bluuebunny/crossref_metadata_2025 huggingface dataset:
Long noncoding RNA actin filament‐associated protein 1 antisense RNA 1 promotes malignant phenotype through binding with lysine‐specific demethylase 1 and repressing HMG box‐containing protein 1 in non‐small‐cell lung cancer
Authors: Yu Shanxun , Yang Daolu , Ye Yunyao , Liu Pei , Chen Zhenyao , Lei Tianyao , Pu Jiaze , Liu Longfa , Wang Zhaoxia
Published: May 2019

The number of documented long noncoding RNAs (lncRNAs) has dramatically increased, and their biological functions and underlying mechanisms in pathological processes, especially cancer, remain to be elucidated. Actin filament‐associated protein 1 antisense RNA 1 (AFAP1‐AS1) is a 6810‐nt lncRNA located on chromosome 4p16.1 that was first reported to be upregulated in esophageal adenocarcinoma tissues and cell lines. Here we reported that AFAP1‐AS1, recruiting and binding to lysine‐specific demethylase 1 (LSD1), was generally overexpressed in human non‐small‐cell lung cancer (NSCLC) tissues using quantitative real‐time PCR. Higher AFAP1‐AS1 expression was significantly correlated with larger tumor size (P = .008), lymph node metastasis (P = .025), higher TNM stage (P = .024), and worse overall survival in NSCLC patients. In vitro experiments revealed that AFAP1‐AS1 downregulation inhibited cell migration and induced apoptosis; AFAP1‐AS1 knockdown also hindered tumorigenesis in vivo. Moreover, mechanistic investigations including RNA immunoprecipitation and ChIP assays validated that AFAP1‐AS1 repressed HMG box‐containing protein 1 (HBP1) expression by recruiting LSD1 to the HBP1 promoter regions in PC‐9 and H1975 cells. Furthermore, HBP1 functions as a tumor suppressor, and its ectopic expression hindered cell proliferation. Rescue assays determined that the oncogenic effect of AFAP1‐AS1 is partially dependent on the epigenetic silencing of HBP1. In conclusion, our results indicate that AFAP1‐AS1 is carcinogenic and that the AFAP1‐AS1/LSD1/HBP1 axis could constitute a new therapeutic direction for NSCLC.
A novel WARS mutation (p.Asp314Gly) identified in a Chinese distal hereditary motor neuropathy family
Authors: Wang Binghao , Li Xiaobo , Huang Shunxiang , Zhao Huadong , Liu Jun , Hu Zhengmao , Lin Zhiqiang , Liu Lei , Xie Yongzhi , Jin Qingwen , Zhao Huihui , Tang Beisha , Niu Qi , Zhang Ruxu
Published: May 2019

Distal hereditary motor neuropathy (dHMN) is a clinically and genetically heterogeneous group of inherited neuropathies characterized by distal limb muscle wasting and weakness with no or minimal sensory abnormalities. To investigate the clinical and genetic features of dHMN caused by WARS mutations in mainland China, we performed Sanger sequencing of the coding and untranslated region (UTR) regions of WARS in 160 unresolved dHMN and Charcot‐Marie‐Tooth (CMT) index patients. We detected a novel heterozygous variant c.941A>G (p.Asp314Gly) of WARS in an index patient from an autosomal dominant dHMN family including five affected members over three generations. The variant completely co‐segregates with the dHMN phenotype in the family, and it was classified as likely pathogenic according to the American College of Medical Genetics and Genomics standards and guidelines. The clinical features included juvenile to adult onset (15‐23 years), distal wasting and weakness, minimal sensory disturbance and length‐dependent motor axonal degeneration with CMT examination score ranging from 6 to 10. Our report further confirms the role of WARS in dHMN and indicates that the variant c.941A>G (p.Asp314Gly) of WARS is related to a mild to moderate affected and later onset phenotype of dHMN.
Parental Perspectives on the Emotional, Relational and Logistical Impacts on Siblings of Youth Who Sexually Offend
Authors: Gervais Christine , Romano Elisa
Published: May 2019

This qualitative study explored parents’ perspectives on the collateral consequences of youth sexual offending on siblings through the analysis of interview data among 16 caregivers from 10 Canadian families. Using thematic coding procedures, findings indicated that parents identified a range of safety, emotional and interpersonal impacts on siblings beginning with the criminal justice and child welfare investigations of the sexual offending and extending to siblings’ relationships with the offending youth, their caregivers and other relatives. Results demonstrate the need for greater acknowledgement of, and parent‐informed interventions that specifically address the impact of youth sexual offending on siblings by professionals and non‐professionals (e.g. relatives) alike.
C4d immunohistochemical stain of formalin‐fixed paraffin‐embedded tissue as a sensitive method in the diagnosis of bullous pemphigoid
Authors: Kamyab Kambiz , Abdolreza Mona , Ghanadan Alireza , Mortazavi Hossein , Nikoo Azita , Motavalli Farhad , Nasimi Maryam
Published: May 2019

Background

Bullous pemphigoid (BP) is the most common type of subepidermal bullous disease. Direct immunofluorescence (DIF) is the gold standard for diagnosis, but it requires a fresh tissue specimen. This study was conducted to evaluate the accuracy of using immunohistochemical (IHC) analysis for the detection of C4d in paraffin‐embedded tissue of BP cases.

