tbuckley/cabot-search huggingface dataset:
Obstructive Sleep Apnea and Diabetes Independently Add to Cardiovascular Risk After Coronary Revascularization
Authors: Chieh Yang Koo, Luciano F. Drager, Rishi Sethi, Hee-Hwa Ho, Thet Hein, Man-Hong Jim, Bee-Choo Tai, Jun-Jie Zhang, Chi-Hang Lee
Journal: Diabetes Care (2017)

Obstructive sleep apnea (OSA) has been shown to be associated with accelerated coronary atherosclerosis (1–3). In the multicenter Sleep and Stent Study, we found that OSA was an independent predictor of major adverse cardiac and cerebrovascular events (MACCE) and cardiovascular mortality after percutaneous coronary intervention (PCI), with adjusted hazard ratios (HR) of 1.57 (95% CI 1.10–2.24) and 2.11 (95% CI 0.91–4.91), respectively (4).

Diabetes mellitus (DM) is an established risk factor of MACCE after PCI and was present in 42% of the patients in the Sleep and Stent Study (4). In this post hoc analysis, we hypothesized that patients with combined OSA and DM were at a particularly high risk of developing MACCE after PCI.

The Sleep and Stent Study was an observational study evaluating the effects of OSA on cardiovascular outcomes in patients undergoing PCI. The detailed methodology and inclusion and exclusion criteria have been published previously (5). After an overnight sleep study, the recruited patients were classified as OSA(+) (apnea-hypopnea index ≥15 events per hour) or OSA(−) (<15 events per hour). Studies have suggested the possible interaction between DM and OSA in glycemic control and the progression of chronic diabetic complications (6–8). As such, the primary aim of this post hoc analysis was to determine whether the effects of OSA in the occurrence of cardiovascular outcomes, defined as MACCE composed of cardiovascular mortality, nonfatal myocardial infarction, or nonfatal stroke, may be modified …
T-Cell Densities in Brain Metastases Are Associated with Patient Survival Times and Diffusion Tensor MRI Changes
Authors: Rasheed Zakaria, Angela Platt-Higgins, Nitika Rathi, Mark Radon, Sumit Das, Kumar Das, Maneesh Bhojak, Andrew Brodbelt, Emmanuel Chavredakis, Michael D. Jenkinson, Philip S. Rudland
Journal: Cancer Research (2017)

Abstract Brain metastases are common and are usually detected by MRI. Diffusion tensor imaging (DTI) is a derivative MRI technique that can detect disruption of white matter tracts in the brain. We have matched preoperative DTI with image-guided sampling of the brain–tumor interface in 26 patients during resection of a brain metastasis and assessed mean diffusivity and fractional anisotropy (FA). The tissue samples were analyzed for vascularity, inflammatory cell infiltration, growth pattern, and tumor expression of proteins associated with growth or local invasion such as Ki67, S100A4, and MMP2, 9, and 13. A lower FA in the peritumoral region indicated more white matter tract disruption and independently predicted longer overall survival times (HR for death = 0.21; 95% confidence interval, 0.06–0.82; P = 0.024). Of all the biological markers studied, only increased density of CD3+ lymphocytes in the same region correlated with decreased FA (Mann–Whitney U, P = 0.037) as well as confounding completely the effect of FA on multivariate survival analyses. We conclude that the T-cell response to brain metastases is not a surrogate of local tumor invasion, primary cancer type, or aggressive phenotype and is associated with patient survival time regardless of these biological factors. Furthermore, it can be assayed by DTI, potentially offering a quick, noninvasive, clinically available method to detect an active immune microenvironment and, in principle, to measure susceptibility to immunotherapy. Significance: These findings show that white matter tract integrity is degraded in areas where T-cell infiltration is highest, providing a noninvasive method to identify immunologically active microenvironments in secondary brain tumors. Cancer Res; 78(3); 610–6. ©2017 AACR.
Neurotransmitter Funneling Optimizes Glutamate Receptor Kinetics
Authors: Alvin Yu, Héctor Salazar, Andrew J.R. Plested, Albert Y. Lau
Journal: Neuron (2017)

