bluuebunny/crossref_metadata_2025 huggingface dataset:
СТРОЕНИЕ ДОЛИНЫ РЕКИ ШУРА-ОЗЕНЬ НА УЧАСТКЕ ЭОЛОВО-АККУМУЛЯТИВНОГО КОМПЛЕКСА “САРЫКУМ” (РЕСПУБЛИКА ДАГЕСТАН), "Геоморфология"
Authors: ГУСАРОВ А.В.
Published: August 2018

В работе, на основе гранулометрического, минералогического анализов и геолого-геофизического профилирования, излагаются результаты изучения строения долины р. Шура-Озень (Республика Дагестан, Россия), берущей начало в низкогорье северо-востока Большого Кавказа и впадающей в Каспийское море в северной части г. Махачкала. В долине реки, на ее участке близ эолово-аккумулятивного комплекса “Сарыкум”, который является одним из крупнейших в Евразии изолированных песчаных массивов, выделены две группы террас, резко различающиеся своим строением. Первая группа - это пойменный комплекс и высокие (V и VI) террасы с закономерным чередованием по профилю пойменных и русловых фаций аллювия нормальной мощности. Вторую группу образуют I, III и IV террасы, в профиле которых очевидна резко увеличенная мощность пойменных фаций аллювия (особенно у IV террасы), представленных, главным образом, разными по гранулометрическому составу песками. Время формирования VI террасы долины реки нами предполагается как доательское (позднегирканское ( ), ранее 44-41 тыс. кал.л.н.), V террасы - как раннехвалынское (ок. 40-33 тыс. кал.л.н.), IV террасы - среднехвалынское (ок. 33-(25)20 тыс. кал.л.н.), между двумя глубокими врезами реки, приуроченными к эльтонской и енотаевской регрессиям палео-Каспия. Время формирования террасы III - поздняя хвалынь (ок. (25)20-12 тыс. кал.л.н.), до мангышлакской регрессии. Возраст низких террас и поймы долины - голоцен. Следовательно, время заложения долины р. Шура-Озень в ее современном виде на данном участке течения, как и время формирования песков Сарыкума как изначально преимущественно пролювиально-дельтовых образований, - свыше 44-41 тыс. кал.л.н. (или 41-37 тыс. л.н.). Анализ гранулометрических спектров аллювиальных отложений позволил сделать важный вывод о том, что наиболее активная фаза формирования дюн эолово-аккумулятивного комп­лекса “Сарыкум” проходила в эпоху, предшествовавшую образованию речных террас, т.е. после формирования пролювиально-дельтовых песков, но до заложения долины р. Шура-Озень. Предполагается генетическая связь реликтовых стадийных прибрежно-морских песчаных кос и галечного берегового вала, расположенных севернее Сарыкума, соответственно с аллювием III и V террас долины реки.
Dutch Managerial Leadership Strategies: Managing Uncertainty Avoidance, Feminine-Related Social Roles, Organisation Prosperity Focus, and Work Orientation within A Polder Framework
Authors: Selvarajah Christopher , Meyer Denny , Waal Andre de , Heijden Beatrice Van der
Published: August 2018

This paper extends Schama’s (1988) notion of moral geography where there is a determinacy link between an ecology and those managing organisations within it. We emphasise that the link is framed by its historical legacy of social ideals. This paper hypothesises that the egalitarian influence of the polder philosophy leads Dutch managers to value cooperative partnership based on consensus decision-making, in a symbiotic relationship between the manager and the community. Structural equation modelling of the data obtained from surveying 808 managers across occupational industry sectors in the Netherlands support this hypothesis. Results reveal that in the Netherlands (1) the external environment has an unique influence, through its impact on managerial behaviour; (2) the external environment has a profound influence on managers’ personal qualities underpinned by their feminine-value-oriented social roles; and (3) organisational prosperity and work orientations are driven by environmental uncertainty avoidance and managers’ feminine-valued social roles.

Keywords: Uncertainty Avoidance, Social Roles, Organisation Prosperity, Work Orientation, Preferred Leadership Styles, Polder Philosophy

To cite this document: Christopher Selvarajah, Denny Meyer, Andre de Waal, and Beatrice Van der Heijden, "Dutch Managerial Leadership Strategies: Managing Uncertainty Avoidance, Feminine-Related Social Roles, Organisation Prosperity Focus, and Work Orientation within A Polder Framework", Contemporary Management Research, Vol.14, No.2, pp. 87-120, 2018.

Permanent link to this document:
http://dx.doi.org/10.7903/cmr.18279
The Chinese E-Commerce Search Advertising Business: A Case Study of Taobao
Authors: Richards Joseph , Li Min
Published: August 2018

Given the rapid growth of the e-commerce market in China, there is a growing need to understand the characteristics of the search advertising strategy employed by dominant e-commerce firms in China. This paper presents a case study to understand the search advertising strategy employed by Taobao based on two sample data sets obtained from the online shopping site taobao.com operated under the Chinese e-commerce giant Alibaba. The first data set contains features about the advertisements displayed after the customer’s search using keyword(s). The second data set contains features about the advertisements clicked by customers. These features and the features specific to customers such as their location, time of search, and time of clicking an advertisement in the data sets are studied to reveal insights into the online advertising strategy employed by Taobao in response to customer searches. The results of data analysis show that there is often a relationship among the variables such as the number of advertisements displayed, prices of advertised products, whether a keyword was used in the search, the time elapsed between the start of search and when an advertisement was clicked, the number of keywords used in search, the likelihood of clicking on an advertisement, and price discounts of advertised products. Specific relationships between these variables are formulated as hypothesis and then tested. The insights gained from the test results can be used to develop better business models for sponsored search advertising.

