tbuckley/cabot-search huggingface dataset:
Prospective Validation of a 21-Gene Expression Assay in Breast Cancer
Authors: Joseph A. Sparano, Robert J. Gray, Della F. Makower, Kathleen I. Pritchard, Kathy S. Albain, Daniel F. Hayes, Charles E. Geyer, Elizabeth C. Dees, Edith A. Perez, John A. Olson, JoAnne Zujewski, Tracy Lively, Sunil S. Badve, Thomas J. Saphner, Lynne I. Wagner, Timothy J. Whelan, Matthew J. Ellis, Soonmyung Paik, William C. Wood, Peter Ravdin, Maccon M. Keane, Henry L. Gomez Moreno, Pavan S. Reddy, Timothy F. Goggins, Ingrid A. Mayer, Adam M. Brufsky, Deborah L. Toppmeyer, Virginia G. Kaklamani, James N. Atkins, Jeffrey L. Berenberg, George W. Sledge
Journal: New England Journal of Medicine (2015)

Prior studies with the use of a prospective-retrospective design including archival tumor samples have shown that gene-expression assays provide clinically useful prognostic information. However, a prospectively conducted study in a uniformly treated population provides the highest level of evidence supporting the clinical validity and usefulness of a biomarker.We performed a prospective trial involving women with hormone-receptor-positive, human epidermal growth factor receptor type 2 (HER2)-negative, axillary node-negative breast cancer with tumors of 1.1 to 5.0 cm in the greatest dimension (or 0.6 to 1.0 cm in the greatest dimension and intermediate or high tumor grade) who met established guidelines for the consideration of adjuvant chemotherapy on the basis of clinicopathologic features. A reverse-transcriptase-polymerase-chain-reaction assay of 21 genes was performed on the paraffin-embedded tumor tissue, and the results were used to calculate a score indicating the risk of breast-cancer recurrence; patients were assigned to receive endocrine therapy without chemotherapy if they had a recurrence score of 0 to 10, indicating a very low risk of recurrence (on a scale of 0 to 100, with higher scores indicating a greater risk of recurrence).Of the 10,253 eligible women enrolled, 1626 women (15.9%) who had a recurrence score of 0 to 10 were assigned to receive endocrine therapy alone without chemotherapy. At 5 years, in this patient population, the rate of invasive disease-free survival was 93.8% (95% confidence interval [CI], 92.4 to 94.9), the rate of freedom from recurrence of breast cancer at a distant site was 99.3% (95% CI, 98.7 to 99.6), the rate of freedom from recurrence of breast cancer at a distant or local-regional site was 98.7% (95% CI, 97.9 to 99.2), and the rate of overall survival was 98.0% (95% CI, 97.1 to 98.6).Among patients with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who met established guidelines for the recommendation of adjuvant chemotherapy on the basis of clinicopathologic features, those with tumors that had a favorable gene-expression profile had very low rates of recurrence at 5 years with endocrine therapy alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00310180.).
A School-Based Intervention for Diabetes Risk Reduction
Authors: Gary D Foster, Barbara Linder, Tom Baranowski, Dan M Cooper, Linn Goldberg, Joanne S Harrell, Francine Kaufman, Marsha D Marcus, Roberto P Treviño, Kathryn Hirst
Journal: New England Journal of Medicine (2010)

We examined the effects of a multicomponent, school-based program addressing risk factors for diabetes among children whose race or ethnic group and socioeconomic status placed them at high risk for obesity and type 2 diabetes.
Interfering with VE-PTP stabilizes endothelial junctions in vivo via Tie-2 in the absence of VE-cadherin
Authors: Maike Frye, Martina Dierkes, Verena Küppers, Matthias Vockel, Janina Tomm, Dagmar Zeuschner, Jan Rossaint, Alexander Zarbock, Gou Young Koh, Kevin Peters, Astrid Fee Nottebaum, Dietmar Vestweber
Journal: The Journal of Experimental Medicine (2015)

