tbuckley/cabot-search huggingface dataset:
Association of Optic Pathways and Brain Structure With Deep Brain Stimulation of the Nucleus Basalis of Meynert for Parkinson Disease Dementia
Authors: Diego de Castro dos Santos, Egberto Reis Barbosa, Rubens Gisbert Cury
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
BMA reopens negotiations over imposed junior doctor contract
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Junior doctors’ representatives have agreed to reopen negotiations on the contract that was imposed on them in acrimonious circumstances in 2016.

Jeeves Wijesuriya, chair of the BMA’s Junior Doctors Committee, said that the association had reached an agreement with NHS Employers to participate in a review and a “formal, collaborative bargaining process” in 2018, with a view to making changes to the contract.

The government’s imposition of the deal in October …
Higher Plasma Methylglyoxal Levels Are Associated With Incident Cardiovascular Disease and Mortality in Individuals With Type 2 Diabetes
Authors: Nordin M.J. Hanssen, Jan Westerink, Jean L.J.M. Scheijen, Yolanda van der Graaf, Coen D.A. Stehouwer, Casper G. Schalkwijk, Ale Algra, Yolanda van der Graaf, Rick D.E. Grobbee, Guy E.H.M. Rutten, Frank L.J. Visseren, Gert Jan de Borst, Jaap L.J. Kappelle, Tim Leiner, Hendrik M. Nathoe
Journal: Diabetes Care (2018)

OBJECTIVE Methylglyoxal (MGO) is a reactive dicarbonyl compound and a potential key player in diabetic cardiovascular disease (CVD). Whether plasma MGO levels are associated with CVD in type 2 diabetes is unknown. RESEARCH DESIGN AND METHODS We included 1,003 individuals (mean ± SD age 59.1 ± 10.5 years, 69.3% male, and 61.6% with prior CVD) with type 2 diabetes from the Second Manifestations of ARTerial disease cohort (SMART). We measured plasma MGO levels and two other dicarbonyls (glyoxal [GO] and 3-deoxyglucosone [3-DG]) at baseline with mass spectrometry. Median follow-up of CVD events was 8.6 years. Data were analyzed with Cox regression with adjustment for sex, age, smoking, systolic blood pressure, total cholesterol, HbA1c, BMI, prior CVD, and medication use. Hazard ratios are expressed per SD Ln-transformed dicarbonyl. RESULTS A total of 287 individuals suffered from at least one CVD event (n = 194 fatal events, n = 146 myocardial infarctions, and n = 72 strokes); 346 individuals died, and 60 individuals underwent an amputation. Higher MGO levels were associated with total (hazard ratio 1.26 [95% CI 1.11–1.42]) and fatal (1.49 [1.30–1.71]) CVD and with all-cause mortality (1.25 [1.11–1.40]), myocardial infarction (1.22 [1.02–1.45]), and amputations (1.36 [1.05–1.76]). MGO levels were not apparently associated with stroke (1.03 [0.79–1.35]). Higher GO levels were significantly associated with fatal CVD (1.17 [1.00–1.37]) but not with other outcomes. 3-DG was not significantly associated with any of the outcomes. CONCLUSIONS Plasma MGO and GO levels are associated with cardiovascular mortality in individuals with type 2 diabetes. Influencing dicaronyl levels may therefore be a target to reduce CVD in type 2 diabetes.
Abstract 18119: Mir-16 Modulates Endothelial Dysfunction After Balloon Injury in a Rat Model of Chronic Peripheral Ischemia
Authors: Sabato Sorrentino, Alberto Polimeni, Claudio Iaconetti, Jolanda Sabatino, Clarice Gareri, Annarita Carino, Francesco Passafaro, Maria Colangelo, Caterina Covello, Alessandra Carvelli, Filomena Caria, Andrea Tavernese, Antonio Curcio, Salvatore De Rosa, Ciro Indolfi
Journal: Circulation (2013)