Methods

A retrospective study was performed on 30 BP cases (confirmed by Hematoxylin and eosin [H&E] and DIF) and 30 controls. IHC studies were performed on formalin‐fixed paraffin‐embedded (FFPE) tissues.

Results

Of 30 BP patients (11 male and 19 female), 27 (90%) were C4d positive and three patients (10%) were C4d negative. The C4d deposits were seen as linear brown stain along the dermoepidermal junction (18 cases), around basal keratinocytes (eight cases), or Civatte‐like (three cases). Two cases revealed more than one pattern in IHC staining. Of 30 control specimens, 26 (86%) cases were C4d negative and four (13.4%) were positive for granular deposits of C4d which were diagnosed as dermatitis herpetiformis.

Conclusion

C4d IHC study is a valuable diagnostic tool with sensitivity of 90% and specificity of 86.7%, and is especially useful in cases in which frozen specimens are not available or FFPE specimens are the only available material for analysis.
Cutaneous plasmacytosis and multinucleate cell angiohistiocytoma‐like lesion in a patient with hepatitis B: A fortuitous triad?
Authors: Roy Simon F. , Ghazawi Feras M. , Tran Diane , Bouffard Danielle
Published: May 2019

A 28‐year‐old woman of Chinese descent, with congenital chronic hepatitis B presented with a 7‐year history of erythematous‐brown papules and plaques on her groins, axillae, and forehead. A first skin biopsy showed findings consistent with two concomitant, yet highly uncommon cutaneous diseases. The presence of lymphoid nodules with germinal centers and clustered polyclonal plasma cells was consistent with cutaneous plasmocytosis. Second, a diffuse proliferation of non‐atypical small vessels (CD31+, CD34+, and HHV8−) in a hypercellular stroma peppered with angulated giant cells (CD163+, CD68−) was suggestive of multinucleate cell angiohistiocytoma (MCAH). Interestingly, the second biopsy of a different plaque on the forehead showed only plasmacytosis and the clinical appearance of both plaques and papules alluded to the distinct presence of both concurrent entities. We speculate the immune modulating effects of chronic hepatitis B may have led to a polyclonal plasmacytic proliferation within the dermis. Furthermore, MCAH has been reported in conjunction with other inflammatory skin diseases such as hidradenitis suppurativa and as such we propose that the MCAH lesion in our case may have arisen as a secondary, reactive process to the cutaneous plasmacytosis.
Global Liquidity, the Private Sector and Debt Sustainability in Sub‐Saharan Africa
Authors: Bonizzi Bruno , Laskaridis Christina , Toporowski Jan
Published: May 2019

This article analyses the effect of changes in international financial markets on the debt dynamics in sub‐Saharan Africa in recent years. A key development is the rise of the private sector as both a lender and a borrower in African debt markets, a process that is associated with the growing integration of the region into global financial markets. The article argues that the Debt Sustainability Framework of the International Monetary Fund and World Bank has taken some steps to account for this growth of private sector, cross‐border debt, but such steps still fall short of what is needed. A full appreciation of the importance of private debt implies, first, that debt sustainability in sub‐Saharan Africa be understood in the context of countries’ integration in global financial markets and the global liquidity cycles that characterize those markets and, second, that the interplay between private and public debt be monitored in order to provide a fuller picture of the impact of private sector debt on fiscal sustainability.
Selling displaced people? A multi‐method study of the public communication strategies of international refugee organisations
Authors: Ongenaert David , Joye Stijn
Published: May 2019

The world has seen a major increase in forced displacement since 2011. As a growing number of states implement restrictive refugee policies, public communication has become essential for refugee organisations. This study analysed, therefore, three international refugee organisations’ discursive strategies towards the recent Syrian crisis, as well as their production and the social context. A critical discourse analysis of international press releases (N=122) and six semi‐structured interviews with press and regional officers revealed that the observed actors largely dehumanise displaced people and subordinate them to the ‘Western self’ and state interests; displaced people hardly ever acquire their own voice. The study found that the medium characteristics of press releases and the importance of media attention result in a depersonalising humanitarian discourse. In addition, there were indications of a post‐humanitarian discourse that reproduced the humanitarian sector's ‘marketisation’. Finally, the examined organisations use the political realist cross‐issue persuasion strategy, displaying displaced people as resettlement objects.
The effects of hypoglycaemia and dementia on cardiovascular events, falls and fractures and all‐cause mortality in older individuals: A retrospective cohort study
Authors: Mattishent Katharina , Richardson Kathryn , Dhatariya Ketan , Savva George M. , Fox Chris , Loke Yoon K.
Published: May 2019

Aims

Older individuals with diabetes are susceptible to harm as the result of hypoglycaemia; however, the consequences of hypoglycaemia in older individuals with dementia are not known. We aimed to test the association between hypoglycaemia and serious adverse events in older patients with diabetes and dementia, and whether the consequences of hypoglycaemia were affected by the presence of dementia.

Materials and methods

This was a cohort study using the Clinical Practice Research Datalink in England (1997‐2016). We selected participants, intervention (exposure) and follow‐up to mirror two hypothetical target randomized controlled trials. The exposure of target trial 1 was hypoglycaemia in patients with dementia. Target trial 2 examined adverse effects of hypoglycaemia according to dementia status. We used Cox proportional hazard regression to estimate adjusted hazard ratios (aHR) for falls, fractures, cardiovascular events and mortality.

