tbuckley/cabot-search huggingface dataset:
Adipogenic Effects and Gene Expression Profiling of Firemaster® 550 Components in Human Primary Preadipocytes
Authors: Emily W.Y. Tung, Vian Peshdary, Remi Gagné, Andrea Rowan-Carroll, Carole L. Yauk, Adéle Boudreau, Ella Atlas
Journal: Environmental Health Perspectives (2017)

Exposure to flame retardants has been associated with negative health outcomes including metabolic effects. As polybrominated diphenyl ether flame retardants were pulled from commerce, human exposure to new flame retardants such as Firemaster® 550 (FM550) has increased. Although previous studies in murine systems have shown that FM550 and its main components increase adipogenesis, the effects of FM550 in human models have not been elucidated.The objectives of this study were to determine if FM550 and its components are active in human preadipocytes, and to further investigate their mode of action.Human primary preadipocytes were differentiated in the presence of FM550 and its components. Differentiation was assessed by lipid accumulation and expression of peroxisome proliferator-activated receptor γ (PPARG), fatty acid binding protein (FABP) 4 and lipoprotein lipase (LPL). mRNA was collected for Poly (A) RNA sequencing and was used to identify differentially expressed genes (DEGs). Functional analysis of DEGs was undertaken in Ingenuity Pathway Analysis.FM550 triphenyl phosphate (TPP) and isopropylated triphenyl phosphates (IPTP), increased adipogenesis in human primary preadipocytes as assessed by lipid accumulation and mRNA expression of regulators of adipogenesis such as PPARγ, CCAAT enhancer binding protein (C/EBP) α and sterol regulatory element binding protein (SREBP) 1 as well as the adipogenic markers FABP4 LPL and perilipin. Poly (A) RNA sequencing analysis revealed potential modes of action including liver X receptor/retinoid X receptor (LXR/RXR) activation, thyroid receptor (TR)/RXR, protein kinase A, and nuclear receptor subfamily 1 group H members activation.We found that FM550, and two of its components, induced adipogenesis in human primary preadipocytes. Further, using global gene expression analysis we showed that both TPP and IPTP likely exert their effects through PPARG to induce adipogenesis. In addition, IPTP perturbed signaling pathways that were not affected by TPP. https://doi.org/10.1289/EHP1318.
The prevalence of atopic dermatitis beyond childhood: A systematic review and meta‐analysis of longitudinal studies
Authors: K. Abuabara, A. M. Yu, J.‐P. Okhovat, I. E. Allen, S. M. Langan
Journal: Allergy (2017)

There are sparse and conflicting data regarding the long-term clinical course of atopic dermatitis (AD). Although often described as a childhood disease, newer population-based estimates suggest the prevalence of pediatric and adult disease may be similar.
Use of urate-lowering therapies is not associated with an increase in the risk of incident dementia in older adults
Authors: Jasvinder A Singh, John D Cleveland
Journal: Annals of the Rheumatic Diseases (2017)

Few recent studies1–3 reported that hyperuricemia may be protective against dementia, a common disease in the elderly associated with significant morbidity and mortality.4 5 We hypothesised that allopurinol or febuxostat use (the two most common urate-lowering therapies (ULTs)) in the elderly will be associated with a higher risk of dementia.

Study methods for this new user design study (a more robust design than a prevalent user design) were similar to those previously reported.6 Patients were eligible for this retrospective cohort study if they were (1) US residents enrolled in Medicare fee-for-service (covers all Americans ≥65 years) with pharmacy coverage, ie, enrolled in Medicare parts A (inpatient care), B (outpatient doctor and laboratory service) and D (prescription drugs) and not enrolled in a Medicare Advantage Plan (a standard approach for analysis)7 during 2006–2012 and (2) filled a new allopurinol (or febuxostat) prescription with a clean baseline period of 365 days with no exposure to either drug. Incident dementia was identified by new occurrence (no diagnosis in the 183-day baseline period) of an International Classification of Diseases, 9th Revision code, 290.xx, 294.1x or 331.2, a valid approach for dementia studies.8 9 We followed each eligible patient until the loss of Medicare coverage, dementia, death or the end of the study period, whichever came first. We used multivariable-adjusted Cox proportional …
The prognostic VALUE of Ki-67 in gastric cancer.
Authors: Antonio Caldeira Fradique, Ligia Bruno Da Costa, Alexandra Pupo, Luisa Quaresma, Gualdino Silva, Fernanda Cabrita, Mateus Marques, Jorge Esteves, Filomena Pina, Guedes Da Silva, Mario Oliveira
Journal: Journal of Clinical Oncology (2013)

