tbuckley/cabot-search huggingface dataset:
Comparative Risk of Venous Thromboembolism in Rheumatoid Arthritis Patients Receiving Tofacitinib Versus Those Receiving Tumor Necrosis Factor Inhibitors: An Observational Cohort Study
Authors: Rishi J. Desai, Ajinkya Pawar, Michael E. Weinblatt, Seoyoung C. Kim
Journal: Arthritis & Rheumatology (2018)

Objective To evaluate the risk of venous thromboembolism ( VTE ) in rheumatoid arthritis ( RA ) patients receiving tofacitinib versus those receiving tumor necrosis factor ( TNF ) inhibitors. Methods RA patients who were initiating treatment with tofacitinib or a TNF inhibitor and had not previously received any biologic agent or tofacitinib were identified from the Truven MarketScan database (2012–2016) or Medicare claims (parts A, B, and D) database (2012–2015). Patients were followed up until treatment discontinuation, treatment switch, insurance disenrollment, or administrative censoring. The outcome of VTE was identified using inpatient claims for pulmonary embolism or deep vein thrombosis. Hazard ratios ( HR s) and 95% confidence intervals (95% CI s) were determined using a Cox proportional hazards model after accounting for confounding through propensity score–based fine‐stratification weighting. HR s were pooled across databases using the inverse variance meta‐analytic method. Results A total of 34,074 RA patients (mean age 50 years; 5.6% tofacitinib initiators) and 17,086 RA patients (mean age 71 years; 5.8% tofacitinib initiators) were identified from the Truven and Medicare databases, respectively. The crude incidence rates of VTE per 100 person‐years were 0.60 (95% CI 0.26–1.19) and 0.34 (95% CI 0.27–0.41) in Truven and 1.12 (95% CI 0.45–2.31) and 0.92 (95% CI 0.76–1.11) in Medicare for patients receiving tofacitinib and patients receiving TNF inhibitors, respectively. Propensity score–adjusted HR s showed no significant differences in the risk of VTE between tofacitinib‐treated and TNF inhibitor–treated patients in either database, with a pooled HR of 1.33 (95% CI 0.78–2.24). Conclusion Occurrence of VTE in a total of 50,865 RA patients initiating treatment with tofacitinib or a TNF inhibitor was infrequent (&lt;1 per 100 person‐years). We observed a numerically higher, but statistically nonsignificant, risk of VTE in RA patients receiving tofacitinib versus those receiving TNF inhibitors.
Inhibition of hypoxia inducible factor-1 α (HIF-1α) by an RNA antagonist, EZN-2968, in vitro and in vivo.
Authors: Lee Greenberger, D Filpula, C Conover, M Westergaard, E Straarup, H Hansen, P Kearney, I Horak
Journal: Cancer Research (2008)

1570  Inhibition of hypoxia inducible factor-1 α (HIF-1α) by an RNA antagonist, EZN-2968, in vitro and in vivo.   1Enzon Pharmaceuticals, 20 Kingsbridge Road, Piscataway, NJ 08854, 2Santaris Pharma, Boge Alle 3, DK-2970 Horsholm, Denmark  HIF-1α is a transcription factor that plays a critical role in angiogenesis, survival, metastasis, drug resistance, and glucose metabolism. Elevated expression of HIF-1α is associated with poor prognosis in cancer patients; it can be elevated in response to hypoxia (due to reduced protein degradation), or when growth factor pathways are hyperactivated. Therefore, down-regulation of HIF1-α by RNA antagonists may have broad therapeutic application. EZN-2968 is a locked nucleic acid (LNA) RNA antagonist that specifically inhibits the expression of HIF-1α. Unlike other RNA antagonists, in LNAs the ribose sugar ring in each monomer is fixed in a RNA-like conformation by the introduction of a methylene bridge, linking the 2′-oxygen and 4′-carbon. This imparts LNA RNA antagonists with higher affinity and resistance against degradation compared with other oligonucleotides. In vitro, in human prostate (15PC3, PC3, DU145) and glioblastoma (U373) cells, EZN-2968 induced a potent, selective, and durable antagonism of HIF-1α expression (IC50 1 to 5 nM), both under normoxic and hypoxic conditions. Additionally, down-regulation of HIF-1α by EZN-2968 led to reduction of its transcriptional targets (VEGF and matrix metalloproteinase 2 proteins) and significant reduction of HUVEC tube formation. In DU145, A549, and U373 cancer cell lines, treatment with EZN-2968 led to apoptosis and inhibition of cell proliferation. In vivo, administration of EZN-2968 to normal mice led to specific, dose-dependent, and highly potent down-regulation of endogenous HIF-1α and VEGF in liver. The effect of a single dose of EZN-2968 (50 mg/kg) lasted at least 4 days but less than 8 days, with a maximum effect of 75% reduction of HIF-1α and 60% reduction of VEGF mRNA 5 days after dosing. In efficacy studies, tumor reduction was found in mice implanted with DU145 cells that were transfected with EZN-2968 prior to implantation and given systemic treatment with EZN-2968 post tumor implantation. In conclusion, EZN-2968 is a potent and selective inhibitor of HIF-1α in vitro and in vivo. Ongoing Phase I studies will determine the optimal dose and schedule of EZN-2968 for the treatment of cancer.
