tbuckley/cabot-search huggingface dataset:
Therapeutic effect of capsaicin nasal treatment in patients with mixed rhinitis unresponsive to intranasal steroids
Authors: L. Van Gerven, B. Steelant, Y. A. Alpizar, K. Talavera, P. W. Hellings
Journal: Allergy (2017)

Abstract Literature is convincing regarding the efficacy of capsaicin nasal treatment in idiopathic rhinitis (IR). However, up to 50% of IR patients do not meet the strict inclusion criteria of the trials conducted so far. As a consequence, the efficacy of capsaicin is unknown in a significant number of IR patients that do not meet the strict inclusion/exclusion criteria (J Allergy Clin Immunol. 2014;133:1332, J Allergy Clin Immunol. 2017; [Epub ahead of print]). “Mixed rhinitis” (MR) patients have more than one major etiologic factor involved in the mucosal pathology. We have no idea about the efficacy of capsaicin nasal spray in these patients nor about the time interval to seek a second application. We report here that capsaicin nasal spray is effective in a broader group of IR than the purely selected ones described before, that subjective nasal hyper‐reactivity is a good predictor of positive outcome, and that the time interval for seeking a second treatment is likely to be shorter in MR patients than in the strictly selected IR patients.
Unmet Needs in Diagnosis and Treatment of Glanzmann’s Thrombasthenia (GT): Perceptions of US Hematologists and Nurses
Authors: Meera B. Chitlur, Michael Recht, Madhvi Rajpurkar, Ellis J. Neufeld, Craig M. Kessler, Mark Reding, Michael Tarantino, David L. Cooper
Journal: Blood (2014)
Targeting BCL11A and KLF1 For The Treatment Of Sickle Cell Disease and β-Thalassemia In Vitro using Antisense Oligonucleotides
Authors: Raechel Peralta, Audrey Low, Aneeza Kim, Sue Murray, Shuling Guo, Sue Freier, Tim M. Townes, Gene Hung
Journal: Blood (2013)
Dual Function of NRP1 in Axon Guidance and Subcellular Target Recognition in Cerebellum
Authors: Ludovic Telley, Christelle Cadilhac, Jean-Michel Cioni, Veronique Saywell, Céline Jahannault-Talignani, Rosa E. Huettl, Catherine Sarrailh-Faivre, Alexandre Dayer, Andrea B. Huber, Fabrice Ango
Journal: Neuron (2016)
Self controlled case series methods: an alternative to standard epidemiological study designs
Authors: Irene Petersen, Ian Douglas, Heather Whitaker
Journal: BMJ (2016)

The self controlled case series (SCCS) method is an epidemiological study design for which individuals act as their own control—ie, comparisons are made within individuals. Hence, only individuals who have experienced an event are included and all time invariant confounding is eliminated. The temporal association between a transient exposure and an event is estimated. SCCS was originally developed for evaluation of vaccine safety, but has since been applied in a range of settings where exact information on the size of the population at risk is lacking or identification of an appropriate comparison group is difficult—eg, for studies of adverse effects of drug treatments. We provide an overview of the SCCS method, with examples of its use, discuss limitations, assumptions, and potential biases that can arise where assumptions are not met, and provide solutions and examples of good practice.
Precise Somatotopic Thalamocortical Axon Guidance Depends on LPA-Mediated PRG-2/Radixin Signaling
Authors: Jin Cheng, Sadhna Sahani, Torben Johann Hausrat, Jenq-Wei Yang, Haichao Ji, Nikolai Schmarowski, Heiko Endle, Xinfeng Liu, Yunbo Li, Rahel Böttche, Konstantin Radyushkin, Hans M. Maric, Anna Hoerder-Suabedissen, Zoltán Molnár, Pierre-Hugues Prouvot, Thorsten Trimbuch, Olaf Ninnemann, Jisen Huai, Wei Fan, Barbara Visentin, Roger Sabbadini, Kristian Strømgaard, Albrecht Stroh, Heiko J. Luhmann, Matthias Kneussel, Robert Nitsch, Johannes Vogt
Journal: Neuron (2016)

Precise connection of thalamic barreloids with their corresponding cortical barrels is critical for processing of vibrissal sensory information. Here, we show that PRG-2, a phospholipid-interacting molecule, is important for thalamocortical axon guidance. Developing thalamocortical fibers both in PRG-2 full knockout (KO) and in thalamus-specific KO mice prematurely entered the cortical plate, eventually innervating non-corresponding barrels. This misrouting relied on lost axonal sensitivity toward lysophosphatidic acid (LPA), which failed to repel PRG-2-deficient thalamocortical fibers. PRG-2 electroporation in the PRG-2
Evaluation of proton pump inhibitor use on treatment outcomes with ledipasvir and sofosbuvir in a real‐world cohort study
Authors: Elliot B. Tapper, Bruce R. Bacon, Michael P. Curry, Douglas T. Dieterich, Steven L. Flamm, Lauren E. Guest, Kris V. Kowdley, Yoori Lee, Naoky C. Tsai, Zobair M. Younossi, Nezam H. Afdhal
Journal: Hepatology (2016)

