tbuckley/cabot-search huggingface dataset:
Immunogenicity of a new routine vaccination schedule for global poliomyelitis prevention: an open-label, randomised controlled trial
Authors: Roland W Sutter, Sunil Bahl, Jagadish M Deshpande, Harish Verma, Mohammad Ahmad, P Venugopal, J Venkateswara Rao, Sharad Agarkhedkar, Sanjay K Lalwani, Abhishek Kunwar, Raman Sethi, Marina Takane, Lalitendu Mohanty, Arani Chatterjee, T Jacob John, Hamid Jafari, R Bruce Aylward
Journal: The Lancet (2015)
Group B Streptococcus Evades Host Immunity by Degrading Hyaluronan
Authors: Stacey L. Kolar, Pierre Kyme, Ching Wen Tseng, Antoine Soliman, Amber Kaplan, Jiurong Liang, Victor Nizet, Dianhua Jiang, Ramachandran Murali, Moshe Arditi, David M. Underhill, George Y. Liu
Journal: Cell Host & Microbe (2015)
High-Value Care
Authors: Aria A. Razmaria
Journal: JAMA (2015)

Lorette A. Stammen, MD; Renée E. Stalmeijer, MSc, PhD; Emma Paternotte, MD; Andrea Oudkerk Pool, MSc; Erik W. Driessen, MSc, PhD; Fedde Scheele, MD, PhD; Laurents P. S. Stassen, MD, PhD
Control of PD-L1 Expression by Oncogenic Activation of the AKT–mTOR Pathway in Non–Small Cell Lung Cancer
Authors: Kristin J. Lastwika, Willie Wilson, Qing Kay Li, Jeffrey Norris, Haiying Xu, Sharon R. Ghazarian, Hiroshi Kitagawa, Shigeru Kawabata, Janis M. Taube, Sheng Yao, Linda N. Liu, Joell J. Gills, Phillip A. Dennis
Journal: Cancer Research (2015)

Alterations in EGFR, KRAS, and ALK are oncogenic drivers in lung cancer, but how oncogenic signaling influences immunity in the tumor microenvironment is just beginning to be understood. Immunosuppression likely contributes to lung cancer, because drugs that inhibit immune checkpoints like PD-1 and PD-L1 have clinical benefit. Here, we show that activation of the AKT-mTOR pathway tightly regulates PD-L1 expression in vitro and in vivo. Both oncogenic and IFNγ-mediated induction of PD-L1 was dependent on mTOR. In human lung adenocarcinomas and squamous cell carcinomas, membranous expression of PD-L1 was significantly associated with mTOR activation. These data suggest that oncogenic activation of the AKT-mTOR pathway promotes immune escape by driving expression of PD-L1, which was confirmed in syngeneic and genetically engineered mouse models of lung cancer where an mTOR inhibitor combined with a PD-1 antibody decreased tumor growth, increased tumor-infiltrating T cells, and decreased regulatory T cells.
Association Between Leukemia and Topical Use of Pimecrolimus—Reply
Authors: David J. Margolis, Katrina Abuabara, Ole J. Hoffstad, Joy Wan, Denise Raimondo, Warren B. Bilker
Journal: JAMA Dermatology (2015)

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 Dermatology 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 Dermatology journal
Statins up-regulate SmgGDS through β1-integrin/Akt1 pathway in endothelial cells
Authors: Tatsuro Minami, Kimio Satoh, Masamichi Nogi, Shun Kudo, Satoshi Miyata, Shin-ichi Tanaka, Hiroaki Shimokawa
Journal: Cardiovascular Research (2015)