Results

In target trial 1, hypoglycaemia was associated with increased risk during a 12‐month follow‐up period for falls and fractures (aHR, 1.94 [95% CI, 1.67‐2.24]), for cardiovascular events (aHR, 2.00 [95% CI, 1.61‐2.48]) and for mortality (aHR, 2.36 [95% CI, 2.09‐2.67]). In target trial 2, the presence of dementia was associated with increased risk of adverse events, following hypoglycaemia, during a 12‐month follow‐up period for falls and factures (aHR, 1.72 [95% CI, 1.51‐1.96]) and for mortality (aHR, 1.27 [95% CI, 1.15‐1.41]), but dementia had no effect on cardiovascular events (aHR, 1.14 [95% CI, 0.95 to 1.36]).

Conclusions

Hypoglycaemia is associated with early increased risk of serious adverse events in older individuals with diabetes and dementia.
Suboptimal oviposition of tephritid flies supports parasitoid wasps
Authors: Xi Xinqiang , Zhang Liang , Zhang Beibei , Dong Yuran , Niklas Karl J. , Sun Shucun
Published: May 2019

1. Female insects lay eggs on low‐quality plants, resulting in progeny with no or low reproductive potential; this is referred to as ‘suboptimal oviposition’ in this study.

2. Here, it is reported
that suboptimal oviposition of a tephritid fly species (Tephritis femoralis) supports the populations of parasitoid wasp species in a Tibetan alpine meadow.

3. Suboptimal oviposition was confirmed because the adult flies emerging from Asteraceae species Anaphalis flavescens flowerheads did not survive cold winters.

4. DNA barcoding of puparia indicated that tephritid larvae developing from suboptimal oviposition hosted populations of at least five parasitoid wasp species. Consequently, suboptimal oviposition has significant effects on parasitoid population dynamics and species diversity.
Role of interleukin‐24 in the tumor‐suppressive effects of interferon‐β on melanoma
Authors: Watanabe Yoshinori , Itoh Munenari , Nakagawa Hidemi , Asahina Akihiko , Nobeyama Yoshimasa
Published: May 2019

Background

Type 1 interferons (IFNs), including IFN‐β, are widely used in adjuvant therapy for patients who undergo surgery for malignant melanoma to inhibit recurrence and in‐transit metastasis. The precise mechanisms underlying the tumor‐suppressive effects of IFN‐β on melanoma are not yet completely understood.

Objective

The purpose was to reveal the mechanisms underlying the tumor‐suppressive effects of IFN‐β via interleukin (IL)‐24.

Methods

Genome‐wide oligonucleotide microarray, quantitative real‐time reverse transcription‐polymerase chain reaction (PCR), enzyme‐linked immunosorbent assay and western blotting assay were performed using four melanoma cell lines (A375, RPMI‐7951, SK‐MEL‐5 and SK‐MEL‐1) treated with natural‐type IFN‐β to assess the expression of IL‐24. Proliferation assay was performed using these melanoma cells and IL‐24 knock‐down melanoma cells.

Results

Genome‐wide microarray analysis detected candidate genes upregulated in IFN‐β‐sensitive cells after treatment with IFN‐β. We focused on IL‐24 among the candidate genes encoding secretory proteins. Peak IL‐24 mRNA expression completely correlated with the order of sensitivity of melanoma cells to IFN‐β. IFN‐β treatment induced extracellular IL‐24 protein in IFN‐β‐sensitive cells, but did not induce intracellular IL‐24 protein. Knock‐down of IL‐24 changed melanoma cells into IFN‐β‐resistant cells. The expression ratio of IL‐22R1, one of the IL‐24 receptors, correlated with the order of sensitivity of melanoma cells to IFN‐β. Treatment with recombinant human IL‐24 did not have any effects on all the melanoma cell lines.

Conclusion

Our data suggest that IFN‐β suppresses the proliferation of melanoma cells through extracellular IL‐24 protein derived from melanoma cells.
Striae reconstructed, a full thickness skin model that recapitulates the pathology behind stretch marks
Authors: Perez‐Aso M. , Roca A. , Bosch J. , Martínez‐Teipel B.
Published: May 2019

Objective

Stretch marks are disfiguring skin lesions that often cause problems of self‐esteem, but little effort has been put to studying this pathology. We therefore analysed cell cultures of dermal fibroblasts isolated from a striae albae, to thereafter reconstruct a full thickness skin model.

Methods

Human Dermal Fibroblasts (HDF) were isolated from a striae distensae (SD) lesion and from the adjacent non‐lesioned skin. The dermis of two full thickness skin models was reconstructed with either striae‐ or normal‐HDF, while the epidermis was in both reconstructed with Normal Human Epidermal Keratinocytes.

