bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ExAC Browser: Displaying reference data information from over 60,000 exomes
Authors: Karczewski Konrad J. , Weisburd Ben , Thomas Brett , Ruderfer Douglas M. , Kavanagh David , Hamamsy Tymor , Lek Monkol , Samocha Kaitlin E. , Cummings Beryl B. , Birnbaum Daniel ,   The Exome Aggregation Consortium, Daly Mark J. , MacArthur Daniel G. 
Published: August 2016

AbstractWorldwide, hundreds of thousands of humans have had their genomes or exomes sequenced, and access to the resulting data sets can provide valuable information for variant interpretation and understanding gene function. Here, we present a lightweight, flexible browser framework to display large population datasets of genetic variation. We demonstrate its use for exome sequence data from 60,706 individuals in the Exome Aggregation Consortium (ExAC). The ExAC browser provides gene- and transcript-centric displays of variation, a critical view for clinical applications. Additionally, we provide a variant display, which includes population frequency and functional annotation data as well as short read support for the called variant. This browser is open-source, freely available, and has already been used extensively by clinical laboratories worldwide.
5‐Bromo‐2′‐deoxyuridine induced effluvium via p53‐mediated CD326‐positive keratinocyte apoptosis in C57BL/6 mice
Authors: Uh Kyung‐Jun , Hwang Woo‐Sung , Bae Ji‐Hyun , Jang Da‐Eun , Yeom Su‐Cheong 
Published: August 2016

AbstractAnagen effluvium develops because of disturbances in the hair follicle cycle, leading to acute and severe hair loss in humans. The objective of this study was to establish a mouse model of anagen effluvium by 5‐bromo‐2′‐deoxyuridine (BrdU) treatment, and evaluate the pathological changes and underlying mechanisms. We treated 9–10‐day‐old pups and 3–7‐week‐old C57BL/6 mice with BrdU. After successfully inducing hair loss in the neonatal pups, microscopic, immunohistochemical and flow cytometry analyses were conducted. BrdU induced early onset alopecia in neonates and caused epidermal thickening and hair shaft breakage. BrdU appeared to incorporate the CD326‐positive keratinocyte layer and induced p53‐related apoptosis. Keratinocyte apoptosis caused immune cell infiltration in the dermal region; M2 macrophages and neutrophils were dominant. The BrdU‐induced hair loss was dose‐dependent, and alopecia was visible at a dose range of 25–200 μg/g bodyweight. The BrdU‐induced anagen effluvium mouse model is novel and easily established by administrating four simple BrdU injections to pups; these mice showed synchronized onset of alopecia symptoms with little individual variation. Moreover, this model showed an alopecia phenotype similar to that of human anagen effluvium with acute, severe and widespread hair loss.
Mutation analysis of IL36RN gene in Japanese patients with palmoplantar pustulosis
Authors: Takahashi Toshifumi , Fujimoto Noriki , Kabuto Miho , Nakanishi Takeshi , Tanaka Toshihiro 
Published: August 2016

AbstractLoss‐of‐function mutations of the IL36RN gene, encoding interleukin‐36 receptor antagonist (IL‐36Ra), have been reported as major pathogenic causes of generalized pustular psoriasis (GPP), especially in cases lacking previous histories of psoriasis vulgaris. Palmoplantar pustulosis (PPP), which is traditionally included among GPP‐related diseases, has a controversial association with IL36RN. While a negative view about the said association has been recently published from Europe, variations of the IL36RN gene show great ethnic differences. In this study, we performed mutation analysis of the IL36RN gene in 88 Japanese patients with PPP and identified three types of single base substitutions in four patients, namely, p.Pro82Leu in two patients, p.Asn47Ser in one and p.Thr123Met in another. All variations were heterozygous and different from previous European reports. We compared the immunohistochemical findings of IL‐36Ra on patients with and without variation of the IL36RN gene; however, no significant differences were observed. Our data and the previous European study suggest that PPP is not associated with mutations of the IL36RN gene.
Comparative morphology of sensilla on antenna, maxillary palp and labial palp of larvae of white‐spotted and yellow‐spotted Asian long‐horned beetle,Anoplophora glabripennisMotschulsky (Coleoptera: Cerambycidae)
Authors: Yang Yuchao , Xu Lili , Ren Lili , Xu Zhichun , Zong Shixiang 
Published: August 2016

