tbuckley/cabot-search huggingface dataset:
肺血栓内膜摘除(PTE)手術を必要とした患者における慢性血栓塞栓性肺高血圧症(CTEPH)の臨床的特性
Authors: Watanabe Masataka, Chikamori Taishiro, Hida Satoshi, Yoshimura Mana, Koizumi Nobutatu, Yamashina Akira, Ogino Hitoshi
Journal: Circulation (2016)
05.06 Specific t cell and b cell distributions characterise subgroups of patients with primary sjögren’s syndrome and are associated with disease activity and pro-inflammatory cytokine expression
Authors: Lucas Le Lann, Quentin Simon, Christophe Jamin, Divi Cornec, Maria-Oriette Borghi, Lorenzo Beretta, Ricard Cervera, Alain Saraux, Rik Lories, Carlo Chizzolini, Marta Alarcón-Riquelme, Jacques-Olivier Pers
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The goal of the IMI PRECISESADS project is to reclassify individuals affected by systemic autoimmune diseases (SADs) into clusters of molecular, instead of clinical entities. In this project, we investigated 40 individuals with primary Sjögren's syndrome (pSS), as diagnosed by the revised American-European classification criteria and 53 healthy controls (HCs) to determine whether a fine flow cytometry analysis of T and B cell distribution in whole blood could cluster individuals according to disease activity. <h3>Methods</h3> Two flow cytometry panels were designed. The first panel was dedicated to T cells and combined CD57, CD45RA, CD62L, CD27, CD38, CD3, CD4, CD8 mAbs. The second panel was dedicated to B cells and combined IgD, TACI, CD5, CD24, CD27, CD38, CD19, CD11b mAbs. Disease activity was determined according to ESSDAI. A Luminex-based system was used to analyse up to 88 cytokines, chemokines and soluble factors in serum of pSS patients and HCs. <h3>Results</h3> A combined analysis of T and B cell distribution highlighted two groups of individuals with a strong cluster of pSS patients in one of them. Indeed, the first cluster (group A) gathers together 24 pSS patients and 5 HCs while group B consists in 16 pSS patients and 49 HCs. Group A was characterised by the association of an increase of activated naïve B cells (IgD<sup>+</sup> CD24<sup>+</sup> CD38<sup>+</sup> CD27<sup>-</sup>), a decrease of memory B cells (IgD<sup>-</sup> CD38<sup>-</sup> CD27<sup>+</sup>), an increase of central memory CD4<sup>+</sup> T cells (CD45RA<sup>-</sup> CD62L<sup>+</sup> CD27<sup>+</sup>), an increase of effector memory CD8<sup>+</sup> T cells (CD45RA<sup>-</sup> CD62L<sup>-</sup> CD27<sup>-</sup>) and a decrease of central memory CD8<sup>+</sup> T cells (CD45RA<sup>-</sup> CD62L<sup>+</sup> CD27<sup>+</sup>) compared to group B and 91% of HCs. Interestingly, group A patients have a higher disease activity score when compared to group B (Mean ESSDAI score 5.0±1.9 versus 3.2±0.9 respectively). Finally, serum pro-inflammatory molecules were markedly up-regulated in group A patients compared to HCs and group B patients. <h3>Conclusions</h3> A fine flow cytometry analysis of T and B cell subsets characterises pSS patients with a higher disease activity score and a pro-inflammatory signature. Similar approaches are ongoing in the context of the PRECISESADS project for other SADs. This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking PRECISESADS grant n° 115565.www.precisesads.eu
Impact of immunoglobulin heavy chain variable region mutational status on the outcome of patients with chronic lymphocytic leukemia harboring isolated 13q deletion.
