tbuckley/cabot-search huggingface dataset:
Short-term exposure to oleate induces lipid droplet formation and long-term growth factor independent survival of breast cancer cells
Authors: Ewa Przybytkowski, Erik Joly, Christopher J. Nolan, Yves Langelier, Marc Prentki
Journal: Cancer Research (2005)

789  Epidemiological studies suggest that metabolic disorders such as obesity and diabetes increase the risk of some cancers. The mechanistic link between these diseases and cancer, however, is not understood. Fatty acids can be an important source of ATP, via oxidation in mitochondria. They can also be esterified into many complex lipids, such as components of cell membranes, triglycerides (TG) or signaling molecules (e.g. ceramide). Of potential importance, many cancers show aberrant lipid metabolism, e.g. overexpression of fatty acid synthase. The abnormal lipid metabolism in cancer cells therefore, combined with the elevated plasma lipids in metabolic conditions, may contribute to cancer progression. To learn more about metabolism of fatty acids in cancer cells and its relationship with cell growth and survival, we studied the effect of exogenous oleate, the most common plasma fatty acid, on transformed (MDA MB 231) and non-transformed (MCF10A) breast cells in culture. We found that oleate (100 μM, delivered in complex with BSA) protects MDA MB 231 breast cancer cells from apoptosis induced by serum withdrawal. Moreover, short-term (6-24 h) preincubation of these cells with oleate promotes growth factor independent survival for many days after removal of oleate from the culture medium. The effect is dose dependent since the period of survival is related to the concentration of oleate used (greater then 60% of cells still alive at day 2, 3, 5 and 9 following preincubation with oleate at 0, 33, 50, 100 μM, respectively). Interestingly, fatty acids metabolism is markedly different between the two cell lines. Oleate exposure leads to rapid accumulation of intracellular TG and formation of lipid droplets in MDA MB 231 cells only. TG accumulation reflects the oleate concentration used and correlates with the duration of serum-free cell survival. Oleate has no long-term effect on cell proliferation, so its effect appears to be anti-apoptotic. The non-transformed MCF10A cells, do not accumulate TG, most likely due to high rates of fat oxidation (10 times that observed in MDA MB 231 cells) and are not protected by oleate and die by apoptosis. The survival mechanism induced by oleate in MDA MB 231 cells in the absence of growth factors is under investigation. Oleate released from lipid droplets by lipolysis can perhaps be used as an alternative energy source. This is however unlikely in MDA MB 231 cells, as these cells poorly oxidize fatty acids and metabolize glucose at high rates irrespective of the presence of serum. Overall the results are consistent with a role for altered lipid metabolism in the long-term survival of some tumor cells. We are presently testing if the survival effect described here applies to other cancer cell lines. Increased knowledge of fatty acid metabolism in cancer cells may open new possibilities for cancer prevention, treatment and improvement in prognosis.
PATHOLOGICAL “SECOND-LOOK” SIGNIFICANTLY ALTERS CLINICAL MANAGEMENT IN ENDOSCOPICALLY RESECTED PT1 COLORECTAL CANCER
Authors: G Antonelli, GL Rampioni Vinciguerra, G Berardi, G Vanella, S Angeletti, E Pilozzi, E Di Giulio
Journal: Endoscopy (2019)

Clinical management of endoscopically resected pT1 colorectal cancers (CRC) is still under debate. Guidelines prudentially suggest subsequent surgery in presence of one or more histological factors linked to increased risk of LNM, but a great variability in histological analysis, LNM rates and clinical management has been reported. Lack of standardization and interobserver variability in reporting histological factors may explain this heterogeneity. This kind of pitfall has been overcomed in surveillance of Barrett's Esophagus, with systematical pathological second opinion, recommended by international guidelines. In pT1-CRC, pathologist second opinion is rarely reported, although “European CRC screening Guidelines” suggest its employment, especially when surgical resection is considered. Main aim of our study was to assess how second opinion of an expert GI pathologist may affect clinical management of pT1-CRC.
Comment on Echouffo-Tcheugui et al. Visit-to-Visit Glycemic Variability and Risks of Cardiovascular Events and All-Cause Mortality: The ALLHAT Study. Diabetes Care 2019;42:486–493
Authors: Louis Monnier, Claude Colette, David Owens
Journal: Diabetes Care (2019)