AbstractThe Asian long‐horned beetle (ALB) is one of the most important wood‐boring insects worldwide that damages broad‐leaved trees, primarily poplar, willow, elm and maple. Based on the color of the spots on the elytra, the beetles are separated into white‐spotted (ALB‐W) and yellow‐spotted (ALB‐Y) Asian long‐horned beetles. In order to clarify the morphology of sensilla on antenna, maxillary palp and labial palp of ALB‐W and ALB‐Y larvae, we studied the typology, morphology, number and distribution of the sensilla by scanning electron microscopy. The results showed that: (i) the antennae of two biotypes had five types of sensilla, including three types of sensilla basiconica (b.) and two types of sensilla twig basiconica (s.tb); numbers of b.1, b.2, b.3 and s.tb1 on antenna were not significantly different (P > 0.05) between two biotypes, and the numbers of s.tb2 were significantly different (P < 0.05); (ii) the maxillary palp of two biotypes had four types of sensilla, including sensilla styloconica (st.), two types of s.tb and digitiform sensilla (ds.); the numbers of st. and ds. on the maxillary palp were not significantly different (P > 0.05) between two biotypes, and the numbers of s.tb1 and s.tb2 were significantly different (P < 0.05); (iii) the labial palp of two biotypes had four types of sensilla, including b., st. and two types of s.tb, and the numbers of b.3, st., s.tb1 and s.tb2 on the labial palp were not significantly different (P > 0.05) between two biotypes. We discuss the relationships between sensilla and damage caused by the larvae inside the host trees.
Chemical meat bait traps versus basic meat bait traps in collection of adult flies
Authors: Açikgöz Halide Nihal , Köse Serdal Kenan , Divrak Duygu 
Published: August 2016

AbstractThe aim of the present study is to compare the effectiveness of chemical meat bait traps and basic meat bait traps for collecting adult flies. Bait traps used to collect these species can be damaged by anthropogenic or environmental effects. In this study, chemical meat bait traps and basic meat bait traps were hung from trees in the garden of the Ankara University Forensic Sciences Institute. This activity was carried out on the first Monday of each month for nine months. During the study, 1894 specimens were collected. Of all these species, 1787 (94.35%) were obtained from chemical meat bait traps (CMBTs), while 107 (5.65%) were obtained from basic meat bait traps (BMBTs). To determine the diversity of species in CMBT and BMBT sample groups in our study, Shannon Wiener and Simpson diversity and dominance indices were used. Shannon Evenness Index was calculated to determine the relationship between species community‐density. Cluster analysis provided a summary of the similarity in species composition of different regions. The CMBT and BMBT trap groups similarity/dissimilarity feature was checked using Bray–Curtis cluster analysis. The number of species collected from CMBTs was considerably higher than in BMBTs. The results of this study will help researchers to save time. In addition, it should be kept in mind that thiamethoxam is harmful to the environment when it contaminates sources of water.
Neighborhood‐Level Drinking Norms and Alcohol Intervention Outcomes in HIV Patients Who Are Heavy Drinkers
Authors: Elliott Jennifer C. , Delker Erin , Wall Melanie M. , Feng Tianshu , Aharonovich Efrat , Tracy Melissa , Galea Sandro , Ahern Jennifer , Sarvet Aaron L. , Hasin Deborah S. 
Published: August 2016