The pleiotropic effects of HMG-CoA reductase inhibitors (statins) independent of cholesterol-lowering effects have attracted much attention. We have recently demonstrated that the pleiotropic effects of statins are partly mediated through up-regulation of small GTP-binding protein dissociation stimulator (SmgGDS) with a resultant Rac1 degradation and reduced oxidative stress. However, it remains to be elucidated what molecular mechanisms are involved. To first determine in what tissue statins up-regulate SmgGDS expression, we examined the effects of two statins (atorvastatin 10 mg/kg per day and pravastatin 50 mg/kg per day for 1 week) on SmgGDS expression in mice in vivo. The two statins increased SmgGDS expression especially in the aorta. Atorvastatin also increased SmgGDS expression in cultured human umbilical venous endothelial cells (HUVEC) and human aortic endothelial cells, but not in human aortic vascular smooth muscle cells. Furthermore, Akt phosphorylation was transiently enhanced only in HUVEC in response to atorvastatin. Then, to examine whether Akt is involved for up-regulation of SmgGDS by statins, we knocked out Akt1 by its siRNA in HUVEC, which abolished the effects by atorvastatin to up-regulate SmgGDS. Furthermore, when we knocked down β1-integrin to elucidate the upstream molecule of Akt1, the effect of atorvastatin to up-regulate SmgGDS was abolished. Finally, we confirmed that Akt activator, SC79, significantly up-regulate SmgGDS in HUVEC. These results indicate that statins selectively up-regulate SmgGDS in endothelial cells, for which the β1-integrin/Akt1 pathway may be involved, demonstrating the novel aspects of the pleiotropic effects of statins.
Is Cancer Pain Control Improved by a Simple WHO Pain Analgesic Ladder Approach Combined With Tumor-Directed Treatment?
Authors: Stein Kaasa
Journal: Journal of Clinical Oncology (2015)

The practical use of the WHO analgesic ladder has evolved over time; is there a need for a formal change? Taking into consideration that pain is the symptom most feared by patients and families, and that studies have demonstrated that 90% of patients with cancer experience pain 1 and only 50% receive adequate pain control in unselected cancer cohorts, 2 there is an urgent need for improvement. The solutions are clearly more complex than simply changingtheWHOanalgesicladder.Systematicpaindiagnosisduring oncology consultations should be incorporated as a minimum requirement into standard inpatient and outpatient consultations. However, it is debatable how to address symptom management in general and pain management specifically in consultations where the primary focus is often how to treat the tumor and prolong life. Cancer pain is affected by many variables, such as tumor type and site, the extent of the disease, cancer therapy, and host factors (sex, genomics, and psychologic and social factors, among others), which challenge a simple solution to pain diagnosis. Is it possible to simplify both pain classification and management, with improved overall pain control as a result? In the article that accompanies this editorial, Bandieri et al 3 challenge the concept of the WHO analgesic ladder, which consists of three steps (nonopioids [step 1], weak opioids [eg, codeine and tramadol; step 2], and strong opioids [eg, morphine, fentanyl, and oxycodone; step 3]), and consider whether a two-step approach will contribute to better overall pain control is questionable. This two-step concept is in accordance with the latest European Association for Palliative Care recommendations. 4
MiR-138 exerts anti-glioma efficacy by targeting immune checkpoints
Authors: Jun Wei, Edjah K. Nduom, Ling-Yuan Kong, Yuuri Hashimoto, Shuo Xu, Konrad Gabrusiewicz, Xiaoyang Ling, Neal Huang, Wei Qiao, Shouhao Zhou, Cristina Ivan, Greg N. Fuller, Mark R. Gilbert, Willem Overwijk, George A. Calin, Amy B. Heimberger
Journal: Neuro-Oncology (2015)