Authors: Gelenis C. Domingo, Samir Dalia, Julio C. Chavez, Estrella M. Carballido, Paibel I. Aguayo-Hiraldo, Kendra Lynn Sweet, Robert M. Crescentini, Lubomir Sokol, Jennifer L. Cultrera, Bijal D. Shah, Jeffrey E. Lancet, Eduardo M. Sotomayor, Rami S. Komrokji, Javier Pinilla-Ibarz
Journal: Journal of Clinical Oncology (2012)

6608 Background: Several prognostic factors can predict the course of chronic lymphocytic leukemia (CLL). Among them, the IGVH mutational status and the presence of cytogenetic abnormalities are the strongest predictors of outcome. Mutated IGVH and deletion 13q independently confer a survival advantage. CLL patients with mutated IGVH in combination with deletion 13q have a better prognosis when compared to their unmutated IGVH counterparts. However, there is limited data on the outcome of patients harboring favorable deletion 13q and the unfavorable unmutated IGVH. This study aimed at identifying patients with these two indicators in order to obtain important prognostic information. Methods: We used the Moffitt Cancer Center Total Cancer Care (TCC) database to find patients with a diagnosis of CLL between January 1993 and December 2009. Individual charts were reviewed for demographic data and CLL cytogenetics, including IGVH mutation status and presence of deletion 13q. We analyzed the impact of having deletion 13q in combination with an unmutated IGVH on the overall survival (OS) for this subset of CLL patients using Kaplan Meier curves with SPSS statistical software. Results: 546 patients were identified during the aforementioned time period with a diagnosis of CLL. Median age was 62.5 years. 144 (26.4%) of these patients had IGVH and cytogenetic analysis available. 53 patients had 13q deletion as their sole genetic abnormality. Patients with unmutated IGVH and positive for deletion 13q were 19/53 (35.8%). Patients with mutated IGVH and positive for deletion 13q were 34/53 (64.2%). Patients with mutated IGVH and positive for deletion 13q had an OS of 17 years. While patients with unmutated IGVH and positive deletion 13q had a lower median OS of 12 years (91.2% vs 78.9%, p=0.05). Hazard ratio for patients with IGVH mutated and positive deletion 13q was 0.4, p=0.05. Conclusions: Mutated IGVH appears to be associated with improved OS in patients with isolated 13q deletion when compared to patients with unmutated IGVH and isolated 13q deletion. Further research is needed to assess these mutations in relation to other cytogenetic abnormalities in CLL.
Repression of Stress-Induced LINE-1 Expression Protects Cancer Cell Subpopulations from Lethal Drug Exposure
Authors: Gulfem Dilek Guler, Charles Albert Tindell, Robert Pitti, Catherine Wilson, Katrina Nichols, Tommy KaiWai Cheung, Hyo-Jin Kim, Matthew Wongchenko, Yibing Yan, Benjamin Haley, Trinna Cuellar, Joshua Webster, Navneet Alag, Ganapati Hegde, Erica Jackson, Tracy Leah Nance, Paul Garrett Giresi, Kuan-Bei Chen, Jinfeng Liu, Suchit Jhunjhunwala, Jeff Settleman, Jean-Philippe Stephan, David Arnott, Marie Classon
Journal: Cancer Cell (2017)
A WHOLE GENOME CRISPR KNOCKOUT SCREEN AND MURINE ENDOSCOPY IDENTIFIES FOXF1 AS A KEY SUPPRESSOR OF COLORECTAL CANCER METASTASIS THAT ACTS THROUGH MTORC SIGNALLING
Authors: L Lee, C Woolley, A Lewis, I Tomlinson
Journal: Gut (2017)

