tbuckley/cabot-search huggingface dataset:
Evidence of an abnormal epithelial barrier in active, untreated and corticosteroid‐treated eosinophilic esophagitis
Authors: D. Simon, B. Page, M. Vogel, C. Bussmann, C. Blanchard, A. Straumann, H.‐U. Simon
Journal: Allergy (2017)

Abstract Background Eosinophilic esophagitis (EoE) is a chronic, immune/antigen‐mediated disease characterized by symptoms related to esophageal dysfunction and an eosinophil‐predominant inflammation. This study has aimed to investigate whether the recently observed sensitization to Candida albicans in patients with EoE is owing to pre‐existing disease and its underlying abnormal epithelial barrier or, alternatively, is linked to corticosteroid ( CS ) therapy. Methods Medical histories, as well as serum and tissue samples of 60 patients with EoE (15 CS naive, 45 with current or previous CS therapy) and 20 controls, stored in the Swiss Eosinophilic Esophagitis Database ( SEED ) and Biobank, were analyzed. We applied Immuno CAP to measure IgE levels and immunofluorescence techniques to examine epithelial barrier components. Results Patients with EoE had higher total IgE levels and were more frequently sensitized to C. albicans than controls. In EoE tissue specimens, increased numbers of eosinophils and mast cells, a higher expression levels of thymic stromal lymphopoietin ( TSLP ), cathelicidin, proteases, that is, the kallikreins ( KLK )‐5 and KLK ‐7, were observed as compared with controls, while reduced expression of lympho‐epithelial Kazal‐type‐related inhibitor ( LEKTI ), filaggrin, E‐cadherin, claudin, occludin, desmoglein‐1 was found, independent of CS therapy. In CS ‐treated EoE, significantly lower numbers of CD 1a+ cells and cathelicidin expression were noted as compared to CS ‐naive EoE. Conclusion This study provides further evidence that EoE is associated with an abnormal epithelial barrier and postulates that CS therapy, by reducing innate immune mechanisms, may promote C. albicans colonization and likely subsequent sensitization.
Considering Bone Marrow Blasts from Nonerythroid Cellularity Improves the Prognostic Evaluation of MDS in the Context of IPSS-R and Permits a Better Risk Assessment of MDS Patients Classified into the Intermediate Risk Category
Authors: Xavier Calvo, Leonor Arenillas, Elisa Luño, Leonor Senent, Esther Alonso, Fernando Ramos, Maria Teresa Ardanaz, Carme Pedro, Mar Tormo, Victor Marco, Julia Montoro, María Díez-Campelo, Salut Brunet, Beatriz Arrizabalaga, Blanca Xicoy, Rafael Andreu, Santiago Bonanad, Andres Jerez, Meritxell Nomdedeu, Ana Ferrer, Guillermo Sanz, Lourdes Florensa
Journal: Blood (2016)
Genome-wide association study of cisplatin-induced peripheral neuropathy (CIPN) in testicular cancer survivors.
Authors: Omar El Charif, Heather E. Wheeler, Taisei Mushiroda, Michiaki Kubo, Eric R Gamazon, Darren R. Feldman, Robert James Hamilton, David J. Vaughn, Clair J. Beard, Chunkit Fung, Costantine Albany, Eileen Johnson, Sophie Fossa, Nancy Cox, Lawrence H. Einhorn, Lois B. Travis, M. Eileen Dolan
Journal: Journal of Clinical Oncology (2016)

