tbuckley/cabot-search huggingface dataset:
Metastasis-Free Survival Is a Strong Surrogate of Overall Survival in Localized Prostate Cancer
Authors: Wanling Xie, Meredith M. Regan, Marc Buyse, Susan Halabi, Philip W. Kantoff, Oliver Sartor, Howard Soule, Noel W. Clarke, Laurence Collette, James J. Dignam, Karim Fizazi, Wendy R. Paruleker, Howard M. Sandler, Matthew R. Sydes, Bertrand Tombal, Scott G. Williams, Christopher J. Sweeney
Journal: Journal of Clinical Oncology (2017)

Purpose Adjuvant therapy for intermediate-risk and high-risk localized prostate cancer decreases the number of deaths from this disease. Surrogates for overall survival (OS) could expedite the evaluation of new adjuvant therapies. Methods By June 2013, 102 completed or ongoing randomized trials were identified and individual patient data were collected from 28 trials with 28,905 patients. Disease-free survival (DFS) and metastasis-free survival (MFS) were determined for 21,140 patients from 24 trials and 12,712 patients from 19 trials, respectively. We evaluated the surrogacy of DFS and MFS for OS by using a two-stage meta-analytic validation model by determining the correlation of an intermediate clinical end point with OS and the correlation of treatment effects on both the intermediate clinical end point and OS. Results Trials enrolled patients from 1987 to 2011. After a median follow-up of 10 years, 45% of 21,140 men and 45% of 12,712 men experienced a DFS and MFS event, respectively. For DFS and MFS, 61% and 90% of the patients, respectively, were from radiation trials, and 63% and 66%, respectively, had high-risk disease. At the patient level, Kendall’s τ correlation with OS was 0.85 and 0.91 for DFS and MFS, respectively. At the trial level, R 2 was 0.86 (95% CI, 0.78 to 0.90) and 0.83 (95% CI, 0.71 to 0.88) from weighted linear regression of 8-year OS rates versus 5-year DFS and MFS rates, respectively. Treatment effects—measured by log hazard ratios—for the surrogates and OS were well correlated ( R 2 , 0.73 [95% CI, 0.53 to 0.82] for DFS and 0.92 [95% CI, 0.81 to 0.95] for MFS). Conclusion MFS is a strong surrogate for OS for localized prostate cancer that is associated with a significant risk of death from prostate cancer.
A Population-Based Study of Abdominal Aortic Aneurysm Treatment in Finland 2000 to 2014
Authors: Matti T. Laine, Sani J. Laukontaus, Reijo Sund, Pekka S. Aho, Ilkka Kantonen, Anders Albäck, Maarit Venermo
Journal: Circulation (2017)

Background: In the event of rupture of an abdominal aortic aneurysm (AAA), mortality is very high. AAA prevalence and incidence of ruptures have been reported to be decreasing. The treatment of AAA has also undergone a change in recent decades with a shift toward endovascular aneurysm repair (EVAR). Our aim was to evaluate how these changes have affected the elective and emergency treatment of AAA and their results in Finland. Methods: All patients treated for AAA in Finland, a country with a population of 5.5 million, during 2000 to 2014 were searched from the registry of the Finnish Institute for Health and Welfare. Data on all patients who had died of AAA during the same time period were obtained from Statistics Finland. The data were combined and analyzed. Results: The annual incidence of ruptured AAA was 16.4 per 100 000 population over 50 years and decreased significantly during the study period. Over half of the 4949 patients who had a ruptured AAA died outside the hospital. Thirty-day mortality after emergency repair was 39.4%. Intact AAA repairs numbered 4956. The absolute number of annual repairs increased during the study period, and the use of EVAR became the dominant method of elective repair. Thirty-day mortality in elective AAA repair dropped significantly from 6.3% in 2000 to 2004 to 2.7% in 2010 to 2014 mostly because of the increased number of EVAR procedures with lower mortality. Long-term mortality in patients treated with EVAR was higher than in patients treated with open repair. Mortality after elective AAA repair was primarily attributable to cardiovascular causes, but there was a slightly higher proportion of AAA-related late deaths in patients treated with EVAR. Conclusions: Ruptured AAA incidence for men &gt;65 years has declined by nearly 30% in Finland, likely because of the decrease in AAA prevalence. The treatment results have improved as well for both elective and emergency repair. Increased use of EVAR has resulted in a decrease of mortality after elective AAA repair, but results of open repair have improved as well. However, late mortality from elective EVAR is surprisingly high in comparison with open repair, which may have been exaggerated by patient selection.
PTU-036 Are lead coats worn at ercp seeded by bacteria? a novel study
Authors: R Nathwani, E Hoy, FA El-Kariem, R Mead, S Greenfield
Journal: Gut (2017)