Introduction  The proportion of patients with metastatic with colorectal cancer (CRC) who are cured of their disease is increasingly, but still low. The spread of cells from the primary tumour to distant sites is a complex process. Two of the key issues to be addressed to understand and prevent metastasis are the development of robust model systems and the robust identification of the molecular drivers.  Method  In this study, we used the novel technique of mouse endoscopy to introduce a syngeneic CRC cell directly under the submucosa of the large intestine of mice. A whole genome CRISPR/Cas9 screen was then performed using the GeCKOv2 library and we take a non-hypothesis driven approach to screen 20 611 genes for drivers of CRC metastasis.  Results  In the metastatic lesions of the mice, a median of 2548 genes were identified. FOXF1 was frequently targetted from this screen and significantly down-regulated in human lung and liver metastasis specimens. Whole transcriptome profiling identified that FOXF1 functions through inhibition of MTOR signalling and inhibition of this pathway significantly reduced metastasis outgrowth in murine models.  Conclusion  Genetic screens provide a comprehensive approach to understanding the drivers of metastasis. These assays allow the analysis of the function of a large number of genes simultaneously to identify those which are important for metastasis. In our approach, using an endoscopically guided orthotopicaly transplanted CRC model, we have identified 6 genes which had good evidence of modulating metastasis risk in our model system and were significantly downregulated in human metastasis cohorts. Several of these are particularly functionally interesting, including FOXF1, MDC1 and SEZ6L. By identifying several genes that modulate the probability of metastasis, we have developed a greater understanding of metastasis biology and identified FOXF1 as a biomarker of prognosis from CRC.  Disclosure of Interest  None Declared
INCIDENCE OF ACUTE TRAUMATIC INJURIES AND MEDICAL COMPLICATIONS IN 34 033 CYCLISTS PARTICIPATING IN A MASS COMMUNITY BASED EVENT – SAFER CYCLING
Authors: Jannelene Killops, Martin Schwellnus, Dina Christina Janse van Rensburg
Journal: British Journal of Sports Medicine (2017)

Background Mass participation in recreational sport (such as cycling) is part of a healthy lifestyle, and is an important component in the primary and secondary prevention of non-communicable diseases (NCD's). However, there is a risk of acute traumatic injuries and acute medical complications during community mass participation cycling races, but this has not been well documented. Objective The objective of this study was to document the incidence of acute traumatic injuries and acute non-traumatic medical complications in a community mass participation cycling race. Design Retrospective cohort study. Setting 109 km cycling race. Participants All 34 033 race starters (males=26 835, females=7 198) to the 2014 Cape Town Cycle Tournament. Assessment Pre-race entry demographic data and race-day medical complications data (all incidents that required assessment by the medical team on race day) were collected. Main Outcome Measurements The incidence (per 1000 race starters) of all complications, acute traumatic injuries and non-traumatic medical complications and serious life threatening complications were determined for all cyclists, and male and female cyclists. Results The incidence (per 1000 starters) of all complications was 6.35, and this was significantly higher in females vs. males (male=5.78, female=8.47; p=0.014). The incidence of serious life-threatening complications was 0.5, and there was a trend toward a higher incidence in female cyclists (female=0.97, males=0.37; p=0.06). Female cyclists also had a significantly higher (p=0.027) incidence of acute traumatic injuries (females=6.53, males=4.47; p=0.027). The incidence of acute non-traumatic medical complications was 1.44 (males=1.30, females=1.94; p=0.203). Conclusions 1/157 race starters (males: 1/173; females: 1/118) at a community based cycling event were injured or developed a medical complication during the race, and the risk is significantly higher in female cyclists. These data indicate the need to develop and implement prevention strategies to reduce the risk of medical complications, specifically traumatic injuries, in female cyclists.