Results

Main observations and pertinent data: Gene expression analysis of cell cultures revealed a generalized decomposition of the Extra Cellular Matrix (ECM), since collagens type I and III, lysyl oxidase (LOX), biglycan, lumican and fibronectin were downregulated, while MMP3 was increased together with a decrease of its natural inhibitors (TIMP1, TIMP2 and PAI‐1). These findings were statistically corroborated for key ECM elements at the protein level (COL1, MMP1 and TGFB1). Interestingly, striae albae fibroblasts retained a pro‐inflammatory phenotype, as suggested by increased gene expression of CXCL8, HAS1 and TNFA. We next reconstructed a full thickness skin model (Striae Reconstructed) with dermal fibroblasts from striae albae. Gene expression analysis showed that the Striae Reconstructed elicited not only ECM decomposition, but also skin ageing, as indicated by the upregulation of P16, PTGS2 and SOD2. Discussion points: Although the epidermis was constructed with normal human epidermal keratinocytes, the Striae Reconstructed presented epidermal atrophy and a dramatic increase of β1‐integrin at the epidermal‐dermal junction providing, for the first time to our knowledge, a rationale showing that the key cell player behind stretch marks are dermal fibroblasts rather than epidermal keratinocytes.

Conclusion

New knowledge: Taken together, our findings shed new light into the aetiology of stretch marks and indicate that the Striae Reconstructed, a new model for in vitro testing and drug screening, may open new avenues for the treatment of stretch marks.
Palygorskite sheets prepared via tape casting for wound healing applications
Authors: de Carvalho Freitas Anna Karla , Puton Bruna Maria Saorin , Peres Ana Paula da Silva , Cansian Rogério Luis , Pergher Sibele Berenice Castella , Acchar Wilson
Published: May 2019

The main objective was to increase the applicability of palygorskite by palygorskite sheets using a tape casting method. The stability of the suspension was investigated and the tapes were characterized by TGA/DTA, XRD, and SEM‐FEG. The antimicrobial activity was analyzed in order to test the applicability of a newly modified drug release system that incorporates neomycin in palygorskite. Preliminary results showed that the palygorskite sheet prepared via the tape casting is promising for wound healing applications.
Sources and solutions for spurious test results in coagulation
Authors: Marlar Richard A. , Rollins‐Raval Marian A.
Published: May 2019

In the coagulation laboratory, much emphasis has been placed on rapid and accurate testing; however, spurious results that are inaccurate and do not reflect the actual status of the patient can potentially lead to an incorrect diagnosis and altered intervention. Errors in coagulation results and interpretation can occur at any point of the process from obtaining the specimen to interpretation and use of the result by the clinician. The main sources of error include the patient's biological and preanalytical variation, analytical testing, and postanalytical use of the reported result(s). This article reviews various sources of error leading to spurious results, providing methods to recognize these aberrant results and presenting solutions for minimizing their occurrence.
Myeloproliferative neoplasms: Diagnostic workup of the cythemic patient
Authors: Wong Waihay J , Pozdnyakova Olga
Published: May 2019

Elevated peripheral blood (PB) cell counts, such as leukocytosis, thrombocytosis, and polycythemia, are often the presenting symptom in patients with myeloproliferative neoplasms (MPN). Because cythemias are nonspecific and may reflect either a reactive or neoplastic process, diagnostic workup of these patients is complicated and requires integration of numerous diagnostic modalities. Careful morphologic evaluation of the PB smear may provide insights into the underlying cause of the abnormal counts (such as the presence of teardrop erythrocytes in myelofibrosis or granulocytic dysplasia with left shift in atypical chronic myeloid leukemia). However, these morphologic findings need to be interpreted in concert with clinical findings and other laboratory results. In recent years, there has been a wealth of new genetic data in the field of MPN and many recurrent mutations have been identified, especially in cases lacking Philadelphia chromosome. Many of these genes impact the diagnosis and/or prognosis. Although certain mutations are preferentially enriched in specific MPN types, none of these mutations are disease defining; therefore, a thorough workup should always include a bone marrow biopsy for morphologic evaluation and diagnosis. This review will describe a comprehensive approach to the diagnosis of various MPN, with an emphasis on the diagnostic and prognostic implications of recurrent mutations in MPN.
The wonderful story of monoclonal antibodies
Authors: Béné Marie C
Published: May 2019

Monoclonal antibodies have become daily partners of both biologists and clinicians, as reagents and therapeutic agents. Behind their odd names and incredible diversity lies an amazing story of inventiveness and daring. This review tries to retrace the major steps of this saga, initiated by the search for anti‐rabbit red blood cell antibodies and currently culminating in amazing molecular constructions saving lives. After some historical and basic reminders, the fields of reagents and drugs will be addressed. This invaluable contribution of immunology to the understanding of both physiology and treatment clearly deserves to be fully recognized.
Oral anticoagulant monitoring: Are we on the right track?
Authors: Onundarson Pall T. , Flygenring Bjorn
Published: May 2019

Vitamin K antagonists (VKAs) cannot be administered without regular monitoring in order to assure their efficacy and safety. Indeed, if well managed, the VKAs appear to be no less efficacious or safe than the newer direct oral anticoagulants (DOACs). Although it is claimed that no regular monitoring of the DOACs is needed, their levels are increasingly being measured under a variety of circumstances, for example, prior to surgery, in suspected overdose, to confirm effective reversal, in patients with malabsorption and to assess patient compliance. Although no therapeutic range has been identified for the DOACs, it has been demonstrated for dabigatran and edoxaban that their antithrombotic effect increases gradually with increasing concentrations and that the risk of major bleeding also gradually increases. Furthermore, it has been determined that almost all dabigatran‐related thrombotic events occur in patients with the lowest quartile concentration of the drug. This suggests that to assure an ideal effect of DOACs in all patients taking them, some form of regular monitoring and dose tailoring should be performed. For the vitamin K antagonists, the best outcome is obtained using formal algorithms and centralized management. Furthermore, data suggest that replacing the standard prothrombin time as a monitoring test may increase the stability of VKA anticoagulation with consequent reduction in thromboembolism without an increase in bleeding. Thus, it is likely that the outcome of all current oral anticoagulants can be improved in the coming years by improving monitoring and tailoring their effect.
Quality management and accreditation in laboratory hematology: Perspectives from India
Authors: Pai Swati , Frater John L
Published: May 2019

