bluuebunny/crossref_metadata_2025 huggingface dataset:
Rosetta FunFolDes – a general framework for the computational design of functional proteins
Authors: Bonet Jaume , Wehrle Sarah , Schriever Karen , Yang Che , Billet Anne , Sesterhenn Fabian , Scheck Andreas , Sverrisson Freyr , Vollers Sabrina , Lourman Roxanne , Villard Melanie , Rosset Stéphane , Correia Bruno E.
Published: July 2018

The robust computational design of functional proteins has the potential to deeply impact translational research and broaden our understanding of the determinants of protein function, nevertheless, it remains a challenge for state-of-the-art methodologies. Here, we present a computational design approach that couples conformational folding with sequence design to embed functional motifs into heterologous proteins. We performed extensive benchmarks, where the most unexpected finding was that the design of function into proteins may not necessarily reside in the global minimum of the energetic landscape, which could have important implications in the field. We have computationally designed and experimentally characterized a distant structural template and a de novo “functionless” fold, two prototypical design challenges, to present important viral epitopes. Overall, we present an accessible strategy to repurpose old protein folds for new functions, which may lead to important improvements on the computational design of functional proteins.
3D-Printed Biodegradable Microswimmer for Drug Delivery and Targeted Cell Labeling
Authors: Ceylan Hakan , Yasa I. Ceren , Yasa Oncay , Tabak A. Fatih , Giltinan Joshua , Sitti Metin
Published: July 2018

Miniaturization of interventional medical devices can leverage minimally invasive technologies by enabling operational resolution at cellular length scales with high precision and repeatability. Untethered micron-scale mobile robots can realize this by navigating and performing in hard-to-reach, confined and delicate inner body sites. However, such a complex task requires an integrated design and engineering strategy, where powering, control, environmental sensing, medical functionality and biodegradability need to be considered altogether. The present study reports a hydrogel-based, biodegradable microrobotic swimmer, which is responsive to the changes in its microenvironment for theranostic cargo delivery and release tasks. We design a double-helical magnetic microswimmer of 20 μm length, which is 3D-printed with complex geometrical and compositional features. At normal physiological concentrations, matrix metalloproteinase-2 (MMP-2) enzyme can entirely degrade the microswimmer body in 118 h to solubilized non-toxic products. The microswimmer can respond to the pathological concentrations of MMP-2 by swelling and thereby accelerating the release kinetics of the drug payload. Anti-ErbB 2 antibody-tagged magnetic nanoparticles released from the degraded microswimmers serve for targeted labeling of SKBR3 breast cancer cells to realize the potential of medical imaging of local tissue sites following the therapeutic intervention. These results represent a leap forward toward clinical medical microrobots that are capable of sensing, responding to the local pathological information, and performing specific therapeutic and diagnostic tasks as orderly executed operations using their smart composite material architectures.
Does Adaptive Protein Evolution Proceed by Large or Small Steps at the Amino Acid Level?
Authors: Bergman Juraj , Eyre-Walker Adam
Published: July 2018

A longstanding question in evolutionary biology is the relative contribution of large and small effect mutations to the adaptive process. We have investigated this question in proteins by estimating the rate of adaptive evolution between all pairs of amino acids separated by one mutational step using a McDonald-Kreitman type approach and genome-wide data from severalDrosophilaspecies. We find that the rate of adaptive evolution is higher amongst amino acids that are more similar. This is partly due to the fact that the proportion of mutations that are adaptive is higher amongst more similar amino acids. We also find that the rate of neutral evolution between amino acids is higher amongst similar amino acids. Overall our results suggest that both the adaptive and non-adaptive evolution of proteins is dominated by substitutions between amino acids that are more similar.
Occurrence and predictive utility of isochronal, equiproportional, and other types of development among arthropods
Authors: Quinn Brady K.
Published: July 2018

In isochronal (ICD) and equiproportional development (EPD), the proportion of total immature (egg, larval, and/or juvenile) development spent in each stage (developmental proportion) does not vary among stages or temperatures, respectively. ICD and EPD have mainly been reported in copepods, and whether they occur in other arthropods is not known. If they did, then rearing studies could be simplified because the durations of later developmental stages could be predicted based on those of earlier ones. The goal of this study was to test whether different taxa have ICD, EPD, or an alternative development type in which stage-specific proportions depend on temperature, termed ‘variable proportional’ development (VPD), and also how well each development type allowed later-stage durations to be predicted from earlier ones. Data for 71 arthropods (arachnids, copepod and decapod crustaceans, and insects) were tested, and most (85.9 %) species were concluded to have VPD, meaning that ICD and EPD do not occur generally. However, EPD predicted later-stage durations comparably well to VPD (within 19-23 %), and thus may still be useful. Interestingly, some species showed a ‘mixed’ form of development, where some stages’ developmental proportions varied with temperature while those of others did not, which should be further investigated.