Many patients with chronic hepatitis C virus (HCV) are on prolonged proton‐pump inhibitor (PPI) therapy and wish to remain on PPI therapy once treatment for HCV starts. A preliminary report recently suggested decrease rates of sustained virological response (SVR) for patients taking concomitant PPI and ledipasvir/sofosbuvir (LDV/SOF). We sought to determine the effect of PPI use on the rate of SVR in a real‐world cohort of 1,979 patients with chronic HCV treated with LDV/SOF. We collected clinical data and pharmacy dispensing records on patients taking 8, 12, or 24 weeks of LDV/SOF ± ribavirin (RBV). The primary outcome was sustained virological response at 12 weeks after treatment completion (SVR12) in a per‐protocol analysis in order to determine the effect of PPI use adjusted for confounders. Statistical adjustment was performed in propensity‐matched analysis. Among treatment completers, SVR12 was achieved in 441 (97.1%) of PPI recipients compared with 1,497 (98.2%) in PPI nonrecipients ( P = 0.19). Neither low‐ nor high‐dose PPI was associated with decreased SVR, although patients taking twice‐daily PPI achieved a lower SVR12 rate (91.2%; 95% confidence interval [CI], 77.0‐97.0; P = 0.046). After propensity matching for PPI use, there were no significant associations between SVR12 and any dose or frequency of PPI use. However, in a sensitivity analysis focusing on patients with cirrhosis, twice‐daily PPI use was associated with lower odds ratio for SVR12 (0.11; 95% CI, 0.02‐0.59). Conclusion: These data from a cohort of real‐world patients receiving hepatitis C antibody therapy with LDF/SOF ± RBV support the prescription labeling suggesting that patients take no more than low‐dose (20‐mg omeprazole equivalents) PPI daily. (H epatology 2016;64:1893‐1899).
Enhanced T cell responses to IL-6 in type 1 diabetes are associated with early clinical disease and increased IL-6 receptor expression
Authors: Christian Hundhausen, Alena Roth, Elizabeth Whalen, Janice Chen, Anya Schneider, S. Alice Long, Shan Wei, Rebecca Rawlings, MacKenzie Kinsman, Stephen P. Evanko, Thomas N. Wight, Carla J. Greenbaum, Karen Cerosaletti, Jane H. Buckner
Journal: Science Translational Medicine (2016)

T cells from diabetic individuals are hyperresponsive to IL-6 stimulation, which could contribute to disease pathogenesis and may be an avenue for therapeutic intervention.
Streptoccocus infection linked with Tourette's syndrome
Authors: Deborah Josefson
Journal: BMJ (1998)

US researchers have uncovered evidence that Tourette's syndrome, a chronic debilitating neurological disorder, may have an immune mediated, infectious basis ( Neurology 1998;50:1530-3).

Tourette's syndrome is characterised by multiple involuntary motor and vocal tics. Additionally, copralalia, the involuntary utterance of obscenities, often shouted, may occur. Since familial clustering occurs, Tourette's is thought to be genetic in origin. An autosomal dominant mode of inheritance has been proposed, but only a small number of those who inherit a single copy of the gene ever develop the syndrome.

Because of this discrepancy, Dr Harvey Singer and colleagues at the Johns Hopkins University School of Medicine …
Crucial Role of miR-433 in Regulating Cardiac Fibrosis
Authors: Lichan Tao, Yihua Bei, Ping Chen, Zhiyong Lei, Siyi Fu, Haifeng Zhang, Jiahong Xu, Lin Che, Xiongwen Chen, Joost PG Sluijter, Saumya Das, Dragos Cretoiu, Bin Xu, Jiuchang Zhong, Junjie Xiao, Xinli Li
Journal: Theranostics (2016)

