bluuebunny/crossref_metadata_2025 huggingface dataset:
Dramatic differences in gut bacterial densities help to explain the relationship between diet and habitat in rainforest ants
Authors: Sanders Jon G , Lukasik Piotr , Frederickson Megan E , Russell Jacob A , Koga Ryuichi , Knight Rob , Pierce Naomi E
Published: March 2017

Abundance is a key parameter in microbial ecology, and important to estimates of potential metabolite flux, impacts of dispersal, and sensitivity of samples to technical biases such as laboratory contamination. However, modern amplicon-based sequencing techniques by themselves typically provide no information about the absolute abundance of microbes. Here, we use fluorescence microscopy and quantitative PCR as independent estimates of microbial abundance to test the hypothesis that microbial symbionts have enabled ants to dominate tropical rainforest canopies by facilitating herbivorous diets, and compare these methods to microbial diversity profiles from 16S rRNA amplicon sequencing. Through a systematic survey of ants from a lowland tropical forest, we show that the density of gut microbiota varies across several orders of magnitude among ant lineages, with median individuals from many genera only marginally above detection limits. Supporting the hypothesis that microbial symbiosis is important to dominance in the canopy, we find that the abundance of gut bacteria is positively correlated with stable isotope proxies of herbivory among canopy-dwelling ants, but not among ground-dwelling ants. Notably, these broad findings are much more evident in the quantitative data than in the 16S rRNA sequencing data. Our results help to resolve a longstanding question in tropical rainforest ecology, and have broad implications for the interpretation of sequence-based surveys of microbial diversity.
WTFgenes: What's The Function of these genes? Static sites for model-based gene set analysis
Authors: Mungall Christopher J. , Holmes Ian H.
Published: March 2017

A common technique for interpreting experimentally-identified lists of genes is to look for enrichment of genes associated to particular ontology terms. The most common technique uses the hypergeometric distribution; more recently, a model-based approach was proposed. These approaches must typically be run using downloaded software, or on a server. We develop a collapsed likelihood for model-based gene set analysis and present WTFgenes, an implementation of both hypergeometric and model-based approaches, that can be published as a static site with computation run in JavaScript on the user's web browser client. Apart from hosting files, zero server resources are required: the site can (for example) be served directly from Amazon S3 or GitHub Pages. A C++11 implementation yielding identical results runs roughly twice as fast as the JavaScript version. WTFgenes is available fromhttps://github.com/evoldoers/wtfgenesunder the BSD3 license. A demonstration for the Gene Ontology is usable athttps://evoldoers.github.io/wtfgo. Contact: Ian Holmesihholmes+wtfgenes@gmail.com.
Estrogen receptor alpha is required in GABAergic, but not glutamatergic, neurons to masculinize the brain
Authors: Wu Melody V. , Tollkuhn Jessica
Published: March 2017

Masculinization of the rodent brain is driven by estrogen signaling during a perinatal critical period. Genetic deletion of estrogen receptor alpha (Esr1/ERα) results in altered hypothalamic-pituitary-gonadal (HPG) axis signaling and a dramatic reduction of male sexual and territorial behaviors. However, the requirement of ERα function in masculinizing distinct classes of neurons, and if these populations mediate components of male-typical behavior, remains unexplored. We deleted ERα in excitatory or inhibitory neurons using either aVglut2orVgatdriver and assessed male behaviors. We find thatVglut2-Cre;Esr1lox/loxmutant males lack ERa in the ventrolateral region of the ventromedial hypothalamus (VMHvl) and posterior ventral portion of the medial amygdala (MePV). These mutants recapitulate the increased serum testosterone levels seen with constitutive ERα deletion, but have none of the behavioral deficits. In contrast,Vgat-Cre;Esr1lox/loxmales with substantial ERα deletion in inhibitory neurons, including those of the principal nucleus of the bed nucleus of the stria terminalis (BNSTpr), posterior dorsal MeA (MePD), and medial preoptic area (MPOA) have normal testosterone levels, but display alterations in mating and territorial behaviors. These mutants also show demasculinized expression of androgen receptor (AR) and estrogen receptor beta (Esr2). Our results demonstrate that ERα masculinizes GABAergic neurons that gate the display of male-typical behaviors.
Unusual 4-arsonoanilinium cationic species in the hydrochloride salt of (4-aminophenyl)arsonic acid and formed in the reaction of the acid with copper(II) sulfate, copper(II) chloride and cadmium chloride
Authors: Smith Graham , Wermuth Urs D.
Published: March 2017