A 12MM, IN-SHOE ORTHOTIC HEEL LIFT ADDED TO STANDARD RUNNING SHOES LOWERS ACHILLES TENDON LOADING
Authors: Simon Bartold
Journal: British Journal of Sports Medicine (2017)

Background Orthotic heel lifts are thought to lower tension in the Achilles tendon, but the evidence supporting this is equivocal. Objective To investigate the effect of a 12 mm in-shoe orthotic heel lift on Achilles tendon loading using transmission mode ultrasonography. Design Controlled study. Setting Laboratory. Patients (or Participants) 12 active males. Interventions (or Assessment of Risk Factors) The propagation speed of ultrasound, which is governed by the elastic modulus and density of tendon and proportional to the tensile load to which it is exposed, was measured in 12 recreationally active men, during shod treadmill walking at matched speeds (3.4 +/− 0.7 km/h), with and without the addition of a heel lift. Vertical ground reaction forces and spatiotemporal gait parameters were simultaneously recorded. Data were acquired at 100 Hz during 10 seconds of steady state walking. Main Outcome Measurements Ultrasound transmission speed maxima (P1, P2) and minima (M1,M2) in the Achilles tendon, vertical ground reaction force peaks, step length, and cadence. Results Ultrasound transmission speed in the Achilles tendon was characterised by 2 maxima (P1,P2) and minima (M1,M2) during walking. Addition of a heel lift to footwear resulted in a 2% increase and a 2% decrease in the first vertical ground reaction force peak and the local minimum respectively (P&lt; 0.05). Ultrasonic velocity in the Achilles tendon (P1, P2, M2) was significantly lower with the addition of an orthotic heel lift (P&lt;0.5). Conclusions Peak ultrasound transmission speed in the Achilles tendon was lower with the addition of a 12 mm orthotic heel lift, indicating that the heel lift reduced tensile load in the Achilles tendon, thereby counteracting the effect of footwear observed in previous studies. These findings support the addition of orthotic heel lifts to footwear in the rehabilitation of Achilles tendon disorders where management aims to lower tension within the tendon.
RELIABILITY, PRECISION OF MEASUREMENT AND MINIMAL DETECTABLE DIFFERENCE OF RIGHT AND LEFT KNEE EXTENSION FORCE SENSE MEASUREMENT IN UNINJURED ADULT MALE FOOTBALL PLAYERS
Authors: Nicholas Clark, Mark Rolleston
Journal: British Journal of Sports Medicine (2017)

Background Proprioception (joint position sense (JPS), kinaesthesia, force sense (FS)) is of interest in knee injury prevention. Recent work reports existing knee proprioception tests are inadequate relative to gaining better understanding of knee functional joint stability and injury aetiology. Objective To determine critical psychometric properties of a new knee extension FS test in uninjured, adult, male football players. Hypotheses: 1. the test would demonstrate good reliability; 2. there would be no between-limb significant differences. Design Between-day (D1/D2) repeated measures. Setting University sensorimotor control laboratory. Participants Twelve university team players (age (mean±SD) 21.1±1.5 years; height 177.5±9.3 cm; mass 77.1±15.4 kg) participated. Interventions Players were seated on an isokinetic dynamometer set to isometric mode, the knee flexed 45°. A knee extension target trial-reproduction trial sequence was repeated five times, FS measured in Newtons (N), between-trial differences designated absolute error (AE), average AE used for analyses. Limb order was randomized for D1 and repeated D2. Main Outcome Measures Systematic error (paired t-test; Cohen's d (d)); relative reliability (ICC 2,k); absolute reliability (standard error of measurement (SEM)); measurement change needed to detect true physiological differences (minimal detectable difference (MDD)); between-limb differences (D2 values; paired t-test). Results There were no significant differences between D1 and D2 values for either limb (P&gt;0.90; d&lt;0.03). The ICC (2,k), SEM and MDD were: right=0.81, 3.3N, 9.1N; left=0.78, 3.8N and 10.4N. There were no significant between-limb differences (P=0.75). Conclusions There was no systematic error. The FS test demonstrated good reliability. The measurement error and change needed to detect true physiological change were established. There were no between-limb differences. The knee extension FS test offers a new knee proprioception test that can be used in studies of knee functional joint stability and injury aetiology in adult male football players.
