tbuckley/cabot-search huggingface dataset:
ひ臓DC活性化のためのCpG組み込み脂質‐DNAナノ粒子のモジュール送達【Powered by NICT】
Authors: Jin Jun-O, Park Haein, Zhang Wei, de Vries Jan Willem, Gruszka Agnieszka, Lee Myung Won, Ahn Dae-Ro, Herrmann Andreas, Kwak Minseok
Journal: Biomaterials (2017)
Platelet function defects in chronic alcoholism: Authors' reply
Authors: D P Mikhailidis, W J Jenkins, M A Barradas, J Y Jeremy, P Dandona
Journal: BMJ (1986)

Dr Bennett offers little evidence to suggest that nursing homes are the "best buy" for our dependent elderly.Perhaps some of the public money being used to fund the expansion in private nursing home places might be better spent on geriatric wards or in helping people to remain in their own homes.
Inhibition of IL-17–committed T cells in a murine psoriasis model by a vitamin D analogue
Authors: Nobuhiro Kusuba, Akihiko Kitoh, Teruki Dainichi, Tetsuya Honda, Atsushi Otsuka, Gyohei Egawa, Saeko Nakajima, Yoshiki Miyachi, Kenji Kabashima
Journal: Journal of Allergy and Clinical Immunology (2017)
Silencing of HSP70 and TRIAP1 Genes in Multiple Myeloma Cell Lines Induces Apoptosis through Apaf-1/Caspase 9 Pathway: New Potential Targets on the Way?
Authors: Veruska Lia Fook Alves, Gisele Wally Braga Colleoni, Daniela Bertolli Zanatta, Bryan E. Strauss
Journal: Blood (2014)
AB1062 Patterns of musculoskeletal system involvement in patients with type i and type ii diabetes mellitus
Authors: TI Adrosy, MI Hanafy, HS Hamoud, AA Negm
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Diabetes mellitus (DM) is a chronic disease, no known cure except in very specific situations. Musculoskeletal Utrasonography (MSUS) has a great sensitivity that can help clinical examination for the detection of peripheral enthesitis associated with DM <h3>Objectives</h3> To study the different patterns of musculoskeletal (MSK) system affection in both types of diabetes mellitus (DM). <h3>Methods</h3> We performed a retrospective single-center study on sixty five patients during the period from May 2014 to February 2015, to evaluate MSK manifestations in diabetic patients at Sayyed Galal University Hospital, Cairo, Egypt. Patients were identified as diabetics based on Diagnosis and Classification of Diabetes Mellitus diagnostic criteria (1997) (1). Clinical data, laboratory investigations, X-ray, musculoskeletal ultrasonography (MSUS) (2) and Bone mineral density was measured using Dual energy X-ray absorptiometry (DEXA) scan (3) were all collected from all patients. <h3>Results</h3> We included 65 diabetic patients; of these 21 patients (32.31%) had type I diabetes while 44 patients (67.69%) had type II diabetes. Age in type I was 24.5±10.5 years while in type II was 50.1±8.44 years (P=0.001). DM type II showed higher BMI (P=0.001), fatigue (P=0.005), shoulder periarthritis (frozen shoulder) (P=0.034), knee osteoarthritis (P=0.002), cheiroarthropathy (P=0.016), anserine bursitis (P=0.001) and plantar fasciitis (P=0.003) than type I. Osteoporosis was found in both types but type II showed more prevalence 13/44 patients (29.5%) while type I showed only 3/21 (14.2%). No statistically significant difference between both groups as regard t-score in the three sites. MSUS showed increased prevalence of quadriceps tendon enthesophytes in type I (P=0.033), while Infrapatellar (P=0.023) and retrocalcaneal bursitis (P=0.001) were more prevalent in type II DM. <h3>Conclusions</h3> Early evaluation of any diabetic patient regarding BMD by DEXA scan and soft tissue by MSUS seems to be beneficial for early detection of any abnormality and therefore early management and prevention of complications. <h3>References</h3> American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2013; 36. Blake GM and Fogelman I. DEXA scanning and its interpretation in osteoporosis. Hosp Med 2003; 64:521–5. Balint PV, Kane D, Wilson H, McInnes IB and Sturrock RD: Ultrasonography of entheseal insertions in the lower limb in spondyloarthropathy. Ann Rheum Dis 2002; 61:905–910. <h3>Disclosure of Interest</h3> None declared
Conscious Sedation Versus General Anesthesia for Transcatheter Aortic Valve Replacement
Authors: Matthew C. Hyman, Sreekanth Vemulapalli, Wilson Y. Szeto, Amanda Stebbins, Prakash A. Patel, Roland A. Matsouaka, Howard C. Herrmann, Saif Anwaruddin, Taisei Kobayashi, Nimesh D. Desai, Prashanth Vallabhajosyula, Fenton H. McCarthy, Robert Li, Joseph E. Bavaria, Jay Giri
Journal: Circulation (2017)

