tbuckley/cabot-search huggingface dataset:
Effects of Saturated Fat, Polyunsaturated Fat, Monounsaturated Fat, and Carbohydrate on Glucose-Insulin Homeostasis: A Systematic Review and Meta-analysis of Randomised Controlled Feeding Trials
Authors: Fumiaki Imamura, Renata Micha, Jason H. Y. Wu, Marcia C. de Oliveira Otto, Fadar O. Otite, Ajibola I. Abioye, Dariush Mozaffarian
Journal: PLoS Medicine (2016)

Background Effects of major dietary macronutrients on glucose-insulin homeostasis remain controversial and may vary by the clinical measures examined. We aimed to assess how saturated fat (SFA), monounsaturated fat (MUFA), polyunsaturated fat (PUFA), and carbohydrate affect key metrics of glucose-insulin homeostasis. Methods and Findings We systematically searched multiple databases (PubMed, EMBASE, OVID, BIOSIS, Web-of-Knowledge, CAB, CINAHL, Cochrane Library, SIGLE, Faculty1000) for randomised controlled feeding trials published by 26 Nov 2015 that tested effects of macronutrient intake on blood glucose, insulin, HbA1c, insulin sensitivity, and insulin secretion in adults aged ≥18 years. We excluded trials with non-isocaloric comparisons and trials providing dietary advice or supplements rather than meals. Studies were reviewed and data extracted independently in duplicate. Among 6,124 abstracts, 102 trials, including 239 diet arms and 4,220 adults, met eligibility requirements. Using multiple-treatment meta-regression, we estimated dose-response effects of isocaloric replacements between SFA, MUFA, PUFA, and carbohydrate, adjusted for protein, trans fat, and dietary fibre. Replacing 5% energy from carbohydrate with SFA had no significant effect on fasting glucose (+0.02 mmol/L, 95% CI = -0.01, +0.04; n trials = 99), but lowered fasting insulin (-1.1 pmol/L; -1.7, -0.5; n = 90). Replacing carbohydrate with MUFA lowered HbA1c (-0.09%; -0.12, -0.05; n = 23), 2 h post-challenge insulin (-20.3 pmol/L; -32.2, -8.4; n = 11), and homeostasis model assessment for insulin resistance (HOMA-IR) (-2.4%; -4.6, -0.3; n = 30). Replacing carbohydrate with PUFA significantly lowered HbA1c (-0.11%; -0.17, -0.05) and fasting insulin (-1.6 pmol/L; -2.8, -0.4). Replacing SFA with PUFA significantly lowered glucose, HbA1c, C-peptide, and HOMA. Based on gold-standard acute insulin response in ten trials, PUFA significantly improved insulin secretion capacity (+0.5 pmol/L/min; 0.2, 0.8) whether replacing carbohydrate, SFA, or even MUFA. No significant effects of any macronutrient replacements were observed for 2 h post-challenge glucose or insulin sensitivity (minimal-model index). Limitations included a small number of trials for some outcomes and potential issues of blinding, compliance, generalisability, heterogeneity due to unmeasured factors, and publication bias. Conclusions This meta-analysis of randomised controlled feeding trials provides evidence that dietary macronutrients have diverse effects on glucose-insulin homeostasis. In comparison to carbohydrate, SFA, or MUFA, most consistent favourable effects were seen with PUFA, which was linked to improved glycaemia, insulin resistance, and insulin secretion capacity.
Laboratory Testing in the Setting of Diabetic Scleredema—Reply
Authors: Soumya Chatterjee
Journal: JAMA (2016)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Abstract 2959: Peptide-linked indolino-benzodiazepine DNA-alkylating agents for use in antibody-drug conjugates (ADCs)
Authors: Manami Shizuka, Alan Wilhelm, Katie Archer, Emily Reid, Nicholas C. Yoder, Chen Bai, Nathan Fishkin, Luke Harris, Erin Maloney, Erica Hong, Rui Wu, Olga Ab, Kate Lai, Surina Sikka, Shan Jin, Jan Pinkas, Ravi Chari, Michael L. Miller
Journal: Cancer Research (2016)