Vascular endothelial (VE)–protein tyrosine phosphatase (PTP) associates with VE-cadherin, thereby supporting its adhesive activity and endothelial junction integrity. VE-PTP also associates with Tie-2, dampening the tyrosine kinase activity of this receptor that can support stabilization of endothelial junctions. Here, we have analyzed how interference with VE-PTP affects the stability of endothelial junctions in vivo. Blocking VE-PTP by antibodies, a specific pharmacological inhibitor (AKB-9778), and gene ablation counteracted vascular leak induction by inflammatory mediators. In addition, leukocyte transmigration through the endothelial barrier was attenuated. Interference with Tie-2 expression in vivo reversed junction-stabilizing effects of AKB-9778 into junction-destabilizing effects. Furthermore, lack of Tie-2 was sufficient to weaken the vessel barrier. Mechanistically, inhibition of VE-PTP stabilized endothelial junctions via Tie-2, which triggered activation of Rap1, which then caused the dissolution of radial stress fibers via Rac1 and suppression of nonmuscle myosin II. Remarkably, VE-cadherin gene ablation did not abolish the junction-stabilizing effect of the VE-PTP inhibitor. Collectively, we conclude that inhibition of VE-PTP stabilizes challenged endothelial junctions in vivo via Tie-2 by a VE-cadherin–independent mechanism. In the absence of Tie-2, however, VE-PTP inhibition destabilizes endothelial barrier integrity in agreement with the VE-cadherin–supportive effect of VE-PTP.
Incidence of Malignancies in Patients With Antineutrophil Cytoplasmic Antibody–Associated Vasculitis Diagnosed Between 1991 and 2013
Authors: Chinar Rahmattulla, Annelies E. Berden, Sophie‐Charlotte Wakker, Marlies E. J. Reinders, Ernst C. Hagen, Ron Wolterbeek, Jan A. Bruijn, Ingeborg M. Bajema
Journal: Arthritis & Rheumatology (2015)

To investigate the incidence of malignancies during longitudinal followup of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), and to examine the effect of immunosuppressive therapy on malignancy risk in these patients.The study population consisted of patients with histopathologically confirmed AAV, diagnosed between 1991 and 2013 at a large university hospital. The mean duration of followup was 10 years. Malignancy incidence was assessed using the Dutch National Pathology Database. Incidence rates from the Netherlands Cancer Registry were used to compare malignancy incidence in the AAV cohort to that in the general Dutch population.Thirty-six of 138 patients with AAV developed a total of 85 malignancies during a mean followup of 9.7 years. The sex-, age-, and calendar year-adjusted malignancy risk was 2.21-fold higher (95% confidence interval [95% CI] 1.64-2.92) than that in the general population. Non-melanoma skin cancers occurred most frequently (standardized incidence ratio 4.23 [95% CI 2.76-6.19]). The incidence rates of other malignancies were not significantly increased. Malignancy risk was associated with the duration of cyclophosphamide (CYC) therapy and, interestingly, was not increased in patients who had received CYC for <1 year.Patients with AAV have a higher risk of malignancy than the general population, but this risk is accounted for solely by non-melanoma skin cancers. Over the years, the risk of other malignancies-specifically bladder and hematologic malignancies-has decreased in patients with AAV. This finding reflects ongoing efforts to reduce CYC exposure by developing new treatment regimens.
Expert patients programme recognises value of patients
Authors: Mark Duman
Journal: BMJ (2003)

Editor—Much has been written about the increasing autonomy of patients and ways in which high quality information needed to further promote this change should be presented and produced.1-3 However, reports show that considerable deficiencies still exist in both the quality and accessibility of information for patients.4

In an era when marketing and brands hold more sway over public opinion than ever before, one has to ask what sort of product would be sold without prior rigorous market testing into its functionality and design? Everything from cars to washing machines is consumer tested before rollout—why should patient information be any different? Still not enough of the patient information available today considers patients' views sufficiently. It's not just a case of having a few colleagues quickly scan a leaflet to rubber stamp it before final production. Patients have to be involved right from the beginning—from deciding whether the information is needed and in what format, right through to reviewing it after it's been in circulation for a while. It is crucial to elicit patients' views on what actually goes into the information—the quality of life information that only patients themselves possess; what it's like to live with a specific condition, or to have to endure potential side effects from treatment. Refreshingly, the expert patients programme recognises and uses this fundamental knowledge.5
Computerized Physician Order Entry–Based System Improves Hepatitis B Virus Screening in Patients Undergoing Chemotherapy
Authors: Joaquín Cabezas, Blanca Sampedro, Cándido Hernández, Javier Crespo
Journal: Journal of Clinical Oncology (2015)

