bluuebunny/crossref_metadata_2025_split huggingface dataset:
BAX and BCL‐2 polymorphisms, as predictors of proliferative vitreoretinopathy development in patients suffering retinal detachment: the Retina 4 project
Authors: Pastor‐Idoate Salvador , Rodríguez‐Hernández Irene , Rojas Jimena , Fernández Itziar , García‐Gutierrez María‐Teresa , Ruiz‐Moreno Jose M. , Rocha‐Sousa Amandio , Ramkissoon Yashin D. , Harsum Steven , MacLaren Robert E. , Charteris David G. , Van Meurs Jan C. , González‐Sarmiento Rogelio , Pastor Jose C. ,   the Genetics on PVR Study Group
Published: May 2015

AbstractPurposeTo compare the distribution of BCL‐2 ‐938C>A (rs2279115) and BAX ‐248G>A (rs4645878) genotypes among European subjects undergoing rhegmatogenous retinal detachment (RRD) surgery in relation to the further development of proliferative vitreoretinopathy (PVR).MethodsA case–control gene association study, as a part of Retina 4 project, was designed. rs2279115 and rs4645878 polymorphisms were analysed in 555 samples from patients with RRD (134 with PVR secondary to surgery). Proportions of genotypes and AA homozygous groups of BCL‐2 and BAX polymorphisms between subsamples were analysed in two phases. Genotypic and allelic frequencies were compared in global sample and in subsamples.ResultsBAX: Differences were observed in the genotype frequencies and in AA carriers between controls and cases in the global series. The odds ratio (OR) of A carriers in the global sample was 1.7 (95% CI: 1.23–2.51). Proportions of genotypes in Spain + Portugal were significant different. The OR of A carriers from Spain and Portugal was 1.8 (95% CI: 1.11–2.95). BCL‐2: No significant differences were observed in genotype frequencies. However, proportions of genotypes in Spain + Portugal were significant. A protective effect (OR: 0.6 95% CI: 0.43–0.96) was found in A carriers from Spain and Portugal.ConclusionsResults suggest that A allele of rs4645878 could be a biomarker of high risk of developing PVR in patients undergoing RD surgery. The possible role of BCL‐2 (inhibitor of necroptosis pathway) as a possible new target in PVR prophylaxis should be investigated.
Basophil activation by mosquito extracts in patients with hypersensitivity to mosquito bites
Authors: Sakakibara Yasuhisa , Wada Taizo , Muraoka Masahiro , Matsuda Yusuke , Toma Tomoko , Yachie Akihiro 
Published: May 2015

Hypersensitivity to mosquito bites (HMB) is a cutaneous disorder belonging to the group of Epstein–Barr virus (EBV)‐associated T/natural killer (NK)‐cell lymphoproliferative diseases, and is primarily mediated by EBV‐infected NK cells. It is characterized by intense local skin reactions accompanied by general symptoms after mosquito bites, and infiltration of EBV‐infected NK cells into the bite sites. However, the mechanisms underlying these reactions have not been fully examined. We recently described the activation of circulating basophils by mosquito extracts in vitro in a patient with HMB. To further investigate this finding, we studied four additional patients with HMB. All patients showed typical clinical features of HMB after mosquito bites and they had NK lymphocytosis and high peripheral blood EBV DNA loads. We found evidence of EBV infection in NK cells through in situ hybridization that detected EBV‐encoded small RNA‐1, and flow cytometry showed HLA‐DR expression on almost all NK cells. Basophil activation tests with the extracts of epidemic mosquitoes Culex pipiens pallens and Aedes albopictus showed positive responses to one or both extracts in all samples from patients with HMB, suggesting the presence of mosquito antigen‐specific IgE and its binding to basophils. In particular, the extract of Aedes albopictus was able to activate basophils in all available patient samples. These results indicate that basophils and/or mast cells activated by mosquito bites may be involved in initiation and development of severe skin reactions to mosquito bites in HMB.
Cooperatively transcriptional and epigenetic regulation of sonic hedgehog overexpression drives malignant potential of breast cancer
Authors: Duan Zhao‐Heng , Wang Hao‐Chuan , Zhao Dong‐Mei , Ji Xiao‐Xin , Song Min , Yang Xiao‐Jun , Cui Wei 
Published: May 2015