Abstract As part of our efforts to expand the available toolbox of cytotoxic payloads for use in antibody-drug conjugates (ADCs), we have recently described the development of the mono-imine-containing indolino-benzodiazepine dimer, IGN-P1 (Miller, et al., AACR 2014 #652). IGN-P1 was conjugated via a protease-cleavable peptidic L-alanine-L-alanine linker to a folate receptor α (FRα)-binding antibody, and an EGFR-binding antibody. The resulting ADCs demonstrated high in vitro potency (IC50 ∼4-100 pM) and specificity towards several cancer cell lines. In vivo, anti-FRα-IGN-P1 induced complete regressions in NCI-H2110 non-small cell lung cancer xenografts following a single dose of 3 μg/kg (linked payload dose, equivalent to 0.18 mg/kg Ab dose). Here we describe the structure-activity relationship of a number of peptide-linked IGN ADCs, leading to the selection of Ab-IGN-P1 for further advancement. The cytotoxic activities of these peptide-IGN conjugates were evaluated in vitro in cancer cell lines with both high and low target antigen expression. We also assessed bystander activity and identified in vitro and in vivo catabolites. We found that the stereochemistry of the peptide linker was crucial for bystander activity and in vivo efficacy. The IGN-P1 ADC exhibited strong bystander activity, which we believe is dictating the strong antitumor activity in vivo. Treatment of low to moderate antigen-expressing models with Ab-IGN-P1 further resulted in tumor regressions at doses as low as 3-10 μg/kg linked payload. These data underscore the potential therapeutic benefit of highly active and specific IGN-P1 conjugates, even for the challenging subset of patients with solid tumors where the target antigen is expressed at lower levels. Citation Format: Manami Shizuka, Alan Wilhelm, Katie Archer, Emily Reid, Nicholas C. Yoder, Chen Bai, Nathan Fishkin, Luke Harris, Erin Maloney, Erica Hong, Rui Wu, Olga Ab, Kate Lai, Surina Sikka, Shan Jin, Jan Pinkas, Ravi Chari, Michael L. Miller. Peptide-linked indolino-benzodiazepine DNA-alkylating agents for use in antibody-drug conjugates (ADCs). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2959.
Prospective Comparison Of Five Viral Infections (HHV6, CMV, EBV, ADV, BKv) After Umbilical Cord Blood (UCB) Vs PBSC Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation (allo-SCT) In Adults
Authors: Berthe-Marie Imbert-Marcille, Lucie Planche, Marie Rimbert, Claire Le Houerou, Céline Bressollette-Bodin, Thierry Guillaume, Amandine Le Bourgeois, Jacques Delaunay, Philippe Moreau, Mohamad Mohty, Patrice Chevallier
Journal: Blood (2013)
Contributions of the Framingham Heart Study to the Epidemiology of Coronary Heart Disease
Authors: George Chen, Daniel Levy
Journal: JAMA Cardiology (2016)

Since its launch in 1948, the Framingham Heart Study has proved critical to shaping and enhancing our understanding of the history and root causes of coronary heart disease (CHD). A modern prototype for population-based studies, the Framingham Heart Study garnered widespread recognition in its early years for identifying risk factors for CHD and stroke and formulating CHD risk scores. Although the study remains iconic for its robust design and successes in uncovering risk factors for CHD, it has undergone transformations during the past 2 decades. The 21st century ushered in a new era in "molecular epidemiology" centered on cutting-edge genetic and "-omics technologies." Framingham Heart Study investigators embraced these opportunities by pioneering genome-wide association studies at the population level and examining CHD through the lens of genetic variation, gene expression, and microRNA signatures. The Framingham Heart Study continues to evolve as it seeks to pinpoint new causes of disease with the hope of advancing personalized approaches to the treatment and prevention of CHD.
Brief Report: Power Doppler Ultrasonography for Detection of Increased Vascularity in the Fascia: A Potential Early Diagnostic Tool in Fasciitis of Dermatomyositis
Authors: Ken Yoshida, Makiko Nishioka, Satoshi Matsushima, Kensuke Joh, Yosuke Oto, Masayuki Yoshiga, Kazuhiro Otani, Haruyasu Ito, Kenichiro Hirai, Kazuhiro Furuya, Taro Ukichi, Kentaro Noda, Isamu Kingetsu, Daitaro Kurosaka
Journal: Arthritis & Rheumatology (2016)

Objective We previously demonstrated that fasciitis is a common lesion of dermatomyositis (DM) that is detectable early after disease onset by en bloc muscle biopsy combined with magnetic resonance imaging (MRI). Power Doppler ultrasonography (PDUS) is a useful method for detection of inflammation and vascularity in rheumatic diseases. We undertook this study to determine whether fasciitis was detectable by PDUS in patients with DM. Methods We prospectively evaluated 7 patients with DM and 7 patients with polymyositis (PM) for the detection of fasciitis with PDUS. MRI and PDUS were both performed in all patients. Fasciitis was histologically confirmed by en bloc biopsy. Results Among all patients with DM, 4 showed signs of fasciitis on MRI, while increased blood flow signals were observed along the fascia by PDUS in 6 DM patients, including 4 patients with early disease (&lt;2 months after the onset of muscle symptoms). Histologically, significant fasciitis was confirmed in 4 patients with DM. In the remaining 3 patients with DM, significant fasciitis was not evident histologically, but mild proliferation of capillaries and mild inflammation were notable in the area of the fascia. Immunohistochemical staining for CD31 indicated abnormal neovascular proliferation in the fascia in patients with DM. None of the PM patients showed signs of fasciitis or increased vascularity by MRI, PDUS, or en bloc biopsy. Conclusion In our limited population, PDUS was useful for the detection of fasciitis associated with DM, especially in the early stage of disease. The increased blood flow signal as detected by PDUS is involved in angiogenesis accompanying fasciitis in patients with DM.
Abstract 2998: Molecular and cellular effects of individual and combinatorial silencing of HSP90 paralogs
Authors: Marissa V. Powers, Robert H. Te Poele, Ravindhi L. Murphy, Emmanuel de Billy, Paul A. Clarke, Paul Workman
Journal: Cancer Research (2016)