Structures having the unusual protonated 4-arsonoanilinium species, namely in the hydrochloride salt, C6H9AsNO3
+·Cl−, (I), and the complex salts formed from the reaction of (4-aminophenyl)arsonic acid (p-arsanilic acid) with copper(II) sulfate, i.e. hexaaquacopper(II) bis(4-arsonoanilinium) disulfate dihydrate, (C6H9AsNO3)2[Cu(H2O)6](SO4)2·2H2O, (II), with copper(II) chloride, i.e. poly[bis(4-arsonoanilinium) [tetra-μ-chlorido-cuprate(II)]], {(C6H9AsNO3)2[CuCl4]}
n
, (III), and with cadmium chloride, i.e. poly[bis(4-arsonoanilinium) [tetra-μ-chlorido-cadmate(II)]], {(C6H9AsNO3)2[CdCl4]}
n
, (IV), have been determined. In (II), the two 4-arsonoanilinium cations are accompanied by [Cu(H2O)6]2+ cations with sulfate anions. In the isotypic complex salts (III) and (IV), they act as counter-cations to the {[CuCl4]2−}
n
or {[CdCl4]2−}
n
anionic polymer sheets, respectively. In (II), the [Cu(H2O)6]2+ ion sits on a crystallographic centre of symmetry and displays a slightly distorted octahedral coordination geometry. The asymmetric unit for (II) contains, in addition to half the [Cu(H2O)6]2+ ion, one 4-arsonoanilinium cation, a sulfate dianion and a solvent water molecule. Extensive O—H...O and N—H...O hydrogen bonds link all the species, giving an overall three-dimensional structure. In (III), four of the chloride ligands are related by inversion [Cu—Cl = 2.2826 (8) and 2.2990 (9) Å], with the other two sites of the tetragonally distorted octahedral CuCl6 unit occupied by symmetry-generated Cl-atom donors [Cu—Cl = 2.9833 (9) Å], forming a two-dimensional coordination polymer network substructure lying parallel to (001). In the crystal, the polymer layers are linked across [001] by a number of bridging hydrogen bonds involving N—H...Cl interactions from head-to-head-linked As—O—H...O 4-arsonoanilinium cations. A three-dimensional network structure is formed. CdII compound (IV) is isotypic with CuII complex (III), but with the central CdCl6 complex repeat unit having a more regular M—Cl bond-length range [2.5232 (12)–2.6931 (10) Å] compared to that in (III). This series of compounds represents the first reported crystal structures having the protonated 4-arsonoanilinium species.
Consumer characteristics as drivers of online information searches
Authors: Gallant Isabelle , Arcand Manon
Published: March 2017

Purpose

The purpose of this study is to investigate consumer characteristics (gender, subjective knowledge of product category, susceptibility to social influence, attitude to internet shopping and internet use) having a bearing on the proportion of online information searches conducted using personal and impersonal information sources, and to explore which of these factors impact the use of electronic word-of-mouth (eWOM).

Design/methodology/approach

A real-time longitudinal design is used to survey 274 consumers about their information searches when shopping for high involvement goods.

Findings

Susceptibility to normative social influence and internet use prove the main drivers of the inclination to resort to the internet to conduct searches using personal information sources. Subjective knowledge also positively impacts the proportion of time spent online conducting searches using personal information sources. Men and consumers with a positive attitude to internet shopping use a greater proportion of impersonal online information sources. Complementary analyses show that the use of eWOM is driven by almost all consumer characteristics (except gender) investigated.

Originality/value

By using a real-time longitudinal approach, this study directly addresses calls for more research into information searches by investigating multi-channel source use in actual purchase situations and minimizing bias relating to forgotten information, while facilitating the collection of more valid data on consumer information search behaviour. The paper also ranks as one of the first to revisit the drivers of the proportion of online information sources in personal and impersonal sources in the era of Web 2.0.
Metformin attenuates renal fibrosis in both AMPKα2‐dependent and independent manners
Authors: Feng Yenan , Wang Shuaixing , Zhang Youyi , Xiao Han
Published: March 2017

Metformin is a well‐known AMP‐activated protein kinase (AMPK) activator, and it has been shown to inhibit organ fibrosis. Whether AMPKα2 mediates metformin protection against renal fibrosis remains unknown. Here, we aimed to investigate the role of the AMPKα2 isoform in mediating the inhibitory effect of metformin on renal fibrosis. Unilateral ureteral obstruction (UUO) was used to induce renal fibrosis in wild‐type (WT) and AMPKα2 knockout (AMPKα2−/−) mice. Metformin treatment was initiated 3 days before UUO and was continued until 7 days after UUO. In WT mice, metformin significantly inhibited UUO‐induced renal fibrosis. In AMPKα2−/− mice, metformin also tended to inhibit UUO‐induced renal fibrosis. Specifically, metformin significantly reduced UUO‐induced transforming growth factor β1 (TGFβ1) mRNA and protein expression in WT mice but not in AMPKα2−/− mice. In contrast, metformin reduced UUO‐induced TGFβ1 downstream Smad3 phosphorylation in both WT and AMPKα2−/− mice, suggesting that this regulation occurs in an AMPKα2‐independent manner. In conclusion, the underlying mechanisms for the protective effects of metformin against renal fibrosis include AMPKα2‐dependent targeting of TGFβ1 production and AMPKα2‐independent targeting of TGFβ1 downstream signalling. In this regard, metformin has an advantage over other AMPK activators for the treatment of renal fibrosis.
An indirect legitimacy argument for a directly elected European Parliament
Authors: LORD CHRISTOPHER
Published: March 2017

Can a directly elected European Parliament help deliver standards by which the European Union can be indirectly legitimated through its component national democracies? This article argues that the Union can be indirectly legitimate where it helps member state democracies meet their own obligations to their own publics. The Union can do just that by managing externalities in ways needed to secure core values of justice, democracy and freedom from arbitrary domination within member states. Yet that poses a predicament: for if any one member state has an interest in imposing negative externalities or in freeriding on positive externalities provided by another, then so may its voters and democratic institutions. The article argues a directly elected European Parliament can help manage that predicament both by identifying externalities and by ensuring their regulation meets standards of public control, political equality and justification owed to individual national democracies.
Correlation between Antimicrobial, Antioxidant Activity, and Polyphenols of Alkalized/Nonalkalized Cocoa Powders
Authors: Todorovic Vanja , Milenkovic Marina , Vidovic Bojana , Todorovic Zoran , Sobajic Sladjana
Published: March 2017

