bluuebunny/crossref_metadata_2025 huggingface dataset:
DEsingle for detecting three types of differential expression in single-cell RNA-seq data
Authors: Miao Zhun , Deng Ke , Wang Xiaowo , Zhang Xuegong
Published: August 2017

The excessive amount of zeros in single-cell RNA-seq data include “real” zeros due to the on-off nature of gene transcription in single cells and “dropout” zeros due to technical reasons. Existing differential expression (DE) analysis methods cannot distinguish these two types of zeros. We developed an R package DEsingle which employed Zero-Inflated Negative Binomial model to estimate the proportion of real and dropout zeros and to define and detect 3 types of DE genes in single-cell RNA-seq data with higher accuracy.

Availability and Implementation

The R package DEsingle is freely available athttps://github.com/miaozhun/DEsingleand is under Bioconductor’s consideration now.

Contact

zhangxg@tsinghua.edu.cn

Supplementary information

Supplementary data are available atbioRxivonline.
Whole exome sequencing of ENU-induced thrombosis modifier mutations in the mouse
Authors: Tomberg Kärt , Westrick Randal J. , Kotnik Emilee N. , Siemieniak David R , Zhu Guojing , Saunders Thomas L. , Cleuren Audrey C. , Ginsburg David
Published: August 2017

Although the Factor V Leiden (FVL) gene variant is the most prevalent genetic risk factor for venous thrombosis, only 10% of FVL carriers will experience such an event in their lifetime. To identify potential FVL modifier genes contributing to this incomplete penetrance, we took advantage of a perinatal synthetic lethal thrombosis phenotype in mice homozygous for FVL (F5L/L) and haploinsufficient for tissue factor pathway inhibitor (Tfpi+/-) to perform a sensitized dominant ENU mutagenesis screen. Linkage analysis conducted in the 3 largest pedigrees generated from the survivingF5L/LTfpi+/-mice (‘rescues’) using ENU-induced coding variants as genetic markers was unsuccessful in identifying major suppressor loci. Whole exome sequencing was applied to DNA from 107 rescue mice to identify candidate genes enriched for ENU mutations. A total of 3,481 potentially deleterious candidate ENU variants were identified in 2,984 genes. After correcting for gene size and multiple testing,Arl6ip5was identified as the most enriched gene, though not reaching genome-wide significance. Evaluation of CRISPR/Cas9 induced loss of function in the top 6 genes failed to demonstrate a clear rescue phenotype. However, a maternally inherited (not ENU-induced)de novomutation (Plcb4R335Q) exhibited significant co-segregation with the rescue phenotype (p=0.003) in the corresponding pedigree. Thrombosis suppression by heterozygousPlcb4loss of function was confirmed through analysis of an independent, CRISPR/Cas9-inducedPlcb4mutation (p=0.01).

Author summary

Abnormal blood clotting in veins (venous thrombosis) or arteries (arterial thrombosis) are major health problems, with venous thrombosis affecting approximately 1 in every thousand individuals annually in the United States. Susceptibility to venous thrombosis is governed by both genes and environment, with approximately 60% of the risk attributed to genetic influences. Though several genetic risk factors are known, >50% of genetic risk remains unexplained. Approximately 5% of people carry the most common known risk factor, Factor V Leiden. However, only 10% of these individuals will develop a blood clot in their lifetime. Mice carrying two copies of the Factor V Leiden mutation together with a mutation in a second gene called tissue factor pathway inhibitor develop fatal thrombosis shortly after birth. To identify genes that prevent this fatal thrombosis, we studied a large panel of mice carrying inactivating gene changes randomly distributed throughout the genome. We identified several genes as potential candidates to alter blood clotting balance in mice and humans with predisposition to thrombosis, and confirmed this protective function for DNA changes in one of these genes (Plcb4).
nextPARS: Parallel probing of RNA structures in Illumina
Authors: Saus Ester , Willis Jesse , Pryszcz Leszek P. , Himmelbauer Heinz , Gabaldón Toni
Published: August 2017

RNA molecules play important roles in virtually every cellular process. These functions are often mediated through the adoption of specific structures that enable RNAs to interact with other molecules. Thus, determining the secondary structures of RNAs is central to understanding their function and evolution. In recent years several sequencing-based approaches have been developed that allow probing structural features of thousands of RNA molecules present in a sample. Here, we describe nextPARS, a novel Illumina-based implementation ofin-vitroparallel probing of RNA structures. Our approach achieves comparable accuracy to previous implementations, while enabling higher throughput and sample multiplexing.
Hundreds of Putative Non-Coding Cis-Regulatory Drivers in Chronic Lymphocytic Leukaemia and Skin Cancer
Authors: Ongen Halit , Delaneau Olivier , Stevens Michael W. , Howald Cedric , Dermitzakis Emmanouil T.
Published: August 2017

