bluuebunny/crossref_metadata_2025 huggingface dataset:
Lymphoid differentiation of hematopoietic stem cells requires efficient Cxcr4 desensitization
Authors: Freitas Christelle , Wittner Monika , Nguyen Julie , Rondeau Vincent , Biajoux Vincent , Aknin Marie-Laure , Gaudin Françoise , Beaussant-Cohen Sarah , Bertrand Yves , Bellanné-Chantelot Christine , Donadieu Jean , Bachelerie Françoise , Espéli Marion , Dalloul Ali , Louache Fawzia , Balabanian Karl
Published: May 2017

The CXCL12/CXCR4 signaling exerts a dominant role in promoting hematopoietic stem and progenitor cell (HSPC) retention and quiescence in bone marrow. Gain-of-function CXCR4 mutations that affect homologous desensitization of the receptor have been reported in the WHIM Syndrome (WS), a rare immunodeficiency characterized by lymphopenia. The mechanisms underpinning this remain obscure. Using a mouse model with a naturally occurring WS-linked gain-of-function Cxcr4 mutation, we explored the possibility that the lymphopenia in WS arises from defects at the HSPC level. We reported that Cxcr4 desensitization is required for quiescence/cycling balance of murine short-term hematopoietic stem cells and their differentiation into multipotent and downstream lymphoid-biased progenitors. Alteration in Cxcr4 desensitization resulted in decrease of circulating HSPCs in five patients with WS. This was also evidenced in WS mice and mirrored by accumulation of HSPCs in the spleen, where we observed enhanced extramedullary hematopoiesis. Therefore, efficient Cxcr4 desensitization is critical for lymphoid differentiation of HSPCs, and its impairment is a key mechanism underpinning the lymphopenia observed in mice and likely in WS patients.
Corticotropin releasing hormone receptor 2 exacerbates chronic cardiac dysfunction
Authors: Tsuda Takuma , Takefuji Mikito , Wettschureck Nina , Kotani Kazuhiko , Morimoto Ryota , Okumura Takahiro , Kaur Harmandeep , Eguchi Shunsuke , Sakaguchi Teruhiro , Ishihama Sohta , Kikuchi Ryosuke , Unno Kazumasa , Matsushita Kunihiro , Ishikawa Shizukiyo , Offermanns Stefan , Murohara Toyoaki
Published: May 2017

Heart failure occurs when the heart is unable to effectively pump blood and maintain tissue perfusion. Despite numerous therapeutic advancements over previous decades, the prognosis of patients with chronic heart failure remains poor, emphasizing the need to identify additional pathophysiological factors. Here, we show that corticotropin releasing hormone receptor 2 (Crhr2) is a G protein–coupled receptor highly expressed in cardiomyocytes and continuous infusion of the Crhr2 agonist, urocortin 2 (Ucn2), reduced left ventricular ejection fraction in mice. Moreover, plasma Ucn2 levels were 7.5-fold higher in patients with heart failure compared to those in healthy controls. Additionally, cardiomyocyte-specific deletion of Crhr2 protected mice from pressure overload-induced cardiac dysfunction. Mice treated with a Crhr2 antagonist lost maladaptive 3′-5′-cyclic adenosine monophosphate (cAMP)–dependent signaling and did not develop heart failure in response to overload. Collectively, our results indicate that constitutive Crhr2 activation causes cardiac dysfunction and suggests that Crhr2 blockade is a promising therapeutic strategy for patients with chronic heart failure.
Protein–Sol: a web tool for predicting protein solubility from sequence
Authors: Hebditch Max , Carballo-Amador M Alejandro , Charonis Spyros , Curtis Robin , Warwicker Jim
Published: May 2017

Motivation

Protein solubility is an important property in industrial and therapeutic applications. Prediction is a challenge, despite a growing understanding of the relevant physicochemical properties.

Results

Protein–Sol is a web server for predicting protein solubility. Using available data for Escherichia coli protein solubility in a cell-free expression system, 35 sequence-based properties are calculated. Feature weights are determined from separation of low and high solubility subsets. The model returns a predicted solubility and an indication of the features which deviate most from average values. Two other properties are profiled in windowed calculation along the sequence: fold propensity, and net segment charge. The utility of these additional features is demonstrated with the example of thioredoxin.

Availability and implementation

The Protein–Sol webserver is available at http://protein-sol.manchester.ac.uk.
Electromagnetic interior transmission eigenvalue problem for inhomogeneous media containing obstacles and its applications to near cloaking
Authors: Li Xiaofei , Li Jingzhi , Liu Hongyu , Wang Yuliang
Published: May 2017

This article is concerned with the invisibility cloaking in electromagnetic wave scattering from a new perspective. We are especially interested in achieving the invisibility cloaking by completely regular and isotropic mediums. Our study is based on an interior transmission eigenvalue problem. We propose a cloaking scheme that takes a three-layer structure including a cloaked region, a lossy layer and a cloaking shell. The target medium in the cloaked region can be arbitrary but regular, whereas the mediums in the lossy layer and the cloaking shell are both regular and isotropic. We establish that there exists an infinite set of incident waves such that the cloaking device is nearly invisible under the corresponding wave interrogation. The set of waves is generated from the Maxwell–Herglotz approximation of the associated interior transmission eigenfunctions. We provide the mathematical design of the cloaking device and sharply quantify the cloaking performance.
Natural and artificial spectral edges in exoplanets
Authors: Lingam Manasvi , Loeb Abraham
Published: May 2017