Many factors can influence antioxidative and antimicrobial characteristics of plant materials. The quality of cocoa as functional food ingredient is influenced through its processing. The main aim of this study was to test if there is difference in polyphenol content, antioxidant capacity, and antimicrobial activity between nonalkalized and alkalized cocoa powders. To estimate polyphenol and flavonoid content in cocoa samples the spectrophotometric microassays were used. Flavan‐3ols were determined with reversed‐phase high‐performance liquid chromatography (RP‐HPLC). Antimicrobial activity against 3 Gram positive bacteria, 4 Gram negative bacteria and 1 strain of yeast was determined using broth microdilution method. Total polyphenol content was 1.8 times lower in alkalized cocoa samples than in natural ones. Epicatechin/catechin ratio was changed due to the process of alkalization in favor of catechin (2.21 in natural and 1.45 in alkalized cocoa powders). Combined results of 3 antioxidative tests (DPPH, FRAP, ABTS) were used for calculation of RACI (Relative Antioxidant Capacity Index) and GAS (Global Antioxidant Score) values that were consistently higher in natural than in alkalized cocoa extracts. Obtained results have shown significant correlations between these values and phenolic content (0.929 ≤ r ≤ 0.957, P < 0.01). Antimicrobial activity varied from 5.0 to 25.0 mg/ml (MICs), while Candida albicans was the most sensitive tested microorganism. Cocoa powders subjected to alkalization had significantly reduced content of total and specific phenolic compounds and reduced antioxidant capacity (P < 0.05), but their antimicrobial activity was equal for Gram‐positive bacteria or even significantly enhanced for Gram‐negative bacteria.
In Vitro Starch Digestibility of Commercial Gluten‐Free Pasta: The Role of Ingredients and Origin
Authors: Marti Alessandra , Abbasi Parizad Parisa , Marengo Mauro , Erba Daniela , Pagani Maria Ambrogina , Casiraghi Maria Cristina
Published: March 2017

Gluten replacement in gluten‐free (GF) products presents major challenges for the food industry in terms of sensorial, technological and nutritional characteristics. The absence of gluten reportedly affects starch digestibility, thus increasing the postprandial glycaemic response. However, the role of ingredients and processing conditions has been addressed only seldom. We investigated the in vitro starch digestibility of 9 commercial GF products (5 Italian pasta and 4 Oriental noodles) differing in formulation and processing conditions. Content of rapidly digestible starch (RDS), slowly digestible starch (SDS), and resistant starch (RS) were assessed and combined with information on starch pasting properties and on the overall protein organization. Oriental noodles presented higher relative levels of RS and RDS than Western‐style pasta, that often had SDS levels compatible with low rates of starch digestion. As regard formulation, presence of multiple ingredients seems to likely increase the RDS level, as did the different protein organization in the various samples.
Affect lability predicts occurrence of suicidal ideation in bipolar patients: a two‐year prospective study
Authors: Ducasse D. , Jaussent I. , Guillaume S. , Azorin J. M. , Bellivier F. , Belzeaux R. , Bougerol T. , Etain B. , Gard S. , Henry C. , Kahn J. P. , Leboyer M. , Loftus J. , Passerieux C. ,   FondaMental Advanced Centers of Expertise in Bipolar Disorders (FACE‐BD) Collaborators, Olié E. , Courtet P.
Published: March 2017

Objective

The aim of our study was to investigate, in bipolar patients, whether affect lability was associated with suicidal ideation incidence during 2‐year follow‐up, and which subtype of affect lability was associated with suicidal ideation.

Method

A total of 319 euthymic or mildly depressed bipolar outpatients recruited in the French FondaMental Advanced Centres of Expertise for Bipolar Disorder were divided into two subgroups according to the occurrence of suicidal ideation during a 2‐year follow‐up. Affect lability was assessed by the French version of the Affect Lability Scale.

Results

Bipolar patients with high affect lability were more likely to report suicidal ideation during follow‐up, even after adjustment for age, study level, rapid cycling, current depression level, anxiety disorder, and lifetime history SA (OR = 2.47; 95% CI [1.15–5.30], P = 0.01). The risk of suicidal ideation increased with the level of affect lability. More specifically, the propensity to switch from neutral to elation affect, from anxious to depressive affect (or inversely), and from neutral to anger affect predicted suicidal ideation.

Conclusion

Reducing affective lability could become a new therapeutic target of suicidal prevention in bipolar disorder.
No cognitive‐enhancing effect of GLP‐1 receptor agonism in antipsychotic‐treated, obese patients with schizophrenia
Authors: Ishøy P. L. , Fagerlund B. , Broberg B. V. , Bak N. , Knop F. K. , Glenthøj B. Y. , Ebdrup B. H.
Published: March 2017

Objective

Schizophrenia is associated with profound cognitive and psychosocial impairments. Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) are used for diabetes and obesity treatment, and animal studies have indicated cognitive‐enhancing effects. In this investigator‐initiated, double‐blind, randomized, placebo‐controlled trial, we tested non‐metabolic effects of exenatide once‐weekly (Bydureon™) in obese, antipsychotic‐treated patients with schizohrenia spectrum disorder.

Method

Before and after 3 months of exenatide (N = 20) or placebo (N = 20) treatment, patients were assessed with the following: Brief Assessment of Cognition in Schizophrenia (BACS), Rey–Osterreith complex figure test (REY), Short‐Form Health Survey (SF‐36), Personal and Social Performance Scale (PSP) and the Positive and Negative Syndrome Scale (PANSS). We used BACS composite score as the main outcome measure.

