bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomised clinical study: Aspergillus niger‐derived enzyme digests gluten in the stomach of healthy volunteers
Authors: Salden B. N. , Monserrat V. , Troost F. J. , Bruins M. J. , Edens L. , Bartholomé R. , Haenen G. R. , Winkens B. , Koning F. , Masclee A. A. 
Published: June 2015

SummaryBackgroundAspergillus niger prolyl endoprotease (AN‐PEP) efficiently degrades gluten molecules into non‐immunogenic peptides in vitro.AimTo assess the efficacy of AN‐PEP on gluten degradation in a low and high calorie meal in healthy subjects.MethodsIn this randomised, double‐blind, placebo‐controlled, cross‐over study 12 healthy volunteers attended to four test days. A liquid low or high calorie meal (4 g gluten) with AN‐PEP or placebo was administered into the stomach. Via a triple‐lumen catheter gastric and duodenal aspirates were sampled, and polyethylene glycol (PEG)‐3350 was continuously infused. Acetaminophen in the meals tracked gastric emptying time. Gastric and duodenal samples were used to calculate 240‐min area under the curve (AUC0–240 min) of ?‐gliadin concentrations. Absolute ?‐gliadin AUC0–240 min was calculated using duodenal PEG‐3350 concentrations.ResultsAN‐PEP lowered α‐gliadin concentration AUC0–240 min, compared to placebo, from low and high calorie meals in stomach (low: 35 vs. 389 μg × min/mL; high: 53 vs. 386 μg × min/mL; P < 0.001) and duodenum (low: 7 vs. 168 μg × min/mL; high: 4 vs. 32 μg × min/mL; P < 0.001) and absolute α‐gliadin AUC0–240 min in the duodenum from low (2813 vs. 31 952 μg × min; P < 0.001) and high (2553 vs. 13 095 μg × min; P = 0.013) calorie meals. In the placebo group, the high compared to low calorie meal slowed gastric emptying and lowered the duodenal α‐gliadin concentration AUC0–240 min (32 vs. 168 μg × min/mL; P = 0.001).ConclusionsAN‐PEP significantly enhanced gluten digestion in the stomach of healthy volunteers. Increasing caloric density prolonged gastric residence time of the meal. Since AN‐PEP already degraded most gluten from low calorie meals, no incremental effect was observed by increasing meal caloric density. ClinicalTrials.gov, Number: NCT01335503; www.trialregister.nl, Number: NTR2780.
Aberrant GSTP1 promoter methylation predicts short‐term prognosis in acute‐on‐chronic hepatitis B liver failure
Authors: Gao S. , Sun F.‐K. , Fan Y.‐C. , Shi C.‐H. , Zhang Z.‐H. , Wang L.‐Y. , Wang K. 
Published: June 2015

SummaryBackgroundGlutathione‐S‐transferase P1 (GSTP1) methylation has been demonstrated to be associated with oxidative stress induced liver damage in acute‐on‐chronic hepatitis B liver failure (ACHBLF).AimTo evaluate the methylation level of GSTP1 promoter in acute‐on‐chronic hepatitis B liver failure and determine its predictive value for prognosis.MethodsOne hundred and five patients with acute‐on‐chronic hepatitis B liver failure, 86 with chronic hepatitis B (CHB) and 30 healthy controls (HC) were retrospectively enrolled. GSTP1 methylation level in peripheral mononuclear cells (PBMC) was detected by MethyLight. Clinical and laboratory parameters were obtained.ResultsGSTP1 methylation levels were significantly higher in patients with acute‐on‐chronic hepatitis B liver failure (median 16.84%, interquartile range 1.83–59.05%) than those with CHB (median 1.25%, interquartile range 0.48–2.47%; P < 0.01) and HC (median 0.80%, interquartile range 0.67–1.27%; P < 0.01). In acute‐on‐chronic hepatitis B liver failure group, nonsurvivors showed significantly higher GSTP1 methylation levels (P < 0.05) than survivors. GSTP1 methylation level was significantly correlated with total bilirubin (r = 0.29, P < 0.01), prothrombin time activity (r = −0.24, P = 0.01) and model for end‐stage liver disease (MELD) score (r = 0.26, P = 0.01). When used to predict 1‐ or 2‐month mortality of acute‐on‐chronic hepatitis B liver failure, GSTP1 methylation showed significantly better predictive value than MELD score [area under the receiver operating characteristic curve (AUC) 0.89 vs. 0.72, P < 0.01; AUC 0.83 vs. 0.70, P < 0.05 respectively]. Meanwhile, patients with GSTP1 methylation levels above the cut‐off points showed significantly poorer survival than those below (P < 0.05).ConclusionsAberrant GSTP1 promoter methylation exists in acute‐on‐chronic hepatitis B liver failure and shows high predictive value for short‐term mortality. It might serve as a potential prognostic marker for acute‐on‐chronic hepatitis B liver failure.
Towards Development of a Dermal Pain Model: In Vitro Activation of Rat and Human Transient Receptor Potential Ankyrin Repeat 1 and Safe Dermal Injection of o‐Chlorobenzylidene Malononitrile to Rat
Authors: Annas Anita , Berg Anna‐Lena , Nyman Eva , Meijer Thomas , Lundgren Viveka , Franzén Bo , Ståhle Lars 
Published: June 2015