A Patient With Multiple Coronary Artery Aneurysms
Authors: Long Jiang Zhang, Fan Zhou
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
The prognostic significance of androgen receptor phosphorylation and the immune infiltrate in prostate cancer
Authors: H.W.G. Gan, M. McAllister, V. Constancio, S. Payne, M.A. Underwood, H.Y. Leung, J. Edwards
Journal: Annals of Oncology (2018)

Background: The phosphorylation of the androgen receptor (AR) at various sites has been associated with diverse functions and clinical outcomes in prostate cancer and the processes underlying phosphorylation at S81 (pAR81) and S213 (pAR213) may possibly be targeted therapeutically. In addition, inflammation upregulates AR and cancer-promoting pathways, and high CD3+ and CD8+ T-cells in the tumour microenvironment have been associated with poorer outcomes. Therefore, this study aims to assess the prognostic value of tumour markers – AR, immune cell infiltrate and proliferation – and develop a combined prognostic score. Methods: Immunohistochemistry was performed for 243 patients with prostate cancer to assess AR, pAR81, pAR213, Ki67, CD3 and CD8. AR expression was evaluated separately based on localisation: tumour or stromal cell, nuclear or cytoplasmic, with nuclear/cytoplasmic ratio (N/C) calculated. These tumour markers were assessed with overall survival and other biomarkers. Results: High Ki67 (p = 0.003), CD8 (p = 0.022), CD3 (p = 0.006), and tumour cytoplasmic AR (p = 0.001) and pAR81 (p = 0.049), were associated with lower survival. Conversely, associated with higher survival were high tumour nuclear AR (p = 0.027) and N/C for AR (p = 3 × 10−4), pAR81(p = 0.032) and pAR213 (p = 0.010). In the stroma, high nuclear AR (p = 0.002), AR N/C (p = 0.041) and cytoplasmic pAR81 (p = 0.039) were associated with better survival. The Phosphorylated Androgen Receptor and Lymphocyte (PARL) score was derived by adding 1 for each of: high CD8, high tumour cytoplasmic pAR81, low tumour pAR213 N/C and low stromal nuclear AR. Patients are stratified into low (0-1), medium (2) and high (3-4) with worsening five-year survival of 88%, 79% and 50% respectively. The PARL score was a significant predictor of survival (p = 0.001), independent of Gleason score, prostate-specific antigen, perineural invasion and serum albumin. Conclusions: CD3+ and CD8+ T-cell infiltration are negative prognostic markers, while the AR has different roles and prognostic values depending on localisation and phosphorylation. The PARL score could be a useful immunohistochemistry-based measure of tumour biomarkers for prognostication and adds value to current clinico-pathological markers. Legal entity responsible for the study: NHS Greater Glasgow and Clyde. Funding: Prostate Cancer UK Wolfson Foundation. Disclosure: All authors have declared no conflicts of interest.