Background: Conscious sedation is used during transcatheter aortic valve replacement (TAVR) with limited evidence as to the safety and efficacy of this practice. Methods: The National Cardiovascular Data Registry Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry was used to characterize the anesthesia choice and clinical outcomes of all US patients undergoing elective percutaneous transfemoral TAVR between April 1, 2014, and June 30, 2015. Raw and inverse probability of treatment-weighted analyses were performed to compare patients undergoing TAVR with general anesthesia with patients undergoing TAVR with conscious sedation on an intention-to-treat basis for the primary outcome of in-hospital mortality, and secondary outcomes including 30-day mortality, in-hospital and 30-day death/stroke, procedural success, intensive care unit and hospital length-of-stay, and rates of discharge to home. Post hoc falsification end point analyses were performed to evaluate for residual confounding. Results: Conscious sedation was used in 1737/10 997 (15.8%) cases with a significant trend of increasing usage over the time period studied ( P for trend&lt;0.001). In raw analyses, intraprocedural success with conscious sedation and general anesthesia was similar (98.2% versus 98.5%, P =0.31). The conscious sedation group was less likely to experience in-hospital (1.6% versus 2.5%, P =0.03) and 30-day death (2.9% versus 4.1%, P =0.03). Conversion from conscious sedation to general anesthesia was noted in 102 of 1737 (5.9%) of conscious sedation cases. After inverse probability of treatment-weighted adjustment for 51 covariates, conscious sedation was associated with lower procedural success (97.9% versus 98.6%, P &lt;0.001) and a reduced rate of mortality at the in-hospital (1.5% versus 2.4%, P &lt;0.001) and 30-day (2.3% versus 4.0%, P &lt;0.001) time points. Conscious sedation was associated with reductions in procedural inotrope requirement, intensive care unit and hospital length of stay (6.0 versus 6.5 days, P &lt;0.001), and combined 30-day death/stroke rates (4.8% versus 6.4%, P &lt;0.001). Falsification end point analyses of vascular complications, bleeding, and new pacemaker/defibrillator implantation demonstrated no significant differences between groups after adjustment. Conclusions: In US practice, conscious sedation is associated with briefer length of stay and lower in-hospital and 30-day mortality in comparison with TAVR with general anesthesia in both unadjusted and adjusted analyses. These results suggest the safety of conscious sedation in this population, although comparative effectiveness analyses using observational data cannot definitively establish the superiority of one technique over another.
Endovascular baroreflex amplification for resistant hypertension: a safety and proof-of-principle clinical study
Authors: Wilko Spiering, Bryan Williams, Jan Van der Heyden, Monique van Kleef, Rob Lo, Jorie Versmissen, Adriaan Moelker, Abraham Kroon, Hannes Reuter, Gary Ansel, Gregg W Stone, Mark Bates, Wilko Spiering, Bryan Williams, Gregg W Stone, Mark Bates
Journal: The Lancet (2017)
Jean-Pierre van Besouw
Authors: Chris Mahony
Journal: BMJ (2017)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Jean-Pierre van Besouw Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Abstract 034: The Effect Of Simvastatin On P-wave Dispersion And Echocardiographic Parameters Among Hypertensive Patients
Authors: Pamela M Pomer, Janet W Elcano
Journal: Circulation Research (2013)