Dysregulation of microRNAs has been implicated in many cardiovascular diseases including fibrosis.Here we report that miR-433 was consistently elevated in three models of heart disease with prominent cardiac fibrosis, and was enriched in fibroblasts compared to cardiomyocytes.Forced expression of miR-433 in neonatal rat cardiac fibroblasts increased proliferation and their differentiation into myofibroblasts as determined by EdU incorporation, α-SMA staining, and expression levels of fibrosis-associated genes.Conversely, inhibition of miR-433 exhibited opposite results.AZIN1 and JNK1 were identified as two target genes of miR-433.Decreased level of AZIN1 activated TGF-β1 while down-regulation of JNK1 resulted in activation of ERK and p38 kinase leading to Smad3 activation and ultimately cardiac fibrosis.Importantly, systemic neutralization of miR-433 or adeno-associated virus 9 (AAV9)-mediated cardiac transfer of a miR-433 sponge attenuated cardiac fibrosis and ventricular dysfunction following myocardial infarction.Thus, our work suggests that miR-433 is a potential target for amelioration of cardiac fibrosis.
Massive parallel sequencing of an African-American basal-like breast cancer: Comparison of primary tumor, metastasis, and xenograft.
Authors: E. Mardis, L. Ding, S. Li, D. E. Larson, K. Chen, J. Wallis, J. Hoog, K. Deshryver, R. Wilson, M. J. Ellis
Journal: Journal of Clinical Oncology (2010)

10500 Background: Massively parallel DNA sequencing technology facilitates new approaches for unbiased characterization of cancer genomes. We have pursued a novel strategy to identify mutations that are positively selected during tumor progression and therefore likely causing patient mortality. Methods: We sequenced four genomes from a 44-year old African-American patient with basal-like breast cancer; obtained from peripheral blood, the primary tumor, a brain metastasis and a first-passage xenograft derived from the primary tumor. We analyzed the data to discover single nucleotide, small deletions and structural variants unique to each sample, and then compared them. Focused PCR and deep read count data was used to validate and establish tumor cell prevalence for each somatic variant. Results: We validated a total of 50 tumor-specific genic mutations, 48 of which are shared across the three tumor samples. The metastasis contained two de novo somatic mutations relative to the primary tumor, and was enriched more than 3-fold for 20 shared mutations, suggesting that they may be driver mutations. The xenograft gained no de novo coding/splice site mutations and retained all primary tumor mutations albeit at different frequencies, suggesting that early passage xenografts largely reflect the source tumor genome at the mutational level. Validated structural variants include 7 translocations, 6 inversions and 29 deletions. Mutation recurrence data from an evaluation of nine enriched genes in >160 breast primary and metastatic tumor samples of different subtypes will be presented at the meeting. Conclusions: The differential mutation frequencies and structural patterns between primary and metastatic tumors suggest that metastatic tumors may arise from minor subpopulations within the primary. Namely, the metastatic and xenografting processes apparently select for cells harboring a distinct subset of the primary tumor mutation repertoire. This study represents an important first step in efforts to catalog all critical somatic changes in breast cancer; facilitating efforts toward personalized treatment of the disease. Support from Susan G Komen for the Cure and U54 HG003079. No significant financial relationships to disclose.
Diffusion Hypoxia and/or Primary Mitochondrial Failure?—Reply
Authors: Jonathan P. Coles, David K. Menon
Journal: JAMA Neurology (2016)

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The Human CD38 Monoclonal Antibody Daratumumab Shows Antitumor Activity and Hampers Leukemia–Microenvironment Interactions in Chronic Lymphocytic Leukemia
Authors: Alba Matas-Céspedes, Anna Vidal-Crespo, Vanina Rodriguez, Neus Villamor, Julio Delgado, Eva Giné, Heleia Roca-Ho, Pablo Menéndez, Elías Campo, Armando López-Guillermo, Dolors Colomer, Gaël Roué, Adrian Wiestner, Paul W.H.I. Parren, Parul Doshi, Jeroen Lammerts van Bueren, Patricia Pérez-Galán
Journal: Clinical Cancer Research (2016)

