tbuckley/cabot-search huggingface dataset:
04.01 Doings and dealings in synovitis: fibroblast-like synoviocyte cell-to-cell organelle transfer is directed by the inflammatory microenvironment
Authors: Ruth A Byrne, Isabel Olmos Calvo, Felix Kartnig, Thomas Karonitsch, Günter Steiner, Johannes Holinka, Peter Ertl, Josef S Smolen, Hans P Kiener
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Fibroblast-like synoviocytes (FLS) form a complex tissue network via long-distance intercellular connexions with wide intercellular matrix spaces. The adaptive synovial tissue response to inflammation likely depends upon the concerted activity of FLS. Using an <i>in-vitro</i> synovial organ culture system, we explore mechanisms of FLS directed cellular cooperation. <h3>Methods</h3> Human FLS were prepared from synovial tissues obtained as discarded specimens following joint arthroplasty. Cells were labelled with cell tracker dyes or specific organelle dyes and cultured in spherical matrigel micromasses. For selected experiments, micromasses were challenged with TNF or IFNγ. Data was acquired by confocal live cell imaging. Analysis of the resulting 4D movies was done using Imaris software. <h3>Results</h3> To examine whether FLS transfer cytoplasmic cargo, we labelled 50% of FLS with green cell tracker dye and the other 50% with Mitotracker. Over time, red labelled organelles accumulated in green labelled cells with a transfer rate of 10% of newly affected cells/day. Confocal live cell imaging revealed that FLS indeed use their long-distance intercellular connexions for transfer of organelles. When micromasses were stimulated with TNF (10 ng/ml) the transfer rate increased by 2-fold when compared to control. By contrast, INFγ-stimulation resulted in decreased organelle transfer. The combined treatment of micromasses with TNF and IFNg, however, increased the transfer rate to a level beyond stimulation with TNF alone. <h3>Conclusions</h3> Our experiments suggest transfer of cytoplasmic cargo, including organelles such as mitochondria between FLS. As transfer is distinctly regulated by the cytokine milieu, organelle transfer seems to be part of the adaptive synovial response to inflammation. These studies may provide insight into how synoviocytes orchestrate their activity. Further studies will demonstrate the significance of directed cargo exchange for the function of the normal as well as the diseased synovium.
脆弱性評価手段:頻繁に引用される機器の使用と文脈の系統的特性化【Powered by NICT】
Authors: J Buta Brian, D Walston Jeremy, G Godino Job, Park Minsun, R Kalyani Rita, Xue Qian-Li, Bandeen-Roche Karen, Varadhan Ravi
Journal: Ageing Research Reviews (2016)
INJURIES IN YOUTH ATHLETICS HAVE MULTIPLE-LEVEL CAUSES THAT CALL FOR AN ECOLOGICAL INTERVENTION APPROACH: A NATIONAL SPORTING COMMUNITY CONSENSUS REPORT
Authors: Jenny Jacobsson, Daniel Bergin, Toomas Timpka, James Nyce, Örjan Dahlström
Journal: British Journal of Sports Medicine (2017)

Background Engaging in competitive sports as a youth can have many health benefits, but recent studies also report a disquieting high injury risk. The long-term purpose of a Swedish research program is to develop a framework for safe athletics training among youth athletes (aged 12–15 years). Objective To establish a national consensus of what causes injuries in youth athletics by compiling the best available experiential knowledge about the underlying causes of injuries sustained by young athletics athletes. Design Qualitative study using focus groups and in-depth interviews for data collection. Setting The Swedish Athletics community divided into seven administrative regions. Participants 79 individuals representing all levels of the sport; officials from the Swedish Athletics Association, coaches, athletes, sports medicine professionals, clubs representatives, and parents. Assessment of Risk Factors Qualitative research methods were used to categorize data, perform a thematic analysis, and execute repeated feed-back cycles to the community to corroborate preliminary results. Main Outcome Measurements Categories resulting from the qualitative analysis were used to construct an explanatory model. Results Injuries in youth athletes were not considered to be strictly the result of discrete causal factors but rather the result of the interactions between factors at different levels. Three major areas of injury causes emerged; the evidence-in-situ for application in daily practice, attitudes among coaches and parents about long-term strategies in youth athletics, and the setting and conditions for participating in the sport. In response, an ecological model for implementation of interventions was outlined that has its focal point in the young athlete's personal zone of athletic development. Conclusions A national consensus process established that if effective and sustainable injury prevention processes are to be introduced in youth athletics, an ecological approach is needed. Such an approach allows a longitudinal development-focused strategy for prevention that spans over an entire athletic career.
有効皮膚保護との相乗的癌光線療法のためのクエンチされたリポソームCe6の近赤外光活性化【Powered by NICT】
Authors: Feng Liangzhu, Tao Danlei, Dong Ziliang, Chen Qian, Chao Yu, Liu Zhuang, Chen Meiwan
Journal: Biomaterials (2017)
Why don’t serum vitamin D concentrations associate with BMD by DXA? A case of being ‘bound’ to the wrong assay? Implications for vitamin D screening
Authors: Richard J Allison, Abdulaziz Farooq, Anissa Cherif, Bruce Hamilton, Graeme L Close, Mathew G Wilson
Journal: British Journal of Sports Medicine (2017)