Introduction: Rising evidence suggests that statins have a positive effect on the prevention of occurrence of atrial fibrillation (AF) in hypertensive patients. P-wave dispersion (PWD) has been known to be an electrocardiographic predictor for the development of AF. We therefore aimed to investigate on the possible effects of statins on p-wave dispersion in hypertensive patients. Method: A total of 27 patients (22 females; mean age, 45±11 years) with hypertension and without history of AF were included in this prospective study. P wave durations and PWD, left ventricular mass (LVMI), left atrial volume index (LAVI), and ratio of early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (e) (E/e’) were measured and compared before and after statin therapy (simvastatin 40mg/day for 3 months). Results: After 3 months of statin therapy, there was no significant change in PWD (pre-statin 39.7 ±10.7, post-statin 33 ± 8.8, p-value 0.30). Baseline and follow up blood pressure, heart rate, LVMI, LAVI and E/e’ ratio were not significantly different before and after simvastatin therapy. No patient developed AF during follow up. Conclusion: Simvastatin (40mg/day) therapy for 3 months did not show significant change on PWD, LVMI, LAVI and E/e’ ratio in hypertensive patients.
Preliminary activity in the first in human study of the first-in-class fatty acid synthase (FASN) inhibitor, TVB-2640.
Authors: Emma Jane Dean, Gerald Steven Falchook, Manish R. Patel, Andrew Jacob Brenner, Jeffrey R. Infante, Hendrik-Tobias Arkenau, Erkut Hasan Borazanci, Juanita Suzanne Lopez, Shubham Pant, Peter Schmid, Arthur E. Frankel, Suzanne Fields Jones, William McCulloch, George Kemble, Marie O'Farrell, Howard Burris
Journal: Journal of Clinical Oncology (2016)

2512 Background: FASN inhibition is a novel approach to cancer treatment involving selective disruption of palmitate biosynthesis that, in tumor cells, leads to apoptosis. TVB-2640 is an oral, first-in-class, small molecule reversible inhibitor of FASN that demonstrates in vivo antitumor effects. We previously reported the results of dose escalation and now present evidence of preliminary activity from the dose expansion. Methods: This ongoing multicenter Phase I trial enrolled patients (pts) with advanced solid tumors with adequate organ function. TVB-2640 was given orally once daily at the MTD (100 mg/m2) as monotherapy (mono) or in combination (combo) with weekly IV paclitaxel (80 mg/m2). Results: The most common AE's seen in both groups [mono, N=53; combo, N=47] were: alopecia (57%), palmar-plantar erythrodysesthesia (PPE) (36%), dry eye (13%), and increased lacrimation (11%). Gr 3 AE's include corneal edema (3%) and PPE (10%). Other toxicities were ≤ Gr 2 and only minor GI symptoms occurred. All toxicities were reversible on dose interruption and no enhancement of paclitaxel toxicity was observed when given with TVB-2640. 3 confirmed RECIST partial responses (cPR) all in combo, and multiple cases of prolonged stable disease (SD) (>16 wks) in both arms was seen. 16 NSCLC pts were accrued: 6 were KRAS Mut and, of those, 3 achieved SD with monotherapy for 17, 24 and 38 wks. 2 pts treated in combo had SD for 24 and 21 wks. One combo NSCLC pt (no prior taxane) was a cPR at week 8 and continues on study at wk 22. 3/12 breast cancer pts treated in combo had SD for 20 (TNBC), 24 and 25 wks. One combo breast cancer pt achieved a cPR at wk 12 and continues on study at wk 24. One cPR was seen in a combo treated pt with peritoneal carcinoma, along with a 58% reduction in CA-125 levels. Further reductions in CA-125 ranging from 58-98%, were seen in 5 of 12 ovarian pts. All ovarian pts had received prior taxanes and most, if not all, were taxane resistant upon study entry. Conclusions: TVB-2640 demonstrated prolonged SD when given in monotherapy and cPR when combined with weekly paclitaxel. Responses were seen across multiple tumor types, including KRASmut NSCLC, ovarian and breast cancer. Further exploration in specific tumor types is ongoing. Clinical trial information: NCT02223247.
Inaccuracies Describing Results of a Lung Cancer Screening Demonstration Project
Authors: Linda L. Humphrey, Mark Deffebach, David E. Midthun
Journal: JAMA Internal Medicine (2017)