Perturbations of the coding genome and their role in cancer development have been studied extensively. However, the non-coding genome’s contribution in cancer is poorly understood (1), not only because it is difficult to define the non-coding regulatory regions and the genes they regulate, but also because there is limited power owing to the regulatory regions’ small size. In this study, we try to resolve this issue by defining modules of coordinated non-coding regulatory regions of genes (Cis Regulatory Domains or CRDs). To do so, we use the correlation between histone modifications, assayed by ChIP-seq, in population samples of immortalized B-cells and skin fibroblasts. We screen for CRDs that accumulate an excess of somatic mutations in chronic lymphocytic leukaemia (CLL) and skin cancer, which affect these cell types, after accounting for somatic mutational patterns and biases. At 5% FDR, we find 90 CRDs with significant excess somatic of mutations in CLL, 60 of which regulate 126 genes, and in skin cancer 59 significant CRDs, 25 of which regulate 37 genes. The genes these CRDs regulate include ones already implicated in tumorigenesis, and are enriched in pathways already implicated in the respective cancers, like the B-cell receptor signalling pathway in CLL and the TGFβ signalling pathway in skin cancer. We discover that the somatic mutations in the significant CRDs of CLL are hitting bases more likely to be functional than the mutations in non-significant CRDs. Moreover, in both cancers, mutational signatures observed in the regulatory regions of significant CRDs deviate significantly from their null sequences. Both results indicate selection acting on CRDs during tumorigenesis. Finally, we find that the transcription factor biding sites that are disturbed by the somatic mutations in significant CRDs are enriched for factors known to be involved in cancer development. We are describing a new powerful approach to discover non-coding regions involved in tumorigenesis in CLL and skin cancer and this approach could be generalized to other cancers.
Rhythms of the Body, Rhythms of the Brain: Respiration, Neural Oscillations, and Embodied Cognition
Authors: Varga Somogy , Heck Detlef H.
Published: August 2017

In spite of its importance as a life-defining rhythmic movement and its constant rhythmic contraction and relaxation of the body, respiration has not received attention in Embodied Cognition (EC) literature. Our paper aims to show that (1) respiration exerts significant and unexpected bottom-up influence on cognitive processes, and (2) it does so by modulating neural synchronization that underlies specific cognitive processes. Then, (3) we suggest that the particular example of respiration may function as a model for a general mechanism through which the body influences cognitive functioning. Finally, (4) we work out the implications for embodied cognition, draw a parallel to the role of gesture, and argue that respiration sometimes plays a double, pragmatic and epistemic, role, which reduces the cognitive load. In such cases, consistent with EC, the overall cognitive activity includes a loop-like interaction between neural and non-neural elements. (141 words)
Strategies for high-throughput focused-beam ptychography
Authors: Jacobsen Chris , Deng Junjing , Nashed Youssef
Published: August 2017

X-ray ptychography is being utilized for a wide range of imaging experiments with a resolution beyond the limit of the X-ray optics used. Introducing a parameter for the ptychographic resolution gainGp(the ratio of the beam size over the achieved pixel size in the reconstructed image), strategies for data sampling and for increasing imaging throughput when the specimen is at the focus of an X-ray beam are considered. The tradeoffs between large and small illumination spots are examined.
Diethyl (1-benzyl-4-phenyl-3-trifluoromethyl-1H-pyrrol-2-yl)phosphonate
Authors: Jezuita Anna , Cal Dariusz , Zagórski Piotr , Ejsmont Krzysztof , Zarychta Bartosz
Published: August 2017

In the title compound, C22H23F3NO3P, the dihedral angles between the pyrrole ring and the benzyl and phenyl rings are 81.38 (7) and 46.21 (8)°, respectively. The ethyl phosphate groups present with P—O—C—C torsion angles of −178.47 (10) and 106.72 (16)°, and an intramolecular C—H...O hydrogen bond occurs. In the extended structure, molecules are linked by C—H...O and C—H...F hydrogen bonds to generate [001] chains.
Punishing tax offenders in France and Great Britain: two criminal policies
Authors: Weidenfeld Katia , Spire Alexis
Published: August 2017

Purpose

Since 2008-2009, the governments in France and Great Britain have encouraged more rigorous penalization of tax evaders. This paper aims to investigate the implementation of these policies on the basis of an important and original empirical material.

Design/methodology/approach

The study done in France relies on interviews conducted with representatives of law enforcement agencies on public statistics and on an innovative database compiled from nearly 600 cases submitted to the judiciary. The comparison with Great Britain is developed through interviews conducted with different participants in the fight against tax fraud and statistical information.

Findings

This paper describes the recent evolution of the machinery for screening tax-related wrongdoings in France and in the UK. It demonstrates that whilst publicly calling for harsh punishment against tax dodgers, in practice, both governments tend to seek a balance between the growing demand for tax equality and the belief that the State should not intervene in the economic realm. This strategy leads to the over-representation of certain categories of taxpayers. Despite the commonalities resulting from the numerous filters before prosecution, the penal strategy takes on two different shapes on either side of the Channel: whereas the British institutions support an “exemplary punitive” system, French regulatory system favours a “quasi-administrative” treatment. The French tax authority continues to use the criminal procedures mainly as a financial instrument for the improved restitution of stolen taxes. The policy of Her Majesty’s Revenue and Customs, supported by the “Sentencing Guidelines”, aims much more at obtaining exemplary convictions.

Originality/value

Based on a large empirical material, this paper highlights the different outcomes of the criminal trials against tax evaders in the two countries.
Develop the recruitment criteria for professionalisation of politicians: a focus to group study
Authors: Ukwatta Wijayantha
Published: August 2017

Purpose

The purpose of this study is to identify the fundamental elements necessary for formulating criteria to be used when recruiting politicians into the Sri Lankan political system with a view to professionalization. By means of a thorough examination of political practice issues, the paper focuses on the possibility of introducing the concept of political professionalization and endeavors to determine the prerequisite conditions needed to resolve or minimize those issues.

Design/methodology/approach

A total of 27 respondents: academics, clergy and journalists were purposively selected for this study and they were divided into three groups to enable data collection through focus group discussions. A thematic analysis method was used to analyze the data.