Sonic hedgehog (Shh), a ligand of Hedgehog signaling pathway, is considered an important oncogene and an exciting potential therapeutic target in several cancers. Comprehensive understanding of the regulation mechanism of Shh in cancer cells is necessary to find an effective approach to selectively block its tumorigenic function. We and others previously demonstrated that nuclear factor‐kappa B (NF‐κB) activation and promoter hypomethylation contributed to the overexpression of Shh. However, the relationship between transcriptional and epigenetic regulation of Shh, and their roles in the malignant phenotype of cancer cells are still not clearly elucidated. In the present study, our data showed that the level of Shh was higher in breast cancer tissues with positive NF‐κB nuclear staining and promoter hypomethylation. In addition, survival analysis revealed that Shh overexpression, but not hypomethylation and NF‐κB nuclear staining, was a poor prognosis indicator for breast cancers. Moreover, in vitro data demonstrated that both NF‐κB activation and hypomethylation in promoter region were positively associated with the overexpression of Shh. Mechanistically, the hypomethylation in Shh promoter could facilitate NF‐κB binding to its site, and subsequently cooperate to induce transcription of Shh. Furthermore, the biological function data indicated that overexpressed Shh enhanced the self‐renewal capacity and migration ability of breast cancer cells, which could be augmented by promoter demethylation and NF‐κB activation. Overall, our findings reveal multiple and cooperative mechanisms of Shh upregulation in cancer cells, and the roles of Shh in tumor malignant behavior, thus suggesting a new strategy for therapeutic interventions to reduce Shh in tumors and improve patients’ prognosis.
Associations between metabolomic‐identified changes of biomarkers and arterial stiffness in subjects progressing to impaired fasting glucose
Authors: Jung Saem , Kim Minjoo , Lee Young Ju , Lee Sang‐Hyun , Lee Jong Ho 
Published: May 2015

SummaryObjectiveWe investigated correlations between age‐related changes in circulating metabolites and arterial stiffness in impaired fasting glucose (IFG).Design, subjects, measurementThis prospective cohort study included 602 healthy, normal fasting glucose (NFG) subjects (30–65 years old) who underwent triennial medical evaluation. After 3 years, 9·3% of subjects developed IFG (n = 56). Age, gender, BMI and fasting glucose were used to match the remaining NFG subjects (n = 546) that were included for the control group (NFG group, n = 80).ResultsAfter 3 years, levels of fasting glucose, insulin and malondialdehyde, and brachial–ankle pulse wave velocity (baPWV) were significantly greater in the IFG group than in the NFG group after adjusting for baseline values. The IFG group had a greater increase in lactosylceramide (P = 0·001, q < 0·05) and a greater reduction in phosphatidylcholine (PC) (18:0/20:4) than the NFG group. Multiple linear regression analysis showed that the change in baPWV was independently and positively associated with changes in fasting glucose and lactosylceramide. In all subjects, lactosylceramide levels positively correlated with changes in baPWV and fasting glucose, while premenopausal women were not shown, and negatively correlated with changes in PC and LDL particle size.ConclusionsThis study indicates that age‐related increase in circulating lactosylceramide is an independent predictor of increased arterial stiffness in subjects with impaired fasting glucose.
Association between salivary amylase (AMY1) gene copy numbers and insulin resistance in asymptomatic Korean men
Authors: Choi Y.‐J. , Nam Y.‐S. , Yun J. M. , Park J. H. , Cho B. L. , Son H.‐Y. , Kim J. I. , Yun J. W. 
Published: May 2015

AbstractAimsSalivary amylase gene (AMY1) copy number variations (CNVs) correlate directly with salivary amylase activity and serum amylase levels. Previously, individuals with high AMY1 CNVs exhibited low postprandial glucose levels and postprandial early insulin surge, suggesting that high AMY1 gene copy numbers may play a role in lowering the risk of insulin resistance.MethodsWe verified the relationship between AMY1 CNVs and homeostatic model assessment–insulin resistance (HOMA‐IR) in a cohort of 1257 Korean men aged 20–65 years who visited two medical centres for regular health check‐ups, and in subgroups of current smokers and regular alcohol drinkers. Individuals with fasting plasma glucose levels > 10.0 mmol/l, HbA1c ≥ 64 mmol/mol (8.0%) or who used oral hypoglycaemic agents or insulin were excluded.ResultsAMY1 CNVs correlated negatively with HOMA‐IR even after adjusting for covariates (e.g. BMI, systolic blood pressure, triacylglycerol, alcohol consumption, smoking and physical activity). When the participants were divided according to current smoking and alcohol consumption habits, negative correlations between AMY1 CNVs and HOMA‐IR were more evident among non‐smokers and regular drinkers and were non‐significant among smokers and non‐regular drinkers.ConclusionsLow AMY1 CNVs correlated with high insulin resistance in asymptomatic Korean men, and such a relationship presented differently according to the status of smoking and alcohol consumption.
Association of IRF8 gene polymorphisms with autoimmune thyroid disease
Authors: Lin Jiunn‐Diann , Wang Yuan‐Hung , Liu Chia‐Hung , Lin Ying‐Chin , Lin Jui‐An , Lin Yuh‐Feng , Tang Kam‐Tsun , Cheng Chao‐Wen 
Published: May 2015