Antibody therapeutic targeting of the immune checkpoints cytotoxic T-lymphocyte-associated molecule 4 (CTLA-4) and programmed cell death 1 (PD-1) has demonstrated marked tumor regression in clinical trials. MicroRNAs (miRNAs) can modulate multiple gene transcripts including possibly more than one immune checkpoint and could be exploited as immune therapeutics. Using online miRNA targeting prediction algorithms, we searched for miRNAs that were predicted to target both PD-1 and CTLA-4. MiR-138 emerged as a leading candidate. The effects of miR-138 on CTLA-4 and PD-1 expression and function in T cells were determined and the therapeutic effect of intravenous administration of miR-138 was investigated in both immune-competent and -incompetent murine models of GL261 glioma. Target binding algorithms predicted that miR-138 could bind the 3′ untranslated regions of CTLA-4 and PD-1, which was confirmed with luciferase expression assays. Transfection of human CD4+ T cells with miR-138 suppressed expression of CTLA-4, PD-1, and Forkhead box protein 3 (FoxP3) in transfected human CD4+ T cells. In vivo miR-138 treatment of GL261 gliomas in immune-competent mice demonstrated marked tumor regression, a 43% increase in median survival time (P = .011), and an associated decrease in intratumoral FoxP3+ regulatory T cells, CTLA-4, and PD-1 expression. This treatment effect was lost in nude immune-incompetent mice and with depletion of CD4+ or CD8+ T cells, and miR-138 had no suppressive effect on glioma cells when treated directly at physiological in vivo doses. MiR-138 exerts anti-glioma efficacy by targeting immune checkpoints which may have rapid translational potential as a novel immunotherapeutic agent.
Phenotyping by magnetic resonance imaging nondestructively measures glomerular number and volume distribution in mice with and without nephron reduction
Authors: Edwin J. Baldelomar, Jennifer R. Charlton, Scott C. Beeman, Bradley D. Hann, Luise Cullen-McEwen, Valeria M. Pearl, John F. Bertram, Teresa Wu, Min Zhang, Kevin M. Bennett
Journal: Kidney International (2015)
Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active-controlled, multicentre, open-label, phase 3, non-inferiority study
Authors: Anthony Mills, Jose R Arribas, Jaime Andrade-Villanueva, Giovanni DiPerri, Jan Van Lunzen, Ellen Koenig, Richard Elion, Matthias Cavassini, Jose Valdez Madruga, Jason Brunetta, David Shamblaw, Edwin DeJesus, Chloe Orkin, David A Wohl, Indira Brar, Jeffrey L Stephens, Pierre-Marie Girard, Gregory Huhn, Andrew Plummer, Ya-Pei Liu, Andrew K Cheng, Scott McCallister
Journal: The Lancet Infectious Diseases (2015)
Lymphatic Vessels, Inflammation, and Immunity in Skin Cancer
Authors: Amanda W. Lund, Terry R. Medler, Sancy A. Leachman, Lisa M. Coussens
Journal: Cancer Discovery (2015)

Skin is a highly ordered immune organ that coordinates rapid responses to external insult while maintaining self-tolerance. In healthy tissue, lymphatic vessels drain fluid and coordinate local immune responses; however, environmental factors induce lymphatic vessel dysfunction, leading to lymph stasis and perturbed regional immunity. These same environmental factors drive the formation of local malignancies, which are also influenced by local inflammation. Herein, we discuss clinical and experimental evidence supporting the tenet that lymphatic vessels participate in regulation of cutaneous inflammation and immunity, and are important contributors to malignancy and potential biomarkers and targets for immunotherapy.The tumor microenvironment and tumor-associated inflammation are now appreciated not only for their role in cancer progression but also for their response to therapy. The lymphatic vasculature is a less-appreciated component of this microenvironment that coordinates local inflammation and immunity and thereby critically shapes local responses. A mechanistic understanding of the complexities of lymphatic vessel function in the unique context of skin provides a model to understand how regional immune dysfunction drives cutaneous malignancies, and as such lymphatic vessels represent a biomarker of cutaneous immunity that may provide insight into cancer prognosis and effective therapy.
Medical Schools in the United States, 2014-2015
Authors: Barbara Barzansky, Sylvia I. Etzel
Journal: JAMA (2015)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Synthesis, characterization and targeting chemotherapy for ovarian cancer of trastuzumab-SN-38 conjugates
Authors: Yuqin Yao, Lin Yu, Xiaolan Su, Yuxi Wang, Wenting Li, Yangpin Wu, Xiangzheng Cheng, Hang Zhang, Xian Wei, Hao Chen, Rundong Zhang, Lantu Gou, Xiaoxin Chen, Yongmei Xie, Bo Zhang, Yonghui Zhang, Jinliang Yang, Yuquan Wei
Journal: Journal of Controlled Release (2015)
Caffeine protects against experimental acute pancreatitis by inhibition of inositol 1,4,5-trisphosphate receptor-mediated Ca<sup>2+</sup>release
Authors: Wei Huang, Matthew C Cane, Rajarshi Mukherjee, Peter Szatmary, Xiaoying Zhang, Victoria Elliott, Yulin Ouyang, Michael Chvanov, Diane Latawiec, Li Wen, David M Booth, Andrea C Haynes, Ole H Petersen, Alexei V Tepikin, David N Criddle, Robert Sutton
Journal: Gut (2015)