Background: Peripheral ischemia is associated with endothelial dysfunction in the coronary district and represents an important predictor of future cardiovascular events such as myocardial infarction and stroke. MicroRNAs (miRs) play an important regulatory role in cells of the vascular wall. Thus, the aim of the present study was to evaluate the role of miRs in mediating remote endothelial dysfunction in a model of peripheral ischemia. Methods and Results: Wistar male rats, were divided into the following groups: no treatment (sham); vascular injury on the carotid artery by balloon catheter (BI); femoral artery ligation (AL); ligation of the femoral artery followed, after 21 days, by balloon injury (AL+BI). At 21-days-evaluation, real time RT-PCR showed a profound up-regulation of miR-16 levels within ECs extracted by injured carotid artery of AL+BI group compared to the BI group. A bioinformatics approach revealed highly conserved binding sites for miR-16 in the 3’UTR of ARHGDIA (Rho-GDP dissociation inhibitor 1), an inhibitor of Rho signaling. Interestingly up-regulation of miR-16 was associated with a reduction of the ARHGDIA-transcript levels and a higher activation of the RhoA pathway, with consequent reduction of nitric oxide bioavailability. Accordingly, inhibition of miR-16 in ECs resulted in increased mRNA and protein levels of eNOS, with increased NO production, while up-regulation of miR-16 resulted in increased NF-kB activation in ECs. Conclusions: The expression levels of miR-16 are increased in the vascular endothelium of injured arteries in rats with a model of chronic peripheral ischemia, over rats without peripheral ischemia. Such modulation of miR-16 levels may play a key role in modulating endothelial dysfunction through modulation of the RhoA signaling pathway and the transcription factor NF-kB.
Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma
Authors: Klaus F Rabe, Parameswaran Nair, Guy Brusselle, Jorge F Maspero, Mario Castro, Lawrence Sher, Hongjie Zhu, Jennifer D Hamilton, Brian N Swanson, Asif Khan, Jingdong Chao, Heribert Staudinger, Gianluca Pirozzi, Christian Antoni, Nikhil Amin, Marcella Ruddy, Bolanle Akinlade, Neil M H Graham, Neil Stahl, George D Yancopoulos, Ariel Teper
Journal: New England Journal of Medicine (2018)

Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. Its effectiveness in reducing oral glucocorticoid use in patients with severe asthma while maintaining asthma control is unknown.We randomly assigned 210 patients with oral glucocorticoid-treated asthma to receive add-on dupilumab (at a dose of 300 mg) or placebo every 2 weeks for 24 weeks. After a glucocorticoid dose-adjustment period before randomization, glucocorticoid doses were adjusted in a downward trend from week 4 to week 20 and then maintained at a stable dose for 4 weeks. The primary end point was the percentage reduction in the glucocorticoid dose at week 24. Key secondary end points were the proportion of patients at week 24 with a reduction of at least 50% in the glucocorticoid dose and the proportion of patients with a reduction to a glucocorticoid dose of less than 5 mg per day. Severe exacerbation rates and the forced expiratory volume in 1 second (FEV1) before bronchodilator use were also assessed.The percentage change in the glucocorticoid dose was -70.1% in the dupilumab group, as compared with -41.9% in the placebo group (P<0.001); 80% versus 50% of the patients had a dose reduction of at least 50%, 69% versus 33% had a dose reduction to less than 5 mg per day, and 48% versus 25% completely discontinued oral glucocorticoid use. Despite reductions in the glucocorticoid dose, in the overall population, dupilumab treatment resulted in a severe exacerbation rate that was 59% (95% confidence interval [CI], 37 to 74) lower than that in the placebo group and resulted in an FEV1 that was 0.22 liters (95% CI, 0.09 to 0.34) higher. Injection-site reactions were more common with dupilumab than with placebo (9% vs. 4%). Transient blood eosinophilia was observed in more patients in the dupilumab group than in the placebo group (14% vs. 1%).In patients with glucocorticoid-dependent severe asthma, dupilumab treatment reduced oral glucocorticoid use while decreasing the rate of severe exacerbations and increasing the FEV1. Transient eosinophilia was observed in approximately 1 in 7 dupilumab-treated patients. (Funded by Sanofi and Regeneron Pharmaceuticals; LIBERTY ASTHMA VENTURE ClinicalTrials.gov number, NCT02528214 .).
Staging of Cutaneous Melanoma
Authors: Peter M. Ferguson, Jeffrey E. Gershenwald, Richard A. Scolyer
Journal: JAMA Network Open (2018)