Quality management (QM), including quality assurance and quality control, was developed in clinical laboratories in North America and Western Europe, but must be implemented worldwide to ensure accurate, reproducible, and clinically useful results. India, a middle income country with a population of over 1.34 billion, has limited budget allotted to health care. As yet accreditation for clinical laboratories is not mandatory, which contributes to challenges in implementing good laboratory practice. This review provides a summary of internationally laid down QM principles and their application in a middle income country like India.
The use of robots and other automated devices in nurses' work: An integrative review
Authors: Kangasniemi Mari , Karki Suyen , Colley Noriyo , Voutilainen Ari
Published: May 2019

Background

Future nursing shortages and advanced technological developments mean that robots and automated devices could play a valuable role in nursing, but little has been published on their use, and outcomes, to date.

Aim

This integrative review identified how robots are currently used in nursing and the outcomes of those initiatives.

Design

This study used integrative review using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses.

Data sources

We searched the CINAHL, PubMed, Web of Science, and Scopus databases for peer‐reviewed papers published in English from January 2010 to August 2018.

Review methods

The five‐stage review process by Whittemore and Knafl was used.

Results

The 25 included papers showed that robots and automated devices were mainly used in nursing to deliver medication, monitor patients, and provide nursing treatments. The outcomes were evaluated in relation to patient safety, working time and workload, usability, and the end users' satisfaction. In addition, the costs, care outcomes, nurses' behaviour, and changes in working procedures were considered.

Conclusions

Robots and automated devices have the potential to develop nurses' work, but more research and critical evaluations are needed to find the most suitable devices and focus on the functions that will provide the best outcomes for nurses' work.
The MTase15 regulates reproduction in the wing‐dimorphic planthopper, Nilaparvata lugens (Hemiptera: Delphacidae)
Authors: Xu N. , Chen H.‐H. , Xue W.‐H. , Yuan X.‐B. , Xia P.‐Z. , Xu H.‐J.
Published: May 2019

S‐Adenosyl‐l‐methionine‐dependent methyltransferases (SAMMTases) modulate important cellular and metabolic activities in both prokaryotes and eukaryotes. Here, we functionally characterized an SAMMTase gene (MTase15) in the migratory brown planthopper (BPH), Nilaparvata lugens, which is the most notorious rice pest in Asia. The cDNA sequence of MTase15 is 2764 nt in length with an open reading frame of 1218 nt encoding 405 amino acid residues. Quantitative real‐time PCR analysis showed that MTase15 was readily detected from egg to adult stages and extensively distributed in various body parts of adult females and males, with slightly high levels in ovary and testis, respectively. In addition, MTase15 was transcriptionally regulated by the insulin signalling pathway in BPH. RNA‐interference‐mediated knockdown of MTase15 (dsMtase15) resulted in deficiencies in vitellogenin synthesis and oogenesis, and female infertility. Males with Mtase15 knockdown retained the capability of producing sperms with normal viability, but less sperm was transferred to wild‐type (wt) females during copulation, and eggs laid by these wt females arrested embryogenesis. These findings not only assign a functional role to MTase15, but also provide a link between the insulin signalling pathway and epigenetic regulation in BPH reproduction.
Theory of mind development in school environment: A case of children with mild intellectual disability learning in inclusive and special education classrooms
Authors: Smogorzewska Joanna , Szumski Grzegorz , Grygiel Paweł
Published: May 2019

Background

This longitudinal study examines the extent to which a school classroom (inclusive vs. special education) is meaningful for theory of mind (ToM) development among children with mild intellectual disability.

Materials and Methods

The participant group consisted of 166 primary school‐aged children (M = 8.1,SD = 0.99), 79 of whom attended inclusive classrooms; the remaining 87 were in special education classrooms.

Results

Although all children developed ToM over time, children's learning of ToM in inclusive classrooms was significantly greater than that seen in special classrooms. The difference remained significant after controlling for age. The present authors have compared children's individual and family characteristics, but there were almost no differences between groups.

Conclusions

The present authors discuss the results in the light of their importance for children's cognitive and social development. The implications for children's education are also considered.
Prevalence and correlates of autism spectrum disorder in Qatar: a national study
Authors: Alshaban Fouad , Aldosari Mohammed , Al‐Shammari Hawraa , El‐Hag Saba , Ghazal Iman , Tolefat Mohamed , Ali Mogahed , Kamal Madeeha , Abdel Aati Nazim , Abeidah Mahmoud , Saad Ahmad Hassan , Dekair Lobna , Al Khasawneh Mohanad , Ramsay Katrina , Fombonne Eric
Published: May 2019

Background

Few epidemiological data on autism spectrum disorders (ASD) exist for Arabic countries. We conducted the first survey of ASD in Qatar, a population with high consanguinity level.

