bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of triple therapy with peginterferon, ribavirin and boceprevir within an early access programme in Spanish patients with hepatitis C genotype 1 with severe fibrosis: SVRw12 analysis
Authors: Calleja Jose L. , Pascasio Juan M. , Ruiz‐Antorán Belén , Gea Francisco , Bárcena Rafael , Larrubia Juan R. , Pérez‐Álvarez Ramón , Sousa Jose M. , Romero‐Gómez Manuel , Solá Ricard , de la Revilla Juan , Crespo Javier , Navarro Jose M. , Arenas Juan I. , Delgado Manuel , Fernández‐Rodríguez Conrado M. , Planas Ramon , Buti Maria , Forns Xavier ,   the Spanish Group for the Study of the Use of Direct‐Acting Drugs Hepatitis C with Severe Fibrosis
Published: August 2014

AbstractBackground & AimsThe addition of protease inhibitors (PIs) changed the hepatitis C virus (HCV) treatment standards and improved sustained viral response (SVR) rates in patients with genotype 1 HCV infection.MethodsProspective, multicentre, national registry that includes naïve and treatment‐experienced patients with HCV genotype 1 infection, who had bridging fibrosis or cirrhosis and were treated with triple therapy (peginterferon alfa‐2a or alfa‐2b, ribavirin and boceprevir) as compassionate use, and in accordance with the Summary of Product Characteristics.ResultsMost of the patients (68.2%) were male, with a mean age of 53 years, 75% (n = 128) had HCV 1b genotype and baseline viral load of 6.2 log. According to prior treatment, 20% of patients were treatment‐naïve and 80% had received prior treatment. Approximately 36.5% of patients (n = 62) reported at least one serious adverse events (SAEs) (total SAEs = 103). The most common SAEs were neutropenia (57.6%), anaemia (47.6%) and grade 3 thrombopenia (25.9%). Patients with albumin <3.5 g/dl and bilirubin >2 mg/dl had an increased relative risk (greater than one‐fold) for SAEs, including infections and hepatic decompensation. In the intent‐to‐treat analysis (n = 170), the overall percentage of patients with SVRw12 was 46.5%. In patients with 1 log decrease at week 4 (lead‐in phase), the overall SVRw12 rate was 67.0%. In the patients initiating triple therapy with boceprevir (n = 139), the global response rate was 56.4%. In a multivariate analysis, an increased probability of achieving SVR was associated with response to prior treatment (relapsers), >1 log decrease in viral load in the lead‐in phase and baseline albumin >3.5 g/dl.ConclusionsTriple therapy in patients with severe fibrosis/cirrhosis is associated with a higher rate of SAE and a lower rate in comparison with patients with mild disease. However, for patients with intact liver function, it could be considered as a treatment option, when other alternatives would not be available.
Anti‐SLA/LP alone or in combination with anti‐Ro52 and fine specificity of anti‐Ro52 antibodies in patients with autoimmune hepatitis
Authors: Zachou Kalliopi , Gampeta Stella , Gatselis Nikolaos K. , Oikonomou Katerina , Goulis John , Manoussakis Menelaos N. , Renaudineau Yves , Bogdanos Dimitrios P. , Dalekos George N. 
Published: August 2014

AbstractBackground & AimsAntibodies (Abs) to soluble liver antigen/liver pancreas (anti‐SLA/LP) are considered markers of worse prognosis and outcome in patients with autoimmune hepatitis (AIH) although this assumption has recently been attributed to their frequent co‐expression with Abs against Ro52 (anti‐Ro52). To assess the clinical significance of anti‐SLA/LP Abs alone or in combination with anti‐Ro52 in AIH patients and determine the immunodominant Ro52 epitopes according to the anti‐SLA/LP status.MethodsTwenty‐three anti‐SLA/LP‐positive and 106 anti‐SLA/LP‐negative AIH patients were included. Anti‐SLA/LP were determined by ELISA using recombinant antigen, and confirmed by immunoblot using cytosolic rat liver fraction or HuH‐7 extract. Anti‐Ro52 Abs were determined by ELISA using recombinant antigen. Epitope mapping was assessed by ELISA using overlapping peptides covering the whole Ro52 protein in 26 AIH patients and 12 patients with Sjögren's syndrome.ResultsAnti‐SLA/LP positivity was not associated with the clinical, laboratory or histological characteristics of AIH patients. Treatment response, corticosteroid withdrawal, relapse after stopping treatment and outcome, were not associated with the presence of anti‐SLA/LP, anti‐Ro52 or double reactivity. Moreover, Ro52 epitope mapping revealed new epitopes unique for AIH and independent from anti‐SLA/LP positivity.ConclusionsNeither anti‐SLA/LP nor anti‐Ro52 Abs or their combination could specify a distinct group of AIH patients in terms of clinical characteristics, treatment response and outcome. Further studies are needed to clarify whether the newly discovered immunodominant epitopes of Ro52 antigen which were associated specifically with AIH have any clinical or pathogenetic significance in AIH.
Quantification of in vivo colonic motor patterns in healthy humans before and after a meal revealed by high‐resolution fiber‐optic manometry
Authors: Dinning P. G. , Wiklendt L. , Maslen L. , Gibbins I. , Patton V. , Arkwright J. W. , Lubowski D. Z. , O'Grady G. , Bampton P. A. , Brookes S. J. , Costa M. 
Published: August 2014