A wireless and artefact-free 128-channel neuromodulation device for closed-loop stimulation and recording in non-human primates
Authors: Andy Zhou, Samantha R. Santacruz, Benjamin C. Johnson, George Alexandrov, Ali Moin, Fred L. Burghardt, Jan M. Rabaey, Jose M. Carmena, Rikky Muller
Journal: Nature Biomedical Engineering (2018)
Ibrutinib for the treatment of Bing-Neel syndrome: a multicenter study
Authors: Jorge J. Castillo, Gilad Itchaki, Jonas Paludo, Marzia Varettoni, Christian Buske, Toby A. Eyre, Julio C. Chavez, Kenneth H. Shain, Samar Issa, M. Lia Palomba, Oren Pasvolsky, David Simpson, Dipti Talaulikar, Constantine S. Tam, Alessandra Tedeschi, Stephen M. Ansell, Lakshmi Nayak, Steven P. Treon
Journal: Blood (2018)
Risk Factors of Subsequent Primary Melanomas in Austria
Authors: Christoph Müller, Judith Wendt, Sabine Rauscher, Raute Sunder-Plassmann, Erika Richtig, Ingrid Fae, Gottfried Fischer, Ichiro Okamoto
Journal: JAMA Dermatology (2018)

Information on risk factors of subsequent melanomas would be helpful to identify patients at risk after the diagnosis of their first melanomas.To determine risk factors of subsequent melanomas.In this retrospective case-control study, 1648 participants with histologically verified cutaneous melanoma diagnosed from January 1, 1968, though March 16, 2015, were recruited from a tertiary referral center as part of the Molecular Markers of Melanoma study. CDKN2A was sequenced in 514 and MC1R in 953 participants. Data were analyzed from March 7, 2008, through March 25, 2015.Phenotypic traits and internal and external risk factors for the development of a second, third, or fourth melanoma.In total, 1648 patients (53.6% men; mean [SD] age, 54 [15] years) were enrolled, including 1349 with single and 299 with multiple primary melanoma. Mean (SD) age at recruitment was 57 (15) years for the single-melanoma and 62 (14) years for the multiple-melanoma groups. From the internal risk factors, family history (odds ratio [OR], 1.76; 95% CI, 1.22-2.55; P = .006), CDKN2A high-risk mutations (OR, 4.03; 95% CI, 1.28-12.70; P = .02), and high numbers of nevi as a phenotypic risk factor (ORs, 2.23 [95% CI, 1.56-3.28, P < .001] for 20-30 smaller nevi and 2.56 [95% CI, 1.50-4.36; P = .003] for 20-30 larger nevi) were significantly associated with the risk of developing a subsequent primary melanoma using multivariate logistic regression analysis. Nonmelanoma skin cancer (OR, 2.57; 95% CI, 1.84-3.58; P < .001) and signs of actinic skin damage, particularly on the back (ORs, 1.91 [95% CI, 1.12-3.25; P = .04] for freckling and 1.92 [95% CI, 1.29-3.08; P = .007] for solar lentigines), additionally increased risk of a subsequent melanoma. All those factors were also associated with an earlier development of the second melanoma. Patients with 3 melanomas developed their second melanoma earlier than patients with only 2 melanomas (mean [SD] age, 55 [15] years for those with 2 primary melanomas; 52 [15] years for those with 3 primary melanomas). Time spent outdoors, solarium use, outdoor occupation, and hair color had no significant associations in these models.According to the results of this study, internal factors (family history and genetic variants), number of nevi, and actinic damage on the back are more relevant for the development of subsequent melanomas than skin phototype or hair color. Patients with many nevi were younger at the time of the diagnosis of their first melanoma. This finding could help to identify persons at increased risk of developing multiple primary melanomas.
GABA and glutamate neurons in the VTA regulate sleep and wakefulness
Authors: Xiao Yu, Wen Li, Ying Ma, Kyoko Tossell, Julia J. Harris, Edward C. Harding, Wei Ba, Giulia Miracca, Dan Wang, Long Li, Juan Guo, Ming Chen, Yuqi Li, Raquel Yustos, Alexei L. Vyssotski, Denis Burdakov, Qianzi Yang, Hailong Dong, Nicholas P. Franks, William Wisden
Journal: Nature Neuroscience (2018)
Long-Term Follow-up after Treatment Discontinuation in Patients with Chronic Myeloid Leukemia: The Korean Imatinib Discontinuation (KID) Study
Authors: Dae Young Zang, Won Sik Lee, Yeung-Chul Mun, Young Rok Do, Sukjoong Oh, Sung-Eun Lee, Soo Young Choi, Dong-Wook Kim
Journal: Blood (2018)
Out-running ‘bad’ diets: beyond weight loss there is clear evidence of the benefits of physical activity
Authors: Stuart M Phillips, Michael J Joyner
Journal: British Journal of Sports Medicine (2018)