AbstractDuring clinical development of analgesics, it is important to have access to pharmacologically specific human pain models. o‐Chlorobenzylidene malononitrile (CS) is a selective and potent agonist of the transient receptor potential ankyrin repeat 1 (TRPA1), which is a transducer molecule in nociceptors sensing reactive chemical species. While CS has been subject to extensive toxicological investigations in animals and human beings, its effects on intradermal or subcutaneous injection have not previously been reported. We have investigated the potential of CS to be used as an agonist on TRPA1 in human experimental pain studies. A calcium influx assay was used to confirm the capacity of CS to activate TRPA1 with >100,000 times the selectivity over the transient receptor potential vanilloid receptor 1. CS dose‐dependently (EC50 0.9 μM) released calcitonin gene‐related peptide in rat dorsal root ganglion cultures, supporting involvement in pain signalling. In a local tolerance study, injection of a single intradermal dose of 20 mM CS to rats resulted in superficial, circular crusts at the injection sites after approximately 4 days. The histopathology evaluation revealed a mild, acute inflammatory reaction in the epidermis and dermis at the intradermal CS injection site 1 day after administration. After 14 days, the epidermal epithelium was fully restored. The symptoms were not considered to be adverse, and it is suggested that doses up to 20 μL of 20 mM CS can be safely administered to human beings. In conclusion, our data support development of a CS human dermal pain model.
Salvinorin A analogues PR‐37 and PR‐38 attenuate compound 48/80‐induced itch responses in mice
Authors: Salaga M , Polepally P R , Zielinska M , Marynowski M , Fabisiak A , Murawska N , Sobczak K , Sacharczuk M , Do Rego J C , Roth B L , Zjawiony J K , Fichna J 
Published: June 2015

Background and PurposeThe opioid system plays a crucial role in several physiological processes in the CNS and in the periphery. It has also been shown that selective opioid receptor agonists exert potent inhibitory action on pruritus and pain. In this study we examined whether two analogues of Salvinorin A, PR‐37 and PR‐38, exhibit antipruritic properties in mice.Experimental ApproachTo examine the antiscratch effect of PR‐37 and PR‐38 we used a mouse model of compound 48/80‐induced pruritus. In order to elucidate the mechanism of action of tested compounds, specific antagonists of opioid and cannabinoid receptors were used. The effect of PR‐37 on the CNS was assessed by measuring motor parameters and exploratory behaviours in mice.Key ResultsPR‐37 and PR‐38, jnjected s.c., significantly reduced the number of compound 48/80‐induced scratching behaviours in mice in a dose‐ and time‐dependent manner. PR‐38 was also active when orally administered. The antiscratch activity of PR‐37 was blocked by the selective κ opioid receptor antagonist, nor‐binaltorphimine, and that of PR‐38 by the selective μ opioid receptor antagonist, β‐funaltrexamine.Conclusion and ImplicationsIn conclusion, a novel framework for the development of new antipruritic drugs derived from salvinorin A has been validated.
Individual Differences in Theory of Mind From Preschool to Adolescence: Achievements and Directions
Authors: Hughes Claire , Devine Rory T. 
Published: June 2015

