bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upper limit of cancer extent on biopsy defining very low‐risk prostate cancer
Authors: Bratt Ola , Folkvaljon Yasin , Loeb Stacy , Klotz Laurence , Egevad Lars , Stattin Pär 
Published: July 2014

ObjectiveTo investigate how much Gleason pattern 3 cancer prostate biopsy specimens may contain without an increased risk of undetected more aggressive cancer, compared with the risk for cancers fulfilling the National Comprehensive Cancer Network (NCCN) criteria for very low‐risk prostate cancer.Patients and MethodsWe identified 1286 men aged <70 years in the National Prostate Cancer Register of Sweden who underwent primary radical prostatectomy (RP) for stage T1c or T2 prostate cancer with Gleason pattern ≤3 only, prostate‐specific antigen (PSA) level of <10 ng/mL and a PSA density of <0.15 ng/mL/mL. The association between the extent of cancer in the biopsies (the number and proportion of positive cores and the total cancer length in the cores in millimetres) and the likelihood of Gleason pattern 4–5 in the RP specimen was analysed with logistic regression.ResultsIn all, 438 (34%) of the 1286 men had Gleason pattern 4–5 in the RP specimen. Increasing number and proportion of positive biopsy cores, as well as increasing biopsy cancer length were both significantly associated with increased risk of upgrading at RP in univariable analysis, but in multivariable analysis only biopsy cancer length remained significant. The 684 men with stage T1c and <8 mm cancer had similar risk of upgrading regardless of whether the number of positive biopsy cores was 1–2 or 3–4 (28% vs 27% risk); upgrading was more common among the remaining men (40%, P < 0.01).ConclusionsMen aged <70 years with stage T1c prostate cancer and 3–4 biopsy cores with Gleason pattern 3 are not more likely to have undetected Gleason pattern 4–5 cancer than men with 1–2 cores with cancer, provided that the total biopsy cancer length is <8 mm. We propose that the definition of very low‐risk prostate cancer is widened accordingly.
δ‐Opioid receptors up‐regulate excitatory amino acid transporters in mouse astrocytes
Authors: Liang Jianfeng , Chao Dongman , Sandhu Harleen K , Yu Yanbing , Zhang Li , Balboni Gianfranco , Kim Dong H , Xia Ying 
Published: July 2014

Background and PurposeAstrocytic excitatory amino acid transporters (EAATs) regulate extracellular glutamate concentrations and play a role in preventing neuroexcitotoxicity. As the δ‐opioid receptor (DOP receptor) is neuroprotective against excitotoxic injury, we determined whether DOP receptor activation up‐regulates EAAT expression and function.Experimental ApproachWe measured mRNA and protein expression of EAAT1, EAAT2 and EAAT3 in cultured mouse astrocytes exposed to a specific DOP receptor agonist (UFP‐512) with or without a DOP receptor antagonist, DOP receptor siRNA or inhibitors of PKC, PKA, PI3K, p38, MAPK, MEK and ERK, and evaluated the function of EAATs by measuring glutamate uptake.Key ResultsAstrocytic DOP receptor mRNA and protein were suppressed by DOP receptor siRNA knockdown. DOP receptor activation increased mRNA and protein expression of EAAT1 and EAAT2, but not EAAT3, thereby enhancing glutamate uptake of astrocytes. DOP receptor‐induced EAAT1 and EAAT2 expression was largely reversed by DOP receptor antagonist naltrindole or by DOP receptor siRNA knockdown, and suppressed by inhibitors of MEK, ERK and p38. DOP receptor‐accelerated glutamate uptake was inhibited by EAAT blockers, DOP receptor siRNA knockdown or inhibitors of MEK, ERK or p38. In contrast, inhibitors of PKA, PKC or PI3K had no significant effect on DOP receptor‐induced EAAT expression.Conclusions and ImplicationsDOP receptor activation up‐regulates astrocytic EAATs via MEK‐ERK‐p38 signalling, suggesting a critical role for DOP receptors in the regulation of astrocytic EAATs and protection against neuroexcitotoxicity. As decreased EAAT expression contributes to pathophysiology in many neurological diseases, including amyotrophic lateral sclerosis, our findings present a new platform for potential treatments of these diseases.
Feleucin‐BO1: A Novel Antimicrobial Non‐Apeptide Amide from the Skin Secretion of the Toad, Bombina orientalis, and Design of a Potent Broad‐Spectrum Synthetic Analogue, Feleucin‐K3
Authors: Hou Xiaojuan , Du Qiang , Li Renjie , Zhou Mei , Wang Hui , Wang Lei , Guo Can , Chen Tianbao , Shaw Chris 
Published: July 2014