You cannot outrun a bad diet has become a rallying phrase for diet-centric approaches to counteracting obesity and poor metabolic health. The phrase is, in our view, often taken to mean that you simply cannot do enough exercise to successfully lose or manage weight over time. Nonetheless, all weight loss paradigms run through energy balance,1 and the concept that you cannot outrun a bad diet is, in our view, inaccurate. Importantly, the simplicity of the phrase does not consider the multitude of other positive effects that physical activity/exercise (ie, running) have on health beyond weight loss. Evidence shows that you can out-exercise/out-work poor nutritional choices, but most people do not since they do not/will not/or cannot, practically, expend sufficient energy to do so. It is incontrovertible that exercise can and does result in weight loss.2 Nonetheless, behavioural and/or metabolic compensatory mechanisms often lessen the predicted weight loss with exercise induced as opposed to diet-induced energy deficits.2 Viewed through the lens of a weight loss approach to …
Role of TLR4 in the gut-brain axis in Parkinson’s disease: a translational study from men to mice
Authors: Paula Perez-Pardo, Hemraj B Dodiya, Phillip A Engen, Christopher B Forsyth, Andrea M Huschens, Maliha Shaikh, Robin M Voigt, Ankur Naqib, Stefan J Green, Jeffrey H Kordower, Kathleen M Shannon, Johan Garssen, Aletta D Kraneveld, Ali Keshavarzian
Journal: Gut (2018)

Objective Recent evidence suggesting an important role of gut-derived inflammation in brain disorders has opened up new directions to explore the possible role of the gut-brain axis in neurodegenerative diseases. Given the prominence of dysbiosis and colonic dysfunction in patients with Parkinson’s disease (PD), we propose that toll-like receptor 4 (TLR4)-mediated intestinal dysfunction could contribute to intestinal and central inflammation in PD-related neurodegeneration. Design To test this hypothesis we performed studies in both human tissue and a murine model of PD. Inflammation, immune activation and microbiota composition were measured in colonic samples from subjects with PD and healthy controls subjects and rotenone or vehicle-treated mice. To further assess the role of the TLR4 signalling in PD-induced neuroinflammation, we used TLR4-knockout (KO) mice in conjunction with oral rotenone administration to model PD. Results Patients with PD have intestinal barrier disruption, enhanced markers of microbial translocation and higher pro-inflammatory gene profiles in the colonic biopsy samples compared with controls. In this regard, we found increased expression of the bacterial endotoxin-specific ligand TLR4, CD3+ T cells, cytokine expression in colonic biopsies, dysbiosis characterised by a decrease abundance of SCFA-producing colonic bacteria in subjects with PD. Rotenone treatment in TLR4-KO mice revealed less intestinal inflammation, intestinal and motor dysfunction, neuroinflammation and neurodegeneration, relative to rotenone-treated wild-type animals despite the presence of dysbiotic microbiota in TLR4-KO mice. Conclusion Taken together, these studies suggest that TLR4-mediated inflammation plays an important role in intestinal and/or brain inflammation, which may be one of the key factors leading to neurodegeneration in PD.
Hepatocellular Carcinoma: A Roadmap to Reduce Incidence and Future Burden
Authors: Amit G Singal, Caitlin C Murphy
Journal: JNCI Journal of the National Cancer Institute (2018)

The incidence of hepatocellular carcinoma (HCC) has sharply risen over the past 20 years in the United States and is now a leading cause of cancer-related death (1).More than 90% of HCC cases in the United States occur in patients with cirrhosis, the end-result from any chronic liver disease including hepatitis C (HCV), hepatitis B (HBV), alcohol-related liver disease, and nonalcoholic fatty liver disease (NAFLD).However, HCC does not occur uniformly across populations and disproportionately affects racial/ethnic minorities, with blacks, Hispanics, and Asians experiencing higher age-specific incidence rates than non-Hispanic whites.In two studies recently published in the Journal, Han et al. and Pham et al. (2,3) used data from the Surveillance, Epidemiology, and End Results program of cancer registries to characterize racial/ethnic differences in incidence and projected future HCC burden.Incidence rates among most racial/ ethnic groups have steadily increased, and both studies project blacks and Hispanics to have the highest rates by 2030.The largest increase in incidence will occur among adults older than age 65 years, particularly among Hispanics.In contrast, incidence among Asians, who had the highest rate in 2000, has declined since 2010.Among subgroups of Asians, Pham et al.(3) observed differences in incidence, with declining incidence rates in Chinese men but increasing rates in others, specifically Japanese and Filipino men and Vietnamese and Laotian women.Declines in HCC incidence among Asians are likely related to improvements in global HBV vaccination and treatment programs.Some Asian countries, such as Taiwan and China, have implemented neonatal HBV vaccination programs and antiviral treatment of HBV-infected individuals, with statistically and clinically significant reductions in HBV-related HCC (4).Differences among Asian subgroups may also be related to nativity (ie, US vs foreign-born) and prevalence of HBV infection (5).