4543 Background: CIPN is a potentially permanent side effect of cisplatin chemotherapy. CIPN remains a major clinical challenge due to lack of effective treatment, impact on quality of life and unexplained inter-individual variability. Methods: Testicular cancer patients (n = 847) given cisplatin-based therapy (median dose: 400 mg/m2) were assessed for responses to the validated EORTC QLQ-CIPN20 questionnaire. Associations were evaluated between frequency of sensory neuropathy and cumulative cisplatin dose, smoking history and age. Using the Illumina HumanOmniExpressExome chip and with imputation, 5.1 million SNPs passed quality control (QC) for GWAS inclusion. A gene-based method, PrediXcan, was used to consider associations between the genetically determined component of gene expression and CIPN. Results: Sensory neuropathy was common (57% having any symptom). CIPN sensory items (n = 8) indicated excellent internal consistency (alpha coefficient = 0.88). Using each patient’s mean sensory neuropathy score, we sorted them into 3 ordinal groups according to severity: 43% none, 41% a little, 16% quite a bit/very much. Only age and smoking status, not dose, were significantly related to sensory neuropathy (OR = 1.04 [95% CI 1.03-1.06] and 1.5 [95% CI 1.2-2.0], respectively). The top 2 SNPs (P = 5 x 10-7) from a GWAS of 677 patients that passed QC, were each associated with greater risk of sensory neuropathy (OR = 1.9 [95% CI 1.5-2.4] and 1.9 [95% CI 1.5-2.5]). These SNPs are expression QTLs for LYPD3 (rs12797447), SNX8 and GSTT1 (rs4757366) in lymphoblastoid cell lines. PrediXcan identified lower predicted expression of RPRD1B in whole blood (5453 genes tested) met genome-wide significance for association with increased sensory neuropathy risk (P = 3 x 10-6). Conclusions: Our traditional GWAS identified several SNPs associated with CIPN that were functionally important due to their association with gene expression. Our gene-based test implicated RPRD1B, known to play a role in cell cycle regulation, as associated with CIPN. Future studies will focus on functional validation, analysis of a replication set and meta-analysis with other CIPN studies to identify drug-independent variants.
Biophysical and biomolecular determination of cellular age in humans
Authors: Jude M. Phillip, Pei-Hsun Wu, Daniele M. Gilkes, Wadsworth Williams, Shaun McGovern, Jena Daya, Jonathan Chen, Ivie Aifuwa, Jerry S. H. Lee, Rong Fan, Jeremy Walston, Denis Wirtz
Journal: Nature Biomedical Engineering (2017)
Infection with a respiratory virus before hematopoietic cell transplantation is associated with alloimmune-mediated lung syndromes
Authors: Birgitta Versluys, Marc Bierings, Jean Luc Murk, Tom Wolfs, Caroline Lindemans, Kors vd Ent, Jaap Jan Boelens
Journal: Journal of Allergy and Clinical Immunology (2017)
A Phase I Dose Finding Trial of Eltrombopag during Consolidation Therapy in Adults with Acute Myeloid Leukemia Employing a Unique Dosing Design: PrE0901, a Precog Study
Authors: Stephen A. Strickland, Hillard M. Lazarus, Xin Victoria Wang, Jan Cerny, Witold B. Rybka, Martin S. Tallman, Mark R. Litzow
Journal: Blood (2016)
Phase Ib study of safety, tolerability, and efficacy of R1507 a monoclonal antibody to IGF-1R in combination with multiple standard chemotherapy regimens in patients with advanced solid malignancies.
Authors: Daruka Mahadevan, Gregory Ryan Sutton, Rafael Arteta-Bulos, Chris J. Bowden, Paul J. E. Miller, Rachel Elizabeth Swart, Mark S. Walker, Pamela N. Munster, Elizabeth Claire Dees, John Marshall, Omid Hamid, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2013)

e13574 Background: R1507 is a human IgG1 Mab that binds to the insulin-like growth factor-1 receptor (IGF-1R), implicated in the pathogenesis of several solid tumor types. IGF-1 or IGF-2 activate the IGF-1R and promote anchorage independent growth of malignant cells. A phase 1b study was conducted to establish the safety, tolerability and efficacy of R1507 in combination with multiple standard oncology regimens. Methods: This was an open-label, multi-center study in advanced stage cancer patients (pts). R1507 (3, 5, 9, 10 and 16 mg/kg IV, Q2W or Q3W) was added to 6 treatment regimens: gemcitabine + erlotinib (GE); paclitaxel + bevacizumab (PB); carboplatin + etoposide (CE); mFOLFOX6 + bevacizumab (FB); capecitabine + trastuzumab (CT); sorafenib (S). All arms started with R1507 dose lower than the recommended single agent dose (level -1). If tolerable, R1507 dose was escalated in subsequent cohorts of pts. Accrual to each regimen was dependent on the number of pts developing a DLT at dose level -1. The study used a 3 + 3 + 6 and a 3 + 9 design. Results: N=104 pts enrolled into regimens 1 to 6: 6% new diagnosis, 93% non-recent diagnosis, and 1% not classified. N=18 withdrew for safety [1 death, 17 AEs]. N=80 withdrew for non-safety reasons [n=61 PD, n=17 refused further treatment, n=1 insufficient response, n=1 ‘other’]. A total of 1337 AEs were reported: any grade, across regimens and doses were nausea, diarrhea, and vomiting. N=123 had grade ≥3 AEs (n=28 dose level -1; n=95 dose level 1) in 60 pts that were myelosuppression, fatigue and mucosal inflammation. ORR (partial response [PR] plus stable disease) of evaluable pts across 6 regimens was 36% with 5 PRs: regimens PB (non-small cell lung cancer, nasopharyngeal cancer), CE (melanoma), FB (colon cancer) and S (gastrointestinal stromal tumor: GIST). The GIST pt (&gt;4 prior therapies) had a PR for 3 years. Three pts (breast cancer, melanoma, adenoid cystic carcinoma) were on study for &gt;1 year. 71% pts had SD ≥ 4 months. Conclusions: R1507 added to 6 standard chemotherapy regimens was well tolerated with no significant safety issues. Trial was terminated early due to discontinued development of R1507. Clinical trial information: NCT00811993.
Neoadjuvant Treatment in Locally Advanced and Borderline Resectable Pancreatic Cancer vs Primary Resectable Pancreatic Cancer
Authors: Marco Del Chiaro, Roberto Valente, Urban Arnelo
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
Shallow Whole Genome Sequencing on Circulating Cell-Free DNA Allows Reliable Noninvasive Copy-Number Profiling in Neuroblastoma Patients
Authors: Nadine Van Roy, Malaïka Van Der Linden, Björn Menten, Annelies Dheedene, Charlotte Vandeputte, Jo Van Dorpe, Geneviève Laureys, Marleen Renard, Tom Sante, Tim Lammens, Bram De Wilde, Frank Speleman, Katleen De Preter
Journal: Clinical Cancer Research (2017)

