bluuebunny/crossref_metadata_2025 huggingface dataset:
Statin use and risk of liver cancer: Evidence from two population‐based studies
Authors: Tran Kim Tu , McMenamin Úna C. , Coleman Helen G. , Cardwell Chris R. , Murchie Peter , Iversen Lisa , Lee Amanda J. , Thrift Aaron P.
Published: May 2019

Epidemiological studies of statin use and liver cancer risk have produced conflicting results. We examined the association between statin use and risk of primary liver cancer in two large independent study populations taking account of important covariates and main indications of statins such as high cholesterol and chronic liver disease. We performed a nested case–control study within the Scottish Primary Care Clinical Informatics Unit (PCCIU) database. Five controls were matched to cases with primary liver cancer and we used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with statin use. We also conducted a prospective cohort study within the UK Biobank using self‐reported statin use and cancer‐registry recorded primary liver cancer outcomes. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs. In the PCCIU case–control analysis, 434 liver cancer cases were matched to 2,103 controls. In the UK Biobank cohort, 182 out of 475,768 participants developed incident liver cancer. Statin use was associated with 39% lower risk of liver cancer in the PCCIU (adjusted OR 0.61, 95% CI 0.43–0.87). When we examined specific subtypes of liver cancer in the UK Biobank, statin use was associated with lower risk of hepatocellular carcinoma (HCC; adjusted HR, 0.48; 95% CI, 0.24–0.94) but not intrahepatic bile duct carcinoma (IBDC; adjusted HR, 1.09; 95% CI, 0.45–2.64). In conclusion, we found a consistent inverse relationship between statin use and risk of primary liver cancer which was only seen for HCC but not IBDC.
Framework for the adoption of e‐commerce: A case of South African retail grocery sector
Authors: Johnson Olufemi , Iyamu Tiko
Published: May 2019

Over the years, the adoption and use of e‐commerce have expanded widely in different organisations across the world, influenced by its potential benefits. Conversely, in spite of the benefits that have been commonly and widely reported, there are minimal adoption and use of e‐commerce by South African businesses, specifically, in the retail sector. The causes to the limited adoption of e‐commerce in South Africa are not known. This empirical study therefore investigates the factors that influence and affect the adoption and use of e‐commerce in the mainstream retail grocery sector in South Africa. A retail organisation was selected and used as a case in the study. Actor‐network theory (ANT) was employed as a lens to guide the analysis of the qualitative data. Based on empirical evidence, the findings, which include business drivers, stock of knowledge, alliance of actors, training and skills, and assimilation of processes, were found important in the adoption and use of e‐commerce. The factors are intended to guide how adoption and use of e‐commerce are conducted in the mainstream retail grocery sector in South Africa.
A mobile edge computing/software‐defined networking‐enabled architecture for vehicular networks
Authors: Muthanna Ammar , Shamilova Regina , Ateya Abdelhamied A. , Paramonov Alexander , Hammoudeh Mohammad
Published: May 2019

This paper presents a system architecture to address the traffic density and the network coverage open research challenges in vehicular networks. This architecture adopts mobile edge computing (MEC) and software‐defined networking (SDN) technologies to increase the overall network reliability and scalability under high traffic density conditions. Then, a device‐to‐device (D2D) clustering method is described to provide network coverage for orphan nodes. The proposed architecture offers a reliable structure to support ultra‐low latency applications. Evaluation results using realistic conditions for various network scenarios show that the proposed MEC/SDN‐enabled vehicular network architecture achieves performance gains of up to 74% in terms of task blocking compared to its baseline implementation.
A carboxymethyl cellulose bone graft carrier delays early bone healing in an ovine model
Authors: Coathup Melanie , Campion Charlie , Blunn Gordon
Published: May 2019

A limitation in the use of calcium phosphate (CaP) is that in its raw form, it comprises blocks or granules, which are limited in their utility for orthopedic surgery and a number of commercial bone grafts are supplied within an aqueous based carboxymethyl cellulose (CMC) putty. Our hypothesis was that CMC combined with a porous silicate‐substituted CaP (SiCaP) scaffold would have no negative effect on bone formation after implantation in an ovine femoral condyle. Defects were either (a) empty or filled with (b) SiCaP granules, (c) CMC‐SiCaP Putty or (d) a SiCaP press‐fit dry block. Scaffolds were identical in composition and remained in vivo for 4, 8, and 12 weeks. Bone apposition rates, bone area, percentage of bone‐implant contact and graft area were quantified. At 4 and 8 weeks, significantly more new bone and percentage of bone‐implant contact was measured within granules when compared with both putty and block scaffolds. At 12 weeks, significantly increased bone was measured for the granules when compared with blocks and no significant difference was found when the granules and putty scaffolds were compared. Results showed the disadvantageous effect that CMC may have on early bone growth and that granules increased new bone formation when compared with a press‐fit block composed of the same material.
Novel Role for Claudin-11 in the Regulation of Osteoblasts via Modulation of ADAM10-Mediated Notch Signaling
Authors: Lindsey Richard C , Xing Weirong , Pourteymoor Sheila , Godwin Catrina , Gow Alexander , Mohan Subburaman
Published: May 2019