AbstractBackgroundThe occurrence of autoimmune thyroid disease (AITD) is known to have a major adverse effect on interferon (INF)‐α treatment. The genetic variant of the INF regulatory factor 8 (IRF8), a type 1 INF regulator, is associated with susceptibility to systemic lupus erythematosus and multiple sclerosis. In this study, we investigated possible associations of the IRF8 polymorphisms, rs17445836 and rs2280381, with AITD in an ethnic Chinese population.Material and methodsIn total, 278 patients with Graves' disease (GD) and 55 patients with Hashimoto's thyroiditis (HT), and 252 healthy controls were enrolled. Polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) and direct sequencing were used for genotyping.ResultsSignificantly lower frequencies of the GA genotype and A allele of rs17445836 were found in the HT group than in the control group (P = 0·028, odds ratio (OR) = 4·71 and P = 0·022, OR = 4·40, respectively). Both rs17445836 and rs2280381 were associated with the presence of an antimicrosomal antibody (AmiA), and rs2280381 was also associated with the presence of an antithyroglobulin antibody (ATA) in AITD. Moreover, rs17445836 was associated with the level of AmiA in AITD.Conclusionsrs17445836 of IRF8 is a possible genetic variant associated with the development of HT. rs17445836 was associated with the production of thyroid antibody, and the GG genotype of rs17445836 was associated with a higher AmiA titre than the GA genotype.
Hypofibrinogenemia and liver disease: a new case of Aguadilla fibrinogen and review of the literature
Authors: Casini A. , Sokollik C. , Lukowski S. W. , Lurz E. , Rieubland C. , de Moerloose P. , Neerman‐Arbez M. 
Published: May 2015

IntroductionFibrinogen storage disease (FSD) is characterized by hypofibrinogenemia and hepatic inclusions due to impaired release of mutant fibrinogen which accumulates and aggregates in the hepatocellular endoplasmic reticulum. Liver disease is variable.AimWe studied a new Swiss family with fibrinogen Aguadilla. In order to understand the molecular peculiarity of FSD mutations, fibrinogen Aguadilla and the three other causative mutations, all located in the γD domain, were modelled.MethodThe proband is a Swiss girl aged 4 investigated because of fatigue and elevated liver enzymes. Protein structure models were prepared using the Swiss‐PdbViewer and POV‐Ray software.ResultsThe proband was found to be heterozygous for fibrinogen Aguadilla: FGG Arg375Trp. Familial screening revealed that her mother and maternal grandmother were also affected and, in addition, respectively heterozygous and homozygous for the hereditary haemochromatosis mutation HFE C282Y. Models of backbone and side‐chain interactions for fibrinogen Aguadilla in a 10‐angstrom region revealed the loss of five H‐bonds and the gain of one H‐bond between structurally important amino acids. The structure predicted for fibrinogen Angers showed a novel helical structure in place of hole ‘a’ on the outer edge of γD likely to have a negative impact on fibrinogen assembly and secretion.ConclusionThe mechanism by which FSD mutations generate hepatic intracellular inclusions is still not clearly established although the promotion of aberrant intermolecular strand insertions is emerging as a likely cause. Reporting new cases is essential in the light of novel opportunities of treatment offered by increasing knowledge of the degradation pathway and autophagy.
Results of a phase I/II open‐label, safety and efficacy trial of coagulation factor IX (recombinant), albumin fusion protein in haemophilia B patients
Authors: Martinowitz U. , Lissitchkov T. , Lubetsky A. , Jotov G. , Barazani‐Brutman T. , Voigt C. , Jacobs I. , Wuerfel T. , Santagostino E. 
Published: May 2015