Joann G. Elmore, MD, MPH; David E. Elder, MBChB, FRCPA; Raymond L. Barnhill, MD; Stevan R. Knezevich, MD, PhD; Gary M. Longton, MS; Linda J. Titus, MA, PhD; Martin A. Weinstock, MD, PhD; Margaret S. Pepe, PhD; Heidi D. Nelson, MD, MPH; Lisa M. Reisch, PhD; Andrea C. Radick, MS; Michael W. Piepkorn, MD, PhD
Reactivation of γ-globin in adult β-YAC mice after ex vivo and in vivo hematopoietic stem cell genome editing
Authors: Chang Li, Nikoletta Psatha, Pavel Sova, Sucheol Gil, Hongjie Wang, Jiho Kim, Chandana Kulkarni, Cristina Valensisi, R. David Hawkins, George Stamatoyannopoulos, André Lieber
Journal: Blood (2018)
Abstract A06: Automated, high-throughput 3D desorption electrospray ionization (DESI) mass spectrometry imaging of a xenograft model of glioblastoma
Authors: Fiona Henderson, Emrys Jones, Joanna Denbeigh, Lidan Christie, Michael A. Batey, Emmanuelle Claude, Kaye J. Williams, Adam McMahon
Journal: Cancer Research (2018)

Abstract Glioblastomas are a highly aggressive brain tumor, which are commonly resistant to chemotherapy and radiotherapy. The heterogeneity of these tumors can cause major problems for diagnosis and therapy. It is therefore important to study these local variations in glioblastoma metabolism, in order to understand tumor development and to guide treatment. Desorption electrospray ionization mass spectrometry (DESI MS) imaging is a technique that can image hundreds of molecules in a 2D tissue section in a single scan, making it an ideal tool for imaging heterogeneity in tumors. Here, 3D DESI-MS imaging has been implemented to reveal lipid heterogeneity in a whole xenograft glioblastoma. In addition, immunofluorescence staining has been used to elucidate the role of hypoxia in lipid heterogeneity. Fifteen sections were taken from a xenograft glioblastoma at 120-um increments for DESI-MS imaging. DESI-MS imaging was carried out in both negative and positive ion mode, using the spatial resolution of 120um, to allow even-sized voxels. An automatic slide loader was used to allow high-throughput imaging. Recently written software at Waters, UK was used to automatically reconstruct a 3D image from the 2D DESI-MS images. Serial sections were used for immunofluorescence staining of carbonic anhydrase-9 (a marker for hypoxia). Sections also underwent H&amp;E staining. High-throughput 3D DESI-MS imaging has been carried out to reveal lipid heterogeneity in a xenograft glioblastoma. Here, 3D DESI-MS imaging reveals segmentation of the tumor based on local lipid expression, which correlates with the histologic mapping of normoxia, hypoxia, and necrosis. Hypoxia is a key contributor to tumor heterogeneity and, importantly, is associated with aggressive tumor development. This work highlights that lipids are playing an important role in glioblastoma heterogeneity. Furthermore, DESI-MS imaging can be used for 3D lipid imaging in an automated fashion, to reveal heterogeneity that is not apparent in H&amp;E stains alone. Citation Format: Fiona Henderson, Emrys Jones, Joanna Denbeigh, Lidan Christie, Michael A. Batey, Emmanuelle Claude, Kaye J. Williams, Adam McMahon. Automated, high-throughput 3D desorption electrospray ionization (DESI) mass spectrometry imaging of a xenograft model of glioblastoma [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A06.
Abstract A52: Arid1a exerts context-dependent oncogenic and tumor suppressor functions in liver cancer
Authors: Xuxu Sun, Sam Wang, Shuyuan Zhang, Hao Zhu
Journal: Cancer Research (2018)

