bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concise Review: Current Status and Future Directions on Research Related to Nonalcoholic Fatty Liver Disease
Authors: Wruck Wasco , Graffmann Nina , Kawala Marie-Ann , Adjaye James 
Published: July 2016

Abstract
Considered a feature of the metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), is associated with insulin resistance, type 2 diabetes, obesity and drug toxicity. Its prevalence is estimated at about 30% in western countries mainly due to sedentary life styles and high fat diets. Genome-wide association studies have identified polymorphisms in several genes, for example, PNPLA3, and TM6SF2 which confer susceptibility to NAFLD. Here, we review recent findings in the NAFLD field with a particular focus on published transcriptomics datasets which we subject to a meta-analysis. We reveal a common gene signature correlating with the progression of the disease from steatosis and steatohepatitis and reveal that lipogenic and cholesterol metabolic pathways are main actors in this signature. We propose the use of disease-in-a-dish models based on hepatocyte-like cells derived from patient-specific induced pluripotent stem cells (iPSC). These will enable investigations into the contribution of genetic background in the progression from NALFD to non-alcoholic steatohepatitis. Furthermore, an iPSC-based approach should aid in the elucidation of the function of new biomarkers, thus enabling better diagnostic tests and validation of potential drug targets.
A method for simultaneous gene overexpression and inactivation in the Corynebacterium glutamicum genome
Authors: Xu Jianzhong , Zhang Junlan , Han Mei , Zhang Weiguo 
Published: July 2016

Abstract
The gene integration method is an important tool to stably express desirable genes in bacteria. To avoid heavy workload and cost, we constructed a rapid and efficient method for genome modification. This method depended on a mobilizable plasmid, which contains a P tac promoter, an introduced multiple cloning site (iMCS), and rrnBT1T2 terminator. Briefly, the mobilizable plasmid pK18-MBPMT with the P tac-iMCS-rrnBT1T2 cartridge derived from pK18mobsacB was prepared to directly integrate hetero-/homologous DNA into the Corynebacterium glutamicum genome. Like our previous method, this method was based on insertional inactivation and double-crossover homologous recombination, which simultaneously achieved gene overexpression and inactivation in the genome without the use of genetic markers. Compared to the previous method, this protocol omitted the construction of a recombinant expression plasmid and clone of the target gene(s) cassette, which significantly decreased the workload, cost, and operational time. Using this method, the heterologous gene amy and the homologous gene lysCT311I were successfully integrated into the C. glutamicum genome at alaT and avtA loci, respectively. Moreover, the operation time of this method was shorter than that of the previous method, especially for repeated integration. This method, which is based on the mobilizable plasmid pK18-MBPMT, thus represents a potentially attractive protocol for the integration of genes in the course of genetic modification of C. glutamicum.
Comparison of four methods of blood loss estimation after cesarean delivery
Authors: Withanathantrige Manoj , Goonewardene Malik , Dandeniya Ranmalie , Gunatilake Pabashani , Gamage Sasini 
Published: July 2016

AbstractObjectiveTo assess agreement between four different methods of blood loss estimation after lower‐segment cesarean delivery (LSCD).MethodsA secondary analysis was undertaken of a randomized controlled trial of three timings of cord clamping during LSCD performed at a center in Sri Lanka between January 21 and April 30, 2013. Eligible women underwent prepartum LSCD at 37–39 weeks of pregnancy. Estimated blood loss (EBL) was assessed by a combined method (direct measurements of spilled blood and sucker bottle volumes, and weighing of surgical towels and drapes before and after use), according to visual assessments by the surgeon and by anesthesiologists, and by measurement of preoperative and postoperative hemoglobin levels.ResultsAmong 156 participants, mean EBL was 502 mL (95% CI 370–618) from the combined method, 506 mL (412–643) calculated from hemoglobin levels, 484 mL (367–621) by the surgeon's estimation, and 491 mL (361–612) by anesthesiologists’ estimation (P = 0.32). Visual assessment of EBL by anesthesiologists had the best intraclass correlation (0.713) and limits of agreement with the combined method. There were no significant differences between the proportion of cases in which anesthesiologists and the surgeon underestimated or overestimated the EBL when compared with the combined method.ConclusionEBL should be ideally obtained by the combined method.
Effective mixing and counting in Bruhat–Tits trees
Authors: KWON SANGHOON 
Published: July 2016