Findings

The main political practice problems were bribery and corruption, the misuse of state resources by politicians, the involvement of family in politics, and unscrupulous and unethical political campaigning. The majority of respondents cited greed for political power, low levels of education and an inadequate understanding of the parliamentary process as the leading factors which cause problems to arise in politics as practiced in Sri Lanka. The analysis revealed three main themes: “knowledge”, “skills” and “values”. Respondents recommended policy initiatives for political recruitment.

Originality/value

The findings suggested that the professionalization of political practice should be promoted by introducing knowledge C skills and values as criteria for political recruitment. And it also suggested that the introduction of professional political practice methods is vitally necessary to reduce political practice issues in the current political scenario of Sri Lanka.
Learning disability market position statements, are they fit for purpose?
Authors: Broadhurst Sarah , Landau Keri
Published: August 2017

Purpose

The purpose of this paper is to review whether current learning disability market position statements (MPS) are actually helping to shape the market and explore their implications for people with learning disabilities and their families.

Design/methodology/approach

Published learning disability MPS were identified via the Institute of Public Care’s MPS database. The quality of the MPS was analysed using a good practice checklist developed by a range of stakeholders.

Findings

Learning disability MPS are not currently fit for purpose. They demonstrate that local authorities are not fully engaging in their market-shaping duties, as required under The Care Act 2014. It is suggested that this is in part due to the lack of recognition that market shaping is a council-wide responsibility and can only be successful if senior officers across the council (and their partners) acknowledge this and are held accountable. Unless this happens, people with learning disabilities will continue to lack the enablers that support them to lead the lives they choose in their communities.

Originality/value

This is the first review of the quality and potential impact of learning disability MPS.
Minority Interest Nation: The Changing Contours of Reporting Scotland on BBC and STV
Authors: Hassan Gerry
Published: August 2017

Scotland's media has traditionally provided one of the central aspects of Scottish distinctiveness, autonomy and identity. This has often historically been viewed unproblematically and uncritically, but in recent times, the selective discourses of the mainstream media have come under increasing scrutiny and challenge, particularly in the recent independence referendum.

This article examines the changing output of BBC and STV, considering in detail the evening news and current affairs programmes of both channels, and charting how they have evolved in media content and output. It also examines wider output and representation by BBC and STV, and concludes by addressing the evolving political and media environment.
Appearance and Textural Properties of Sheared Low Concentration Potato Protein Gels—Impact of Drying Method, pH, and Ionic Strength
Authors: Schmidt Jesper Malling , Larsen Lotte Bach , Hammershøj Marianne
Published: August 2017

The objective was to prepare sheared gels of potato protein concentrate and evaluate the effect of pH (3, ∼4, ∼7), ionic strength (15 or 200 mM) and protein drying conditions (spray or freeze drying) on the final appearance and rheological characteristics. Heat‐set gels 3 % (w/w) at a high ionic strength (200 mM) resulted in an inhomogeneous appearance with presence of clots, while low ionic strength (15 mM) gave homogenous structures. Gels prepared at pH 3 became transparent while preparation above pH 3.0 resulted in high turbidity. Heat treatment and cooling resulted in gelation for all samples except freeze dried powder at pH 3.0. Flow curves during shear from 0.1 to 100 s−1 were fitted by the Herschel–Bulkley model indicating shear thinning behavior for all samples except the freeze dried sample at pH 3 which displayed a Newtonian behavior. Oscillatory measurements after shear indicated viscus behavior (phase angle above 45°) for the spray dried sample at pH 3, and gelled behavior (phase angle above 45°) for the remaining gelled samples. Structure recovery was observed after shear in all samples except at pH 3.0. The data shows potato protein can be used as ingredient in protein beverages.
Optimization of Ripe Olive Processing with a Single Lye Treatment
Authors: Brenes Manuel , Romero Concepción , García‐García Pedro
Published: August 2017

The development of a method for darkening black ripe olives during the washing step with a single NaOH treatment and preservation liquid was studied. Olives of the Hojiblanca cultivar were darkened at pilot plant scale, packed, sterilized, and analyzed after 2 mo of storage at ambient temperature. It was found that the use of a mixture of preservation liquid:water at a ratio of 1:1 during the first washing gave rise to darker olives with slightly better firmness and no effect on sensory quality. However, care must be taken with the concentration of acetic acid in the preservation solution, as a content of this organic acid higher than 25 g/L can cause adverse effects on olive color due to the low pH that can be reached in the flesh of the fruit. Additionally, the re‐use of the preservation solution in the first washing resulted in enrichment in antioxidant compounds of the packed product. Black ripe olives processed with preservation liquid had a total phenolic content of 629 mg/kg, whereas those with only tap water had 376 mg/kg, in particular hydroxytyrosol and hydroxytyrosol‐4‐glucoside. These findings mean that it is possible to get darker olives with higher contents in bioactive substances by reusing the preservation liquid during the darkening step of black ripe olives.
Effects of intrinsic sources of spatial autocorrelation on spatial regression modelling
Authors: Teng Shuqing N. , Xu Chi , Sandel Brody , Svenning Jens‐Christian
Published: August 2017

Detecting and dealing with spatial autocorrelation (SA) are indispensable steps in analyses of geospatial data. Despite consensus that SA originates from both extrinsic factors and intrinsic interactions, previous studies on regression analysis of spatially autocorrelated data have rarely controlled for intrinsic sources in addition to extrinsic ones to assess ceteris paribus (i.e. causal) effects of interest, with the strict exogeneity assumption that errors containing unexplained variance are uncorrelated with explanatory variables for all observations. This assumption becomes invalid when intrinsic SA is not an external process modelled as errors and needs to be controlled for.

