tbuckley/cabot-search huggingface dataset:
Impact of diabetes and sex in heart failure with reduced ejection fraction patients from the ASIAN‐HF registry
Authors: Chanchal Chandramouli, Tiew‐Hwa Katherine Teng, Wan Ting Tay, Jonathan Yap, Michael R. MacDonald, Jasper Tromp, Limin Yan, Bambang Siswanto, Eugenio B. Reyes, Tachapong Ngarmukos, Cheuk‐Man Yu, Chung‐Lieh Hung, Inder Anand, A. Mark Richards, Lieng Hsi Ling, Judith G. Regensteiner, Carolyn S.P. Lam
Journal: European Journal of Heart Failure (2018)
Exploring the relationship of hyaluronic acid molecular weight and active targeting efficiency for designing hyaluronic acid-modified nanoparticles
Authors: Lu Zhong, Yanying Liu, Lu Xu, Qingsong Li, Dongyang Zhao, Zhenbao Li, Huicong Zhang, Haotian Zhang, Qiming Kan, Jin Sun, Zhonggui He
Journal: Asian Journal of Pharmaceutical Sciences (2018)

Although it is reported that the targeting ability of hyaluronic acid (HA)-based nanoparticles (NPs) is molecular weight (MW) dependent, the influence of HA MW on targeting efficiency of HA-functionalized NPs and the underlying mechanism remain elusive. In this study, we constituted three HA-functionalized Dox-loaded NPs (Dox/HCVs) different HA MWs (7, 63, and 102 kDa) and attempted to illustrate the effects of HA MW on the targeting efficiency. The three Dox/HCVs had similar physiochemical and pharmaceutical characteristics, but showed different affinity to CD44 receptor. Furthermore, Dox/HCV-63 exerted the best targeting effect and the highest cytotoxicity compared with Dox/HCV-7 and Dox/HCV-102. It was interesting to found that both the HA-CD44 binding affinity and induced CD44 clustering by HA-based NPs were HA MW-dependent, the two of which determine the apparent targeting efficacy of Dox/HCV NPs in the conflicting directions. Those results laid a good foundation for rationally designing HA-based NPs in cancer therapy.
Will the Debate Over e-Cigarettes Start Cooling Down?
Authors: Theodore L. Wagener
Journal: JAMA Network Open (2018)

Maciej L. Goniewicz, PharmD, PhD; Danielle M. Smith, MPH; Kathryn C. Edwards, PhD; Benjamin C. Blount, PhD; Kathleen L. Caldwell, PhD; Jun Feng, PhD; Lanqing Wang, PhD; Carol Christensen, PhD; Bridget Ambrose, PhD; Nicolette Borek, PhD; Dana van Bemmel, PhD; Karen Konkel, PhD; Gladys Erives, PhD; Cassandra A. Stanton, PhD; Elizabeth Lambert, MSc; Heather L. Kimmel, PhD; Dorothy Hatsukami, PhD; Stephen S. Hecht, PhD; Raymond S. Niaura, PhD; Mark Travers, PhD; Charles Lawrence, PhD; Andrew J. Hyland, PhD
Gene Silencing in the Right Place at the Right Time
Authors: Anna Gutkin, Dan Peer
Journal: Molecular Therapy (2018)

(Molecular Therapy 26, 2539–2541; November 2018) Anna Gutkin was inadvertently misspelled in the original article. Her name appears correctly in this Correction and has been corrected online. The authors apologize for this error. Gene Silencing in the Right Place at the Right TimeGutkin et al.Molecular TherapyOctober 23, 2018In BriefThe CNS in general and the brain, in particular, remain difficult to target for drug or gene delivery. This is mainly due to the presence of a highly restrictive barrier that lines the blood vessels within the brain, termed the blood-brain barrier (BBB). The BBB protects the brain from invading organisms and neurotoxins, regulates the uptake of essential nutrients, and also prevents the entrance of therapeutic agents.1 In recent years, there has been a tremendous effort to develop new methods for delivering different types of therapeutic agents to the brain but, unfortunately, without much success. Full-Text PDF Open Archive
Abstract P269: Cardio-Ankle Vascular Index and the Risk of Cardiovascular Outcomes and All-cause Mortality: A Systematic Review
Authors: Kunihiro Matsushita, Ning Ding, Esther Kim
Journal: Circulation (2018)

