tbuckley/cabot-search huggingface dataset:
Type I Interferons in Autoimmune Disease
Authors: Mary K. Crow, Mikhail Olferiev, Kyriakos A. Kirou
Journal: Annual Review of Pathology Mechanisms of Disease (2018)

Type I interferons, which make up the first cytokine family to be described and are the essential mediators of antivirus host defense, have emerged as central elements in the immunopathology of systemic autoimmune diseases, with systemic lupus erythematosus as the prototype. Lessons from investigation of interferon regulation following virus infection can be applied to lupus, with the conclusion that sustained production of type I interferon shifts nearly all components of the immune system toward pathologic functions that result in tissue damage and disease. We review recent data, mainly from studies of patients with systemic lupus erythematosus, that provide new insights into the mechanisms of induction and the immunologic consequences of chronic activation of the type I interferon pathway. Current concepts implicate endogenous nucleic acids, driving both cytosolic sensors and endosomal Toll-like receptors, in interferon pathway activation and suggest targets for development of novel therapeutics that may restore the immune system to health.
Could plasma EBV DNA kinetics predict long-term disease-free survival in metastatic nasopharyngeal carcinoma?
Authors: L. Guoying, H. Liang, W.-X. Xia, Y.-Q. Xiang, X. Lv, X. Guo, Y.-H. Yu, S.-H. Lv, K.-Y. Liu, W.-Z. Qiu, X.-J. Huang, W.-Z. Li
Journal: Annals of Oncology (2018)
Portuguese in vitro antibiotic susceptibilities favor current nontuberculous mycobacteria treatment guidelines
Authors: Vera Durão, Anabela Silva, Rita Macedo, Paulo Durão, André Santos-Silva, Raquel Duarte
Journal: Pulmonology (2018)

Nontuberculous mycobacteria (NTM) are increasingly recognized as causative agents of opportunistic infections in humans for which effective treatment is challenging. There is, however, very little information on the prevalence of NTM drug resistance in Portugal. Our aim was to analyze the drug susceptibility testing (DST) performed in NTM at the Portuguese National Health Institute Dr. Ricardo Jorge from February 2003 to February 2016. A total of 262 DST were included in the analysis. Most (94%) M. avium intracellulare complex isolates showed in vitro susceptibility to clarithromycin. All M. kansasii isolates were susceptible to rifampicin and ethambutol and 97.1% were susceptible to isoniazid. The majority of rapidly-growing mycobacteria (RGM) demonstrated in vitro susceptibility to amikacin, clarithromycin and cefoxitin. However, in RGM there was a marked increase on the relative risk of having sulfamethoxazole resistance in isolates resistant to ciprofloxacin compared to susceptible isolates. Tested NTM in Portugal revealed in vitro susceptibility to most of the antimicrobials currently recommended for treatment. However, our results also suggest that sulfamethoxazole should be avoided in treatment of RGM resistant to ciprofloxacin (or vice versa). Further trials that correlate the in vitro DST results with the clinical outcome are needed in order to reach conclusions on efficient antimicrobial therapy.
Removal of visa cap for doctors is not temporary, home secretary insists
Authors: Abi Rimmer
Journal: BMJ (2018)

The lifting of the cap on the number of visas available to doctors from outside the European Economic Area is not a temporary measure, the UK home secretary has said, despite previously stating that it would be.

The cap of 20 700 a year on tier 2 skilled worker visas had meant that thousands of applications for visas for doctors who had been offered jobs in the NHS had been refused. In June the Home Office announced that it would remove restrictions on the number of visas available to doctors and nurses.1

However, a …
Tim-3 expression and its role in hepatocellular carcinoma
Authors: Feifei Liu, Yanning Liu, Zhi Chen
Journal: Journal of Hematology & Oncology (2018)