AbstractBackgroundUntil recently, investigations of the normal patterns of motility of the healthy human colon have been limited by the resolution of in vivo recording techniques.MethodsWe have used a new, high‐resolution fiber‐optic manometry system (72 sensors at 1‐cm intervals) to record motor activity from colon in 10 healthy human subjects.Key ResultsIn the fasted colon, on the basis of rate and extent of propagation, four types of propagating motor pattern could be identified: (i) cyclic motor patterns (at 2–6/min); (ii) short single motor patterns; (iii) long single motor patterns; and (iv) occasional retrograde, slow motor patterns. For the most part, the cyclic and short single motor patterns propagated in a retrograde direction. Following a 700 kCal meal, a fifth motor pattern appeared; high‐amplitude propagating sequences (HAPS) and there was large increase in retrograde cyclic motor patterns (5.6 ± 5.4/2 h vs 34.7 + 19.8/2 h; p < 0.001). The duration and amplitude of individual pressure events were significantly correlated. Discriminant and multivariate analysis of duration, gradient, and amplitude of the pressure events that made up propagating motor patterns distinguished clearly two types of pressure events: those belonging to HAPS and those belonging to all other propagating motor patterns.Conclusions & InferencesThis work provides the first comprehensive description of colonic motor patterns recorded by high‐resolution manometry and demonstrates an abundance of retrograde propagating motor patterns. The propagating motor patterns appear to be generated by two independent sources, potentially indicating their neurogenic or myogenic origin.
The impact of olfactory dysfunction on interoceptive awareness
Authors: Krajnik Jacqueline , Kollndorfer Kathrin , Notter Lisbeth A. , Mueller Christian A. , Schöpf Veronika 
Published: August 2014

AbstractThis study aimed to investigate how the impairment of the olfactory system influences interoception. Interoception is known as the awareness of one's body or the sense of the condition of the body; more precisely, this construct is defined as the processing, representation, and perception of the internal physical state. Interoceptive sensitivity and chemosensory performance were assessed in 77 subjects, including 43 functional anosmics, 18 hyposmics, and 16 healthy controls. Interoceptive awareness was predicted by odor detection threshold, as well as the duration of olfactory loss in patients who suffered from reduced olfactory function—the longer the olfactory impairment, the worse the perception of bodily signals. The results of this study will significantly contribute to the basic understanding of the multifaceted effects of olfactory alterations.
Use of Porcine Luteinizing Hormone at Oestrous Onset in a Protocol for Fixed‐Time Artificial Insemination in Gilts
Authors: Ulguim RR , Fontana DL , Rampi JZ , Bernardi ML , Wentz I , Bortolozzo FP 
Published: August 2014

ContentsThe aim of this study was to evaluate the effect of porcine luteinizing hormone (pLH) given at oestrous onset in gilts, by different routes and doses, on the interval between onset of oestrus and ovulation (IOEO) and reproductive performance using a single fixed‐time artificial insemination (FTAI). A total of 153 gilts were submitted to oestrous detection at 8‐h intervals and assigned to three groups: control – without hormone application and inseminated at 0, 24 and 48 h after oestrous onset; VS2.5FTAI – 2.5 mg pLH by the vulvar submucosal route at oestrous onset and a single FTAI 16 h later; IM5FTAI – 5 mg pLH by the intramuscular route at oestrous onset and a single FTAI 16 h later. More VS2.5FTAI gilts (47.1%; p < 0.05) ovulated within 24 h after oestrous onset than control gilts (25.5%) whereas IM5FTAI gilts had an intermediate percentage (31.4%; p > 0.05). The IOEO tended to be shorter (p = 0.06) in VS2.5FTAI (30.2 ± 1.4 h) than in control (34.7 ± 1.4 h) gilts, but there was no difference (p > 0.05) between control and IM5FTAI (32.8 ± 1.4 h) gilts. Farrowing rate was not different (p > 0.05) among treatments. Total born piglets (TB) was lower (p < 0.05) in VS2.5FTAI (12.3 ± 0.4) than in control gilts (14.1 ± 0.4), whereas intermediate TB was observed in IM5FTAI gilts (13.3 ± 0.4). Due to the advancement of ovulation, reduction of the hormonal dose and the ease of application, the vulvar submucosal route would be the best option for FTAI protocols, but their negative impact on litter size remains to be elucidated. Taking into account the good fertility results obtained in IM5FTAI gilts whose ovulation was not advanced, the possibility of a single FTAI without any hormonal treatment should be further investigated, to establish reliable FTAI protocols for gilts.
Efficient Estimation of the Partly Linear Additive Hazards Model with Current Status Data
Authors: Lu Xuewen , Song Peter X.‐K. 
Published: August 2014