AbstractIn this article, we provide a state‐of‐the‐science overview of research on normative individual differences in theory of mind. We begin by examining achievements in research on individual differences in theory of mind in the preschool years and more recent work on middle childhood and adolescence. In doing so, we outline several converging lines of evidence for social influences on individual differences in theory of mind, and assess the claim that individual differences in theory of mind matter for children's social lives. We then evaluate two conceptualizations of individual differences in theory of mind: the developmental lag and genuine differences accounts. By placing the study of individual differences in theory of mind center stage, we aim to highlight fruitful avenues for research on normative variation in theory of mind both within and beyond the preschool years.
Evaluation of the Surface Treatment on Bone Healing in a Transmucosal 1‐mm Area of Implant Abutment: An Experimental Study in the Rabbit Tibia
Authors: Gehrke Sergio Alexandre , da Silva Neto Ulisses Tavares 
Published: June 2015

AbstractPurposeThe objective of the present study was to investigate the effect on bone tissue healing patterns in 1‐mm area treated in the transmucosal surface of the abutment in the tibia of rabbits.Materials and MethodsForty‐six abutments were divided into two groups: control group (CG) with 14 abutments with smooth surface and experimental group (EG) with 32 abutments presenting a 1‐mm area of the transmucosal surface treated through sandblasting with microparticles of titanium oxide followed by acid etching. Five samples of each group were analyzed using an optical laser profilometer for surface roughness characterization. Thirty‐six Morse taper implants (3.5 mm in diameter and 7 mm in length) were inserted 1.5 mm subcrestal into the tibiae of nine rabbits. The implants were removed after 8, 10, and 12 weeks for histological analysis. The histological slides were prepared and analyzed qualitatively in relation to the new bone at the interface bone‐abutment and quantitatively, in relation to bone height from the base of the implant. These data were computed and statistically compared inside the groups using analysis of variance and the U‐test between groups for same time.ResultsBoth groups exhibited bone growth in the direction and over the surface of the abutments, with good healing. However, the EG group showed an increased height of bone formation in the crestal direction, and highly significant differences were observed (p < .001) between these measured values.ConclusionsUnder the limitations of the present study, histological follow‐up at 8, 10, and 12 weeks showed that transmucosal 1‐mm area of implant abutment with treatment of the surface facilitated the maintenance of bone height around the abutment compared with the same abutment with the totally smooth surface.
A quantification of regenerated bone tissue in human sinus biopsies: influences of anatomical region, age and sex
Authors: Reich Karoline Maria , Huber Christian Domitian , Heimel Patrick , Ulm Christian , Redl Heinz , Tangl Stefan 
Published: June 2015

AbstractObjectivesSinus augmentation is a standard procedure to increase vertical bone supply for dental implants in the atrophic posterior maxilla. Despite the longstanding application of this method, information about some basic factors that could potentially influence bone regeneration after sinus augmentation is rare. The objective of this study was therefore to quantify the impact of the maxillary region (premolar/molar) and patients' age and sex on bone regeneration after sinus grafting.Material and methodsSinus augmentation procedures were performed in 107 patients (66 female: 52.8 ± 11.0 years, 41 male: 50.6 ± 11.3 years). After 6 ± 1 months, 201 sinus biopsies were harvested and histomorphometrically analysed. Height (oldHt) and bone volume fraction of pristine bone (oldBV/TV), as well as the amount of new bone (newBV/TV) and bone‐to‐bone substitute contact (BBSC) in the augmentation area, were assessed.ResultsIn women, newBV/TV in the augmented sinus decreased significantly by 0.22 ± 0.08% per year. In men, no similar trend was observed. There were strong influences of the maxillary region and the dimensions of the host bone. In the premolar region, newBV/TV was 23.1 ± 7.9% and 25.1 ± 10.1%; in the molar region, newBV/TV averaged 20.4 ± 9.4% and 17.8 ± 8.8% for women and men, respectively. The greater the thickness of the wall of the sinus floor (mainly in the former premolar region), the greater was the amount of new bone tissue formed in the spaces in‐between bone substitute particles.ConclusionsThese empirical results derived from a large human sample, link factors that influence the quality of biomaterial integration to the known clinical risks for the success of dental implants.
A meta‐analysis of functional group responses to forest recovery outside of the tropics
Authors: Spake Rebecca , Ezard Thomas H. G. , Martin Philip A. , Newton Adrian C. , Doncaster C. Patrick 
Published: June 2015