Highlights

Whether arthropod development is generally isochronal or equiproportional was tested

Developmental proportions of most species’ stages varied with temperature

Many species had ‘mixed’ development between variable and equiproportional types

The general occurrence of isochronal and equiproportional development was rejected

Equiproportional development did make reasonable predictions of stage durations
Computationally Reconstructing Cotranscriptional RNA Folding Pathways from Experimental Data Reveals Rearrangement of Non-Native Folding Intermediates
Authors: Yu Angela M , Gasper Paul M. , Strobel Eric J. , Watters Kyle E. , Chen Alan A. , Lucks Julius B.
Published: July 2018

The series of RNA folding events that occur during transcription, or a cotranscriptional folding pathway, can critically influence the functional roles of RNA in the cell. Here we present a method, Reconstructing RNA Dynamics from Data (R2D2), to uncover details of cotranscriptional folding pathways by predicting RNA secondary and tertiary structures from cotranscriptional SHAPE-Seq data. We applied R2D2 to the folding of the Escherichia coli Signal Recognition Particle (SRP) RNA sequence and show that this sequence undergoes folding through non-native intermediate structures that require significant structural rearrangement before reaching the functional native structure. Secondary structure folding pathway predictions and all-atom molecular dynamics simulations of folding intermediates suggest that this rearrangement can proceed through a toehold mediated strand displacement mechanism, which can be disrupted and rescued with point mutations. These results demonstrate that even RNAs with simple functional folds can undergo complex folding processes during synthesis, and that small variations in their sequence can drastically affect their cotranscriptional folding pathways.

Highlights

- Computational methods predict RNA structures from cotranscriptional SHAPE-Seq data

- The E. coli SRP RNA folds into non-native structural intermediates cotranscriptionally

- These structures rearrange dynamically to form an extended functional fold

- Point mutations can disrupt and rescue cotranscriptional RNA folding pathways
A Ca2+-ATPase Regulates E-cadherin Biogenesis and Epithelial-Mesenchymal Transition in Breast Cancer Cells
Authors: Dang Donna K. , Makena Monish Ram , Llongueras José P. , Prasad Hari , Ko Myungjun , Bandral Manuj , Rao Rajini
Published: July 2018

Progression of benign tumors to invasive, metastatic cancer is accompanied by the epithelial to mesenchymal transition (EMT), characterized by loss of the cell-adhesion protein E-cadherin. Although silencing mutations and transcriptional repression of the E-cadherin gene have been widely studied, not much is known about post-translational regulation of E-cadherin in tumors. We show that E-cadherin is tightly co-expressed with the secretory pathway Ca2+-ATPase isoform 2, SPCA2 (ATP2C2), in breast tumors. Loss of SPCA2 impairs surface expression of E-cadherin and elicits mesenchymal gene expression through disruption of cell adhesion in tumorspheres and downstream Hippo-YAP signaling. Conversely, ectopic expression of SPCA2 in triple negative breast cancer (TNBC) elevates baseline Ca2+ and YAP phosphorylation, enhances post-translational expression of E-cadherin, and suppresses mesenchymal gene expression. Thus, loss of SPCA2 phenocopies loss of E-cadherin in the Hippo signaling pathway and EMT-MET transitions, consistent with a functional role for SPCA2 in E-cadherin biogenesis. Furthermore, we show that SPCA2 suppresses invasive phenotypes, including cell migration in vitro and tumor metastasis in vivo. Based on these findings, we propose that SPCA2 functions as a key regulator of EMT and may be a potential therapeutic target for treatment of metastatic cancer.

Implications

Post-translational control of E-cadherin and the Hippo pathway by calcium signaling regulates epithelial mesenchymal transition in breast cancer cells.
Crystal structure of tetrakis(1,1,1,5,5,5-hexafluoroacetylacetonato)hafnium(IV)
Authors: Schwandt W. Franklin , Woods Toby J. , Girolami Gregory S.
Published: July 2018

The crystal structure of the title compound, [Hf(C5HF6O2)4], has been determined. The asymmetric unit contains two Hf(hfac)4 molecules (hfac = 1,1,1,5,5,5-hexafluoroacetylacetonate); both are located on general positions and have identical structures apart from the disorder involving three CF3 groups in one of the two molecules. The molecules of Hf(hfac)4 are arranged in layers that are parallel to the ab plane, and the coordination geometry of each hafnium(IV) center is a distorted square antiprism. An interesting aspect of the structure is that the hfac ligands are arranged so that the Hf(hfac)4 molecules have idealized 2 point symmetry, in which two of the hfac groups bridge between the two squares. Although all other M(β-diketonate)4 compounds of Hf (and Zr) also have square-antiprismatic geometries; in almost all of them the ligands are arranged so that the molecules have 222 point symmetry (in which none of the hfac ligands bridges between the two squares). The factors that favor one structure over another are not clear.
National corporate governance, GMI ratings and earnings management
Authors: El-Helaly Moataz , Shehata Nermeen F. , El-Sherif Reem
Published: July 2018

Purpose

The purpose of this paper is to assess the association between country-level corporate governance and earnings management (EM). It aims to investigate whether the Governance Metrics International (GMI; acquired by Morgan Stanley Capital International in 2014) rating for national corporate governance on a country level is a significant explanatory variable for the country-level EM score or otherwise.

Design/methodology/approach

In a sample of 280 country-year observations during the period from 2000 to 2009, the paper measures national corporate governance quality using GMI ratings scores and whether the corporate governance model is Anglo Saxon or otherwise.

Findings

The findings of this study show that corporate governance is a significant indicator of lower EM levels in a country.

Practical implications

Corporate governance rating firms play a vital role in public markets. GMI provides country-level corporate governance ratings to assess the quality of corporate governance in several countries. The findings of this study show preliminary evidence that GMI ratings of corporate governance provide good guidance to investors on the quality of corporate governance in a country.