AbstractThis paper focuses on efficient estimation, optimal rates of convergence and effective algorithms in the partly linear additive hazards regression model with current status data. We use polynomial splines to estimate both cumulative baseline hazard function with monotonicity constraint and nonparametric regression functions with no such constraint. We propose a simultaneous sieve maximum likelihood estimation for regression parameters and nuisance parameters and show that the resultant estimator of regression parameter vector is asymptotically normal and achieves the semiparametric information bound. In addition, we show that rates of convergence for the estimators of nonparametric functions are optimal. We implement the proposed estimation through a backfitting algorithm on generalized linear models. We conduct simulation studies to examine the finite‐sample performance of the proposed estimation method and present an analysis of renal function recovery data for illustration.
Image analysis of skin color heterogeneity focusing on skin chromophores and the age‐related changes in facial skin
Authors: Kikuchi Kumiko , Masuda Yuji , Yamashita Toyonobu , Kawai Eriko , Hirao Tetsuji 
Published: August 2014

Background/purposeHeterogeneity with respect to skin color tone is one of the key factors in visual perception of facial attractiveness and age. However, there have been few studies on quantitative analyses of the color heterogeneity of facial skin. The purpose of this study was to develop image evaluation methods for skin color heterogeneity focusing on skin chromophores and then characterize ethnic differences and age‐related changes.MethodsA facial imaging system equipped with an illumination unit and a high‐resolution digital camera was used to develop image evaluation methods for skin color heterogeneity. First, melanin and/or hemoglobin images were obtained using pigment‐specific image‐processing techniques, which involved conversion from Commission Internationale de l'Eclairage XYZ color values to melanin and/or hemoglobin indexes as measures of their contents. Second, a spatial frequency analysis with threshold settings was applied to the individual images. Cheek skin images of 194 healthy Asian and Caucasian female subjects were acquired using the imaging system. Applying this methodology, the skin color heterogeneity of Asian and Caucasian faces was characterized.ResultsThe proposed pigment‐specific image‐processing techniques allowed visual discrimination of skin redness from skin pigmentation. In the heterogeneity analyses of cheek skin color, age‐related changes in melanin were clearly detected in Asian and Caucasian skin. Furthermore, it was found that the heterogeneity indexes of hemoglobin were significantly higher in Caucasian skin than in Asian skin.ConclusionWe have developed evaluation methods for skin color heterogeneity by image analyses based on the major chromophores, melanin and hemoglobin, with special reference to their size. This methodology focusing on skin color heterogeneity should be useful for better understanding of aging and ethnic differences.
Islet xenotransplantation: what is the optimal age of the islet‐source pig?
Authors: Nagaraju Santosh , Bottino Rita , Wijkstrom Martin , Trucco Massimo , Cooper David K. C. 
Published: August 2014

AbstractBackgroundThe need for pig islet xenotransplantation in patients with type 1 diabetes is compelling; however, the ideal age at which islets should be isolated from the donor pig remains uncertain. Pig islet transplantation in primates, as a valuable pre‐clinical model, has been explored using adult, neonatal, fetal pig islets, and also pancreatic primordia from pig embryos as beta cell donors. Neonatal pig islets have some advantages over adult and fetal islets, but the optimal age within the first month of life at which neonatal islets should be isolated and transplanted is as yet unclear.MethodsIn an attempt to answer this question, we carried out a literature search, but limited the search primarily to evidence in the clinically‐relevant pig‐to‐non‐human primate model.ResultsWe identified surprisingly few studies in this model directed to this topic. Even in pig‐to‐rodent models, there were few definitive data.ConclusionFrom the few data available to us, we conclude that pancreatectomy and islet isolation from neonatal pigs may have advantages over adult pigs and that isolation during the first week of life may have minor advantages over later weeks.
Simulations of the West African Monsoon with a Superparameterized Climate Model. Part II: African Easterly Waves
Authors: McCrary Rachel R. , Randall David A. , Stan Cristiana 
Published: August 2014