Here, we aimed to assess the extent to which not controlling for intrinsic SA negatively affects model performance, specifically in terms of type I error rate and unbiasedness of coefficient estimates, and to identify models that are able to handle these problems. To this end, we applied two categories of regression models that do (intrinsic category) or do not (extrinsic category) explicitly control for intrinsic SA to artificial data generated with both SA sources. These models included the extended spatial Durbin model (ESDM) and its nested models. Four analytic scenarios simulated modelling conditions with increasing complexity of variables omitted during modelling. The two more complex scenarios involved additional violations of strict exogeneity.

We found that intrinsic—just as extrinsic—SA can produce incorrect type I error rates, if not explicitly controlled for. Failing to control for intrinsic SA also generated bias in estimates of ceteris paribus effects. However, ESDM from the intrinsic category exhibited consistently good performance in dealing with intrinsic SA across all the scenarios, but suffered other violations of strict exogeneity.

Overall, model specification should control for both extrinsic and intrinsic processes generating SA in spatial data to provide reliable type I error rates and unbiased estimates of ceteris paribus effects. Given the likely widespread occurrence in observational spatial data of unknown or unmeasurable processes, ESDM should be a generally preferred starting point to explore the optimal model specification for estimating ceteris paribus effects, with due caution to other violations of strict exogeneity.
What constitutes ‘good practice’ in early intervention for psychosis? Analysis of clinical guidelines
Authors: Corsico Paolo , Griffin‐Doyle Michelle , Singh Ilina
Published: August 2017

Background

Early Intervention in Psychosis (EIP) services have been implemented with the dual aims of preventing harmful outcomes associated with early‐onset psychosis and improving prognosis. However, concerns have been raised regarding the ethical implications of involving young people inEIPservices. One way to ensure high ethical standards and promote good practice inEIPdelivery is through governance of clinical practice. This study aimed to investigate the normative dimensions of good practice inEIPthrough examination of clinical guideline documents published in England over the past 15 years.

Methods

A total of 14 clinical guidelines and relevant policy documents forEIPwere retrieved and analysed using a mixed inductive and deductive thematic approach. Themes were derived from the data itself, whereas the development of broader categories was performed through a constant comparison with the scientific literature describing ethical issues inEIP.

Results

Ethical touchpoints of good practice inEIPincluded both procedural and substantive factors, which were seen to be interdependent and mutually constitutive. These ethical touchpoints were largely implicit in the documents analysed. Procedural requirements ofEIPservice delivery consisted of norms and rules pertaining toEIPservice structure, adherence to codes of ethics, inclusivity, patient and family centredness and appropriate treatment provision. Substantive factors consisted of moral attributes that should be cultivated by healthcare professionals working inEIP: competency, empathy, sensitivity and trustworthiness.

Conclusions

We argue that, to ensure good practice inEIP, procedural and substantive ethical expectations embedded inEIPguideline documents should be made explicit inEIPservice and care delivery. We suggest that the procedural and substantive factors highlighted in this paper contribute useful dimensions for the eventual evaluation of good practice inEIPservices across England.
Contrasting effects of cyclophosphamide on anti‐CTL‐associated protein 4 blockade therapy in two mouse tumor models
Authors: Iida Yuichi , Harashima Nanae , Motoshima Takanobu , Komohara Yoshihiro , Eto Masatoshi , Harada Mamoru
Published: August 2017

Immune checkpoint blockade is a promising anticancer therapy, but must be used in combination with other anticancer therapies to increase its therapeutic efficacy. Cyclophosphamide (CP) is a chemotherapeutic drug that shows immune‐modulating effects. In this study, we examined the effect of CP on anti‐CTL‐associated protein 4 (CTLA‐4) blockade therapy in two mouse tumor models. Drastic tumor regression was observed in the CT26 colon carcinoma model after i.p. injection of CP (100 mg/kg) followed by anti‐CTLA‐4 antibody. However, administration in the reverse order increased apoptosis in tumor‐specific CD8+ T cells. In the RENCA renal carcinoma model, the antitumor effect of combination therapy was marginal and the tumor‐bearing state reduced body weight with an increased serum level of interleukin‐6. Interestingly, although CP monotherapy increased myeloid‐derived suppressor cells (MDSCs) in the spleens of both models, subsequent anti‐CTLA‐4 therapy increased MDSCs only in RENCA‐bearing mice. Additionally, the serum levels of chemokine ligand 2 and C‐X‐C motif chemokine 10 were increased by the combination therapy only in RENCA‐bearing mice and in vivo depletion of Gr‐1+ cells augmented the antitumor effect to some degree. These results reveal a contrasting effect of CP on anti‐CTLA‐4 therapy between the two mouse tumor models. Cyclophosphamide augments the antitumor effect of anti‐CTLA‐4 therapy in CT26‐bearing hosts, whereas CP after anti‐CTLA‐4 therapy attenuates this effect through induction of apoptosis in tumor‐reactive T cells. Alternatively, CP‐induced MDSCs can be increased by anti‐CTLA‐4 therapy only in RENCA‐bearing hosts with an elevated level of interleukin‐6.
Dermokine contributes to epithelial–mesenchymal transition through increased activation of signal transducer and activator of transcription 3 in pancreatic cancer
Authors: Huang Chaohao , Xiang Yukai , Chen Shengchuan , Yu Huajun , Wen Zhengde , Ye Tingting , Sun Hongwei , Kong Hongru , Li Dapei , Yu Dinglai , Chen Bicheng , Zhou Mengtao
Published: August 2017