Abstract ARID1A, an ATP-dependent SWI/SNF chromatin remodeling complex component, is hypothesized to be one of the most commonly mutated tumor suppressors in human cancer. Using mouse liver cancer models, we sought to elucidate the functional consequences of ARID1A gain and loss. Surprisingly, mice with liver-specific Arid1a deficiency were resistant to chemical- and MYC-induced liver carcinogenesis, while ARID1A overexpression accelerated tumorigenesis when combined with a variety of oncogenes, indicating an important role during tumor initiation. Mechanistically, Arid1a promoted tumor initiation by increasing cytochrome P450-mediated oxidative stress. In human HCCs, late ARID1A loss has been observed upon metastatic spread, suggesting that deleterious mutations do occur after tumor initiation. Indeed, both homozygous and heterozygous loss after liver tumor formation in mice were sufficient to drive progression and metastasis. Intriguingly, the Arid1a haploinsufficient state was sufficient to globally increase chromatin occupancy and downregulate metastasis suppressor genes within tumors. In summary, ARID1A can play both tumor-suppressive and oncogenic roles in liver cancer in a temporally dependent manner, explaining the expression and mutation patterns seen in human HCC. Citation Format: Xuxu Sun, Sam Wang, Shuyuan Zhang, Hao Zhu. Arid1a exerts context-dependent oncogenic and tumor suppressor functions in liver cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A52.
Determinants of Response to Roflumilast in Severe Chronic Obstructive Pulmonary Disease. Pooled Analysis of Two Randomized Trials
Authors: Fernando J. Martinez, Klaus F. Rabe, Peter M. A. Calverley, Leonardo M. Fabbri, Sanjay Sethi, Emilio Pizzichini, Andrew McIvor, Antonio Anzueto, Vijay K. T. Alagappan, Shahid Siddiqui, Colin Reisner, Sofia Zetterstrand, Jonas Román, Debasree Purkayastha, Nitin Bagul, Stephen I. Rennard
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Roflumilast reduces exacerbations in patients with severe chronic obstructive pulmonary disease associated with chronic bronchitis and a history of exacerbations. Further characterization of patients most likely to benefit is warranted.Objectives: Define characteristics that most robustly identify patients who derive greatest exacerbation risk reduction with roflumilast.Methods: Predefined, pooled analyses of REACT (Roflumilast in the Prevention of COPD Exacerbations While Taking Appropriate Combination Treatment; NCT01329029) and RE2SPOND (Roflumilast Effect on Exacerbations in Patients on Dual [LABA/ICS] Therapy; NCT01443845) multicenter, randomized, double-blind, placebo-controlled studies. The primary endpoint was rate of moderate or severe exacerbations per patient per year.Measurements and Main Results: In the overall intention-to-treat population (n = 4,287), roflumilast reduced moderate or severe exacerbations by 12.3% (rate ratio, 0.88, 95% confidence interval, 0.80–0.97; P = 0.0086) and severe exacerbations by 16.1% (0.84; 0.71–0.99; P = 0.0409) versus placebo. The reduction in moderate or severe exacerbations with roflumilast was most pronounced in patients who had been hospitalized for an exacerbation in the prior year (0.74; 0.63–0.88; P = 0.0005); had more than two exacerbations in the prior year (0.79; 0.65–0.96; P = 0.0160); or had baseline eosinophils ≥150 cells/μl (0.81; 0.71–0.93; P = 0.0020), ≥150 to <300 cells/μl (0.84; 0.71–0.98; P = 0.0282), or ≥300 cells/μl (0.77; 0.61–0.97; P = 0.0264). Similar subgroup results were noted for severe exacerbations. In patients with prior hospitalization and higher baseline blood eosinophil concentrations, roflumilast reduced moderate or severe exacerbations by 34.5% at ≥150 cells/μl (0.65; 0.52–0.82; P = 0.0003) and 42.7% at ≥300 cells/μl (0.57; 0.37–0.88; P = 0.0111) versus placebo.Conclusions: This prespecified, pooled analysis confirms the benefit of roflumilast in decreasing exacerbations in patients with prior hospitalization for exacerbation, greater exacerbation frequency, and higher (≥150 cells/μl, ≥150 to <300 cells/μl, or ≥300 cells/μl) baseline blood eosinophil count.
Dynamic Handwriting Analysis for the Assessment of Neurodegenerative Diseases: A Pattern Recognition Perspective
Authors: Donato Impedovo, Giuseppe Pirlo
Journal: IEEE Reviews in Biomedical Engineering (2018)

