tbuckley/cabot-search huggingface dataset:
Re: Marzia Del Re, Elisa Biasco, Stefania Crucitta, et al. The Detection of Androgen Receptor Splice Variant 7 in Plasma-derived Exosomal RNA Strongly Predicts Resistance to Hormonal Therapy in Metastatic Prostate Cancer Patients. Eur Urol 2017;71:680–7
Authors: Ugo De Giorgi, Vincenza Conteduca, Emanuela Scarpi
Journal: European Urology (2017)
Comparison of methods available for identification of Mycobacterium chimaera
Authors: E. Lecorche, S. Haenn, F. Mougari, S. Kumanski, N. Veziris, H. Benmansour, L. Raskine, L. Moulin, E. Cambau, A. Aubry, F. Brossier, A. Chauffour, J. Jaffre, V. Jarlier, J. Robert, W. Sougakoff
Journal: Clinical Microbiology and Infection (2017)
Krüppel-Like Factor 4 Regulation of Cholesterol-25-Hydroxylase and Liver X Receptor Mitigates Atherosclerosis Susceptibility
Authors: Zhao Li, Marcy Martin, Jin Zhang, Hsi-Yuan Huang, Liang Bai, Jiao Zhang, Jian Kang, Ming He, Jie Li, Mano R. Maurya, Shakti Gupta, Guangjin Zhou, Panjamaporn Sangwung, Yong-Jiang Xu, Ting Lei, Hsien-Da Huang, Mohit Jain, Mukesh K. Jain, Shankar Subramaniam, John Y.-J. Shyy
Journal: Circulation (2017)

Atherosclerosis is a multifaceted inflammatory disease involving cells in the vascular wall (eg, endothelial cells [ECs]), as well as circulating and resident immunogenic cells (eg, monocytes/macrophages). Acting as a ligand for liver X receptor (LXR), but an inhibitor of SREBP2 (sterol regulatory element-binding protein 2), 25-hydroxycholesterol, and its catalyzing enzyme cholesterol-25-hydroxylase (Ch25h) are important in regulating cellular inflammatory status and cholesterol biosynthesis in both ECs and monocytes/macrophages.Bioinformatic analyses were used to investigate RNA-sequencing data to identify cholesterol oxidation and efflux genes regulated by Krüppel-like factor 4 (KLF4). In vitro experiments involving cultured ECs and macrophages and in vivo methods involving mice with Ch25h ablation were then used to explore the atheroprotective role of KLF4-Ch25h/LXR.Vasoprotective stimuli increased the expression of Ch25h and LXR via KLF4. The KLF4-Ch25h/LXR homeostatic axis functions through suppressing inflammation, evidenced by the reduction of inflammasome activity in ECs and the promotion of M1 to M2 phenotypic transition in macrophages. The increased atherosclerosis in apolipoprotein E-/-/Ch25h-/- mice further demonstrates the beneficial role of the KLF4-Ch25h/LXR axis in vascular function and disease.KLF4 transactivates Ch25h and LXR, thereby promoting the synergistic effects between ECs and macrophages to protect against atherosclerosis susceptibility.