Purpose: Neuroblastoma (NB) is a heterogeneous disease characterized by distinct clinical features and by the presence of typical copy-number alterations (CNAs). Given the strong association of these CNA profiles with prognosis, analysis of the CNA profile at diagnosis is mandatory. Therefore, we tested whether the analysis of circulating cell-free DNA (cfDNA) present in plasma samples of patients with NB could offer a valuable alternative to primary tumor DNA for CNA profiling.Experimental Design: In 37 patients with NB, cfDNA analysis using shallow whole genome sequencing (sWGS) was compared with arrayCGH analysis of primary tumor tissue.Results: Comparison of CNA profiles on cfDNA showed highly concordant patterns, particularly in high-stage patients. Numerical chromosome imbalances as well as large and focal structural aberrations including MYCN and LIN28B amplification and ATRX deletion could be readily detected with sWGS using a low input of cfDNA.Conclusions: In conclusion, sWGS analysis on cfDNA offers a cost-effective, noninvasive, rapid, robust and sensitive alternative for tumor DNA copy-number profiling in most patients with NB. Clin Cancer Res; 23(20); 6305-14. ©2017 AACR.
Sharing Clinical Research Data—Finding the Right Balance
Authors: Bernard Lo, Steven N. Goodman
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Infographic: Ankle sprain treatment and prevention timeline
Authors: Kasper W Janssen
Journal: British Journal of Sports Medicine (2017)

As most sports medicine practitioners know, evidence of effectiveness does not equal successful implementation. To progress in the field, practical tools are needed to bridge the gap between research and practice.1 To support this process, the Dutch Association of Sport and Exercise Medicine developed a Knowledge Transfer Scheme, integrating existing implementation research frameworks into a tool, which has been developed specifically to bridge the gap between knowledge derived from research on the one side and evidence-based usable information and tools for practice on the other.1 We applied this scheme to interventions preventing ankle ligament injury.

Step 1 in the transfer scheme is to describe the problem in practice. The Knowledge Transfer Group (KTG) determined the following problem as a starting point: …
The Effect of Activated Prothrombin-Complex Concentrate (FEIBA) on Joint and Muscle Bleeding in Patients with Hemophilia A and Antibodies to Factor VIII
Authors: Lisbeth J. M. Sjamsoedin, Lily Heijnen, Eveline P. Mauser-Bunschoten, Jaap L. van Geijlswijk, Hans van Houwelingen, Paul van Asten, Jan J. Sixma
Journal: New England Journal of Medicine (1981)

Original Article from The New England Journal of Medicine — The Effect of Activated Prothrombin-Complex Concentrate (FEIBA) on Joint and Muscle Bleeding in Patients with Hemophilia A and Antibodies to Factor VIII — A Double-Blind Clinical Trial
Out of stock: summit highlights global lack of access to contraceptives
Authors: Rebecca Coombes
Journal: BMJ (2017)

