tbuckley/cabot-search huggingface dataset:
Canada’s Amendment to Patented Drug Price Regulation
Authors: Brittany Humphries, Feng Xie
Journal: JAMA (2019)

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
Identification of retrograde peristalsis determines the afferent limb during double-balloon ERCP: the tidal wave sign
Authors: Tetsuya Iwasaki, Tomofumi Akasaka, Yuko Sakakibara, Shoichi Nakazuru, Hisashi Ishida, Eiji Mita
Journal: Endoscopy (2019)

Double-balloon endoscopy is used in endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered gastrointestinal anatomy [1]. In this procedure, it is difficult to identify the afferent limb of a Roux-en-Y anastomosis; therefore, intraluminal injection of indigo carmine and carbon dioxide enterography has been used [2] [3]. We report a novel method to identify the afferent limb.
AE 光疗和系统治疗登记数据库的 TREAT eDelphi 练习
Authors: L.A.A. Gerbens, C.J. Apfelbacher, A.D. Irvine, S. Barbarot, R.J. Booij, A.E. Boyce, M. Deleuran, L.F. Eichenfield, M.H. Hof, M.A. Middelkamp‐Hup, A. Roberts, J. Schmitt, C. Vestergaard, D. Wall, S. Weidinger, P.R. Williamson, C. Flohr, P.I. Spuls
Journal: British Journal of Dermatology (2019)

特应性皮炎 (AE) 的严重程度有时候需要强效药物治疗,但尚无很多信息帮助医生选择正确治疗。不同药物的已公布试验难以评估,因为它们包括已精心选择的患者,并以不同方式测量疗效。在一个登记数据库中采集的在研究性试验以外实际使用这些药物的患者的数据可能提供更好的长期真实生活经验,前提是每个人都以相同方式(“结局指标”)报告他们的观察结果。在这项研究中,国际特应性湿疹治疗 (TREAT) 登记任务组实施了一项在线练习,以就应当测量和报告至 AE 登记数据库的最小变量集达成一致。向 36 个国家的 479 名参与者发送了 119 个可能项目的初始列表:主要是医生,还有护士、研究者、患者、行业和监管机构代表;86% 给出了答复,按从 0(不重要)到 9(非常重要)为各项目评分。通过另外两轮削减此列表;在每一轮后反馈答复总结,并邀请参与者保留或变更他们的原始答案。最后,42 名参与者参与了共识会议,就一组核心的 49 个基线项目和 20 个随访项目达成了一致。希望在未来试验中标准化结局指标将能弥补证据的空白并改善 AE 患者的治疗。但是,正如伴随社论所指出的那样,结局指标的统一只是创建有效登记数据库所面临的众多挑战之一。
Abstract 17386: LPA Variants and Aortic Stenosis - a Large-Scale Case-Control Study Using Electronic Health Records
Authors: Hao Yu Chen, Line Dufresne, Hannah Burr, Athithan Ambikkumar, Niko Yasui, Kevin Luk, Dilrini K Ranatunga, Rachel A Whitmer, Mark Lathrop, James C Engert, George Thanassoulis
Journal: Circulation (2017)

Background: Elevated lipoprotein(a) levels are a causal factor for aortic stenosis (AS). However, large-scale replication of associations between LPA polymorphisms and AS, their interactions with a...
Running promotes chronicity of arthritis by local modulation of complement activators and impairing T regulatory feedback loops
Authors: Isabelle Cambré, Djoere Gaublomme, Nadia Schryvers, Stijn Lambrecht, Rik Lories, Koen Venken, Dirk Elewaut
Journal: Annals of the Rheumatic Diseases (2019)