Dermokine (DMKN) was first identified in relation to skin lesion healing and skin carcinoma. Recently, its expression was associated with pancreatic cancer tumorigenesis, although its involvement remains poorly understood. Herein, we showed that DMKN loss of function in Patu‐8988 and PANC‐1 pancreatic cancer cell lines resulted in reduced phosphorylation of signal transducer and activator of transcription 3, and increased activation of ERK1/2 and AKT serine/threonine kinase. This decreased the proliferation ability of pancreatic ductal adenocarcinoma (PDAC) cells. In addition, DMKN knockdown decreased the invasion and migration of PDAC cells, partially reversed the epithelial–mesenchymal transition, retarded tumor growth in a xenograft animal model by decreasing the density of microvessels, and attenuated the distant metastasis of human PDAC in a mouse model. Taken together, these data suggested that DMKN could be a potential prognostic biomarker and therapeutic target in pancreatic cancer.
CENP‐R acts bilaterally as a tumor suppressor and as an oncogene in the two‐stage skin carcinogenesis model
Authors: Okumura Kazuhiro , Kagawa Naoko , Saito Megumi , Yoshizawa Yasuhiro , Munakata Haruka , Isogai Eriko , Fukagawa Tatsuo , Wakabayashi Yuichi
Published: August 2017

CENP‐R is a component of the CENP‐O complex, including CENP‐O, CENP‐P, CENP‐Q, CENP‐R, and CENP‐U and is constitutively localized to kinetochores throughout the cell cycle in vertebrates. CENP‐R‐deficient chicken DT40 cells are viable and show a very minor effect on mitosis. To investigate the functional roles of CENP‐R in vivo, we generated CENP‐R‐deficient mice (Cenp‐r−/−). Mice heterozygous or homozygous for Cenp‐r null mutation are viable and healthy, with no apparent defect in growth and morphology, indicating Cenp‐r is not essential for normal development. Accordingly, to investigate the role of the Cenp‐r gene in skin carcinogenesis, we subjected Cenp‐r−/− mice to the 7,12‐dimethylbenz(a)anthracene (DMBA)/TPA chemical carcinogenesis protocol and monitored tumor development. As a result, Cenp‐r−/− mice initially developed significantly more papillomas than control wild‐type mice. However, papillomas in Cenp‐r−/− mice showed a decrease of proliferative cells and an increase of apoptotic cells. As a result, they did not grow bigger and some papillomas showed substantial regression. Furthermore, papillomas in Cenp‐r−/− mice showed lower frequency of malignant conversion to squamous cell carcinomas. These results indicate Cenp‐r functions bilaterally in cancer development: during early developmental stages, Cenp‐r functions as a tumor suppressor, but during the expansion and progression of papillomas it functions as a tumor‐promoting factor.
Re‐evaluation of lung to thorax transverse area ratio immediately before birth in predicting postnatal short‐term outcomes of fetuses with isolated left‐sided congenital diaphragmatic hernia: A single center analysis
Authors: Kido Saki , Hidaka Nobuhiro , Sato Yuka , Fujita Yasuyuki , Miyoshi Kina , Nagata Kouji , Taguchi Tomoaki , Kato Kiyoko
Published: August 2017

We aimed to investigate whether the lung‐to‐thorax transverse area ratio (LTR) immediately before birth is of diagnostic value for the prediction of postnatal short‐term outcomes in cases of isolated left‐sided congenital diaphragmatic hernia (CDH). We retrospectively reviewed the cases of fetal isolated left‐sided CDH managed at our institution between April 2008 and July 2016. We divided the patients into two groups based on LTR immediately before birth, using a cut‐off value of 0.08. We compared the proportions of subjects within the two groups who survived until discharge using Fisher's exact test. Further, using Spearman's rank correlation, we assessed whether LTR was correlated with length of stay, duration of mechanical ventilation, and supplemental oxygen. Twenty‐nine subjects were included (five with LTR < 0.08, and 24 with LTR ≥ 0.08). The proportion of subjects surviving until discharge was 40% (2/5) for patients with LTR < 0.08, as compared with 96% (23/24) for those with LTR ≥ 0.08. LTR measured immediately before birth was negatively correlated with the postnatal length of stay (Spearman's rank correlation coefficient, rs = −0.486), and the duration of supplemental oxygen (rs = −0.537). Further, the duration of mechanical ventilation was longer in patients with a lower LTR value. LTR immediately before birth is useful for the prediction of postnatal short‐term outcomes in fetuses with isolated left‐sided CDH. In particular, patients with prenatal LTR value less than 0.08 are at increased risk of postnatal death.
Simultaneous coloration and functional finishing of cotton fabric using Ag/ZnO nanocomposite
Authors: Avazpour Soniya , Karimi Loghman , Zohoori Salar
Published: August 2017