Technological civilizations may rely upon large-scale photovoltaic arrays to harness energy from their host star. Photovoltaic materials, such as silicon, possess distinctive spectral features, including an ‘artificial edge' that is characteristically shifted in wavelength shortwards of the ‘red edge' of vegetation. Future observations of reflected light from exoplanets would be able to detect both natural and artificial edges photometrically, if a significant fraction of the planet's surface is covered by vegetation or photovoltaic arrays, respectively. The stellar energy thus tapped can be utilized for terraforming activities by transferring heat and light from the day side to the night side on tidally locked exoplanets, thereby producing detectable artefacts.
Exploring Different Mutations at a Single Amino Acid Position of Cucumber green mottle mosaic virus Replicase to Attain Stable Symptom Attenuation
Authors: Liu Liming , Peng Bin , Zhang Zhenwei , Wu Yang , Miras Manuel , Aranda Miguel A. , Gu Qinsheng
Published: May 2017

Cucumber green mottle mosaic virus (CGMMV) is a member of the genus Tobamovirus (family Virgaviridae) that causes serious economic losses in cucurbit crops. A possibility for CGMMV control is the use of cross-protection, for which stable attenuated isolates are required. In this study, an infectious clone was constructed for the hn isolate of CGMMV. Unexpectedly, this clone carried a nonconserved mutation involving a single nucleotide change resulting in the replacement of Arg by Cys at residue 284 of the replicase protein; this mutation correlated with delayed symptom induction and RNA accumulation, as shown in time-course experiments. Sequencing of the viral progeny showed that restoration of wild-type symptoms and increased RNA accumulation correlated with reversion of the mutation to the wild-type sequence, a phenomenon that occurred at approximately 7 to 10 days postinoculation. Thus, Arg284 seems to be crucial but not strictly necessary for virus infection. Subsequently, four other mutants in the triplet encoding Arg284 were constructed and assayed. Results showed that symptoms and their timing were diverse for the different mutants, with enhanced pathogenicity and RNA accumulation always correlating with reversion to Arg284. Therefore, the nature of the mutation strongly influenced the genetic stability of the mutant. At least two mutants were identified for which reversion did not occur by 30 days postinoculation, and these were defined as good candidates to attain stable symptom attenuation that could be useful in cross-protection.
Methotrexate as effective and safe choice for the treatment of rheumatoid arthritis
Authors: Kumar Vivek , Prakash Jaya , Kumar Ajai , Tripathy Baishnab C. , Gupta Varsha , Khan Mohammad Yahiya
Published: May 2017

Background:

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. For controlling the disease activity, various therapeutic modalities are used. Each of them have advantages and limitations. This study analyzes effectiveness and toxicity of methotrexate (MTX) on liver and lipid functions in selected RA patients and controls.

Methods:

This study included samples of patients with RA who were on MTX therapy and had long-term follow-up. The control and patient samples were used for analysis of lipid parameters, inflammatory markers as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), essential mineral accumulation, and liver and kidney function test.

Results:

Hemoglobin was reduced in RA patients; however, ESR, CRP and pain on the visual analog scale were significantly higher as compared to controls. Their alanine aminotransferase, aspartate aminotransferase and uric acid were within normal ranges. Serum magnesium was significantly reduced in RA patients. They showed higher values for zinc, phosphorous, and copper. They had borderline dyslipidemia.

Conclusions:

MTX was found to be safe and effective for treatment of RA. The liver function test of RA patients was normal. They had disturbances in mineral accumulation, suggesting the requirement of mineral evaluation and supplementation especially of magnesium in RA patients. The treatment was beneficial in reducing inflammation and reducing the activity of the disease. The treatment was also beneficial for lipid parameters reducing the risk of cardiovascular disease. The study supports MTX as the good choice for treatment of RA.
Are cephalomedullary interlocking screws superior to standard interlocking screws in subtrochanteric femoral fractures with an intact lesser trochanter?
Authors: Konopka Geoffrey , Ritchey Andrew , Ambrose Catherine G. , Galpin Matthew , Munz John W. , Achor Timothy S. , Choo Andrew , Gary Joshua L.
Published: May 2017

Background:

Subtrochanteric femoral fractures often are treated with cephalomedullary nails, but standard intramedullary nails may be sufficient to treat many subtrochanteric femoral fractures. We hypothesized that standard intramedullary nailing of subtrochanteric femoral fractures with an intact lesser trochanter is not inferior to cephalomedullary nailing.

Methods:

We performed a retrospective analysis of patients treated with an intramedullary device for a proximal femoral fracture within 5 cm of the lesser trochanter between January 1, 2011 and December 31, 2013. We compared standard and cephalomedullary nails with regards to fracture union, nonunion, and alignment. Exclusion criteria included comminution involving the lesser trochanter, intertrochanteric fractures, use of a plate, or pathologic fractures.