Objectives The mechanisms driving onset of joint inflammation in arthritides such as rheumatoid arthritis and spondyloarthritis and the conversion to disease chronicity are poorly understood. We hypothesised mechanostrain could play an instrumental role herein by engaging local and/or systemic pathways, thereby attenuating disease course and outcome. Methods The development of collagen antibody-induced arthritis (CAIA) in C57BL/6 mice was evaluated both clinically and histologically under different loading regimens: control, voluntary running or hindpaw unloading. Bone surface porosity was quantified by high-resolution µ-CT. Gene expression analyses were conducted by microarrays and qPCR on microdissected entheses, murine and human synovial tissues (both normal and inflamed). Serum cytokines and chemokines were measured by ELISA. The influence of complement activation and T regulatory (Treg) cell function on the induction and resolution phase of disease was studied by respectively pharmacological modulation and conditional Treg depletion. Results Voluntary running strongly impacts the course of arthritis by impairing the resolution phase of CAIA, leading to more persistent inflammation and bone surface porosity. Mechanical strain induced local complement activation, increased danger-associated molecular pattern expression, activating Fcγ receptors as well as changes in fibroblast phenotype. Interestingly, complement C5a receptor blockade inhibited the enhanced joint pathology caused by voluntary running. Moreover, Treg depletion led to a loss of disease resolution in CAIA mice, which was not observed under voluntary running conditions. Conclusions Running promotes onset and chronicity of arthritis by local upregulation of complement activators and hampering regulatory T cell feedback loops.
Abstract 15959: N-6 Polyunsaturated Fatty Acids in RBC Membranes and Estimated Desaturase Activities and Risk of Sudden Cardiac Death
Authors: Stephanie E Chiuve, Nancy R Cook, M V Moorthy, J M Gaziano, Hannia Campos, Christine M Albert
Journal: Circulation (2015)

Introduction: Fatty acids in cell membranes modify the propensity for ventricular arrhythmias. In experimental studies, linoleic acid (LA;18:2n-6) has anti-arrhythmic effects, but its association with sudden cardiac death (SCD) risk has been inconsistent. Further, little is known about circulating levels of other n-6 polyunsaturated fatty acids(PUFA) and SCD risk. Methods: In a case-control analysis nested within 6 prospective cohort studies, we measured RBC levels of LA, γ-linolenic acid (GLA;18:3n-6), dihomo- γ-linoleic acid (DGLA;20:3n-6) and arachiodonic acid (AA; 20:4n-6) in 442 cases of SCD and 852 controls matched on age, sex, race, antecedent CVD, smoking status and fasting status using risk-set sampling. We estimated the activity of 2 key enzymes in n-6 PUFA metabolism, Δ-6desaurase (D6D), which converts LA to GLA, and Δ-5desaturase (D5D), which converts DGLA to AA, using their product to precursor ratios. The multivariable relative risks (RR) were estimated by conditional logistic regression adjusted for other CVD risk factors and n-3 PUFAs in each cohort separately and then combined with random effects meta-analyses. Results: DGLA was positivity linearly associated with risk of SCD while higher levels of AA were associated with lower risk of SCD. Additionally, higher D5D activity (DGLA/AA), representing greater metabolism of DGLA to AA, was inversely associated with risk (Table). Although LA demonstrated a U-shaped relation, with a nadir in SCD risk in quintile 3, the quadratic relation was not significant (p, quadratic trend = 0.95). Neither GLA nor D6D activity (GLA/LA) were associated with risk of SCD (Table). Conclusions: Higher RBC DGLA and lower RBC AA were associated with greater risk of SCD and greater estimated activity of the D5D was associated with lower risk. These n-6 PUFAs are not determined by n-6 PUFA intake and thus research on the regulation of DGLA and AA in cell membranes is warranted and may identify novel targets for SCD prevention.
Abstract MP50: Serum Metabolomic Profile of Incident Diabetes
Authors: Casey M Rebholz, Bing Yu, Zihe Zheng, Patrick Chang, Adrienne Tin, Anna Köttgen, Lynne E Wagenknecht, Josef Coresh, Eric Boerwinkle, Elizabeth Selvin
Journal: Circulation (2018)