Introduction  A 2015 report highlighted potential for transmission of infection with duodenoscopes. Another publication (Endoscopy (2015) 47 493–502) described an outbreak of VIM-2 producing Pseudomonas aeruginosa and carbapenem-resistant Enterobacteriaceae (CRE). The Centre for Disease Control, USA reported that exposure to duodenoscopes was associated with transmission of CRE through bile. At ERCP bile leaks from the scope onto clothing worn. No studies have looked at bacterial seeding from the duodenoscope to protective clothing, which may increase risk of patient-to-patient transmission. Current practice at our unit does not involve sterilisation of protective clothing between procedures or after. At their discretion, staff may wear plastic aprons over a lead apron which is then discarded.  Aim  Our unique study investigated whether ERCP was associated with bacterial seeding from duodenoscope to protective lead or plastic aprons.  Method  30 lead or plastic aprons worn by doctors carrying out ERCP between August-September 2016 were swabbed. Swabs were taken for routine culture and microscopy, CRE and pseudomonas from the chest, abdominal and pelvic regions. Swabs were taken pre and post ERCP from the outermost layer ie the lead or plastic apron. Doctors wore the same identifiable coat at each list.  Results  78 swabs were collected. 33/78 from plastic aprons, 44/78 from lead aprons and 1/78 unidentifiable. 25/78 from the chest, 28/78 abdominal and 22/78 pelvic. 3/78 swabs unlabelled. Only 16/78 grew no organism. Organisms grown included:  33/62 were non-pathogenic skin organisms: skin flora, Coag negative staphylococcus, Diphtheroids, Micrococcus and Massilia Timoniae. 11/62 were environmental contaminants: Acinetobacter, Arthrobacter, Bacillus species, Microbacterium, Moraxella. The remaining 18 isolates (highlighted above) grew Coliforms and Pseudomonas which may have originated from bile or small bowel equally distributed on lead and plastic aprons. Swabs from 28/33 plastic aprons grew organisms as did 33/44 from lead.  Conclusion  This study highlights that ERCP carries a considerable risk of bacterial seeding from the scope to lead coats which may transmit infection to patients, a significant safety concern. Additional barrier protection with plastic aprons worn over the lead may reduce risk of transmission providing the plastic is discarded after each case. We believe lead aprons must be thoroughly decontaminated at the end of a list. We have informed our infection control.  Disclosure of Interest  None Declared
THE USE AND MODIFICATION OF INJURY PREVENTION EXERCISES BY PROFESSIONAL YOUTH SOCCER TEAMS
Authors: James O'Brien, Warrren Young, Caroline Finch
Journal: British Journal of Sports Medicine (2017)

Background The efficacy of injury prevention exercise programs (IPEPs) for amateur youth soccer has been established, but little is known about their adaptability to other soccer populations. Objective This study aimed to assess the use of individual injury prevention exercises by professional youth soccer teams, against the industry-standard, FIFA 11+ program. Design Prospective observational study. Setting A European professional youth soccer academy. Participants Soccer coaches, fitness coaches and physiotherapists (n=18) from four teams. Data collection The teams' chosen IPEPs (total 160 sessions) were observed across one season and documented on a standardized form. The use of each FIFA 11+ exercise was coded as “performed” (in its original form), “performed modified” or “not performed”. Main Outcome Measurements The primary outcome measure was the proportion of the 160 observed sessions containing each individual exercise in original or modified forms. The secondary outcome measure was the staff members' reasons for using and modifying FIFA 11+ exercises. Results On average, individual FIFA 11+ exercises were conducted in original form in 12% of the sessions (range 0–33%), and in modified form in 28% of sessions (range 2–62%). The five most frequently observed exercises, in either original or modified form, were “bench” (72%), “squats” (69%),“running straight” (68%), “single-leg stance” (66%), and “sideways bench” (64%). Staff modified exercises to add variation, progression, and individualization, and to align with specific training formats and goals. Conclusions Professional youth soccer teams often use injury prevention exercises similar to those in the FIFA 11+, but tailor them considerably to fit their implementation context. These findings will inform the design and delivery of future, context-specific IPEPs.
つかまえどころのない内因性脂肪細胞PPARγアゴニスト:ライニング容疑者【Powered by NICT】
Authors: Hallenborg Philip, K Petersen Rasmus, Kouskoumvekaki Irene, W Newman John, Madsen Lise, Kristiansen Karsten
Journal: Progress in Lipid Research (2016)
Africa's medical brain drain
Authors: Joseph N Ana
Journal: BMJ (2005)