Results:

Fifty patients with 52 subtrochanteric femoral fractures met the inclusion criteria, with 39 men and 11 women. Thirteen fractures were treated with a standard, locked intramedullary nail, of which nine had adequate follow-up (69%). All nine fractures healed uneventfully. Thirty-nine fractures were treated with a cephalomedullary nail in 38 patients, of which 30 had adequate follow-up (77%). There were two nonunions that required revision surgery (5%) in the cephalomedullary group. There was no statistically significant difference between the two groups with respect to fracture union, nonunion, or revision surgery (P=0.59 Fisher Exact Test).

Conclusions:

Subtrochanteric femoral fractures with an intact lesser trochanter can be successfully treated with standard locking nails. This study is underpowered to determine if standard locking or cephalomedullary locking is superior to the other, but all failures occurred in the cephalomedullary group.
Female exposure to endocrine disrupting chemicals and fecundity: a review
Authors: Mínguez-Alarcón Lidia , Gaskins Audrey J.
Published: May 2017

Purpose of review

Endocrine disrupting chemicals (EDCs) have been known for their ability to interfere with aspects of hormone action resulting in adverse health consequences among animals and humans; however, the effects of EDCs on human fecundity have shown inconsistent findings. This review summarizes the most recent epidemiologic literature from humans on the potential effects of female exposure to nonpersistent EDCs, specifically bisphenol A (BPA), phthalates, parabens, and triclosan, on fecundity, measured by markers of reproductive hormones, markers of ovulation or ovarian reserve, IVF outcomes, and time-to-pregnancy.

Recent findings

Although the epidemiologic literature on this topic is growing, the evidence supporting an association between female urinary concentrations of BPA, phthalates, parabens and triclosan, and fecundity remains unclear. The heterogeneous results could be due to methodological differences in recruitment populations (fertile vs. subfertile), study designs (prospective vs. retrospective), assessment of exposure (including differences in the number and timing of urine samples and differences in the analytical methods used to assess the urinary concentrations), residual confounding due to diet or other lifestyle factors, and coexposures to other chemicals.

At present, there is limited evidence to conclude that female exposure to nonpersistent EDCs affect fecundity in humans. Further studies focusing on exposure to mixtures of EDCs are needed.
Teaching Caregivers in Early Intervention
Authors: Sawyer Brook E. , Campbell Philippa H.
Published: May 2017

The overarching research aim of this study was to examine learning opportunities available for caregivers during early intervention sessions. Of specific interest were providers' purposeful (i.e., explicit) teaching behaviors and opportunities from which caregivers might learn incidentally. Relations between teaching behaviors, caregiver characteristics (i.e., education and level of engagement during early intervention visit), child disability type, and provider demographic characteristics (i.e., discipline, years of experience) were also investigated. A sample of 265 videotaped early intervention home visits conducted by multidisciplinary providers were rated using the Natural Environments Rating Scale–Revised. Incidental learning opportunities were frequently available, but provider use of purposeful teaching strategies was infrequent. Differences in teaching behavior were associated with caregiver level of engagement, caregiver education, child disability type, and provider discipline. No differences in teaching behavior were found for providers' years of experience.
Preschool Teachers' Use of Pyramid Model Practices in Mainland China
Authors: Luo Li , Snyder Patricia , Clark Cinda L. , Hong Xiumin
Published: May 2017

The social domain is 1 of 5 preschool curricular domains in mainland China. Chinese preschool teachers are expected to use teaching practices that foster young children's social competence. The purpose of this study was to explore a small sample of Chinese preschool teachers' use of teaching and behavior support practices associated with the Pyramid Model. Twenty preschool classrooms in mainland China were observed using the prepublication version of the Teaching Pyramid Observation Tool for Preschool Classrooms (L. Fox, M. L. Hemmeter, & P. Snyder, 2008). In addition, each teacher completed a social–emotional teaching practices survey. Results indicated that Chinese teachers were observed to use, on average, about 31% of key teaching practices associated with the Pyramid Model. They were implementing more universal promotion practices than targeted social–emotional teaching practices. Chinese teachers generally were not observed to be teaching behavior expectations and social problem solving, nor were they developing individualized interventions for children with the most persistent challenging behavior. Correlational analyses suggested that observed implementation of Pyramid Model practices generally was not related to self-reported use of these practices. Limitations and implications of the present study along with considerations for future research are discussed.
Expression of Phosphoinositide 3-Kinase p110α and p110β Subunits and PIK3CA Mutation in Patients With Advanced Gastric Carcinoma
Authors: Kim Kyungeun , Lee Hyoun Wook
Published: May 2017

