bluuebunny/crossref_metadata_2025_split huggingface dataset:
Forkhead box protein P3 (Foxp3) expression serves as an early chronic inflammation marker of squamous cell differentiation and aggressive pathology of urothelial carcinomas in neurological patients
Authors: Phé Véronique , Rouprêt Morgan , Cussenot Olivier , Chartier‐Kastler Emmanuel , Gamé Xavier , Compérat Eva 
Published: January 2015

ObjectiveTo establish whether the expression of forkhead box protein P3 (Foxp3) provides specific diagnostic information about neurological patients with urothelial carcinoma of the bladder (UCB).Patients and MethodsUCB tissue samples from neurological patients were retrieved and compared with control samples. The expression of Foxp3 was analysed via immunohistochemistry of microarray tissue sections. The correlation between Foxp3 expression, histological parameters and tumour stage was assessed.ResultsOverall, 20 UCB tissue samples and 20 others without UCB from neurological patients, and 46 UCB tissue samples from non‐neurological patients were analysed. The distribution of pT of UCB in the neurological patients was as follows: one low‐grade pTa (5%), three high‐grade pTa (15%), three pT1(15%), one pT2(5%), seven pT3(35%) and five pT4(25%). Squamous cell differentiation was seen in nine UCB samples (45%). Foxp3 expression was detected in tumour tissues, including one pTa high grade, one pT1, one pT2, five pT3 and five pT4 tumours. Foxp3 was expressed in 11/13 muscle‐invasive tumours. All tumours displaying squamous cell differentiation expressed Foxp3. Foxp3 was not expressed in the pT3 tumours that displayed sarcomatoid and micropapillary properties. Among the bladder samples without UCB from neurological patients, no expression of Foxp3 was observed. Among the UCB samples from the non‐neurological patients, only seven displayed squamous cell differentiation. All tumours that displayed squamous cell differentiation expressed Foxp3, including one pTa high grade, four pT3 and two pT4 tumours. Other tumours displaying urothelial differentiation did not express Foxp3. The expression of Foxp3 correlated to squamous cell differentiation in neurological (P = 0.004) and non‐neurological UCB tissue (P < 0.001). In neurological, but not non‐neurological UCB tissue, the expression of Foxp3 correlated with the muscle‐invasive stage (P = 0.022).ConclusionsElevated expression of Foxp3 appears to be a characteristic of neurological patients presenting with aggressive UCB and squamous cell differentiation. Targeting Foxp3 may represent a novel strategy to improve anti‐tumour immunotherapy for UCB.
Intermediate analysis of a phase II trial assessing gemcitabine and cisplatin in locoregional or metastatic penile squamous cell carcinoma
Authors: Houédé Nadine , Dupuy Laura , Fléchon Aude , Beuzeboc Philippe , Gravis Gwenaëlle , Laguerre Brigitte , Théodore Christine , Culine Stéphane , Filleron Thomas , Chevreau Christine 
Published: January 2015

ObjectiveTo perform a phase II study evaluating a combination of gemcitabine and cisplatin in a population of patients with squamous cell carcinoma (SCC) of the penis and unresected locoregional lymph nodes and/or distant metastases, who had a poor prognosis with no standard of chemotherapy.Patients and MethodsEligible patients had histologically confirmed SCC of the penis with unresected locoregional lymph nodes and/or distant metastases, at initial diagnosis or at relapse, and measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Patients were treated with a combination of gemcitabine 1250 mg/m2 on day 1 over 30 min and cisplatin 50 mg/m2 on day 1 over 1 h, every 2 weeks. The primary endpoint was the objective response rate; secondary endpoints were time to progression (TTP) and overall survival (OS).ResultsIn all, 25 patients were included in the first phase of the study between February 2004 and January 2010 and received a median of five cycles. For the intent‐to‐treat population, two patients (95% confidence interval [CI] 0.98–26.0) presented an objective response and 13 patients (52%) had stable disease (95% CI 35.5–76.8). The median TTP was at 5.48 months (95% CI 2.40–11.73). After a median follow‐up of 26.97 months (95% CI 17.77, not reached), nine patients were still alive. The median OS and 2‐year OS rate were respectively estimated at 14.98 months (95% CI 9.76–32.9) and 39.32% (95% CI 19.15–59.03). Eleven patients had a serious adverse event (44%), 24% being relied to chemotherapy.ConclusionEvery 2 weeks' administration of the combination of gemcitabine and cisplatin showed non‐significant responses in patients with unresected locoregional or metastatic penile SCC. Despite manageable side‐effects, this combination cannot be recommended as a standard of care, due to disappointing response rates seen in this negative study. Further regimens should be explored to improve the OS of these patients with poor prognosis.
THE DETERMINANTS OF PRICE IN ONLINE AUCTIONS: MORE EVIDENCE FROM QUANTILE REGRESSION
Authors: Sun Chia‐Hung D. , Chiu Yi‐Bin , Hsu Ming‐Fei 
Published: January 2015