Originality/value

This paper is the first empirical attempt to examine the association between country-level corporate governance, GMI ratings for country-level corporate governance and EM.
Private school vouchers for expanding secondary school access? The case of Tanzania
Authors: Baum Donald R. , Cilliers Jacobus
Published: July 2018

Purpose

The purpose of this paper is to provide insight into the current contributions of private schools to education provision in Tanzania, and to consider the feasibility of a school voucher program to contribute to the expansion of the secondary school system, compared to the alternative expansion of public secondary education.

Design/methodology/approach

The study offers an analysis of current educational circumstances and educational goals in Tanzania, and projects differential costs and outcomes associated with various options for expanding secondary education. Data come from two sources: a census of the private schooling market in the Morogoro Urban district, conducted as part of the World Bank’s Systems Approach for Better Education Results initiative; and Tanzania’s National Panel Survey 2010–2011.

Findings

For those students unable to cover the full cost of secondary education, findings suggest that a targeted private school voucher would be an efficient and equitable policy mechanism for secondary school expansion. Such an approach would ease the financial burden on government for constructing all new schools, yet assure access for the most vulnerable.

Originality/value

The implementation of school voucher programs is increasing in low-income countries. It is important for policy makers to carefully consider the appropriateness of this type of policy intervention for their particular educational contexts. This paper models an approach by which researchers and policymakers can assess the educational circumstances of a particular location, and determine the potential effectiveness of a private school voucher policy.
Slow moving stock problem: empirical evidence from Malaysia
Authors: Nawawi Anuar , Salin Ahmad Saiful Azlin Puteh
Published: July 2018

Purpose

The purpose of this study is to identify weaknesses in the internal control of the stock management processes and provide recommendations to improve those weaknesses. The study also analyses whether the current stock management processes are adequately documented and updated regularly.

Design/methodology/approach

One company involved in the automotive industry was selected as a case study and its stock management examined, focusing on the processes involved and the reliability of the current inventory system. Data were collected via interviews with the selected staff and document analysis on various financial and non-financial company records.

Findings

The results show that there are loopholes and weaknesses in the current stock management system. This is because of poor technology and a lack of exposure and knowledge of staff involved in the stock management system.

Research limitations/implications

As this research is based on one company as a study case, generalization must be done with precaution. Access to certain important documents was denied because of the confidentiality.

Practical/implications

This study will help companies in the automotive sector to improve their stock management process, allowing for more efficient cost control and better services to customers. Specifically, this study identifies weaknesses in the current inventory management and provides recommendations to overcome those weaknesses. This will indirectly prevent fraud and theft and safeguard the cash flow of the company by improving the operation of the procurement and spare parts stock control department.

Originality/value

This study is original, as it focuses on a company that operates in the automotive sector, which is rare in the internal control literature, particularly in developing markets such as Malaysia. It contains examinations of various internal documents that are generally difficult to be accessed by researchers for the publication in an academic journal.
Improvement of recovery parameters using patient‐controlled epidural analgesia for video‐assisted thoracoscopic surgery lobectomy in enhanced recovery after surgery: A prospective, randomized single center study
Authors: Zejun Niu , Wei Feng , Lin Lyu , He Dong , Haichen Chu
Published: July 2018

Background

We compared the effects of thoracic epidural analgesia (TEA) to conventional patient‐controlled analgesia (PCA) on several postoperative parameters of recovery after elective video‐assisted thoracoscopic (VATS) lobectomy.

Methods

Ninety‐eight patients undergoing elective VATS lobectomy were enrolled. The primary endpoint was pain score. Recovery of bowel function, length of stay in the postanesthesia care unit (PACU), duration of postoperative hospital stay, and complications were assessed. Continuous variables were expressed and compared between groups using either a two‐tailed Student's t or Mann‐Whitney U test. Recovery of bowel function was compared using the log‐rank test.

Results

Baseline characteristics between the groups were similar. Dynamic pain scores on postoperative days (PODs) 0–2 were significantly lower in the TEA group, as were resting pain scores on PODs 1 and 2 (P < 0.05). The mean duration to first flatus (16 ± 0.7 vs. 26 ± 0.7 hours; P < 0.001) and the mean length of stay in the PACU (34 vs. 67 minutes; P = 0.027) were shorter in the TEA compared to the PCA group, respectively. The only difference in postoperative complications was regarding confusion (5 TEA vs. 18 PCA patients; P = 0.002). No difference in overall length of stay was noted.