The claudin (Cldn) family comprises 27 members of 20 to 34 kDa transmembrane tight junction proteins. In addition to Cldns’ established canonical role as barriers controlling paracellular flow of molecules, a distinct noncanonical role for them as mediators of cell signaling is now emerging. In our studies evaluating Cldn family expression levels during osteoblast differentiation, Cldn-11 showed the largest increase (60-fold). Immunohistochemistry studies revealed high Cldn-11 expression in trabecular (Tb) bone lining cells. Micro-CT analysis of femurs and vertebrae of Cldn-11 knock-out (KO) mice at 12 weeks of age exhibited a 40% (p < 0.01) reduction in Tb bone volume adjusted for tissue volume compared with control mice, a change caused by significant reductions in Tb number and thickness and increase in Tb separation. Histomorphometry and serum biomarker studies revealed that reduced bone formation, not increased resorption, is the cause for reduced Tb bone volume in the Cldn-11 KO mice. Cldn-11 KO osteoblasts expressed reduced ALP and BSP, whereas Cldn-11 overexpression in MC3T3-E1 cells increased expression of ALP and BSP. Mechanistically, Cldn-11 interacted with tetraspanin (Tspan)3 in osteoblasts, and Tspan3 knockdown reduced osteoblast differentiation. Because members of the Tspan family regulate cell functions via Notch signaling, we evaluated whether Cldn-11/Tspan3 regulates Notch signaling in osteoblasts. Accordingly, Notch targets Hey1 and Hey2 were significantly upregulated in Cldn-11 overexpressing cultures but downregulated in both Cldn-11 KO and Tspan3 knockdown osteoblasts. Because ADAM10 has been shown to interact with Tspan family members to regulate Notch signaling, we evaluated whether Cldn-11 regulates ADAM10 expression. Cldn-11 overexpressing cells express more mature ADAM10, and an ADAM10 inhibitor blocked the Cldn-11 effect on osteoblast differentiation. Based on these data, we propose Cldn-11 as a novel component of an osteoblast cell surface protein complex, comprising Tspan3 and ADAM10, which regulates Notch signaling and cell differentiation. © 2019 American Society for Bone and Mineral Research.
Knockdown of lncRNA‐UCA1 inhibits cell viability and migration of human glioma cells by miR‐193a‐mediated downregulation of CDK6
Authors: Xin Haibin , Liu Nina , Xu Xiaosheng , Zhang Jinwu , Li Yu , Ma Yongchao , Li Guoqiang , Liang Junjun
Published: May 2019

Background

Long noncoding RNA urothelial carcinoma‐associated 1 (lncRNA‐UCA1) is generally recognized as an oncogenic molecule in several human malignant tumors. However, the available evidence does not necessarily imply an unequivocal causal function of UCA1 in glioblastoma. The current study was aimed to probe the biological function of lncRNA‐UCA1 in human glioblastoma cell lines. Besides, we further investigated the potential mechanisms.

Methods

Cell viability, apoptosis, as well as migration and invasion were measured using a commercial cell counting kit‐8, flow cytometry, and 24‐Transwell assay, respectively. LncRNA‐UCA1, microRNA‐193a (miR‐193a), and CDK6 at messenger RNA levels were evaluated by quantitative real‐time polymerase chain reaction method. Protein level was examined by Western blot analysis. RNA immunoprecipitation was utilized to validate lncRNA‐UCA1 associated with miR‐193a. Luciferase activity assay was used to identify the miR‐193a‐targeted CDK6 3′‐untranslated region.

Results

lncRNA‐UCA1 knockdown weakened cell viability, augmented apoptosis progression, as well as suppressed migration and invasion behaviors in glioblastoma cells, whereas lncRNA‐UCA1 silence exhibited the opposite functions. lncRNA‐UCA1 functioned as an endogenous sponge of miR‐193a. miR‐193a silence reversed the biological function of lncRNA‐UCA1 knockdown on U‐118 MG cells. miR‐193a negatively regulated the expression of CDK6, and it affected the U‐118 MG cells through regulating CDK6 expression. CDK6 overexpression abrogated the blockage of PI3K/AKT, mitogen‐activated protein kinase (MAPK), and Notch signaling pathways. Furthermore, lncRNA‐UCA1 and miR‐193a could affect these signaling cascades through regulating CDK6 expression. The regulatory mechanisms of lncRNA‐UCA1 were further consolidated in clinical specimens.