ABSTRACTThis study explores how seller reputations affect auction prices and concludes that earlier findings may be biased due to the misspecification of seller reputation. This paper contributes to the literature by offering significant empirical evidence using Taiwanese internet auction data. Our study reveals that the influence of seller reputations on auction prices is significant, irrespective of the assumptions of linear or non‐linear relationships with price. However, failure to consider the non‐linear setting of seller reputation leads us to underestimate the impact of reputation when the seller's reputation score is low, but overestimates it when the seller's reputation becomes high. Using quantile regression, this study finds evidence of considerable differences in their impact on auction prices that are dependent on the distribution of price levels.
Number of teeth and 5‐year mortality in an elderly population
Authors: Hirotomi Toshinobu , Yoshihara Akihiro , Ogawa Hiroshi , Miyazaki Hideo 
Published: January 2015

AbstractObjectivesSeveral epidemiological studies have shown the association between tooth loss and mortality. However, the impact of number of teeth on mortality has not yet been fully addressed in an elderly population with many teeth. Thus, the purpose of this cohort study was to assess the possible role of number of teeth as a predictor of mortality in the elderly.MethodsThe subjects included in this study were generated from a cohort study started in 1998. Oral examinations and the completion of a questionnaire were carried out. A total of 600 subjects aged 70 years were enrolled at baseline. All the subjects were in good general health and did not require any special care for their daily activities. The 5‐year mortality data were collected after the baseline survey. After excluding those with incomplete data, 569 subjects were analyzed. The Kaplan–Meier method was used to analyze survival curves and a Cox regression model to clarify the impact of the number of remaining teeth on the 5‐year mortality.ResultsDuring the follow‐up period, 25 (4.4%) subjects died. Subjects with 20 teeth or more had a significantly lower mortality rate (2.5%) than those with 19 teeth or fewer (6.1%, log‐rank test, P = 0.036). Even after adjusting for confounders including gender, BMI, serum albumin level, current smoking status, education, number of family members living together and a history of chronic diseases, the risk of all‐cause mortality was significantly associated with the number of remaining teeth (P = 0.047) with a hazard ratio of 0.96, indicating that there was a 4% point increase in the 5‐year survival rate per additional tooth retained at the age of 70.ConclusionThe findings of this study suggest that retaining more teeth might be a useful indicator for longevity of older people.
Fel d 1‐derived synthetic peptide immuno‐regulatory epitopes show a long‐term treatment effect in cat allergic subjects
Authors: Couroux P. , Patel D. , Armstrong K. , Larché M. , Hafner R. P. 
Published: January 2015

SummaryBackgroundCat‐PAD, the first in a new class of synthetic peptide immuno‐regulatory epitopes (SPIREs), was shown to significantly improve rhinoconjunctivitis symptoms in subjects with cat allergy up to 1 year after the start of a short course of treatment.ObjectiveTo evaluate the long‐term effects of Cat‐PAD on rhinoconjunctivitis symptoms following standardized allergen challenge 2 years after treatment.MethodsIn a randomized, double‐blind, placebo‐controlled, parallel group study, subjects were exposed to cat allergen in an environmental exposure chamber (EEC) before and after treatment with two regimens of Cat‐PAD (either eight doses of 3 nmol or four doses of 6 nmol) given intradermally over a 3‐month period. In this follow‐up study, changes from baseline in rhinoconjunctivitis symptoms were reassessed 2 years after the start of treatment.ResultsThe primary endpoint showed a mean reduction in total rhinoconjunctivitis symptom scores of 3.85 units in the 4 × 6 nmol Cat‐PAD group compared to placebo 2 years after the start of treatment (P = 0.13), and this difference was statistically significant in the secondary endpoint at the end of day 4 when the cumulative allergen challenge was greatest (P = 0.02). Consistent reductions in nasal symptoms of between 2 and 3 units were observed for 4 × 6 nmol Cat‐PAD compared to placebo between the 2 and 3 h time points on days 1–4 of EEC challenge at 2 years (P < 0.05). The 8 × 3 nmol dose did not show a meaningful effect in this study.Conclusion and Clinical RelevanceA persistent, clinically meaningful reduction in rhinoconjunctivitis symptoms was observed on EEC challenge 2 years after the start of a short course of treatment with 4 × 6 nmol Cat‐PAD. This study is the first to provide evidence of a long‐term therapeutic effect with this new class of SPIREs.
Children with atopic dermatitis show clinical improvement after Lactobacillus exposure
Authors: Wang I.‐J. , Wang J.‐Y. 
Published: January 2015