Keywords: Online Search, Sponsored Search, Online Advertising, Taobao

To cite this document: Joseph Richards and Min Li, "The Chinese E-Commerce Search Advertising Business: A Case Study of Taobao", Contemporary Management Research, Vol.14, No.2, pp. 121-142, 2018.

Permanent link to this document:
http://dx.doi.org/10.7903/cmr.18285
Erythrocyte‐Membrane‐Camouflaged Nanoplatform for Intravenous Glucose‐Responsive Insulin Delivery
Authors: Fu Yu , Liu Wei , Wang Lu‐yao , Zhu Bi‐yue , Qu Meng‐ke , Yang Liu‐qing , Sun Xun , Gong Tao , Zhang Zhi‐rong , Lin Qing , Zhang Ling
Published: August 2018

An artificial “closed‐loop” system that mimics the glucose‐responsive insulin secretion of pancreas β‐cells can potentially improve the treatment efficacy for diabetes. Herein, a lipid bilayer‐coated polymeric nanoparticle (NP) with “core–shell” structure is designed. As far as it is known, it is the first and only intravenous nanoplatform utilizing enzymatic‐oxidation scheme to achieve glucose‐responsive insulin delivery so far. Ethoxy acetal–derivatized dextran nanoparticles (Ace‐DEX NPs) are constructed as “inner core” loaded with insulin, and coloading glucose oxidase (GOx) and catalase (CAT) endow the “inner core” excellent glucose‐sensitive ability. Red blood cell membrane (RBCm)‐derived coating is adopted as “outer shell.” It collectively provides a closed microenvironment for GOx‐based enzymatic‐oxidation scheme and camouflages it from elimination. Above all, the anchored glucose transporters (GLUTs) on the “outer shell” are able to sense blood glucose levels and facilitate the transport of outer blood glucose getting inside. Under a hyperglycemic condition, the internalized glucose is catalytically converted into gluconic acid with the aid of the GOx and subsequently triggers acid degradation of the “inner core” to secrete insulin. By governing the blood glucose levels on an automatic and continuous basis, the RBCm‐Ace‐DEX NPs can effectively respond to hyperglycemia and turn to resting conditions under normoglycemia.
Topical hydrogel patches of vinyl monomers containing mupirocin for skin injuries: Synthesis and evaluation
Authors: Ahmad Sarfaraz , Usman Minhas Muhammad , Ahmad Mahmood , Sohail Muhammad , Abdullah Orva , Khan Kifayat Ullah
Published: August 2018

The aim of this study was to formulate and evaluate acrylic acid‐based topical hydrogel patches of mupirocin for new pharmaceutical controlled release application. These cross‐linked hydrogel patches were synthesized by modified aqueous‐based polymerization technique. Acrylic acid was cross‐linked with 2‐acrylamido‐2‐methylpropanesulfonic acid (AMPS) with the help of cross‐linker N,N‐methylenebisacrylamide (MBA). Hydrogel patches were characterized by FTIR, TGA, DSC, SEM, swelling behavior, in vitro percent drug release at different pH, permeation across skin, ex vivo drug retention study, and irritation evaluation of mupirocin‐loaded hydrogels. Developed patches were spherical, thick, adhesive and with good elastic strength. FTIR confirmed the cross‐linking and formation of new structure having appropriate characteristics needed for controlled release delivery system. Dug (mupirocin) release through rabbit's skin was evaluated by Franz diffusion cell and up to 3,991.95 μg/L.5 cm2 was permeated, and drug retention in skin revealed substantial retention up to 1,261 μg/L.5 cm2. Formulated hydrogel patches were nonirritant to the skin up to 48 hr as validated by Draize patch test. Enhanced retention of drug in skin demonstrated good potential of topical delivery for skin bacterial infections.
Evaluating the readability and suitability of construction occupational safety and health materials designed for workers
Authors: Sinyai Clayton , MacArthur Brenda , Roccotagliata Thomas
Published: August 2018

Introduction

Printed materials for training and hazard communication are an essential part of occupational safety and health programs, but must be understood by their intended audience.

Methods

Researchers collected 103 safety training handouts, brochures, and Safety Data Sheets and scored them for readability and suitability using four standard health communication instruments: the SMOG test, the Flesch‐Kincaid Reading Ease Assessment, the SAM (Suitability Assessment of Materials), and CCI (the CDC Clear Communication Index).

Results

Some of the materials used unfamiliar and technical terms. The SAM and CCI checklists revealed several elements of design and layout known to facilitate communication and comprehension, but missing from most of the materials scored.

Conclusion

Occupational safety and health professionals preparing curricula and handouts for distribution to workers should incorporate some form of readability and suitability assessment to help ensure their written materials are clear and comprehensible to all segments of their audience.
Clinical courses of children with trisomy 13 receiving intensive neonatal and pediatric treatment
Authors: Nishi Eriko , Takasugi Mizue , Kawamura Rie , Shibuya Soichi , Takamizawa Shigeru , Hiroma Takehiko , Nakamura Tomohiko , Kosho Tomoki
Published: August 2018