In this study, colored cotton fabric with special functions, including self‐cleaning, anti‐bacterial, and ultraviolet (UV) blocking were prepared by applying zinc oxide as a photocatalyst and using silver nanoparticles as both a novel class of colorant for coloration and an agent capable of modifying the zinc oxide nanoparticles. The homogenous distribution of Ag/ZnO nanocomposite on the fibre surface was confirmed by field emission scanning electron microscopy (FE‐SEM), Energy‐dispersive X‐ray spectroscopy (EDS) and X‐ray mapping. X‐ray diffraction patterns showed the presence of the nanocomposite on the treated cotton fabric. The results indicated that adding silver nanoparticles to zinc oxide led to better self‐cleaning properties, even the photocatalytic activity of ZnO had no negative effect on fabric colour. Moreover, this process imparted proper anti‐bacterial properties and UV‐blocking activity to cotton fabrics.
Relation of oxygen uptake to work rate in prepubertal healthy children – reference for VO2/W‐slope and effect on cardiorespiratory fitness assessment
Authors: Tompuri Tuomo , Lintu Niina , Laitinen Tomi , Lakka Timo A.
Published: August 2017

Purpose

Exercise testing by cycle ergometer allows to observe the interaction between oxygen uptake (VO2) and workload (W), and VO2/W‐slope can be used as a diagnostic tool. Respectively, peak oxygen uptake (VO2PEAK) can be estimated by maximal workload. We aim to determine reference for VO2/W‐slope among prepubertal children and define agreement between estimated and measured VO2PEAK.

Methods

A total of 38 prepubertal children (20 girls) performed a maximal cycle ergometer test with respiratory gas analysis. VO2/W‐slopes were computed using linear regression. Agreement analysis by Bland and Altman for estimated and measured VO2PEAK was carried out including limits of agreement (LA). Determinants for VO2/W‐slopes and estimation bias were defined.

Results

VO2/W‐slope was in both girls and boys ≥9·4 and did not change with exercise level, but the oxygen cost of exercise was higher among physically more active children. Estimated VO2PEAK had 6·4% coefficient of variation, and LA varied from 13% underestimation to 13% overestimation. Bias had a trend towards underestimation along lean mass proportional VO2PEAK. The primary determinant for estimation bias was VO2/W‐slope (β = −0·65; P<0·001).

Conclusion

The reference values for VO2/W‐slope among healthy prepubertal children were similar to those published for adults and among adolescents. Estimated and measured VO2PEAK should not be considered to be interchangeable because of the variation in the relationship between VO2 and W. On other hand, variation in the relationship between VO2 and W enables that VO2/W‐slope can be used as a diagnostic tool.
Significant arterial complications after pancreas transplantation—A single‐center experience and review of literature
Authors: Yadav Kunal , Young Shamar , Finger Erik B. , Kandaswamy Raja , Sutherland David E. R. , Golzarian Jafar , Dunn Ty B.
Published: August 2017

Arterial fistulas and pseudoaneurysms are rarely described significant arterial complications associated with pancreas transplantation that sometimes present with herald or catastrophic bleeding. We herein describe our institutional case series with a focus on management and outcomes. Of 2256 pancreas transplants, 24 arterial complications were identified in 23 recipients. Chart review was performed to describe the clinical characteristics, treatments, and outcomes of the complications (pseudoaneurysm, arterial enteric/cystic/ureteric fistula, or arteriovenous fistula). Of these 23 patients, 57% had a failed allograft at the time of the complication. Nine patients underwent primary surgical repair of 10 complications, 13 were treated by endovascular methods, and one patient by medical management. In total, 3 embolized patients rebled, 2 of which had failed allografts prior to treatment. Of those with graft function that were treated by embolization alone, all retained graft function. Diagnosis of arterial complications requires a high degree of suspicion and should involve early systemic angiography to evaluate the pancreatic vasculature. Management can be endovascular or surgical and should be individualized. We report our center's evolution from a predominantly surgical to endovascular approach as a definitive vs stabilizing therapy, with selective coiling mostly reserved for well‐defined peripheral lesions in patients with a functioning allograft.
Single‐Dose and Multiple‐Dose Pharmacokinetics of Vaniprevir in Healthy Men
Authors: Caro L , de Hoon J , Depré M , Cilissen C , Miller J , Gao W , Panebianco D , Guo Z , Troemel SL , Anderson MS , Uemura N , Butterton J , Wagner J , Wright DH
Published: August 2017

Vaniprevir is an inhibitor of the hepatitis C virus (HCV) NS3/4A protease. The aim of these double‐blind, placebo‐controlled phase I studies was to evaluate the safety and pharmacokinetics of vaniprevir in healthy male volunteers. The primary objective for both studies was the safety and tolerability of vaniprevir. Single‐dose and steady‐state pharmacokinetics were also assessed. In both studies, there was no apparent relationship between the frequency or intensity of adverse events and vaniprevir dose. At single doses >20 mg, the plasma area under the curve (AUC)0–∞ and maximum concentration (Cmax) increased in a greater‐than‐dose‐proportional manner. The geometric mean ratios (GMRs; fed/fasted) were 1.22 and 0.79 for AUC0–∞ and Cmax, respectively. Following multiple doses, GMR accumulations for AUC0–12h and Cmax (day 14/day 1) ranged from 1.53 to 1.90 and from 1.41 to 1.92, respectively. These data support the use of vaniprevir with peginterferon and ribavirin in patients with HCV infection.
Oral Apolipoprotein A‐I Mimetic D‐4F Lowers HDL‐Inflammatory Index in High‐Risk Patients: A First‐in‐Human Multiple‐Dose, Randomized Controlled Trial
Authors: Dunbar Richard L. , Movva Rajesh , Bloedon LeAnne T. , Duffy Danielle , Norris Robert B. , Navab Mohamad , Fogelman Alan M. , Rader Daniel J.
Published: August 2017