Caffeine reduces toxic Ca2+ signals in pancreatic acinar cells via inhibition of inositol 1,4,5-trisphosphate receptor (IP3R)-mediated signalling, but effects of other xanthines have not been evaluated, nor effects of xanthines on experimental acute pancreatitis (AP). We have determined effects of caffeine and its xanthine metabolites on pancreatic acinar IP3R-mediated Ca2+ signalling and experimental AP.Isolated pancreatic acinar cells were exposed to secretagogues, uncaged IP3 or toxins that induce AP and effects of xanthines, non-xanthine phosphodiesterase (PDE) inhibitors and cyclic adenosine monophosphate and cyclic guanosine monophosphate (cAMP/cGMP) determined. The intracellular cytosolic calcium concentration ([Ca2+]C), mitochondrial depolarisation and necrosis were assessed by confocal microscopy. Effects of xanthines were evaluated in caerulein-induced AP (CER-AP), taurolithocholic acid 3-sulfate-induced AP (TLCS-AP) or palmitoleic acid plus ethanol-induced AP (fatty acid ethyl ester AP (FAEE-AP)). Serum xanthines were measured by liquid chromatography-mass spectrometry.Caffeine, dimethylxanthines and non-xanthine PDE inhibitors blocked IP3-mediated Ca2+ oscillations, while monomethylxanthines had little effect. Caffeine and dimethylxanthines inhibited uncaged IP3-induced Ca2+ rises, toxin-induced Ca2+ release, mitochondrial depolarisation and necrotic cell death pathway activation; cAMP/cGMP did not inhibit toxin-induced Ca2+ rises. Caffeine significantly ameliorated CER-AP with most effect at 25 mg/kg (seven injections hourly); paraxanthine or theophylline did not. Caffeine at 25 mg/kg significantly ameliorated TLCS-AP and FAEE-AP. Mean total serum levels of dimethylxanthines and trimethylxanthines peaked at >2 mM with 25 mg/kg caffeine but at <100 µM with 25 mg/kg paraxanthine or theophylline.Caffeine and its dimethylxanthine metabolites reduced pathological IP3R-mediated pancreatic acinar Ca2+ signals but only caffeine ameliorated experimental AP. Caffeine is a suitable starting point for medicinal chemistry.
Abstract P061: Dietary Intake of Saturated Fat by Food Source and Incident Coronary Heart Disease: the Zutphen Elderly Study
Authors: Janette de Goede, Sabita S Soedamah-Muthu, Eirini Trichia, Johanna M Geleijnse, Daan Kromhout
Journal: Circulation (2015)