Introduction: Arterial stiffness is widely used as an index of arteriosclerosis and is associated with cardiovascular disease (CVD). Recently, cardio-ankle vascular index (CAVI) was developed as a measurement of arterial stiffness that is independent of blood pressure at the time of arterial stiffness evaluation. The associations of CAVI with CVD events and all-cause mortality have not been extensively assessed. We therefore systematically reviewed the studies reporting CAVI and relevant outcomes. Methods: We searched for both prospective and cross-sectional studies using MEDLINE, Embase, and Cochrane from inception to April 11, 2017. Two independent reviewers screened the retrieved papers, extracted relevant data and assessed the risk of bias. Any discrepancy was solved by discussion or a third reviewer. Heterogeneity among studies was assessed using the I 2 statistic. We pooled the results of studies that were sufficiently homogeneous. Results: Among 1,519 records, we identified 9 cohort studies (n=5,292) and 17 cross-sectional eligible studies (n=7,309). All 9 cohort studies reported the outcome of composited CVD (498 cases), but the categorization/modeling of CAVI was not consistent across those studies. The pooled hazard ratio (HR) of CVD for the highest vs. lowest CAVI category in 3 studies was borderline significant (pooled HR=1.34 [0.95, 1.87], p=0.092) (I 2 = 25.2%, p=0.263). For 3 studies examining the continuous association between CAVI and CVD, 1standard deviation (SD) increment of CAVI was significantly associated with CVD risk (pooled HR=1.22 [1.03, 1.45], p=0.023) (I 2 = 27.1%, p=0.253). Only 3 cohort studies investigated CAVI and all-cause mortality, and none of them reported a significant association. All 17 cross-sectional studies reported higher CAVI values in patients with CVD compared to those without CVD, with statistical significance in most studies. Conclusions: CAVI was generally higher in patients with CVD compared to their counterparts. In terms of the prospective prognostic value of CAVI, we found a limited number of studies, but they indicated a modest association between CAVI and CVD risk. Our systematic review highlighted the need for large prospective studies to assess the usefulness of CAVI as a predictor of CVD and mortality.
Trastuzumab Therapy for 9 Weeks vs 1 Year for Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer
Authors: Zachary R. McCaw, Fei Jiang, Lee-Jen Wei
Journal: JAMA Oncology (2018)

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 Oncology 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 Oncology journal
Updated Results from the Phase 2 Centaurus Study of Daratumumab (DARA) Monotherapy in Patients with Intermediate-Risk or High-Risk Smoldering Multiple Myeloma (SMM)
Authors: Ola Landgren, Michele Cavo, Ajai Chari, Yael C Cohen, Andrew Spencer, Peter M. Voorhees, Jane Estell, Irwindeep Sandhu, Matthew Jenner, Catherine Williams, Niels WCJ van de Donk, Meral Beksac, Hartmut Goldschmidt, Philippe Moreau, Steven Kuppens, Rajesh Bandekar, Tobias Neff, Annelore Cortoos, Pamela L Clemens, Ming Qi, Homer Adams, Craig C Hofmeister
Journal: Blood (2018)
Tezepelumab, an anti–thymic stromal lymphopoietin monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: A randomized phase 2a clinical trial
Authors: Eric L. Simpson, Jane R. Parnes, Dewei She, Sarah Crouch, William Rees, May Mo, René van der Merwe
Journal: Journal of the American Academy of Dermatology (2018)