Conclusions

Compared to PCA, TEA provided better postoperative pain control after VATS lobectomy and facilitated postoperative recovery of bowel function without increasing the length of hospital stay. This beneficial effect of TEA might be attributed to the attenuation of sympathetic hyperactivation, improved analgesia, and reduced opioid use.
Predicting invasion risk of 16 species of eucalypts using a risk assessment protocol developed for Brazil
Authors: Ziller Sílvia R. , de Sá Dechoum Michele , Dudeque Zenni Rafael
Published: July 2018

Risk analyses are predictive systems designed to detect the risk of invasion by non‐native species. Although eucalypts are often considered moderately invasive given the extent of cultivation on a global scale, some species are widely recognized as invasive for transforming and impacting natural areas in several countries. These problems may be due to propagule pressure derived from human interest in forest production and aesthetic values. Risk analyses were carried out for 16 eucalypt species cultivated in Brazil using a protocol adapted from an Australian model to Brazilian conditions. The species were: Corymbia citriodora, Corymbia maculata, Corymbia torelliana, Eucalyptus benthamii, Eucalyptus brassiana, Eucalyptus camaldulensis, Eucalyptus cloeziana, Eucalyptus dunnii, Eucalyptus globulus, Eucalyptus grandis, Eucalyptus pellita, Eucalyptus robusta, Eucalyptus saligna, Eucalyptus tereticornis, Eucalyptus urophylla and Eucalyptus viminalis. Results indicate high risk for seven species, moderate risk for eight species and low risk for one species. The only low risk species is E. dunnii, while the highest risk scores refer to C. torelliana, E. tereticornis and E. grandis. These results are consistent with the history of invasion of the species around the world and should be considered for plantations especially when investment capacity to prevent and permanently control spread is low or not associated with forest certification standards. Risk analysis is a valid tool for discriminating between species and making decisions on species to be introduced or cultivated. The results of this study show that there are many species that can be cultivated without incurring biological invasions.
Among seven testis‐specific molecular markers, SPEM1 appears to have a significant clinical value for prediction of sperm retrieval in azoospermic men
Authors: Hashemi M.‐S. , Mozdarani H. , Ghaedi K. , Nasr‐Esfahani M. H.
Published: July 2018

Background

To achieve sperm retrieval in azoospermic men, predicting the success rate seems to be necessary.

Objectives

In the present study we aimed to assess expression of seven molecular markers [ESX1, DAZ, DAZL (pre‐meiotic markers), ZMYND15, PRM1, TNP1, and SPEM1 (post‐meiotic markers)] to predict the success of sperm retrieval.

Materials and Methods

In this study, 63 azoospermic men [16 OA (obstructive azoospermia) and 47 NOA (nonobstructive azoospermia)] undergoing testicular tissue microdissection (micro‐TESE) for intracytoplasmic sperm injection (ICSI). Expression levels of these target genes were determined by real‐time reverse transcription polymerase chain reaction using the DDCt method, and efficacy of each gene was compared by receiver operating characteristic (ROC) curve analysis.

Results

Expression of post‐meiotic transcripts significantly decreases in NOA and its subgroups (SCOS: Sertoli cell only syndrome, MA: maturation arrest, and HS: hypospermatogenesis) with spermatogenic failure compared to normal spermatogenesis (OA), with an exception of ZMYND15 for the HS group. These findings suggest the differential expression of the post‐meiotic ZMYND15 marker is in accordance with histological findings and can discriminate HS from SCOS and MA. Post‐meiotic markers were significantly reduced in negative vs. positive sperm retrieval groups.

Discussion and Conclusion

Among the seven markers, SPEM1 had the best positive prediction power (96%) and negative prediction power (85%) at a 0.086 cutoff with the area under the curve (AUC) of 0.91 for receiver operating characteristic 4 (ROC) to predict the micro‐TESE outcome.
Knowledge, experience and attitudes towards skin‐to‐skin contact following Caesarean sections among health professionals in Vietnam
Authors: Tran Hoang Thi , Nippita Tanya , Nguyen Phuong Thi Kim , Nguyen Phuong Thi Thu , Huynh Thuy Thi Diem , Hua Oanh Thi Le , Roberts Christine L.
Published: July 2018

Aim

This study explored knowledge, experience and attitudes of health professionals towards early essential newborn care and skin‐to‐skin contact following Caesarean sections in a tertiary hospital in Central Vietnam.

Method

We conducted a cross‐sectional descriptive study using an anonymous questionnaire in March 2016. Health professionals from obstetrics, anaesthesiology and neonatology departments were surveyed.

Results

All of the 204 surveys were returned, accounting for 82% of total staff involved in the care for women and newborns with Caesarean sections. Correct knowledge of early essential newborn care was lowest among anaesthesiology staff. Health professionals reported that ≥90% of Caesarean section births they attended in the preceding week had skin‐to‐skin contact. Approximately 16% obstetricians, 71% midwives, 49% anaesthesiology and 76% neonatology staff considered the current frequency of skin‐to‐skin contact to be about right. The remainder considered the current rate too high. All professional groups identified the main difficulties of conducting skin‐to‐skin contact as the temperature in the operating theatre and the need for additional staff. Other concerns included increasing the risk of the baby of falling off, prolonging the operation and difficulty to monitor mothers.

Conclusion

The study identifies issues where improvements can be made in the implementation of skin‐to‐skin contact following Caesarean sections.
Retrospective study recommends endoscopy when diagnosing lymphocytic colitis or eosinophilic gastrointestinal disorder in children with abdominal pain
Authors: Tilma Jens , Tilma Jørgen , Tilma Karen
Published: July 2018

Aim

This study assessed the prevalence, clinical presentation and outcome of lymphocytic colitis (LC) and eosinophilic gastrointestinal disease (EGID) in children with severe, recurrent abdominal pain (RAP), by describing the predominant symptoms, diagnostic approaches and treatment options.