Feleucins‐BV1 and ‐BV2 are recently described prototypes of a novel antimicrobial non‐apeptide (AMP) family identified in the skin secretion of the bombinid toad, Bombina variegata. They are encoded on different precursors that also encode a novel bombinin. Here we describe the identification of feleucin‐BO1 (FLGLLGSLLamide) which is co‐encoded with a different novel bombinin, named feleucin precursor‐associated bombinin (FPA‐bombinin‐BO), from the skin secretion of Bombina orientalis. Synthetic feleucin‐BO1 displayed activity against a reference Gram‐positive bacterium. Staphylococcus aureus (MIC 34 μm) but was inactive (> 250 μm) against the Gram‐negative bacterium, Escherichia coli, and the yeast, Candida albicans. This pattern of activity was similar to that of the prototypes. Design and synthesis of a cationicity‐enhanced analogue, feleucin‐K3 (F‐K3), in which the amino acid residues at positions 3 (G), 6 (G) and 7 (S) of feleucin‐BO1 were substituted with Lys (K) residues, resulted in a peptide with significantly enhanced potency and spectrum of activity. The MICs of F‐K3 against the reference micro‐organisms were 7 μm (S. aureus), 14 μm (E. coli) and 7 μm (C. albicans). These data indicate that the skin secretions of amphibians can continue to provide novel peptide templates for the rational design of analogues with possible therapeutic utility.
Are urinary levels of high mobility group box 1 markers of active nephritis in anti-neutrophil cytoplasmic antibody-associated vasculitis?
Authors: de Souza A W S , Abdulahad W H , Sosicka P , Bijzet J , Limburg P C , Stegeman C A , Bijl M , Westra J , Kallenberg C G M 
Published: July 2014

Summary
The objective of this study is to evaluate urinary high mobility group box 1 (HMGB1) levels as markers for active nephritis in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in comparison with urinary CD4+ effector memory T cells and urinary monocyte chemoattractant protein-1 (MCP-1). Twenty-four AAV patients with active nephritis and 12 healthy controls (HC) were evaluated. In nine patients, samples were also obtained during remission. Urinary levels of HMGB1 were measured by Western blot. CD4+T cells and CD4+ effector memory T cells (CD4+CD45RO+CCR7-) were determined in urine and whole blood by flow cytometry. Measurement of urinary levels of MCP-1 and serum HMGB1 levels were performed by enzyme-linked immunosorbent assay (ELISA). AAV patients with active nephritis had higher median intensity of HMGB1 in urine than HC [10·3 (7·05–18·50) versus 5·8 (4·48–7·01); P = 0·004]. Both urinary HMGB1 and MCP-1 levels decreased significantly from active nephritis to remission. The urinary MCP-1/creatinine ratio correlated with Birmingham Vasculitis Activity Score (BVAS) (P = 0·042). No correlation was found between the HMGB1/creatinine ratio and 24-h proteinuria, estimated glomerular filtration rate (eGFR), MCP-1/creatinine ratio, BVAS and serum HMGB1. A positive correlation was found between urinary HMGB1/creatinine ratio and CD4+T cells/creatinine ratio (P = 0·028) and effector memory T cells/creatinine ratio (P = 0·039) in urine. Urinary HMGB1 levels are increased in AAV patients with active nephritis when compared with HC and patients in remission, and urinary HMGB1 levels are associated with CD4+T cells and CD4+ effector memory T cells in urine. Measurement of urinary HMGB1 may be of additional value in identifying active glomerulonephritis in AAV patients.
Impaired decision‐making and selective cortical frontal thinning in Cushing's syndrome
Authors: Crespo Iris , Esther Granell‐Moreno , Santos Alicia , Valassi Elena , Yolanda Vives‐Gilabert , De Juan‐Delago Manel , Webb Susan M. , Gómez‐Ansón Beatriz , Resmini Eugenia 
Published: July 2014