Tezepelumab (AMG 157/MEDI9929), a first-in-class monoclonal antibody, targets thymic stromal lymphopoietin, a cytokine that is implicated in the pathogenesis of atopic dermatitis (AD).We sought to evaluate the efficacy and safety of tezepelumab in adults with moderate to severe AD.In this phase 2a study (NCT02525094), 113 patients were randomized 1:1 to subcutaneous tezepelumab 280 mg or placebo every 2 weeks, plus class 3 topical corticosteroids (TCS). The primary endpoint was the week 12 response rate for a ≥50% reduction in the Eczema Area and Severity Index (EASI50). Secondary endpoints including EASI75, Investigator's Global Assessment, SCORAD 50, SCORAD 75, pruritus numeric rating and 5-D itch scales, and exploratory endpoints (including EASI90) were assessed at weeks 12, and 16 (post hoc).A numerically greater percentage of tezepelumab plus TCS-treated patients achieved EASI50 (64.7%) versus placebo plus TCS (48.2%; P = .091). Numerical improvements over placebo were demonstrated for week 12 secondary and exploratory endpoints, with further improvements at week 16. Treatment-emergent adverse events were similar between treatment groups.Greater than expected response rates in placebo-treated patients were possibly attributable to TCS.Although not statistically significant, numerical improvements over placebo for all week 12 endpoints were demonstrated, with greater week 16 responses.
Whole-exon sequencing of human myeloma cell lines shows mutations related to myeloma patients at relapse with major hits in the DNA regulation and repair pathways
Authors: Benoît Tessoulin, Agnès Moreau-Aubry, Géraldine Descamps, Patricia Gomez-Bougie, Sophie Maïga, Alban Gaignard, David Chiron, Emmanuelle Ménoret, Steven Le Gouill, Philippe Moreau, Martine Amiot, Catherine Pellat-Deceunynck
Journal: Journal of Hematology & Oncology (2018)

Human myeloma cell lines (HMCLs) are widely used for their representation of primary myeloma cells because they cover patient diversity, although not fully. Their genetic background is mostly undiscovered, and no comprehensive study has ever been conducted in order to reveal those details. We performed whole-exon sequencing of 33 HMCLs, which were established over the last 50 years in 12 laboratories. Gene expression profiling and drug testing for the 33 HMCLs are also provided and correlated to exon-sequencing findings. Missense mutations were the most frequent hits in genes (92%). HMCLs harbored between 307 and 916 mutations per sample, with TP53 being the most mutated gene (67%). Recurrent bi-allelic losses were found in genes involved in cell cycle regulation (RB1, CDKN2C), the NFκB pathway (TRAF3, BIRC2), and the p53 pathway (TP53, CDKN2A). Frequency of mutations/deletions in HMCLs were either similar to that of patients (e.g., DIS3, PRDM1, KRAS) or highly increased (e.g., TP53, CDKN2C, NRAS, PRKD2). MAPK was the most altered pathway (82% of HMCLs), mainly by RAS mutants. Surprisingly, HMCLs displayed alterations in epigenetic (73%) and Fanconi anemia (54%) and few alterations in apoptotic machinery. We further identified mutually exclusive and associated mutations/deletions in genes involved in the MAPK and p53 pathways as well as in chromatin regulator/modifier genes. Finally, by combining the gene expression profile, gene mutation, gene deletion, and drug response, we demonstrated that several targeted drugs overcome or bypass some mutations. With this work, we retrieved genomic alterations of HMCLs, highlighting that they display numerous and unprecedented abnormalities, especially in DNA regulation and repair pathways. Furthermore, we demonstrate that HMCLs are a reliable model for drug screening for refractory patients at diagnosis or at relapse.
Measured energy content of frequently purchased restaurant meals: multi-country cross sectional study
Authors: Susan B Roberts, Sai Krupa Das, Vivian Marques Miguel Suen, Jussi Pihlajamäki, Rebecca Kuriyan, Matilda Steiner-Asiedu, Amy Taetzsch, Alex K Anderson, Rachel E Silver, Kathryn Barger, Amy Krauss, Leila Karhunen, Xueying Zhang, Catherine Hambly, Ursula Schwab, Andresa de Toledo Triffoni-Melo, Priscila Giacomo Fassini, Salima F Taylor, Christina Economos, Anura V Kurpad, John R Speakman
Journal: BMJ (2018)