To the Editor We are writing to convey our concerns about an Editorial by Redberg and O’Malley1 accompanying an article2 describing the preliminary results of the Veterans Health Administration (VA)’s lung cancer screening demonstration project.
Neural Stimulation: Multiplexed Optogenetic Stimulation of Neurons with Spectrum-Selective Upconversion Nanoparticles (Adv. Healthcare Mater. 17/2017)
Authors: Xudong Lin, Ying Wang, Xian Chen, Runhuai Yang, Zixun Wang, Jingyu Feng, Haitao Wang, King W. C. Lai, Jufang He, Feng Wang, Peng Shi
Journal: Advanced Healthcare Materials (2017)

An all-optical neural stimulation strategy is demonstrated by utilizing spectrum-tunable NaYF4 based upconversion nanoparticles, which are used as transducers to absorb near-infrared energy and to emit visible light for stimulating neurons expressing channelrhodopsin proteins by Feng Wang, Peng Shi, and co-workers in article 1700446. Depending on the different dopants in the particles, the spectrum of their upconverted emission can be tuned to accommodate different opsin proteins for multiplexed and combinatorial neural stimulation, which is systematically characterized in cultured primary neurons as well as in rodent animals.
THU0075 The relationship between disease activity and disability is mediated by pain and fatigue in early rheumatoid arthritis
Authors: S Twigg, EMA Hensor, P Emery, AW Morgan, A Tennant
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Disability in early rheumatoid arthritis (RA) is correlated with disease activity. However, the relationship between these two clinical outcomes is relatively under-investigated. Understanding how disability is driven by disease activity will allow targeted interventions to improve function in early RA, alongside the suppression of inflammation. <h3>Objectives</h3> To identify mediators in the relationship between disease activity and disability in early RA. <h3>Methods</h3> Cases with new consultant-made diagnoses of RA were recruited to Yorkshire Early Arthritis Register within 24 months of symptom onset. At the baseline assessment, clinical variables were collected including the 3 variable disease activity score from counts of 28 tender and swollen joints and C-reactive protein (DAS28), Health Assessment Questionnaire (HAQ) and visual analogue scores (VAS) of pain and fatigue. Structural equation models (SEM) were constructed to evaluate the relationship between DAS28, HAQ, pain, symptom duration (SD), age and fatigue. <h3>Results</h3> Of 721 cases included, 482 were female and 239 male. Median age was 58 for both genders and median HAQ was 1.25 and 1.00 for women and men, respectively. A path model within a SEM framework (Figure 1) was a good fit to the data (Chi square 7.528, df=6, p=0.2748; CFI 0.997; RMSEA 0.027). However, the model could not be applied simultaneously to both genders; although estimates of regression coefficients did not vary between males and females (metric invariance), model intercepts were different. In earlier models, age was not a significant predictor and regressions of fatigue on DAS28 were not significant: the effect of DAS28 upon fatigue was fully mediated by pain. Standardised coefficients of direct and indirect effects of DAS28 on HAQ are shown in Table 1, together with Sobel tests for significance of mediator variables. The greatest effect upon HAQ was the direct effect from DAS28, but some of the effect of DAS28 on HAQ was partially mediated by pain. Furthermore, the effect of pain upon HAQ was also partially mediated through fatigue. According to the Sobel test, pain and fatigue were significant mediators in both females and males. <h3>Conclusions</h3> DAS28 dominates the impact upon HAQ in early RA; pain is shown to be an important mediator of the effects of DAS28 on HAQ, while fatigue is important as a mediator of the effect of pain on HAQ. This adds to previous evidence that pain is a driver of fatigue in RA (1) and suggests that interventions to manage pain could be important adjuncts to supression of inflammation in early RA, in order to optimise function. <h3>References</h3> Druce KL, Jones GT, Macfarlane GJ, Basu N. (2015) Arthritis &amp; Rheumatology, 67: 2303. <h3>Disclosure of Interest</h3> None declared
Abstract 17865: Leisure Time Physical Activity in Middle Age Participants and Risk of Incident Atrial Fibrillation: A Dose-Response Meta-Analysis
Authors: Nitin K Kulkarni, Ambarish Pandey, Sushil Garg, Bryan Park, Curtiss Moore, Helen Mayo, Jose Joglar, Richard Wu, Jarett Berry
Journal: Circulation (2016)