A theme issue by, for, and about Africa Results from Ugandan programme preventing maternal transmission of HIVEditor-Since the efficacy of antiretroviral drugs in preventing HIV transmission from mother to child was first shown, much effort has been devoted in many countries in Africa to implement sustainable regimens. [1]2][3][4] To identify potential reasons affecting uptake we evaluated the five year performance of a programme at St Francis Hospital Nsambya in Kampala, Uganda.The programme included voluntary counselling and confidential HIV testing for pregnant women and administration of antiretroviral prophylaxis in the peripartum period (zidovudine or nevirapine) for HIV positive women.Overall 24 133 women received counselling, 76% (18 384) agreed to be tested, and 2011 (10.9%) were HIV positive; 1341 (66.7% of the HIV positive women) were enrolled in the programme and received antiretroviral drugs.Acceptance of the test increased from 72.7% (9103/12 524) in 2000-2 to 79.9% (9281/11 609) in 2003-4, when a drug access programme became available in the hospital.Acceptance of the test and enrolment in the programme were lower in married or cohabitating women (test acceptance rate 72.9% (7735/10 605)) than single women (78% (860/1106)), indicating that the fear of being identified as HIV positive in the family is still a strong limiting factor and that men could have an important role.Acceptance of the test was lower in women belonging to the local tribe in Kampala (Baganda), probably because of fear of being recognised by hospital health workers.Higher education was associated with a lower prevalence of HIV and a higher enrolment in the programme, confirming that education can have a key role not only in protecting against HIV but also in allowing HIV positive people to benefit from existing measures against the spread of HIV.
粘土ナノ粒子ゲルによる局在化によるBMPの生理的用量での骨誘導【Powered by NICT】
Authors: Gibbs D.M.R., Black C.R.M., G Hulsart-Billstrom, P Shi, E Scarpa, Oreffo R.O.C., J I Dawson
Journal: Biomaterials (2016)
Soluble CD40-ligand levels are associated with vascular superoxide production and eNOS coupling in human vessels: Interrelationships with homocysteine biosynthetic pathway
Authors: C A Antoniades, C Shirodaria, P Leeson, O Baarholm, A Antonopoulos, R Pillai, C Ratnatunga, D Tousoulis, H Refsum, C Stefanadis, K M Channon
Journal: Journal of the American College of Cardiology (2008)
Local dornase alfa treatment reduces NETs-induced airway obstruction during severe RSV infection
Authors: Bart Cortjens, Rineke de Jong, Judith G Bonsing, Job B M van Woensel, Adriaan F G Antonis, Reinout A Bem
Journal: Thorax (2017)

Respiratory syncytial virus (RSV) infection is characterised by airway obstruction with mucus plugs, containing DNA networks in the form of neutrophil extracellular traps (NETs). We investigated the effect of dornase alfa on histopathological NETs-induced airway obstruction and viral load in an age-relevant calf model of severe bovine RSV disease. As compared with the control animals, dornase alfa treatment resulted in a strong reduction of NETs-induced airway obstruction. Viral load in the lower respiratory tract was not different between the two groups. We conclude that NETs form a relevant target for treatment of airway obstruction in severe RSV disease.
PTPN2 regulates T cell lineage commitment and αβ versus γδ specification
Authors: Florian Wiede, Jarrod A. Dudakov, Kun-Hui Lu, Garron T. Dodd, Tariq Butt, Dale I. Godfrey, Andreas Strasser, Richard L. Boyd, Tony Tiganis
Journal: The Journal of Experimental Medicine (2017)