Hepatocellular carcinoma (HCC) is one of the most common tumors in the world, and its mortality is still on the rise. Limited treatments and low chemotherapy sensitivity of HCC make new therapeutic strategies urgently needed. With the rise of immune checkpoint blockade, anti-CTLA-4 antibodies and anti-PD-1 antibodies have shown therapeutic effects in various tumors. T cell immunoglobulin mucin-3 (Tim-3), a newly discovered immune checkpoint molecule, plays a major role in the development of HCC. Tim-3 can be used to evaluate the prognosis and therapeutic effects in HCC, and Tim-3 intervention has shown anti-tumor effects in preclinical experiments. This review summarizes findings regarding Tim-3 and HCC in recent years and discusses the rationale of Tim-3 as a therapeutic target for HCC.
Comparative analysis of overall survival using propensity score between first- and second-generation EGFR-TKI: Real world data of 1354 patients with EGFR mutant NSCLC
Authors: K. Ito, K. Murotani, A. Kubo, E. Kunii, H. Taniguchi, J. Shindo, K. Asada, K. Imaizumi, K. Tanaka, N. Inui, M. Okuno, O. Hataji, S. Hayai, T. Abe, T. Kimura, T. Tsuda, T. Yamaguchi, Y. Oya, T. Yoshida, T. Hida
Journal: Annals of Oncology (2018)
Abstract B05: Hippo effector YAP directly regulates the expression of PD-L1 transcripts in EGFR-TKI-resistant lung adenocarcinoma
Authors: Chaeuk Chung, Daehye Lee
Journal: Clinical Cancer Research (2018)

Abstract Developments of EGFR-TKI and immunotherapy targeting the PD1/PD-L1 pathway are considered the most important medical breakthroughs in lung cancer treatment. Nowadays, third-generation EGFR TKI is widely used for T790M positive first and second EGFR-TKI resistant lung cancer patients. Immunotherapy is powerful option for lung cancer patients without drug targets and chemotherapy-resistant patients. It also has changed the concept of conventional anticancer therapy in the point of regulating tumor microenvironment. There are many studies linking these two important pathways. Recent studies demonstrated that PD-L1 expression is significantly correlated to the mutation status of EGFR, and activation of EGFR signaling can also induce the expression of PD-L1. However, the real linker between PD-L1 and EGFR signaling remains to be revealed. Our previous study revealed that the Hippo pathway effector YAP confers EGFR-TKI resistance in lung adenocarcinoma, and inhibition of YAP restores sensitivity to EGFR-TKIs. Thus, we examined whether PD-L1 is relevant in terms of conferring EGFR-TKI resistance and whether YAP directly regulates the expression of PD-L1 in this context. First, we compared the expression levels of PD-L1 and YAP between EGFR-TKI-resistant PC9 cells and the parental PC9 adenocarcinoma cells. The expression levels of both YAP and PD-L1 were markedly higher in the EGFR-TKI-resistant cells compared to the parental cells, suggesting differential expression pattern between two cell types. YAP knockdown significantly decreased the expression of PD-L1 in the EGFR-TKI-resistant cells, while YAP overexpression increased the expression of PD-L1 in the parental PC9 cells. Then, our results revealed that YAP regulates the transcription of PD-L1, and the YAP/TEAD complex binds to the PD-L1 promoter. Surprisingly, knockdown of PD-L1 was sufficient to decrease cell proliferation and wound healing in the EGFR-TKI-resistant PC9 cells. These data suggest a PD1-independent oncogenic function of PD-L1. The Hippo effector YAP plays a crucial role in linking the PD-L1 and EGFR-TKI resistance by directly regulating the expression of PD-L1 in lung cancer. Targeting PD-L1 directly or via YAP could provide an effective therapeutic strategy for EGFR-TKI-resistant lung Citation Format: Chaeuk Chung, Daehye Lee. Hippo effector YAP directly regulates the expression of PD-L1 transcripts in EGFR-TKI-resistant lung adenocarcinoma [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr B05.
Cholangiocarcinoma with a metastatic umbilical lesion
Authors: David Harrington, Christina George, Hazem Ibrahim, Sanjay Bhagani
Journal: BMJ (2018)