Ionotropic glutamate receptors (iGluRs) mediate neurotransmission at the majority of excitatory synapses in the brain. Little is known, however, about how glutamate reaches the recessed binding pocket in iGluR ligand-binding domains (LBDs). Here we report the process of glutamate binding to a prototypical iGluR, GluA2, in atomistic detail using unbiased molecular simulations. Charged residues on the LBD surface form pathways that facilitate glutamate binding by effectively reducing a three-dimensional diffusion process to a spatially constrained, two-dimensional one. Free energy calculations identify residues that metastably bind glutamate and help guide it into the binding pocket. These simulations also reveal that glutamate can bind in an inverted conformation and also reorient while in its pocket. Electrophysiological recordings demonstrate that eliminating these transient binding sites slows activation and deactivation, consistent with slower glutamate binding and unbinding. These results suggest that binding pathways have evolved to optimize rapid responses of AMPA-type iGluRs at synapses.
Reply to Wijmans <i>et al.</i>: Optical Coherence Tomography: A Valuable Novel Tool for Assessing the Alveolar Compartment in Interstitial Lung Disease?
Authors: Lida P. Hariri, David C. Adams, John C. Wain, Michael Lanuti, Ashok Muniappan, Amita Sharma, Thomas V. Colby, Mari Mino-Kenudson, Eugene J. Mark, Richard L. Kradin, Hannah Goulart, Melissa J. Suter
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Opioid Stewardship and the Surgeon
Authors: Patrick R. Varley, Brian S. Zuckerbraun
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
Challenges and trends in apomorphine drug delivery systems for the treatment of Parkinson's disease
Authors: Nrupa Borkar, Huiling Mu, René Holm
Journal: Asian Journal of Pharmaceutical Sciences (2017)

Parkinson's disease (PD) is a chronic debilitating disease affecting approximately 1% of the population over the age of 60. The severity of PD is correlated to the degree of dopaminergic neuronal loss. Apomorphine has a similar chemical structure as the neurotransmitter dopamine and has been used for the treatment of advanced PD patients. In PD patients, apomorphine is normally administered subcutaneously with frequent injections because of the compound's extensive hepatic first-pass metabolism. There is, hence, a large unmet need for alternative administrative routes for apomorphine to improve patient compliance. The present review focuses on the research and development of alternative delivery of apomorphine, aiming to highlight the potential of non-invasive apomorphine therapy in PD, such as sublingual delivery and transdermal delivery.
Reactivity of IgM antibodies elicited by PEGylated liposomes or PEGylated lipoplexes against auto and foreign antigens
Authors: Hidenori Ando, Amr S. Abu Lila, Munehira Kawanishi, Taro Shimizu, Keiichiro Okuhira, Yu Ishima, Tatsuhiro Ishida
Journal: Journal of Controlled Release (2017)
Abdominal Handlebar Injury
Authors: Jurriën Stiekema, Joep P. M. Derikx
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
Abstract 48: Targeting IL-1 signaling to improve tumor response to erlotinib in HNSCC
Authors: Andrean Simons, Aditya Stanam, Adam Koch, Madelyn Espinosa-Cotton, Katherine Gibson-Corley
Journal: Clinical Cancer Research (2017)

Abstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) including erlotinib have demonstrated poor clinical response rates for head and neck squamous cell carcinoma (HNSCC) to date compared to the EGFR monoclonal antibody cetuximab. Therefore we seek to identify molecular mechanisms involved in tumor response to erlotinib and ultimately improve the anti-tumor efficacy of erlotinib for HNSCC patients. We have shown that erlotinib-treated HNSCC cell lines induced the expression and secretion of a wide variety of genes involved in inflammation and immune response including interleukin-1 (IL-1) and interleukin-6 (IL-6) compared to control-treated cells. The secretion of IL-6 from HNSCC cells in response to erlotinib was found to be triggered by MyD88-dependent IL-1 signaling and suppression of IL-1 signaling (using a neutralizing IL-1α antibody) significantly enhanced the anti-tumor efficacy of erlotinib in vivo. In erlotinib-resistant HNSCC cell lines, IL-1 signaling was significantly upregulated compared to their respective parental cell lines. Blockade of IL-1 signaling using a neutralizing IL-1α antibody or an IL-1 receptor (IL-1R) antagonist was able to significantly suppress the growth of erlotinib-resistant HNSCC xenografts as a single agent and in combination with erlotinib which was associated with reduced immune cell recruitment and angiogenesis. Altogether, blockade of the IL-1 pathway may represent a novel strategy to improve tumor response to erlotinib and other EGFR TKIs in HNSCC patients. Citation Format: Andrean Simons, Aditya Stanam, Adam Koch, Madelyn Espinosa-Cotton, Katherine Gibson-Corley. Targeting IL-1 signaling to improve tumor response to erlotinib in HNSCC [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 48.
Novel magnetic resonance technique for functional imaging of cystic fibrosis lung disease
Authors: Sylvia Nyilas, Grzegorz Bauman, Gregor Sommer, Enno Stranzinger, Orso Pusterla, Urs Frey, Insa Korten, Florian Singer, Carmen Casaulta, Oliver Bieri, Philipp Latzin
Journal: European Respiratory Journal (2017)

Lung function tests are commonly used to monitor lung disease in cystic fibrosis (CF). While practical, they cannot locate the exact origin of functional impairment. Contemporary magnetic resonance imaging (MRI) techniques provide information on the location of disease but the need for contrast agents constrains their repeated application. We examined the correlation between functional MRI, performed without administration of contrast agent, and lung clearance index (LCI) from nitrogen multiple-breath washout (N 2 -MBW). 40 children with CF (median (range) age 12.0 (6–18) years) and 12 healthy age-matched controls underwent functional and structural MRI and lung function tests on the same day. Functional MRI provided semiquantitative measures of perfusion ( R Q ) and ventilation ( R FV ) impairment as percentages of affected lung volume. Morphological MRI was evaluated using CF-specific scores. LCI measured global ventilation inhomogeneity. MRI detected functional impairment in CF: R FV 19–38% and R Q 16–35%. R FV and R Q correlated strongly with LCI (r=0.76, p&lt;0.0001 and r=0.85, p&lt;0.0001, respectively), as did total morphology score (r=0.81, p&lt;0.0001). All indices differed significantly between patients with CF and healthy controls (p&lt;0.001). Noninvasive functional MRI is a promising method to detect and visualise perfusion and ventilation impairment in CF without the need for contrast agents.
Effects of Diabetes and Glycemic Control on Risk of Hepatocellular Carcinoma After Seroclearance of Hepatitis B Surface Antigen
Authors: Terry Cheuk-Fung Yip, Vincent Wai-Sun Wong, Henry Lik-Yuen Chan, Yee-Kit Tse, Alice Pik-Shan Kong, Kelvin Long-Yan Lam, Grace Chung-Yan Lui, Grace Lai-Hung Wong
Journal: Clinical Gastroenterology and Hepatology (2017)
Targeting both tumour-associated CXCR2<sup>+</sup> neutrophils and CCR2<sup>+</sup> macrophages disrupts myeloid recruitment and improves chemotherapeutic responses in pancreatic ductal adenocarcinoma
Authors: Timothy M Nywening, Brian A Belt, Darren R Cullinan, Roheena Z Panni, Booyeon J Han, Dominic E Sanford, Ryan C Jacobs, Jian Ye, Ankit A Patel, William E Gillanders, Ryan C Fields, David G DeNardo, William G Hawkins, Peter Goedegebuure, David C Linehan
Journal: Gut (2017)