BackgroundHeavy alcohol consumption can be harmful, particularly for individuals with HIV. There is substantial variability in response to interventions that aim to reduce drinking. Neighborhood drinking norms may explain some of this variability among HIV‐infected patients. Therefore, we investigated whether neighborhood‐level drinking norms modified response to alcohol intervention among HIV‐infected heavy drinkers.MethodsHeavily‐drinking HIV comprehensive care patients (n = 230) completed 1 of 3 brief alcohol interventions (an educational intervention, a motivational interviewing [MI] intervention, or an MI intervention with a technological enhancement called HealthCall). Drinking was reported at baseline and end of treatment (60 days). Neighborhood‐level drinking norms were obtained from a separate general population study.ResultsPatients’ reductions in drinks per drinking day in response to MI (as compared with the educational control) were more pronounced in neighborhoods with more permissive drinking norms. In contrast, patients’ reductions in drinks per drinking day in response to MI plus HealthCall did not significantly vary between neighborhoods with different drinking norms. Norms did not evidence significant interactions with intervention condition for 3 other exploratory drinking outcomes (drinking frequency, binge frequency, and maximum quantity).ConclusionsNeighborhood‐level drinking norms help explain differential response to an alcohol MI intervention among HIV‐infected patients. This study suggests the utility of considering neighborhood context as an effect modifier of alcohol interventions.
Neovascular age‐related macular degeneration is not associated with coronary heart disease in a Chinese Population: a population‐based study
Authors: Hu Chao‐Chien , Lin Herng‐Ching , Sheu Jau‐Jiuan , Kao Li‐Ting 
Published: August 2016

AbstractPurposeThis case–control study aimed to explore the association between prior coronary heart disease (CHD) and neovascular age‐related macular degeneration (AMD) using a population‐based data set in Taiwan.MethodsWe analysed data sourced from the Taiwan Longitudinal Health Insurance Database 2005. The study consisted of 1970 patients with neovascular AMD as cases and 5910 age‐ and sex‐matched controls. We performed a conditional logistic regression to examine the odds ratio (OR) and its corresponding 95% confidence interval (CI) for previously diagnosed CHD between cases and controls.ResultsOf the 7880 sampled patients, 24.5% had a prior history of CHD; CHD was found in 25.7% of cases and in 22.7% of controls (p = 0.008). The conditional logistic regression analysis indicated that the OR for prior CHD for cases was 1.17 [95% confidence interval (CI): 1.04–1.32] compared to the controls. However, after adjusting for patient's monthly income, geographic location, urbanization level, age, hyperlipidaemia, diabetes and hypertension, we failed to observe an association between prior CHD and AMD (OR = 1.03, 95% CI = 0.91–1.17). Additionally, the medical comorbidities of hyperlipidaemia (adjusted OR = 1.29, 95% CI = 1.15–1.45), hypertension (adjusted OR = 1.20, 95% CI = 1.05–1.37) and diabetes (adjusted OR = 1.47, 95% CI = 1.32–1.65) were significantly associated with AMD.ConclusionsThis study presented no significant difference in the odds of prior CHD between patients with AMD and those without AMD after adjusting for comorbidities and sociodemographic characteristics in a Chinese population.
Mode of perfusion influences infarct size, coronary flow and stress kinases in the isolated mouse heart
Authors: Bliksøen M. , Rutkovskiy A. , Vaage J. , Stensløkken K.‐O. 
Published: August 2016

AbstractAimThe isolated, retrogradely perfused heart (modified Langendorff model) is a widely used method in experimental heart research. The presence of an intraventricular balloon is necessary to get functional measurements. We have previously shown that the balloon induces phosphorylation of some suggested cardioprotective mitogen‐activated protein kinases (MAPK): P38‐MAPK, ERK 1/2 and JNK. We hypothesized that the balloon could influence cardioprotection, protect against ischaemia reperfusion injury and interfere with coronary flow.Methods and ResultsIsolated mouse hearts were perfused for 5, 10, 20, 40 and 60 min with a balloon in the left ventricle. We found a wavelike phosphorylation of all MAPK while AKT displayed a gradual dephosphorylation when compared to non‐perfused hearts. Hearts were subjected to 20 min of stabilization with or without the balloon, followed by 35 min of ischaemia and 120 min of reperfusion. Although the MAPK were phosphorylated, the infarcts were larger in the balloon group. When the balloon was present during the entire protocol, compared to removal at the end of ischaemia, the infarct size was also larger, especially in the endocardial layer. The balloon reduced post‐ischaemic endocardial coronary flow, despite a higher average flow, indicating a hyperperfused epicard. Blocking the balloon‐induced ERK 1/2 phosphorylation during stabilization did not affect infarct size. The effect of post‐conditioning was influenced by the balloon, showing reduced infarct size when the balloon was present.ConclusionThe balloon used for pressure measurements may contributes to cell death possibly by reducing endocardial coronary flow.
Eosinophilic drug reactions detected by a prospective pharmacovigilance programme in a tertiary hospital
Authors: Ramírez Elena , Medrano‐Casique Nicolás , Tong Hoi Y. , Bellón Teresa , Cabañas Rosario , Fiandor Ana , González‐Ramos Jessica , Herranz Pedro , Trigo Elena , Muñoz Mario , Borobia Alberto M. , Carcas Antonio J. , Frías Jesús 
Published: August 2016