Results

Repeated measures analysis of variance on BACS composite score showed significant effect of ‘Time’ (P < 0.001), no effect of ‘Group’ (P = 0.64) and no ‘Time*Group’ interaction (P = 0.77). For REY, SF‐36, PSP and PANSS, only significant ‘Time’ effects were found.

Conclusion

The non‐significant results of this first clinical trial exploring non‐metabolic effects of a long‐acting GLP‐1RA in patients with schizophrenia could reflect a general problem of translating cognitive‐enhancing effects of GLP‐1RAs from animals to humans or be explained by factors specifically related to schizophrenia spectrum patients with obesity such as antipsychotic treatment.
Clinical high risk for psychosis: the association between momentary stress, affective and psychotic symptoms
Authors: van der Steen Y. , Gimpel‐Drees J. , Lataster T. , Viechtbauer W. , Simons C. J. P. , Lardinois M. , Michel T. M. , Janssen B. , Bechdolf A. , Wagner M. , Myin‐Germeys I.
Published: March 2017

Objective

The aim of this study was to assess associations between momentary stress and both affective and psychotic symptoms in everyday life of individuals at clinical high risk (CHR), compared to chronic psychotic patients and healthy controls, in search for evidence of early stress sensitization. It also assessed whether psychotic experiences were experienced as stressful.

Method

The experience sampling method was used to measure affective and psychotic reactivity to everyday stressful activities, events and social situations in 22 CHR patients, 24 patients with a psychotic disorder and 26 healthy controls.

Results

Multilevel models showed significantly larger associations between negative affect (NA) and activity‐related stress for CHR patients than for psychotic patients (P = 0.008) and for CHR compared to controls (P < 0.001). Similarly, the association between activity‐related stress and psychotic symptoms was larger in CHR than in patients (P = 0.02). Finally, the association between NA and symptoms (P < 0.001) was larger in CHR than in patients.

Conclusion

Stress sensitization seems to play a role particularly in the early phase of psychosis development as results suggest that CHR patients are more sensitive to daily life stressors than psychotic patients. In this early phase, psychotic experiences also contributed to the experience of stress.
Questionable diagnostic benefit of the commercially available panel of bee venom components
Authors: Arzt L. , Bokanovic D. , Schrautzer C. , Schwarz I. , Laipold K. , Aberer W. , Sturm G. J.
Published: March 2017

For many years, only the major allergen rApi m 1 has been available on the ImmunoCAP system for routine diagnosis of bee venom (BV) allergy. Now, there are five components available, and we aimed to detect the sensitivity and specificity of rApi m 1, 2, 3, 5, and 10 in BV‐allergic patients. We further evaluated the sensitivity of rApi m 1 and 2 of an alternative platform and investigated possible differences in the sensitization profile between monosensitization and clinically relevant double sensitization. Analysis of the whole panel of BV allergens of the CAP system still resulted in a lower sensitivity than analysis of the combination of rApi m 1 and 2 of the Immulite (71.6% vs 85.8%). Sensitization rate of rApi m 5 was more than doubled in double‐sensitized patients, while there was no difference for rApi m 2. The benefit of the commercially available panel of BV components is questionable, due to the insufficient sensitivity and still unavailable important cross‐reacting allergens.
Sevoflurane‐induced isoelectricEEGand burst suppression: differential and antagonistic effect of added nitrous oxide
Authors: Niu B. , Xiao J. Y. , Fang Y. , Zhou B. Y. , Li J. , Cao F. , Tian Y. K. , Mei W.
Published: March 2017

The objective of this study was to investigate whether nitrous oxide influenced theED50 of sevoflurane for induction of isoelectric electroencephalogram (ED50isoelectric) differently from its influence on theED50 of sevoflurane for electroencephalogram burst suppression (ED50burst). In a prospective, randomised, double‐blind, parallel group, up–down sequential allocation study, 77ASAphysical status 1 and 2 patients received sevoflurane induction and, after tracheal intubation, were randomly allocated to receive sevoflurane with either 40% oxygen in air (control group) or 60% nitrous oxide in oxygen mixture (nitrous group). TheED50isoelectricin the two groups was determined using Dixon's up and down method, starting at 2.5% with 0.2% step size of end‐tidal sevoflurane. The electroencephalogram was considered as isoelectric when a burst suppression ratio of 100% lasted > 1 min. The subsequent concentrations of sevoflurane administered were determined by the presence or absence of isoelectric electroencephalogram in the previous patient in the same group. TheED50isoelectricin the nitrous group 4.08 (95%CI, 3.95–4.38)% was significantly higher than that in the control group 3.68 (95%CI, 3.50–3.78)% (p < 0.0001). The values forED50burstwere 3.05 (95%CI, 2.66–3.90)% and 3.02 (95%CI, 3.00–3.05)% in nitrous group and control group, respectively (p = 0.52). The addition of 60% nitrous oxide increasesED50isoelectric, but not theED50burstof sevoflurane. Neither result indicates an additive effect of anaesthetic agents, as might be expected, and possible reasons for this are discussed.
Plasma long‐chain omega‐3 polyunsaturated fatty acids and macular pigment in subjects with family history of age‐related macular degeneration: the Limpia Study
Authors: Merle Bénédicte M. J. , Buaud Benjamin , Korobelnik Jean‐François , Bron Alain , Delyfer Marie‐Noëlle , Rougier Marie‐Bénédicte , Savel Hélène , Vaysse Carole , Creuzot‐Garcher Catherine , Delcourt Cécile
Published: March 2017

Purpose

In numerous epidemiological studies, omega‐3 polyunsaturated fatty acids (PUFAs) have been associated with a decreased risk of age‐related macular degeneration (AMD). Beyond their structural, functional and neuroprotective roles, omega‐3 PUFAs may favour the retinal accumulation of lutein and zeaxanthin and thus increase macular pigment optical density (MPOD). We examined the associations of MPOD with plasma omega‐3 PUFAs in subjects with family history of AMD.