The association between bone mineral density (BMD) and serum25-hydroxyvitamin D (25(OH)D) concentration is weak, particularly in certain races (eg, BlackAfrican vs Caucasian) and in athletic populations. We aimed to examine if bioavailable vitamin D rather than serum 25(OH)D was related to markers of bone health within a racially diverse athletic population.In 604 male athletes (Arab (n=327), Asian (n=48), Black (n=108), Caucasian (n=53) and Hispanic (n=68)), we measured total 25(OH)D, vitamin D-binding protein and BMD by DXA. Bioavailable vitamin D was calculated using the free hormone hypothesis.From 604 athletes, 21.5% (n=130) demonstrated severe 25(OH)D deficiency, 37.1% (n=224) deficiency, 26% (n=157) insufficiency and 15.4% (n=93) sufficiency. Serum 25(OH)D concentrations were not associated with BMD at any site. After adjusting for age and race, bioavailable vitamin D was associated with BMD (spine, neck and hip). Mean serum vitamin D binding protein concentrations were not associated with 25(OH)D concentrations (p=0.392).Regardless of age or race, bioavailable vitamin D and not serum 25(OH)D was associated with BMD in a racially diverse athletic population. If vitamin D screening is warranted, clinicians should use appropriate assays to calculate vitamin D binding protein and bioavailable vitamin D levels concentrations than serum 25(OH)D. In turn, prophylactic vitamin D supplementation to 'correct' insufficient athletes should not be based on serum 25(OH)D measures.
BERIL-1: Biomarker results from targeted sequencing of circulating tumor DNA (ctDNA) and archival tissue in a randomized phase II study of buparlisib (BKM120) or placebo plus paclitaxel in patients with head and neck squamous cell carcinoma (HNSCC).
Authors: Lisa F. Licitra, Sandrine J. Faivre, Marie Chol, Nadia Solovieff, Douglas Robinson, Emmanuelle DiTomaso, Samit Hirawat, Denis Soulieres
Journal: Journal of Clinical Oncology (2016)

6045 Background: A phase II, placebo-controlled study of buparlisib (BUP) and paclitaxel (PAC) in patients (pts) with platinum-pretreated recurrent/metastatic HNSCC (NCT01852292) met its primary endpoint, demonstrating improved clinical benefit with BUP + PAC vs PAC alone: median progression-free survival (mPFS) was 4.6 vs 3.5 months, overall response rate (ORR) was 39% vs 14%, and median overall survival (mOS) at data cut-off was 10.0 vs 6.5 months. Exploratory analyses were conducted to identify biomarkers of improved clinical benefit. Methods: A total of 158 pts received BUP + PAC or placebo + PAC (n = 79 each). ctDNA from 109 plasma samples and genomic DNA from 84 archival tissue samples collected at screening were analyzed by next-generation sequencing with panels of 542 and 44 genes, respectively. Human papillomavirus (HPV) status was assessed by immunohistochemistry in 143 archival tissue samples. Results: Based on ctDNA, in 43 (39%) pts with TP53 alteration, mOS (8.4 vs 5.7 months; hazard ratio [HR] 0.49, 95% CI: 0.22–1.12) and ORR (33% vs 8%) were improved with BUP + PAC vs PAC alone. In 83 (76%) pts with low mutational load ( < 13 variants), mOS was improved (12.6 vs 6.4 months; HR 0.57, 95% CI: 0.31–1.07). TP53 alteration and mutational load in ctDNA were not associated with improved mPFS. Based on archival tissue, in 52 (62%) pts with TP53 alteration, mPFS (5.0 vs 2.2 months; HR 0.45, 95% CI: 0.23–0.89), mOS (11.0 vs 5.8 months; HR 0.45, 95% CI: 0.21–0.98), and ORR (38% vs 8%) were improved for BUP + PAC vs PAC alone. In 115 (80%) pts with HPV-negative status, mPFS (3.7 vs 2.3 months), mOS (9.1 vs 5.8 months), and ORR (40% vs 11%) were improved. PIK3CA alteration (9 [8%] pts in ctDNA; 16 [13%] pts in archival tissue) and phosphatidylinositol 3-kinase pathway alteration (27 [25%] pts in ctDNA; Lui et al. Cancer Discov 2013) were not associated with improved tumor response. Conclusions: Exploratory analyses suggest that BUP + PAC may be effective in pts with TP53-altered, HPV-negative HNSCC, or with low mutational load. Further analyses of OS and prognostic/predictive markers will be presented. Clinical trial information: NCT01852292.
Correlatoin of apoptosis signaling in primary pediatric BCP-ALL xenograft cells with the kinetics of engraftment in vivo in a NOD/SCID model and patient outcome
Authors: M. Queudeville, S. M. Eckhoff, K. Debatin, L. H. Meyer
Journal: Journal of Clinical Oncology (2009)