Activation of phosphoinositide 3-kinase (PI3K) is pivotal for the activity of the oncogenic PI3K/AKT signaling pathway. This study assessed the expression of 2 PI3K isoform proteins, p110α and p110β, and PIK3CA mutational status in advanced gastric carcinoma (AGC) and their correlation with clinicopathologic factors. Tissue microarray blocks were generated from 99 AGCs and immunohistochemically stained for p110α and p110β. Analysis of mutations in the PIK3CA gene, which encodes p110α, was performed using the PNAClamp PIK3CA Mutation Detection kit. Of the 99 tumors, positivity was seen in 62 (62.6%) for p110α and 97 (98.0%) for p110β with variable intensity and extent of staining. The median H-scores were 40 (range: 0 to 300) for p110α and 180 (range: 0 to 300) for p110β. Isoform p110α was more highly expressed in tumors with a lower pathologic T stage (P=0.035) and TNM stage (P=0.165), while p110β was not significantly associated with clinicopathologic factors. Samples with high p110α expression had a trend toward longer overall survival (OS) although it was not statistically significant (P=0.271), whereas high p110β expression correlated with shorter OS (P=0.016). In addition, p110β was an independent factor for poor prognosis in multivariate analysis for OS. Eight (8.1%) samples had PIK3CA mutations in exon 9. Mutational status at this locus was not significantly correlated with clinicopathologic factors. These results imply that p110β could have a more important role in the progression and aggressiveness of AGC than p110α and has potential as a prognostic biomarker in patients with AGC.
Outbreaks of nontuberculous mycobacteria
Authors: Sood Geeta , Parrish Nikki
Published: May 2017

Purpose of review

The purpose of this review is to summarize the emerging literature on nontuberculous mycobacteria outbreaks in healthcare settings. As our ability to identify mycobacterial species develops, we are better able to recognize epidemiologic connections and better understand the prevalence and importance of these outbreaks and pseudo-outbreaks in healthcare settings.

Recent findings

The number of outbreaks related to nontuberculous outbreaks is increasing because of heightened awareness and better diagnostic tests for species level identification of mycobacteria. Outbreaks in healthcare settings have been related to cardiac surgery, plastic surgery, including medical tourism, colonized humidifiers and heater–cooler devices, imperfect disinfection, and hospital water sources. Mycobacteria have a predilection to form biofilms, are resistant to disinfection and are prevalent in hospital water systems. Patients with structural lung disease like cystic fibrosis patients are at particularly high risk for mycobacterial infection. It has been thought that acquisition in this patient population is from common environmental exposure; however, there is increasing evidence that transmission in this patient population can occur through either direct or indirect patient-to-patient spread.

Mycobacteria outbreaks in healthcare settings have been underrecognized. As we identify additional clusters of infection with better diagnostic tools and heightened awareness, we will likely need better infection control practices to prevent infections in healthcare settings.
Noninvasive Thermometry in High-Intensity Focused Ultrasound Ablation
Authors: Zhou Yufeng
Published: May 2017

High-intensity focused ultrasound (HIFU) is emerging as an effective and promising treatment modality for the formation of coagulative necrosis inside the cancer/tumor noninvasively. To guarantee the efficacy and efficiency of HIFU ablation, the temperature field and consequent thermal dose should be monitored accurately in a high temporal and spatial resolution in real time. However, because of the significant variations of the tissue properties and deep penetration of HIFU beam, especially in the abdominal application, noninvasive thermometry is a very challenging topic, which may hamper the wide acceptance of HIFU by physicians worldwide. In this article, currently available thermometry techniques are reviewed, and their translation from hyperthermia range to the higher temperature for irreversible lesion production is discussed. With the technology improvement and/or development of new approaches, the performance of noninvasive thermometry may meet the clinical requirements.
Effect of Fc-γ Receptor Polymorphism on Rituximab-Mediated B Cell Depletion in ABO-Incompatible Adult Living Donor Liver Transplantation
Authors: Sakai Hiroshi , Tanaka Yuka , Tazawa Hirofumi , Shimizu Seiichi , Verma Sapana , Ohira Masahiro , Tahara Hiroyuki , Ide Kentaro , Ishiyama Kohei , Kobayashi Tsuyoshi , Onoe Takashi , Ohdan Hideki
Published: May 2017

Background

The affinity of IgG Fc receptor (FcγR) for rituximab, an anti-CD20 IgG1, differs based on single-nucleotide polymorphisms (SNPs) in FcγRs. This study aimed to explore the effect of such SNPs on clinical response to rituximab and outcomes in patients of ABO-incompatible (ABOi) living donor liver transplantation (LDLT).

Methods

SNPs of FCGR2A[131H/R] and FCGR3A[158F/V], alleles encoding FcγR, were identified in 20 patients desensitized with rituximab before ABOi LDLT. The effect of these SNPs on B cell elimination and outcomes was analyzed in the patients.

Results

The isoform encoded by FCGR2A[131H/H] had a higher affinity for IgG1, and accordingly, the effects of rituximab on B cells were more profound in individuals with FCGR2A[131H/H] than in individuals with FCGR2A[131H/R or R/R]. Specifically, the time to B-cell reappearance in the peripheral blood was significantly delayed, and total serum IgM levels were significantly lower early after LDLT in individuals with FCGR2A[131H/H], even though these SNPs did not significantly affect the reduction of antiblood group A/B antibodies. The incidence of blood stream infection was also significantly higher in individuals with FCGR2A[131H/H], and this SNP was associated with poor prognosis. Despite no significant effect of FCGR3A[158F/V] on survival after ABOi liver grafts, the incidence of infection was significantly higher in individuals with FCGR3A[158F/V or F/F] than in individuals with FCGR3A[158V/V].