Methods

This cross‐sectional survey was conducted from 2015 to 2018 in Qatar school‐age children (N = 176,960) from national and immigrant families. Children diagnosed with ASD were identified through medical centers and special needs schools. Records were abstracted and supplemented by parental interviews. Additionally, children attending 93 schools were screened; ASD case status was confirmed in random samples of screen‐positive and screen‐negative children. Prevalence was estimated after taking into account different sampling fractions and participation rates at each survey phase.

Results

One thousand three hundred and ninety‐three children already diagnosed with ASD were identified. Among 9,074 school survey participants, 760 screen‐negative children and 163 screen‐positive children were evaluated; 17 were confirmed to have ASD including five children newly diagnosed. Prevalence was 1.14% (95% CI: 0.89–1.46) among 6‐ to 11‐year‐olds. ASD was reported in full siblings/extended relatives in 5.9% (95% CI: 0.042–0.080)/11.8% (95% CI: 0.095–0.146) families. First‐degree consanguinity in Qatari cases (45%) was comparable to known population levels. Among 844 ASD cases (mean age: 7.2 years; 81% male), most children experienced language delay (words: 75.1%; phrase speech: 91.4%), and 19.4% reported developmental regression. At the time of the survey, persisting deficits in expressive language (19.4%) and peer interactions (14.0%) were reported in conjunction with behavioral problems (ADHD: 30.2%; anxiety: 11.0%). In multivariate logistic regression, ASD severity was associated with parental consanguinity, gestational diabetes, delay in walking, and developmental regression.

Conclusions

ASD prevalence in Qatar is consistent with recent international studies. The methods employed in this study should help designing comparable surveys in the region. We estimated that 187,000 youths under age 20 have ASD in Gulf countries. This figure should assist in planning health and educational services for a young, fast‐growing population.
Circulating complement‐1q tumor necrosis factor‐α‐related protein isoform 5 levels are low in type 2 diabetes patients and reduced by dapagliflozin
Authors: Zhang Cheng , Luo Yong , Liu Rui , Li Xiaoqiang , Yang Mengliu , Zhang Yu , Li Ling , Mou Huaming , Guo Lian , Li Jing , Liu Hua , Yang Gangyi , Zhang Xianxiang
Published: May 2019

Aims/Introduction

As a member of the tumor necrosis factor‐α‐related protein family, complement‐1q tumor necrosis factor‐α‐related protein isoform 5 (CTRP5) has been found to be associated with obesity and insulin resistance (IR). Previous studies in humans and animals have reported contradictory results related to the association between CTRP5 and IR. The purpose of the present study was to explore the relationship between CTRP5 and IR through a cross‐sectional study and drug intervention study of type 2 diabetes patients.

Materials and Methods

A cross‐sectional study was carried out with 118 newly diagnosed patients with type 2 diabetes and 116 healthy adults. In an interventional study, 78 individuals with newly diagnosed type 2 diabetes received sodium–glucose cotransporter 2 inhibitor (dapagliflozin) treatment for 3 months. Circulating CTRP5 concentrations were measured by enzyme‐linked immunosorbent assay.

Results

Serum CTRP5 concentrations were markedly reduced in patients with type 2 diabetes when compared with those of healthy individuals (P < 0.01). When considering the study population as a whole, individuals with IR (homeostasis model of assessment of IR ≥2.78) had lower CTRP5 concentrations than the individuals without IR (homeostasis model of assessment of IR <2.78; P < 0.01). Serum CTRP5 negatively correlated with age, body mass index, waist‐to‐hip ratio, Systolic blood pressure, triglyceride, total cholesterol, glycated hemoglobin, fasting blood glucose, 2‐h blood glucose, fasting insulin and homeostasis model of assessment of IR. After 12 weeks of sodium–glucose cotransporter 2 inhibitor treatment, serum CTRP5 levels in type 2 diabetes patients were significantly reduced accompanied with ameliorated glycometabolism and IR compared with before treatment (P < 0.01).

Conclusions

CTRP5 is likely a marker for type 2 diabetes in humans.
Prolonged overall survival following metastasectomy in stage IV melanoma
Authors: Elias M.L. , Behbahani S. , Maddukuri S. , John A.M. , Schwartz R.A. , Lambert W.C.
Published: May 2019

Background/Objectives

Current literature supports mixed conclusions regarding the outcomes of metastasectomy in Stage IV melanoma. The objective of this national study was to determine the associations of non‐primary site surgery with overall survival (OS) in Stage IV melanoma.

Methods

The National Cancer Database (NCDB) was queried for all Stage IV melanoma cases diagnosed from 2004 to 2015. Cases missing treatment/staging data or undergoing palliative treatment were excluded (remaining n = 14 034). Patients were separated into ‘metastasectomy’ (n = 4214, 30.0%) and ‘non‐metastasectomy’ (n = 9820, 70.0%) cohorts. Survival outcomes were analysed using Kaplan–Meier and Cox proportional hazards regressions.