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study group (1) reported that, based on a post hoc analysis, visit-to-visit variability of fasting blood glucose (FBG) is positively associated with all-cause mortality but not with cardiovascular events in subjects without diabetes, while the association is not statistically significant in those with diabetes. Glycemic variability was assessed from FBG values at baseline, 24 months, and 48 months in persons without cardiovascular disease prior to a follow-up period of up to several years. Metrics of glycemic variability …
Association of Parent Training With Child Language Development
Authors: Megan Y. Roberts, Philip R. Curtis, Bailey J. Sone, Lauren H. Hampton
Journal: JAMA Pediatrics (2019)

<h3>Importance</h3> Training parents to implement strategies to support child language development is crucial to support long-term outcomes, given that as many as 2 of 5 children younger than 5 years have difficulty learning language. <h3>Objective</h3> To examine the association between parent training and language and communication outcomes in young children. <h3>Data Sources</h3> Searches of ERIC, Academic Search Complete, PsycINFO, and PsycARTICLES were conducted on August 11, 2014; August 18, 2016; January 23, 2018; and October 30, 2018. <h3>Study Selection</h3> Studies included in this review and meta-analysis were randomized or nonrandomized clinical trials that evaluated a language intervention that included parent training with children with a mean age of less than 6 years. Studies were excluded if the parent was not the primary implementer of the intervention, the study included fewer than 10 participants, or the study did not report outcomes related to language or communication. <h3>Data Extraction and Synthesis</h3> Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were applied to a total of 31 778 articles identified for screening, with the full text of 723 articles reviewed and 76 total studies ultimately included. <h3>Main Outcomes and Measures</h3> Main outcomes included language and communication skills in children with primary or secondary language impairment and children at risk for language impairment. <h3>Results</h3> This meta-analysis included 59 randomized clinical trials and 17 nonrandomized clinical trials including 5848 total participants (36.4 female [20.8%]; mean [SD] age, 3.5 [3.9] years). The intervention approach in 63 studies was a naturalistic teaching approach, and 16 studies used a primarily dialogic reading approach. There was a significant moderate association between parent training and child communication, engagement, and language outcomes (mean [SE] Hedges<i>g,</i>−0.33 [0.06];<i>P</i> &lt; .001). The association between parent training and parent use of language support strategies was large (mean [SE] Hedges<i>g,</i>0.55 [0.11],<i>P</i> &lt; .001). Children with developmental language disorder had the largest social communication outcomes (mean [SE] Hedges<i>g</i>, 0.37 [0.17]); large and significant associations were observed for receptive (mean [SE] Hedges<i>g</i>, 0.92 [0.30]) and expressive language (mean [SE] Hedges<i>g</i>, 0.83 [0.20]). Children at risk for language impairments had moderate effect sizes across receptive language (mean [SE] Hedges<i>g</i>, 0.28 [0.15]) and engagement outcomes (mean [SE] Hedges<i>g</i>, 0.36 [0.17]). <h3>Conclusions and Relevance</h3> The findings suggest that training parents to implement language and communication intervention techniques is associated with improved outcomes for children and increased parent use of support strategies. These findings may have direct implications on intervention and prevention.
Primary Spinal Poorly Differentiated Neuroendocrine Tumor Displayed on FDG PET/CT
Authors: Guohua Shen, Huan Ma, Lili Pan, Minggang Su, Anren Kuang
Journal: Clinical Nuclear Medicine (2019)

Abstract 18 F-FDG PET/CT imaging provides valuable information in the evaluation and staging of spinal tumors. Herein, we report the case of a 57-year-old man who presented with a sudden paraplegia below the fifth thoracic vertebra due to cord compression of a spinal lesion. After spinal canal decompression and spinal lesion biopsy, the diagnosis was a poorly differentiated neuroendocrine tumor. Subsequent PET/CT revealed that it was a primary site, showing intense FDG uptake. He was eventually referred for palliative radiotherapy.
BCL2 Amplicon Loss and Transcriptional Remodeling Drives ABT-199 Resistance in B Cell Lymphoma Models
Authors: Xiaohong Zhao, Yuan Ren, Matthew Lawlor, Bijal D. Shah, Paul M.C. Park, Tint Lwin, Xuefeng Wang, Kenian Liu, Michelle Wang, Jing Gao, Tao Li, Mousheng Xu, Ariosto S. Silva, Kaplan Lee, Tinghu Zhang, John M. Koomen, Huijuan Jiang, Praneeth R. Sudalagunta, Mark B. Meads, Fengdong Cheng, Chengfeng Bi, Kai Fu, Huitao Fan, William S. Dalton, Lynn C. Moscinski, Kenneth H. Shain, Eduardo M. Sotomayor, Gang Greg Wang, Nathanael S. Gray, John L. Cleveland, Jun Qi, Jianguo Tao
Journal: Cancer Cell (2019)
National, regional, and worldwide estimates of low birthweight in 2015, with trends from 2000: a systematic analysis
Authors: Hannah Blencowe, Julia Krasevec, Mercedes de Onis, Robert E Black, Xiaoyi An, Gretchen A Stevens, Elaine Borghi, Chika Hayashi, Diana Estevez, Luca Cegolon, Suhail Shiekh, Victoria Ponce Hardy, Joy E Lawn, Simon Cousens
Journal: The Lancet Global Health (2019)