Conclusions

Our findings indicate FCGR SNPs influence the effect of rituximab on B-cell depletion and are possibly predisposing factors for infectious complications after ABOi LDLT. This study will be a good foundation for further studies on larger cohorts.
Association between a functional polymorphism rs10830963 inmelatonin receptor 1Band risk of gestational diabetes mellitus: an updated meta-analysis
Authors: Xiangyuan Yu , Qianqian Wang , Linyuan Qin , Lingxiang Peng , Zaiming Chen , Xiumei Qin , Yuchun Wang , Qingfeng Shi , Hongping Yu
Published: May 2017

The melatonin receptor 1B(MTNR1B) as a candidate gene for gestational diabetes mellitus (GDM) on the basis of its association with T2DM, β-cells function and fasting plasma glucose (FPG) level. Many studies have investigated the association betweenMTNR1Bpolymorphism rs10830963 C>G and GDM risk, but the conclusion is inconsistent. PubMed, Google Scholar and CNKI databases were searched to identify eligible studies. Pooled OR with corresponding 95% CI was used to estimate the strength of the association between rs10830963 and GDM risk using a fixed- or random-effect model. 12 eligible studies with a number of 4,782 GDM patients and 5,605 controls were included in this meta-analysis. Results indicated that the variant G allele of rs10830963 polymorphism was significantly associated with an increased risk of GDM (CG vs. CC: OR=1.23, 95%CI= 1.12–1.34,Pheterogeneity= 0.23; GG vs. CC: OR=1.74, 95%CI=1.41–2.15,Pheterogeneity= 0.002). In the stratified analysis by ethnicity, similar results were found in Asians (CG vs. CC: OR=1.15, 95%CI= 1.04–1.28,Pheterogeneity= 0.74; GG VS. CC: OR=1.48, 95%CI=1.23–1.78,Pheterogeneity= 0.08) and in Caucasians (CG vs. CC: OR=1.49, 95%CI=1.25–1.77, Pheterogeneity= 0.28; GG vs. CC: OR=2.68, 95%CI=2.03–3.54,Pheterogeneity= 0.58).
Single molecule mechanics reveal Kif15 as an active molecular ratchet with acute strain sensitivity
Authors: McHugh T. , Drechsler H. , McAinsh A. D. , Carter N. J. , Cross R. A.
Published: May 2017

Human Kif15 is a tetrameric kinesin-12 that contributes critically to bipolar spindle assembly in eukaryotes. Here we examine its single molecule mechanics. Under hindering loads, Kif15 steps predominantly towards microtubule plus ends, with its forestep:backstep ratio decreasing exponentially with load and stall occurring at ~6pN. Between steps, Kif15 binds stably, usually via a single head domain. By complete contrast, under assisting loads, Kif15 detaches rapidly, even in AMPPNP. Furthermore, Kif15 can autoinhibit, via an interaction requiring its C-terminus. Autoinhibited Kif15 binds microtubules nucleotide-independently, resists both hindering and assisting loads, and is further stabilized by Tpx2, which interacts with the Kif15 C-terminus. Our data reveal the mechanics of Kif15 to be extraordinarily sensitive to loading direction. When unloaded, it walks rapidly; when pulled forwards it slips and when pulled backwards it grips. We discuss the implications of this unique mechanical behaviour for the roles of Kif15 in spindle function.
Evaluation of Chromatin Accessibility in Prefrontal Cortex of Schizophrenia Cases and Controls
Authors: Bryois Julien , Garrett Melanie E , Song Lingyun , Safi Alexias , Giusti-Rodriguez Paola , Johnson Graham D , Demur Alfonso Buil , Fullard John F , Roussos Panos , Sklar Pamela , Akbarian Schahram , Haroutunian Vahram , Stockmeier Craig A , Wray Gregory A , White Kevin P , Liu Chunyu , Reddy Timothy E , Ashley-Koch Allison , Sullivan Patrick F , Crawford Gregory E
Published: May 2017

Schizophrenia genome-wide association (GWA) studies have identified over 150 regions of the genome that are associated with disease risk, yet there is little evidence that coding mutations contribute to this disorder. To explore the mechanism of non-coding regulatory elements in schizophrenia, we performed ATAC-seq on adult prefrontal cortex brain samples from 135 individuals with schizophrenia and 137 controls, and identified 118,152 ATAC-seq peaks. These accessible chromatin regions in brain are highly enriched for SNP-heritability for schizophrenia (10.6 fold enrichment, P=2.4×10−4, second only to genomic regions conserved in Eutherian mammals) and replicated in an independent dataset (9.0 fold enrichment, P=2.7×10−4). This degree of enrichment of schizophrenia heritability was higher than in open chromatin found in 138 different cell and tissue types. Brain open chromatin regions that overlapped highly conserved regions exhibited an even higher degree of heritability enrichment, indicating that conservation can identify functional subsets within regulatory elements active in brain. However, we did not identify chromatin accessibility differences between schizophrenia cases and controls, nor did we find an interaction of chromatin QTLs with case-control status. This indicates that although causal variants map within regulatory elements, mechanisms other than differential chromatin may govern the contribution of regulatory element variation to schizophrenia risk. Our results strongly implicate gene regulatory processes involving open chromatin in the pathogenesis of schizophrenia, and suggest a strategy to understand the hundreds of common variants emerging from large genomic studies of complex brain diseases.
Reconfiguration of Dominant Coupling Modes in Mild Traumatic Brain Injury Mediated by δ-band Activity: a Resting State MEG Study
Authors: Antonakakis Marios , Dimitriadis Stavros I. , Zervakis Michalis , Papanicolaou Andrew C. , Zouridakis George
Published: May 2017