Methods

We performed a retrospective follow‐up study at a Danish regional hospital by reviewing the histology reports of the children who had undergone gastrointestinal endoscopy for RAP. Data were retrieved from the medical records of those who met the diagnostic criteria for LC and, or, EGID from 2011 to 2016. The study population comprised 381 patients who underwent a diagnostic process to clarify RAP.

Results

A total of 74 patients (39 females) aged 2–17 years, with severe RAP as the most predominant symptom underwent gastrointestinal endoscopy. This identified 16/74 (21.6%) with LC (n = 6) and, or, EGID (n = 11), which equated to 4.2% with RAP. No biochemical patterns of abnormalities were found. Medical treatment and, or, diet generally induced and maintained clinical remission.

Conclusion

We found 16 children with LC and, or, EGID. The predominant symptom was severe RAP. All patients had a macroscopically normal mucosa at endoscopy, a specific histopathological feature and no characteristic biochemical findings. Endoscopy should be considered in these cases.
General intelligence was associated with academic achievement but not fitness in adolescents after one year
Authors: Gil‐Espinosa Francisco Javier , Chillón Palma , Cadenas‐Sanchez Cristina
Published: July 2018

Aim

This study investigated whether general intelligence could predict physical fitness and academic achievements one year later.

Methods

We recruited 129 Spanish adolescents (57.4% boys) with a mean age of 13.6 ± 0.7 years old from a convenience sample of a single public‐funded school. The first step was to assess general intelligence during the 2015–2016 school year using the D48 nonverbal test. A year later, we collected data on fitness and academic achievements. Cardiorespiratory fitness was measured with the 20‐m endurance shuttle run test, muscular strength with the standing long jump and flexibility with the sit and reach test. Academic achievement was measured using school grades. The findings were assessed using three models with different variables.

Results

One year later, general intelligence at baseline was marginally significantly associated with flexibility (p = 0.079) and mathematics (p = 0.084) in the first model, with mathematics (p = 0.029) and geography and history (p = 0.016) in the second model and with geography and history (p = 0.022) in the third model. All the analyses were controlled by age, sex, fitness and academic achievement.

Conclusion

General intelligence may not predict fitness, but it may predict academic achievements in adolescents one year later. Further studies are needed to examine our findings.
Literature review informs clinical guidelines for pain management during screening and laser photocoagulation for retinopathy of prematurity
Authors: Pirelli Anna , Savant Levet Patrizia , Garetti Elisabetta , Ancora Gina , Merazzi Daniele , Bellieni Carlo Valerio , Lago Paola ,   the Pain Study Group of the Italian Society of Neonatology
Published: July 2018

Aim

The aim of this study was to carry out a literature review and develop clinical guidelines for pain prevention and control during screening and laser photocoagulation for retinopathy of prematurity (ROP) in neonatal intensive care units (NICUs).

Methods

The Italian Society of Neonatology assessed papers published between 1986 and June 2017 and used the Grading of Recommendations, Assessment, Development and Evaluation approach, to develop new guidelines on pain and ROP.

Results

The Society's pain experts assessed the full texts of 47 papers, including randomised or quasi‐randomised controlled trials and case–control studies on nonpharmacological and pharmacological measures used in NICUs during the screening and laser photocoagulation of neonates for ROP. The literature suggested methods for reducing the stress and pain associated with ROP screening procedures. The panel concluded that the literature showed that it was feasible to provide laser photocoagulation for ROP in spontaneously breathing patients with adequate analgesia.

Conclusion

This literature review on managing pain in infants with ROP in NICUs led to the development of national guidelines, which will help physicians and nurses to reduce the stress and pain experienced by premature newborn infants during unavoidable screening and treatment for ROP.
Normal DNA methylation status in sperm from a somatic cell cloned bull and their fertilized embryos
Authors: Yamanaka Ken‐Ichi , Yamashita Kyoko , Khatun Hafiza , Wada Yasuhiko , Tatemoto Hideki , Sakatani Miki , Takenouchi Naoki , Takahashi Masashi , Watanabe Shinya
Published: July 2018

Epigenetic reprogramming confers totipotency even during somatic cell nuclear transfer (SCNT), which has been used to clone various animal species. However, as even apparently healthy cloned animals sometimes have aberrant epigenetic status, the harmful effects of these defects could be passed onto their offspring. This is one of the biggest obstacles for the application of cloned animals for livestock production. Here, we investigated the DNA methylation status of four developmentally regulated genes (PEG3, XIST, OCT4, and NANOG) in sperms from a cloned and a non‐cloned bull, and blastocysts obtained by in vitro fertilization using those sperms and SCNT. We found no differences in the methylation status of the above genes between cloned and non‐cloned bull sperms. Moreover, the methylation status was also similar in blastocysts obtained with cloned and non‐cloned bull sperms. In contrast, the methylation status was compromised in the SCNT blastocysts. These results indicate that sperm from cloned bulls would be adequately reprogrammed during spermatogenesis and, thus, could be used to produce epigenetically normal embryos. This study highlights the normality of cloned bull offspring and supports the application of cloned cattle for calf production.
Measuring social support for healthy eating and physical activity in obesity
Authors: Rieger Elizabeth , Sellbom Martin , Murray Kristen , Caterson Ian
Published: July 2018

Objectives

This study sought to investigate the psychometric properties of two commonly used measures of social support in obesity, namely, the Social Support for Eating Habits (SSEH) and Social Support for Physical Activity (SSPA) scales.