10043 Background: We previously identified the importance of intact apoptosis signaling for treatment response in pediatric ALL and AML by analyzing two key apoptogenic events, caspase-3 activation and cytochrome c release. A correlation of both events was exclusively found in the groups of patients with good response to treatment, showing that intact apoptosis signaling is a critical feature for favorable outcome. Using a NOD/SCID mouse model for pediatric BCP-ALL we found that short time from transplant to overt leukemia in the recipient mice (short time to leukemia, TTLshort) determines poor patient outcome. Methods: In this study we investigated the importance of deficient apoptosis signaling for leukemia engraftment in this model. The apoptosis signaling parameters cytochrome c release and caspase-3 activation were analyzed in 17 ALL xenografts (TTLshort n = 5, TTLlong n = 12) by flowcytometry in relation to TTL. Results: A significant correlation of both apoptosis parameters was found in the TTLlong group only (P = .017). Importantly, patients showing TTLlong revealed a superior outcome compared to TTLshort patients. Proficient apoptosis signaling was only found in blast cells from recipients where the corresponding patient had favorable prognostic factors such as TEL/AML1-positivity (P = .023), no hyperleucocytosis (P = .012), no relapse (P = .038), and no early relapse (P = .017). In contrast, the correlation of cytochrome c release and caspase-3 activation was absent in the groups with poor prognosis. We also found a direct positive correlation between TTL and cytochrome c (P = .022) and caspase-3 activation (P = .048), indicating that short engraftment may be due to deficient apoptosis signaling. Conclusions: Our finding in the NOD/SCID/huALL model matches our results in pediatric ALL and AML to conclude that the functional integrity of a downstream apoptotic checkpoint is an important feature regulating leukemia biology. Thus, deficient apoptosis signaling appears to determine rapid engraftment of leukemia cells in the NOD/SCID model in vivo and consequently poor patient outcome. No significant financial relationships to disclose.
ORAL HEALTH OF UK ATHLETES AND IMPACT ON PERFORMANCE
Authors: Julie Gallagher
Journal: British Journal of Sports Medicine (2017)

Background Previous research indicates that poor oral health is common in elite athletes and is associated with negative self-reported impacts on wellbeing, training and performance. However the strength of evidence is limited. Objective We aimed to conduct a methodologically robust study of oral health, the determinants of oral health and associated self-reported impacts across different sports using a trained and calibrated examiner and validated outcome measures. Design Cross-sectional observational clinical and questionnaire study of representative samples of elite (Olympic and professional) athletes. Setting Athlete medical and training facilities. Participants 300 UK athletes aged 18 years and over, on podium placement/potential programmes or participating as professional athletes. Interventions (or Assessment of Risk Factors) We measured dental caries, erosion, periodontal health, wisdom teeth infections, self-reported oro-facial trauma, oral health preventive and risk behaviours and potential for behaviour change. Main Outcome Measurements We used validated clinical indices for caries, erosion and periodontal health. Self-reported impact on athlete performance was measured using a modification of the OSTRC overuse injury questionnaire. Results One third (33%) of athletes had caries into dentine and 35% had erosion with dentine exposed in at least one tooth. One quarter (24%) had chronic inflammatory periodontitis, however only 6% reported oro-facial trauma related to their sport. Many athletes (49%-83%) reported consumption of sports drinks, bars and gels during training and competition. Most (96%) athletes reported good oral hygiene habits. One third (34%) reported a negative impact on performance. Conclusions UK elite athletes have significant levels of oral disease with one third reporting a negative impact. Despite most athletes reporting beneficial oral health behaviours, additional health promotion and preventive measures are required to mitigate risk factors and reduce self-reported performance impacts.
The challenge to interpret conflicting results and the need of a univocal definition for germinal centres in primary Sjögren’s syndrome
Authors: Alessia Alunno, Francesco Carubbi, Roberto Giacomelli, Roberto Gerli
Journal: Annals of the Rheumatic Diseases (2017)