Methods

The Limpia study is a double‐blind, placebo‐controlled, prospective randomized clinical trial performed in 120 subjects. Subjects with at least one parent treated for neovascular AMD, aged 40–70, with a best corrected visual acuity (BCVA) >20/25, free of late AMD and other major eye conditions and with no use of supplement containing lutein or zeaxanthin the preceding year were recruited in Bordeaux and Dijon, France. At baseline, MPOD within 1° of eccentricity was measured by modified Heidelberg retinal analyser (Heidelberg, Germany) and plasma omega‐3 PUFAs by gas chromatography. Medical history and lifestyle data were collected from a standardized questionnaire. Associations of MPOD with plasma omega‐3 PUFAs were assessed at the baseline examination, using mixed linear models adjusted for age, gender, centre, body mass index, smoking, plasma high‐density lipoprotein (HDL) cholesterol and lutein+zeaxanthin.

Results

After multivariate adjustment, high MPOD was significantly associated with higher level of plasma docosapentaenoic acid (DPA) (β = 0.029, 95% CI: 0.003, 0.055; p = 0.03). Plasma alpha linolenic, eicosapentaenoic and docosahexaenoic acids were not significantly associated with MPOD.

Conclusion

In the Limpia study, high MPOD within 1° was significantly associated with higher plasma levels of omega‐3 DPA.
Transformation of hepatitis C antiviral treatment in a national healthcare system following the introduction of direct antiviral agents
Authors: Moon A. M. , Green P. K. , Berry K. , Ioannou G. N.
Published: March 2017

Background

Highly effective direct antiviral agents (DAAs) for hepatitis C virus (HCV) were introduced recently. Their utilisation has been limited by high cost and low access to care.

Aim

To describe the effect of DAAs on HCV treatment and cure rates in the United States Veterans Affairs (VA) national healthcare system.

Methods

We identified all HCV antiviral treatment regimens initiated from 1 January 1999 to 31 December 2015 (n = 105 369) in the VA national healthcare system, and determined if they resulted in sustained virological response (SVR).

Results

HCV antiviral treatment rates were low (1981–6679 treatments/year) in the interferon era (1999–2010). The introduction of simeprevir and sofosbuvir in 2013 and ledipasvir/sofosbuvir and paritaprevir/ombitasvir/ritonavir/dasabuvir in 2014 were followed by increases in annual treatment rates to 9180 in 2014 and 31 028 in 2015. The number of patients achieving SVR was 1313 in 2010, the last year of the interferon era, and increased 5.6‐fold to 7377 in 2014 and 21‐fold to 28 084 in 2015. The proportion of treated patients who achieved SVR increased from 19.2% in 1999 and 36.0% in 2010 to 90.5% in 2015. Within 2015, monthly treatment rates ranged from 727 in July to 6868 in September correlating with the availability of funds for DAAs.

Conclusions

DAAs resulted in a 21‐fold increase in the number of patients achieving HCV cure. Treatment rates in 2015 were limited primarily by the availability of funds. Further increases in funding and cost reductions of DAAs in 2016 suggest that the VA could cure the majority of HCV‐infected Veterans in VA care within the next few years.
Associations of CYP2C9 and CYP2A6 Polymorphisms with the Concentrations of Valproate and its Hepatotoxin Metabolites and Valproate‐Induced Hepatotoxicity
Authors: Zhao Mingming , Zhang Ti , Li Guofei , Qiu Feng , Sun Yaxin , Zhao Limei
Published: March 2017

The aim of this study was to compare genetic polymorphisms and concentrations of hepatotoxic metabolites in patients with epilepsy and liver injury and those with normal liver function receiving valproate monotherapy to identify risk factors for VPA‐induced hepatotoxicity. A total of 279 Chinese patients with epilepsy were divided into an abnormal liver function (ANLFT) group (n = 79) and a normal liver function (NLFT) group (n = 200). Polymerase chain reaction–restriction fragment length polymorphism PCR‐RFLP and nested PCR were applied to identify the frequency of two SNPs in candidate genes. Serum concentrations of VPA and its major metabolites were determined by Ultra‐Performance Liquid Chromatography–tandem mass spectrometry UPLC‐MS/MS. Significant differences were found in genotype distributions of CYP2A6 and CYP2C9 between the two groups. The values of 4‐ene‐VPA and 2,4‐diene‐VPA in the ANLFT group were significantly higher than in the NLFT group. Only CYP2A6 polymorphisms had associations with the concentrations of 4‐ene‐VPA and 2,4‐diene‐VPA. CYP2A6*1/*4 and CYP2A6*4/*4 variant carriers had higher CDR4‐ene‐VPA and CDR2,4‐diene‐VPA values than CYP2A6*1/*1 carriers. The logistic regression analysis showed that CYP2C9 and CYP2A6 were significant risk factors for hepatotoxicity by increasing the risk by 7.50 and 5.13 times, respectively. These findings provide preliminary evidence that CYP2A6 and CYP2C9 are associated with hepatotoxicity. However, only the CYP2A6 polymorphism was found to be associated with concentrations of 4‐ene‐VPA and 2,4‐diene‐VPA. Potential important risk factors include mutated genotypes of CYP2C9 and CYP2A6 and higher concentrations of VPA, 4‐ene‐VPA and 2,4‐diene‐VPA.
Is estrogen exposure a protective factor for pancreatic neuroendocrine tumours in female patients with multiple endocrine neoplasia syndrome type 1?
Authors: Qiu Wei , Christakis Ioannis , Stewart Ashley A. , Vodopivec Danica M. , Silva‐Figueroa Angelica , Chen Huiqin , Woodard Terri L. , Halperin Daniel M. , Lee Jeffrey E. , Yao James C. , Perrier Nancy D.
Published: March 2017