TO THE EDITOR: In the clinical opinion update by Hwang et al, the authors reviewed the most important issues related to hepatitis B virus (HBV) screening in patients who are about to receive cytotoxic chemotherapy for the treatment of malignant diseases. This update notes the importance of screening all patients who are going to be treated with anti-CD20 therapy. The authors also point out that this screening should be extended to patients with high risk factors for HBV infection. Then, when a patient who is hepatitis B surface antigen (HBsAg) positive/hepatitis B core antibody (anti-HBc) positive is identified, antiviral treatment should be started just before or at the same time as chemotherapy. In contrast, patients who are HBsAg negative/anti-HBc positive could be carefully observed with ALT and HBV-DNA levels. In the article by Hwang et al, Spain is included as a country with HBV prevalence greater than 2%. We believe this statement is currently obsolete and should be corrected. Because of the universal vaccination program started circa 1992, the HBV prevalence in Spain is now approximately 0.7% (HBsAg positive). However, this 0.7% prevalence in HBsAg does not disqualify, in our opinion, a universal HBsAg screening for all patients scheduled to receive systemic cancer therapy. As Hwang et al succinctly mentioned, previous studies have shown that universal screening for HBsAg is not only cost effective but actually cost saving when compared with no screening or screening only high-risk individuals before starting chemotherapy, particularly when the prevalence of HBsAg in the low-risk population is greater than 0.20%. Finally, one aspect that we miss in this special article is the mention of currently available innovative strategies to facilitate this HBV screening in the hospital setting, where the majority of immunosuppressive therapies are prescribed. We are referring specifically to the use of the computerized physician order entry–based (CPOE) systems that apply to this subject. As we previously have demonstrated, the use of this CPOE system in our hospital increased theHBV screening rate from less than 50% to 94% forHBsAg and from less than 30% to 85% for anti-HBc in patients for whom a biologic drug was prescribed. In conclusion, we consider it reasonable to recommend universal HBsAg (and anti-HBc) screening for all patients scheduled to receive systemic cancer therapies or other immunosuppressive therapies, adding when available or feasible the potential benefits of new tools such as CPOE systems together with educational efforts to improve the HBV screening rates.
Poor Documentation of Inflammatory Bowel Disease Quality Measures in Academic, Community, and Private Practice
Authors: Joseph D. Feuerstein, Natalia E. Castillo, Sana S. Siddique, Jeffrey J. Lewandowski, Kathy Geissler, Manuel Martinez-Vazquez, Chandrashekhar Thukral, Daniel A. Leffler, Adam S. Cheifetz
Journal: Clinical Gastroenterology and Hepatology (2015)
Targeting ceramide synthase 6–dependent metastasis-prone phenotype in lung cancer cells
Authors: Motoshi Suzuki, Ke Cao, Seiichi Kato, Yuji Komizu, Naoki Mizutani, Kouji Tanaka, Chinatsu Arima, Mei Chee Tai, Kiyoshi Yanagisawa, Norie Togawa, Takahiro Shiraishi, Noriyasu Usami, Tetsuo Taniguchi, Takayuki Fukui, Kohei Yokoi, Keiko Wakahara, Yoshinori Hasegawa, Yukiko Mizutani, Yasuyuki Igarashi, Jin-ichi Inokuchi, Soichiro Iwaki, Satoshi Fujii, Akira Satou, Yoko Matsumoto, Ryuichi Ueoka, Keiko Tamiya-Koizumi, Takashi Murate, Mitsuhiro Nakamura, Mamoru Kyogashima, Takashi Takahashi
Journal: Journal of Clinical Investigation (2015)