SummaryContext and objectiveCushing's syndrome (CS) is caused by a glucocorticoid excess. This hypercortisolism can damage the prefrontal cortex, known to be important in decision‐making. Our aim was to evaluate decision‐making in CS and to explore cortical thickness.Subjects and methodsThirty‐five patients with CS (27 cured, eight medically treated) and thirty‐five matched controls were evaluated using Iowa gambling task (IGT) and 3 Tesla magnetic resonance imaging (MRI) to assess cortical thickness. The IGT evaluates decision‐making, including strategy and learning during the test. Cortical thickness was determined on MRI using freesurfer software tools, including a whole‐brain analysis.ResultsThere were no differences between medically treated and cured CS patients. They presented an altered decision‐making strategy compared to controls, choosing a lower number of the safer cards (P < 0·05). They showed more difficulties than controls to learn the correct profiles of wins and losses for each card group (P < 0·05). In whole‐brain analysis, patients with CS showed decreased cortical thickness in the left superior frontal cortex, left precentral cortex, left insular cortex, left and right rostral anterior cingulate cortex, and right caudal middle frontal cortex compared to controls (P < 0·001).ConclusionsPatients with CS failed to learn advantageous strategies and their behaviour was driven by short‐term reward and long‐term punishment, indicating learning problems because they did not use previous experience as a feedback factor to regulate their choices. These alterations in decision‐making and the decreased cortical thickness in frontal areas suggest that chronic hypercortisolism promotes brain changes which are not completely reversible after endocrine remission.
Sonic Hedgehog mutations are not a common cause of congenital hypopituitarism in the absence of complex midline cerebral defects
Authors: Paulo Sabrina Soares , Fernandes‐Rosa Fábio L. , Turatti Wendy , Coeli‐Lacchini Fernanda Borchers , Martinelli Carlos E. , Nakiri Guilherme S. , Moreira Ayrton C. , Santos Antônio C. , de Castro Margaret , Antonini Sonir R. 
Published: July 2014

SummaryContext and ObjectiveSonic Hedgehog (SHH) and GLI2, an obligatory mediator of SHH signal transduction, are holoprosencephaly (HPE)‐associated genes essential in pituitary formation. GLI2 variants have been found in patients with congenital hypopituitarism without complex midline cerebral defects (MCD). However, data on the occurrence of SHH mutations in these patients are limited. We screened for SHH and GLI2 mutations or copy number variations (CNV) in patients with congenital hypopituitarism without MCD or with variable degrees of MCD.Patients and MethodsDetailed data on clinical, laboratory and neuroimaging findings of 115 patients presenting with congenital hypopituitarism without MCD, septo‐optic dysplasia or HPE were analysed. The SHH and GLI2 genes were directly sequenced, and the presence of gene CNV was analysed by multiplex ligation‐dependent probe amplification (MLPA).ResultsAnterior pituitary deficiency was found in 74% and 53% of patients with SOD or HPE, respectively. Diabetes insipidus was common in patients with HPE (47%) but infrequent in patients with congenital hypopituitarism or SOD (7% and 8%, respectively). A single heterozygous nonsense SHH mutation (p.Tyr175Ter) was found in a patient presenting with hypopituitarism and alobar HPE. No other SHH mutations or CNV were found. Nine GLI2 variations (8 missense and 1 frameshift) including a homozygous and a compound heterozygous variation were found in patients with congenital hypopituitarism or SOD, but not in HPE patients. No GLI2 CNV were found.ConclusionSHH mutations or copy number variations are not a common cause of congenital hypopituitarism in patients without complex midline cerebral defects. GLI2 variants are found in some patients with congenital hypopituitarism without complex midline cerebral defects or septo‐optic dysplasia. However, functional analyses of these variants are needed to strengthen genotype–phenotype relationship.
Children's Explanations as a Window Into Their Intuitive Theories of the Social World
Authors: Rhodes Marjorie 
Published: July 2014

AbstractSocial categorization is an early emerging and robust component of social cognition, yet the role that social categories play in children's understanding of the social world has remained unclear. The present studies examined children's (N = 52 four‐ and five‐year olds) explanations of social behavior to provide a window into their intuitive theories of how social categories constrain human action. Children systematically referenced category memberships and social relationships as causal‐explanatory factors for specific types of social interactions: harm among members of different categories more than harm among members of the same category. In contrast, they systematically referred to agents' mental states to explain the reverse patterns of behaviors: harm among members of the same category more than harm among members of different categories. These data suggest that children view social category memberships as playing a causal‐explanatory role in constraining social interactions.
Peer Assessment of Aviation Performance: Inconsistent for Good Reasons
Authors: Roth Wolff‐Michael , Mavin Timothy J. 
Published: July 2014