Design

Cross‐sectional and longitudinal study design.

Methods

Participants were 200 adults with obesity taking part in a 12‐month cognitive behavioural weight loss programme. At pre‐treatment, participants completed the SSEH and SSPA as well as measures of social support, motivation, self‐efficacy, and health‐related quality of life to assess concurrent validity. Predictive validity was assessed in terms of baseline SSEH and SSPA scores predicting post‐treatment weight while controlling for pre‐treatment weight.

Results

Factor analysis supported a two‐factor solution for both the SSEH (‘Encouragement’ and ‘Discouragement’) and SSPA (‘Participation’ and ‘Punishment’) scales, with each subscale demonstrating acceptable internal consistency. While the results provided some support for the concurrent validity of the SSEH Discouragement and SSPA Participation subscales, there was mixed support for the SSEH Encouragement subscale and poor support for the SSPA Punishment subscale. No support was found in terms of predictive validity.

Conclusions

The findings question the validity of the SSEH and SSPA scales in obesity, with behaviours deemed to be supportive in non‐obese populations not necessarily perceived as such by people with obesity. The development of a psychometrically sound measure of social support in the obesity context is needed.

Statement of contribution

What is already known on this subject?

Social support is a robust predictor of positive health outcomes.

There is mixed support for the association between social support and weight‐related outcomes in obesity.

Discrepant findings may be due to social support measures of questionable reliability and validity in obesity.

What does this study add?

The SSEH and SSPA scales have questionable validity in obesity.

Behaviours deemed to be supportive by family and friends may not be perceived as such by individuals with obesity.

A psychometrically sound measure of social support in the obesity context is needed.
Clinical variability in inherited glycosylphosphatidylinositol deficiency disorders
Authors: Bellai‐Dussault Kara , Nguyen Thi Tuyet Mai , Baratang Nissan V. , Jimenez‐Cruz Daniel A. , Campeau Philippe M.
Published: July 2018

It is estimated that 0.5% of all mammalian proteins have a glycosylphosphatidylinositol (GPI)‐anchor. GPI‐anchored proteins (GPI‐APs) play key roles, particularly in embryogenesis, neurogenesis, immune response and signal transduction. Due to their involvement in many pathways and developmental events, defects in the genes involved in their synthesis and processing can result in a variety of genetic disorders for which affected individuals display a wide spectrum of features. We compiled the clinical characteristics of 202 individuals with mutations in the GPI biosynthesis and processing pathway through a review of the literature. This review has allowed us to compare the characteristics and the severity of the phenotypes associated with different genes as well as highlight features that are prominent for each. Certain combinations, such as seizures with aplastic/hypoplastic nails or abnormal alkaline phosphatase levels suggest an inherited GPI deficiency, and our review of all clinical findings may orient the management of inherited GPI deficiencies.
Mutations in known disease genes account for the majority of autosomal recessive retinal dystrophies
Authors: Patel N. , Alkuraya H. , Alzahrani S.S. , Nowailaty S.R. , Seidahmed M.Z. , Alhemidan A. , Ben‐Omran T. , Ghazi N.G. , Al‐Aqeel A. , Al‐Owain M. , Alzaidan H.I. , Faqeih E. , Kurdi W. , Rahbeeni Z. , Ibrahim N. , Abdulwahab F. , Hashem M. , Shaheen R. , Abouelhoda M. , Monies D. , Khan A.O. , Aldahmesh M.A. , Alkuraya Fowzan S.
Published: July 2018

Retinal dystrophies (RDs) are hereditary blinding eye conditions that are highly variable in their clinical presentation. The remarkable genetic heterogeneity that characterizes RD was a major challenge in establishing the molecular diagnosis in these patients until the recent advent of next‐generation sequencing. It remains unclear, however, what percentage of autosomal recessive RD remain undiagnosed when all established RD genes are sequenced. We enrolled 75 families in which RD segregates in an apparently autosomal recessive manner. We show that the yield of a multigene panel that contains known RD genes is 67.5%. The higher yield (82.3%) when whole exome sequencing was implemented instead was often due to hits in genes that were not included in the original design of the panel. We also show the value of homozygosity mapping even during the era of exome sequencing in uncovering cryptic mutations. In total, we describe 45 unique likely deleterious variants (of which 18 are novel including one deep intronic and one genomic deletion mutation). Our study suggests that the genetic heterogeneity of autosomal recessive RD is approaching saturation and that any new RD genes will probably account for only a minor role in the mutation burden.
Wheat stocks and the cointegration of wheat prices
Authors: Slade Peter , Gray Richard
Published: July 2018

We examine the effect of wheat stocks on the relationship between port and inland wheat prices in western Canada after the dissolution of the Canadian Wheat Board in 2012. Standard statistical tests find no evidence that the port price is cointegrated with inland prices. We argue that large harvests in 2013–2014 and 2014–2015 are responsible for this lack of cointegration. A simple theoretical model demonstrates how wheat stocks drive a wedge between inland and port prices. After including wheat stocks in the cointegrating vector, we find the expected cointegrating relationships between the port and inland prices. Using an error correction model, we show that a 10% increase in the wheat stocks reduces producer prices in Alberta and Manitoba by 6% and 4%, respectively. We conclude by discussing policy options for reducing the size of wheat stocks on the prairies.
Chronic opioid use and clinical outcomes in lung transplant recipients: A single‐center cohort study
Authors: Drees David , Tumin Dmitry , Miller Rebecca , Kirkby Stephen , Bhalla Tarun , Tobias Joseph D. , Hayes Don
Published: July 2018

Introduction

Chronic opioid use is common after organ transplantation, and has been associated with poor outcomes in transplantation of abdominal organs. However, little is known about possible influences of chronic opioid use on outcomes of lung transplantation (LTx).