A Team-Based Online Game Improves Blood Glucose Control in Veterans With Type 2 Diabetes: A Randomized Controlled Trial
Authors: B. Price Kerfoot, David R. Gagnon, Graham T. McMahon, Jay D. Orlander, Katherine E. Kurgansky, Paul R. Conlin
Journal: Diabetes Care (2017)

Rigorous evidence is lacking whether online games can improve patients' longer-term health outcomes. We investigated whether an online team-based game delivering diabetes self-management education (DSME) to patients via e-mail or mobile application (app) can generate longer-term improvements in hemoglobin A1c (HbA1c).Patients (n = 456) on oral diabetes medications with HbA1c ≥58 mmol/mol were randomly assigned between a DSME game (with a civics booklet) and a civics game (with a DSME booklet). The 6-month games sent two questions twice weekly via e-mail or mobile app. Participants accrued points based on performance, with scores posted on leaderboards. Winning teams and individuals received modest financial rewards. Our primary outcome measure was HbA1c change over 12 months.DSME game patients had significantly greater HbA1c reductions over 12 months than civics game patients (-8 mmol/mol [95% CI -10 to -7] and -5 mmol/mol [95% CI -7 to -3], respectively; P = 0.048). HbA1c reductions were greater among patients with baseline HbA1c >75 mmol/mol: -16 mmol/mol [95% CI -21 to -12] and -9 mmol/mol [95% CI -14 to -5] for DSME and civics game patients, respectively; P = 0.031.Patients with diabetes who were randomized to an online game delivering DSME demonstrated sustained and meaningful HbA1c improvements. Among patients with poorly controlled diabetes, the DSME game reduced HbA1c by a magnitude comparable to starting a new diabetes medication. Online games may be a scalable approach to improve outcomes among geographically dispersed patients with diabetes and other chronic diseases.
脳由来神経栄養をトランスフェクトした間葉系幹細胞スフェロイドを用いた先端細胞移植技術による脊髄損傷の治療【Powered by NICT】
Authors: Uchida Satoshi, Hayakawa Kentaro, Ogata Toru, Tanaka Sakae, Kataoka Kazunori, Itaka Keiji
Journal: Biomaterials (2016)
Association Between Adherence to Pharmacotherapy and Outcomes in Type 2 Diabetes: A Meta-analysis
Authors: Kamlesh Khunti, Samuel Seidu, Setor Kunutsor, Melanie Davies
Journal: Diabetes Care (2017)

A previous study suggests an association between poor medication adherence and excess mortality in chronic disease. The purpose of this study was to assess the association between medication adherence and risk of cardiovascular disease (CVD), all-cause mortality, and hospitalization in type 2 diabetes.We conducted an electronic search on many electronic databases from inception to 27 April 2016. We selected randomized controlled trials and case-control and cohort studies reporting on CVD, all-cause mortality, or hospitalization outcomes by adherence in adults with type 2 diabetes. Two reviewers independently screened for eligible studies and extracted outcome data. Pooled relative risks (RRs) were calculated using a random-effects meta-analysis; risk of bias in each of the included studies was assessed using the GRADE approach.Eight observational studies were included (n = 318,125). The mean rate of poor adherence was 37.8% (95% CI 37.6-38.0). Adjusted estimates were provided by five studies only. The RRs of good (≥80%) versus poor adherence to medication were 0.72 (95% CI 0.62-0.82, I2 = 0%, three studies) for all-cause mortality and 0.90 (0.87-0.94, I2 = 63%, seven studies) for hospitalization. No evidence of small study bias was observed. Only one study reported CVD outcomes by adherence.We identified no trials reporting on outcomes by adherence, suggesting a systematic failure to include this information. Pooled estimates from available observational studies suggest that good medication adherence is associated with reduced risk of all-cause mortality and hospitalization in people with type 2 diabetes, although bias cannot be excluded as an explanation for these findings.