Sphingolipids make up a family of molecules associated with an array of biological functions, including cell death and migration. Sphingolipids are often altered in cancer, though how these alterations lead to tumor formation and progression is largely unknown. Here, we analyzed non–small-cell lung cancer (NSCLC) specimens and cell lines and determined that ceramide synthase 6 (CERS6) is markedly overexpressed compared with controls. Elevated CERS6 expression was due in part to reduction of microRNA-101 (miR-101) and was associated with increased invasion and poor prognosis. CERS6 knockdown in NSCLC cells altered the ceramide profile, resulting in decreased cell migration and invasion in vitro, and decreased the frequency of RAC1-positive lamellipodia formation while CERS6 overexpression promoted it. In murine models, CERS6 knockdown in transplanted NSCLC cells attenuated lung metastasis. Furthermore, combined treatment with l-α-dimyristoylphosphatidylcholine liposome and the glucosylceramide synthase inhibitor D-PDMP induced cell death in association with ceramide accumulation and promoted cancer cell apoptosis and tumor regression in murine models. Together, these results indicate that CERS6-dependent ceramide synthesis and maintenance of ceramide in the cellular membrane are essential for lamellipodia formation and metastasis. Moreover, these results suggest that targeting this homeostasis has potential as a therapeutic strategy for CERS6-overexpressing NSCLC.
Opportunities to Improve Care for Surgery Patients
Authors: O. Joe Hines
Journal: JAMA Surgery (2015)

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
Probabilistic non-linear registration with spatially adaptive regularisation
Authors: I.J.A. Simpson, M.J. Cardoso, M. Modat, D.M. Cash, M.W. Woolrich, J.L.R. Andersson, J.A. Schnabel, S. Ourselin
Journal: Medical Image Analysis (2015)

This paper introduces a novel method for inferring spatially varying regularisation in non-linear registration. This is achieved through full Bayesian inference on a probabilistic registration model, where the prior on the transformation parameters is parameterised as a weighted mixture of spatially localised components. Such an approach has the advantage of allowing the registration to be more flexibly driven by the data than a traditional globally defined regularisation penalty, such as bending energy. The proposed method adaptively determines the influence of the prior in a local region. The strength of the prior may be reduced in areas where the data better support deformations, or can enforce a stronger constraint in less informative areas. Consequently, the use of such a spatially adaptive prior may reduce unwanted impacts of regularisation on the inferred transformation. This is especially important for applications where the deformation field itself is of interest, such as tensor based morphometry. The proposed approach is demonstrated using synthetic images, and with application to tensor based morphometry analysis of subjects with Alzheimer's disease and healthy controls. The results indicate that using the proposed spatially adaptive prior leads to sparser deformations, which provide better localisation of regional volume change. Additionally, the proposed regularisation model leads to more data driven and localised maps of registration uncertainty. This paper also demonstrates for the first time the use of Bayesian model comparison for selecting different types of regularisation.
IFN-γ–Producing T-Helper 17.1 Cells Are Increased in Sarcoidosis and Are More Prevalent than T-Helper Type 1 Cells
Authors: Joris Ramstein, Caroline E. Broos, Laura J. Simpson, K. Mark Ansel, Sara A. Sun, Melissa E. Ho, Prescott G. Woodruff, Nirav R. Bhakta, Laura Christian, Christine P. Nguyen, Bobby J. Antalek, Bryan S. Benn, Rudi W. Hendriks, Bernt van den Blink, Mirjam Kool, Laura L. Koth
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Pulmonary sarcoidosis is classically defined by T-helper (Th) cell type 1 inflammation (e.g., IFN-γ production by CD4(+) effector T cells). Recently, IL-17A-secreting cells have been found in lung lavage, invoking Th17 immunity in sarcoidosis. Studies also identified IL-17A-secreting cells that expressed IFN-γ, but their abundance as a percentage of total CD4(+) cells was either low or undetermined.Based on evidence that Th17 cells can be polarized to Th17.1 cells to produce only IFN-γ, our goal was to determine whether Th17.1 cells are a prominent source of IFN-γ in sarcoidosis.We developed a single-cell approach to define and isolate major Th-cell subsets using combinations of chemokine receptors and fluorescence-activated cell sorting. We subsequently confirmed the accuracy of subset enrichment by measuring cytokine production.Discrimination between Th17 and Th17.1 cells revealed very high percentages of Th17.1 cells in lung lavage in sarcoidosis compared with controls in two separate cohorts. No differences in Th17 or Th1 lavage cells were found compared with controls. Lung lavage Th17.1-cell percentages were also higher than Th1-cell percentages, and approximately 60% of Th17.1-enriched cells produced only IFN-γ.Combined use of surface markers and functional assays to study CD4(+) T cells in sarcoidosis revealed a marked expansion of Th17.1 cells that only produce IFN-γ. These results suggest that Th17.1 cells could be misclassified as Th1 cells and may be the predominant producer of IFN-γ in pulmonary sarcoidosis, challenging the Th1 paradigm of pathogenesis.
Mechanisms Contributing to the Progression of Ischemic and Nonischemic Dilated Cardiomyopathy
Authors: Anita A. Kelkar, Javed Butler, Erik B. Schelbert, Stephen J. Greene, Arshed A. Quyyumi, Robert O. Bonow, Ira Cohen, Mihai Gheorghiade, Michael J. Lipinski, Wei Sun, Dror Luger, Stephen E. Epstein
Journal: Journal of the American College of Cardiology (2015)
Tobacco companies take UK to court over “standardised packaging” regulations
Authors: Clare Dyer
Journal: BMJ (2015)

