multicenter, randomized, double blind study of selinexor versus placebo in patients with advanced, unresectable, dedifferentiated liposarcoma (DDLS).
Authors: Mrinal M. Gounder, Andrew J. Wagner, Neeta Somaiah, Richard F. Riedel, Gary K. Schwartz, Steven Attia, Albiruni R.A. Razak, Lee D. Cranmer, Scott H. Okuno, Mohammed M. Milhem, Cassandra Choe-Juliak, Sharon Shacham, Michael G. Kauffman, Sant P. Chawla
Journal: Journal of Clinical Oncology (2016)

TPS11072 Background: DDLS represents progression from low- to high-grade non-lipogenic morphology within well-differentiated liposarcoma (WDLS) with the potential to metastasize and a higher mortality rate. Selinexor is an oral, selective inhibitor of nuclear export that specifically blocks XPO1, leading to the nuclear accumulation and re-activation of tumor suppressor proteins and growth modulators. Selinexor demonstrated potent anti-tumor activity in liposarcoma (LPS) cell line and murine models. Sarcoma patients received selinexor in two Phase 1 studies, resulting in stable disease in 14/18 (78%) of patients with advanced LPS; notably, 6 of these had stable disease ≥ 4 months. Tumor reduction of 2-23% was noted in 14 patients. There were no clinically significant cumulative toxicities. Hence, we designed a Phase 2/3 multi-center, randomized, double blind study to assess whether selinexor can improve progression-free survival (PFS) of patients with advanced unresectable DDLS compared to placebo. Methods: Eligible patients have DDLS with measurable disease, radiologic evidence of progressive disease (PD) within 6 months, and have had at least one prior line of systemic therapy. Patients with pure WDLS, myxoid/round cell or pleomorphic subtypes are not eligible. Patients will be randomized 1:1 (selinexor:placebo) during Phase 2, and 2:1 during Phase 3 and will receive selinexor 60 mg or placebo twice weekly on a 42 day cycle until PD or intolerability. Patients with PD on placebo can crossover to selinexor. The primary endpoint is PFS. The study is powered to detect a 50% improvement with selinexor versus placebo. Secondary endpoints include overall survival and response rate. Planned total sample size (Phase 2+3) is 245. Enrollment began in January 2016. Clinical trial information: NCT02606461.
Erratum: Corrigendum: Circuit specificity in the inhibitory architecture of the VTA regulates cocaine-induced behavior
Authors: Nicholas J Edwards, Hugo A Tejeda, Marco Pignatelli, Shiliang Zhang, Ross A McDevitt, Jocelyn Wu, Caroline E Bass, Bernhard Bettler, Marisela Morales, Antonello Bonci
Journal: Nature Neuroscience (2017)
Abstract 272: Pharmacological Testing Of Novel Atrial-specific Ion Channel Blockers Establishes Human Pluripotent Stem Cell Derived Atrial Cardiomyocytes As A Predictive Pre-clinical Model For Selective Pharmacology
Authors: Harsha Deepti Devalla, Arie O Verkerk, Robert Passier
Journal: Circulation Research (2013)

Background: Atrial Fibrillation (AF) is the most prevalent arrhythmia affecting two and half million people in the United States alone. Medical therapy is the choice of treatment in a large number of cases and current drug discovery programs by pharmaceutical industries are aimed at developing atrial-specific ion channel blockers. Most of the current selective pharmacology studies however, are carried out in animal models such as dogs and guinea pigs. Human pluripotent stem cell derived cardiomyocytes provide a promising alternative in this respect. Aim: To establish an in vitro pre-clinical model of selective pharmacology for testing atrial-specific pharmacological compounds using human pluripotent stem cell (hPSC) derived atrial-like cardiomyocytes. Methods &amp; Results: We have successfully generated atrial-like cardiomyocytes from differentiating human embryonic stem cells by modulating retinoic acid signaling. Molecular identity of these cardiomyocytes was established by whole genome microarray while the functional identity was confirmed by voltage patch clamp techniques. At the electrophysiological level, hPSC-derived atrial-like cardiomyocytes exhibit shorter action potentials, increased Ito1 density and increased steady state currents (combination of IKr, IKs and IKur) as expected for atrial cardiomyocytes. In order to validate the use of these cells for selective pharmacology, novel IKur and IKACh blockers (currently in clinical trials/pre-clinical development) were tested and their effect was assessed by electrophysiology. hPSC-derived atrial-like cardiomyocytes showed prolongation of action potential in response to IKur and IKACh blockers whereas the effect was minimal on hPSC-derived ventricular-like cardiomyocytes. These findings are being compared against multiple ion-channel blockers such as Dronaderone. Conclusions: Modulation of retinoic acid signaling drives differentiating human pluripotent stem cells to atrial-like cardiomyocytes which have been validated as a pre-clinical screening model for testing novel atrial-specific pharmacological compounds.
Low-burden TP53 mutations in chronic phase of myeloproliferative neoplasms: association with age, hydroxyurea administration, disease type and JAK2 mutational status
Authors: B Kubesova, S Pavlova, J Malcikova, J Kabathova, L Radova, N Tom, B Tichy, K Plevova, B Kantorova, K Fiedorova, M Slavikova, V Bystry, J Kissova, B Gisslinger, H Gisslinger, M Penka, J Mayer, R Kralovics, S Pospisilova, M Doubek
Journal: Leukemia (2017)