Transient receptor potential vanilloid 4–expressing macrophages and keratinocytes contribute differentially to allergic and nonallergic chronic itch
Authors: Jialie Luo, Jing Feng, Guang Yu, Pu Yang, Madison R. Mack, Junhui Du, Weihua Yu, Aihua Qian, Yujin Zhang, Shenbin Liu, Shijin Yin, Amy Xu, Jizhong Cheng, Qingyun Liu, Roger G. O'Neil, Yang Xia, Liang Ma, Susan M. Carlton, Brian S. Kim, Kenneth Renner, Qin Liu, Hongzhen Hu
Journal: Journal of Allergy and Clinical Immunology (2017)
Prise en charge non chirurgicale des doubles sténoses tumorales biliaires et duodénales
Authors: C Pesenti, E Bories, V Moutardier, C Danisi, M Giovannini
Journal: Endoscopy (2004)

Objectif: Evaluer la faisabilité et l’efficacité d’un traitement non chirurgical simultané des sténoses malignes duodénaleset biliaires symptomatiques par prothèses duodénales métalliques et prothèses biliaires ou drainage trans-hépatique percutané écho guidé. Patients et Méthodes: Entre mars 2000 et août 2003 nous avons traité 13 patients (9 hommes et 4 femmes; âge moyen 68,9 ans) présentant une double sténose maligne symptomatique avec occlusion haute et ictère. Il s’agissait de patients présentant des cancers à un stade avancé, considérés comme inopérables et pour lesquels seul un traitement palliatif était envisageable (5 tumeurs duodénales, 4 tumeurs pancréatiques, 2 tumeurs de la vésicule biliaire, 1 tumeur ampullaire, 1 tumeur antrale). Les prothèses duodénales étaient toutes posées endoscopiquement. Le drainage biliaire était assuré soit par uneprothèse métallique posée par CPRE, soit par ponction écho guidée trans hépatique (en cas d’échec de la CPRE) permettant la pose d’une prothèse biliaire et/ou d’un drain percutané externe. Les malades étaient suivis jusqu’à leur décès. Les critères de jugement étaient: le taux de réussite, la reprise alimentaire, la disparition de l’ictère, la morbiditéet la mortalité. Résultats: Onze patients (84,7%) ont pu être traités »totalement«, à la fois de leur sténose duodénale et de leur sténose biliaire. Neuf patients ont eu une prothèse biliaire mise en place soit par CPRE (5 patients = 38,4%), soit par voie percutané (4 patients = 30,7%). Deux patients (15,3%) ont eu un drainage biliaire percutané externe définitif sans pose d’endoprothèse en raison d’une sténose biliaire infranchissable tant en CPRE que par voie trans hépatique. Tous ces patients ont été améliorés sur le plan digestif avec une disparition du tableau d’occlusion haute. Sur le plan biliaire, 9 de ces 11 patients ont été améliorés (diminution de l’ictère, du prurit, de la bilirubine et des PAL). Deux de ces 11 patients n’ont pas été améliorés sur le plan biliaire du fait d’une progression tumorale hépatique. Deux patients (15,3%) n’ont pas pu être traités »totalement«: 1 patient pour lequel il n’a pas été possible de placer de prothèse (ni duodénale, ni biliaire), 1 patient qui a eu une prothèse duodénale mais sans drainage biliaire possible. Aucun patient traité »totalement« n’a présenté de récidive de sténose biliaire ou digestive. Aucune complication, ni mortalité imputable aux différentes procédures n’est à rapporter. La médiane de survie était de 35 jours, et tous les décès étaient liés à la progression du cancer. Conclusion: En cas de double sténose maligne duodénale et biliaire, la pose simultanée d’une prothèse duodénale métallique et sur le plan biliaire d’une prothèse ou d’un drainage externe trans hépatique, offre une alternative intéressante à la double dérivation chirurgicale. Ce traitement palliatif parait en effet aussi efficace que l’option chirurgicale, mais sans la morbidité ou la mortalité associée à cette dernière.