Four of the world’s biggest tobacco companies are taking the UK government to court over “standardised packaging” rules for cigarettes, which are due to come into force in May 2016.

Philip Morris International, British American Tobacco, Imperial Tobacco, and Japan Tobacco International claim that the government has stolen their intellectual property and deprived them of billions of pounds by denying them the right to use any form of branding on cigarette packs.

All cigarette packets manufactured for the United Kingdom and Ireland must have a standard pack design from May …
P41 Genetic variation in biliary transporters as a susceptibility factor for cholangiocarcinoma
Authors: C Wadsworth, P Dixon, J Wong, M Chapman, S McKay, A Sharif, D Spalding, S Pereira, H Thomas, S Taylor-Robinson, J Whittaker, C Williamson, S Khan
Journal: Gut (2010)

Introduction  Cholangiocarcinoma (CC) is increasing in incidence globally but its pathogenesis remains poorly understood. Chronic inflammation of the bile duct and cholestasis are major risk factors but most cases in the West are sporadic. Genetic polymorphisms in biliary transporter proteins have been implicated in benign biliary disease and, in the case of progressive familial cholestasis, have been associated with childhood onset of CC. A recent case-control study of a single nucleotide polymorphism c.3972C>T (rs3740066) in ABCC2, reported an association with CC.  Aim  To investigate five biologically plausible candidate genes as susceptibility factors for cholangiocarcinoma; ABCB11 (BSEP); ABCB4 (MDR3); ABCC2 (MRP2); ATP8B1 (FIC1) and NR1H4 (FXR).  Method  Germline DNA was collected from 172 Caucasian individuals with confirmed CC. A control cohort of 256 healthy Caucasian patients was included in the analysis. 73 SNPs were selected using the HapMap database in Haploview 4.1 (build 22; MAF >0.05, pair-wise comparisons only) to capture the majority of common genetic variation around the five candidate loci. Genotyping was undertaken with a competitive allele-specific PCR based robotic genotyping system. Confirmation of Hardy-Weinberg equilibrium and Cochran-Armitage trend testing were performed using PLINK v1.07. Haplotype frequencies were compared using haplo.stats v1.4.4.  Results  All 73 SNPs were in Hardy-Weinberg Equilibrium. Four SNPs in ABCB11 were associated with altered susceptibility to CC, including the V444A polymorphism (c.1331T>C, rs2287622, p  Conclusion  This is the largest study to date of biliary transporter polymorphisms as susceptibility factors for CC. The previously reported association between SNP rs3 740 066 in ABCC2 and CC was not replicated. Haplotypes in ATP8B1 demonstrated a significant difference between CC and control groups. There was also a trend towards significant association of V444A with CC. V444A has been strongly implicated in other cholestatic diseases. Given the biological plausibility of polymorphisms in ABCB11 and ATP8B1 as risk modifiers for CC, further study in a validation cohort is required.