Background: While higher rates of atrial fibrillation (AF) have been observed among athletes, modestly higher levels of leisure time physical activity (LTPA) have been associated with a lower risk ...
Significance of definitions of relapse after discontinuation of oral antivirals in HBeAg‐negative chronic hepatitis B
Authors: George V. Papatheodoridis, Spilios Manolakopoulos, Tung‐Hung Su, Spyros Siakavellas, Chun‐Jen Liu, Anastasia Kourikou, Hung‐Chih Yang, Jia‐Horng Kao
Journal: Hepatology (2017)

Relapses are observed in most hepatitis B e antigen (HBeAg)‐negative chronic hepatitis B patients who discontinue treatment with nucleos(t)ide analogues (NAs); however, the rates of relapse vary widely among studies, and whether all patients with relapse need retreatment is unclear. The aim of this study was to assess the impact of different definitions on the rates of posttreatment relapse and therefore on the probability of retreatment in patients who have discontinued effective long‐term NA therapy. In total, 130 HBeAg‐negative chronic hepatitis B patients without cirrhosis and before NA treatment were included. All had on‐therapy virological remission for ≥24 months and close follow‐up for ≥12 months after stopping NA treatment or until retreatment, which started on stringent predefined criteria. Relapses rates based on several predetermined definitions of virological and perhaps biochemical criteria were assessed. The median duration of therapy was 60 months and the median duration of on‐therapy virological remission was 43 months. During a median off‐NAs follow‐up of 15 months, no patient experienced liver decompensation or died. Cumulative relapse rates were 2%‐49%, 4%‐73%, 11%‐82%, and 16%‐90% at 3, 6, 12, and 24 months, respectively, whereas cumulative retreatment rates were 15%, 22%, and 40% at 6, 12, and 24 months, respectively, after discontinuation of NA therapy. No patient characteristic was independently associated with the probability of relapse based on at least two definitions or of retreatment. Conclusion : In HBeAg‐negative chronic hepatitis B patients who discontinue NA therapy, the definition of relapse has a great impact on off‐NAs relapse rates and potentially on the probability of retreatment. Regardless of definition, off‐NAs relapses cannot be easily predicted by patient characteristics. A substantial proportion of such patients may not require retreatment if stringent criteria are adopted. (H epatology 2017).
Could Autophagy Induced by Misfolded Mutant α<sub>1</sub>‐Antitrypsin Z in Synovitis Explain the Association of α<sub>1</sub>‐Antitrypsin Z With Increased Anti–Citrullinated Protein Antibody Production in Rheumatoid Arthritis? Comment on the Article by McCarthy et al
Authors: David Hutchinson, Paul Eggleton
Journal: Arthritis & Rheumatology (2017)

We read with interest the paper “Genetic variation of the alpha-1-antitrypsin (AT) gene is associated with increased autoantibody production in rheumatoid arthritis” by McCarthy et al. A strong association between mutant alpha-1-antitrypsin Z (ATZ) and ACPA production was noted in RA (1). The authors suggest that alpha-1-antitrypsin deficiency (ATD) may give rise to a tendency towards ACPA production. We suggest that it is the abnormal mutant protein ATZ itself that induces autophagy resulting in ACPA production in inflammatory cells such as macrophages rather than as a consequence of ATD per se. We feel this is likely to occur in the context of established synovitis rather than preceding the development of RA.