Prognostication of pancreatic adenocarcinoma by expression of thymidine phosphorylase (TP) and its correlation with survival
Authors: S. Hashmi, G. Black, D. Bell, A. Steg, M. Johnson, R. B. Diasio, M. W. Saif
Journal: Journal of Clinical Oncology (2007)

4606 Background: Preclinical studies have indicated that TP is one of the most useful markers of tumor response to capecitabine; with elevated TP expression resulting in higher intratumor levels of 5-FU. TP level in the tumor may be associated directly with survival and may be up-regulated by XRT. Methods: Twenty patients (pts) who had newly diagnosed locally advanced pancreatic cancer, age ≥ 19 years, ECOG PS 0–2, and adequate organ function received 50.4 Gy XRT with capecitabine 1,600 mg/m 2 M-F x 6 wks determined from our phase I study (JCO, Dec 2005). Following capecitabine-XRT, stable and responding pts received capecitabine 2,000mg/m 2 x 14 days every 3 wks till progression. Restaging was performed every 9 wks. Tumor specimens were procured with EUS-FNA prior and week 2 after starting capecitabine-XRT to evaluate TP mRNA levels by RT-PCR. Results: TP levels were elevated post-XRT when compared to pre-XRT TP (p= 0.01). Each of the 20 pts had at least one observation of TP. Mean TP level of each pt was obtained by averaging the pre-XRT and post-XRT TP levels. If one value was missing, then the other value was used for the mean TP level. Mean TP level was significantly associated with survival using the Cox proportional hazards model (p= 0.0072). Pts were separated into two groups - those with high baseline TP level and those with lower TP level with a cut off value of 213.85 using median of mean TP level. It was observed that group with higher TP levels had better survival as compared to the group with lower TP levels. However, the survival curves of these two groups crossed over after 18 months. Conclusions: Our study suggests that the higher the TP level in tumor post-XRT, the better the survival. This is most probably due to a higher accumulation of 5-FU in tumor due to up-regulation of TP. Possible explanation for the two groups crossing over after 18 months may include heterogeneity in TP due to a difference in pharmacogenomics or idiosyncratic drug toxicity profile of capecitabine. Further studies of long-term effects of treatment with a larger number of pts are needed to study exact effects of capecitabine and XRT, and to evaluate the differential role of TP with survival. [Table: see text]
01.10 Peripheral blood plasmacytoid dendritic cells in early rheumatoid arthritis
Authors: Faye AH Cooles, Amy E Anderson, Dennis W Lendrem, Julie Norris, Arthur G Pratt, Catharien MU Hilkens, John D Isaacs
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Plasmacytoid dendritic cells (pDCs) primarily produce type 1 interferons but also present antigen. pDCs migrate towards inflammatory sites and, in established RA, are reduced in peripheral blood but increased in synovium. We questioned their role in early disease by studying circulating pDCs in early, drug-naïve RA patients. <h3>Materials and methods</h3> Drug-naïve early RA patients and healthy controls were recruited. Peripheral blood flow cytometry identified pDCs (CD20<sup>-</sup>CD19<sup>-</sup>CD3<sup>-</sup>CD203<sup>-</sup>CD14<sup>-</sup>HLADR<sup>+</sup>CD1c<sup>-</sup>Cd11c<sup>-</sup>CD141<sup>-</sup>CD123<sup>+</sup>). Frequency was calculated (percentage of lymphocytes) and activation/co-stimulation molecule expression quantified. Some RA patients were sampled longitudinally. The whole blood interferon gene signature (IGS) was defined as the mean expression (RT-PCR) of <i>MxA, IFI6, OAS1, ISG15</i> and <i>IFI44L</i>. pDCs were flow sorted and their transcriptome analysed by NanoString nCounter technology. Significance when p&lt;0.05. <h3>Results</h3> 44 early RA patients (median age 57 [33–84], male:female 3:4) and 30 healthy controls (median age 37 [23–62], male:female 3:2) were studied. pDC frequency was significantly reduced in early RA, most markedly in seropositive (n=25) patients where it associated with increased CCR7 expression. CD86, HLA-DR and CD40 expression was comparable between early RA and healthy controls with no effect of serostatus (univariate linear regression (age and sex corrected) and Mann-Whitney U tests). Longitudinal analysis of early RA patients (n=15) demonstrated significant reduction in CD86, HLA-DR and CD40 expression during the first 12 months of symptoms but no change in CCR7 expression or pDC frequency (Wilcoxon signed-rank tests). There was no significant association between the IGS and pDC frequency or phenotype (linear regression). The pDC transcriptome was examined in 8 early RA patients and 4 healthy controls (age and sex matched). Differentially expressed genes (R Core team 2016) and Ingenuity Pathway Analysis suggested increased proliferation and reduced apoptosis in early RA but no increased activation. <h3>Conclusions</h3> This is the first detailed examination of pDCs in early RA. The reduced frequency at diagnosis, alongside a comparatively activated phenotype, suggests possible migration to the synovium of potential pathogenic relevance. Furthermore, transcriptomic analysis highlighted a possible expansion of pDCs in early RA, via enhanced proliferation and reduced death. Synovial analysis will be essential to identify a pDC contribution to RA pathogenesis.