Let ${\mathcal{T}}$ be a locally finite tree, $\unicode[STIX]{x1D6E4}$ be a discrete subgroup of $\,\operatorname{Aut}\,({\mathcal{T}})$ and $\widetilde{F}$ be a $\unicode[STIX]{x1D6E4}$-invariant potential. Suppose that the length spectrum of $\unicode[STIX]{x1D6E4}$ is not arithmetic. In this case, we prove the exponential mixing property of the geodesic translation map $\unicode[STIX]{x1D719}:\unicode[STIX]{x1D6E4}\backslash S{\mathcal{T}}\rightarrow \unicode[STIX]{x1D6E4}\backslash S{\mathcal{T}}$ with respect to the measure $m_{\unicode[STIX]{x1D6E4},F}^{\unicode[STIX]{x1D708}^{-},\unicode[STIX]{x1D708}^{+}}$ under the assumption that $\unicode[STIX]{x1D6E4}$ is full and $(\unicode[STIX]{x1D6E4},\widetilde{F})$ has a weighted spectral gap. We also obtain the effective formula for the number of $\unicode[STIX]{x1D6E4}$-orbits with weights in a Bruhat–Tits tree ${\mathcal{T}}$ of an algebraic group.
Champion of the Gaeilgeoirí: John Charles McQuaid and the Irish-language mass
Authors: Bruce James P. 
Published: July 2016

AbstractIn 1963 the Second Vatican Council voted overwhelmingly to introduce the vernacular into Roman Catholic worship. The Irish hierarchy decided that both Irish and English speakers should be catered for in the reformed liturgy. Within a few years John Charles McQuaid, archbishop of Dublin, had gained a widespread reputation as having gone further than his fellow bishops in the provision of masses in Irish. At the same time he was criticised for his lack of enthusiasm towards other areas of liturgical reform. This dichotomy stemmed from McQuaid’s deep dismay at the church’s new ecumenical direction and the possibility that it would lead to shared worship between Catholics and Protestants. Yet, as a senior prelate in the Catholic Church, he was obliged to implement each of the Council’s decrees, including those concerning the liturgy. McQuaid’s response was to introduce Vatican-approved changes to the mass, while simultaneously protecting the traditional liturgy he cherished. So he tried to re-establish the Latin rite on the same terms as those he had arranged for the Irish mass. Had he succeeded, the result would have been a reduction in the use of an English vernacular which he found offensive to his Catholic sensibilities.
The reduction of Leinster and the origins of the Tudor conquest of Ireland,c.1534–46
Authors: Heffernan David 
Published: July 2016

AbstractThe government’s incursion into the midlands lordships of the O’Connors and O’Mores in 1546 is often identified as the root of the Tudor conquest of Ireland. Conversely, the years from 1535 to 1546 have been depicted as a period wherein a conciliatory approach to Gaelic Ireland was favoured. This paper argues that the origins of the Tudor conquest lie in the 1530s following the Kildare Rebellion. At this time a majority of senior officials in Ireland urged the regional conquest of the lordships of the O’Byrnes, O’Tooles and MacMurrough Kavanaghs in Wicklow and Carlow. This strategy was not adopted as Henry VIII refused to finance such a costly endeavour. Consequently a cheap political alternative now known as ‘surrender and regrant’ was briefly adopted in the early 1540s. However in 1546 the officials who favoured regional intervention in Leinster succeeded in initiating an incursion into the midlands. In light of the links between the campaign for the reduction of south Leinster in the 1530s and the incursion into the midlands in 1546, this paper argues that the origins of the Tudor conquest of Ireland can be traced to the campaign for the reduction of south Leinster in the mid-1530s.
Epidemiological trends for hospital admissions for acute rotavirus gastroenteritis in Belgium following the introduction of routine rotavirus vaccination and the subsequent switch from lyophilized to liquid formulation of Rotarix™
Authors: RAES M. , STRENS D. , KLEINTJENS J. , BIUNDO E. , MOREL T. , VYSE A. 
Published: July 2016