During the last few years, rich-club (RC) organization has been studied as a possible brain-connectivity organization model for large-scale brain networks. At the same time, empirical and simulated data of neurophysiological models have demonstrated the significant role of intra-frequency and inter-frequency coupling among distinct brain areas. The current study investigates further the importance of these couplings using recordings of resting-state magnetoencephalographic activity obtained from 30 mild traumatic brain injury (mTBI) subjects and 50 healthy controls. Intra-frequency and inter-frequency coupling modes are incorporated in a single graph to detect group differences within individual rich-club subnetworks (type I networks) and networks connecting RC nodes with the rest of the nodes (type II networks). Our results show a higher probability of inter-frequency coupling for (δ−γ1), (δ−γ2), (θ−β), (θ−γ2), (α−γ2), (γ1−γ2) and intra-frequency coupling for (γ1−γ1) and (δ−δ) for both type I and type II networks in the mTBI group. Additionally, mTBI and control subjects can be correctly classified with high accuracy (98.6%), whereas a general linear regression model can effectively predict the subject group using the ratio of type I and type II coupling in the (δ, θ), (δ, β), (δ, γ1), and (δ, γ2) frequency pairs. These findings support the presence of an RC organization simultaneously with dominant frequency interactions within a single functional graph. Our results demonstrate a hyperactivation of intrinsic RC networks in mTBI subjects compared to controls, which can be seen as a plausible compensatory mechanism for alternative frequency-dependent routes of information flow in mTBI subjects.
Phenotype-driven transitions in regulatory network structure
Authors: Padi Megha , Quackenbush John
Published: May 2017

Complex traits and diseases like human height or cancer are often not caused by a single mutation or genetic variant, but instead arise from multiple factors that together functionally perturb the underlying molecular network. Biological networks are known to be highly modular and contain dense “communities” of genes that carry out cellular processes, but these structures change between tissues, during development, and in disease. While many methods exist for inferring networks, we lack robust methods for quantifying changes in network structure. Here, we describe ALPACA (ALteredPartitionsAcrossCommunityArchitectures), a method for comparing two genome-scale networks derived from different phenotypic states to identify condition-specific modules. In simulations, ALPACA leads to more nuanced, sensitive, and robust module discovery than currently available network comparison methods. We used ALPACA to compare transcriptional networks in three contexts: angiogenic and non-angiogenic subtypes of ovarian cancer, human fibroblasts expressing transforming viral oncogenes, and sexual dimorphism in human breast tissue. In each case, ALPACA identified modules enriched for processes relevant to the phenotype. For example, modules specific to angiogenic ovarian tumors were enriched for genes associated with blood vessel development, interferon signaling, and flavonoid biosynthesis. In comparing the modular structure of networks in female and male breast tissue, we found that female breast has distinct modules enriched for genes involved in estrogen receptor and ERK signaling. The functional relevance of these new modules indicate that not only does phenotypic change correlate with network structural changes, but also that ALPACA can identify such modules in complex networks.

Significance statement

Distinct phenotypes are often thought of in terms of unique patterns of gene expression. But the expression levels of genes and proteins are driven by networks of interacting elements, and changes in expression are driven by changes in the structure of the associated networks. Because of the size and complexity of these networks, identifying functionally significant changes in network topology has been an ongoing challenge. We describe a new method for comparing networks derived from related conditions, such as healthy and disease tissue, and identifying emergent modules associated with the phenotypic differences between the conditions. We show that this method can find both known and previously unreported pathways involved in three contexts: ovarian cancer, tumor viruses, and breast tissue development.
A metastable polymorphic form of the antifungal anilinopyrimidine active pyrimethanil
Authors: Eberlin Alex R. , Frampton Christopher S.
Published: May 2017

A second metastable form of the title compound, C12H13N3 (systematic name: 4,6-dimethyl-N-phenylpyrimidin-2-amine), was isolated from an attempted co-crystallization experiment with meso-erythriol in dimethyl sulfoxide (DMSO). The crystals of form 2 at 120 K are monoclinic, space group P21/n with Z′ = 4 compared to the previously reported triclinic form with Z′ = 2 [Sun et al. (2011). Acta Chim. Sin.
69, 1909–1914]. The four independent molecules in the asymmetric unit form two discrete dimeric units through a concerted pair of N—H...N hydrogen bonds with a graph-set notation of R
2
2(8). The origin of the polymorphic behaviour is revealed in that the conformation of each dimer present in the asymmetric unit of the structure is unique and determined by the rotation of the second molecule in the dimer with respect to the first.
5-Fluoro-1-[(1-{[(1S,2R,6R,8S,9R)-4,4,11,11-tetramethyl-3,5,7,10,12-pentaoxatricyclo[7.3.0.02,6]dodecan-8-yl]methyl}-1H-1,2,3-triazol-4-yl)methyl]-2,3-dihydro-1H-indole-2,3-dione
Authors: Qachchachi Fatima-Zahrae , Mague Joel T. , Kandri Rodi Youssef , Haoudi Amal , El Hadrami El Mestafa , Essassi El Mokhtar
Published: May 2017