A 59 year old man with a renal transplant and well controlled HIV infection presented with an enlarging, firm, and intermittently discharging crusted umbilical nodule (fig 1). He gave a history of …
ASTRIS: A real world treatment study of osimertinib in patients (pts) with EGFR T790M-positive non-small cell lung cancer (NSCLC) - European subset
Authors: M. Tiseo, A. Santo, M.J. Hochmair, T. Geldart, G. Metro, E. Hanrahan, K. Lamberg, T. Moran, C. Nyhus, A. Paredes, J.F. Vansteenkiste, D. Vicente, M. Miranda, J. Rigas, F. de Marinis
Journal: Annals of Oncology (2018)
Ras homolog gene family H (RhoH) deficiency induces psoriasis-like chronic dermatitis by promoting TH17 cell polarization
Authors: Norimasa Tamehiro, Kyoko Nishida, Yu Sugita, Kunihiro Hayakawa, Hiroyo Oda, Takeshi Nitta, Miwa Nakano, Akiko Nishioka, Reiko Yanobu-Takanashi, Motohito Goto, Tadashi Okamura, Reiko Adachi, Kazunari Kondo, Akimichi Morita, Harumi Suzuki
Journal: Journal of Allergy and Clinical Immunology (2018)
Characteristics of myeloproliferative neoplasms in patients exposed to ionizing radiation following the Chernobyl nuclear accident
Authors: Larysa Poluben, Maneka Puligandla, Donna Neuberg, Christine R. Bryke, Yahsuan Hsu, Oleksandr Shumeiko, Xin Yuan, Olga Voznesensky, German Pihan, Miriam Adam, Ernest Fraenkel, Roni Rasnic, Michal Linial, Sergiy Klymenko, Steven P. Balk, Paula G. Fraenkel
Journal: American Journal of Hematology (2018)

Myeloproliferative neoplasms (MPNs) driver mutations are usually found in JAK2, MPL, and CALR genes; however, 10%-15% of cases are triple negative (TN). A previous study showed lower rate of JAK2 V617F in primary myelofibrosis patients exposed to low doses of ionizing radiation (IR) from Chernobyl accident. To examine distinct driver mutations, we enrolled 281 Ukrainian IR-exposed and unexposed MPN patients. Genomic DNA was obtained from peripheral blood leukocytes. JAK2 V617F, MPL W515, types 1- and 2-like CALR mutations were identified by Sanger Sequencing and real time polymerase chain reaction. Chromosomal alterations were assessed by oligo-SNP microarray platform. Additional genetic variants were identified by whole exome and targeted sequencing. Statistical significance was evaluated by Fisher's exact test and Wilcoxon's rank sum test (R, version 3.4.2). IR-exposed MPN patients exhibited a different genetic profile vs unexposed: lower rate of JAK2 V617F (58.4% vs 75.4%, P = .0077), higher rate of type 1-like CALR mutation (12.2% vs 3.1%, P = .0056), higher rate of TN cases (27.8% vs 16.2%, P = .0366), higher rate of potentially pathogenic sequence variants (mean numbers: 4.8 vs 3.1, P = .0242). Furthermore, we identified several potential drivers specific to IR-exposed TN MPN patients: ATM p.S1691R with copy-neutral loss of heterozygosity at 11q; EZH2 p.D659G at 7q and SUZ12 p.V71 M at 17q with copy number loss. Thus, IR-exposed MPN patients represent a group with distinct genomic characteristics worthy of further study.
The gut microbiome: Relationships with disease and opportunities for therapy
Authors: Juliana Durack, Susan V. Lynch
Journal: The Journal of Experimental Medicine (2018)

Over the past decade, our view of human-associated microbes has expanded beyond that of a few species toward an appreciation of the diverse and niche-specialized microbial communities that develop in the human host with chronological age. The largest reservoir of microbes exists in the distal gastrointestinal tract, both in the lumen, where microbes facilitate primary and secondary metabolism, and on mucosal surfaces, where they interact with host immune cell populations. While local microbial-driven immunomodulation in the gut is well described, more recent studies have demonstrated a role for the gut microbiome in influencing remote organs and mucosal and hematopoietic immune function. Unsurprisingly, therefore, perturbation to the composition and function of the gut microbiota has been associated with chronic diseases ranging from gastrointestinal inflammatory and metabolic conditions to neurological, cardiovascular, and respiratory illnesses. Considerable effort is currently focused on understanding the natural history of microbiome development in humans in the context of health outcomes, in parallel with improving our knowledge of microbiome-host molecular interactions. These efforts ultimately aim to develop effective approaches to rehabilitate perturbed human microbial ecosystems as a means to restore health or prevent disease. This review details the role of the gut microbiome in modulating host health with a focus on immunomodulation and discusses strategies for manipulating the gut microbiome for the management or prevention of chronic inflammatory conditions.
DPYD genotype-guided dose individualization of fluoropyrimidine therapy: A prospective safety and cost-analysis on DPYD variants DPYD*2A, c.2846A&gt;T, c.1679T&gt;G and c.1236G&gt;A
Authors: L.M. Henricks, C.A.T.C. Lunenburg, F.M. de Man, D. Meulendijks, G.W.J. Frederix, E. Kienhuis, G.-J.M. Creemers, A. Baars, V.O. Dezentjé, H. Rosing, J.H. Beijnen, E. van Werkhoven, A.B.P. van Kuilenburg, R.H.N. van Schaik, R.H.J. Mathijssen, J.J. Swen, H. Gelderblom, A. Cats, H.-J. Guchelaar, J.H.M. Schellens
Journal: Annals of Oncology (2018)
Abstract 12482: Efficacy and Safety of Canagliflozin in Patients With Type 2 Diabetes Based on History of Cardiovascular Disease or Cardiovascular Risk Factors
Authors: Michael J Davies, Katherine Merton, Ujjwala Vijapurkar, Jacqueline Yee, Rong Qiu
Journal: Circulation (2016)