e15172 Background: Gastric carcinoma is the second cause of cancer mortality worldwide. In Portugal, a country with a high incidence of the disease, it is also the second leading cause of cancer mortality. The gravity of this situation and the advanced stage of disease at presentation warrants a search of a new prognostic indicator. We studied in patients (pts) with gastric cancer, both diffuse and intestinal types, several possible prognostic indicators, such as: weight, nutrition status, Ki-67, p53, Cerb2, and cadherin E. The results showed that Ki-67, an indicator of cell proliferation, may play an important role as a prognostic indicator because it is easily assessed by immunohistochemistry, is observed in both intestinal and in diffuse tumor types, and is related with tumor size, depth of invasion and the pattern of lymphatic spread. Methods: A total of 50 pts with gastric carcinoma (25 diffuse and 25 intestinal types) undergoing radical gastrectomy with extended lymphadenectomy (D2 and a few D3 types ) were prospectively studied by immunohistochemistry for the determination of Ki-67 in biopsied tissue and gastrectomy specimens. A relationship between the Ki-67 and various other prognostic factors, like histological tumor type, tumor location, number of involved lymph nodes, depth of invasion, sex and stage was established. Results: A total of 50 tumor specimens and an equal number of biopsies were evaluated for Ki-67 overexpression. Ten tumors (20%) presented a Ki-67 &lt; 50%, 13 tumors (26%) showed a Ki-67 &gt;50% &lt; 74%, and 27 tumors (54%) had a Ki-67 &gt; 75%. It was found that tumors with a low Ki-67 expression have a more proximal location, the histological type was either mixed or diffuse, tend to invade superficially the gastric wall, they don’t have metastases in distal lymph nodes, and are diagnosed in early stages of the disease. Conclusions: In this study, the Ki-67 overexpression showed prognostic value in both diffuse and intestinal type gastric cancer patients.
Rice Consumption and Squamous Cell Carcinoma of the Skin in a United States Population
Authors: Anala Gossai, M. Scot Zens, Tracy Punshon, Brian P. Jackson, Ann E. Perry, Margaret R. Karagas
Journal: Environmental Health Perspectives (2017)

Background: Rice contains arsenic, a known skin carcinogen. Rice intake has been associated with arsenic-related skin lesions in South Asia, but its association with skin cancers is as yet unknown. Objectives: We aimed to investigate whether rice intake contributes to urinary arsenic concentration and risk of squamous cell carcinoma (SCC) of the skin in a U.S. population. Methods: Rice consumption was assessed using a food frequency questionnaire administered as part of a population-based case–control study of 487 SCC cases and 462 age- and gender-matched controls. Arsenic concentration in household tap water and urine samples were measured using inductively coupled mass spectrometry (ICP-MS) and high-resolution ICP-MS, respectively. Odds ratios (OR) for SCC associated with the frequency of rice consumption were estimated using logistic regression, with adjustment for age, gender, and caloric intake. Results: Those who reported any rice consumption had higher urinary arsenic concentrations than those who did not consume rice, and the association was most pronounced among those with <1μg/L arsenic in their household water (19.2% increase in total urinary arsenic, 95% CI: 5.0, 35.3%). Any rice consumption was associated with a 1.5-fold (95% CI: 1.1, 2.0) higher odds of SCC compared with those who reported no rice consumption, and the relation appeared to be largely among those with <1μg/L water arsenic. Conclusion: Rice consumption may be related to the occurrence of SCC in the United States, especially among those with relatively low drinking water arsenic exposure. https://doi.org/10.1289/EHP1065
Efficacy of recommended drugs against soil transmitted helminths: systematic review and network meta-analysis
Authors: Wendelin Moser, Christian Schindler, Jennifer Keiser
Journal: BMJ (2017)