Abstract Purpose: To establish a proof-of-concept for the efficacy of the anti-CD38 antibody daratumumab in the poor prognosis CD38+ chronic lymphocytic leukemia (CLL) subtype. Experimental Design: The mechanism of action of daratumumab was assessed in CLL primary cells and cell lines using peripheral blood mononuclear cells to analyze antibody-dependent cell cytotoxicity (ADCC), murine and human macrophages to study antibody-dependent cell phagocytosis (ADCP), or human serum to analyze complement-dependent cytotoxicity (CDC). The effect of daratumumab on CLL cell migration and adhesion to extracellular matrix was characterized. Daratumumab activity was validated in two in vivo models. Results: Daratumumab demonstrated efficient lysis of patient-derived CLL cells and cell lines by ADCC in vitro and ADCP both in vitro and in vivo whereas exhibited negligible CDC in these cells. To demonstrate the therapeutic effect of daratumumab in CLL, we generated a disseminated CLL mouse model with the CD38+ MEC2 cell line and CLL patient–derived xenografts (CLL-PDX). Daratumumab significantly prolonged overall survival of MEC2 mice, completely eliminated cells from the infiltrated organs, and significantly reduced disease burden in the spleen of CLL-PDX. The effect of daratumumab on patient-derived CLL cell dissemination was demonstrated in vitro by its effect on CXCL12-induced migration and in vivo by interfering with CLL cell homing to spleen in NSG mice. Daratumumab also reduced adhesion of CLL cells to VCAM-1, accompanied by downregulation of the matrix metalloproteinase MMP9. Conclusions: These unique and substantial effects of daratumumab on CLL viability and dissemination support the investigation of its use in a clinical setting of CLL. Clin Cancer Res; 23(6); 1493–505. ©2016 AACR.
Consolidation Therapy with Subcutaneous Alemtuzumab Following Induction Treatment with Oral FC (Fludarabine and Cyclophosphamide) in Previously Untreated Patients Aged 65-70 Years with Advanced Stage Chronic Lymphocytic Leukemia (CLL): A Phase II Trial of the FCGCLL/MW.
Authors: Alain Delmer, Stéphane Leprêtre, Bruno Cazin, Pierre Feugier, Olivier Tournilhac, Michel Leporrier, Brigitte Dreyfus, Béatrice Mahé, Catherine Thieblemont, Marine Divine, Vincent Lévy, Véronique Leblond, Florence Cymbalista, Rémy Letestu
Journal: Blood (2006)
Abstract 2287: A model system to treat T-cell acute lymphoblastic leukemia with JAK inhibitors
Authors: Emilee Senkevitch, Julie Hixon, Wenqing Li, Scott Durum
Journal: Cancer Research (2015)

Abstract The IL-7 Receptor signaling pathway is necessary for the proliferation and survival of T cells. Together with collaborators, we have shown that 9% of patients with T cell acute lymphoblastic leukemia (T-ALL) have gain of function mutations in IL-7R exon 6. These mutations promote homodimerization of IL-7Rα subunits, resulting in constitutive activation of this pathway via JAK1. Approximately 20% of T-ALL patients fail to respond to conventional chemotherapy, so there is a need for additional options for these patients. We hypothesized that JAK inhibitors could be used to treat T-ALL patients, particularly those with IL-7R mutations. We established a cell line model of T-ALL driven by constitutive IL-7R signaling which grew as a leukemia in RAG1-/- mice. The model cells were established by transforming the D1 thymocyte cell line with a mutated IL-7Rα derived from a patient sequence. These cells termed D1_hIL7R_P1 are also GFP+ which allows us to monitor the proliferation of the cells in vivo. D1_hIL7R_P1 cells delivered intravenously result in an aggressive leukemia with morbidity within 18-21 days. Currently we are studying the chemotherapeutic effects of two JAK inhibitors, Ruxolitinib and Tofacitinib on T-ALL. The maximum tolerated doses for Tofacitinib and Ruxolitinib are 50 mg/kg and 150 mg/kg, respectively. Ruxolitinib appears to be the most effective, showing a reduction of leukemogenesis detected in blood and tissues after just three days of oral treatment. Additionally, we have obtained samples derived from pediatric T-ALL patients. Once growth kinetics in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice is established, we will proceed to study the efficacy of the JAK inhibitors with human leukemia cells. Citation Format: Emilee Senkevitch, Julie Hixon, Wenqing Li, Scott Durum. A model system to treat T-cell acute lymphoblastic leukemia with JAK inhibitors. [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 2287. doi:10.1158/1538-7445.AM2015-2287
More patients with oesophageal and gastric cancers are getting curative treatment plans
Authors: Susan Mayor
Journal: BMJ (2016)

The proportion of patients with oesophageal and gastric cancers in England and Wales who have curative treatment plans has increased in the past six years, but one in six is still diagnosed only after emergency admission to hospital, an audit has shown.1

Cancers of the oesophagus and stomach are the fifth most common cancers in the United Kingdom, but prognosis remains poor because many patients experience symptoms only when their disease is fairly advanced, so it is diagnosed at a late stage. The five …
Hip, hip, hooray!
Authors: Adam Weir, Johannes L Tol, Gustaaf Reurink
Journal: British Journal of Sports Medicine (2016)

There is plenty to celebrate in this Olympic year's issue from the Dutch Association of Sports Medicine.