In the title molecule, C23H25FN4O7, the dihedral angle between the indole skeleton (r.m.s. deviation = 0.022 Å) and the triazole moiety is 74.67 (7)°. The molecules pack in a three-dimensional network in the crystal, being linked by C—H...O and N—H...O hydrogen bonds.
Systemic-attachment formulation for families of children with autism
Authors: Hudson Mark , Dallos Rudi , McKenzie Rebecca
Published: May 2017

Purpose

Case formulation has gained increasing prominence as a guide to intervention across a range of clinical problems. It offers a contrasting orientation to diagnosis and its value is considered in the context of clinical work with autistic spectrum disorders (ASD). The purpose of this paper is to argue that case formulation integrating attachment, systemic and narrative perspectives offers a valuable way forward in assisting people with the diagnosis and their families.

Design/methodology/approach

The literature on ASD and related conditions is reviewed to examine levels of co-morbidity, consider the role of parental mental health difficulties and explore the issues inherent with current approaches to diagnosis.

Findings

ASD is found to have a high level of co-morbidity with other difficulties, such as anxiety and insecure attachment. Research findings, alongside the authors own clinical experience, are developed to suggest that formulation can allow the possibility of early intervention based on a holistic appraisal of the array of difficulties present prior to a diagnosis.

Originality/value

It is argued that the use of this systemic-attachment formulation approach could offset the exacerbation in ASD and related conditions, and deterioration in families’ mental health, whilst they face long waiting times for a diagnosis.
Transition tools and access to adult primary care
Authors: Erickson Warfield Marji , Crossman Morgan K. , Neumeyer Ann Martha , O’Brien Julie , Kuhlthau Karen A.
Published: May 2017

Purpose

The transition from pediatric to adult health care is challenging for youth with autism spectrum disorder (ASD). Many tools have been developed to facilitate transition but studies have not assessed their utility or readiness to be implemented in primary care practices. The purpose of this paper is to rate existing health care transition tools to identify tools ready for use in primary care clinics and develop a set of transition principles.

Design/methodology/approach

Four pediatric and family medicine providers from community health centers reviewed 12 transition tools and provided ratings and in-depth responses about the usefulness and feasibility of each tool through online surveys and telephone interviews. A conference call was used to discuss the findings and develop a set of transition principles.

Findings

The top rated tools included three youth self-management tools, two tools focused on ASD information and one tool focused on communication. No one tool was top rated by all providers and none of the tools was ready to be implemented without revisions. The transition principles developed focused on the use of selected tools to involve all youth in regular conversations about transition at every well child visit beginning at age 14 and adapting that process for youth with special needs.

Originality/value

This study is unique in asking primary care providers to assess the applicability of incorporating existing and publicly available transition tools in their own practices and developing a set of transition principles.
Outcomes-based commissioning for social care in extra care housing: is there a future?
Authors: Smith Randall , Darton Robin , Cameron Ailsa , Johnson Eleanor K. , Lloyd Liz , Evans Simon , Atkinson Teresa June , Porteus Jeremy
Published: May 2017

Purpose

The purpose of this paper is to provide an overview of the process of commissioning adult social care services in England. It reflects the literature on commissioning at the strategic level followed by a section on operational or micro-commissioning. The rest of the paper focusses on the emergence of ideas about outcomes-based commissioning (OBC) in the field of adult social care and ends with critical consideration of the effectiveness of OBC in adult social care as applied to support and care provided in extra care housing.

Design/methodology/approach

The review of strategic and operational commissioning in adult social care in England (and Scotland in brief) is based on both policy documents and a review of the literature, as are the sources addressing OBC in adult social care particularly in extra care housing settings.

Findings

The core of this paper focusses on the challenges to the implementation of OBC in adult social care in the context of provision for residents in extra care housing. Of central importance are the impact of the squeeze on funding, increasing costs as a result of demographic change and the introduction of a national living wage plus the focus on the needs of service users through the idea of person-centred care and resistance to change on the part of adult social care staff and workers in other relevant settings.

Originality/value

Addressing the implementation of OBC in adult social care in England in the context of extra care housing.
An empirical investigation of tourist’s choice of service delivery options
Authors: Kaushik Arun Kumar , Rahman Zillur
Published: May 2017

Purpose

This paper aims to offer and examine a conceptual model of tourist innovativeness toward self-service technologies (SSTs) to confirm whether tourists prefer service delivery by SSTs over employees in an offline hospitality environment.