Abstract 343: Upregulated S1P Lyase Exerts Cardioprotective Effects through Inhibiting S1P/HIF-1a-Mediated Oxidative/Nitrative Stress during Myocardial Ischemia/Reperfusion
Authors: Ling Tao, Wenjun Yan, Fen Zhou, Fuyang Zhang, Lu Sun, Haichang Wang, Yan Qu
Journal: Circulation Research (2013)

Sphingosine-1-phosphate (S1P) signaling directs a diverse array of biological processes, such as anti-apoptosis, promoting in[[Unable to Display Character: &amp;#64258;]]ammatory, and inducing fibrosis. Therefore, S1P levels need to be tightly controlled through the delicate interplay of its generating enzymes and its degrading enzymes. S1P lyase (SPL1) is a stress-activated enzyme responsible for irreversible S1P catabolism. This study was designed to determine the role of SPL1 in ischemia/reperfusion (I/R) induced cardiac dysfunction and the underlying mechanisms. Mice were subjected to 40 minutes left coronary artery occlusion followed by reperfusion for 24 hours, 1 week, or 4 weeks. First, we observed that SPL1 expression in cardiac tissue was upregulated by about 4-fold in response to I/R (n=6, P &lt;0.01 versus sham). Further, oral administration of THI (an SPL1 inhibitor, 25 mg/L, daily) increased plasma S1P level and deteriorated I/R-induced apoptosis and fibrosis determined 1 week after I/R (all P &lt;0.05 versus I/R + saline group), and cardiac dysfunction (ejection fraction: 39.1 ± 3.1% in I/R + THI group versus 50.7 ± 2.8% in I/R + saline group determined 4 weeks after I/R, P &lt;0.05). After 1 week of I/R, hearts from THI-fed mice exhibited increased hypoxia-inducible factor-1α (HIF-1α) expression, along with significant oxidative/nitrative damage as evidenced by gp91 phox , inducible nitric oxide synthase (iNOS), and 3-nitrotyrosine abundance (all P &lt;0.05 versus vehicle). To define the underlying mechanisms of SPL1 in I/R-induced heart injury, neonatal rat ventricular myocytes were cultured and submitted to hypoxia/reoxygenation (H/R, 9 hours/3 hours) with or without THI treatment. Importantly, THI significantly increased gp91 phox , iNOS, and 3-nitrotyrosine level, as well as apoptosis (n=8, all P &lt;0.05 versus H/R), all of which were inhibited by pretreatment with HIF-1α siRNA (all P &lt;0.05 versus scramble RNA). The present study demonstrated for the first time that SPL1 is remarkably upregulated during I/R and protects heart from I/R-induced S1P/HIF-1α-mediated oxidative/nitrative stress, suggesting SPL1 as a potential targets of therapy for ischemic heart disease.
The accelerated blood clearance phenomenon of PEGylated nanoemulsion upon cross administration with nanoemulsions modified with polyglycerin
Authors: Yuqing Su, Lirong Wang, Kaifan Liang, Mengyang Liu, Xinrong Liu, Yanzhi Song, Yihui Deng
Journal: Asian Journal of Pharmaceutical Sciences (2017)

For investigating the accelerated blood clearance (ABC) phenomenon of polyglycerin modified nanoemulsions upon cross administration with polyethylene glycol (PEG) covered nanoemulsion, we used the 1,2-distea-royl-sn-glycero-3-phosphoethanolamine-n-polyglycerine-610 and the 1,2-distearoyl-n-glycero-3-phosphoethanolamine-n-[me-thoxy(polyethylene glycol)-2000] as modify materials, the dialkylcarbocyanines as fluorescence indicator. Exhausted macrophages rat model was established and new material containing polycarboxyl structure was synthesized. The microplate reader and the in vivo optical imaging system were applied to measure the concentration of nanoemulsions in tissues. The results show that the first dose of polyglycerin modified nanoemulsion can induce the ABC phenomenon of the second dose of PEGylated nanoemulsion. With the increase in the amount of the surface polyglycerin, the extent of the ABC phenomenon decreases. Liver accumulation has positive relationship with the ABC phenomenon. Furthermore, kupffer cells in liver can get more immune information from polyhydroxy structure than polycarboxyl group in the modify compound. The results of our work imply that the polycarboxyl structure has advantages to eliminate the ABC phenomenon.