John Nguyen/PA

Halima Lila, from Tanzania, Sophie, a youth campaigner, and Margaret Bolaji, from the Ugandan Adolescent Youth and Health Forum join a queue of 214 women, each representing one million women and girls from developing countries, outside a mock “No Contraceptives” clinic in Soho, London, to highlight the plight of those across the world who don’t have access to the contraceptives, advice, and services they need. The protest came on the opening day of the 2017 Family …
The tumor suppressor Caveolin-1 is a putative substrate for Elongation Factor-2 Kinase: a possible mechanism in cell transformation and tumor invasion.
Authors: Ladan Fakhrzadeh, Petra Pham, Jin-Ming Yang, William N. Hait
Journal: Cancer Research (2006)

5136   Elongation factor-2 kinase (eEF-2K; a.k.a. calmodulin-dependent kinase III) is a structurally unique enzyme (Ryazanov, 1997) that regulates protein translation and is overexpressed in many human cancer cell lines and tumor tissues (Bagaglio DM 1993, Parmer TG 1999, Hait WN 1996). To date, it’s only known substrate is eEF-2, where it phosphorylates serines and threonines within α-helical segments of the protein. Overexpression of eEF-2K promotes proliferation (Calberg U 1991 and survival whereas inhibition promotes cell death (Parmer TG 1997, Yang, J 2001, Arora S 2003). Therefore, we sought to uncover other potential substrates for this enzyme more directly involved in malignant transformation. Caveolin-1 (Cav-1) is a scaffolding protein involved in the suppression of Src family tyrosine kinases, Neu, protein kinase C isoforms, H-Ras, EGFR, and G-proteins. The tumor suppressor activity of Cav-1 appears to be mediated through the interaction of the Cav-1-scaffolding domain (CSD; residue 81-101) with specific motifs within these co-regulated proteins. Disruption of this interaction through mutation or post-translational modification of the CSD activates signaling, increases cell proliferation, invasion and metastasis. Loss of Cav-1 function occurs as a consequence of phosphorylation and or deregulation of its CSD. However, the responsible kinase(s) has not been identified. We were struck by the possibility that eEF-2K could represent this putative enzyme since several serine/threonine phosphorylation sites exist within the α-helical portion of the CSD. Therefore, we explored the regulation of Cav-1 by eEF-2K in glioma cell lines [C6, T98G, U87] and eEF-2K+/+ and eEF-2K-/- murine embryo fibroblasts (MEFs). Purified eEF-2K increased phosphorylation of immunoprecipitated Cav-1. Increased eEF-2 kinase activity decreased Cav-1 protein and promoted anchorage-independent cell growth on poly-HEMA coated plates or colony formation in soft agar, produced resistance to anoikis as measured by Annexin V assay, and increased cell invasion through Matrigel. siRNA knockdown or NH125, a selective inhibitor of the kinase, decreased phosphorylation of Cav-1, increased Cav-1 expression, and increased Cav-1 tumor suppression as shown by decreased ability to invade Matrigel and decreased anoikis. Cells treated with geldanamycin, an Hsp90 antagonist that destabilizes eEF-2 kinase, gave identical results. Flow cytometry revealed that NH125 decreased S phase accumulation in eEF-2K+/+ MEFs but had no effect in eEF-2K-/- MEFS. These data mark Cav-1 as a putative substrate for eEF-2K and suggest additional roles for eEF-2K in malignant transformation.
Abstract 25: Polyphenolic - Ellagic Acid Suppresses Mitophagy- Induced Necrotic Cell Death During Doxorubicin Cardiotoxicity
Authors: Rimpy Dhingra, Abhinav Dhingra, Rahul Jayas, Lorrie A. Kirshenbaum
Journal: Circulation Research (2015)