Using G100 (Glucopyranosyl Lipid A) to transform the sarcoma tumor immune microenvironment.
Authors: Seth Pollack, Edward Y. Kim, Ernest U. Conrad, Ryan Blair O'Malley, Sara Cooper, Bailey Donahue, Lee D. Cranmer, Hailing Lu, Elizabeth Trice Loggers, Tailor Hain, Darin J Davidson, Lynn Bonham, Venu Gopal Pillarisetty, Gabrielle Kane, Stanley R. Riddell, Robin Lewis Jones
Journal: Journal of Clinical Oncology (2016)

11017 Background: Tumor associated macrophages (TAM) are critical for immune evasion in many tumors. We hypothesized that combining G100, a TLR4 agonist that stimulates innate immunity and increases inflammation preclinically, with radiation (rads) would drive TAM to an M1 phenotype, creating a strong T-cell response. Methods: We began an investigator-sponsored, phase I study for patients (pts) with met. sarcoma and a tumor safely injectable in an outpt clinic. We treated two, 6 pt cohorts with 5 or 10 mcg G100 in 8 weekly intra-tumor (IT) injections. Rads was given to the injected tumor at a dose of 30 + Gy in <5 fractions. Pre and post treatment biopsies were required. Results: 12 pts were enrolled; each cohort accrued in less than 3 months demonstrating feasibility of IT injection sarcoma trials. Sarcoma subtypes included: 6 pts with leiomyosarcoma (LMS), 2 with synovial and 1 each with myxofibrosarcoma, chondrosarcoma, epithelioid and undifferentiated round cell sarcoma (URCS). Pts had a median of 3 prior systemic therapy regimens (range 0-5). The mean max diameter of the injected tumor was 5.5 cm (range 1- 12.4 cm). No pts had attributable grade 3 or higher toxicity (CTCAE v4.03). All pts had local control of the injected lesion and completed the planned therapy, with the exception of the URCS, which resolved completely 3 wks after starting injections. Interestingly, that pt also had a marked increase in the overlap between TCR repertoire in the pre-treatment tumor and the pre and post treatment blood (13.4% to 21.5%), suggesting systemic expansion of tumor specific T cells. One pt with metastatic LMS had a dramatic reduction in TAM generally, and specifically M2-type TAM with infiltrating CD11B+ cells expressing M2 markers (CD163, CD206 and CD155) decreasing markedly even as HLA-DR increased, consistent with an immune activating, M1 TAM phenotype. This pt had SD with regression in a distant, untreated paraspinal tumor. Conclusions: In advanced sarcomas, G100 IT at 5 or 10 µg/dose were well tolerated and induced local and systemic immune changes. Longer f/u is needed to understand its clinical and potentially immunologic impact. Updated clinical and immune monitoring data will be presented. 20 mcg IT is being evaluated alone and with rads. Clinical trial information: NCT02180698.