Introduction: Treatment of patients with type 2 diabetes mellitus (T2DM) and a history of cardiovascular (CV) disease or CV risk factors may present clinical challenges due to the presence of comorbid conditions and use of concomitant medications. Canagliflozin (CANA), an SGLT2 inhibitor, has been shown to improve glycemic control, body weight, and blood pressure (BP) with a favorable tolerability profile in a broad range of patients with T2DM. This post hoc analysis assessed the efficacy and safety of CANA in patients with T2DM based on CV disease history/risk factors. Methods: These analyses were based on pooled data from four 26-week, placebo (PBO)-controlled, Phase 3 studies that evaluated CANA 100 and 300 mg in patients with T2DM (N = 2313; mean A1C, 8.0%; body weight, 89 kg; systolic BP [SBP], 128 mmHg). Changes from baseline in A1C, body weight, and SBP at Week 26 were assessed in subgroups of patients based on history of CV disease (Y/N), history of hypertension (Y/N), baseline statin use (Y/N), and number of CV risk factors (0/1 vs ≥2). Safety was based on adverse event (AE) reports. Results: CANA 100 and 300 mg lowered A1C, body weight, and SBP versus PBO in patients with or without CV disease history/risk factors ( Table ). At Week 26, A1C reductions with CANA 100 and 300 mg relative to PBO were generally similar in patients with history of CV disease (–0.95% and –1.07%) versus no CV disease (–0.71% and –0.90%), history of hypertension (–0.72% and –0.89%) versus no hypertension (–0.73% and –0.95%), baseline statin use (–0.77% and –0.99%) versus no statin use (–0.69% and –0.85%), and ≥2 CV risk factors (–0.74% and –1.02%) versus 0/1 CV risk factor (–0.72% and –0.87%). Similar body weight and SBP reductions were also seen with CANA versus PBO across subgroups. Incidence of AEs, AEs leading to discontinuation, and serious AEs was similar across subgroups. Conclusions: CANA was efficacious and generally well tolerated in patients with T2DM regardless of CV disease history/risk factors.
Estimate of long-term relapse-free survival (RFS) and analysis of baseline factors associated with RFS in the COMBI-AD trial
Authors: R. Dummer, D. Schadendorf, A. Hauschild, M. Santinami, V.G. Atkinson, M. Mandala, V. Chiarion Sileni, J. Larkin, M.S. Nyakas, C. Dutriaux, A. Haydon, L. Mortier, C. Robert, J. Schachter, X. Feng, E. de Jong, B. Mookerjee, R. Kefford, J.M. Kirkwood, G.V. Long
Journal: Annals of Oncology (2018)
The Nuclear Receptor PPARγ Controls Progressive Macrophage Polarization as a Ligand-Insensitive Epigenomic Ratchet of Transcriptional Memory
Authors: Bence Daniel, Gergely Nagy, Zsolt Czimmerer, Attila Horvath, David W. Hammers, Ixchelt Cuaranta-Monroy, Szilard Poliska, Petros Tzerpos, Zsuzsanna Kolostyak, Tristan T. Hays, Andreas Patsalos, René Houtman, Sascha Sauer, Jean Francois-Deleuze, Fraydoon Rastinejad, Balint L. Balint, H. Lee Sweeney, Laszlo Nagy
Journal: Immunity (2018)
Successful intracranial delivery of trastuzumab by gene-therapy for treatment of HER2-positive breast cancer brain metastases
Authors: Inbal Zafir-Lavie, Shay Sherbo, Haim Goltsman, Felix Badinter, Eilam Yeini, Paula Ofek, Reem Miari, Osnat Tal, Atar Liran, Tamar Shatil, Simi Krispel, Nir Shapir, Garry A. Neil, Itai Benhar, Amos Panet, Ronit Satchi-Fainaro
Journal: Journal of Controlled Release (2018)
A Promising Skills-Based Intervention to Reduce Blood Pressure in Individuals With Stroke and Transient Ischemic Attack
Authors: Joosup Kim, Amanda G. Thrift
Journal: JAMA Neurology (2018)