The multistep process of TP53 mutation expansion during myeloproliferative neoplasm (MPN) transformation into acute myeloid leukemia (AML) has been documented retrospectively. It is currently unknown how common TP53 mutations with low variant allele frequency (VAF) are, whether they are linked to hydroxyurea (HU) cytoreduction, and what disease progression risk they carry. Using ultra-deep next-generation sequencing, we examined 254 MPN patients treated with HU, interferon alpha-2a or anagrelide and 85 untreated patients. We found TP53 mutations in 50 cases (0.2–16.3% VAF), regardless of disease subtype, driver gene status and cytoreduction. Both therapy and TP53 mutations were strongly associated with older age. Over-time analysis showed that the mutations may be undetectable at diagnosis and slowly increase during disease course. Although three patients with TP53 mutations progressed to TP53-mutated or TP53-wild-type AML, we did not observe a significant age-independent impact on overall survival during the follow-up. Further, we showed that complete p53 inactivation alone led to neither blast transformation nor HU resistance. Altogether, we revealed patient's age as the strongest factor affecting low-burden TP53 mutation incidence in MPN and found no significant age-independent association between TP53 mutations and hydroxyurea. Mutations may persist at low levels for years without an immediate risk of progression.
It’s About the Weight Loss
Authors: Bruce M. Wolfe, Elizaveta Walker
Journal: JAMA Surgery (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
For-Profit Medical Education
Authors: George Mychaskiw
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Adnectin-Based Design of Chimeric Antigen Receptor for T Cell Engineering
Authors: Xiaolu Han, Gunce E. Cinay, Yifan Zhao, Yunfei Guo, Xiaoyang Zhang, Pin Wang
Journal: Molecular Therapy (2017)

Although chimeric antigen receptor (CAR)-engineered T cell therapy has achieved encouraging clinical trial results for treating hematological cancers, further optimization can likely expand this therapeutic success to more patients and other cancer types. Most CAR constructs used in clinical trials incorporate single chain variable fragment (scFv) as the extracellular antigen recognition domain. The immunogenicity of nonhuman scFv could cause host rejection against CAR T cells and compromise their persistence and efficacy. The limited availability of scFvs and slow discovery of new monoclonal antibodies also limit the development of novel CAR constructs. Adnectin, a class of affinity molecules derived from the tenth type III domain of human fibronectin, can be an alternative to scFv as an antigen-binding moiety in the design of CAR molecules. We constructed adnectin-based CARs targeting epithelial growth factor receptor (EGFR) and found that compared to scFv-based CAR, T cells engineered with adnectin-based CARs exhibited equivalent cell-killing activity against target H292 lung cancer cells in vitro and had comparable antitumor efficacy in xenograft tumor-bearing mice in vivo. In addition, with optimal affinity tuning, adnectin-based CAR showed higher selectivity on target cells with high EGFR expression than on those with low expression. This new design of adnectin CARs can potentially facilitate the development of T cell immunotherapy for cancer and other diseases.
Analysis of Fine-Needle Biopsy vs Fine-Needle Aspiration in Diagnosis of Pancreatic and Abdominal Masses: A Prospective, Multicenter, Randomized Controlled Trial
Authors: Bin Cheng, Yueming Zhang, Qian Chen, Bo Sun, Zhuang Deng, Hongbo Shan, Lizhou Dou, Jinglin Wang, Yawen Li, Xiujiang Yang, Tianan Jiang, Guoliang Xu, Guiqi Wang
Journal: Clinical Gastroenterology and Hepatology (2017)
Novel promoters and coding first exons in DLG2 linked to developmental disorders and intellectual disability
Authors: Claudio Reggiani, Sandra Coppens, Tayeb Sekhara, Ivan Dimov, Bruno Pichon, Nicolas Lufin, Marie-Claude Addor, Elga Fabia Belligni, Maria Cristina Digilio, Flavio Faletra, Giovanni Battista Ferrero, Marion Gerard, Bertrand Isidor, Shelagh Joss, Florence Niel-Bütschi, Maria Dolores Perrone, Florence Petit, Alessandra Renieri, Serge Romana, Alexandra Topa, Joris Robert Vermeesch, Tom Lenaerts, Georges Casimir, Marc Abramowicz, Gianluca Bontempi, Catheline Vilain, Nicolas Deconinck, Guillaume Smits
Journal: Genome Medicine (2017)

Tissue-specific integrative omics has the potential to reveal new genic elements important for developmental disorders. Two pediatric patients with global developmental delay and intellectual disability phenotype underwent array-CGH genetic testing, both showing a partial deletion of the DLG2 gene. From independent human and murine omics datasets, we combined copy number variations, histone modifications, developmental tissue-specific regulation, and protein data to explore the molecular mechanism at play. Integrating genomics, transcriptomics, and epigenomics data, we describe two novel DLG2 promoters and coding first exons expressed in human fetal brain. Their murine conservation and protein-level evidence allowed us to produce new DLG2 gene models for human and mouse. These new genic elements are deleted in 90% of 29 patients (public and in-house) showing partial deletion of the DLG2 gene. The patients' clinical characteristics expand the neurodevelopmental phenotypic spectrum linked to DLG2 gene disruption to cognitive and behavioral categories. While protein-coding genes are regarded as well known, our work shows that integration of multiple omics datasets can unveil novel coding elements. From a clinical perspective, our work demonstrates that two new DLG2 promoters and exons are crucial for the neurodevelopmental phenotypes associated with this gene. In addition, our work brings evidence for the lack of cross-annotation in human versus mouse reference genomes and nucleotide versus protein databases.