Results

On univariate analysis, patients with Stage IV melanoma undergoing metastasectomy (median survival: 15.67 month) had greater overall survival compared with those not receiving non‐primary surgery (median survival: 7.13 month; 5‐year OS 13.2% vs. 5.6%, P < 0.001). M1a patients that underwent non‐primary metastasectomy (median survival: 46.36 month) showed greater survival than those that did not (median survival: 15.31 month; P < 0.001). Metastasectomy was undertaken more frequently for cutaneous (M1a) metastasis compared with non‐M1a metastasis (34.6% vs. 28.4%, P < 0.001). Of those receiving metastasectomy, 20.3% also received primary site resection, 33.6% radiation, 26.5% chemotherapy and 31.5% immunotherapy. Controlling for covariates on Cox proportional hazard analysis, all metastasectomy patients demonstrated longer survival [Hazard Ratio = 0.519, P < 0.001; CI 95% (0.495–0.545)] as well as when analysing solely M1a metastasectomy patients [Hazard Ratio = 0.546, P < 0.001; CI 95% (0.456–0.653)], lung (M1b) metastasectomy patients [Hazard Ratio = 0.389, P < 0.001; CI 95% (0.328–0.462)] and visceral (M1c) metastasectomy patients [Hazard Ratio = 0.474, P < 0.001; CI 95% (0.434–0.517)].

Conclusion

Metastasectomy for Stage IV melanoma is independently associated with improved OS in metastatic cases involving the skin, lung and visceral organs.
Assessing whether cancer stage is needed to evaluate measures of hospital surgical performance
Authors: Lavery Jessica A. , Lipitz‐Snyderman Allison , Li Diane G. , Bach Peter B. , Panageas Katherine S.
Published: May 2019

Rational, aims, and objectives

While public reports of hospital‐level surgical quality measures are becoming increasingly common in health care, a comprehensive national assessment of surgical quality across multiple cancer sites has yet to be developed. Fee‐for‐service (FFS) Medicare claims present a potential resource from which to measure outcomes following cancer surgery given the national scope of patients and providers. However, due to the administrative nature of the data, clinical cancer information such as stage is not recorded. Leveraging the Surveillance, Epidemiology, and End Results (SEER) registry linked to FFS Medicare claims to analyse outcomes for patients whom we ultimately know stage information, we determined whether Medicare claims are suitable for measuring provider quality following cancer surgery by assessing the extent to which the lack of stage information modifies assessments of provider performance.

Methods

We identified patients aged 66 and older undergoing cancer surgery between 2011 and 2013 from SEER‐Medicare. We compared the changes in the risk‐standardized rates (RSRs), decile rankings, and c‐statistics with and without risk adjustment for cancer stage for three measures of hospital performance: 30‐day mortality, surgical complications, and unplanned readmissions.

Results

The RSR changed by at most 11.4% for mortality and by less than 4% for complications and readmissions, indicating that measures of hospital performance were stable with and without adjustment for stage. The relative performance of hospitals was also stable, as demonstrated by fewer than 20% of hospitals changing decile rank. The c‐statistic declined by less than 2% across all measures, indicating that model fit was not substantially worsened without this information.

Conclusion

These findings support the use of FFS Medicare claims for hospital‐level analyses of short‐term outcomes following cancer surgery. Quality reporting based on these analyses can be used to help patients choose among hospitals and for evaluating policies to improve surgical cancer care.
LABOR LAWS AND CORPORATE INVESTMENT
Authors: Marciukaityte Dalia
Published: May 2019

In the United States, the costs of unionized labor are higher in states without right‐to‐work (RTW) laws. I show that unionized firms located in these states invest less. These firms have about 4 percentage point lower capital expenditures (normalized by net property, plant, and equipment) than other firms. I confirm these findings by examining a natural experiment created by the adoption of RTW laws in Oklahoma and examining union certification elections using regression discontinuity design.
Improving the three‐dimensional printability of taro paste by the addition of additives
Authors: Huang Meng‐sha , Zhang Min , Bhandari Bhesh , Liu Yaping
Published: May 2019

The aim of this study was to explore the 3D printing ability of taro paste affected by five different food additives (sodium alginate [SA], sodium carboxymethyl cellulose, xanthan gum, guar gum, and whey protein). Rheological tests indicated that all samples showed shear‐thinning behavior and the apparent viscosity, storage modulus G′, and loss modulus G″ were all improved. The texture and moisture distribution were also affected by different additives. Samples added with SA exhibited the best performance on printing behavior with smooth outlook and less dimensional variability of printed cuboids (−0.76%, −0.60%, −0.50% in length, width, and height, respectively). Taking printing time and quality of printed cuboids into account, a nozzle diameter of 0.84 mm, a nozzle moving speed of 25 mm/s, and a extrusion rate of 13 mm3/s were considered to be the suitable parameters.

Practical Applications

Compared with the normal food mixed system for 3D printing, the results indicated that taro–gum mixtures showed shear‐thinning behavior, apparent viscosity, printing behavior with smooth outlook, and less dimensional variability of printed cuboids were all improved, which is hopeful for further application in 3D food printing.
Three‐dimensional damage morphologies of thermomechanically deformed sintered nanosilver die attachments for power electronics modules
Authors: AGYAKWA P. , DAI J. , LI J. , MOUAWAD B. , YANG L. , CORFIELD M. , JOHNSON C.M.
Published: May 2019

A time‐lapse study of thermomechanical fatigue damage has been undertaken using three‐dimensional X‐ray computer tomography. Morphologies were extracted from tomography data and integrated with data from microscopy modalities at different resolution levels. This enables contextualization of some of the fine‐scale properties which underpin the large‐scale damage observed via tomography. Lateral views of crack development are presented, which show networks analogous to mud‐cracks. Crack fronts which develop in the most porous regions within the sintered attachment layer travel across the boundary into the copper substrate. The propagation characteristics of these cracks within the substrate are analysed. Evidence is provided of heterogeneous densification within the sintered joint under power cycling, and this is shown to play a major role in driving the initiation and propagation of the cracks. Examination of the texture (differing levels of X‐ray absorption) of virtual cross‐sectional images reveals the origins of the nonuniformity of densification. Finally, cracks within the sintered joint are shown to have a negligible impact on the conduction pathway of the joint due to their aspect ratio and orientation with respect to the assembly.