Chronic obstructive pulmonary disease (COPD) is the most prevalent disease manifestation of ATD (2). Given the evidence that ACPA+ve RA arises as a consequence of chronic lung disease (3), it is important to consider whether ATD as a consequence of its strong observed association with COPD confers an increased risk of ACPA+ve RA.

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RESPITE: switching to riociguat in pulmonary arterial hypertension patients with inadequate response to phosphodiesterase-5 inhibitors
Authors: Marius M. Hoeper, Gérald Simonneau, Paul A. Corris, Hossein-Ardeschir Ghofrani, James R. Klinger, David Langleben, Robert Naeije, Pavel Jansa, Stephan Rosenkranz, Laura Scelsi, Ekkehard Grünig, Carmine Dario Vizza, MiKyung Chang, Pablo Colorado, Christian Meier, Dennis Busse, Raymond L. Benza
Journal: European Respiratory Journal (2017)

A proportion of pulmonary arterial hypertension (PAH) patients do not reach treatment goals with phosphodiesterase-5 inhibitors (PDE5i). RESPITE investigated the safety, feasibility and benefit of switching from PDE5i to riociguat in these patients. RESPITE was a 24-week, open-label, multicentre, uncontrolled study. Patients in World Health Organization (WHO) functional class (FC) III, with 6-min walking distance (6MWD) 165–440 m, cardiac index &lt;3.0 L·min −1 ·m −2 and pulmonary vascular resistance &gt;400 dyn·s·cm −5 underwent a 1–3 day PDE5i treatment-free period before receiving riociguat adjusted up to 2.5 mg maximum t.i.d . Exploratory end-points included change in 6MWD, WHO FC, N -terminal prohormone of brain natriuretic peptide (NT-proBNP) and safety. Of 61 patients enrolled, 51 (84%) completed RESPITE. 50 (82%) were receiving concomitant endothelin receptor antagonists. At week 24, mean± sd 6MWD had increased by 31±63 m, NT-proBNP decreased by 347±1235 pg·mL −1 and WHO FC improved in 28 patients (54%). 32 patients (52%) experienced study drug-related adverse events and 10 (16%) experienced serious adverse events (2 (3%) study drug-related, none during the PDE5i treatment-free period). Six patients (10%) experienced clinical worsening, including death in two (not study drug-related). In conclusion, selected patients with PAH may benefit from switching from PDE5i to riociguat, but this strategy needs to be further studied.
Carbon Nanomaterials: Carbon Nanomaterials in Biological Studies and Biomedicine (Adv. Healthcare Mater. 17/2017)
Authors: Nagappa L. Teradal, Raz Jelinek
Journal: Advanced Healthcare Materials (2017)

In Review number 1700574, Nagappa L. Teradal and Raz Jelinek highlight applications of carbon nanotubes, graphene, and carbon dots in biosensing, drug delivery, bioimaging, tissue engineering, and regenerative medicine. In particular, their unique physical properties and relative biocompatibility make carbon nanomaterials attractive vehicles for biological uses.
Synthetic oligosaccharides can replace animal-sourced low–molecular weight heparins
Authors: Yongmei Xu, Kasemsiri Chandarajoti, Xing Zhang, Vijayakanth Pagadala, Wenfang Dou, Debra Moorman Hoppensteadt, Erica M. Sparkenbaugh, Brian Cooley, Sharon Daily, Nigel S. Key, Diana Severynse-Stevens, Jawed Fareed, Robert J. Linhardt, Rafal Pawlinski, Jian Liu
Journal: Science Translational Medicine (2017)

A synthetic homogeneous low–molecular weight heparin provides a safe and effective therapeutic alternative.