Management of children with trisomy 13 (T13) is controversial because of a paucity of evidence of the natural history, especially focusing on efficacy of treatment. There has been no report regarding natural history of children with T13 receiving intensive neonatal and pediatric treatment without cardiac surgery, although several reports have suggested efficacy of cardiac surgery. To describe the detailed and comprehensive natural history of children with T13 receiving intensive neonatal and pediatric treatment without cardiac surgery, we reviewed clinical information of 24 children with full T13 (15 boys, 9 girls) who were admitted to Nagano Children's Hospital from 1994 to 2016. Intensive neonatal and pediatric treatment without cardiac surgery was provided through careful discussion with the parents. We detailed accurate frequencies of complications, survival, underlying factors and the final modes of death, and psychomotor development of survivors. Unpublished complications including aortopulmonary window, pulmonary‐ductus‐descending aorta‐trunk, biliary system abnormalities, eosinophilic enteritis, and neuroblastoma were described. Accurate frequencies of congenital heart defects (92%) and laryngomalacia and/or tracheomalacia (42%) were determined. The median survival time was 451 days and the 1‐year survival rate was 54%. The major underlying factor associated with death was congenital heart defects and heart failure (63%) and the major final mode of death was heart failure (50%). Long‐term survivors appeared to show slow but constant psychomotor development. Intensive neonatal and pediatric treatment without cardiac surgery for children with T13 is efficient for survival and psychomotor development, and could be a reasonable choice for parents having fetuses or children with T13.
De novo variant in KIF26B is associated with pontocerebellar hypoplasia with infantile spinal muscular atrophy
Authors: Wojcik Monica H. , Okada Kyoko , Prabhu Sanjay P. , Nowakowski Dan W. , Ramsey Keri , Balak Chris , Rangasamy Sampath , Brownstein Catherine A. , Schmitz‐Abe Klaus , Cohen Julie S. , Fatemi Ali , Shi Jiahai , Grant Ellen P. , Narayanan Vinodh , Ho Hsin‐Yi Henry , Agrawal Pankaj B.
Published: August 2018

KIF26B is a member of the kinesin superfamily with evolutionarily conserved functions in controlling aspects of embryogenesis, including the development of the nervous system, though its function is incompletely understood. We describe an infant with progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to the involvement of anterior horn cells and ventral (motor) nerves. We performed whole exome sequencing on the trio and identified a de novo KIF26B missense variant, p.Gly546Ser, in the proband. This variant alters a highly conserved amino acid residue that is part of the phosphate‐binding loop motif and motor‐like domain and is deemed pathogenic by several in silico methods. Functional analysis of the variant protein in cultured cells revealed a reduction in the KIF26B protein's ability to promote cell adhesion, a defect that potentially contributes to its pathogenicity. Overall, KIF26B may play a critical role in the brain development and, when mutated, cause pontocerebellar hypoplasia with arthrogryposis.
Intrafamilial clinical variability in four families with incontinentia pigmenti
Authors: Mariath Luiza M. , Santa Maria Fernanda D. , Poziomczyk Cláudia S. , Travi Giovanni M. , Wachholz Gabriela E. , De Souza Stephanie R. , Kiszewski Ana E. , Schuler‐Faccini Lavínia
Published: August 2018

Incontinentia Pigmenti (IP) is an X‐linked rare genodermatosis caused by mutations in the IKBKG gene, which is essential to NF‐κB pathway activation and thus fundamental for cell survival. Our objective was to study the intrafamilial clinical variability in IP by investigating how the signs of IP, and especially dental anomalies, vary within affected families. Four families, encompassing a total of 15 IP familial cases, were included in the study. The patients were subjected to clinical examination and collection of family histories for assessment of intrafamilial clinical variability. All familial cases carried the IKBKGdel recurrent deletion. A noticeable intrafamilial clinical variability was observed in all studied families, with mild and severe cases co‐occurring within a same family. Additionally, to best of our knowledge, our study was the first to address the variability of dental defects within IP families, and here too, our results reveal remarkable differences among affected relatives. A number of as yet unidentified genes might act as modifiers, influencing disease expressivity. Our study found important clinical variability within four IP families and contributes to the understanding of the genetic background involved in IP expressivity.
Novel compound heterozygous EPG5 mutations consisted with a missense mutation and a microduplication in the exon 1 region identified in a Japanese patient with Vici syndrome
Authors: Shimada Shino , Hirasawa Kyoko , Takeshita Akiko , Nakatsukasa Hidetsugu , Yamamoto‐Shimojima Keiko , Imaizumi Taichi , Nagata Satoru , Yamamoto Toshiyuki
Published: August 2018

Vici syndrome is a rare, autosomal recessive, multisystem disorder, characterized by agenesis of the corpus callosum, cataracts, psychomotor delay, cardiomyopathy, hypopigmentation, and recurrent infections. Mutations in the ectopic P‐granules autophagy protein 5 homolog gene (EPG5), which encodes a key autophagy regulator, are responsible for this syndrome. A 3‐year‐old Japanese girl manifesting similar symptoms to those found in patients with Vici syndrome showed intractable diarrhea, rather than immunodeficiency. Whole exome sequencing identified only a heterozygous variant in EPG5, NM_020964.2(EPG5):c.3389A > C (p.His1130Pro), which was inherited from her mother. Sequencing analyses of the EPG5 messenger RNA showed only an altered nucleotide “C” at position, c.3389, indicating decreased expression of the wild‐type allele. Microarray‐based comparative genomic hybridization revealed a de novo microduplication in the exon 1 region. Large exon deletions and duplications of EPG5 have never been reported so far. This was considered the cause of the decreased expression of the wild‐type allele. In conclusion, we successfully identified novel compound heterozygous mutations in EPG5 in a patient who was clinically considered to have Vici syndrome.
Silver Russel syndrome in an aboriginal patient from Australia
Authors: Poulton Cathryn , Azmanov Dimitar , Atkinson Vanessa , Beilby John , Ewans Lisa , Gration Dylan , Dreyer Lauren , Shetty Vinutha , Peake Ciara , McCormack Emma , Palmer Richard , Lewis Barry , Dawkins Hugh , Broley Stephanie , Baynam Gareth
Published: August 2018

Silver‐Russell syndrome (SRS OMIM 180860) is a rare, albeit well‐recognized disorder characterized by severe intrauterine and postnatal growth retardation. It remains a clinical diagnosis with a molecular cause identifiable in approximately 60%–70% of patients.