Low birthweight (LBW) of less than 2500 g is an important marker of maternal and fetal health, predicting mortality, stunting, and adult-onset chronic conditions. Global nutrition targets set at the World Health Assembly in 2012 include an ambitious 30% reduction in LBW prevalence between 2012 and 2025. Estimates to track progress towards this target are lacking; with this analysis, we aim to assist in setting a baseline against which to assess progress towards the achievement of the World Health Assembly targets.We sought to identify all available LBW input data for livebirths for the years 2000-16. We considered population-based national or nationally representative datasets for inclusion if they contained information on birthweight or LBW prevalence for livebirths. A new method for survey adjustment was developed and used. For 57 countries with higher quality time-series data, we smoothed country-reported trends in birthweight data by use of B-spline regression. For all other countries, we estimated LBW prevalence and trends by use of a restricted maximum likelihood approach with country-level random effects. Uncertainty ranges were obtained through bootstrapping. Results were summed at the regional and worldwide level.We collated 1447 country-years of birthweight data (281 million births) for 148 countries of 195 UN member states (47 countries had no data meeting inclusion criteria). The estimated worldwide LBW prevalence in 2015 was 14·6% (uncertainty range [UR] 12·4-17·1) compared with 17·5% (14·1-21·3) in 2000 (average annual reduction rate [AARR] 1·23%). In 2015, an estimated 20·5 million (UR 17·4-24·0 million) livebirths were LBW, 91% from low-and-middle income countries, mainly southern Asia (48%) and sub-Saharan Africa (24%).Although these estimates suggest some progress in reducing LBW between 2000 and 2015, achieving the 2·74% AARR required between 2012 and 2025 to meet the global nutrition target will require more than doubling progress, involving both improved measurement and programme investments to address the causes of LBW throughout the lifecycle.Bill & Melinda Gates Foundation, The Children's Investment Fund Foundation, United Nations Children's Fund (UNICEF), and WHO.
Immunotherapy of Endothelin-1 Receptor Type A for Pulmonary Arterial Hypertension
Authors: Yong Dai, Xiao Chen, Xiaoxiao Song, Xijun Chen, Wenrui Ma, Jibin Lin, Hailang Wu, Xiajun Hu, Yanzhao Zhou, Hongrong Zhang, Yuhua Liao, Zhihua Qiu, Zihua Zhou
Journal: Journal of the American College of Cardiology (2019)
PLAN-DO-STUDY-ACT APPROACH FOR IMPLEMENTING SPLIT REGIMEN OVER SINGLE DOSE (IMPROVES STUDY)
Authors: G Vanella, C Hassan, M De Bellis, M Giardini, E Grasso, F Laterza, O Tarantino, E Di Giulio
Journal: Endoscopy (2019)

Split-dose regimen for colonoscopy is recommended by international guidelines, but its adoption is still suboptimal. The Plan-Do-Study-Act approach (PDSA) is a scientific method used to promote continuous quality improvement of complex processes. The aim of this study was to assess whether PDSA is able to improve adherence to split-dose regimen.
Dynamic monitoring of ctDNA reveals that acquired NF2 mutations confer resistance to HER2 targeted therapy in HER2-mutant breast cancer
Authors: X. Li, J. Ma, B. Pan, Z. Zhao, M. Li
Journal: Annals of Oncology (2019)