We read with interest the article by Haacke et al 1 demonstrating that the presence of germinal centres (GCs) in minor salivary glands (MSG) of patients with primary Sjogren’s syndrome (pSS) does not differ between subjects developing non-Hodgkin’s lymphoma (NHL) and those who do not develop this complication. In recent years the prognostic role of MSG histopathology has been a matter of intense debate. The severity of the inflammatory infiltrate as defined by the focus score (FS) and/or by the presence of ectopic lymphoid structures (ELS) has been associated with a severe clinical picture characterised by extraglandular manifestations as well as NHL.2–5 Although the calculation of FS is rather intuitive and reproducible,6 making the comparison of different studies easy, discrepancies arise with …
Use of Alternative Medicine for Cancer and Its Impact on Survival
Authors: Skyler B Johnson, Henry S Park, Cary P Gross, James B Yu
Journal: JNCI Journal of the National Cancer Institute (2017)

There is limited available information on patterns of utilization and efficacy of alternative medicine (AM) for patients with cancer. We identified 281 patients with nonmetastatic breast, prostate, lung, or colorectal cancer who chose AM, administered as sole anticancer treatment among patients who did not receive conventional cancer treatment (CCT), defined as chemotherapy, radiotherapy, surgery, and/or hormone therapy. Independent covariates on multivariable logistic regression associated with increased likelihood of AM use included breast or lung cancer, higher socioeconomic status, Intermountain West or Pacific location, stage II or III disease, and low comorbidity score. Following 2:1 matching (CCT = 560 patients and AM = 280 patients) on Cox proportional hazards regression, AM use was independently associated with greater risk of death compared with CCT overall (hazard ratio [HR] = 2.50, 95% confidence interval [CI] = 1.88 to 3.27) and in subgroups with breast (HR = 5.68, 95% CI = 3.22 to 10.04), lung (HR = 2.17, 95% CI = 1.42 to 3.32), and colorectal cancer (HR = 4.57, 95% CI = 1.66 to 12.61). Although rare, AM utilization for curable cancer without any CCT is associated with greater risk of death.
Peter Joseph Wilkinson Monks
Authors: P Sleight, V Sleight, A Dawson, N Januszewski
Journal: BMJ (2017)

Peter Joseph Wilkinson Monks was born in Warrington, Cheshire, and studied medicine at St Bartholomew’s Hospital, London. His preclinical training was relocated to Cambridge during the war. He was a medical student and junior doctor during the second world war, treating casualties of the London Blitz and experiencing direct bombing of the hospital itself. After the war, in the Royal Naval Volunteer Reserve, he met and married Phyl (Phyllis), a young officer in the WRNS.