SummaryBackgroundThe role of probiotics in the treatment of atopic dermatitis (AD) is not clearly established. Further clinical trials with new probiotic formulations are warranted.ObjectivesTo assess the effects of Lactobacillus paracasei (LP) and Lactobacillus fermentum (LF), and their mixture on the disease severity, quality of life, and immune biomarkers of children with AD.MethodA double‐blind, prospective, randomized placebo‐controlled study was conducted on 220 children aged 1–18 years with moderate‐to‐severe AD (Trial number: NCT01635738). The children were randomized to receive LP, LF, LP + LF mixture, and placebo for 3 months. Changes in severity scoring of atopic dermatitis (SCORAD), Family Dermatology Life Quality Index (FDLQI), and Children's Dermatology Life Quality Index (CDLQI) scores in the different groups and at different visits were evaluated. Skin prick tests, levels of IgE, IFN‐γ, IL‐4, TGF‐β, and TNF‐α, and urine biomarkers were also evaluated.ResultsChildren who received LP, LF, and LP + LF mixture showed lower SCORAD scores than the placebo group (P < 0.001), and this difference remained even at 4 months after discontinuing the probiotics. The FDLQI and CDLQI scores were lower in the LP, LF, and LP + LF mixture group than in the placebo group (P = 0.02 and 0.03). IgE, TNF‐α, urine eosinophilic protein X, and 8‐OHdG levels decreased, whereas IFN‐γ and TGF‐β increased in the probiotic groups, but these did not reach statistical significance except for IL‐4 (P = 0.04). In subgroup analyses, SCORAD scores significantly decreased after probiotic treatment especially in children younger than age 12, with breastfeeding > 6 months, and with mite sensitization (P < 0.001).ConclusionSupplementation of a probiotic mixture of LP and LF is associated with clinical improvement in children with AD.
Mechanism of glutamine inhibition of cytosolic phospholipase a2 (cPLA2): Evidence of physical interaction between glutamine-Induced mitogen-activated protein kinase phosphatase-1 and cPLA2
Authors: Lee C-H , Kim H-K , Jeong J-S , Lee Y-D , Jin Z Wu , Im S-Y , Lee H-K 
Published: January 2015

Summary
Non-essential amino acid L-glutamine (Gln) possesses anti-inflammatory activity via deactivating cytosolic phospholipase A2 (cPLA2). We showed previously that Gln deactivated cPLA2 indirectly via dephosphorylating p38 mitogen-activated protein kinase (MAPK), the major kinase for cPLA2 phosphorylation, through inducing MAPK phosphatase-1 (MKP-1). In this study, we investigated the precise mechanism underlying Gln deactivation of cPLA2. In lipopolysaccharide (LPS)-treated mice, Gln injection resulted in dephosphorylation of phosphorylated cPLA2 (p-cPLA2), which coincided with rapid Gln induction of MKP-1. MKP-1 small interfering RNA (siRNA) abrogated the ability of Gln to induce MKP-1 as well as the dephosphorylation of cPLA2. Co-immunoprecipitation and in-situ proximity ligation assay revealed a physical interaction between MKP-1 and p-cPLA2. In a murine model of allergic asthma, we also demonstrated the physical interaction between MKP-1 and p-cPLA2. Furthermore, Gln suppressed various allergic asthma phenotypes, such as neutrophil and eosinophil recruitments into the airway, airway levels of T helper type 2 (Th2) cytokines [interleukin (IL)-4, IL-5 and IL-13], airway hyperresponsiveness, mucin production and metabolites (leukotriene B4 and platelet-activating factor) through inhibiting cPLA2 in a MKP-1-dependent manner. These data suggest that MKP-1 uses cPLA2, in addition to p38, as a substrate, which further potentiates the anti-inflammatory action of Gln.
Indolamine 2,3-dioxygenase expression by monocytes and dendritic cell populations in hepatitis C patients
Authors: Schulz S , Landi A , Garg R , Wilson J A , van Drunen Littel-van den Hurk S 
Published: January 2015