We report a 4‐year‐old Australian Aboriginal girl who was born at 32 weeks gestation with features strongly suggestive of SRS, after extensive investigation she was referred to our undiagnosed disease program (UDP). Genomic sequencing was performed which identified a heterozygous splice site variant in IGF2 which is predicted to be pathogenic by in‐silico studies, paternal allelic origin, de novo status, and RNA studies on fibroblasts. We compare clinical findings with reported patients to add to the knowledge base on IGF2 variants and to promote the engagement of other Australian Aboriginal families in genomic medicine.
Digging the Sigma‐Hole of Organoantimony Lewis Acids by Oxidation
Authors: Yang Mengxi , Tofan Daniel , Chen Chang‐Hong , Jack Kevin M. , Gabbaï François P.
Published: August 2018

The development of group 15 Lewis acids is an area of active investigation that has led to numerous advances in anion sensing and catalysis. While phosphorus has drawn considerable attention, emerging research shows that organoantimony(III) reagents may also act as potent Lewis acids. Comparison of the properties of SbPh3, Sb(C6F5)3, and SbArF3 with those of their tetrachlorocatecholate analogues SbPh3Cat, Sb(C6F5)3Cat, and SbArF3Cat (Cat=o‐O2C6Cl4, ArF=3,5‐(CF3)2C6H3) demonstrates that the Lewis acidity of electron deficient organoantimony(III) reagents can be readily enhanced by oxidation to the +V state—as verified by binding studies, organic reaction catalysis, and computational studies. The results are rationalized by explaining that oxidation of the antimony center leads to a lowering of the accepting σ* orbital and a deeper carving of the associated σ‐hole.
Tunable Electronic and Magnetic Properties of Graphene‐Embedded Transition Metal‐N4 Complexes: Insight From First‐Principles Calculations
Authors: Cao Xinrui , Li Xiao‐Fei , Hu Wei
Published: August 2018

Motivated by the development of transition‐metal‐nitrogen‐carbon (TM‐N‐C) materials for catalysts and molecular electronics, we investigated the electronic and magnetic properties of TMN4‐graphene materials with different central atoms (TM=Ti, V, Cr, Mn, Fe, Co, Ni and Cu) and different concentrations. The first‐principles results show that a widely tunable magnetic moment in the range from 0 to 4 μB can be obtained in this kind of material by varying the central TM atom, and a regular transition of the electronic property from metallic to half‐metallic and to semiconducting characteristics is observed in MnN4‐graphene upon changing the concentration. We find that the peculiar relationship between the electronic characteristics of graphene and its lattice parameters plays a decisive role in determining the electronic and magnetic properties. Our findings are useful for the design of TM‐N‐C materials for catalysis, spintronics, and molectronics.
Differences in anticipatory versus reactive stress to social evaluative threat in adults versus adolescents with autism
Authors: Taylor Julie Lounds , Muscatello Rachael A. , Corbett Blythe A.
Published: August 2018

Social evaluative threat is a potent activator of the hypothalamic‐pituitary‐adrenocortical (HPA) axis in typically developing (TD) populations. Studies have shown that children and adolescents with autism spectrum disorder (ASD) show a blunted cortisol response to this type of stressor; yet, a previous study in adults with ASD reported a more prototypical stress response. The current study compared 24 adolescents and 17 adults with ASD to investigate a possible developmental lag in autism resulting in a more adaptive stress response to social evaluation with development. Participants were exposed to the trier social stress test (TSST), and salivary cortisol was collected before and after stress induction. Multilevel modeling revealed that relative to adolescents, young adults with ASD evidenced a significant increase in cortisol in response to anticipatory stress, and 23.5% were classified as anticipatory responders. Adolescents, however, had a significant change in slope in response to the TSST, with 37.5% classified as reactive responders. In both groups, the majority of participants did not have a robust stress response to the TSST as would be expected in TD participants. Findings suggest significant differences in the cortisol trajectory; adults with ASD were more likely to show an anticipatory response to being socially evaluated, which was maintained throughout the stressor, whereas the adolescents had a more reactive response pattern with no anticipatory response. Further research is needed to determine if such patterns are adaptive or deleterious, and to determine underlying factors that may contribute to distinct stress profiles and to the overall diminished stress responses. Autism Res 2018, 11: 1276–1285. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

Many individuals have increased stress when being socially evaluated. The current study shows that adults with ASD have increased stress in anticipation of a task in which individuals are required to give a speech to unfamiliar raters, while adolescents with ASD tend to show a stress response only during the task itself. Further research is necessary to understand whether developmental influences on stress response in ASD have significant impacts on other areas of functioning often affected by stress.
Metallo‐Organozymes with Specific Proteolytic Activity
Authors: Embaby Ahmed M. , Lelieveldt Lianne P. W. M. , Diness Frederik , Meldal Morten
Published: August 2018

Metallopeptides that show efficiency and selectivity in peptide bond cleavage in water at room temperature and neutral conditions are presented. These small and versatile organozymes take advantage of metal‐coordinating building blocks that are strategically positioned centrally in a peptide backbone or in a peptide macrocycle. This approach provided peptide–metal complexes with scaffolds capable of utilizing the peptide functionality for productive binding of fluorogenic FRET peptide substrates, subsequently leading to highly selective peptide bond cleavage. The ligand chemistry has been optimized to provide an easy access to new metallo‐peptides with the ability to cleave previously inaccessible peptide bonds. Evolutionary principles of stepwise selection and variation offered by combinatorial methods were used and were guided by molecular modeling to develop catalytic metallo‐peptides that mimic metalloproteases.
Ligand‐Controlled Doping Effects in Alloy Nanoclusters Au4Ag23 and Au5Ag24
Authors: Du Yang , Guan Zong‐Jie , Wen Zhao‐Rui , Lin Yu‐Mei , Wang Quan‐Ming
Published: August 2018