Reactive oxygen species (ROS) play a major role in cardiac dysfunction during myocardial ischemia. ROS production has been linked to oxidative stress injury and mitochondrial perturbations including permeability transition pore opening (mPTP), loss of mitochondrial membrane potential ([[Unable to Display Character: &amp;#8710;]]Ψm) and necrotic cell death. Previously we identified the inducible Bcl-2 protein, Bnip3 as critical regulator of mitochondrial function and cell death of ventricular myocytes. Polyphenolic compounds including ellagic acid from pomegranate, have strong anti-oxidant properties. The effects of ellagic acid on oxidative stress injury in the heart has not been explored. In this report, we provide new compelling evidence that ellagic acid suppressed mitochondrial ROS production, loss of [[Unable to Display Character: &amp;#8710;]]Ψm and necrotic cell death of cardiac myocytes induced by doxorubicin (DOX) or hypoxia. We further show mechanistically that the cytoprotective effects of ellagic acid were related to the transcriptional repression of Bnip3. In contrast to vehicle treated cells, cells treated with DOX or hypoxia displayed a marked increase in Bnip3 expression and mitochondrial association, concordant with increased ROS, mPTP, and loss of [[Unable to Display Character: &amp;#8710;]]Ψm. Consistent with these mitochondrial defects there was a marked increase in mitophagy as confirmed by the dual emission Mitokeima probe that detects autophagic degradation by labelling mitochondria containing autophagosomes fused with lysosome. Mitophagy was accompanied by a marked increase in LDH release, loss of nuclear HMGB1 immunostaining and cell death. Interestingly, cells treated with ellagic acid were resistant to mitochondrial and the cytotoxic effects of DOX displaying reduced ROS production, mitophagy and were indistinguishable from vehicle treated control cells with respect to cell viability. Notably, Dox-induced Bnip3 expression was dramatically reduced in cells treated with ellagic acid. Hence, the findings of the present study demonstrate that ellagic acid suppresses mitochondrial perturbations and cell death of cardiac myocytes by mechanism that links to the repression of mitochondrial Bnip3.
Diphtheria toxoid and N -trimethyl chitosan layer-by-layer coated pH-sensitive microneedles induce potent immune responses upon dermal vaccination in mice
Authors: Pim Schipper, Koen van der Maaden, Vincent Groeneveld, Mitchel Ruigrok, Stefan Romeijn, Sven Uleman, Cees Oomens, Gideon Kersten, Wim Jiskoot, Joke Bouwstra
Journal: Journal of Controlled Release (2017)

Dermal immunization using antigen-coated microneedle arrays is a promising vaccination strategy. However, reduction of microneedle sharpness and the available surface area for antigen coating is a limiting factor. To overcome these obstacles, a layer-by-layer coating approach can be applied onto pH-sensitive microneedles. Following this approach, pH-sensitive microneedle arrays (positively charged at coating pH 5.8 and nearly uncharged at pH 7.4) were alternatingly coated with negatively charged diphtheria toxoid (DT) and N-trimethyl chitosan (TMC), a cationic adjuvant. First, the optimal DT dose for intradermal immunization was determined in a dose-response study, which revealed that low-dose intradermal immunization was more efficient than subcutaneous immunization and that the EC50 dose of DT upon intradermal immunization is 3-fold lower, as compared to subcutaneous immunization. In a subsequent immunization study, microneedle arrays coated with an increasing number (2, 5, and 10) of DT/TMC bilayers resulted in step-wise increasing DT-specific immune responses. Dermal immunization with microneedle arrays coated with 10 bilayers of DT/TMC (corresponding with ± 0.6 μg DT delivered intradermally) resulted in similar DT-specific immune responses as subcutaneous immunization with 5 μg of DT adjuvanted with aluminum phosphate (8-fold dose reduction). Summarizing, the layer-by-layer coating approach onto pH-sensitive microneedles is a versatile method to precisely control the amount of coated and dermally-delivered antigen that is highly suitable for dermal immunization.
Dynamics of Telomere Length Reflect the Clonal Suppression Seen with the Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia
Authors: Monika Haubitz, Elisabeth Oppliger Leibundgut, Ingrid Helsen, Dania Hiltbrunner, Bart Burington, Oliver G. Ottmann, Gary Spitzer, Olatoyosi Odenike, Michael A McDevitt, Alexander Röth, David S. Snyder, Gabriela M. Baerlocher
Journal: Blood (2016)
Stepped care targeting psychological distress in head and neck cancer survivors: Effectiveness of watchful waiting and guided self-help.
Authors: A.M. Krebber, Pim Cuijpers, B.I. Witte, R. de Bree, A. van Straten, G.M. Eeckhout, A.T.F. Beekman, C.R. Leemans, I.M. Verdonck-de Leeuw
Journal: Annals of Oncology (2016)
First LINE Treatment of Aplastic Anemia with Thymoglobuline in Europe and ASIA: Outcome of 976 Patients Treated 2001-2012.
Authors: Andrea Bacigalupo, Rosi Oneto, Schrezenmeier Hubert, Dufour Carlo, Seiji Kojima, Surapol Issaragrisi, Dae Chul Jeong, Xiaofan Zhou, Yizhou Zheng, Hoechsmann Britta, Carlos Vallejo
Journal: Blood (2016)