IntroductionrIX‐FP is a coagulation factor IX (recombinant), albumin fusion protein with more than fivefold half‐life prolongation over other standard factor IX (FIX) products available on the market.AimThis prospective phase II, open‐label study evaluated the safety and efficacy of rIX‐FP for the prevention of bleeding episodes during weekly prophylaxis and assessed the haemostatic efficacy for on‐demand treatment of bleeding episodes in previously treated patients with haemophilia B.MethodsThe study consisted of a 10–14 day evaluation of rIX‐FP pharmacokinetics (PK), and an 11 month safety and efficacy evaluation period with subjects receiving weekly prophylaxis treatment. Safety was evaluated by the occurrence of related adverse events, and immunogenic events, including development of inhibitors. Efficacy was evaluated by annualized spontaneous bleeding rate (AsBR), and the number of injections to achieve haemostasis.ResultsSeventeen subjects participated in the study, 13 received weekly prophylaxis and 4 received episodic treatment only. No inhibitors were detected in any subject. The mean and median AsBR were 1.25, and 1.13 respectively in the weekly prophylaxis arm. All bleeding episodes were treated with 1 or 2 injections of rIX‐FP. Three prophylaxis subjects who were treated on demand prior to study entry had >85% reduction in AsBR compared to the bleeding rate prior to study entry.ConclusionThis study demonstrated the efficacy for weekly routine prophylaxis of rIX‐FP to prevent spontaneous bleeding episodes and for the treatment of bleeding episodes. In addition no safety issues were detected during the study and an improved PK profile was demonstrated.
Open‐label phase 2 study of faldaprevir, deleobuvir and ribavirin in Japanese treatment‐naive patients with chronic hepatitis C virus genotype 1 infection
Authors: Yatsuhashi Hiroshi , Kodani Nobuyoshi , Ugai Hiroyuki , Omata Masao 
Published: May 2015

AimThe safety and efficacy of the NS3/4A protease inhibitor faldaprevir in combination with the non‐nucleoside NS5B polymerase inhibitor deleobuvir and ribavirin in Japanese treatment‐naive patients with chronic genotype 1 hepatitis C virus (HCV) infection was evaluated.MethodsIn this multicenter, open‐label phase 2 study, patients were assigned to 8 weeks of treatment with 80 mg (group 1) or 120 mg (group 2) faldaprevir once daily (q.d.) in combination with deleobuvir 600 mg twice daily and weight‐based ribavirin. This was followed by a 24‐week treatment with faldaprevir 120 mg q.d. in combination with peginterferon‐α‐2a and ribavirin. The primary objective was safety; virological response at weeks 4 and 8 was a secondary endpoint.ResultsTwelve and 13 patients were treated in group 1 and 2, respectively; all were infected with HCV genotype 1b. All patients experienced a drug‐related adverse event (AE). The frequency of individual events was generally numerically greater in group 2 than 1. The most common AEs were nausea (66.7%, group 1; 76.9%, group 2) and vomiting (33.3%, group 1; 61.5%, group 2). Virological response at weeks 4 and 8 was achieved by 11 (91.7%) patients in group 1; in group 2, 12 (92.3%) patients achieved virological response at week 4 and all at week 8. All patients who achieved the week 8 endpoint achieved sustained virological response at week 12.ConclusionFaldaprevir 80 or 120 mg q.d. in combination with deleobuvir and ribavirin was tolerable and had similar efficacy in Japanese patients with HCV genotype 1 infection. ClinicalTrials.gov: NCT01528735.
Markers of renal disease and function are associated with systemic inflammation in HIV infection
Authors: Gupta SK , Kitch D , Tierney C , Melbourne K , Ha B , McComsey GA ,   AIDS Clinical Trials Group Study A5224s Team
Published: May 2015