<b>Objective</b>&nbsp;To evaluate efficacies of anthelmintic drugs against soil transmitted helminths in terms of cure rates and egg reduction rates. <b>Design</b>&nbsp;Systematic review and network meta-analysis. <b>Data Sources</b>&nbsp;PubMed, ISI Web of Science, Embase, ScienceDirect, the Cochrane Central Register of Clinical Trials, and the World Health Organization library database from 1960 until 31 December 2016. <b>Study selection</b>&nbsp;Randomised controlled trials evaluating the efficacy of a single dose regimen of albendazole, mebendazole, levamisole, and pyrantel pamoate against <i>Ascaris lumbricoides</i>, hookworm (<i>Necator americanus</i> and <i>Ancylostoma duodenale</i>) and <i>Trichuris trichiura.</i> The primary outcomes included cure rates analysed by network meta-analysis with mixed logistic regression models and egg reduction rates with mixed linear models. <b>Results</b>&nbsp;55 and 46 randomised controlled trials were included in the analysis of cure rates and egg reduction rates, respectively. All drugs were highly efficacious against <i>A lumbricoides</i>. Albendazole showed the highest efficacy against hookworm infections with a cure rate of 79.5% (95% confidence interval 71.5% to 85.6%) and an egg reduction rate of 89.6% (81.9% to 97.3%). All drugs had low efficacy against <i>T trichiura</i>, with mebendazole showing the highest cure rate of 42.1% (25.9% to 60.2%) and egg reduction rate of 66.0% (54.6% to 77.3%). Estimates for the years 1995 and 2015 showed significant reductions in efficacy of albendazole against <i>T trichiura</i>: by 2015 the egg reduction rates fell from 72.6% (53.7% to 91.5%) to 43.4% (23.5% to 63.3%; P=0.049) and the cure rates fell from 38.6% (26.2% to 52.7%) to 16.4 (7.7% to 31.3%; P=0.027). <b>Conclusions</b>&nbsp;All four currently recommended drugs show limitations in their efficacy profile. While only albendazole showed good efficacy against hookworm infection, all drugs had low efficacy against <i>T trichiura</i>. The decrease in efficacy of albendazole against <i>T trichiura</i> over the past two decades is of concern. The findings indicate the need for strengthening efforts to develop new drug treatments, with a particular focus on drugs against <i>T trichiura</i>.
Progress in the March to Precision Cancer Medicine
Authors: Eric K. Nakakura
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
Genome-wide association studies identified loci contribute to phenotypic variance of gastric cancer
Authors: Caiwang Yan, Meng Zhu, Tongtong Huang, Fei Yu, Guangfu Jin
Journal: Gut (2017)

We read with great interest the article by Mocellin et al ,1 who conducted a comprehensive meta-analysis that nominated 11 germline variants at nine loci significantly associated with gastric cancer (GC) with high level of summary evidence. Moreover, they also identified 38 single nucleotide polymorphisms (SNPs) with intermediate quality significant associations. Most of these loci were resulted from hypothesis-driven studies based on biological relevance, but most of these studies were small sample size and might lead to publication bias. In order to further evaluate their relevance with GC in individual large studies, we analysed these variants directly or their strong linkage disequilibrium SNPs using existing genome-wide association study (GWAS) datasets (including 2631 cases and 4373 controls) in Chinese populations, including those from Nanjing and Beijing populations conducted by our group2 and from Henan and Shanxi populations conducted by the USA National Cancer Institute.3 

After exclusion of the …
Notice of Retraction and Replacement: Favini et al. Comparative Trends in Payment Adjustments Between Safety-Net and Other Hospitals Since the Introduction of the Hospital Readmission Reduction Program and Value-Based Purchasing. <i>JAMA</i>. 2017;317(15):1578-1580.
Authors: Nathan Favini, Jason M. Hockenberry, Matlin Gilman, Sanjula Jain, Michael K. Ong, E. Kathleen Adams, Edmund R. Becker
Journal: JAMA (2017)

Notice of Retraction and Replacement: Favini et al. Comparative Trends in Payment Adjustments Between Safety-Net and Other Hospitals Since the Introduction of the Hospital Readmission Reduction Program and Value-Based Purchasing. JAMA. 2017;317(15):1578-1580.
Trends in Cancer Research&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: Carl Voegtlin
Journal: JNCI Journal of the National Cancer Institute (1942)