AbstractBoth active and passive forest restoration schemes are used in degraded landscapes across the world to enhance biodiversity and ecosystem service provision. Restoration is increasingly also being implemented in biodiversity offset schemes as compensation for loss of natural habitat to anthropogenic development. This has raised concerns about the value of replacing old‐growth forest with plantations, motivating research on biodiversity recovery as forest stands age. Functional diversity is now advocated as a key metric for restoration success, yet it has received little analytical attention to date. We conducted a meta‐analysis of 90 studies that measured differences in species richness for functional groups of fungi, lichens, and beetles between old‐growth control and planted or secondary treatment forests in temperate, boreal, and Mediterranean regions. We identified functional‐group–specific relationships in the response of species richness to stand age after forest disturbance. Ectomycorrhizal fungi averaged 90 years for recovery to old‐growth values (between 45 years and unrecoverable at 95% prediction limits), and epiphytic lichens took 180 years to reach 90% of old‐growth values (between 140 years and never for recovery to old‐growth values at 95% prediction limits). Non‐saproxylic beetle richness, in contrast, decreased as stand age of broadleaved forests increased. The slow recovery by some functional groups essential to ecosystem functioning makes old‐growth forest an effectively irreplaceable biodiversity resource that should be exempt from biodiversity offsetting initiatives.
Attributes of God: Conceptual Foundations of a Foundational Belief
Authors: Shtulman Andrew , Lindeman Marjaana 
Published: June 2015

AbstractAnthropomorphism, or the attribution of human properties to nonhuman entities, is often posited as an explanation for the origin and nature of God concepts, but it remains unclear which human properties we tend to attribute to God and under what conditions. In three studies, participants decided whether two types of human properties—psychological (mind‐dependent) properties and physiological (body‐dependent) properties—could or could not be attributed to God. In Study 1 (n = 1,525), participants made significantly more psychological attributions than physiological attributions, and the frequency of those attributions was correlated both with participants’ religiosity and with their attribution of abstract, theological properties. In Study 2 (n = 99) and Study 3 (n = 138), participants not only showed the same preference for psychological properties but were also significantly faster, more consistent, and more confident when attributing psychological properties to God than when attributing physiological properties. And when denying properties to God, they showed the reverse pattern—that is, they were slower, less consistent, and less confident when denying psychological properties than when denying physiological properties. These patterns were observed both in a predominantly Christian population (Study 2) and a predominantly Hindu population (Study 3). Overall, we argue that God is conceptualized not as a person in general but as an agent in particular, attributed a mind by default but attributed a body only upon further consideration.
Immunology of metal allergies
Authors: Schmidt Marc , Goebeler Matthias 
Published: June 2015

SummaryAllergic contact hypersensitivity to metal allergens is a common health concern worldwide, greatly impacting affected individuals with regard to both quality of life and their ability to work. With an estimated 15–20 % of the Western population hypersensitive to at least one metal allergen, sensitization rates for metallic haptens by far outnumber those reported for other common triggers of allergic contact dermatitis such as fragrances and rubber. Unfortunately, the prevalence of metal‐induced hypersensitivity remains high despite extensive legislative efforts to ban/reduce the content of allergy‐causing metals in recreational and occupational products.Recently, much progress has been made regarding the perception mechanisms underlying the inflammatory responses to this unique group of contact allergens. This review summarizes recent advances in our understanding of this enigmatic disease. Particular emphasis is put on the mechanisms of innate immune activation and T cell activation by common metal allergens such as nickel, cobalt, palladium, and chromate.
Optimal Pricing of Two Successive‐Generation Products with Trade‐in Options under Uncertainty
Authors: Yin Rui , Li Hongmin , Tang Christopher S. 
Published: June 2015

ABSTRACTTo entice consumers to purchase both current and next generation products, many manufacturers and retailers offer trade‐in programs that allow buyers of the first generation product to trade‐in the product and purchase the new generation product at a lower price. By considering the interactions between “forward‐looking” consumers and a firm when a trade‐in program is offered, we analyze a two‐period dynamic game to determine the optimal prices of two successive‐generation products in equilibrium, and examine the conditions under which trade‐in programs are beneficial to the firm. Our model incorporates market heterogeneity (valuation of the first generation product varies among the consumer population), product uncertainty (the incremental value of the new product is uncertain before its introduction), and consumers' forward‐looking behavior (consumers take future product valuation and prices into consideration when making purchasing decisions). With the trade‐in option, we show that consumers are willing to pay a price that is higher than their valuations of the current product. Furthermore, trade‐in programs are more beneficial to the firm when: (i) the durability of the current product is high; (ii) the market heterogeneity is low; or (iii) the uncertainty level (or the expected incremental value) of the new product is high. Finally, when the incremental value of the new product is more uncertain, consumers are more willing to purchase the current product because of the “option” value of the trade‐in programs and thus trade‐in programs can be more beneficial to the firm in this case.
GCK monogenic diabetes and gestational diabetes: possible diagnosis on clinical grounds
Authors: Flack J. R. , Ross G. P. , Cheung N. W. 
Published: June 2015