Abstract
The relationship between African easterly waves and convection is examined in two coupled general circulation models: the Community Climate System Model (CCSM) and the “superparameterized” CCSM (SP-CCSM). In the CCSM, the easterly waves are much weaker than observed. In the SP-CCSM, a two-dimensional cloud-resolving model replaces the conventional cloud parameterizations of CCSM. Results show that this allows for the simulation of easterly waves with realistic horizontal and vertical structures, although the model exaggerates the intensity of easterly wave activity over West Africa. The simulated waves of SP-CCSM are generated in East Africa and propagate westward at similar (although slightly slower) phase speeds to observations. The vertical structure of the waves resembles the first baroclinic mode. The coupling of the waves with convection is realistic. Evidence is provided herein that the diabatic heating associated with deep convection provides energy to the waves simulated in SP-CCSM. In contrast, horizontal and vertical structures of the weak waves in CCSM are unrealistic, and the simulated convection is decoupled from the circulation.
Incidence and predictors of surgical site infections following caesarean sections at Bugando Medical Centre, Mwanza, Tanzania
Authors: Mpogoro Filbert J , Mshana Stephen E , Mirambo Mariam M , Kidenya Benson R , Gumodoka Balthazar , Imirzalioglu Can 
Published: August 2014

Abstract

Background
Surgical site infection (SSI) is the second most common infectious complication after urinary tract infection following a delivery by caesarean section (CS). At Bugando Medical Centre there has no study documenting the epidemiology of SSI after CS despite the large number of CSs performed and the relatively common occurrence of SSIs.

Methods
This was a prospective cohort study involving pregnant women who underwent a CS between October 2011 and February 2012 at Bugando Medical Centre. A total of 345 pregnant women were enrolled. Preoperative, intraoperative and postoperative data were collected using a standardized questionnaire. Wound specimens were collected and processed as per standard operative procedures; and susceptibility testing was carried out using a disc diffusion technique. Data was analyzed using STATA version 11.

Results
The overall cumulative incidence of SSI was 10.9% with an incidence rate of 37.5 per 10,000 people/day (95% CI, 26.8-52.4). The median time from CS to the development of SSI was 7 days (interquartile range [IQR] = 6–9 days). Six independent risk factors for post caesarean SSI as identified in this study by multivariate analysis are: hypertensive disorders of pregnancy (HR: 2.5; 95% CI, 1.1-5.6; P = 0.021), severe anaemia (HR: 3.8; 95% CI, 1.2-12.4, P = 0.028), surgical wound class III (HR: 2.4; 95% CI, 1.1-5.0; P = 0.021), multiple vaginal examinations (HR: 2.5; 95% CI, 1.2-5.1; P = 0.011), prolonged duration of operation (HR: 2.6; 95% CI, 1.2-5.5; P = 0.015) and an operation performed by an intern or junior doctor (HR: 4.0; 95% CI, 1.7-9.2; P = 0.001). Staphylococcus aureus was the most common organism (27.3%), followed by Klebsiella pneumoniae (22.7%). Patients with a SSI had a longer average hospital stay than those without a SSI (12.7 ± 6.9 vs. 4 ± 1.7; P < 0.0001) and the case fatality rate among patients with a SSI was 2.9%.

Conclusion
SSIs are common among women undergoing CSs at Bugando Medical Centre. SSIs were commonly associated with multiple factors. Strategies to control these factors are urgently needed to control SSIs post CS at Bugando Medical Centre and other centres in developing countries.
Subcortical hyperintensity volumetrics in Alzheimer’s disease and normal elderly in the Sunnybrook Dementia Study: correlations with atrophy, executive function, mental processing speed, and verbal memory
Authors: Ramirez Joel , McNeely Alicia A , Scott Christopher JM , Stuss Donald T , Black Sandra E 
Published: August 2014

Abstract
Introduction
Subcortical hyperintensities (SHs) are radiological entities commonly observed on magnetic resonance imaging (MRI) of patients with Alzheimer’s disease (AD) and normal elderly controls. Although the presence of SH is believed to indicate some form of subcortical vasculopathy, pathological heterogeneity, methodological differences, and the contribution of brain atrophy associated with AD pathology have yielded inconsistent results in the literature.