Abstract HSP90 is an ATP-dependent molecular chaperone critical for the folding, stability and function of over 350 client proteins, including many that are oncogenic. Pharmacologic inhibition of the essential ATPase domain inhibits HSP90 function and produces a well-documented molecular and cellular response comprising depletion of client proteins, induction of heat shock proteins and reduction of tumor cell proliferation. There are four paralogs within the HSP90 family, HSP90α, HSP90β, GRP94 and TRAP1, and it is not currently clear what precise role each one plays in the molecular and therapeutic response to HSP90 inhibitors. Here we use an siRNA approach to selectively reduce the expression of each HSP90 paralog, alone or in combination, in an attempt to dissect the individual roles of each chaperone in the molecular and cellular response associated with pharmacologic HSP90 inhibition. In the human cancer models used we found that by simultaneously silencing HSP90α and HSP90β we could phenocopy aspects of pharmacologic HSP90 inhibition including reduction of cell proliferation, induction of HSP72 and other HSF-1 target genes and depletion of oncogenic client proteins. Through analysing representative HSP90 client proteins we observed interesting patterns of paralog-dependence that were related to their overall sensitivity to pharmacologic HSP90 inhibition. Our results reveal the importance of HSP90 paralogs in particular aspects of the molecular and cellular response to pharmacologic HSP90 inhibition. Citation Format: Marissa V. Powers, Robert H. Te Poele, Ravindhi L. Murphy, Emmanuel de Billy, Paul A. Clarke, Paul Workman. Molecular and cellular effects of individual and combinatorial silencing of HSP90 paralogs. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2998.
Abstract 3980: Combined detection of serum Dickkopf-1 and its autoantibodies to diagnose esophageal squamous cell carcinoma
Authors: Yu-Hui Peng, Yi-Wei Xu, En-Min Li, Li-Yan Xu
Journal: Cancer Research (2016)

Abstract Esophageal squamous cell carcinoma (ESCC) can be treated effectively if diagnosed at an early stage. We evaluated whether measurement of Dickkopf-1 (DKK1) in combination of DKK1 autoantibodies in serum may benefit early diagnosis of ESCC. Serum DKK1 and DKK1 autoantibodies were measured by enzyme-linked immunosorbent assay in a training cohort (185 ESCC samples vs. 97 normal controls) and validated in a validation cohort (104 ESCC samples vs. 53 normal controls). Receiver operating characteristics (ROC) was applied to calculate diagnostic accuracy. The serum levels of DKK1 and DKK1 autoantibody were significantly higher in ESCC patients than in controls, respectively (P&amp;lt;0.0001). Measurement of serum DKK1 demonstrated an area under curve (AUC) of 0.709 [95% confidence interval (CI), 0.647-0.771], 37.3% sensitivity, and 90.7% specificity in the training set and an AUC of 0.697 (95% CI, 0.613-0.780), 41.3% sensitivity, and 84.9% specificity in the validation set. Testing of DKK1 and DKK1 autoantibodies together effectively improved the diagnostic accuracy for ESCC versus normal controls compared with either test alone (AUC 0.769, 95% CI 0.715-0.823, 50.3% sensitivity, and 90.7% specificity in the training cohort; AUC 0.752, 95% CI 0.675-0.829, 50.0% sensitivity, and 84.9% specificity in the validation cohort). Importantly, the diagnostic performance of the combination of DKK1 and DKK1 autoantibodies persisted in early ESCC patients (AUC 0.780, 95% CI, 0.699-0.862, 50.0% sensitivity, and 90.7% specificity in the training cohort; AUC 0.745, 95% CI, 0.626-0.865, 53.8% sensitivity, and 84.9% specificity in the validation cohort). Furthermore, the levels of serum DKK1 or DKK1 autoantibody after surgical resection were lower, respectively, compared with the corresponding preoperative samples (P&amp;lt;0.05). Our results suggest that measurement of DKK1 combined with DKK1 autoantibodies is a potentially valuable tool for the early detection of ESCC. Citation Format: Yu-Hui Peng, Yi-Wei Xu, En-Min Li, Li-Yan Xu. Combined detection of serum Dickkopf-1 and its autoantibodies to diagnose esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3980.
Syncope While Driving in Denmark—Reply
Authors: Anna-Karin Numé, Mark A. Hlatky, Martin H Ruwald
Journal: JAMA Internal Medicine (2016)