Sports medicine in Holland is in celebratory mood after its recognition as a full medical specialty. Fifteen years of campaigning, hard work and determination have paid off. Big thanks to the chairman, board, staff and members of the special committees who worked tirelessly to make this happen. They faced many hurdles which they have successfully taken to achieve this great feat.

Most care provided by the 129 Dutch sports medicine physicians will now be covered by the national healthcare insurance, signalling a new era. Getting the word out to athletes, to patients with chronic conditions (who will benefit from more exercise) and to general practitioners is now …
Avoiding catastrophes: seeking synergies among the public health, environmental protection, and human security sectors
Authors: Peter Stoett, Peter Daszak, Cristina Romanelli, Catherine Machalaba, Ronald Behringer, Frank Chalk, Stephen Cornish, Simon Dalby, Braulio Ferreira de Souza Dias, Zaryab Iqbal, Tom Koch, Florian Krampe, Marieme Lo, Keith Martin, Kyle Matthews, Jason W Nickerson, James Orbinski, Andrew Price-Smith, Anne-Hélène Prieur-Richard, Adnan Raja, David M Secko, Adan Suazo, Ashok Swain
Journal: The Lancet Global Health (2016)

Global health catastrophes have complex origins, often rooted in social disruption, poverty, conflict, and environmental collapse. Avoiding them will require a new integrative analysis of the links between disease, armed conflict, and environmental degradation within a socioecological vulnerability and human security context. Exploring these connections was the aim of Avoiding Catastrophe: Linking Armed Conflict, Harm to Ecosystems, and Public Health, an expert workshop held in May 4–6, 2016, at Concordia University in Montreal, QC, Canada.
An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients With Acute Liver Injury or Failure
Authors: Dean W. Roberts, William M. Lee, Jack A. Hinson, Shasha Bai, Christopher J. Swearingen, R. Todd Stravitz, Adrian Reuben, Lynda Letzig, Pippa M. Simpson, Jody Rule, Robert J. Fontana, Daniel Ganger, K. Rajender Reddy, Iris Liou, Oren Fix, Laura P. James
Journal: Clinical Gastroenterology and Hepatology (2016)
P1-068: Comparison of RECIST, WHO criteria, and serum CEA for evaluation of tumor response to chemotherapy in non-small cell lung cancer
Authors: Futoshi Ishiguro, Tatsuya Katayama, Takayuki Fukui, Shoichi Mori, Shunzo Hatooka, Masayuki Shinoda, Tetsuya Mitsudomi
Journal: Journal of Thoracic Oncology (2007)
Relationship between socio-economic status and education grade on Breslow thickness and ulceration in clinical stage I-II AJCC skin melanoma: Analysis from a single institution prospectively collected data base.
Authors: M. Mandala, G. Imberti, D. Piazzalunga, M. Belfiglio, L. Milesi, B. Merelli, K. di Biagio, R. Labianca, A. Milesi, C. Tondini
Journal: Journal of Clinical Oncology (2010)

e19004 Background: Breslow thickness (BT) and ulceration predict survival inprimary cutaneous melanoma (PCM). We investigatedthe influence of the socio-economic (SEC) status and educational grade on BT and ulceration inclinical stage I-II AJCC PCM. Methods: The study included all consecutive patients with PCM, diagnosed, treated and followed up prospectively between November 1998 and December 2008. Age, gender, education grade, SEC status, family context, site of the primary lesion, BT, ulceration, lymph node status were collected. Education grade was categorised into four groups: primary school; middle school; high school and higher degree. SEC classes were classified as: Classe 1: manager/professionals; class 2: craftsman, clerks, manual workers; class 3: housewives; retired; unemployed. Results: A total of 1,432 consecutive patients were included. Median age was 51 years, 55.7% of them were female. For the whole population, mean BT was 1.2 (± 2.4) mm, and ulceration was present in 251 patients (18.1%). In univariate analysis, male gender, lower education grade, SEC 2 and 3 classes, and age > 60 had a higher probability of thicker Breslow (0-1 vs. 1-3 vs. > 3 mm) and ulceration (yes/not). In a multivariate and stepwise analysis, male gender (OR 1.536, 95% CI 1.177-2.006), class 2 (OR 2.091, 95% CI 1.149-3.807), class 3 (OR 3.155, 95% CI 1.905-5.227 ) and patients > 60 yrs living alone (OR 2.16, 95% CI 1.32-3.53) remained statistically significant for BT, lower education for ulceration. Conclusions: This is the first prospective monoinstitutional study demonstrating that male gender, education grade and the some socioeconomic features are associated with thicker PCM and ulceration at diagnosis. Ongoing analysis on disease free and overall survival will show if these factors also have an influence on disease outcome for these patients. No significant financial relationships to disclose.