Objective Chemokine pathways are co-opted by pancreatic adenocarcinoma (PDAC) to facilitate myeloid cell recruitment from the bone marrow to establish an immunosuppressive tumour microenvironment (TME). Targeting tumour-associated CXCR2 + neutrophils (TAN) or tumour-associated CCR2 + macrophages (TAM) alone improves antitumour immunity in preclinical models. However, a compensatory influx of an alternative myeloid subset may result in a persistent immunosuppressive TME and promote therapeutic resistance. Here, we show CCR2 and CXCR2 combined blockade reduces total tumour-infiltrating myeloids, promoting a more robust antitumour immune response in PDAC compared with either strategy alone. Methods Blood, bone marrow and tumours were analysed from PDAC patients and controls. Treatment response and correlative studies were performed in mice with established orthotopic PDAC tumours treated with a small molecule CCR2 inhibitor (CCR2i) and CXCR2 inhibitor (CXCR2i), alone and in combination with chemotherapy. Results A systemic increase in CXCR2 + TAN correlates with poor prognosis in PDAC, and patients receiving CCR2i showed increased tumour-infiltrating CXCR2 + TAN following treatment. In an orthotopic PDAC model, CXCR2 blockade prevented neutrophil mobilisation from the circulation and augmented chemotherapeutic efficacy. However, depletion of either CXCR2 + TAN or CCR2 + TAM resulted in a compensatory response of the alternative myeloid subset, recapitulating human disease. This was overcome by combined CCR2i and CXCR2i, which augmented antitumour immunity and improved response to FOLFIRINOX chemotherapy. Conclusion Dual targeting of CCR2 + TAM and CXCR2 + TAN improves antitumour immunity and chemotherapeutic response in PDAC compared with either strategy alone.
Abstract 11105: New Blood Pressure Control Target for Diabetic Patients of 140/90 mmHg is Confirmed by the JPAD Trial
Authors: Hirofumi Soejima, Takeshi Morimoto, Sadanori Okada, Mio Sakuma, Masafumi Nakayama, Shiro Uemura, Masao Kanauchi, Naofumi Doi, Hideaki Jinnouchi, Seigo Sugiyama, Masako Waki, Yoshihiko Saito, Hisao Ogawa
Journal: Circulation (2014)

Introduction:  In 2013, the blood pressure (BP) control target for diabetic patients was changed in USA and Europe; however, there was a paucity of supporting evidence.   Hypothesis:  We investigated whether 140/90 mmHg or 130/80 mmHg was a better BP control target.   Methods:  We followed the cohort of 2536 Japanese primary prevention of atherosclerosis with aspirin for diabetes (JPAD) patients from May 2002 to July 2013, a median of 8.3 years. Primary end points were ischemic heart disease, stroke, peripheral arterial disease, or sudden death. BP of the JPAD patients was recorded on average 6 times. Based on the mean value of BP, we divided the patients into two groups: a high 140 BP (H140) group (n=674; systolic BP≥140 mmHg or diastolic BP≥90 mmHg or both); or, a low 140 BP (L140) group (n=1862; systolic BP   Results:  The incidence of primary end points was significantly higher in the H140 group than in the L140 group (P  In the comparison among the three groups (H140, M130-140, L130), the incidence of the end points was significantly higher in the H140 group than in the L130 group (HR 1.85, Figure). There was no significant difference between the M130-140 and the L130 groups (HR 0.97, Figure).   Conclusions: Utilizing the JPAD cohort, this study serves to validate the guidelines in USA and Europe. 140/90 mmHg is a significantly better BP control target for diabetics.
Surviving Ovarian Cancer: An Affair between Defective DNA Repair and RB1
Authors: Guang Peng, Gordon B. Mills
Journal: Clinical Cancer Research (2017)