A single dose of the apolipoprotein (apo)A‐I mimetic peptide D‐4F rendered high‐density lipoprotein (HDL) less inflammatory, motivating the first multiple‐dose study. We aimed to assess safety/tolerability, pharmacokinetics, and pharmacodynamics of daily, orally administered D‐4F. High‐risk coronary heart disease (CHD) subjects added double‐blinded placebo or D‐4F to statin for 13 days, randomly assigned 1:3 to ascending cohorts of 100, 300, then 500 mg (n = 62; 46 men/16 women). D‐4F was safe and well‐tolerated. Mean ± SD plasma D‐4F area under the curve (AUC, 0–8h) was 6.9 ± 5.7 ng/mL*h (100 mg), 22.7 ± 19.6 ng/mL*h (300 mg), and 104.0 ± 60.9 ng/mL*h (500 mg) among men, higher among women. Whereas placebo dropped HDL inflammatory index (HII) 28% 8 h postdose (range, 1.25–0.86), 300–500 mg D‐4F effectively halved HII: 1.35–0.57 and 1.22–0.63, respectively (P < 0.03 vs. placebo). Oral D‐4F peptide dose predicted HII suppression, whereas plasma D‐4F exposure was dissociated, suggesting plasma penetration is unnecessary. In conclusion, oral D‐4F dosing rendered HDL less inflammatory, affirming oral D‐4F as a potential therapy to improve HDL function.
Repair of neonatal brain injury: bringing stem cell‐based therapy into clinical practice
Authors: Wagenaar Nienke , Nijboer Cora H , van Bel Frank
Published: August 2017

Hypoxic‐ischaemic brain injury is one of most important causes of neonatal mortality and long‐term neurological morbidity in infants born at term. At present, only hypothermia in infants with perinatal hypoxic‐ischaemic encephalopathy has shown benefit as a neuroprotective strategy. Otherwise, current treatment options for neonatal brain injury mainly focus on controlling (associated) symptoms. Regeneration of the injured neonatal brain with stem cell‐based therapies is emerging and experimental results are promising. At present, increasing efforts are made to bring stem cell‐based therapies to the clinic. Among all progenitor cell types, mesenchymal stromal (stem) cells seem to be most promising for human use given their neuroregenerative properties and favourable safety profile. This review summarizes the actual state, potential hurdles and possibilities of stem cell‐based therapy for neonatal brain injury in the clinical setting. An early version of this paper was presented at the Groningen Early Intervention Meeting which was held in April 2016.
Safety and efficacy of semaglutide once weekly vs sitagliptin once daily, both as monotherapy inJapanese people with type 2 diabetes
Authors: Seino Yutaka , Terauchi Yasuo , Osonoi Takeshi , Yabe Daisuke , Abe Nobuyuki , Nishida Tomoyuki , Zacho Jeppe , Kaneko Shizuka
Published: August 2017

Aims

To assess the safety and efficacy of monotherapy with once‐weekly subcutaneous (s.c.) semaglutide vs sitagliptin in Japanese people with type 2 diabetes (T2D).

Methods

In this phase IIIa randomized, open‐label, parallel‐group, active‐controlled, multicentre trial, Japanese adults with T2D treated with diet and exercise only or oral antidiabetic drug monotherapy (washed out during the run‐in period) received once‐weekly s.c. semaglutide (0.5 or 1.0 mg) or once‐daily oral sitagliptin 100 mg. The primary endpoint was number of treatment‐emergent adverse events (TEAEs) after 30 weeks.

Results

Overall, 308 participants were randomized and exposed to treatment, with similar baseline characteristics across the groups. In total, 2.9% of participants in both the semaglutide 0.5 mg and the sitagliptin group prematurely discontinued treatment, compared with 14.7% in the semaglutide 1.0 mg group. The majority of discontinuations in the semaglutide 0.5 and 1.0 mg groups were attributable to adverse events (AEs). More TEAEs were reported in semaglutide‐ vs sitagliptin‐treated participants (74.8%, 71.6% and 66.0% in the semaglutide 0.5 mg, semaglutide 1.0 mg and sitagliptin groups, respectively). AEs were mainly mild to moderate. Gastrointestinal AEs, most frequently reported with semaglutide, diminished in frequency over time. The mean glycated haemoglobin (HbA1c [baseline 8.1%]) decreased by 1.9% and 2.2% with semaglutide 0.5 and 1.0 mg, respectively, vs 0.7% with sitagliptin (estimated treatment difference [ETD] vs sitagliptin −1.13%, 95% confidence interval [CI] −1.32; −0.94, and −1.44%, 95% CI −1.63; −1.24; bothP < .0001). Body weight (baseline 69.3 kg) was reduced by 2.2 and 3.9 kg with semaglutide 0.5 and 1.0 mg, respectively (ETD −2.22 kg, 95% CI −3.02; −1.42 and −3.88 kg, 95% CI −4.70; −3.07; bothP < .0001).

Conclusions

In Japanese people with T2D, more TEAEs were reported with semaglutide than with sitagliptin; however, the semaglutide safety profile was similar to that of other glucagon‐like peptide‐1 receptor agonists. Semaglutide significantly reduced HbA1c and body weight compared with sitagliptin.
Lean body mass and creatine kinase are associated with reduced inflammation in obesity
Authors: Bekkelund Svein I. , Jorde Rolf
Published: August 2017

Background

Obesity is associated with inflammation, but the role of lean mass and creatine kinase (CK) on the inflammatory process is less known. We investigated the associations between lean mass, CK and fat mass upon inflammatory parameters in an overweight and obese adult population.