Neurodegenerative diseases, for instance Alzheimer's disease (AD) and Parkinson's disease (PD), affect the peripheral nervous system, where nerve cells send messages that control muscles in order to allow movements. Sick neurons cannot control muscles properly. Handwriting involves cognitive planning, coordination, and execution abilities. Significant changes in handwriting performance are a prominent feature of AD and PD. This paper addresses the most relevant results obtained in the field of online (dynamic) analysis of handwritten trials by AD and PD patients. The survey is made from a pattern recognition point of view, so that different phases are described. Data acquisition deals not only with the device, but also with the handwriting task. Feature extraction can deal with function and parameter features. The classification problem is also discussed along with results already obtained. This paper also highlights the most profitable research directions.
Anticardiolipin and anti-beta 2 glycoprotein-I antibodies disappearance in patients with systemic lupus erythematosus and antiphospholipid syndrome while on belimumab
Authors: Savino Sciascia, Elena Rubini, Massimo Radin, Irene Cecchi, Daniela Rossi, Dario Roccatello
Journal: Annals of the Rheumatic Diseases (2018)

The current management of antiphospholipid syndrome (APS) centres on attenuating the procoagulant state while balancing the haemorrhagic risks.1 This approach relies mainly on a thromboprophylaxis strategy rather than targeting pathogenic antiphospholipid antibodies (aPL)-mediated pathways.

Herewith, we report the aPL disappearance in three patients with APS associated to systemic lupus erythematous (SLE) while on treatment with belimumab, potentially paving the way for development of new targeted therapies for APS. Belimumab is a monoclonal antibody that works by blocking the B-lymphocyte stimulator and avoiding B-cell activation.2 It is the first biological drug approved for the treatment of autoantibody positive SLE in active phase and it has shown its capability to reduce the antibodies levels, including anti-double stranded-DNA.3 Intriguingly, in murine models of APS in the setting of SLE, belimumab …
Cutaneous Eruption Secondary to Immunotherapy for Metastatic Melanoma Limited to Sites of Locoregional Melanoma Metastases
Authors: Marie Donaldson, Joshua L. Owen, Jennifer N. Choi
Journal: JAMA Dermatology (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 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
The brighter the light, the deeper the shadow: Morality also fuels aggression, conflict, and violence
Authors: Robert Böhm, Isabel Thielmann, Benjamin E. Hilbig
Journal: Behavioral and Brain Sciences (2018)

Abstract We argue that, in addition to the positive effects and functionality of morality for interactions among in-group members as outlined in the target article, morality may also fuel aggression and conflict in interactions between morality-based out-groups. We summarize empirical evidence showing that negative cognitions, emotions, and behaviors are particularly likely to appear between out-groups with opposing moral convictions.