Detailed clinical and molecular evaluation of large cohorts of exceptional survivors provides an unprecedented opportunity to identify mechanisms underlying long-term survival that can drive future therapeutic approaches and biomarker development. Exceptional survivors of high-grade serous ovarian cancer demonstrate concurrent disruption of homologous recombination DNA repair and retinoblastoma protein. Clin Cancer Res; 24(3); 508-10. ©2017 AACRSee related article by Garsed et al., p. 569.
Abstract B36: Contrasting views on the role of mesenchymal stem cells in tumor progression: A systematic review
Authors: Ahmed Kolade Oloyo, Michael Sean Pepper
Journal: Cancer Research (2017)

Abstract The role of mesenchymal stem cells (MSCs) in the progression of tumor remains controversial. Strong experimental evidences support both inhibitory and stimulatory roles of MSCs on tumor growth. To assess factors responsible for contrasting effects of MSCs on tumor growth, we did a systematic review of existing literature on the effect of MSCs on tumor growth from 01/01/00 - 01/05/16. A total of 168 original research articles with 315 experiments were assessed. Factors considered in the complex relationship between MSCs and tumor growth include: type of experiments (in-vivo, in-vitro), experimental models for the in-vivo studies (syngeneic or xenogeneic), immune status of the experimental animal (competent or deficient), sources and types of cancer and MSCs, status of the MSCs (naïve or engineered), methods of inducing cancer as well as methods of administering the MSCs in vivo and methods used in the in vitro experiments (co-culture or conditioned media). 55% of the studies favor the stimulatory effect of MSCs on tumor growth. The type of experiment is divided almost evenly, as about 53% of all the experiments were conducted in-vitro with 60% of the cancer cells exposed to the MSCs via co-culture methods. 78% of the in-vivo experiments were xenogeneic and 63% of these were carried out in immunocompetent animals. About 80% of both MSCs and cancer cells were sourced from human and 86% of these MSCs were used in their naïve form while 14% were engineered to produce factors that could alter the activity of the MSC itself or that of the cancer cells. About 61% of the MSCs were derived from bone marrow while 15% each were derived from adipose tissues and umbilical cord the remaining 8% MSCs were derived from other various tissues. Tumor growth was inhibited in 86% of experiments that used engineered MSCs. Tumor growth was inhibited in 82% of experiment that used umbilical cord MSCs while tumor growth was promoted in 62% of experiment that employed bone marrow MSCs, but the effect of MSCs on tumor growth was about 57% and 43% stimulatory and inhibitory respectively when adipose tissue derived MSCs were used. Thus several factors determine what effect MSCs would have on the progression of tumor growth. Note: This abstract was not presented at the conference. Citation Format: Ahmed Kolade Oloyo, Michael Sean Pepper. Contrasting views on the role of mesenchymal stem cells in tumor progression: A systematic review [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B36.
Abstract 19786: Deficiency of miR-1954 Triggers Cardiac Fibrosis by Targeting Sp1 and Tsp1
Authors: Sudhiranjan Gupta, Ana P Takano
Journal: Circulation (2016)

Introduction: Cardiac fibrosis which is a severe pathologic manifestation resulting from an injury to the myocardium due to pressure overload, ischemic insult or metabolic stress. In recent years, ...
Drug Trials Snapshots and Sexless Drug Labels—Reply
Authors: John Whyte, Janet Woodcock, Junyang Wang
Journal: JAMA Internal Medicine (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 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
Temsirolimus in Combination with Bendamustine and Rituximab (BeRT) for the Treatment of Relapsed Mantle Cell and Follicular Lymphoma: Final Phase I/II Results
Authors: Georg Hess, Wagner Karola, Paul LaRosee, Ulrich Keller, Johannes Atta, Mathias Witzens-Harig, Anne Crombé, Christoph Medler, Peter Borchmann, Ulrich Bitz, Christian Lerchenmüller, Matthias Theobald, Martin H. Dreyling
Journal: Blood (2016)