Abstract Objective To measure the energy content of frequently ordered meals from full service and fast food restaurants in five countries and compare values with US data. Design Cross sectional survey. Setting 223 meals from 111 randomly selected full service and fast food restaurants serving popular cuisines in Brazil, China, Finland, Ghana, and India were the primary sampling unit; 10 meals from five worksite canteens were also studied in Finland. The observational unit was frequently ordered meals in selected restaurants. Main outcome measure Meal energy content, measured by bomb calorimetry. Results Compared with the US, weighted mean energy of restaurant meals was lower only in China (719 (95% confidence interval 646 to 799) kcal versus 1088 (1002 to 1181) kcal; P&lt;0.001). In analysis of variance models, fast food contained 33% less energy than full service meals (P&lt;0.001). In Finland, worksite canteens provided 25% less energy than full service and fast food restaurants (mean 880 (SD 156) versus 1166 (298); P=0.009). Country, restaurant type, number of meal components, and meal weight predicted meal energy in a factorial analysis of variance (R 2 =0.62, P&lt;0.001). Ninety four per cent of full service meals and 72% of fast food meals contained at least 600 kcal. Modeling indicated that, except in China, consuming current servings of a full service and a fast food meal daily would supply between 70% and 120% of the daily energy requirements for a sedentary woman, without additional meals, drinks, snacks, appetizers, or desserts. Conclusion Very high dietary energy content of both full service and fast food restaurant meals is a widespread phenomenon that is probably supporting global obesity and provides a valid intervention target.
Comparison of Overall Survival Between Preoperative Chemotherapy and Chemoradiotherapy for Resectable Pancreatic Adenocarcinoma
Authors: Ali A. Mokdad, Rebecca M. Minter, Adam C. Yopp, Matthew R. Porembka, Sam C. Wang, Hong Zhu, Mathew M. Augustine, John C. Mansour, Michael A. Choti, Patricio M. Polanco
Journal: Journal of the National Comprehensive Cancer Network (2018)

Background: Preoperative therapy is being increasingly used in the treatment of resectable pancreatic cancer. Because there are only limited data on the optimal preoperative regimen, we compared overall survival (OS) between preoperative chemotherapy (CT) and preoperative chemoradiotherapy (CRT) in resectable pancreatic adenocarcinoma. Patients and Methods: Patients receiving preoperative therapy and resection for clinical T1–3N0–1M0 adenocarcinoma of the pancreas were identified in the National Cancer Database for 2006 through 2012. We constructed inverse probability of treatment weights to balance baseline group differences, and compared OS between CT and CRT, as well as pathologic and postoperative findings. Results: We identified 1,326 patients (CT: 616; CRT: 710). Differences in OS were not significant between CRT and CT (median survival, 25 vs 26 months; P=.10; weight-adjusted hazard ratio, 0.89; 95% CI, 0.77–1.02). Compared with patients in the CT group, those in the CRT group had lower pathologic T stage (ypT0/T1/T2: 36% vs 21%; P<.01), less lymph node involvement (ypN1: 35% vs 59%; P<.01), and fewer positive resection margins (14% vs 21%; P=.01), but had more postoperative unplanned readmissions (9% vs 6%; P=.01) and increased 90-day mortality (7% vs 4%; P=.03). Those in the CRT group were also less likely to receive postoperative therapy (26% vs 51%; P<.01). Conclusions: Preoperative CT and CRT have similar OS, but CRT is associated with more favorable pathologic features at the cost of higher postoperative morbidity and mortality. Additional trials investigating preoperative therapy are needed for patients with resectable pancreatic cancer.
Endoscopic vacuum therapy with open-pore film drainage for colonic anastomotic leakage in a morbidly obese patient
Authors: Ingo Wallstabe, Phuong Nguyen, Ingolf Schiefke, Arved Weimann
Journal: Endoscopy (2018)

Endoscopic vacuum therapy (EndoVAC) is a well-established treatment for anastomotic leakage after rectal surgery and there are a variety of other possible applications [1] [2]. In the literature, there is only one case of EndoVAC being used after colon surgery, which was for treatment of an abscess [3]. We describe the first case of EndoVAC usage for a typical anastomotic leak after colon surgery that was located 30 cm from the anus and with direct connection to the abdominal cavity.
Lymphotoxin alpha functional germline genetic variant: A future prognostic factor in colorectal cancer?
Authors: M.S. Rocha, F. Pinheiro, B. Cardoso, M. Del Rio, A. Lojo Teira, M. Pires, E. Bastos, R. Ribeiro
Journal: Annals of Oncology (2018)