Background: Metabolomic profiling offers the potential to reveal metabolic pathways relevant to diabetes pathophysiology and to improve diabetes risk prediction. Methods: We prospectively analyzed metabolites and incident diabetes from baseline (1987-1989) through December 31, 2015 in a subset of 2,939 Atherosclerosis Risk in Communities (ARIC) Study participants with metabolomics data and without diabetes at baseline. Metabolomic profiling was conducted in stored serum specimens collected at baseline using a reverse phase, untargeted ultra-performance liquid chromatography tandem mass spectrometry approach. Results: Among the 245 named compounds we identified, 7 metabolites were significantly associated with incident diabetes after Bonferroni correction and covariate adjustment (age, sex, race, center, batch, education, blood pressures, body mass index, lipids, smoking, physical activity, history of cardiovascular disease, eGFR, fasting glucose). These 7 metabolites consisted of a xenobiotic (erythritol) and compounds involved in amino acid metabolism [isoleucine, leucine, valine, asparagine, 3-(4-hydoxyphenyl)lactate] and glucose metabolism (trehalose). Higher levels of the metabolites were associated with an increased risk of incident diabetes, with the exception of asparagine which was associated with a lower risk of diabetes (HR per 1 SD increase: 0.78, 95% CI: 0.71, 0.85; p=4.19x10 -8 ). The 7 metabolites improved the prediction of incident diabetes beyond fasting glucose and established risk factors (C statistic for model with vs. without 7 metabolites, respectively: 0.744 vs. 0.735; p-value for difference in C statistics=0.001). Conclusions: Branched chain amino acids may play a role in diabetes development. Our study is the first to report asparagine as a protective biomarker of diabetes risk. The serum metabolome reflects known and novel metabolic disturbances that improve diabetes prediction.
T-cell bispecific antibodies in node-positive breast cancer: novel therapeutic avenue for MHC class I loss variants
Authors: M. Messaoudene, T.P. Mourikis, J. Michels, Y. Fu, M. Bonvalet, M. Lacroix-Trikki, B. Routy, A. Fluckiger, S. Rusakiewicz, M.P. Roberti, S. Cotteret, C. Flament, V. Poirier-Colame, N. Jacquelot, F. Ghiringhelli, A. Caignard, A.M.M. Eggermont, G. Kroemer, A. Marabelle, M. Arnedos, C. Vicier, S. Dogan, F. Jaulin, S -J Sammut, W. Cope, C. Caldas, S. Delaloge, N. McGranahan, F. André, L. Zitvogel
Journal: Annals of Oncology (2019)

BackgroundTumor-infiltrating lymphocytes (TILs) represent a prognostic factor for survival in primary breast cancer (BC). Nonetheless, neoepitope load and TILs cytolytic activity are modest in BC, compromising the efficacy of immune-activating antibodies, which do not yet compete against immunogenic chemotherapy.Patients and methodsWe analyzed by functional flow cytometry the immune dynamics of primary and metastatic axillary nodes [metastatic lymph nodes (mLN)] in early BC (EBC) after exposure to T-cell bispecific antibodies (TCB) bridging CD3ε and human epidermal growth factor receptor 2 (HER2) or Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 (CEACAM5), before and after chemotherapy. Human leukocyte antigen (HLA) class I loss was assessed by whole exome sequencing and immunohistochemistry. One hundred primary BC, 64 surrounding 'healthy tissue' and 24 mLN-related parameters were analyzed.ResultsHLA loss of heterozygosity was observed in EBC, at a clonal and subclonal level and was associated with regulatory T cells and T-cell immunoglobulin and mucin-domain-3 expression restraining the immuno-stimulatory effects of neoadjuvant chemotherapy. TCB bridging CD3ε and HER2 or CEACAM5 could bypass major histocompatibility complex (MHC) class I loss, partially rescuing T-cell functions in mLN.ConclusionTCB should be developed in BC to circumvent low MHC/peptide complexes.
KLF15 regulates endobiotic and xenobiotic metabolism
Authors: Shuxin Han, Jonathan W. Ray, Preeti Pathak, David R. Sweet, Rongli Zhang, Huiyun Gao, Nisha Jain, Erik H. Koritzinsky, Keiichiro Matoba, Weixiong Xu, E. Ricky Chan, Daniel I. Simon, Mukesh K. Jain
Journal: Nature Metabolism (2019)
Could Differences in Treatment Between Trial Arms Explain the Reduction in Prostate Cancer Mortality in the European Randomized Study of Screening for Prostate Cancer?
Authors: Sigrid V. Carlsson, Marianne Månsson, Sue Moss, Maciej Kwiatkowski, Franz Recker, Teuvo L.J. Tammela, Chris Bangma, Monique J. Roobol, Anssi Auvinen, Jonas Hugosson
Journal: European Urology (2019)
Rheumatoid Arthritis Disease Activity Predicting Incident Clinically Apparent Rheumatoid Arthritis–Associated Interstitial Lung Disease: A Prospective Cohort Study
Authors: Jeffrey A. Sparks, Xintong He, Jie Huang, Elaine A. Fletcher, Alessandra Zaccardelli, H. Maura Friedlander, Ritu R. Gill, Hiroto Hatabu, Mizuki Nishino, David J. Murphy, Christine K. Iannaccone, Taysir G. Mahmoud, Michelle L. Frits, Bing Lu, Ivan O. Rosas, Paul F. Dellaripa, Michael E. Weinblatt, Elizabeth W. Karlson, Nancy A. Shadick, Tracy J. Doyle
Journal: Arthritis & Rheumatology (2019)