Objective

Pancreatic neuroendocrine tumours (PNETs) are the most common cause of death in patients with multiple endocrine neoplasia type 1 (MEN1). Women have been shown to have improved survival, which may suggest a possible protective effect of female sex hormones. The aim of this study was to evaluate the relationship between estrogen exposure and PNET tumourigenesis, tumour growth and survival in female MEN1 patients with these tumours.

Design

We performed a retrospective chart review of the existing MEN1 database in our institution. Detailed information about female patients’ menstrual and reproductive history, and PNET clinicopathologic characteristics was collected. Questionnaires regarding estrogen exposure were used to collect information that was missing in the database.

Patients

Of 293 confirmed MEN1 cases, 141 women met the inclusion criteria.

Measurements

We used measures of cumulative estrogen exposure time (CEET), parity, live birth pregnancies and bilateral oophorectomy to estimate estrogen exposure.

Results

There was no significant association between CEET and time to PNET diagnosis (hazard ratio = 0·966, P = 0·380). For the correlation between estrogen exposure and PNET type, size, numbers, distant metastasis, lymph node metastasis, lymphovascular invasion, AJCC (American Joint Committee on Cancer) stage and overall survival, only CEET was significantly correlated with PNET size (P = 0·043).

Conclusions

In female patients with MEN1, estrogen exposure may inhibit PNET growth. A demonstrable protective effect against PNET tumourigenesis, tumour growth and survival of patients with these tumours may require a larger cohort.
Hand–arm bimanual intensive therapy: a new direction
Authors: Charles Jeanne
Published: March 2017

This commentary is on the original article by Bleyenheuft et al. on pages 625–633 of this issue.
Farmers at the heart of the ‘human capital revolution’? Decomposing the numeracy increase in early modern Europe†
Authors: Tollnek Franziska , Baten Joerg
Published: March 2017

Did the early development of skills and numerical abilities occur primarily in urban centres and among the elite groups of society? This study assesses the human capital of different occupational groups in the early modern period and partially confirms this finding: skilled and professional groups had higher levels of numeracy and literacy than persons in unskilled occupations. However, there was another large group that developed substantial human capital and represented around one‐third of the total population: farmers. By analysing numeracy and literacy evidence from six countries in Europe and Latin America, we argue that farmers contributed significantly to the formation of human capital and, consequently, to modern economic growth.
Gender, life cycle, and family ‘strategies’ among the poor: the Barcelona workhouse, 1762–1805
Authors: Carbonell‐Esteller Montserrat , Marfany Julie
Published: March 2017

Poor relief has received less attention from historians of southern Europe compared with northern Europe. This article seeks to challenge the frequent assumption that the strength of family ties in southern Europe mitigated the need for welfare provision. It provides new data for men and boys entering the Barcelona workhouse in the period 1780–1803, and compares these with data from an earlier study of women and girls who entered the same institution over the period 1762–1805. We establish the characteristics of those who sought relief in terms of age, place of origin, marital status, and occupation. We use the information on reasons for entry and exit to ascertain family circumstances. We show that there were significant differences between males and females in terms of why they entered and left, and length of stay, particularly among the elderly. The bulk of the population of the workhouse, however, was comprised of children and adolescents. For this group, entry into the workhouse represented not just a temporary solution to life cycle poverty and periodic unemployment, but also a longer‐term strategy aimed at smoothing entry into the labour market.
Reflexivity and academic writing: How supervisors deal with self‐discovery in student teachers' bachelor's theses
Authors: Studer Patrick
Published: March 2017

In light of the Bologna reform, professional and vocational schools have progressively moved towards becoming formal higher education institutions. In this context, Universities of Teacher Education (UTE) in Switzerland have undergone significant changes with respect to their role in society over the past decades. One of the major changes in this process concerns the training of research skills in formal teacher education. Part of this training includes writing assignments, such as the bachelor's thesis, with which students demonstrate their ability to participate in scientific discourses. This paper analyses the degree to which students engage in personal reflexivity when carrying out academic writing tasks, focusing, in particular, on how reflexivity is appraised by their thesis supervisors. The analysis of bachelor's theses and their evaluations from one Swiss UTE show that thesis supervisors show ambivalent and contradictory attitudes towards the self‐reflective engagement of their students.
Localized scleroderma: clinical and epidemiological features with emphasis on adulthood‐ versus childhood‐onset disease differences
Authors: Lis‐Święty A. , Skrzypek‐Salamon A. , Ranosz‐Janicka I. , Brzezińska‐Wcisło L.
Published: March 2017

Background

Localized scleroderma is a rare inflammatory skin disorder that affects the skin and sometimes underlying subcutaneous tissue, muscles or bones. The disease has two modes of onset: juvenile‐ (JLS) and adult‐onset (aLoS). Clinical features have impact on diagnostic and treatment recommendations, but no consensus on the disease management depending on the age at diagnosis was given.