Objectives

We assessed whether long‐term chronic opioid use influenced clinical outcomes among LTx recipients at our program.

Methods

We retrospectively evaluated chronic opioid use among bilateral LTx recipients ages 12 and older followed at our institution 1‐5 years post‐transplant. Chronic opioid use was defined as ≥3 months of consecutive prescribed use. Outcomes included survival, hospitalization, emergency department and urgent care visits, forced expiratory volume in one second (FEV1), and allograft rejection.

Results

Twenty‐one patients ages 15‐50 years met inclusion criteria. On multivariable analysis, initiation of chronic opioid use was followed by increased mortality hazard (hazard ratio=7.1; 95% confidence interval [CI]: 1.1, 45.0, P = 0.037) and decreased FEV1 (‐16%; 95% CI: ‐24%, ‐7%; P < 0.001), although no differences were observed in risk of acute care visits, inpatient admission, or chronic rejection.

Conclusion

This analysis presents the first evidence that late‐onset chronic opioid use may be associated with decreased lung function and increased mortality after LTx. Therefore, evaluation of chronic opioid use should be included in the routine monitoring of transplant recipients, to better define the impact of this risk factor on LTx outcomes.
The association between the incidence of intestinal graft‐vs‐host disease and antibiotic use after allogeneic hematopoietic stem cell transplantation
Authors: Hidaka Daisuke , Hayase Eiko , Shiratori Souichi , Hasegawa Yuta , Ishio Takashi , Tateno Takahiro , Okada Kohei , Goto Hideki , Sugita Junichi , Onozawa Masahiro , Nakagawa Masao , Kahata Kaoru , Endo Tomoyuki , Hashimoto Daigo , Teshima Takanori
Published: July 2018

Intestinal microbiota plays an important role in the regulation of allogeneic immune reaction after allogeneic hematopoietic stem cell transplantation (allo‐SCT). Intestinal graft‐vs‐host disease (GVHD) is one of the major causes of mortality after allo‐SCT and often complicated with intestinal dysbiosis. Recent studies suggest that antibiotic‐induced dysbiosis is a risk factor for intestinal GVHD. We retrospectively evaluated the impacts of antibiotic use on the incidence of intestinal GVHD occurring before day 100 after allo‐SCT. Among 213 patients who underwent allo‐SCT, 200 patients achieving engraftment were analyzed. Antibiotics were classified into carbapenem, quinolone, penicillin, cephem, and glycopeptide. Among 128 patients who developed acute GVHD, intestinal GVHD developed in 36 patients. Patients with intestinal GVHD received significantly longer administration of carbapenem and glycopeptide compared to those without it in periengraftment period. In multivariate analysis, use of carbapenem for greater than 7 days was associated with an increased risk of intestinal GVHD. However, use of antibiotics for greater than 7 days was not associated with poor overall survival and high nonrelapse mortality. Long use of carbapenem in periengraftment period may be a risk for intestinal GVHD. Prospective studies are required to validate our findings.
Pediatric cutaneous T‐cell post‐transplant lymphoproliferative disorder: Case report and review of the literature
Authors: Rogers Thomas S. , McGevna Laura , Cook Deborah L.
Published: July 2018

Post‐transplant lymphoproliferative disease (PTLD) is a rare lymphoid and/or plasmacytic proliferation that occurs in the context of immunosuppression because of solid organ transplantation (SOT) and allogeneic hematopoietic stem cell transplantation (HSCT). PTLD is the most common cancer in children who receive a SOT or HSCT, occurring in up to 13% of these patients. The majority of PTLDs are extracutaneous B‐cell lymphomas, with only 12% to 14%, representing the T‐cell phenotype. PTLDs can involve the skin and behave like an aggressive lymphoma, and are among the most serious and potentially fatal complications of transplantation. Here we present a case report and review of the literature of pediatric cutaneous PTLD.
Panniculitis in a patient with pathologic complete response to talimogene laherparepvec treatment for recurrent, in‐transit melanoma
Authors: Long Thomas H. , Shinohara Michi M. , Argenyi Zsolt B. , Thompson John A. , Gardner Jennifer M.
Published: July 2018

Talimogene laherparepvec (T‐VEC) is a novel intralesional oncolytic genetically modified herpes simplex virus type 1 vector for the treatment of unresectable cutaneous, subcutaneous, and nodal melanoma. Although immunological therapies such as T‐VEC offer therapeutic promise, they carry a risk of immune‐related adverse events (irAEs), the full spectrum of which is incompletely understood. We report a 63‐year‐old previously healthy man with cutaneous melanoma of the right ankle and progressive right lower extremity in‐transit metastases despite systemic therapy with immunomodulatory and molecularly targeted treatments. T‐VEC treatment resulted in a complete pathologic response on scouting biopsies. Biopsy of the right lateral calf showed lobular and septal panniculitis with lymphoplasmacytic infiltrate and lipophages. Gomori methenamine silver (GMS) stain and acid‐fast bacilli (AFB) stains were negative, and no polarizable foreign material was noted. T‐VEC was discontinued due to complete pathologic response and, in part, concern for development of irAEs including this panniculitis and an early concomitant autoimmune colitis. This case highlights a previously unreported irAE with this novel treatment for advanced cases of melanoma.
Liraglutide relieves cardiac dilated function than DPP‐4 inhibitors
Authors: Hiramatsu Takeyuki , Asano Yuko , Mabuchi Masatsuna , Imai Kentaro , Iguchi Daiki , Furuta Shinji
Published: July 2018