In the thymus, hematopoietic progenitors commit to the T cell lineage and undergo sequential differentiation to generate diverse T cell subsets, including major histocompatibility complex (MHC)-restricted αβ T cell receptor (TCR) T cells and non-MHC-restricted γδ TCR T cells. The factors controlling precursor commitment and their subsequent maturation and specification into αβ TCR versus γδ TCR T cells remain unclear. Here, we show that the tyrosine phosphatase PTPN2 attenuates STAT5 (signal transducer and activator of transcription 5) signaling to regulate T cell lineage commitment and SRC family kinase LCK and STAT5 signaling to regulate αβ TCR versus γδ TCR T cell development. Our findings identify PTPN2 as an important regulator of critical checkpoints that dictate the commitment of multipotent precursors to the T cell lineage and their subsequent maturation into αβ TCR or γδ TCR T cells.
DEVELOPMENT OF A SKIN CANCER PREVENTION PROGRAMM FOR OUTDOOR ATHLETS
Authors: Nina Nachtigall
Journal: British Journal of Sports Medicine (2017)

Background Melanoma and non- melanoma skin cancer show the highest increase of any form of cancer during the last 20 years. Objective We wanted to know if we could find an increased rate of skin cancer precursors (actinic keratosis) in outdoor sportsmen. Design Setting and Patients 900 patients with actinic keratosis (age 35–75) were investigated in their outdoor sport behaviour. Corresponding to the sport ( where, when, how long) we calculated the cumulative dose of sun with “UV Index hours”. The kind of tumor and tumor precursors were counted and the skin damage characterized with a confocal laser microscope. A healthy aged group was used for statistical analysis. Results 27 different outdoor sports were found in our groups of patients. Watersport and skiing are known for a higher sun exposure, but only a few patients without statistical significance to the control collective were detected. But, in contrast, we found a 8.5 fold increased risk of skin cancer among golfers. Conclusions We were able to give another hint for the relation of skin cancer development and the higher increase in outdoor sportsmen. From these data we developed in the UIPM for the athletes a "skin tumor prevention program". With this program the individual risk and the individual damage is analysed based on the cumulative UV-Dose of training and competition. Athletes, trainers and officials should be more sensitized in skin cancer prevention.
APRIN, a highly expressed gene in the brain and reproductive tissues is silenced in malignancies of the breast, prostate and ovary
Authors: Peter Geck, Viktoria Denes
Journal: Cancer Research (2006)

431   Background. Differentiation programs are hormonally regulated in the reproductive tissues and appear to fail in cancer. We searched for the genetic elements involved and found a novel hormone-induced differentiation factor APRIN, which was mapped on chromosome 13, next to BRCA2. Deletions (loss of heterozygosity) in the BRCA2 region in prostate, breast, ovarian and other cancers indicated a cryptic suppressor gene in the APRIN area. Objective. Deletions targeting the APRIN gene may indicate that the loss of APRIN is a critical factor in cancer progression. The objective of the present work is to investigate this hypothesis. Based on our previous studies, we extended our analysis of APRIN expression in reproductive cancers and analyzed the genetic and epigenetic mechanisms of silencing. Methods. We used clinical samples from invasive ductal breast adenocarcinomas, prostate adenocarcinomas and ovarian cancer to assess APRIN expression. Our immunohistochemistry results were compared with microarray and SAGE data. We also analyzed APRIN expression in vitro, in cell lines from reproductive cancers. In samples where APRIN expression was absent, we performed both genetic and epigenetic analyses to study the molecular mechanisms. In the extensive CpG island of the APRIN promoter methylation can repress promoter activity. We performed promoter methylation studies using various techniques and innovative applications. R e s u l t s. Our data indicated downregulation or silencing of APRIN expression in up to 90% of the clinical samples we analyzed. In contrast, in normal tissues in the same samples and in control biopsies APRIN was highly expressed. Microarray and SAGE data were also consistent with our immuno-histochemistry results and showed that in most breast and ovarian cancer cell lines APRIN was lost or downregulated. In prostate adenocarcinomas, however, APRIN losses were less manifest and showed clonal morphology. We found DNA methylation in the APRIN promoter in samples where APRIN was silenced. Conclusions. APRIN, a conserved chromatin factor is highly expressed in the nervous and reproductive systems. We showed that it is a mediator in hormonally regulated differentiation in reproductive organs. We also showed that early on in the oncogenic process, the loss of APRIN expression contributes to reproductive and other malignancies through epigenetic mechanisms. Our results will help to establish novel epigenetic markers in early diagnosis and prognosis.
PTH-021 A novel scissor and loop technique for endoscopic resection and closure of esd defects: resection of gastric submucosal tumour
Authors: K Kandiah, S Subramaniam, D Poller, A Higginson, P Bhandari
Journal: Endoscopy (2017)