SUMMARYThis study describes epidemiological trends for acute rotavirus gastroenteritis (RVGE) in Belgium in children aged ⩽5 years during the period June 2007 to May 2014 after the introduction of routine rotavirus (RV) vaccination. This period encompassed the switch from lyophilized to the liquid formulation of Rotarix™ (GlaxoSmithKline, Belgium) in August 2011. Uptake of RV vaccine remained consistently high throughout the study period with Rotarix the brand most often used. RV was present in 9% (1139/12 511) of hospitalized cases with acute gastroenteritis included in the study. Epidemiological trends for hospital admissions for RVGE remained consistent throughout the study period, with no evidence of any change associated with the switch from lyophilized to liquid formulation of Rotarix. This suggests both formulations perform similarly, with the liquid formulation not inferior regarding ability to reduce hospital admissions for acute RVGE in children aged ⩽5 years. A strong seasonal effect was observed with most RVGE occurring in the winter months but with some variability in intensity, with highest incidence found in those aged 6–24 months. The main observation was the decreased number of hospital admissions for RVGE in Belgium that occurred during winter 2013/2014.
Creating a lesion-specific “roadmap” for ambulatory care following surgery for complex congenital cardiac disease
Authors: Wernovsky Gil , Lihn Stacey L. , Olen Melissa M. 
Published: July 2016

AbstractOver the past 20 years, the successes of neonatal and infant surgery have resulted in dramatically changed demographics in ambulatory cardiology. These school-aged children and young adults have complex and, in some cases, previously unexpected cardiac and non-cardiac consequences of their surgical and/or transcatheter procedures. There is a growing need for additional cardiac and non-cardiac subspecialists, and coordination of care may be quite challenging. In contrast to hospital-based care, where inpatient care protocols are common, and perioperative expectations are more or less predictable for most children, ambulatory cardiologists have evolved strategies of care more or less independently, based on their education, training, experience, and individual styles, resulting in highly variable follow-up strategies. We have proposed a combination proactive–reactive collaborative model with a patient’s primary cardiologist, primary-care provider, and subspecialists, along with the patient and their family. The goal is to help standardise data collection in the ambulatory setting, reduce patient and family anxiety, increase health literacy, measure and address the non-cardiac consequences of complex cardiac disease, and aid in the transition to self-care as an adult.
Efficacy of PARP inhibition in Pde6a mutant mouse models for retinitis pigmentosa depends on the quality and composition of individual human mutations
Authors: Jiao K , Sahaboglu A , Zrenner E , Ueffing M , Ekström P A R , Paquet-Durand F 
Published: July 2016

AbstractRetinitis pigmentosa (RP), an inherited blinding disease, is caused by a variety of different mutations that affect retinal photoreceptor function and survival. So far there is neither effective treatment nor cure. We have previously shown that poly(ADP-ribose)polymerase (PARP) acts as a common and critical denominator of cell death in photoreceptors, qualifying it as a potential target for future therapeutic intervention. A significant fraction of RP-causing mutations affect the genes for the rod photoreceptor phosphodiesterase 6A (PDE6A) subunit, but it is not known whether they all engage the same death pathway. Analysing three homozygous point mutations (Pde6a R562W, D670G, and V685M) and one compound heterozygous Pde6aV685M/R562W mutation in mouse models that match human RP patients, we demonstrate excessive activation of PARP, which correlated in time with the progression of photoreceptor degeneration. The causal involvement of PARP activity in the neurodegenerative process was confirmed in organotypic retinal explant cultures treated with the PARP-selective inhibitor PJ34, using different treatment time-points and durations. Remarkably, the neuroprotective efficacy of PARP inhibition correlated inversely with the strength of the genetically induced insult, with the D670G mutant showing the best treatment effects. Our results highlight PARP as a target for neuroprotective interventions in RP caused by PDE6A mutations and are a first attempt towards personalized, genotype-matched therapy development for RP. In addition, for each of the different mutant situations, our work identifies windows of opportunity for an optimal treatment regimen for further in vivo experimentation and possibly clinical studies.
Structure and activation of pro-activin A
Authors: Wang Xuelu , Fischer Gerhard , Hyvönen Marko 
Published: July 2016