His initial appointment was as surgeon lieutenant at Greenwich Hospital, and …
01.04 Enrichment of activated cd141+ dendritic cells in inflammatory arthritis
Authors: Mary Canavan, Trudy McGarry, Kate Killick, Barry Moran, Deborah Cluxton, Carl Orr, Siobhan Wade, Hannah Convery, Sarah Wade, Ronan Mullan, Jean Fletcher, Douglas Veale, Ursula Fearon
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Dendritic cell (DC) are a heterogeneous group of antigen presenting cells that can be subdivided into CD1c and CD141<sup>+</sup>DC. CD141<sup>+</sup>DC were first discovered in 2010 and little is known about their function in health or disease. No previous studies on CD141<sup>+</sup>DC in inflammatory arthritis (IA) have been performed therefore our aim was to examine if these newly described DC play a pathogenic role in IA. <h3>Methods</h3> CD141<sup>+</sup>DC were purified from SFMC/PBMC, stimulated and stained with a panel of DC specific activation markers. CD141<sup>+</sup>DC were cocultured with T cells for 6d basally or in the presence of TREM-1 after which intracellular cytokine production was assessed by flow cytometry. Supernatants from DC-T cell cocultures were used to treat synovial fibroblasts and the expression of adhesion molecules, cytokines and MMPs was measured. CD141<sup>+</sup>DC were also identified in synovial-tissue by immunohistology/flow cytometry for CD141/CLEC9A/TREM-1. Finally using sorted populations of CD141<sup>+</sup>DC from SFMC and PBMC, RNA sequencing was performed and differentially expressed genes and interaction network analysis were identified using the DeSeq2 R package, Ingenuity<sup>®</sup> Pathway Analysis (IPA) and InnateDB and Cytoscape. <h3>Results</h3> SF-CD141<sup>+</sup>DC are significantly enriched compared to WB and express higher levels of activation markers CD80/CD86 and CD40. SF-CD141<sup>+</sup>DC induced both CD8<sup>+</sup> and CD4<sup>+</sup>T cell proliferation, granzyme B production from CD8<sup>+</sup> and TNFα, IFNγ and GMCSF from CD4<sup>+</sup>T cells. Supernatants from CD141<sup>+</sup>DC activated T cells subsequently induced synovial fibroblast expression of ICAM-1, IL-6, IL-8, MMP1 and MMP3. SF-CD141<sup>+</sup>DC expressed significantly higher levels of the the hypoxia marker TREM-1, activation of which further induces expression of CD80, CD86 and CD40. Coculture of these TREM-1 activated CD141<sup>+</sup>DC with CD3<sup>+</sup> T cells increased IFNγ and IL-17a production. Finally RNASeq analysis revealed that there are 2089 differentially expressed genes between SF-CD141<sup>+</sup>DC and PBMC CD141<sup>+</sup>DC, with induction of a number of key network pathways identified in SF CD141<sup>+</sup> DC, including energy metabolism, chemokine and cytokine signalling. <h3>Conclusion</h3> CD141<sup>+</sup> DC are enriched in the IA joint in an active state. RNASeq analysis revealed they are distinct from blood CD141<sup>+</sup>DC and our <i>in vitro</i> data would support the hypothesis that these CD141<sup>+</sup>DC contribute to synovial inflammation and joint destruction.
Metabolomics as a tool to identify biomarkers to predict and improve outcomes in reproductive medicine: a systematic review
Authors: Timothy Bracewell-Milnes, Srdjan Saso, Hossam Abdalla, Dimitrios Nikolau, Julian Norman-Taylor, Mark Johnson, Elaine Holmes, Meen-Yau Thum
Journal: Human Reproduction Update (2017)

Infertility is a complex disorder with significant medical, psychological and financial consequences for patients. With live-birth rates per cycle below 30% and a drive from the Human Fertilisation and Embryology Authority (HFEA) to encourage single embryo transfer, there is significant research in different areas aiming to improve success rates of fertility treatments. One such area is investigating the causes of infertility at a molecular level, and metabolomics techniques provide a platform for studying relevant biofluids in the reproductive tract. The aim of this systematic review is to examine the recent findings for the potential application of metabolomics to female reproduction, specifically to the metabolomics of follicular fluid (FF), embryo culture medium (ECM) and endometrial fluid. To our knowledge no other systematic review has investigated this topic. English peer-reviewed journals on PubMed, Science Direct, SciFinder, were systematically searched for studies investigating metabolomics and the female reproductive tract with no time restriction set for publications. Studies were assessed for quality using the risk of bias assessment and ROBIN-I. There were 21 studies that met the inclusion criteria and were included in the systematic review. Metabolomic studies have been employed for the compositional analysis of various biofluids in the female reproductive tract, including FF, ECM, blastocoele fluid and endometrial fluid. There is some weak evidence that metabolomics technologies studying ECM might be able to predict the viability of individual embryos and implantation rate better than standard embryo morphology, However these data were not supported by randomized the controlled trials (RCTs) which showed no evidence that using metabolomics is able to improve the most important reproductive outcomes, such as clinical pregnancy and live-birth rates. This systematic review provides guidance for future metabolomic studies on biofluids of the female reproductive tract, with a summary of the current findings, promise and pitfalls in metabolomic techniques. The approaches discussed can be adapted by other metabolomic studies. A range of sophisticated modern metabolomic techniques are now more widely available and have been applied to the analysis of the female reproductive tract. However, this review has revealed the paucity of metabolomic studies in the field of fertility and the inconsistencies of findings between different studies, as well as a lack of research examining the metabolic effects of various gynecological diseases. By incorporating metabolomic technology into an increased number of well designed studies, a much greater understanding of infertility at a molecular level could be achieved. However, there is currently no evidence for the use of metabolomics in clinical practice to improve fertility outcomes.