The syntheses and properties of two bimetallic nanoclusters [Au4Ag23(C≡CtBu)10(dppf)4Cl7](PF6)2 and [Au5Ag24(C≡CC6H4‐p‐tBu)16(dppf)4Cl4](PF6)3 are reported. The Au atoms distributed in both the cores and the surface motifs are clearly determined. The two nanoclusters show distinctly different geometric structures and electronic properties, which are attributed to the subtle changes in the surface alkynyl structures.
Bioinformatic removal of NUMT‐associated variants in mitotiling next‐generation sequencing data from whole blood samples
Authors: Ring Joseph David , Sturk‐Andreaggi Kimberly , Alyse Peck Michelle , Marshall Charla
Published: August 2018

Nuclear mitochondrial DNA segments (NUMTs) have arisen because of the transposition of segments of the mitochondrial DNA genome (mitogenome) into the nuclear genome. When using a “mitotiling” strategy, NUMTs may be more readily amplified when targeting the entire mitogenome compared to the control region, as hundreds of primers are required for complete sequencing coverage. In samples with a high percentage of nuclear DNA copies per cell, such as whole blood, NUMT coenrichment may be exacerbated. The present study examined bioinformatic approaches for removing NUMTs and NUMT‐associated variants (NAVs) from next‐generation sequence data generated using two mitotiling kits (Precision ID and QIAseq). Across 16 samples with low mtDNA copy number, NUMT coenrichment produced 890 NAVs with >5% variant frequency. The use of the consensus sequence to eliminate NUMT reads proved to be effective for QIAseq data, and resulted in >85% NAV removal in Precision ID data. This method was bolstered by NAV filtering in Precision ID analysis. Alternative high stringency mapping to the revised Cambridge Reference Sequence (rCRS) and the human genome reference GRCh38 for the QIAseq data caused a reduction in mitogenome coverage without complete NUMT removal. These bioinformatic solutions facilitate mitotiling sequence data analysis for low‐level variant detection.
What drove the health system reforms in the Kingdom of Saudi Arabia? An analysis
Authors: Rahman Redwanur , Alsharqi Omar Z.
Published: August 2018

Purpose

The primary objective of this article is to present the key directions taken by the Saudi health care system, following the announcement of the Saudi Vision 2030. The changing international scenario, together with reduced oil revenues, high population growth, emerging lifestyle diseases, and demands for better quality of care, has impacted the development of the Saudi health system. The government is now ardently pursuing private sector development and has initiated privatization and marketization as a core strategy of reforms in its health system. This article posits that the current economic conditions of the KSA and local and global market dynamics are the primary drivers for these reforms.

Methods

This study is based on a scoping literature review.

Findings

The intended reforms will have very limited contribution to improving the population's health, and the study remains inconclusive.

Conclusion

The Kingdom took a protective approach in reforming its health sector. The social values that undergird the government actions, especially, how much priority it gives to maintain status quo in the social and economic fabric vis‐à‐vis economic growth and development, have exerted a significant influence on whether the KSA chooses a pro‐government or a pro‐market approach; however, this could lead to a hybrid model of health care system.
Responsiveness of the urban primary health care delivery system in Bangladesh: A comparative analysis
Authors: Hamid Syed Abdul , Begum Afroza
Published: August 2018

This study analyses the responsiveness of outpatient care to assess the quality of urban primary health care among all 5 types of health care providers in Bangladesh, namely, the Urban Primary Health Care Services Delivery Project, the NGO Health Services Delivery Project (NHSDP), NGOs, private hospitals, and the Ministry of Health and Family Welfare (MOHFW). Other than some public‐private comparisons, there is an absolute knowledge gap regarding responsiveness in urban health systems, particularly in the context of Bangladesh, and this gap motivates this study. The study used primary data collected from 810 randomly selected outpatients. The survey used a structured questionnaire on all 7 domains of responsiveness of outpatient care suggested by the World Health Organization. The estimated mean responsiveness score reveals that overall, approximately 33% of the patients rated the responsiveness of the system as poor. In reported responsiveness, the NHSDP was ranked at the top and the MOHFW at the bottom. The latter is quite expected. Overall, prompt attention and autonomy were the worst‐performing domains, and choice of provider, dignity, and clear communication were the better‐performing ones. The results suggest the need to improve the degree of responsiveness of all domains, especially those that are more concerned with access to health care, namely, prompt attention, dignity, clear communication, and confidentiality. The Ministry of Health and Family Welfare facilities should give additional consideration to promote prompt attention, autonomy, and quality of basic amenities. Private facilities should also provide additional stress on improving prompt attention and autonomy. The nontherapeutic quality of health care needs to be emphasized in the medical education system. Further research based on household surveys could be worthwhile to measure responsiveness more comprehensively.
What is the supporting role of health care providers from the perspective of patients with renal allograft rejection? A qualitative study
Authors: Ebadzadeh Mohammad Reza , Nouhi Esmat , Farokhzadian Jamileh , Mangolian Shahrbabaki Parvin
Published: August 2018

Coping with the new conditions for patients with renal allograft rejection is a complex phenomenon influenced by a number of factors. It appears that the supportive role of health care providers in many aspects is 1 of the most important factors in patient satisfaction, increased quality of life, and application of proper coping mechanisms. This study explored the perceptions of patients with renal allograft rejection about the supportive role of health care providers.