Lay Description

This paper concerns the use of three‐dimensional (3D) X‐ray tomography, a nondestructive technique, to perform cradle‐to‐grave studies of sintered nanosilver die‐attachments under operation. Sintered nanosilver die‐attachments have been proposed as a more reliable and environmentally friendly alternative to solder alloy joints for emerging power electronics module designs. However, their degradation mechanisms are not as well understood. This same sample‐study is about observing how the fine‐scale structure of a sintered attachment evolves and degrades over time. Using 3D tomography affords otherwise infeasible perspectives, such as virtual cross‐sections in the lateral plane of the attachment. These perspectives provide qualitative information which elucidates the degradation mechanisms. They demonstrate, for example, that the structure of the sintered attachment densifies under operation, and a consequence of this is the formation of shrinkage cracks in the most porous regions, much like mud‐cracks. Other imaging techniques (metallographic etching and scanning electron microscopy) have been used in correlation with 3D renderings of these cracks to analyse their propagation and reveal their relationship both with the internal structure of the sintered attachment itself, and the structure of the substrate to which it is joined. It is shown that the cracks develop within the sintered attachment layer and eventually cross over into the substrate. A comparison of two sintered attachments with contrasting bulk porosities allows the effect of initial bond quality on crack development to be examined.
How is alpha‐synuclein cleared from the cell?
Authors: Stefanis Leonidas , Emmanouilidou Evangelia , Pantazopoulou Marina , Kirik Deniz , Vekrellis Kostas , Tofaris George K.
Published: May 2019

The levels and conformers of alpha‐synuclein are critical in the pathogenesis of Parkinson's Disease and related synucleinopathies. Homeostatic mechanisms in protein degradation and secretion have been identified as regulators of alpha‐synuclein at different stages of its intracellular trafficking and transcellular propagation. Here we review pathways involved in the removal of various forms of alpha‐synuclein from both the intracellular and extracellular environment. Proteasomes and lysosomes are likely to play complementary roles in the removal of intracellular alpha‐synuclein species, in a manner that depends on alpha‐synuclein post‐translational modifications. Extracellular alpha‐synuclein is cleared by extracellular proteolytic enzymes, or taken up by neighboring cells, especially microglia and astrocytes, and degraded within lysosomes. Exosomes, on the other hand, represent a vehicle for egress of excess burden of the intracellular protein, potentially contributing to the transfer of alpha‐synuclein between cells. Dysfunction in any one of these clearance mechanisms, or a combination thereof, may be involved in the initiation or progression of Parkinson's disease, whereas targeting these pathways may offer an opportunity for therapeutic intervention.

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This article is part of the Special Issue “Synuclein”.
Nurses' practices in the preparation and administration of intramuscular injections in mental health: A cross‐sectional study
Authors: Legrand Guillaume , Guiguet‐Auclair Candy , Viennet Hervé , Aumeran Claire , Reynaud Dominique , Badrikian Laurence , Debost‐Legrand Anne
Published: May 2019

Background

Intramuscular injections (IMIs) remain a frequent practice in mental health. Few studies have examined the issue of nurses' practices concerning IMI in this domain, and none considered specifically hygiene. Finally, no study appears to have looked at emergency situations and their possible influence on practices. The principal objective of our study was to assess the practices associated with IMI in mental health, especially the hygiene‐related practices. The secondary objectives were as follows: 1) to assess the practices for the preparation and administration of IMI in mental health for criteria other than hygiene and 2) to determine whether professional experience and emergency situations influence these practices.

Design

Single‐centre cross‐sectional study in a psychiatric Hospital and adherence to the STROBE guidelines.

Methods

The participating nurses all worked with inpatients, and all volunteered for the study. A self‐administered questionnaire was sent to all participants. The questionnaire included questions about knowledge and practices associated with IMI, some considered in two different situations: emergencies and planned injections. The distribution of the responses was tested by the chi‐squared test or Fisher's exact test, as appropriate, or by McNemar's chi‐squared test or Friedman's nonparametric chi‐squared test for matched data.

Results

Response rate was 48.6%. Overall, 81% of nurses reported correct handwashing before preparation, 87.5% responded that the dorsogluteal site is currently recommended for IMI, and 74.6% that they did not know the "Z track" technique. In planned injections, 58.7% reported that the choice of needle was determined, at least in part, by the patient's body mass index. In emergency situations, adherence to guidelines was less frequent for all types of practices.

Conclusions

This study shows the need to improve practices for the frequently used procedure of IMI among mental health nurses.

Relevance to clinical practice

Better professional education appears necessary to develop optimal practices, especially in emergency situations.
Smartphone‐based clinical diagnostics and atrial fibrillation: the need to avoid being out of sight
Authors: Leggio M. , Villano A. , Fusco A.
Published: May 2019

Click here to view the Review by Dr. Hernández‐Neuta et al.