Objective

To identify these features which differentiate aLoS from JLS.

Methods

A review of the literature was carried out using the MEDLINE to identify studies assessing demographics, subtype distribution, extracutaneous manifestations, comorbidities, delay at diagnosis and outcome in JLS and aLoS. Non‐English articles, reviews, case reports, treatment trials that did not investigate long‐term outcomes and studies with the fused data for children and adults were excluded. The analysed papers were published between June 1986 and December 2016.

Results

Fifty‐five studies describing JLS or/and aLoS were included for analysis. Female: male ratio in aLoS was higher than in JLS. Adults presented with plaque and generalized subtype more often than paediatric patients. Linear subtype, musculoskeletal, neurologic and ophthalmologic involvement were more frequent, among children. aLoS was likely to be associated with increased prevalence of lichen sclerosus. There was significant delay in diagnosis in both groups of patients. Recurrences of disease were independent of its onset mode. aLoS patients had more poor quality of life scores than did JLS patients. As only a few studies or no studies assessing specified disease subtypes were identified, this limited the ability to compare the adult and paediatric patients with these subtypes.

Conclusion

Despite more favourable course of aLoS, a thorough understanding of the broad spectrum of domains related to physical, mental, emotional and social functioning of patients seems to be important to the proper management of disease. LoS heterogeneity makes it important to develop universal classification criteria.
In Search of a Consistent Solution to Allocation of Joint Production
Authors: Weidema Bo P.
Published: March 2017

Three consistency problems are identified that arise when partitioning a product system with joint production according to an allocation key, such as revenue or mass of the joint products, namely: lacking consistency of rationales and procedures; lacking consistency of monetary, mass, and energy balances in the partitioned product systems; and lacking consistency of results across model resolution and classification of the intermediate flows. Different solutions to these consistency problems are described, including the attempt of ecoinvent to solve the third consistency problem with a system model that uses revenue allocation at the point of substitution. The problems with the different practical implementations are described. For each of the three consistency problems, a solution is proposed and combined into a single consistent solution. The consistency of rationales and procedures is ensured by asking only one question at a time and performing a separate allocation and calculation for each question. The problem of maintaining monetary, mass, and energy balances is solved by a generalized allocation correction. The identified problem with consistency of results across model resolution and classification is solved by redefining the point of substitution. It is described what consequences the solutions will have if their results are misused for decision making that will shift demand between products.
Characterization of anti-inflammatory effect and possible mechanism of action of Tibouchina granulosa
Authors: Sobrinho Andrea P , Minho Alan S , Ferreira Leide L C , Martins Gabriel R , Boylan Fabio , Fernandes Patricia D
Published: March 2017

Objectives

Tibouchina granulosa, popularly known as ‘quaresmeira’, belong to a genus widely used in the traditional medicine as infusions from their leaves. Other species of Tibouchina are used as antibacterial, antioxidant or antileishmanial. In this work, our objectives were to investigate the biological effects of T. granulosa in models of acute inflammation.

Methods

Chemical analysis showed the presence of proanthocyanidins and flavonoids. Infusions from leaves of T. granulosa (1, 3, 10, 30 or 100 mg/kg) were orally administered to mice, and the anti-inflammatory effects were evaluated by the formalin-induced licking response, inhibition of carrageenan-induced cell migration into subcutaneous air pouch (SAP) and inhibition of inflammatory mediator production in inflammatory exudate collected from SAP.

Key findings

Our data indicate that tested doses of T. granulosa infusion reduced cell migration, protein extravasated to SAP and cytokine production (i.e. TNF-α and IL-10). All doses also inhibited the first and second phase of formalin-induced licking response.

Conclusions

Taken together, our results indicate that leaves of T. granulosa present anti-inflammatory effect and can be useful in the preparation of new phytomedicines.
Trigonelline and vildagliptin antidiabetic effect: improvement of insulin signalling pathway
Authors: Aldakinah Amat-Alrazaq A , Al-Shorbagy Muhammad Y , Abdallah Dalaal M , El-Abhar Hanan S
Published: March 2017

Objectives

Trigonelline (TRG) is known to have an antidiabetic efficacy; however, its mechanism is not entirely elucidated.

Methods

Hence, its effect on insulin signaling, besides its effectiveness in combination with vildagliptin (VLD) in a Type 2 diabetes model has been tested.

Key findings

TRG (50 mg/kg; p.o) lowered serum glucose, fructosamine, insulin, and HOMA-IR index and increased insulin sensitivity in soleus muscle via augmenting insulin receptor autophosphorylation (IR-PH), pT308-Akt, and glucose transporter 4 (GLUT4). Additionally, it reduced muscle advanced glycation end products and lipid peroxides with increased glutathione. TRG showed an anti-lipidemic effect lowering serum and/or muscle total cholesterol, triglycerides, and FFAs to decrease body weight, and visceral/epididymal indices. Furthermore, VLD (3 and 10 mg/kg, p.o) increased IR-PH, pT308-Akt, and GLUT4 to improve insulin signaling. The combined effect of TRG with the low dose of VLD was mostly confined to the reduction of the aberrant lipid profile.