Material and methods

Body composition examined by dual‐energy X‐ray absorptiometry, high‐sensitivity C‐reactive protein (hs‐CRP), erythrocyte sedimentation rate (ESR), CK and supplementary clinical parameters were measured in 454 overweight and obese individuals. This is a secondary analysis from a cohort of obese individuals treated with Vitamin D.

Results

Mean age was 47·6 ± 11·4 years and mean body mass index 34·6 ± 3·9 kg/m2. Lean mass correlated negatively with hs‐CRP (r = −0·127, P = 0·042) and ESR (r = −0·381, P < 0·001). Median lean mass in the lower ESR quartile was significantly higher than in the upper quartile (P < 0·001) but not between lower and upper hs‐CRP quartiles (P = 0·114). CK was negatively correlated with hs‐CRP (r = −0·151, P < 0·001) and ESR (r = −0·240, P < 0·001). Median CK in the lower hs‐CRP and ESR quartiles were significantly higher than in the upper quartiles (P < 0·001 for both). Conversely, fat mass was positively associated with hs‐CRP and ESR.

Conclusions

Inflammatory parameters were related to reduced lean mass and CK in an overweight and obese population. Hypothetically, lean mass has a favourable effect on obesity‐related inflammation, and CK may play a role as an inhibitor of inflammation in obesity.
MULTIFACETED AID FOR LOW‐INCOME STUDENTS AND COLLEGE OUTCOMES: EVIDENCE FROM NORTH CAROLINA
Authors: Clotfelter Charles T. , Hemelt Steven W. , Ladd Helen F.
Published: August 2017

We study the evolution of a campus‐based aid program for low‐income students that began with grant‐heavy financial aid and later added a suite of nonfinancial supports. We find little to no evidence that program eligibility during the early years (2004–2006), in which students received additional institutional grant aid and few nonfinancial supports, improved postsecondary progress, performance, or completion. In contrast, program‐eligible students in more recent cohorts (2007–2010), when the program supplemented grant‐heavy aid with an array of nonfinancial supports, were more likely to meet credit accumulation benchmarks toward timely graduation and earned higher grade point averages than their barely ineligible counterparts. (JEL I21, I23, I24, J08)
Blood cell count in antipsychotic‐naive patients with non‐affective psychosis
Authors: Garcia‐Rizo Clemente , Casanovas Marta , Fernandez‐Egea Emilio , Oliveira Cristina , Meseguer Ana , Cabrera Bibiana , Mezquida Gisela , Bioque Miquel , Kirkpatrick Brian , Bernardo Miquel
Published: August 2017

Background

Schizophrenia is a complex medical entity with a reduced life expectancy, mostly due to an increased prevalence of cardiovascular diseases compared to the general population. An unbalanced immune response and a pro‐inflammatory state might underlie this process. In treated patients, abnormal white blood cell (WBC), lymphocyte and neutrophil count suggests atypical immune response related to clinical variables. We aimed to test the hypothesis that newly diagnosed naïve patients with non‐affective psychosis would show abnormal blood cell count values after controlling for potential confounding factors compared to matched controls.

Methods

Seventy‐five patients were compared with 80 controls matched for age, gender, body mass index and smoking. Analyses were conducted before and after controlling for smoking.

Results

Patients and controls displayed similar mean values (×103/μL [SD]) for WBC count 7.02 [2.2] vs 6.50 [1.7] (P = .159), neutrophil count 4.25 [1.8] vs 3.84 [1.3] (P = .110) and monocyte count 0.43 [0.2] vs 0.40 [0.1] (P = .326). After controlling for smoking, 38 non‐smoking patients showed a higher WBC and neutrophil count compared with 49 matched controls. Respective means of 7.01 [2.2] vs 5.97 [1.4] (P = .011) for WBC and 4.24 [1.9] vs 3.51 [1.2] (P = .028) for neutrophil count. Monocyte count showed an increased mean value 0.43 [0.2] vs 0.36 [0.1] with a trend towards signification (P = .063).

Conclusions

These results suggest that abnormal immune response is present before the effects of medication and other confounders had taken place. Increased immune parameters might underlie the high ratio of medical co‐morbidities described in schizophrenia.
Using the resurrection approach to understand contemporary evolution in changing environments
Authors: Franks Steven J. , Hamann Elena , Weis Arthur E.
Published: August 2017

The resurrection approach of reviving ancestors from stored propagules and comparing them with descendants under common conditions has emerged as a powerful method of detecting and characterizing contemporary evolution. As climatic and other environmental conditions continue to change at a rapid pace, this approach is becoming particularly useful for predicting and monitoring evolutionary responses. We evaluate this approach, explain the advantages and limitations, suggest best practices for implementation, review studies in which this approach has been used, and explore how it can be incorporated into conservation and management efforts. We find that although the approach has thus far been used in a limited number of cases, these studies have provided strong evidence for rapid contemporary adaptive evolution in a variety of systems, particularly in response to anthropogenic environmental change, although it is far from clear that evolution will be able to rescue many populations from extinction given current rates of global changes. We also highlight one effort, known as Project Baseline, to create a collection of stored seeds that can take advantage of the resurrection approach to examine evolutionary responses to environmental change over the coming decades. We conclude that the resurrection approach is a useful tool that could be more widely employed to examine basic questions about evolution in natural populations and to assist in the conservation and management of these populations as they face continued environmental change.