To evaluate rheumatoid arthritis (RA) disease activity and risk of RA-associated interstitial lung disease (RA-ILD).We investigated disease activity and risk of RA-ILD using the Brigham RA Sequential Study (BRASS, 2003-2016). All patients were diagnosed as having RA according to accepted criteria. Disease Activity Scores in 28 joints (DAS28) and covariate data were measured prospectively at annual study visits. Diagnosis of RA-ILD was determined by review of images from clinically indicated chest computed tomography scans. We analyzed patients without RA-ILD at baseline. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for RA-ILD, using annually updated DAS28 data, with adjustment for known RA-ILD risk factors (age, sex, smoking status, RA duration, and serologic status). We performed alternative analyses that did not censor at the time of missing DAS28 data and included adjustment for use of methotrexate, use of glucocorticoids, presence of bone erosions, and presence of rheumatoid nodules.Among 1,419 participants, the mean ± SD age was 55.8 ± 14.2 years, and 68.6% were seropositive for either cyclic citrullinated peptide or rheumatoid factor. We identified 85 incident cases of RA-ILD during a mean ± SD follow-up duration of 8.9 ± 4.2 years per patient. The moderate/high disease activity group had a multivariable HR of 2.22 (95% CI 1.28-3.82) for RA-ILD compared to the remission/low disease activity group. Risk of RA-ILD increased across disease activity categories: multivariable HR 1.00 (reference) for remission, 1.41 (95% CI 0.61-3.28) for low disease activity, 2.08 (95% CI 1.06-4.05) for moderate disease activity, and 3.48 (95% CI 1.64-7.38) for high disease activity (P for trend = 0.001). For each unit increase in the DAS28, the risk of RA-ILD increased by 35% (95% CI 14-60%). Results were similar in analyses that included follow-up for missing DAS28 data and with adjustment for use of methotrexate, use of glucocorticoids, presence of bone erosions, or presence of rheumatoid nodules.Active articular RA was associated with an increased risk of developing RA-ILD. These results suggest that decreasing systemic inflammation may alter the natural history of RA-ILD development.
Long‐Term Physical Activity and Subsequent Risk for Rheumatoid Arthritis Among Women: A Prospective Cohort Study
Authors: Xinyi Liu, Sara K. Tedeschi, Bing Lu, Alessandra Zaccardelli, Cameron B. Speyer, Karen H. Costenbader, Elizabeth W. Karlson, Jeffrey A. Sparks
Journal: Arthritis & Rheumatology (2019)

Objective To evaluate the effects of long‐term physical activity on subsequent risk of rheumatoid arthritis ( RA ) in a prospective cohort study. Methods This study investigated physical activity and RA risk among women from the Nurses' Health Study II (1989–2015). Physical activity exposures and covariates were prospectively obtained using biennial questionnaires. Two rheumatologists independently reviewed the medical records of women who self‐reported a new diagnosis of RA on biennial questionnaires and who screened positive for RA based on a supplemental survey. All incident RA cases met the 1987 American College of Rheumatology ( ACR ) or 2010 ACR /European League Against Rheumatism ( EULAR ) classification criteria for RA . The primary analysis investigated the long‐term cumulative average number of hours spent in recreational physical activity 2–8 years prior to the RA diagnosis, a time span chosen to reduce the potential for reverse causation bias, since early RA affects physical activity prior to diagnosis. Estimated Cox regression hazard ratios ( HR s) with 95% confidence intervals (95% CI s) were used to assess the risk of RA serologic phenotypes (all, seropositive, or seronegative) in relation to physical activity categories. The analyses were adjusted for body mass index ( BMI ) at age 18 years and time‐varying potential confounders, and the mediating effect of updated BMI on the interaction between physical activity and RA risk was quantified. Results Among the 113,366 women analyzed, 506 incident RA cases (67.0% with seropositive RA ) were identified during 2,428,573 person‐years of follow‐up. After adjustment for confounders, including smoking, dietary quality, and BMI at age 18 years, increasing cumulative average total hours of recreational physical activity was associated with a reduced risk of RA , as follows: HR 1.00 for &lt;1 hour/week (reference), HR 1.00 (95% CI 0.78–1.29) for 1 to &lt;2 hours/week, HR 0.92 (95% CI 0.72–1.17) for 2 to &lt;4 hours/week, HR 0.84 (95% CI 0.63–1.12) for 4 to &lt;7 hours/week, and HR 0.67 (95% CI 0.47–0.98) for ≥7 hours/week ( P for trend = 0.02). The proportion of the effect between physical activity and RA mediated by updated BMI was 14.0% ( P = 0.002) for all RA and 20.0% ( P = 0.001) for seropositive RA . Conclusion Higher levels of physical activity were associated with reduced RA risk. These results add to the literature implicating metabolic factors in the pathogenesis of RA .
Abstract O.29: Transcriptional Profiling Discriminates Complete and Incomplete KD from Human Adenovirus
Authors: Preeti Jaggi, Asuncion Mejias, Adriana Tremoulet, Jane Burns, Wei Wang, Octavio Ramilo
Journal: Circulation (2015)