A microsensing system for the in vivo real-time detection of local drug kinetics
Authors: Genki Ogata, Yuya Ishii, Kai Asai, Yamato Sano, Fumiaki Nin, Takamasa Yoshida, Taiga Higuchi, Seishiro Sawamura, Takeru Ota, Karin Hori, Kazuya Maeda, Shizuo Komune, Katsumi Doi, Madoka Takai, Ian Findlay, Hiroyuki Kusuhara, Yasuaki Einaga, Hiroshi Hibino
Journal: Nature Biomedical Engineering (2017)
THE RELIABILITY OF TWO-DIMENSIONAL (2D) BIOMECHANICAL VARIABLES DURING MULTIDIRECTIOANAL SINGLE LEG LANDING
Authors: Ahmed Alahmari, Lee Herrington, Richard Jones, Anmin Liu, Ziyad Neamatallah
Journal: British Journal of Sports Medicine (2017)

Background The knee joint is one of the most frequently injured joint in sports. Sport injury is mostly non-contact in nature and often occur during single leg landings (SLL). SLL are also a common task performed in many sports. The reliability of different landing tests has been examined in the literature, but mostly limited to one test and most studies did not report the standard error of measurement (SEM) of their measurement. Although three-dimensional (3D) motion analysis is the gold standard for examining lower limb biomechanics, its extension to a clinical setting or to a larger sample size is limited. Therefore, researchers have examined 2D motion analysis and found it a good alternative. Objective To establish the reliability and SEM of a 2D movement analysis system to measure the kinematics of lower extremity during multidirectional SLL. Design Test-retest reliability study. Setting University laboratory. Patients (or Participants) 12 moderately active university students. Assessment of Risk Factors 2D knee and hip frontal plane kinematics were collected for both legs while the subjects performed multidirectional SLL. A retest session was repeated one week later. Main Outcome Measurements Frontal plane projection angle (FPPA) and hip adduction angle. Results The ICC for the different variables ranged between 0.67 and 0.96, indicating good to excellent reliability for all 2D variables in all tasks. SEM ranging between 0.69° and 2.7° which can be an evidence for small measurement error. Conclusions The 2D biomechanical variables were reliable when examining multidirectional SLL tasks in a moderately active healthy population. Furthermore, multidirectional SLL is a reliable test to examine the lower extremity biomechanics.
Supporting Women’s Autonomy in Prenatal Testing
Authors: Josephine Johnston, Ruth M. Farrell, Erik Parens
Journal: New England Journal of Medicine (2017)

Interview with Josephine Johnston on fetal genetic sequencing and the challenges involved in ensuring fully informed consent. (10:14)Download Current prenatal screening practices and the complexity of genomic science create a risk that early, noninvasive fetal genetic sequencing will be integrated into care without the robust informed consent processes necessary for respecting women's autonomy.
Bcl-2 inhibitor uploaded upconversion nanophotosensitizers to overcome the photodynamic therapy resistance of cancer through adjuvant intervention strategy
Authors: Xiaomin Liu, Zhongqi Fan, Li Zhang, Zheng Jin, Dongmei Yan, Youlin Zhang, Xiaodan Li, Langping Tu, Bin Xue, Yulei Chang, Hong Zhang, Xianggui Kong
Journal: Biomaterials (2017)
THE INCIDENCE OF ILLNESS DECREASES OVER A 6-YEAR PERIOD DURING THE SUPER RUGBY TOURNAMENTS: A PROSPECTIVE COHORT STUDY INVOLVING 96 959 PLAYER DAYS
Authors: Martin Schwellnus, Audrey Jansen van Rensburg, Dina Christina Janse van Rensburg, Charl Janse van Rensburg, Esme Jordaan, Wayne Derman, Clint Readhead
Journal: British Journal of Sports Medicine (2017)