Design/methodology/approach

Tourists’ perceived usefulness (PU) of SSTs and need for interaction (NI) with service employees have been taken as crucial mediating variables to examine the effects of perceived ease of use and technology readiness index personality dimensions toward SST and employee-based service adoption.

Findings

Findings reveal that both “NI” and “PU” play significant roles in Technology Readiness and Acceptance Model (TRAM) when tourists select one of two service delivery options – SSTs and service employees.

Research limitations/implications

The foremost limitation of the study is its dependence on domestic tourist samples. However, such samples were chosen because tourists comprising these samples tend to use similar service delivery options more, in turn increasing their use of SSTs available in sample hotels.

Practical implications

The study gives a deeper understanding of TRAM with an extremely crucial mediating variable (NI) in an offline service context. It also provides useful insights to service providers and policy makers for developing new strategies and policies to enhance user experience.

Social implications

This study recommends the usage of numerous SSTs by tourists.

Originality/value

During extensive literature review carried out in this research, no study was found that proposed such an effective framework in an offline service context.
Chinese travelers’ preferences for hotel amenities
Authors: Kucukusta Deniz
Published: May 2017

Purpose

This research aims to investigate how Chinese leisure travelers value hotel amenities when they book hotel rooms in Hong Kong.

Design/methodology/approach

The research method was based on a conjoint analysis approach. Conjoint models were developed to determine how people make decisions and what they really value in products or services.

Findings

Price had the highest average importance value, followed by airport/local area shuttles, wireless internet, breakfast and quality of coffee/tea. Price, airport/local area shuttles and wireless internet were rated as being relatively more important than breakfast and quality of coffee/tea.

Research limitations/implications

This research has some limitations in terms of the generalizability of its findings to all hotels and travelers. First, only four hotel amenities were considered. Second, the research focused on Chinese leisure travelers staying in hotels in Hong Kong. Finally, the sample only consisted of leisure travelers.

Practical implications

This research shows that providing complimentary breakfast and free access to quality coffee/tea when a hotel already provides a shuttle service and free wireless internet does not add much value to the overall hotel product from the customer’s point of view. Moreover, it provides insights into how hotel professionals can customize and select the amenities they provide to impress their customers.

Originality/value

This research has significant implications for hotel managers’ efforts to formulate and implement strategies or tactics in their daily operations or long-term plans through the selection of hotel amenities.
Fun, inspiration and discovery: from momentary experiences to overall evaluations
Authors: Liu Wei , Sparks Beverley , Coghlan Alexandra
Published: May 2017

Purpose

This paper aims to use a concurrent mixed method approach to explore the key variables that can influence customer experience at a food and wine event.

Design/methodology/approach

A concurrent mixed methods approach, using a participant-generated image (PGI) method, together with a recall survey, provided images with associated narratives, descriptive statistics, correlations and hierarchical multiple regression analysis to explore how attendees appraise their experiences based on their goals and the link between experience appraisals and overall evaluations.

Findings

Through the PGI method (N = 25), the authors determined that customer experience at the event could be viewed as a hierarchical model, comprising a fundamental sensory experience together with three higher-order customer experience components (fun, discovery and inspiration). A separate concurrent recall study (N = 598) demonstrated the relationship between the same four customer experience components and overall satisfaction as well as recommendation and repeat visitation.

Practical implications

The results suggest that to promote positive customer experiences, along with the product of the event itself, event managers should focus on activity programs that are fun, inspirational and novel, as well as sensory.

Originality/value

This study focuses on a single case study of an event to examine and extend our understanding of customer experience. The use of a concurrent mixed methods approach provides us with different types of data from two separate samples of participants. By integrating data from each study the authors are able to build a conceptual model of the salient dimensions of customer experience and then quantitatively analyze how these salient dimensions are related to outcome variables.
Entrepreneurial risk taking: themes from the literature and pointers for future research
Authors: Tipu Syed Awais Ahmad
Published: May 2017

Purpose

Given the critical mass of literature on entrepreneurial risk-taking, the purpose of this paper is to assess the contribution to the knowledge so far by exploring important themes in the literature on entrepreneurial risk-taking.

Design/methodology/approach

The review is organized around four themes: nature of entrepreneurial risk-taking; antecedents of entrepreneurial risk-taking; context of entrepreneurial risk-taking; and outcomes of entrepreneurial risk-taking. The author critically evaluates the literature on each theme and presents the pointers for future research.

Findings

Literature does provide a holistic view encapsulating different dimensions of entrepreneurial risk-taking, but it has produced largely inconsistent findings in terms of risk and gender, risk propensity of entrepreneurs in comparison to non-entrepreneurs and the outcomes of entrepreneurial risk-taking. Organizational antecedents, non-financial measures and ethical- and health-related consequences of entrepreneurial risk are underexplored. Inconclusive literature also implies that the risk may not be a distinguishing or important factor for undertaking an entrepreneurial endeavor. Therefore, it is pertinent to explore the critical factors entrepreneurs consider (or not consider) while marshalling their resources to embark on an entrepreneurial journey. This posits the need to explore an entrepreneur’s informal approach toward risk-taking.

Originality/value

Suggested pointers of future research will potentially enhance the theoretical understanding of entrepreneurial risk-taking.