Introduction: Associations of saturated fatty acids (SFA) with coronary heart disease (CHD) may depend on their food source. We examined the association of SFA intake from different food sources, with 15-year incidence of coronary heart disease (CHD) in elderly men in the Netherlands. Methods: Data were collected from 686 elderly men from the Zutphen Elderly Study, aged 65-85 years with no CHD or diabetes mellitus. At baseline (1985), habitual diet was assessed with a cross-check dietary history method. Information on vital status and incidence of CHD (fatal CHD and nonfatal myocardial infarction) until July 1, 2000 was assessed through municipal population registries and hospital or GP records. Hazard ratios (HR) were calculated with Cox proportional-hazards models, adjusted for age, lifestyle (smoking, BMI, physical activity, socioeconomic status, and alcohol consumption) and dietary factors including total energy, carbohydrates, protein, monounsaturated fatty acids, trans fatty acids and dietary fibre. In addition, substitution models were used to estimate the exchange of 2 en% SFA from different sources, i.e. dairy, meat, and plant or butter SFA. Results: During 15 years of follow-up, we observed 132 incident CHD events. Across tertiles (T), the intake of SFA ranged from 14.2 (T1) to 21.7 (T3) energy percent (en%). Plant or butter SFA contributed for 37 en% to total SFA intake, followed by dairy (27%) and meat (17%). Total SFA intake correlated most strongly with plant or butter SFA (r=0.71). Spearman correlation coefficients of total SFA with dairy and meat were 0.34 and 0.09 respectively (all p&lt;0.05). The intake of total SFA was not significantly associated with CHD (HR: 0.76; 95%CI: 0.41-1.39) for T3 vs T1. HRs for plant or butter SFA, dairy SFA, and meat SFA were 0.96 (0.55-1.69), 0.82 (0.48-1.40), and 1.64 (0.89-3.04) respectively, for the top compared to the bottom tertile. A 2 en% higher intake of SFA from dairy or meat, exchanged with plant or butter SFA, resulted in a HR of 0.98 (95% CI: 0.79-1.20) for dairy and 1.12 (0.75-1.66) for meat. The HR (95% CI) for an exchange of 2 en% SFA from dairy with SFA from meat was 1.15 (95% CI: 0.80-1.66). Conclusion: In Dutch elderly men, total SFA or SFA from specific food sources were not significantly associated with incident CHD. The association of SFA from meat with CHD deserves further attention.
Role of Hormonal Treatment in Prostate Cancer Patients with Nonmetastatic Disease Recurrence After Local Curative Treatment: A Systematic Review
Authors: Roderick C.N. van den Bergh, Niels J. van Casteren, Thomas van den Broeck, Eve R. Fordyce, William K.M. Gietzmann, Fiona Stewart, Steven MacLennan, Saeed Dabestani, Joaquim Bellmunt, Michel Bolla, Erik Briers, Philip Cornford, Steven Joniau, Malcolm D. Mason, Vsevolod Matveev, Henk G. van der Poel, Theo H. van der Kwast, Olivier Rouvière, Thomas Wiegel, Thomas B. Lam, Nicolas Mottet
Journal: European Urology (2015)
European Symposium on Precision Medicine in Allergy and Airways Diseases: Report of the European Union Parliament Symposium (October 14, 2015)
Authors: A. Muraro, W. J. Fokkens, S. Pietikainen, D. Borrelli, I. Agache, J. Bousquet, V. Costigliola, G. Joos, V. J. Lund, L. K. Poulsen, D. Price, C. Rolland, T. Zuberbier, P. W. Hellings
Journal: Allergy (2015)

The European Academy of Allergy and Clinical Immunology (EAACI), the European Rhinologic Society (ERS), and the European Medical Association (EMA) organized, on October 14, 2015, a symposium in the European Parliament in Brussels on Precision Medicine in Allergy and Airways Diseases, hosted by MEP David Borrelli, and with active participation of the EU Commissioner for Health and Food Safety Vytenis Andriukaitis, MEP Sirpa Pietikainen, Chair of the European Parliament Interest Group on Allergy and Asthma, the European Respiratory Society (ERS), the European Federations of Allergy and Airways Diseases Patients Associations (EFA), the Global Allergy and Asthma European Network (Ga2len), Allergic Rhinitis and Its Impact on Asthma (ARIA), and the Respiratory Effectiveness Group (REG). The socioeconomic impact of allergies and chronic airways diseases cannot be underestimated, as they represent the most frequently diagnosed chronic noncommunicable diseases in the EU; 30% of the total European population is suffering from allergies and asthma, and more than half are deprived from adequate diagnosis and treatment. Precision medicine represents a novel approach, embracing four key features: personalized care based on molecular, immunologic, and functional endotyping of the disease, with participation of the patient in the decision-making process of therapeutic actions, and considering predictive and preventive aspects of the treatment. Implementation of precision medicine into clinical practice may help to achieve the arrest of the epidemic of allergies and chronic airways diseases. Participants underscored the need for optimal patient care in Europe, supporting joint action plans for disease prevention, patient empowerment, and cost-effective treatment strategies.
Time-Dependent Measurement of Adverse Events
Authors: Shelley Ji Eun Hwang, Karen Byth, Pablo Fernandez-Penas
Journal: JAMA Dermatology (2015)

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