Background: Preclinical studies suggest that HER2 mutations lead to constitutive HER2 activation, but knowledge about effective treatment options and clinical resistance mechanisms remain uncharacterized. Methods: We performed dynamic monitoring of > 300 serial plasma samples collected from 49 metastatic breast cancer patients used targeted sequencing of 425 clinically relevant genes, to detect HER2 mutations and track resistance to HER2-targeted treatments in HER2-mutant breast cancer. Results: We identified activating HER2 mutations (S310F, D769Y, V777L, 778insGSP) in ctDNA and paired tissue samples from four patients with ER positive/HER2-amplification negative metastatic breast cancer, who had developed resistance to multi-line (>3) endocrine therapy. Two patients achieved a durable partial response (approximately 1 years) to trastuzumab combined with everolimus. Intriguingly however, analysis of ctDNA revealed that the NF2 mutation was acquired from a patient with HER2S310F/V777L who had developed resistance to HER2-targeted treatments. We showed that HER2S310F/D769Y/V777L/778insGSP mutations were constitutively active, and T47D and MCF7 overexpressing HER2S310F/V777L/778insGSP were sensitive to HER2 targeted therapies combined with everolimus. Consistent with our clinical findings, NF2 knockdown in HER2 S310F/V777L/778insGSP overexpressing T47D and MCF7 contributed to HER2-targeted therapy resistance. Furthermore, MEK inhibitor remarkably sensitized NF2 knockdown and HER2 mutations co-expressing T47D and MCF7 cells to trastuzumab. Conclusions: Dynamic monitoring of ctDNA could provide the candidate resistance genes for metastatic HER2-mutant breast cancer. Our findings validated NF2 mutations as a potential mechanism of resistance to HER2-targeted therapy, and the combined use of HER2 and ERK inhibitors may overcome resistance to HER2 targeted therapy in HER2-mutant breast cancer. Legal entity responsible for the study: Dalian Medical University. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Identification of rare coding variants in <i>TYK2</i> protective for rheumatoid arthritis in the Japanese population and their effects on cytokine signalling
Authors: Tomoki Motegi, Yuta Kochi, Koichi Matsuda, Michiaki Kubo, Kazuhiko Yamamoto, Yukihide Momozawa
Journal: Annals of the Rheumatic Diseases (2019)

Objective Although genome-wide association studies (GWAS) have identified approximately 100 loci for rheumatoid arthritis (RA), the disease mechanisms are not completely understood. We evaluated the pathogenesis of RA by focusing on rare coding variants. Methods The coding regions of 98 candidate genes identified by GWAS were sequenced in 2294 patients with RA and 4461 controls in Japan. An association analysis was performed using cases and controls for variants, genes and domains of TYK2. Cytokine responses for two associated variants (R231W, rs201917359; and R703W, rs55882956) in TYK2 as well as a previously reported risk variant (P1004A, rs34536443) for multiple autoimmune diseases were evaluated by reporter assays. Results A variant in TYK2 (R703W) showed a suggestive association (p=5.47×10 −8 , OR=0.48). We observed more accumulation of rare coding variants in controls in TYK2 (p=3.94×10 −12 , OR=0.56). The four-point-one, ezrin, radixin, moesin (FERM; 2.14×10 −3 , OR=0.66) and pseudokinase domains (1.63×10 −8 , OR=0.52) of TYK2 also showed enrichment of variants in controls. R231W in FERM domain especially reduced interleukin (IL)-6 and interferon (IFN)-γ signalling, whereas P1104A in kinase domain reduced IL-12, IL-23 and IFN-α signalling. R703W in pseudokinase domain reduced cytokine signals similarly to P1104A, but the effects were weaker than those of P1104A. Conclusions The FERM and pseudokinase domains in TYK2 were associated with the risk of RA in the Japanese population. Variants in TYK2 had different effects on cytokine signalling, suggesting that the regulation of selective cytokine signalling is a target for RA treatment.
THE USEFULNESS OF SPYGLASS PERORAL CHOLANGIOSCOPY IN THE DIAGNOSIS OF BILIARY LESIONS AND TREATMENT OF DIFFICULT BILE STONES: SINGLE-CENTER, RETROSPECTIVE, COHORT STUDY
Authors: F Younis, A Philips, E Scapa, O Shibolet, E Santo
Journal: Endoscopy (2019)