AbstractActivins are growth factors with multiple roles in the development and homeostasis. Like all TGF-β family of growth factors, activins are synthesized as large precursors from which mature dimeric growth factors are released proteolytically. Here we have studied the activation of activin A and determined crystal structures of the unprocessed precursor and of the cleaved pro-mature complex. Replacing the natural furin cleavage site with a HRV 3C protease site, we show how the protein gains its bioactivity after proteolysis and is as active as the isolated mature domain. The complex remains associated in conditions used for biochemical analysis with a dissociation constant of 5 nM, but the pro-domain can be actively displaced from the complex by follistatin. Our high-resolution structures of pro-activin A share features seen in the pro-TGF-β1 and pro-BMP-9 structures, but reveal a new oligomeric arrangement, with a domain-swapped, cross-armed conformation for the protomers in the dimeric protein.
Light-melt adhesive based on dynamic carbon frameworks in a columnar liquid-crystal phase
Authors: Saito Shohei , Nobusue Shunpei , Tsuzaka Eri , Yuan Chunxue , Mori Chigusa , Hara Mitsuo , Seki Takahiro , Camacho Cristopher , Irle Stephan , Yamaguchi Shigehiro 
Published: July 2016

AbstractLiquid crystal (LC) provides a suitable platform to exploit structural motions of molecules in a condensed phase. Amplification of the structural changes enables a variety of technologies not only in LC displays but also in other applications. Until very recently, however, a practical use of LCs for removable adhesives has not been explored, although a spontaneous disorganization of LC materials can be easily triggered by light-induced isomerization of photoactive components. The difficulty of such application derives from the requirements for simultaneous implementation of sufficient bonding strength and its rapid disappearance by photoirradiation. Here we report a dynamic molecular LC material that meets these requirements. Columnar-stacked V-shaped carbon frameworks display sufficient bonding strength even during heating conditions, while its bonding ability is immediately lost by a light-induced self-melting function. The light-melt adhesive is reusable and its fluorescence colour reversibly changes during the cycle, visualizing the bonding/nonbonding phases of the adhesive.
Biotic interchange between the Indian subcontinent and mainland Asia through time
Authors: Klaus Sebastian , Morley Robert J. , Plath Martin , Zhang Ya-Ping , Li Jia-Tang 
Published: July 2016

AbstractBiotic interchange after the connection of previously independently evolving floras and faunas is thought to be one of the key factors that shaped global biodiversity as we see it today. However, it was not known how biotic interchange develops over longer time periods of several million years following the secondary contact of different biotas. Here we present a novel method to investigate the temporal dynamics of biotic interchange based on a phylogeographical meta-analysis by calculating the maximal number of observed dispersal events per million years given the temporal uncertainty of the underlying time-calibrated phylogenies. We show that biotic influx from mainland Asia onto the Indian subcontinent after Eocene continental collision was not a uniform process, but was subject to periods of acceleration, stagnancy and decrease. We discuss potential palaeoenvironmental causes for this fluctuation.
Association of pasta consumption with body mass index and waist-to-hip ratio: results from Moli-sani and INHES studies
Authors: Pounis G , Castelnuovo A Di , Costanzo S , Persichillo M , Bonaccio M , Bonanni A , Cerletti C , Donati M B , de Gaetano G , Iacoviello L ,   on behalf of the Moli-sani and INHES investigators
Published: July 2016

Abstract
Background/Objectives:
Pasta as a traditional component of Mediterranean diet (MeD) in Italy has not been studied in detail in the management of body weight. This study aimed at evaluating the association of pasta intake with body mass index (BMI) and waist-to-hip ratio, in two large epidemiological datasets.

Subjects/Methods:
A total of 14 402 participants aged ⩾35 years randomly recruited from the general population of the Molise region (Moli-sani cohort) and 8964 participants aged >18 years from all over Italy (Italian Nutrition & HEalth Survey, INHES) were separately analyzed. The European Prospective Investigation into Cancer and Nutrition (EPIC)-food frequency questionnaire and one 24-h dietary recall were used for dietary assessment. Weight, height, waist and hip circumference were measured in Moli-sani or self-reported in INHES. Residuals methodology corrected for either total energy intake or body weight was used for the analysis of pasta intake.

Results:
Higher pasta intake was associated with better adhesion to MeD in both genders (P for both<0.001). In the Moli-sani study, after multivariable analysis, pasta-energy residuals were negatively associated with BMI in women but not in men (β-coef=−0.007, P=0.003 for women and β-coef=−0.001, P=0.58 for men). When pasta intake-body weight residuals were used, pasta intake was significantly and negatively associated with BMI in crude and multi-adjusted models (including adhesion to MeD) in both genders and Moli-sani and INHES studies (for all β-coef<0, P<0.05). In the Moli-sani study, pasta-body weight residuals were significantly and negatively associated with waist and hip circumference and waist-to-hip ratio (for all β-coef<0, P<0.05).