AimWe conducted a prospective evaluation of all eosinophilic drug reactions (EDRs) through the Prospective Pharmacovigilance Program from Laboratory Signals at Hospital to find out the incidence and distribution of these entities in our hospital, their causative drugs, and predictors.MethodsAll peripheral eosinophilia >700 × 106 cells l−1 detected at admission or during hospitalisation, were prospectively monitored over 42 months. The spectrum of the localised or systemic manifestation of EDR, the incidence, the distribution of causative drugs, and the predictors were analysed.ResultsThe incidence of EDR was 16.67 (95% Poisson confidence interval [CI]: 9.90–25.98) per 10 000 admissions. Of 274 cases of EDR, 154 (56.2%) cases in 148 patients were asymptomatic hypereosinophilia. In the remaining 120 (43.8%) cases, there was other involvement. Skin and soft tissue reactions were detected in 36 (13.1%) cases; visceral EDRs in 19(7.0%) cases; and drug‐induced eosinophilic cutaneous and visceral manifestations were detected in the remaining 65 (23.7%) cases, 64 of which were potential drug reaction with eosinophilia and systemic symptoms (DRESS). After adjusting for age, sex, and hospitalisation wards, predictors of symptomatic eosinophilia were earlier onset of eosinophilia (hazard ratio [HR], 10.49; 95%CI: 3.13–35.16) higher eosinophil count (HR, 8.51; 95%CI: 3.28–22.08), and a delayed onset of corticosteroids (HR, 1.34; 95%CI: 1.01–1.73). A higher eosinophil count in patients with DRESS was significantly associated with greater impairment of liver function, prolonged hospitalisation, higher cumulative doses of corticosteroids, and if hypogammaglobinaemia was detected, a reactivation of human‐herpesvirus 6 was subsequently detected.ConclusionsHalf (53.3%, 64/120 cases) of symptomatic EDRs were potential DRESS. The main predictor of severity of EDR was an early severe eosinophilia.
Gene‐specific DNA methylation may mediate atypical antipsychotic‐induced insulin resistance
Authors: Burghardt Kyle J , Goodrich Jacyln M , Dolinoy Dana C , Ellingrod Vicki L 
Published: August 2016

ObjectivesAtypical antipsychotics (AAPs) carry a significant risk of cardiometabolic side effects, including insulin resistance. It is thought that the insulin resistance resulting from the use of AAPs may be associated with changes in DNA methylation. We aimed to identify and validate a candidate gene associated with AAP‐induced insulin resistance by using a multi‐step approach that included an epigenome‐wide association study (EWAS) and validation with site‐specific methylation and metabolomics data.MethodsSubjects with bipolar disorder treated with AAPs or lithium monotherapy were recruited for a cross‐sectional visit to analyze peripheral blood DNA methylation and insulin resistance. Epigenome‐wide DNA methylation was analyzed in a discovery sample (n = 48) using the Illumina 450K BeadChip. Validation analyses of the epigenome‐wide findings occurred in a separate sample (n = 72) using site‐specific methylation with pyrosequencing and untargeted metabolomics data. Regression analyses were conducted controlling for known confounders in all analyses and a mediation analysis was performed to investigate if AAP‐induced insulin resistance occurs through changes in DNA methylation.ResultsA differentially methylated probe associated with insulin resistance was discovered and validated in the fatty acyl CoA reductase 2 (FAR2) gene of chromosome 12. Functional associations of this DNA methylation site with untargeted phospholipid‐related metabolites were also detected. Our results identified a mediating effect of this FAR2 methylation site on AAP‐induced insulin resistance.ConclusionsGoing forward, prospective, longitudinal studies assessing comprehensive changes in FAR2 DNA methylation, expression, and lipid metabolism before and after AAP treatment are required to assess its potential role in the development of insulin resistance.
Understanding ironic criticism and empathic praise: The role of emotive communication
Authors: Agostino Alba , Im‐Bolter Nancie , Stefanatos Arianna K. , Dennis Maureen 
Published: August 2016