Summary
Dendritic cells (DCs) play an important role in the induction of the primary immune response to infection. DCs may express the tryptophan-catabolizing enzyme indolamine2,3-dioxygenase (IDO), which is an inducer of immune tolerance. Because there is evidence that chronic hepatitis C virus (HCV) infection leads to functional impairment of certain DC populations, we analysed IDO expression in DCs and monocytes from chronically infected and recovered HCV patients. The IDO1 and -2 expression was increased significantly in the monocytes of chronic HCV patients but, interestingly, not in those from recovered patients. The myeloid DCs from chronically infected HCV patients also showed enhanced IDO1 expression, while no change in either IDO1 or -2 was found for plasmacytoid DCs. Up-regulation of IDO1 gene expression was confirmed by the presence of enhanced kynurenine/tryptophan ratios in the plasma from chronic HCV patients. Increased IDO1 and -2 expression was also observed in monocytes from healthy donors infected with an adapted mutant of the HCV JFH-1 strain ex vivo, confirming a direct effect of HCV infection. These changes in IDO expression could be prevented by treatment with the IDO inhibitor 1-methyl tryptophan (1-mT). Furthermore, maturation of monocyte-derived DCs from chronically infected HCV patients, as well as well as monocyte-derived DCs infected ex vivo with HCV, was impaired, but this was reversed by 1-mT treatment. This suggests that IDO inhibitors may be used to treat chronic HCV patients in vivo, in conjunction with current therapies, or to activate DCs from patients ex vivo, such that they can be administered back as a DC-based therapeutic vaccine.
Gender bias in lupus: does immune response initiated in the gut mucosa have a role?
Authors: Gaudreau M-C , Johnson B M , Gudi R , Al-Gadban M M , Vasu C 
Published: January 2015

SummaryThe risk of developing systemic lupus erythematosus (SLE) is approximately nine times higher among women compared to men. However, very little is understood concerning the underlying mechanisms that contribute to this gender bias. Further, whether there is a link between immune response initiated in the gut mucosa, the progression of SLE and the associated gender bias has never been investigated. In this report, we show a potential link between the immune response of the gut mucosa and SLE and the gender bias of lupus for the first time, to our knowledge. Both plasma cell- and gut-imprinted- α4β7 T cell frequencies were significantly higher in the spleen and gut mucosa of female (SWR × NZB)F1 (SNF1) mice compared to that of their male counterparts. Importantly, female SNF1 mice not only showed profoundly higher CD45+ immune cell densities, but also carried large numbers of interleukin (IL)-17-, IL-22- and IL-9-producing cells in the lamina propria (LP) compared to their male counterparts. Intestinal mucosa of female SNF1 mice expressed higher levels of a large array of proinflammatory molecules, including type 1 interferons and Toll-like receptors 7 and 8 (TLR-7 and TLR-8), even before puberty. Our work, therefore, indicates that the gut immune system may play a role in the initiation and progression of disease in SLE and the associated gender bias.
Ligation‐assisted endoscopic enucleation for the treatment of colorectal submucosal tumours originating in the muscularis propria
Authors: Guo J. , Wang S. , Liu Z. , Sun S. , Liu X. , Wang S. , Ge N. , Wang G. 
Published: January 2015

AbstractAimA ligation‐assisted endoscopic enucleation (EE‐L) technique was developed and was evaluated to determine its efficacy and safety for treating colorectal submucosal tumours (< 10 mm) originating in the muscularis propria.MethodEE‐L was used to treat 13 patients between January 2011 and January 2014. The tumour was sucked into a transparent cap and ligated at its base by a rubber band ligature attached to the tip of the endoscope. With the creation of a pseudo‐stalk, the tumour was then enucleated using endoscopic dissection and the wound was closed with clips.ResultsAll tumours [median diameter 6.8 (4–10) mm] were successfully enucleated [procedure time 19 (11–27) min]. Histopathological examination identified 11 (84.6%) to be leiomyoma and 2 (15.4%) low‐risk gastrointestinal stromal tumours. No perforations or massive haemorrhage occurred and there were no recurrences during a follow‐up of 3–39 months.ConclusionEE‐L is a successful technique for the removal of small colorectal tumours in the muscularis propria with few complications and enables a histopathological diagnosis. In this study, all the resected lesions had a benign pathology.
The technique of sacral nerve modulation
Authors: Martellucci J. 
Published: January 2015