Conclusions:
As a traditional component of MeD, pasta consumption was negatively associated with BMI, waist circumference and waist-to-hip ratio and with a lower prevalence of overweight and obesity.
Nm23H1 mediates tumor invasion in esophageal squamous cell carcinoma by regulation of CLDN1 through the AKT signaling
Authors: Kuo K-T , Chen C-L , Chou T-Y , Yeh C-T , Lee W-H , Wang L-S 
Published: July 2016

AbstractEsophageal cancer is a lethal malignancy worldwide. Previously, low expression of metastasis suppressor Nm23H1 and tight junction (TJ) protein claudin-1 (CLDN1) have been known to correlate with poor prognosis in esophageal squamous cell carcinoma (ESCC). However, the molecular interaction between them has not been clarified. In the present study, we first examined the expression of Nm23H1 and CLDN1 in 74 surgical ESCC samples by immunohistochemistry (IHC) to verify their clinicopathologic significance. The biologic effects of Nm23H1 gene silencing or overexpression in ESCC cell lines were then studied by migration and invasion studies, and its regulation on CLDN1 expression was also investigated by western blot analysis. Moreover, the expression of Nm23H1 and CLDN1 at the same invasion front of ESCC tumors was verified by immunofluorescence. The results showed a significantly positive correlation between the expression of Nm23H1 and CLDN1 (γ=0.296, P=0.011) in surgical specimens, especially for the 34 tumors with lymph-node metastasis (γ=0.455, P=0.007). In ESCC cell lines, silencing of Nm23H1 expression markedly enhanced cell invasiveness, accompanied by increased Akt phosphorylation and decreased CLDN1 expression. Conversely, Nm23H1-expressed transfectants exhibited reduced invasiveness, decreased Akt phosphorylation and correspondingly increased CLDN1 expression. Regain of CLDN1 expression in ESCC cells significantly suppressed invasiveness, but did not influence the Akt phosphorylation. Moreover, treating Nm23H1-depleted cells with the AKT inhibitor MK2206 recovered CLDN1 expression, and diminished the invasiveness of ESCC cells. Finally, decreased expressions of both CLDN1 and E-cadherin were observed at the invasive front of the Nm23H1-negative tumors. Overall, our current study documented that reduced Nm23H1 expression activates the AKT signaling pathway, results in diminished CLDN1 expression and potentiates invasiveness of ESCC cells. Enhancement of Nm23H1 expression, inhibition of the AKT signaling pathway, or combined, might be a potential treatment strategy in selective ESCC patients.
Metformin inhibits Branched Chain Amino Acid (BCAA) derived ketoacidosis and promotes metabolic homeostasis in MSUD
Authors: Sonnet Davis S. , O’Leary Monique N. , A. Gutierrez Mark , Nguyen Steven M. , Mateen Samiha , Hsu Yuehmei , P. Mitchell Kylie , J. Lopez Antonio , Vockley Jerry , Kennedy Brian K. , Ramanathan Arvind 
Published: July 2016

AbstractMaple Syrup Urine Disease (MSUD) is an inherited disorder caused by the dysfunction in the branched chain keto-acid dehydrogenase (BCKDH) enzyme. This leads to buildup of branched-chain keto-acids (BCKA) and branched-chain amino acids (BCAA) in body fluids (e.g. keto-isocaproic acid from the BCAA leucine), leading to numerous clinical features including a less understood skeletal muscle dysfunction in patients. KIC is an inhibitor of mitochondrial function at disease relevant concentrations. A murine model of intermediate MSUD (iMSUD) shows significant skeletal muscle dysfunction as by judged decreased muscle fiber diameter. MSUD is an orphan disease with a need for novel drug interventions. Here using a 96-well plate (liquid chromatography- mass spectrometry (LC-MS) based drug-screening platform we show that Metformin, a widely used anti-diabetic drug, reduces levels of KIC in patient-derived fibroblasts by 20–50%. This Metformin-mediated effect was conserved in vivo; Metformin-treatment significantly reduced levels of KIC in the muscle (by 69%) and serum (by 56%) isolated from iMSUD mice and restored levels of mitochondrial metabolites (e.g. AMP and other TCA). The drug also decreased the expression of mitochondrial branched chain amino transferase (BCAT) which produces KIC in skeletal muscle. This suggests that Metformin can restore skeletal muscle homeostasis in MSUD by decreasing mitochondrial KIC production.