AbstractResearch into expertise is relatively common in cognitive science concerning expertise existing across many domains. However, much less research has examined how experts within the same domain assess the performance of their peer experts. We report the results of a modified think‐aloud study conducted with 18 pilots (6 first officers, 6 captains, and 6 flight examiners). Pairs of same‐ranked pilots were asked to rate the performance of a captain flying in a critical pre‐recorded simulator scenario. Findings reveal (a) considerable variance within performance categories, (b) differences in the process used as evidence in support of a performance rating, (c) different numbers and types of facts (cues) identified, and (d) differences in how specific performance events affect choice of performance category and gravity of performance assessment. Such variance is consistent with low inter‐rater reliability. Because raters exhibited good, albeit imprecise, reasons and facts, a fuzzy mathematical model of performance rating was developed. The model provides good agreement with observed variations.
25‐Hydroxyvitamin D and Ankle‐Brachial Blood Pressure Index in Adults without Peripheral Artery Disease
Authors: Amer Muhammad , Narotsky David L. , Qayyum Rehan 
Published: July 2014

ABSTRACTBackgroundInverse association between lower level of 25‐hydroxyvitamin D [25(OH)D] and higher prevalence of peripheral arterial disease (PAD) among individuals with cardiovascular diseases (CVD) is known. Less is known about the relationship between 25(OH)D and ankle‐brachial blood pressure index (ABPI) in asymptomatic adults. We hypothesized a nonlinear relationship between 25(OH)D and ABPI in asymptomatic adults without PAD.MethodsData from the continuous NHANES (2001–2004) was used. Minimum of the two reported ABPI value was chosen for each individual (>18 years). Linear regression models with spline adjusted for demographic and traditional risk factors for CVD were used to examine nonlinear relationship between 25(OH)D and ABPI. Mean changes in ABPI per 10 ng/mL change in 25(OH)D were reported.ResultsMean (SD) age and 25(OH)D levels of 4979 participants (48% females) were 60.4 (13.22) years and 22.1 (8.68) ng/mL, respectively, while mean (SD) ABPI was 1.07 (0.15). We observed positive association between 25(OH)D and ABPI both in the univariable and multivariable regression models (all p < 0.05). In univariable regression with spline, a significant increase in ABPI (ß = 0.03, 95% CI: 0.02–0.04) was observed until 25(OH)D reached but not above 27 ng/mL. Similarly, in multivariable spline models, 25(OH)D was positively associated with ABPI (ß = 0.02, 95% CI: 0.01–0.03) only up to 27 ng/mL.ConclusionsIn asymptomatic adults without PAD, rising serum 25(OH)D concentration but not above 27 ng/mL was associated with statistically significant increase in ABPI.
Continuity and change in children's longitudinal neural responses to numbers
Authors: Emerson Robert W. , Cantlon Jessica F. 
Published: July 2014

AbstractHuman children possess the ability to approximate numerical quantity nonverbally from a young age. Over the course of early childhood, children develop increasingly precise representations of numerical values, including a symbolic number system that allows them to conceive of numerical information as Arabic numerals or number words. Functional brain imaging studies of adults report that activity in bilateral regions of the intraparietal sulcus (IPS) represents a key neural correlate of numerical cognition. Developmental neuroimaging studies indicate that the right IPS develops its number‐related neural response profile more rapidly than the left IPS during early childhood. One prediction that can be derived from previous findings is that there is longitudinal continuity in the number‐related neural responses of the right IPS over development while the development of the left IPS depends on the acquisition of numerical skills. We tested this hypothesis using fMRI in a longitudinal design with children ages 4 to 9. We found that neural responses in the right IPS are correlated over a 1–2‐year period in young children whereas left IPS responses change systematically as a function of children's numerical discrimination acuity. The data are consistent with the hypothesis that functional properties of the right IPS in numerical processing are stable over early childhood whereas the functions of the left IPS are dynamically modulated by the development of numerical skills.
Skin and glucocorticoids: effects of local skin glucocorticoid impairment on skin homeostasis
Authors: Nikolakis Georgios , Zouboulis Christos C. 
Published: July 2014