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 Internal Medicine 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 Internal Medicine journal
Abstract 3382: A physiological model of the tumor microenvironment for screening drug delivery systems
Authors: Yuan Tang, Fariborz Soroush, Sudhir Deosarkar, Bin Wang, Balabhaskar Prabhakarpandian, Mohammad Kiani
Journal: Cancer Research (2016)

Abstract Tumor drug delivery is a complex phenomenon affected by several elements in addition to drug or delivery vehicle's physico-chemical properties. Tumor microvasculature has many unique features including unusual transport characteristics, high interstitial pressure, and enhanced permeability and retention (EPR) effect. Current in vitro models of tumor drug delivery are oversimplified and, as a result, show poor correlation with in vivo performance. The objective of this study is to develop and characterize a synthetic 3D solid tumor - endothelium model in a novel microfluidic platform that mimics the tumor microenvironment observed in vivo. The novel synthetic tumor model consists of a vascular network of tumor derived endothelial cells forming a complete lumen in communication with 3D solid tumors. Primary human breast tumor associated endothelial cells (HBTAECs) were co-cultured under physiological fluid flow conditions with 3D tumor cells from metastastic (MDA-MB-231) or non-metastatic (MCF-7) origins to study the effect of metastatic potential on the integrity of the adjacent endothelial cell lining. Extravasation of fluorescently labeled liposomes across the endothelium to the tumors was measured following HBTAECs treatment with normal media, tumor conditioned media (TCM), or TNF-α. Tight junction formation was characterized using ZO-1 immunostaining. MDA-MB-231 cells quickly invaded into the vascular network from their primary culture location whereas MCF-7 cells rarely grew beyond the boundary of tumor origin. Permeability of liposomes across the endothelium was significantly higher with TCM treatment compared to both control and TNF-α treated cells (P &amp;lt; 0.01, one-way ANOVA). ZO-1 staining indicated strong tight junction formation when HBTAECs were treated with normal media as compared to TCM or TNF-α. We have successfully established an in vitro 3D tumor - endothelial cell co-culture model in a novel microfluidic platform that closely mimics the tumor microenvironment in vivo. This system reproduces the tumor permeability and retention (EPR) effect on a chip. This realistic in vitro model can have great potential in applications such as cell-cell/cell-drug carrier interaction studies, drug delivery carrier screening, and drug efficacy testing. Citation Format: Yuan Tang, Fariborz Soroush, Sudhir Deosarkar, Bin Wang, Balabhaskar Prabhakarpandian, Mohammad Kiani. A physiological model of the tumor microenvironment for screening drug delivery systems. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3382.
Abstract 1604: TMPRSS4 induces invasion and proliferation of prostate cancer cells through induction of Slug and cyclin D1
Authors: Yunhee Lee, Semi Kim
Journal: Cancer Research (2016)

Abstract TMPRSS4 is a novel type II transmembrane serine protease found at the cell surface that is highly expressed in pancreatic, colon, and other cancer tissues. Previously, we demonstrated that TMPRSS4 mediates tumor cell invasion, migration, and metastasis. We also found that TMPRSS4 activates the transcription factor activating protein-1 (AP-1) to induce cancer cell invasion. Here, we explored TMPRSS4-mediated cellular functions and the underlying mechanisms. TMPRSS4 induced Slug, an epithelial-mesenchymal transition (EMT)-inducing transcription factor, and cyclin D1 through activation of AP-1, composed of c-Jun and activating transcription factor (ATF)-2, which resulted in enhanced invasion and proliferation of PC3 prostate cancer cells. In PC3 cells, not only c-Jun but also Slug was required for TMPRSS4-mediated proliferation and invasion. Interestingly, Slug induced phosphorylation of c-Jun and ATF-2 to activate AP-1, establishing a positive feedback loop between Slug and AP-1, and thus induced cyclin D1, leading to enhanced proliferation. Using data from The Cancer Genome Atlas, we found that Slug expression positively correlated with that of c-Jun and cyclin D1 in human prostate cancers. This study demonstrates that TMPRSS4 modulates both invasion and proliferation via Slug and cyclin D1, which is a previously unrecognized pathway that may regulate metastasis and cancer progression. Citation Format: Yunhee Lee, Semi Kim. TMPRSS4 induces invasion and proliferation of prostate cancer cells through induction of Slug and cyclin D1. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1604.