Background: The diagnosis of Kawasaki disease (KD) is often difficult to distinguish from HAdV. Objective: 1) To characterize the specific transcriptional profiles of KD patients versus acute HAdV infection 2) To determine whether the molecular distance to health (MDTH) score (a molecular score that reflects the perturbation derived from whole genome transcriptional analysis) correlates with response to therapy. Methods: Whole blood RNA samples collected in Tempus tubes were analyzed using Illumina chips and GeneSpring software 7.4 from 76 pediatric patients with complete KD, 13 with incomplete KD, and 19 patients with HadV, and 20 age- and sex-matched healthy controls (HC). We used class comparison algorithms (Mann-Whitney p&lt; 0.01, Benjamini-Hochberg, and 1.25- fold change filter) and modular analysis to define the KD profiles; class prediction algorithm was used to identify genes that best differentiate KD and HAdV. Results: Statistical group comparisons identified 7,899 genes differentially expressed in 39 complete KD patients versus HC (KD biosignature). This signature was validated in another 37 patients with complete KD and in 13 patients with incomplete KD. Modular analysis in children with complete KD demonstrated overexpression of inflammation, neutrophils, myeloid cell, coagulation cascade, and cell cycle genes. The class prediction algorithm identified 25-classifier genes that differentiated children with KD vs HAdV infection in two independent cohorts of patients with 92% (95% CI [73%-99%]) sensitivity and 90% [67%-98%] specificity. MDTH scores in KD patients significantly correlated with the baseline c-reactive protein (R=0.29, p=0.008) and was four fold higher than in children with HAdV (p&lt;0.01). In addition, KD patients that remained febrile 36 hours after treatment with IVIG (non-responders) demonstrated higher baseline, pre-treatment MDTH values compared with responders [12,290 vs. 5572 respectively; p=0.009]. Conclusion: Transcriptional signatures can be used as a tool to discriminate between KD and HAdV infection, and may also provide prognostic information.
Clinical and biological predictors of response to standardised paediatric colitis therapy (PROTECT): a multicentre inception cohort study
Authors: Jeffrey S Hyams, Sonia Davis Thomas, Nathan Gotman, Yael Haberman, Rebekah Karns, Melanie Schirmer, Angela Mo, David R Mack, Brendan Boyle, Anne M Griffiths, Neal S LeLeiko, Cary G Sauer, David J Keljo, James Markowitz, Susan S Baker, Joel Rosh, Robert N Baldassano, Ashish Patel, Marian Pfefferkorn, Anthony Otley, Melvin Heyman, Joshua Noe, Maria Oliva-Hemker, Paul A Rufo, Jennifer Strople, David Ziring, Stephen L Guthery, Boris Sudel, Keith Benkov, Prateek Wali, Dedrick Moulton, Jonathan Evans, Michael D Kappelman, M Alison Marquis, Francisco A Sylvester, Margaret H Collins, Suresh Venkateswaran, Marla Dubinsky, Vin Tangpricha, Krista L Spada, Bradley Saul, Jessie Wang, Jose Serrano, Kevin Hommel, Urko M Marigorta, Greg Gibson, Ramnik J Xavier, Subra Kugathasan, Thomas Walters, Lee A Denson
Journal: The Lancet (2019)
Abstract 12496: Relationship between Clinical Trial Site Enrollment With Participant Characteristics and Study Outcome -the HIJ-CREATE Sub-study
Authors: Hiroshi Ogawa, Dai Okayama, Hiroyuki Arashi, Erisa Kawada-Watanabe, Jun-ichi Yamaguchi, Atsushi Takagi, Nobuhisa Hagiwara
Journal: Circulation (2013)

Background: It is increasingly common for clinical trials to have numerous sites in operation in order to enroll the required number of participants. As a result, baseline characteristics, protocol...
Distinct hippocampal engrams control extinction and relapse of fear memory
Authors: Anthony F. Lacagnina, Emma T. Brockway, Chelsea R. Crovetti, Francis Shue, Meredith J. McCarty, Kevin P. Sattler, Sean C. Lim, Sofia Leal Santos, Christine A. Denny, Michael R. Drew
Journal: Nature Neuroscience (2019)