Background: Lymphotoxin alpha (LTa) is a pro-inflammatory cytokine expressed by inflammatory cells with a role in the regulation of tumor microenvironment (TM). A putatively functional genetic polymorphism in LTA, at locus +80 (Thr26Asn, rs1041981), has been associated with altered expression of LTa. Here, we sought to evaluate whether this polymorphism associates with 2 main endpoints (progression-free survival (PFS) and overall survival(OS)) in colorectal cancer (CRC). Methods: This retrospective cohort study was conducted in 166 CRC patients from a single tertiary hospital. Whole blood was used to isolate genomic DNA. Genotyping of LTA +80 C > A was performed through real time-PCR allelic discrimination using specific Taqman probes, and confirmed by sequencing. Retrospective data and long-term outcomes were reviewed. Age and gender-adjusted logistic regression analyses were undertaken. Analyses were conducted after stratification by baseline lymphocyte count (LC) (LC < 1x103/µL vs > 1x103/µL). Kaplan-Meier curves with Log-Rank test were used. Subsequent multivariate Cox regression proportional hazards models were calculated (P for retention > 0.1). Results: Participants' median age was 65.9 (IR, 57.5-74.3) years, the majority were males (63%), and 58% with colon cancer. At diagnosis, 45,2% were stage III and 18,1% stage IV. The median follow up time was approximately 4 years (IQR, 25.5-67.0 months). We found a significant association in carriers of the A-allele to have lower LC on linear trend analysis (P for trend = 0.013). Multivariate comparisons between LTA genotypes of additive model showed an independent protective effect for heterozygous compared with C-homozygous in the association with disease progression (HR = 0.5, 95CI = 0.3-0.97, P = 0.041), only in subjects with baseline LC > 1x103/µL. In this group, a significant independent protective effect for all-cause mortality was observed in A-carriers (HR = 0.4, 95CI = 0.1-0.97, P = 0.042). Conclusions: This LTA genetic variant in subjects with baseline LC > 1x103/µL is associated with PFS and OS in CRC. The understanding of the impact of this polymorphisms on the evolution of the disease can bring us new information on TM regulation. Legal entity responsible for the study: Ricardo Ribeiro. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
FDA Approval Summary: Pertuzumab for Adjuvant Treatment of HER2-Positive Early Breast Cancer
Authors: Lynn J. Howie, Nancy S. Scher, Laleh Amiri-Kordestani, Lijun Zhang, Bellinda L. King-Kallimanis, Yasmin Choudhry, Jason Schroeder, Kirsten B. Goldberg, Paul G. Kluetz, Amna Ibrahim, Rajeshwari Sridhara, Gideon M. Blumenthal, Richard Pazdur, Julia A. Beaver
Journal: Clinical Cancer Research (2018)

Abstract On December 20, 2017, the FDA granted regular approval to pertuzumab in combination with trastuzumab and chemotherapy for the adjuvant treatment of patients with HER2-positive early breast cancer (EBC) at high risk of recurrence. Approval was based on data from the APHINITY trial, which randomized patients to receive pertuzumab or placebo in combination with trastuzumab and chemotherapy. After 45.4-month median follow-up, the proportion of invasive disease-free survival (IDFS) events in the intent-to-treat population was 7.1% (n = 171) in the pertuzumab arm and 8.7% (n = 210) for placebo [hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.67–1.00; P = 0.047]. The proportion of IDFS events in patients with hormone receptor–negative disease was 8.2% (n = 71) and 10.6% (n = 91) in the pertuzumab and placebo arms, respectively (HR, 0.76; 95% CI, 0.56–1.04). The proportion of IDFS events for patients with node-positive disease was 9.2% (n = 139) and 12.1% (n = 181) in the pertuzumab and placebo arms, respectively (HR, 0.77; 95% CI, 0.62–0.96). Adverse reactions in ≥30% of patients receiving pertuzumab were diarrhea, nausea, alopecia, fatigue, peripheral neuropathy, and vomiting. From a regulatory standpoint, the benefits of the addition of pertuzumab to adjuvant treatment outweighed the risks for patients with EBC at high risk of recurrence.
Commensals Suppress Intestinal Epithelial Cell Retinoic Acid Synthesis to Regulate Interleukin-22 Activity and Prevent Microbial Dysbiosis
Authors: Mayara Grizotte-Lake, Guo Zhong, Kellyanne Duncan, Jay Kirkwood, Namrata Iyer, Irina Smolenski, Nina Isoherranen, Shipra Vaishnava
Journal: Immunity (2018)
Targeting interleukin-13 in idiopathic pulmonary fibrosis: from promising path to dead end
Authors: Marlies S. Wijsenbeek, Mirjam Kool, Vincent Cottin
Journal: European Respiratory Journal (2018)

<b>Targeting IL-4/IL-13 with SAR156597 failed to demonstrate an effect on lung function decline for patients with idiopathic pulmonary fibrosis; these results are in line with the negative results of two other trials targeting IL-13 in this disease</b>http://ow.ly/J0HF30mAB3J