<h3>Introduction</h3> Endoscopic submucosal dissection (ESD) is a technique developed in Japan to enable curative en-bloc resection of early gastrointestinal neoplasia. This technique has been slow to be adopted in the West due to the lack of training, endoscopic knives requiring significant manual dexterity and a high rate of complications. Efforts have been made to improve training but until recently, there have been few advances improving endoscopic knife technology and the development of devices to reduce complications. We present a video demonstrating the utility of a novel scissor-type knife which can potentially make ESD accessible to Western endoscopists and the use of a novel large defect ligation device. <h3>Method</h3> Various types of endoscopic knives (eg. insulated tip,hook,triangular,needle) have traditionally been used in ESD. The scissor-type knife was developed to facilitate the accurate grasping of tissue prior to dissection. The outer segment of the scissor arms are insulated and the inner segment of the arms have thin cutting blades for dissection. This knife is rotatable, thereby enabling dissection of difficult to access tissue. The novel large defect ligating loop device is a detachable plastic endoloop which can be dropped freely into the lumen. This is then caught and easily clipped along the edges of the defect. Finally the loop closure device can be reattached to the loop and ligate the defect. <h3>Results</h3> A 72-year-old man was found to have a large SM tumour in the upper body (lesser curve) of his stomach. Assessment with enhanced endoscopic imaging showed normal gastric mucosa surface pattern. Endoscopic ultrasound showed that the lesion was of submucosa in origin. The case was discussed in the Upper GI MDT. A scissor-type knife enabled controlled mucosal incision and SM dissection even on retroflexion. Haemostasis was maintained using the scissor type knife, which is able to carry out the function of a haemostatic forceps, negating the need to change instruments during the procedure. The large resection defect was closed using a novel ligating device that is approximated like a purse string. There were no immediate or late complications. The patient was routinely discharged home the next morning. <h3>Conclusion</h3> Novel scissor-type knives are technically easy to use even when the access is challenging. This type of knife can perform mucosal incision, SM dissection and maintain haemostasis effectively. A detachable large defect ligator can effectively close large ESD defects. Both novel devices have the potential to help facilitate the uptake of ESD in the West. <h3>Disclosure of Interest</h3> K. Kandiah: None Declared, S Subramaniam: None Declared, D Poller: None Declared, A Higginson: None Declared, P Bhandari Conflict with: Receives educational grants from Fujifilm, Olympus and Pentax
Kindlin-2 Association with Rho GDP-Dissociation Inhibitor α Suppresses Rac1 Activation and Podocyte Injury
Authors: Ying Sun, Chen Guo, Ping Ma, Yumei Lai, Fan Yang, Jun Cai, Zhehao Cheng, Kuo Zhang, Zhongzhen Liu, Yeteng Tian, Yue Sheng, Ruijun Tian, Yi Deng, Guozhi Xiao, Chuanyue Wu
Journal: Journal of the American Society of Nephrology (2017)

Alteration of podocyte behavior is critically involved in the development and progression of many forms of human glomerular diseases. The molecular mechanisms that control podocyte behavior, however, are not well understood. Here, we investigated the role of Kindlin-2, a component of cell-matrix adhesions, in podocyte behavior in vivo . Ablation of Kindlin-2 in podocytes resulted in alteration of actin cytoskeletal organization, reduction of the levels of slit diaphragm proteins, effacement of podocyte foot processes, and ultimately massive proteinuria and death due to kidney failure. Through proteomic analyses and in vitro coimmunoprecipitation experiments, we identified Rho GDP-dissociation inhibitor α (RhoGDI α ) as a Kindlin-2–associated protein. Loss of Kindlin-2 in podocytes significantly reduced the expression of RhoGDI α and resulted in the dissociation of Rac1 from RhoGDI α , leading to Rac1 hyperactivation and increased motility of podocytes. Inhibition of Rac1 activation effectively suppressed podocyte motility and alleviated the podocyte defects and proteinuria induced by the loss of Kindlin-2 in vivo . Our results identify a novel Kindlin-2–RhoGDI α –Rac1 signaling axis that is critical for regulation of podocyte structure and function in vivo and provide evidence that it may serve as a useful target for therapeutic control of podocyte injury and associated glomerular diseases.