AbstractAimThe aim of this review was to summarize current knowledge and recommendations regarding the technique of implantation of the electrode in performing sacroneuromodulation (SNM) and the available information on programming parameters and implantation algorithms.MethodAll English‐language articles published from January 1985 to December 2013 that reported the SNM surgical technique and results were considered for inclusion. Data were considered useful for the present review only if related to: (i) peripheral nerve evaluation; (ii) temporary nerve stimulation; (iii) definitive impulse generator placement; and (iv) parameters programming.ResultsThe literature search revealed 193 potentially relevant studies from initial electronic search terms and eligibility criteria, and these studies were evaluated in detail. In total, 41 studies were included in the final analysis. Of the studies reviewed, the majority (n = 37) were prospective or retrospective case series. Only three randomized clinical trials were eligible for inclusion.ConclusionAlthough the technique seems to be standardized, several steps still need to be clarified in order to define the best way to perform the procedure and then to maximize the outcome.
Regional, age and sex differences in baseline characteristics of patients enrolled in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS)
Authors: Bethel M. A. , Green J. B. , Milton J. , Tajar A. , Engel S. S. , Califf R. M. , Holman R. R. ,   on behalf of the TECOS Executive Committee
Published: January 2015

AimsTo report baseline characteristics and cardiovascular (CV) risk management by region, age, sex and CV event type for 14 724 participants in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), a randomized, double‐blind, placebo‐controlled trial exploring whether sitagliptin added to usual type 2 diabetes (T2DM) care affects time to first event in the composite endpoint of CV death, non‐fatal myocardial infarction (MI), non‐fatal stroke or unstable angina hospitalization.MethodsTECOS enrolled patients aged ≥50 years, with T2DM and CV disease from 38 countries in five regions: North America, Eastern Europe, Western Europe, Asia Pacific and Latin America. Participants had a glycated haemoglobin concentration of 6.5–8.0% (48–64 mmol/mol) and were receiving oral and/or insulin‐based antihyperglycaemic therapy. Analysis of variance or logistic regression was used to compare regional CV risk factors and treatments, referenced to North America.ResultsPatients had a mean [1 standard deviation (SD)] age of 66 (8) years, a median (interquartile range) diabetes duration of 9.4 (4.9, 15.3) years, and a mean (SD) body mass index 30.2 (5.7) kg/m2. Compared with North America, blood pressure and lipids were higher in all regions. Statin use was lowest in Latin America (68%) and Eastern Europe (70%) and aspirin use was lower compared with North America in all regions except Asia Pacific. Achievement of treatment targets did not differ by age group or insulin usage, but men and participants with previous MI were more likely than women or those with previous stroke or peripheral arterial disease to reach most treatment goals.ConclusionThe CV risk factors of participants in TECOS are reasonably controlled, but differences in CV risk management according to region, sex and history of disease exist. This diversity will enhance the generalizability of the trial results.
Self‐reported activity and functioning in daily life; the perspective of persons with haemophilia living in Sweden
Authors: Brodin Elisabeth , Baghaei Fariba , Sunnerhagen Katharina S. 
Published: January 2015

AbstractObjectivesTo investigate the self‐estimated function, activity and participation in daily life of persons with severe or moderate haemophilia A and B (PWH) living in Sweden. The secondary aim was to explore the differences between participants with early treatment onset and later.MethodsThe Haemophilia Activity List (HAL), Arthritis Impact Measurement Scales (AIMS2) and Impact on Participation and Autonomy (IPA‐S) were distributed by mail to 225 PWH with an invitation to participate in the study. The median and min–max are given for the different domains; a higher value indicates more disability.ResultsEighty‐four PWH (18–80 years) participated. The HAL indicated more problems in the legs [40 (0–100)] than in self‐care [4 (0–92)] and household tasks [3 (0–87)]. The AIMS2 scores confirmed this (physical activity 12 (0–64.5) as well as somewhat reduced autonomy outdoors [IPA‐S 17.5 (0–90)]. More limitations in daily life were reported by participants with later treatment onset.ConclusionThe PWH reported greater disability in the domains related to activities using the lower extremities compared to domains related to upper extremity. This study pointed out the need of using different questionnaires to capture patients own perspective and as useful supplement to other clinical assessment instruments.