Third Molar Extraction and Persistent Use of Opioids
Authors: Brett L. Ferguson, Stuart E. Lieblich, Thomas B. Dodson
Journal: JAMA (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 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
Abstract 9567: Melatonin Treatment Improves Adipose-derived Mesenchymal Stem Cell Therapy for Acute Lung Ischemia-reperfusion Injury
Authors: Sarah Chua, Tzu -Hsien Tsai, Jiunn-Jye Sheu, Hon-Kan Yip
Journal: Circulation (2013)

Background: This study investigated whether melatonin-treated adipose-derived mesenchymal stem cells (ADMSC) offered superior protection against acute lung ischemia-reperfusion (IR) injury. Method and Results: Adult male SD rats (n=30) were randomized equally into 5 groups: sham controls, lung IR-saline, lung IR-melatonin, lung IR-melatonin-normal ADMSC, and lung IR-melatonin-apoptotic ADMSC. Arterial oxygen saturation was lowest in lung IR-saline; lower in lung IR-melatonin than sham controls, lung IR-melatonin-normal ADMSC, and lung IR-melatonin-apoptotic ADMSC; lower in lung IR-melatonin-normal ADMSC than sham controls and lung IR-melatonin-apoptotic ADMSC; lower in lung IR -melatonin-apoptotic ADMSC than sham controls (p&lt;0.0001 in each case). Right ventricular systolic blood pressure (RVSBP) showed a reversed pattern amongst all groups (all p&lt;0.0001). Changes in histological scoring of lung parenchymal damage and CD68+ cells showed a similar pattern compared to RVSBP in all groups (all p&lt;0.001). Changes in inflammatory protein expressions such as VCAM-1, ICAM-1, oxidative stress, TNF-α, NF-κB, PDGF and angiotensin-II receptor, and changes in apoptotic protein expressions of cleaved caspase 3 and PARP, and mitochondrial Bax, displayed identical patterns compared to RVSBP in all groups (all p&lt;0.001). Numbers of antioxidant (GR+, GPx+, NQO-1+) and endothelial cell biomarkers (CD31+ and vWF+) were lower in sham controls, lung IR-saline, and lung IR-melatonin than lung IR- melatonin-normal ADMSC, and lung IR-melatonin-apoptotic ADMSC, and lower in lung IR-melatonin-normal ADMSC than lung IR-melatonin-apoptotic ADMSC (p&lt;0.001 in each case). Conclusion: When the animals were treated with melatonin the apoptotic ADMSC were superior to normal ADMSC for protection of lung from acute IR injury. Key words: acute ischemia-reperfusion lung injury, inflammation, oxidative stress, adipose-derived mesenchymal stem cells, melatonin
Publisher Correction: Ultraviolet radiation–induced DNA damage is prognostic for outcome in melanoma
Authors: Lucas D. Trucco, Piyushkumar A. Mundra, Kate Hogan, Pablo Garcia-Martinez, Amaya Viros, Amit K. Mandal, Nicolas Macagno, Caroline Gaudy-Marqueste, Donald Allan, Franziska Baenke, Martin Cook, Clare McManus, Berta Sanchez-Laorden, Nathalie Dhomen, Richard Marais
Journal: Nature Medicine (2018)
CCR2 enhances CD25 expression by FoxP3+ regulatory T cells and regulates their abundance independently of chemotaxis and CCR2+ myeloid cells
Authors: Yifan Zhan, Nancy Wang, Ajithkumar Vasanthakumar, Yuxia Zhang, Michael Chopin, Stephen L. Nutt, Axel Kallies, Andrew M. Lew
Journal: Cellular and Molecular Immunology (2018)
Venetoclax in Combination with FLAG-IDA Chemotherapy (FLAG-V-I) for Fit, Relapsed/Refractory AML Patients: Interim Results of a Phase 1b/2 Dose Escalation and Expansion Study
Authors: Courtney D. DiNardo, Maher Albitar, Tapan M. Kadia, Kiran Naqvi, Kenneth Vaughan, Antonio Cavazos, Sherry A. Pierce, Koichi Takahashi, Steven M. Kornblau, Farhad Ravandi, Jorge E. Cortes, Hagop M. Kantarjian, Marina Y. Konopleva
Journal: Blood (2018)