Journal Article Trends in Cancer Research Get access Carl Voegtlin Carl Voegtlin Chief National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 2, Issue 4, February 1942, Pages 309–315, https://doi.org/10.1093/jnci/2.4.309 Published: 01 February 1942
Discrimination of Germline <i>EGFR</i> T790M Mutations in Plasma Cell-Free DNA Allows Study of Prevalence Across 31,414 Cancer Patients
Authors: Yuebi Hu, Ryan S. Alden, Justin I. Odegaard, Stephen R. Fairclough, Ruthia Chen, Jennifer Heng, Nora Feeney, Rebecca J. Nagy, Jayshree Shah, Bryan Ulrich, Martin Gutierrez, Richard B. Lanman, Judy E. Garber, Cloud P. Paweletz, Geoffrey R. Oxnard
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Plasma cell-free DNA (cfDNA) analysis is increasingly used clinically for cancer genotyping, but may lead to incidental identification of germline-risk alleles. We studied EGFR T790M mutations in non–small cell lung cancer (NSCLC) toward the aim of discriminating germline and cancer-derived variants within cfDNA. Experimental Design: Patients with EGFR-mutant NSCLC, some with known germline EGFR T790M, underwent plasma genotyping. Separately, deidentified genomic data and buffy coat specimens from a clinical plasma next-generation sequencing (NGS) laboratory were reviewed and tested. Results: In patients with germline T790M mutations, the T790M allelic fraction (AF) in cfDNA approximates 50%, higher than that of EGFR driver mutations. Review of plasma NGS results reveals three groups of variants: a low-AF tumor group, a heterozygous group (∼50% AF), and a homozygous group (∼100% AF). As the EGFR driver mutation AF increases, the distribution of the heterozygous group changes, suggesting increased copy number variation from increased tumor content. Excluding cases with high copy number variation, mutations can be differentiated into somatic variants and incidentally identified germline variants. We then developed a bioinformatic algorithm to distinguish germline and somatic mutations; blinded validation in 21 cases confirmed a 100% positive predictive value for predicting germline T790M. Querying a database of 31,414 patients with plasma NGS, we identified 48 with germline T790M, 43 with nonsquamous NSCLC (P &amp;lt; 0.0001). Conclusions: With appropriate bioinformatics, plasma genotyping can accurately predict the presence of incidentally detected germline risk alleles. This finding in patients indicates a need for genetic counseling and confirmatory germline testing. Clin Cancer Res; 23(23); 7351–9. ©2017 AACR.
Targeted diflomotecan- and camptothecin-containing somatostatin analogs specifically inhibit the growth of SCLCs rich in somatostatin receptors
Authors: Philip G. Kasprzyk, Ann Savola, Mark Carlson, Yeelana Shen, Jundong Zhang, Jeanne M. Comstock, Xiaojun Zou, John E. Taylor, Mark Telliot, Caroline Touvay, Jesse Dong
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

566 

Receptors for somatostatin are found in a number of human tumors, especially SCLC. Diflomotecan and camptothecin were linked to a SSTR2 somatostatin analog each with novel linkers that target the tumor cells expressing SSTR2 receptors. The camptothecin and diflomotecan conjugates retained high-affinity to sst2 receptor in the in vitro binding assays. In vitro internalization was both time and temperature dependent and was observed only in the cells expressing sst2 receptors. Internalization was blocked by a specific sst2 receptor antagonist. Potent in vitro cytotoxicity was observed only in the cells expressing sst2 receptors. Cytotoxicity was blocked by specific sst2 receptor antagonists suggesting that binding and internalization were required to bring the cytotoxic agents into the cells. We evaluated the effects of these two original analogs in the NCI-H69, SCLC xenograft model (sst2 receptor positive) and in the negative control HT-29 colon xenograft model (sst2 receptor negative). Nude mice bearing the tumors were administered the analogs on a qwk x 6, i.v. schedule at doses equivalent to 1 to 6-fold of the MTD of the parent cytotoxic agents. The results of the in vivo experiments suggest that specific cytotoxic efficacy could be observed at doses up to 6X the parent cytotoxic with no added toxicity. Preliminary acute toxicity analysis showed that the analogs did not decrease white blood count, neutrophils, and platelets while camptothecin and diflomotecan did. Taken together, it seems that the somatostatin-directed cytotoxic conjugates selectively target the cancer cells expressing SSTR2 receptors in vitro and in vivo .
Lower back pain app: an exercise programme for the management of low back pain
Authors: Marina B Pinheiro, Gustavo C Machado
Journal: British Journal of Sports Medicine (2017)

Lower Back Pain App.