AbstractThe role of skin as a de novo source of glucocorticoids and the importance of cutaneous glucocorticoidogenesis as a homeostatic mechanism in human skin is highlighted by Slominski et al. in a recently published issue. Impairment of glucocorticoidogenesis through noxious stimuli, such as UVB, can explain pathophysiology of skin diseases (e.g. rosacea). In addition to keratinocytes, melanocytes and fibroblasts, cutaneous adnexes also play a significant role as targets and sources of glucocorticoids, because they express most of the enzymes required for steroidogenesis. Glucocorticoids are also involved in the pathogenesis of acne lesions, affecting sebum production in vivo and in vitro. Certain steroidogenic enzymes, such as 11β‐hydroxysteroid dehydrogenase, are upregulated in acne lesions. On this background, the paper by Slominski et al. provides further insights into dermatoendocrinology, with emphasis on the importance of an impairment of the skin's own hypothalamic–pituitary–adrenal‐like axis in the pathophysiology of several skin diseases.
Genetic diversity within sea trout population from an intensively stocked southern Baltic river, based on microsatellite DNA analysis
Authors: Bernaś R. , Burzyński A. , Dębowski P. , Poćwierz‐Kotus A. , Wenne R. 
Published: July 2014

AbstractSea trout, Salmo trutta L., populations in the Slupia River basin have been affected by mass stocking with smolts and fry. This work is focused on a small‐scale differentiation in sea trout populations from one basin with a strong emphasis on the relationship between wild and hatchery origin fish. A total of 216 sea trout were genotyped at 10 microsatellite loci. Global FST obtained by amova was low at 0.0165. Pairwise FST were significant for all tests except wild and stocked adults. The highest pairwise difference was found between the hatchery sample and Kwacza (FST = 0.038). Analysis of the genetic structure revealed micro‐geographical differentiation with four subpopulations. The quality of the artificial spawning was found not to be adequate with a high risk of adverse effects to the whole population. All future stocking actions in the basin should consider the existing population structures.
Differences in Gastric Mucosal Microbiota Profiling in Patients with Chronic Gastritis, Intestinal Metaplasia, and Gastric Cancer Using Pyrosequencing Methods
Authors: Eun Chang Soo , Kim Byung Kwon , Han Dong Soo , Kim Seon Young , Kim Kyung Mo , Choi Bo Youl , Song Kyu Sang , Kim Yong Sung , Kim Jihyun F. 
Published: July 2014

AbstractBackgroundHelicobacter pylori (H. pylori) infection plays an important role in the early stage of cancer development. However, various bacteria that promote the synthesis of reactive oxygen and nitrogen species may be involved in the later stages. We aimed to determine the microbial composition of gastric mucosa from the patients with chronic gastritis, intestinal metaplasia, and gastric cancer using 454 GS FLX Titanium.MethodsGastric mucosal biopsy samples were collected from 31 patients during endoscopy. After the extraction of genomic DNA, variable region V5 of the 16S rRNA gene was amplified. PCR products were sequenced using 454 high‐throughput sequencer. The composition, diversity, and richness of microbial communities were compared between three groups.ResultsThe composition of H. pylori‐containing Epsilonproteobacteria class appeared to be the most prevalent, but the relative increase in the Bacilli class in the gastric cancer group was noticed, resulting in a significant difference compared with the chronic gastritis group. By analyzing the Helicobacter‐dominant group at a family level, the relative abundance of Helicobacteraceae family was significantly lower in the gastric cancer group compared with chronic gastritis and intestinal metaplasia groups, while the relative abundance of Streptococcaceae family significantly increased. In a UPGMA clustering of Helicobacter‐dominant group based on UniFrac distance, the chronic gastritis group and gastric cancer group were clearly separated, while the intestinal metaplasia group was distributed in between the two groups. The evenness and diversity of gastric microbiota in the gastric cancer group was increased compared with other groups.ConclusionsIn Helicobacter predominant patients, the microbial compositions of gastric mucosa from gastric cancer patients are significantly different to chronic gastritis and intestinal metaplasia patients. These alterations of gastric microbial composition may play an important, as‐yet‐undetermined role in gastric carcinogenesis of Helicobacter predominant patients.