Background Illness accounts for a significant proportion of consultations with team physicians. Furthermore, intercontinental travel is a risk factor for illness in teams participating in the annual 16-week Super Rugby Tournament. Objective To determine if the incidence of illness in players participating in the Super Rugby Tournaments changed after illness prevention strategies were recommended before the 2013 tournament. Design Prospective cohort study. Setting Super Rugby Tournaments from 2010 to 2015 (6-year period). Participants Elite rugby players from five South African Super Rugby teams (average squad size=30 players). Assessment Participating teams and players were followed daily during the ≈16 week competition period for 6 years (96 959 player days). Team physicians recorded daily squad size and completed a daily illness log using an online injury and illness registration system (100% compliance). Following data analysis of the 2010 tournament resulting in two publications in 2012, recommendations to prevent illness were introduced before the 2013 tournament. Furthermore, in 2014, detailed written illness prevention guidelines were distributed to all team physicians. Main Outcome Measurements Incidence of illness (illness per 1000 player days). Results The incidence of illness (per 1000 player days; 95% CI) for each year was as follows: 2010 (14.3; 12.2–16.8), 2011 (12.2; 10.3–14.3), 2012 (12.4; 10.6–14.3), 2013 (4.8; 3.8–5.9), 2014 (6.5; 5.3–7.9) and 2015 (6.1; 5.1–7.2). The incidence of all illness in the period 2013 to 2015 was significantly lower in each year compared to the incidence of illness in each year during the period 2010 to 2012. Conclusions In this 6-year prospective cohort study, there was a significant reduction in the incidence of illness in the years following the publication of illness data in 2012. We suggest that the illness prevention recommendations, introduced from 2013, could account for this reduction in illness incidence.
04.22 Circadian clock and fibrosis
Authors: Steven O’Reilly
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background and aims</h3> Systemic sclerosis (SSc) is an autoimmune inflammatory condition resulting in fibrosis of the skin. The circadian clock is an autonomous clock that is inherent in every cell and perturbations of the clock are associated with a variety of diseases including inflammatory diseases. BMAL1 is a core component of the clock and binds with the protein CLOCK to regulate a variety of processes. We aim to evaluate the role of BMAL1 in fibrosis. <h3>Materials and methods</h3> Primary healthy dermal fibroblasts were cultured from healthy donors and then transfected with small interfering RNA to BMAL1 or siRNA scramble after 72 hours the cells were harvested and analysed for BMAL1, collagen1, alpha Sma, Sirtuin-1 and alpha tubulin as a loading control, by immunoblotting. In some experiments the same experimental conditions were followed but some cells were incubated additionally with the Sirtuin-1 activator Resveratrol. In separate experiments TGF-β1 was incubated or not with healthy fibroblasts and after 48 hours the cells were lysed and analysed for Sirtuin-1 levels by immunoblot. <h3>Results</h3> The siRNA mediated knockdown of BMAL1 was achieved after 72 hours in healthy dermal fibroblasts. The siRNA-mediated depletion of BMAL1 led to an increase in collagen1 protein levels and also a decreased expression of the HDAC Sirtuin-1. Co incubation of siRNA to BMAL1 and the Sirtuin-1 activator resveratrol led to repression of the increased collagen1 levels. Incubation of the pro-fibrotic TGF-β1 did not alter the levels of Sirtuin-1 convincingly. <h3>Conclusion</h3> The circadian clock protein BMAL1 regulates collagen expression through altering the levels of the HDAC Sirtuin-1. Reduced Sirtuin-1 appears important in SSc, however, TGF-β1 does not appear to be reducing this. Circadian clock disruption is important in skin fibrosis.
Use of needle-based confocal laser endomicroscopy in the diagnosis of multifocal intraductal papillary mucinous neoplasm with high grade dysplasia
Authors: Yun-Lu Feng, Ai-Ming Yang, Xi Wu, Zhilan Meng, Xiaoyan Chang, Zhiyong Liang, Junchao Guo
Journal: Endoscopy (2017)

A 64-year-old woman with newly diagnosed type 2 diabetes mellitus was admitted with intermittent abdominal pain of 3 years’ duration. Computed tomography (CT) showed multifocal pancreatic cystic lesions with a dilated main pancreatic duct and calcification of a cyst wall ([Fig. 1]), raising suspicion of a mucinous neoplasm of the pancreas.