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 Neurology 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 Neurology journal
Abstract B24: Characterization of somatically acquired regulatory mutations in high-risk neuroblastoma
Authors: Jo Lynne Harenza, Gregory Chen, John M. Maris
Journal: Cancer Research (2018)

Abstract Neuroblastoma is a childhood cancer of the developing peripheral nervous system and is uniquely characterized by a broad spectrum of phenotypes ranging from spontaneous tumor regression to relentless progression. The 5-year survival rate for children in the low- and intermediate-risk groups is over 95%; however, children with high-risk disease have a 40-50% likelihood of survival despite aggressive multimodal therapy. High-risk neuroblastomas harbor relatively few protein coding mutations at diagnosis, with the oncogenic mechanisms underlying MYCN amplification and ALK activation remaining obscure. We therefore hypothesized that characterizing high-risk neuroblastoma noncoding genetic variation will define gene regulatory mechanisms driving tumor progression, and that somatically acquired noncoding mutations alter critical neurodevelopmental gene regulatory regions. Here, we have integrated neuroblastoma cell line histone ChIP-Seq (N = 10), ATAC-Seq (N = 12), and RNA-Seq (N = 39) with high-risk patient (N = 105) whole-genome mutation data to define the landscape of noncoding somatic events dysregulating enhancers and promoters in high-risk neuroblastoma. We found a significantly higher number of mutations per patient in high-risk and stage 4 patients, compared to other risk groups (Wilcox Whigh-low = 129.5, p = 1.47e-07; Whigh-int = 70, p = 3.66e-08) and stages (WStage4-Stage3 = 86, p = 2.68e-3; WStage4-Stage4s= 65.5, p = 1.21e-12). We found a median of 1,809 somatic noncoding single nucleotide mutations per patient, and a subset of these recurrently mutate sequences underlying super-enhancer peaks of 102 genes. An additional subset lie within CCCTC-binding factor (CTCF) motifs (a median of 5 mutations per patient), suggesting potential dysregulation of chromosome looping in neuroblastoma. Understanding noncoding drivers of oncogenic gene expression and translating these basic science discoveries to the clinic is a critical step towards changing the devastating course of this disease. Citation Format: Jo Lynne Harenza, Gregory Chen, John M. Maris. Characterization of somatically acquired regulatory mutations in high-risk neuroblastoma [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr B24.
Comment on Andersen et al. Risk-Factor Trajectories Preceding Diabetic Polyneuropathy: ADDITION-Denmark. Diabetes Care 2018;41:1955–1962
Authors: Vincent Rigalleau, Maxime Lecocq, Marine Rigo, Marie Monlun, Pauline Poupon, Laurence Blanco, Laure Alexandre, Magali Haissaguerre, Kamel Mohammedi
Journal: Diabetes Care (2018)

We were interested in the article by Andersen et al. (1), who showed that diabetic polyneuropathy (DPN) was related to baseline HbA1c and its increase in 452 participants with type 2 diabetes in the Danish arm of the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION-Denmark) (1). If HbA1c trajectories influence DPN, it could be improved by treatment. In the Kumamoto trial, the vibration perception thresholds (VPT) stabilized in patients on intensive glucose control, whereas they increased from 22 to 37 V in those on conventional treatment (2).

Andersen et al. (1) cautiously mentioned that their results may not apply to people with type 2 diabetes clinically diagnosed later in the disease course, with higher HbA1c that changed …
GW29-e0476 Deep Phenotyping the Cardiovascular Disease in National Health and Nutrition Examination Survey 1999-2014: Presenting the Full Picture
Authors: Xiaodong Zhuang, Lizhen Liao, Ao Ni, Daya Yang, Shaozhao Zhang, Huimin Zhou, Xiuting Sun, Xiangbin Zhong, Zhimin Du, Xueqin Wang, Xinxue Liao
Journal: Journal of the American College of Cardiology (2018)
Standardized Uniform Reporting and Indications for Bariatric and Metabolic Surgery
Authors: Paulina Salminen
Journal: JAMA Surgery (2018)

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