Medical.

Android 2.1 or later, iOS 8.0 or later.

US$1.49.

We have recently conducted a systematic review of smartphone apps for the self-management of low back pain.1 Of the 61 included apps, ‘Lower Back Pain App’ had the highest quality score (mean 3.94, range 0–5), as assessed using the Mobile Application Rating Scale (MARS).2 This app offers a 10-week exercise programme that aims to improve low back pain symptoms. Before starting the exercise programme, users are required to answer three screening questions addressing leg pain symptoms (numbness), mechanism of injury (accident or trauma), age ( 50 years) and pain characteristics (constant pain at night). Where the answer is ‘yes’ for any of the questions, a …
Objective measurement and clinical significance of IDO1 protein in hormone receptor-positive breast cancer
Authors: Daniel E. Carvajal-Hausdorf, Nikita Mani, Vamsidhar Velcheti, Kurt A. Schalper, David L. Rimm
Journal: Journal for ImmunoTherapy of Cancer (2017)

<h3>Background</h3> Immunostimulatory therapies targeting immune-suppressive pathways produce durable responses in advanced solid tumors. Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting oxidoreductase that catalyzes the degradation of tryptophan to kynurenine. IDO induces immune tolerance by downregulating CD8+ and effector CD4+ T cell responses. IDO1, the most active isoform, is expressed in diverse tumor types and can be targeted using small molecule inhibitors. We used an objective, in situ assay to measure IDO1 in a collection of hormone receptor-positive breast cancers (HR+ BC). <h3>Methods</h3> IDO1 protein was measured using quantitative immunofluorescence in 362 stage I-III HR+ BC represented in tissue microarrays. IDO1 levels were determined in the tumor and stroma, and stratified using median cut-point. Associations between IDO1, clinico-pathological features and CD3+, CD8+, CD20+ and FOXP3 tumor-infiltrating lymphocytes were examined using χ<sup>2</sup> and Mann-Whitney tests. Survival was studied using Kaplan-Meier estimator and a proportional hazards model. All tests were two-sided. <h3>Results</h3> IDO1 protein was observed in 76.2% of HR+ BC. There was no association between IDO1 and major clinico-pathological characteristics. Increased IDO1 correlated with decreased CD20+ infiltration (<i>P</i>&nbsp;=&nbsp;0.0004) but not with CD3+, CD8+ or FOXP3 levels. Elevated IDO1 expression was associated with worse 20-year overall survival (log-rank <i>P</i>&nbsp;=&nbsp;0.02, HR&nbsp;=&nbsp;1.39, 95% C.I.: 1.05-1.82). IDO1 scores were independently associated with outcome in multivariable analysis. <h3>Conclusions</h3> IDO1 protein is expressed in the majority of HR+ BC and is an independent negative prognostic marker. Additionally, IDO1 expression is negatively associated with tumor B-cell infiltration. Measurement of IDO1 has the potential to identify a population that might derive benefit from IDO1 blockade.
Biometric monitoring devices for assessing end points in clinical trials: developing an ecosystem
Authors: Stephen P. Arnerić, Jesse M. Cedarbaum, Sean Khozin, Spyros Papapetropoulos, Derek L. Hill, Michael Ropacki, Jane Rhodes, Penny A. Dacks, Lynn D. Hudson, Mark Forrest Gordon, Volker D. Kern, Klaus Romero, George Vradenburg, Rhoda Au, Daniel R. Karlin, Maurizio F. Facheris, Cheryl J. Fitzer-Attas, Ottavio V. Vitolo, Jian Wang, Bradley M. Miller, Jeffrey A. Kaye
Journal: Nature Reviews Drug Discovery (2017)
Chronic IL-33 expression predisposes to virus-induced asthma exacerbations by increasing type 2 inflammation and dampening antiviral immunity
Authors: Rhiannon B. Werder, Vivian Zhang, Jason P. Lynch, Natale Snape, John W. Upham, Kirsten Spann, Simon Phipps
Journal: Journal of Allergy and Clinical Immunology (2017)