This study was conducted with a qualitative research approach and content analysis. Participants were 19 patients with renal allograft rejection in teaching hospitals in southeastern Iran who were selected by purposive sampling. Data were collected through semistructured interviews and analyzed by qualitative content analysis.

During content analysis, 2 categories emerged: empathy and emotional support and educational counseling. These themes reflect the nature of patient perceptions of the supportive role of health care providers.

The findings suggest that the supportive role of health care providers plays an important role in the promoting a feeling of comfort, reliability, and security in patients with renal allograft rejection and improves their coping mechanisms. These findings give health care providers greater motivation to provide comprehensive care from knowledge of their supportive role.
Using Linked Text Sets to Promote Advocacy and Agency Through a Critical Lens
Authors: Batchelor Katherine E.
Published: August 2018

The author shares three preservice teachers’ linked text sets, including young adult literature and other media forms, and their critiques of the linked text sets, centering on a self‐selected social justice topic: racism and the importance of the Black Lives Matter movement, rape culture, and ending the stigma behind mental health. The author ends with discussion of how the preservice teachers felt advocacy and agency through creating and then critiquing their linked text sets and what recognizing their implicit biases means to their future students and teaching. The author hopes that by sharing what these three preservice teachers found in their critiques of their work, other educators may be able to not only use these text sets and suggested text additions and create new linked text sets for their students, but also think about their own curricular decisions through a critical lens.
miR‐383 promotes cholangiocarcinoma cell proliferation, migration, and invasion through targeting IRF1
Authors: Wan Peiqi , Chi Xiaojv , Du Qiang , Luo Jing , Cui Xiao , Dong Kun , Bing Yan , Heres Caroline , Geller David A.
Published: August 2018

Interferon regulatory factor 1 (IRF1) has been found to serve as a tumor suppressor in cholangiocarcinoma, and enabled prediction of clinical progression and prognosis in our previous study. The objective of the current study is to screen and identify valuable microRNAs (miR), which target IRF1 to regulate cholangiocarcinoma cell proliferation, migration, and invasion. High expression of miR‐383 was observed in cholangiocarcinoma tissues and cells. Meanwhile, we found the predicted binding site of miR‐383 on the IRF1 3′‐untranslated region (3′‐UTR) according to the miR target database. The miR‐383 expression was negatively related to IRF1 messeneger RNA (mRNA) and protein expression in cholangiocarcinoma tissue samples, and miR‐383 negatively regulated IRF1 mRNA and protein expression in cholangiocarcinoma cells. Subsequently, we conducted a luciferase reporter assay to prove the predicted binding site miR‐383 on IRF1 3′‐UTR. Moreover, the results of the rescue study suggested that IRF1 was a functional target of miR‐383 involved in regulating cholangiocarcinoma cell proliferation, migration, and invasion. Finally, we evaluated the clinical and prognostic significance of miR‐383 in cholangiocarcinoma cases, and found that high expression of miR‐383 was correlated with advanced tumor stage, large tumor size, present vascular invasion, and metastasis, and acted as an unfavorable independent prognostic factor. In conclusion, miR‐383 serves as a tumor‐suppressive miR to regulate cholangiocarcinoma cell proliferation, migration, and invasion via directly targeting IRF1.
Retracted: Long noncoding RNA MALAT1 alleviates lipopolysaccharide‐induced inflammatory injury by upregulating microRNA‐19b in murine chondrogenic ATDC5 cells
Authors: Pan Lin , Liu Deheng , Zhao Lei , Wang Liqin , Xin Miaomiao , Li Xingfu
Published: August 2018

Osteoarthritis is the most frequent chronic bone‐joint disease in middle‐aged and older people worldwide. This study investigated the effects of long noncoding RNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) on lipopolysaccharide (LPS)‐induced murine chondrogenic ATDC5 cell inflammatory injury. Cell viability and apoptosis were assessed using cell counting kit‐8 assay and annexin V‐phycoerythrin (PE) staining, respectively. The expression levels of interleukin‐1β (IL)‐1β, IL‐6, IL‐8, tumor necrosis factor α (TNF‐α), MALAT1, and microRNA‐19b (miR)‐19b were measured using quantitative reverse‐transcription polymerase chain reaction. Enzyme‐linked immunosorbent assay was conducted to detect the concentrations of IL‐1β, IL‐6, IL‐8, and TNF‐α in culture supernatant of ATDC5 cells. Expressions of key factors involved in cell apoptosis, proinflammatory response, Wnt/β‐catenin, and nuclear factor κB (NF‐κB) pathways were analyzed using Western blot analysis. We found that LPS treatment remarkably induced ATDC5 cell apoptosis and inflammatory injury. MALAT1 was upregulated in LPS‐stimulated ATDC5 cells. Overexpression of MALAT1 significantly reversed the LPS‐induced ATDC5 cell inflammatory injury, while suppression of MALAT1 had opposite effects. Further results showed that MALAT1 positively regulated the expression of miR‐19b in ATDC5 cells. Knockdown of miR‐19b reversed the protective effect of MALAT1 on LPS‐induced ATDC5 cells. In addition, MALAT1 reduced LPS‐induced Wnt/β‐catenin and NF‐κB pathways activation in ATDC5 cells by upregulating miR‐19. To conclude, our research verified that MALAT1 alleviated LPS‐induced ATDC5 cell inflammatory injury by upregulating miR‐19b and inactivating Wnt/β‐catenin and NF‐κB pathways. This finding will be helpful for further understanding the critical roles of MALAT1 and miR‐19b in osteoarthritis and may provide possible targets for osteoarthritis diagnosis and treatment.
Impact of curcumin on sirtuins: A review
Authors: Zendedel Elham , Butler Alexandra E , Atkin Stephen L , Sahebkar Amirhossein
Published: August 2018