Conclusions

The beneficial effect of TRG on insulin sensitivity and glucose/ lipid homeostasis is mediated by the enhancement of the insulin signaling and antioxidant property. Moreover, the positive impact of VLD on pT308-Akt is an integral part in insulin signaling, and hence its antidiabetic effect.
Self‐reported sleep quantity, quality and sleep hygiene in elite athletes
Authors: Knufinke Melanie , Nieuwenhuys Arne , Geurts Sabine A. E. , Coenen Anton M. L. , Kompier Michiel A. J.
Published: March 2017

Sleep is essential for recovery and performance in elite athletes. While actigraphy‐based studies revealed suboptimal sleep in athletes, information on their subjective experience of sleep is scarce. Relatively unexplored is also the extent to which athletes’ sleep is adversely affected by environmental conditions and daytime behaviours, that is sleep hygiene. This study aimed to provide insight in sleep quantity, quality and its putative association with sleep hygiene. Participants were 98 elite (youth) athletes competing at the highest (inter‐)national level. Sleep quantity, quality and sleep hygiene were assessed once covering a 1‐month period by using established (sub)clinical questionnaires, and repeatedly during 7 consecutive days. Sleep quality was generally healthy, although 41% of all athletes could be classified as ‘poor sleeper’, and 12% were identified as having a sleep disorder. Daily self‐monitoring revealed sleep durations of 8:11 ± 0:45 h, but elevated wake after sleep onset of 13 ± 19 min. Sleep quality, feeling refreshed, and morning vigor were moderate at best. Regarding sleep hygiene, general measures revealed irregular sleep–wake patterns, psychological strain and activating pre‐sleep behaviours. At the daily level, blue‐light exposure and late‐evening consumption of heavy meals were frequently reported. General sleep hygiene revealed significant associations with sleep quality (0.45 < r > 0.50; P < 0.001). Results indicate that there is ample room for optimization, specifically in onset latency and in wake after sleep onset. Subtle improvements in sleep seem possible, and optimizing sleep hygiene, such as regular sleep–wake patterns and reducing psychological strain, may facilitate this sleep upgrading process.
Long‐term trends in chronic hepatitis B virus infection associated liver transplantation outcomes in the United States
Authors: Young K. , Liu B. , Bhuket T. , Younossi Z. , Saab S. , Ahmed A. , Wong R. J.
Published: March 2017

With effective antiviral therapies, rates of hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) and decompensated liver disease requiring liver transplantation (LT) are expected to decrease. We aim to evaluate overall trends in LT waitlist registrations, waitlist survival and likelihood of receiving LT among chronic HBV patients in the United States. Using the United Network for Organ Sharing database, we retrospectively evaluated adults (age≥18) with chronic HBV (with and without HCC) listed for LT from 1992 to 1996 (Era 1) vs 1997 to 2004 (Era 2) vs 2005‐2015 (Era 3). Multivariate Cox‐regression models evaluated probability of waitlist survival and receiving LT. Overall, 6797 chronic HBV adults were listed for LT. While the total number of HBV patients listed for LT remained stable, the proportion of HBV patients with HCC increased from 5.4% in Era 1 to 39.0% in Era 3. Compared to Era 1, waitlist mortality was higher in Era 2 (HR: 4.55, P<.001) and Era 3 (HR: 3.63, P<.001). However, in the most recent era, waitlist mortality significantly improved (compared to 2005‐2007: 2008‐2011: HR: 0.74, P=.05, 95% CI: 0.55‐0.99; 2012‐2015: HR: 0.53, P<.001, 95% CI: 0.38‐0.75). Probability of receiving LT was also lower with latter time periods (compared to 2005‐2007: 2008‐2011: HR: 0.77, P<.001 95% CI: 0.68‐0.86; 2012‐2015: HR: 0.61, P<.001, 95% CI: 0.54‐0.69). Although the number of HBV patients requiring LT remained stable, the proportion of HBV patients with HCC continues to rise. The decrease in waitlist mortality and lower likelihood of LT among HBV patients may reflect the effectiveness of antiviral therapies in delaying disease progression in the current era.
Recent theoretical, neural, and clinical advances in sustained attention research
Authors: Fortenbaugh Francesca C. , DeGutis Joseph , Esterman Michael
Published: March 2017

Models of attention often distinguish among attention subtypes, with classic models separating orienting, switching, and sustaining functions. Compared with other forms of attention, the neurophysiological basis of sustaining attention has received far less notice, yet it is known that momentary failures of sustained attention can have far‐ranging negative effects in healthy individuals, and lasting sustained attention deficits are pervasive in clinical populations. In recent years, however, there has been increased interest in characterizing moment‐to‐moment fluctuations in sustained attention, in addition to the overall vigilance decrement, and understanding how these neurocognitive systems change over the life span and across various clinical populations. The use of novel neuroimaging paradigms and statistical approaches has allowed for better characterization of the neural networks supporting sustained attention and has highlighted dynamic interactions within and across multiple distributed networks that predict behavioral performance. These advances have also provided potential biomarkers to identify individuals with sustained attention deficits. These findings have led to new theoretical models explaining why sustaining focused attention is a challenge for individuals and form the basis for the next generation of sustained attention research, which seeks to accurately diagnose and develop theoretically driven treatments for sustained attention deficits that affect a variety of clinical populations.
Quine against Lewis (and Carnap) on Truth by Convention
Authors: Morris Sean
Published: March 2017

Many commentators now view Quine's ‘Truth by Convention’ as a flawed criticism of Carnap. Gary Ebbs argued recently that Quine never intended Carnap as his target. Quine's criticisms were part of his attempt to work out his own scientific naturalism. I agree that Carnap was not Quine's target but object that Quine's criticisms were wholly internal to his own philosophy. Instead, I argue that C.I. Lewis held the kind of truth‐by‐convention thesis that Quine rejects. This, however, leaves Carnap out of the picture. I then show how Quine came to see the earlier criticisms as also having force against Carnap.