ObjectivesBoth renal disease and systemic inflammation predict non‐AIDS‐defining events and overall mortality in HIV‐infected patients. Here, we sought to determine the relationships between renal disease and circulating inflammation markers.MethodsWe performed a secondary analysis of AIDS Clinical Trials Group Study A5224s to determine if markers of renal disease [urine protein:creatinine ratio (uPCR), urine albumin:creatinine ratio (uACR), and estimated glomerular filtration rate (eGFR), using Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) creatinine and cystatin C‐creatinine] were associated with markers of systemic inflammation [high‐sensitivity C‐reactive protein, interleukin‐6, tumour necrosis factor (TNF)‐α, soluble TNF‐α receptor I (sTNFRI), sTNFRII, and soluble vascular cellular and intercellular adhesion molecules]. We correlated these renal and inflammatory markers prior to antiretroviral initiation and after 96 weeks of therapy.ResultsWe found that eGFR (estimated using CKD‐EPI cystatin C‐creatinine), uPCR, and uACR were significantly correlated with most assessed markers of systemic inflammation prior to antiretroviral initiation. uPCR and eGFR (using CKD‐EPI cystatin C‐creatinine), but not uACR, remained significantly correlated with most of the assessed inflammatory markers after 96 weeks of antiretroviral therapy (ART). Most of these correlations, although statistically significant, were < 0.50. eGFR using CKD‐EPI creatinine was much less frequently associated with inflammation markers and only significantly correlated with sTNFR1 at week 0 and with sTNFRI and II at week 96.ConclusionsRenal disease and function were associated with systemic inflammation in HIV infection, both before and after ART. Systemic inflammation may partially explain the relationships between proteinuria, albuminuria, and reduced renal function and future adverse outcomes.
The influence of washing and selection processes on the contents of glycoalkaloid and other toxic compounds during industrial chip production
Authors: Rytel Elżbieta , Tajner‐Czopek Agnieszka , Kita Agnieszka , Miedzianka Joanna , Bronkowska Monika 
Published: May 2015

SummaryThe aim of this study was to determine the influence of pretreatment selection and washing processes of potatoes on the manual and optic control on the contents of nitrates (V), and glycoalkaloids after the peeling and frying processes are applied in the industrial production of potato chips. The highest reduction in nitrate quantity was found after the manual selection process of the potatoes and their slicing, as well as after frying the chips. The preselection process of the raw material, slicing and rinsing the potato slices, as well as frying the chips, had the largest influence on the losses of glycoalkaloids. In these samples, 74% remained after pretreatment of the raw material, 29% remained after slicing, and 10% remained in the chips after frying relative to the unpeeled potatoes.
Encrustations of the urinary catheter and prevention strategies: a literature review
Authors: Marcone Marchitti Claudia , Boarin Mattia , Villa Giulia 
Published: May 2015

ABSTRACTPatients with an indwelling urinary catheter are at risk of developing urinary tract infection: for each day of the catheter remaining in situ, there is an increasing risk from 3% to 7% for infection to appear. One of the main complications of catheterization is the onset of encrustations, frequently resulting in obstruction of the catheter. Aim of this study is to describe the problem of indwelling urinary catheter encrustation and prevention strategies. A narrative review of the literature was conducted. Indwelling urinary catheter encrustations originate more easily when urine contains high concentrations of poorly soluble constituents and when the state of the urinary tract enables their precipitation as an alkaline urinary pH, often associated with the presence of bacteria urease‐producers, for instance Proteus mirabilis. Urease can generate crystals and this process keeps going until the accumulation of crystalline deposits block the urine flow within the catheter lumen. The literature suggests that there are manifold pharmacological and non‐pharmacological strategies to prevent encrustations. The literature analysis suggests that the permanence of the catheter could potentially be one of the most relevant causes of encrustation. The catheterization duration is the most important risk factor for bacteriuria, essential for the process of encrustation to start off. There are many prevention strategies, among which promotion of nucleation pH (pHn) supplementation in the daily diet with liquids containing citrate; this is the most simple and suitable for all patients being inexpensive and effective.
Evaluating vehicle painting plans in an automobile assembly plant using an integrated AHP‐PROMETHEE approach
Authors: Oliveira Márcia , Fontes Dalila B. M. M. , Pereira Teresa 
Published: May 2015

AbstractThe painting activity is one of the most complex and important activities in automobile manufacturing. The inherent complexity of the painting activity and the frequent need for repainting usually turn the painting process into a bottleneck in automobile assembly plants, which is reflected in higher operating costs and longer overall cycle times. One possible approach for optimizing the performance of the paint shop is to improve the efficiency of the color planning. This can be accomplished by evaluating the relative merits of a set of vehicle painting plans. Since this problem has a multicriteria nature, we resort to the multicriteria decision analysis (MCDA) methodology to tackle it. A recent trend in the MCDA field is the development of hybrid approaches that are used to achieve operational synergies between different methods. Here we apply, for the first time, an integrated approach that combines the strengths of the analytic hierarchy process (AHP) and the Preference Ranking Organization METHod for Enrichment Evaluations (PROMETHEE), aided by Geometrical Analysis for Interactive Aid (GAIA), to the problem of assessing alternative vehicle painting plans. The management of the assembly plant found the results of value and is currently using them in order to schedule the painting activities such that an enhancement of the operational efficiency of the paint shop is obtained. This efficiency gain has allowed the management to bid for a new automobile model to be assembled at this specific plant.