Methods
Using the Lesion Explorer (LE) MRI processing pipeline for SH quantification and brain atrophy, this study examined SH volumes of interest and cognitive function in a sample of patients with AD (n = 265) and normal elderly controls (n = 100) from the Sunnybrook Dementia Study.

Results
Compared with healthy controls, patients with AD were found to have less gray matter, less white matter, and more sulcal and ventricular cerebrospinal fluid (all significant, P <0.0001). Additionally, patients with AD had greater volumes of whole-brain SH (P <0.01), periventricular SH (pvSH) (P <0.01), deep white SH (dwSH) (P <0.05), and lacunar lesions (P <0.0001). In patients with AD, regression analyses revealed a significant association between global atrophy and pvSH (P = 0.02) and ventricular atrophy with whole-brain SH (P <0.0001). Regional volumes of interest revealed significant correlations with medial middle frontal SH volume and executive function (P <0.001) in normal controls but not in patients with AD, global pvSH volume and mental processing speed (P <0.01) in patients with AD, and left temporal SH volume and memory (P <0.01) in patients with AD.

Conclusions
These brain-behavior relationships and correlations with brain atrophy suggest that subtle, yet measurable, signs of small vessel disease may have potential clinical relevance as targets for treatment in Alzheimer’s dementia.
Altered phenotype and Stat1 expression in Toll-like receptor 7/8 stimulated monocyte-derived dendritic cells from patients with primary Sjögren’s syndrome
Authors: Vogelsang Petra , Karlsen Marie , Brun Johan G , Jonsson Roland , Appel Silke 
Published: August 2014

Abstract
Introduction
Dendritic cells (DC) are the most potent antigen-presenting cells of the immune system, involved in both initiating immune responses and maintaining tolerance. Dysfunctional and via toll-like receptor (TLR) ligands activated DC have been implicated in the development of autoimmune diseases, but their role in the etiology of Sjögren’s syndrome, a chronic inflammatory autoimmune disease characterized by progressive mononuclear cell infiltration in the exocrine glands, has not been revealed yet. Therefore, the aim of this study was to investigate phenotype and functional properties of immature and TLR7/8 stimulated monocyte-derived DC (moDC) of patients with primary Sjögren’s syndrome (pSS) and compare them to healthy controls.

Methods
The phenotype, apoptosis susceptibility and endocytic capacity of moDC were analyzed by flow cytometry. Secretion of cytokines was measured by enzyme-linked immunosorbent assay (ELISA) and multiplex Luminex analyses in moDC cell culture supernatants. The expression of TLR7 was analyzed by flow cytometry and real-time quantitative polymerase chain reaction (qPCR). Expression of Ro/Sjögren’s syndrome-associated autoantigen A (Ro52/SSA), interferon regulatory factor 8 (IRF-8), Bim, signal transduction and activators of transcription (Stat) 1, p-Stat1 (Tyrosin 701), p-Stat1 (Serin 727), Stat3, pStat3 (Tyrosin 705) and glyceraldehyde 3-phosphatase dehydrogenase (GAPDH) was measured by Western blotting. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) family members were quantified using the ELISA-based TransAM NF-κB family kit.

Results
We could not detect differences in expression of co-stimulatory molecules and maturation markers such as cluster of differentiation (CD) 86, CD80, CD40 or CD83 on moDC from patients compared to healthy controls. Moreover, we could not observe variations in apoptosis susceptibility, Bim and Ro52/SSA expression and the endocytic capacity of the moDC. However, we found that moDC from pSS patients expressed increased levels of the major histocompatibility complex (MHC) class II molecule human leukocyte antigen (HLA)-DR. We also found significant differences in cytokine production by moDC, where increased interleukin (IL)-12p40 secretion in mature pSS moDC correlated with increased RelB expression. Strikingly, moDC from pSS patients matured for 48 hours with TLR7/8 ligand CL097 expressed significantly less Stat1.

Conclusion
Our results suggest a role for moDC in the pathogenesis of Sjögren’s syndrome.
Rhodium-catalyzed Intramolecular Dehydrogenative Aryl–Aryl Coupling Using Air as Terminal Oxidant
Authors: Baars Hannah , Unoh Yuto , Okada Takeshi , Hirano Koji , Satoh Tetsuya , Tanaka Ken , Bolm Carsten , Miura Masahiro 
Published: August 2014

Abstract
Intramolecular dehydrogenative cyclization involving twofold Csp2–H bond cleavages directed by the amino- or carboxy group proceeds smoothly when using a rhodium–copper catalyst system under air as the terminal oxidant. A variety of fluorene derivatives can be prepared by the environmentally benign procedure.