Curcumin is a bioactive phytochemical that modulates several physiological and cellular processes leading to therapeutic effects against different diseases. Sirtuins are highly conserved nicotine adenine dinucleotide‐dependent proteins that regulate the activity of target enzymes and transcription factors by deacetylation. Curcumin possesses both antioxidant and anti‐inflammatory properties and has been shown to increase sirtuin‐1 (SIRT1) by activating small molecules. Upregulation of SIRT1 by curcumin has been reported to confer protective effects against a range of neurological disorders including glutamate excitotoxicity, β‐amyloid‐induced cell death in cortical neurons, cerebral ischemic damage, and stroke. Activation of AMPK and SIRT1 by curcumin has also been noted to mediate the protective effects of curcumin against ischemia/reperfusion injury, cardiac fibrosis, diabetes, and lipid metabolism abnormalities. These protective effects of SIRT1 activation are partly mediated by the deacetylation of p53 and reduction of apoptosis. In this review, we summarize the role of SIRT1 in mediating the pharmacological effects of curcumin in several diseases.
Piperlongumine inhibits angiotensin II‐induced extracellular matrix expression in cardiac fibroblasts
Authors: Wu Xianchuang , Liu Yuxin , An Jihong , Li Jiahuan , Lv Weiling , Geng Shengnan , Zhang Yongzhou
Published: August 2018

Piperlongumine (PL), a single component isolated from Piper longum, has been reported to possess anti‐inflammatory, antibacterial, antiangiogenic, antioxidant, antitumor, and antidiabetic activities. However, its role in cardiac fibrosis remains to be clarified. Therefore, we determined the effects of PL on cardiac fibroblasts (CFs) proliferation, and extracellular matrix (ECM) production under angiotensin II (Ang II) conditions, and further investigated the underlying molecular mechanism. Our data revealed that PL inhibited the proliferation and migration of CFs induced by Ang II. In addition, PL blocked the transformation of CFs to myofibroblasts induced by Ang II, as well as decreased cellular reactive oxygen species (ROS) production and malondialdehyde level in Ang II‐stimulated CFs. Furthermore, PL significantly suppressed the Ang II‐increased phosphorylation of extracellular regulated protein kinase 1/2 (ERK1/2) in CFs. Taken together, the results of the current study demonstrated that PL inhibits Ang II‐induced cell proliferation, migration, and ECM expression in CFs through the inactivation of the ERR1/2 signaling pathway. These data strongly suggest that PL may be a promising therapeutic candidate for the treatment of cardiac fibrosis.
MiR‐27a‐5p regulates apoptosis of liver ischemia‐reperfusion injury in mice by targeting Bach1
Authors: Xing Yu , Li Jing , Li Shi‐peng , Xi Jiri , Ma Ning , Liu Lei , Wang Jin‐Shan , Cai Jin‐Zhen
Published: August 2018

Ischemia‐reperfusion (I/R) injury causes cellular dysfunction and a series of immune or apoptotic reactions. Bach1 is a mammalian transcription factor that represses Hmox1, which encodes heme oxygenase‐1 (HO‐1) that can degrade heme into free iron, carbon monoxide, and biliverdin, to play an important role in antioxidant, anti‐inflammatory, and antiapoptotic activities. MicroRNAs (miRNAs) can be found in a variety of eukaryotic cells and viruses, a class of noncoding small RNAs that are encoded by endogenous genes. The aims of this study were to determine whether miR‐27a‐5p targets Bach1 and regulates cellular death; the dual‐luciferase reporter assay was used to detect this and the results showed that miR‐27a‐5p significantly decreased the luciferase activity of the Bach1 3′‐untranslated region. MiR‐27a‐5p was increased in mice during hepatic I/R and Bach1 was decreased. By transfecting the AML12 cells with the mimic, inhibitor miR‐27a‐5p in hypoxia/reoxygenation (H/R) models showed that overexpression of miR‐27a‐5p decreased Bach1 messenger RNA, upregulated HO‐1 expression, and promoted antiapoptotic Bcl‐2 and downregulated proapoptotic caspase‐3 gene expression. In contrast, the miR‐27a‐5p inhibitor yielded the opposite results. Meanwhile, transfection with Bach1 small interference RNA obviously upregulated the protein levels of HO‐1 and resulted in an increase in Bcl‐2 and a decrease in caspase‐3 protein levels. Thus, we can conclude that miR‐27a‐5p is relevant to liver I/R injury and overexpression of miR‐27a‐5p may alleviate apoptosis in H/R injury by targeting Bach1 in vitro.
The effect of ICRT‐3 on Wnt signaling pathway in head and neck cancer
Authors: Sogutlu Fatma , Kayabasi Cagla , Ozmen Yelken Besra , Asik Aycan , Gasimli Roya , Dogan Fatma , Yilmaz Süslüer Sunde , Biray Avcı Cigir , Gunduz Cumhur
Published: August 2018