AbstractAimTo determine if the previously published clinical criteria for identifying glucokinase monogenic diabetes [GCK gene mutation in maturity‐onset diabetes of the young (GCK‐MODY)], an elevated antenatal fasting blood glucose of 5.5–8.0 mmol/l, an increment of < 4.6 mmol/l at 2 h in an oral glucose tolerance test and slim are applicable in a large multi‐ethnic cohort of women with gestational diabetes.MethodsWe analysed de‐identified data from all women with gestational diabetes, diagnosed using the Australasian Diabetes in Pregnancy Society (1998) Australian criteria at our institution between 1993 and 2013, making comparisons among those with complete antenatal data including: diagnostic oral glucose tolerance test results meeting the above criteria; pregestational BMI; birth outcomes; and postpartum oral glucose tolerance test data. We categorized these women into two groups: Group A1 had a BMI ≤ 21 kg/m2 and Group A2 had a BMI > 21 kg/m2 and < 25 kg/m2.ResultsOf the 302 women meeting the study entry criteria, we had complete data including a postpartum oral glucose tolerance test result for 171 women: 54 in Group A1 and 117 in Group A2. Ethnicity was significantly different between the groups. The oral glucose tolerance test and postpartum HbA1c results identified few women ( < 14%) in Group A1 and Group A2 who still had ‘possible GCK‐MODY’.ConclusionsOur findings indicate that previously recommended clinical criteria for the identification of women likely to have GCK‐MODY lack specificity in a cohort of women with multi‐ethnic backgrounds. Using these criteria to select women for testing for GCK‐MODY in pregnancy would therefore be costly and is likely to yield few women positive for this condition.
Impact of empagliflozin added on to basal insulin in type 2 diabetes inadequately controlled on basal insulin: a 78‐week randomized, double‐blind, placebo‐controlled trial
Authors: Rosenstock J. , Jelaska A. , Zeller C. , Kim G. , Broedl U. C. , Woerle H. J. ,   on behalf of the EMPA‐REG BASAL trial investigators
Published: June 2015

AimsTo investigate the efficacy and tolerability of empagliflozin added to basal insulin‐treated type 2 diabetes.MethodsPatients inadequately controlled [glycated haemoglobin (HbA1c) >7 to ≤10% (>53 to ≤86 mmol/mol)] on basal insulin (glargine, detemir, NPH) were randomized to empagliflozin 10 mg (n = 169), empagliflozin 25 mg (n = 155) or placebo (n = 170) for 78 weeks. The baseline characteristics were balanced among the groups [mean HbA1c 8.2% (67 mmol/mol), BMI 32.2 kg/m2]. The basal insulin dose was to remain constant for 18 weeks, then could be adjusted at investigator's discretion. The primary endpoint was change from baseline in HbA1c at week 18. Key secondary endpoints were changes from baseline in HbA1c and insulin dose at week 78.ResultsAt week 18, the adjusted mean ± standard error changes from baseline in HbA1c were 0.0 ± 0.1% (−0.1 ± 0.8 mmol/mol) for placebo, compared with −0.6 ± 0.1% (−6.2 ± 0.8 mmol/mol) and −0.7 ± 0.1% (−7.8 ± 0.8 mmol/mol) for empagliflozin 10 and 25 mg, respectively (both p < 0.001). At week 78, empagliflozin 10 and 25 mg significantly reduced HbA1c, insulin dose and weight vs placebo (all p < 0.01), and empagliflozin 10 mg significantly reduced systolic blood pressure vs placebo (p = 0.004). Similar percentages of patients had confirmed hypoglycaemia in all groups (35–36%). Events consistent with urinary tract infection were reported in 9, 15 and 12% of patients on placebo, empagliflozin 10 and 25 mg, and events consistent with genital infection were reported in 2, 8 and 5%, respectively.ConclusionsEmpagliflozin for 78 weeks added to basal insulin improved glycaemic control and reduced weight with a similar risk of hypoglycaemia to placebo.