Introduction

Diabetes mellitus is a progressive disease with cardiovascular complications. This study evaluated the effects of liraglutide, a glucagon‐like peptide‐1 analogue and the dipeptidyl peptidase 4 inhibitors sitagliptin and linagliptin on cardiac function in type 2 diabetes patients with renal impairment.

Materials and Methods

A total of 139 patients who were referred because of suboptimal glycaemic control were randomly assigned to liraglutide 0.9 mg/d (n = 45), sitagliptin 50 mg/d, (n = 49) or linagliptin 5 mg/d (n = 45) at enrolment and were evaluated. Blood glucose, glycosylated haemoglobin and serum creatinine were assayed every 3 months for 48 months. Echocardiography was performed every 12 months for 48 months.

Results

Compared with baseline, fasting glucose, postprandial glucose, and systolic and diastolic pressure, but not estimated glomerular filtration rate, significantly decreased in all three groups. Albuminuria decreased from 24 to 48 months with liraglutide, but only from 24 to 30 months with sitagliptin and linagliptin. Diastolic function, assessed by E/e′ or left atrial dimension improved only with liraglutide.

Conclusions

Liraglutide was effective for glucose and blood pressure control, reduced albuminuria and improved diastolic function. Diastolic function was not improved by sitagliptin and linagliptin.
ANTI‐POACHING AGREEMENTS IN LABOR MARKETS
Authors: Shy Oz , Stenbacka Rune
Published: July 2018

We analyze competition for experienced workers among wage‐setting firms. The firms can design poaching offers with higher wages to workers who switch from rivals relative to wages paid to their own existing employees. We evaluate the profit and welfare effects of anti‐poaching agreements that eliminate poaching offers as a recruiting method. Anti‐poaching agreements increase industry profits, whereas workers are made worse off. We show that the effects of anti‐poaching agreements on total welfare are determined by the magnitude of workers' switching costs and the productivity change associated with switching employers. (JEL L41, L40, J42)
IS MORE COMPETITION ALWAYS BETTER? AN EXPERIMENTAL STUDY OF EXTORTIONARY CORRUPTION
Authors: Ryvkin Dmitry , Serra Danila
Published: July 2018

Using a laboratory experiment, we assess whether increasing competition among public officials reduces extortionary corruption. We find that increasing the number of providers has no effect on bribe demands when citizens' search costs are high, but it increases corruption when search costs are low. The effect is absent in a parallel setting framed as a standard market, which we attribute to citizens using a nonsequential search strategy as opposed to sequential search in the corruption setting. We conclude that efforts to reduce search costs, such as infrastructure investments, are preferable to anti‐corruption policies aimed at increasing the number of providers. (JEL D73, D49, C91)
Encapsulation of young donor age dopaminergic grafts in a GDNF‐loaded collagen hydrogel further increases their survival, reinnervation, and functional efficacy after intrastriatal transplantation in hemi‐Parkinsonian rats
Authors: Moriarty Niamh , Cabré Sílvia , Alamilla Verónica , Pandit Abhay , Dowd Eilís
Published: July 2018

Biomaterials have been shown to significantly improve the outcome of cellular reparative approaches for Parkinson's disease in experimental studies because of their ability to provide transplanted cells with a supportive microenvironment and shielding from the host immune system. However, given that the margin for improvement in such reparative therapies is considerable, further studies are required to fully investigate and harness the potential of biomaterials in this context. Given that several recent studies have demonstrated improved brain repair in Parkinsonian models when using dopaminergic grafts derived from younger foetal donors, we hypothesized that encapsulating these cells in a supportive biomaterial would further improve their reparative efficacy. Thus, this study aimed to determine the impact of a GDNF‐loaded collagen hydrogel on the survival, reinnervation, and functional efficacy of dopaminergic neurons derived from young donors. To do so, hemi‐Parkinsonian (6‐hydroxydopamine‐lesioned) rats received intrastriatal transplants of embryonic day 12 cells extracted from the rat ventral mesencephalon either alone, in a collagen hydrogel, with GDNF, or in a GDNF‐loaded collagen hydrogel. Methamphetamine‐induced rotational behaviour was assessed at three weekly intervals for a total of 12 weeks, after which rats were sacrificed for postmortem assessment of graft survival. We found that, following intrastriatal transplantation to the lesioned striatum, the GDNF‐loaded collagen hydrogel significantly increased the survival (4‐fold), reinnervation (5.4‐fold), and functional efficacy of the embryonic day 12 dopaminergic neurons. In conclusion, this study further demonstrates the significant potential of biomaterial hydrogel scaffolds for cellular brain repair approaches in neurodegenerative diseases such as Parkinson's disease.