The effect of Wnt pathway in head and neck cancer could not be elucidated, even though the aberrant Wnt signaling plays a key role in the development of many types of cancer. The inhibitor of β‐catenin responsive transcription (ICRT‐3) blocks the Wnt signaling pathway by binding to β‐catenin, which is a coactivator of the Wnt signaling pathway and a promising agent for inhibiting aberrant signaling. In our study, we aimed to evaluate the effect of ICRT‐3 on the cytotoxicity, apoptosis, cell cycle progression, migration, and gene expressions in head and neck cancer stem cell (HNCSC) and hypopharynx cancer. The effect of this compound on cytotoxicity and cell viability in FaDu and HNCSC line was assessed by using the water‐soluble tetrazolium salt‐1 method. The effect of ICRT‐3 on apoptosis was detected by using Annexin V and caspase‐3, caspase‐9 kit, on cell cycle progression by cycle test plus DNA reagent kit, on gene expression by dual luciferase reporter assay, and on migration activity by wound healing assay in both cell lines. ICRT‐3 was determined to have cytotoxic and apoptotic effect in both cell lines. In addition, it was also found that the administration of ICRT‐3 caused cell cycle arrest and significant decrease in gene expression level and migration ability of the cells.
AZD9291 promotes autophagy and inhibits PI3K/Akt pathway in NSCLC cancer cells
Authors: Zhang Zhirui , Zhang Mengxiao , Liu Hao , Yin Wu
Published: August 2018

AZD9291, a third‐generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI), is highly selective against EGFR T790M‐mutant non–small cell lung cancer (NSCLC). On investigating the growth inhibitory effects of AZD9291 on NSCLC and the underlying mechanism, we found that AZD9291 can trigger autophagy‐mediated cell death in both A549 and H1975 cells by increasing the expression of phosphatidylethanolamine‐modified microtubule‐associated protein light‐chain 3 (LC3) and decreasing the expression of p62. In the presence of the autophagy inhibitor chloroquine, the AZD9291‐induced increase in LC3 level was further augmented. AZD9291 decreased the levels of phosphoinositide‐3 kinase (PI3K), protein kinase B (Akt), and phosphorylated Akt. AZD9291‐induced cell death was enhanced by Akt knockdown, and the levels of both EGFR and phosphorylated EGFR were decreased by AZD9291. AZD9291 was also found to significantly suppress the tumor growth in H1975 xenograft nude mice. Thus, AZD9291 was found to induce autophagy, decrease in EGFR levels, and show a strong inhibitory effect on NSCLC both in vitro and in vivo. Furthermore, the PI3K/Akt signaling pathway was found to play a critical role in AZD9291‐induced cell death.
MicroRNAs in cancer drug resistance: Basic evidence and clinical applications
Authors: Ghasabi Mehri , Mansoori Behzad , Mohammadi Ali , Duijf Pascal HG , Shomali Navid , Shirafkan Naghmeh , Mokhtarzadeh Ahad , Baradaran Behzad
Published: August 2018

Development of drug resistance has considerably limited the efficacy of cancer treatments, including chemotherapy and targeted therapies. Hence, understanding the molecular mechanisms underpinning the innate or the acquired resistance to these therapies is critical to improve drug efficiency and clinical outcomes. Several studies have implicated microRNAs (miRNA) in this process. MiRNAs repress gene expression by specific binding to complementary sequences in the 3' region of target messenger RNAs (mRNAs), followed by target mRNA degradation or blocked translation. By targeting molecules specific to a particular pathway within tumor cells, the new generation of cancer treatment strategies has shown significant advantages over conventional chemotherapy. However, the long‐term efficacy of targeted therapies often remains poor, because tumor cells develop resistance to such therapeutics. Targeted therapies often involve monoclonal antibodies (mAbs), such as those blocking the ErB/HER tyrosine kinases, epidermal growth factor receptor (cetuximab) and HER2 (trastuzumab), and those inhibiting vascular endothelial growth factor receptor signaling (e.g., bevacizumab). Even though these are among the most used agents in tumor medicine, clinical response to these drugs is reduced due to the emergence of drug resistance as a result of toxic effects in the tumor microenvironment. Research on different types of human cancers has revealed that aberrant expression of miRNAs promotes resistance to the aforementioned drugs. In this study, we review the mechanisms of tumor cell resistance to mAb therapies and the role of miRNAs therein. Emerging treatment strategies combine therapies using innovative miRNA mimics or antagonizers with conventional approaches to maximize outcomes of patients with cancer.
Rosmarinic acid inhibits nicotine‐induced C‐reactive protein generation by inhibiting NLRP3 inflammasome activation in smooth muscle cells
Authors: Yao Yang , Mao Junjun , Xu Shouzhu , Zhao Lei , Long Lihui , Chen Lin , Li Dongmin , Lu Shemin
Published: August 2018

Atherosclerosis is widely known to be a chronic inflammatory disease. C‐reactive protein (CRP), an important inflammatory factor, plays an essential role in the pathogenesis of atherosclerosis. Nicotine, the main addictive component of cigarette, has been shown to induce the production of CRP. The aim of this study was to investigate the effect of rosmarinic acid (RA), a polyphenol with antiinflammatory activity, on nicotine‐induced elevation of CRP in vascular smooth muscle cells (VSMCs). We found that pretreatment of VSMCs with RA attenuated nicotine‐induced expression of CRP in a time‐ and dose‐dependant manner. In addition, RA also inhibited the activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome and reactive oxygen species (ROS) production resulting from nicotine treatment in VSMCs. To confirm these findings in vivo, we constructed a nicotine‐induced atherosclerosis rat model. RA did not significantly reduce the serum nicotine level of the rats, whereas it significantly decreased the levels of serum lipids, including concentrations of cholesterol, triglycerides, and low‐density lipoprotein cholesterol, and the serum level of CRP. RA also led to diminished nicotine‐induced activation of NLRP3 inflammasome and elevation in the CRP level in the aortic tissue of the model rats. The results of this study suggested a protective role of RA in nicotine‐induced atherosclerosis by inhibiting the ROS–NLRP3 inflammasome–CRP axial, and RA therefore represented a potential effective therapeutic approach to atherosclerosis, in particular for those who smoke.