To assess the efficacy and safety of the SpyGlass for the diagnosis and treatment of indeterminate biliary strictures and difficult bile duct stones in patients treated at a tertiary care center.
Correction: Genome scanning with array CGH delineates regional alterations in mouse islet carcinomas
Authors: G. Hodgson, J.H. Hager, S. Volik, S. Hariono, M. Wernick, D. Moore, N. Nowak, D.G. Albertson, D. Pinkel, C. Collins, D. Hanahan, J.W. Gray
Journal: Nature Genetics (2001)
Variation in radiotherapy after breast conserving surgery in patients aged 75 years or older between hospitals is not reflected in the locoregional recurrence risk
Authors: A.Z. de Boer, N.A. de Glas, P.J. Marang-van de Mheen, O.M. Dekkers, S. Siesling, J.E.A. Portielje, E. Bastiaannet, G.-J. Liefers
Journal: Annals of Oncology (2019)

Background: Breast conserving surgery (BCS) followed by radiotherapy is the standard treatment for early stage breast cancer. As a result of uncertainty about the absolute benefit of radiotherapy in older patients, there is variation in the proportion of patients receiving radiotherapy after BCS. In this study, we assessed the variation between hospitals in the Netherlands among patients aged 75 years or older and evaluated its impact on locoregional recurrence risk. Methods: Eligible patients diagnosed between 2003 and 2009 were selected from the Netherlands Cancer Registry. Since directly comparing treated and untreated patients would lead to bias due to confounding by indication, the impact of omission of radiotherapy on locoregional recurrence risk was assessed using individual patient data with hospital as instrumental variable. To this end, hospitals were sorted according to the proportion of radiotherapy given and subsequently the cohort was divided into three equally sized groups (radiotherapy high, middle and low) which were analysed using Fine and Gray regression models. This procedure was repeated stratified by age and comorbidity. Results: Overall, 2390 patients were included. In the "radiotherapy high" group 96% of the patients underwent radiotherapy compared to 88.0% in the "radiotherapy middle" group and 72.2% in the "radiotherapy low" group. Compared to the "radiotherapy high" group, no significant difference in locoregional recurrence risk was observed for the "radiotherapy middle" group (adjusted sHR 1.58, 95% CI: 0.74-3.40, p = 0.240) or "radiotherapy low" group (adjusted sHR 1.76, 95%: 0.81-3.81, p = 0.150). Variation in the proportion of patients undergoing radiotherapy increased with increasing age and comorbidity, however, no significant difference in locoregional recurrence risk was seen between the constructed radiotherapy groups stratified by age and comorbidity. Conclusions: This study shows that omission of radiotherapy after BCS among patients aged 75 years or older is not uncommon in the Netherlands. However, the observed variation in proportion of patients receiving radiotherapy between hospitals was not reflected in the locoregional risk. Legal entity responsible for the study: Leiden University Medical Center. Funding: ZonMw. Disclosure: All authors have declared no conflicts of interest.
Racial Inequality in Prostate Cancer Outcomes—Socioeconomics, Not Biology
Authors: Channing J. Paller, Lin Wang, Otis W. Brawley
Journal: JAMA Oncology (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 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 Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Co-delivery of latanoprost and timolol from micelles-laden contact lenses for the treatment of glaucoma
Authors: Jiawen Xu, Ying Ge, Ruixuan Bu, Anan Zhang, Shasha Feng, Jian Wang, Jingxin Gou, Tian Yin, Haibing He, Yu Zhang, Xing Tang
Journal: Journal of Controlled Release (2019)
Attention-deficit/hyperactivity disorder in elite athletes: a narrative review
Authors: Doug Hyun Han, David McDuff, Donald Thompson, Mary E Hitchcock, Claudia L Reardon, Brian Hainline
Journal: British Journal of Sports Medicine (2019)

Attention-deficit/hyperactivity disorder (ADHD) is a common brain developmental disorder in the general population that may be even more prevalent in elite athletes in certain sports. General population studies of ADHD are extensive and have reported on prevalence, symptoms, therapeutic and adverse effects of treatment and new clinical and research findings. However, few studies have reported on prevalence, symptoms and treatments of ADHD in elite athletes. This narrative review summarises the literature on symptoms, comorbidities, effects of ADHD on performance and management options for elite athletes with ADHD. The prevalence of ADHD in student athletes and elite athletes may be 7%–8%. The symptoms and characteristics of ADHD play a role in athletes’ choice of a sport career and further achieving elite status. Proper management of ADHD in elite athletes is important for safety and performance, and options include pharmacologic and psychosocial treatments.