Ironic criticism and empathic praise are forms of social communication that influence the affective states of others in a negative or positive way. In a sample of 76 typically developing children and adolescents (mean age = 11 years; 4 months; SD: 2 years; 8 months), we studied how understanding of emotional expression (facial expression of emotion) and emotive communication (affective theory of mind) was related to the ability to understand negatively valenced ironic criticism and positively valenced empathic praise. We modelled comprehension of irony and empathy in school‐aged children in relation to age and understanding of emotional expression and emotive communication. As expected, children showed significantly better understanding of emotional expression than emotive communication, which requires understanding why someone might mask their inner emotions. Meditational analyses showed that emotive communication partially mediated the relation between age and understanding ironic criticism and empathic praise. These findings suggest that the development of understanding irony and empathy over the school‐age years is associated with affective attributions or affective theory of mind.
Statement of contribution

What is already known on this subject?

Theory of mind has been found to be related to the developmental understanding of social communication.

Correct interpretation of facial emotional cues is also important for interpreting social communication.

What does this study add?

Affective components (i.e., affective theory of mind) also contribute to the development of social communication.

Emotive communication, the ability to modulate one's emotional expression according to social display rules may be predictive of social communication competency.
Synthesis and biological evaluation of novel flavanone derivatives as potential antipsychotic agents
Authors: Gu Hong‐shun , Chen Xi , Zhang Jian‐wei , Zhang Lan , Li Lin 
Published: August 2016

In this study, a series of novel flavanone derivatives were designed and synthesized, and the antipsychotic activities of the target compounds were evaluated in vitro and in vivo. The results showed that synthesized compounds 7a–7g decreased the activity of dopamine D2 receptors in HEK293 cells co‐transfected with D2 receptor/G protein α16a, with IC50 values of 0.051–0.35 μm. Compounds 7a–7g inhibited the over‐production of nitric oxide stimulated by lipopolysaccharide/interferon‐γ in BV‐2 microglial cells. In mice, intragastric administration of 7d, 7e, and 7g reversed the increase in locomotor activity induced by MK‐801 (an antagonist of NMDA receptors) and decreased the hyperactivity of climbing behavior induced by apomorphine (a dopamine receptor agonist). These results suggest that some of the novel flavanone derivatives have potential antipsychotic effects and may be useful in the treatment of schizophrenia.
Elevation of Vδ1 T cells in peripheral blood and livers of patients with primary biliary cholangitis
Authors: Hua F , Wang L , Rong X , Hu Y , Zhang J M , He W , Zhang F C 
Published: August 2016

Summary
Primary biliary cholangitis (PBC), hitherto called primary biliary cirrhosis, is a cholestatic liver disease of unclear aetiology with autoimmune features. Accumulating evidence revealed that γδ T cells were involved in the development of autoimmune diseases. As one of γδ T cells subsets, however, the role of Vδ1 T cells in the immunopathogenesis of PBC is poorly understood. We analysed peripheral blood Vδ1 T cells in PBC patients in active stage (ASP, n = 18), adequate responders (AR, n = 10) and inadequate responders (IAR, n = 4) to ursodeoxycholic acid (UDCA) and an age-matched healthy control group (n = 16) by flow cytometric analysis. The ASP group exhibited a significantly higher proportion and absolute number of Vδ1 T cells, which were also observed in immunofluorescence staining of liver biopsy specimens of PBC patients. Moreover, these Vδ1 T cells expressed a series of activation markers and intracellular cytokines, which may contribute to the immunopathogenesis of PBC. Our study will help to clarify the role of Vδ1 T cells in the development of PBC.