Conclusion

lncRNA‐UCA1 silence reduced cell viability, promoted apoptosis progression, while impeding the migration and invasion of glioblastoma cells by miR‐193a‐mediated silence of CDK6, with blockage of PI3K/AKT, MAPK, and Notch pathways.
microRNA‐96 promotes osteoblast differentiation and bone formation in ankylosing spondylitis mice through activating the Wnt signaling pathway by binding to SOST
Authors: Ma Shu , Wang Dan‐Dan , Ma Cheng‐Yuan , Zhang Yan‐Dong
Published: May 2019

Ankylosing spondylitis (AS) refers to a type of arthritis manifested with chronic inflammation of spine joints. microRNAs (MiRNAs) have been identified as new therapeutic targets for inflammatory diseases. In this study, we evaluated the influence of microRNA‐96 (miR‐96) on osteoblast differentiation together with bone formation in a murine model of AS. The speculated relationship that miR‐96 could bind to sclerostin (SOST) was verified by dual luciferase reporter assay. After successful model establishment, the mice with AS and osteoblasts isolated from mice with AS were treated with mimics or inhibitors of miR‐96, or DKK‐1 (a Wnt signaling inhibitor). The effects of gain‐ or loss‐of‐function of miR‐96 on the inflammatory cytokine release (IL‐6, IL‐10, and TNF‐α), alkaline phosphatase (ALP) activity, calcium nodule formation, along with the viability of osteoblasts were determined. It was observed that miR‐96 might target and regulate SOST. Besides, miR‐96 was expressed at a high level in AS mice while SOST expressed at a low level. TOP/FOP‐Flash luciferase reporter assay confirmed that miR‐96 activated the Wnt signaling pathway. Moreover, AS mice overexpressing miR‐96 exhibited increased contents of IL‐6, IL‐10 and TNF‐α, ALP activity, calcium nodule numbers, and viability of osteoblasts. In contrast, inhibition of miR‐96 resulted in suppression of the osteoblast differentiation and bone formation. In conclusion, the study implicates that overexpressing miR‐96 could improve osteoblast differentiation and bone formation in AS mice via Wnt signaling pathway activation, highlighting a potential new target for AS treatment.
Low glucose availability alters the expression of genes involved in initial adhesion of human glioblastoma cancer cell line SF767
Authors: Aftab Saira , Shakoori Abdul Rauf
Published: May 2019

Studying the metabolic pathways of cancer cells is considered as a key to control cancer malignancies and open windows for effective drug discovery against cancer. Of all the properties of a tumor, metastasis potential is a defining characteristic. Metastasis is controlled by a variety of factors that directly control the expression of cell adhesion proteins. In this study we have investigated the expression of cell to cell and cell to matrix adhesion protein genes during the initial phases of attachment of human glioblastoma cancer cell line SF767 (66Y old human female: UCSF Neurosurgery Tissue Bank) to the attachment surface under (Cell culture treated polystyrene plate bottom) glucose‐rich and glucose‐starved conditions. The aim was to imitate the natural microenvironment of glucose availability to cancer cells inside a tumor that triggers epithelial to mesenchymal transition (EMT). In this study, we have observed the gene expression of epithelial and mesenchymal isoforms of cadherin (E‐CAD and N‐CAD) and Ig like cell adhesion molecules (E‐CAM and N‐CAM) along with Integrin family subunits for the initial attachment of cancer cells. We observed that high glucose environments promoted cell survival and cell adhesion, whereas low glucose accelerated EMT by downregulating the expression level of integrin, E‐CAD, and N‐CAD, and upregulation of N‐CAM during early period of cell adhesion. Low glucose availability also downregulated variety of structural and regulatory genes, such as zinc finger E‐box binding home box 1A), cytokeratin, Snail, and β catenin, and upregulation of hypoxia‐inducible factor 1, matrix metalloprotease 13/Collagenase 3, vimentim, p120, and fructose 1,6 bisphosphatase. Glucose conditions are more efficient for cancer studies in this case glioblastoma cells.
Long noncoding RNA MALAT‐1 inhibits apoptosis and matrix metabolism disorder in interleukin‐1β‐induced inflammation in articular chondrocytes via the JNK signaling pathway
Authors: Gao Gui‐Cheng , Cheng Xi‐Gao , Wei Qiang‐Qiang , Chen Wei‐Cai , Huang Wen‐Zhou
Published: May 2019

Proinflammatory cytokine such as interleukin (IL)‐1β causes inflammation of articular cartilage. In this current study, we explored the chondroprotective effects of long noncoding RNA (lncRNA) MALAT‐1 on cell proliferation, apoptosis, and matrix metabolism in IL‐1β‐induced inflammation in articular chondrocytes. Articular chondrocytes from knee joints of normal rats were isolated and cultured, followed by identification through observation of toluidine blue and COL II immunocytochemical stainings. The proliferation of chondrocytes at passage 2 was detected by the 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay. The inflammatory chondrocytes induced by 10 ng/mL IL‐1β were observed and identified by toluidine blue and COL II immunocytochemical stainings. pcDNA 3.1 and pcDNA‐MALAT‐1 were transfected in the chondrocytes. Ultrastructure of chondrocytes was observed by using a transmission electron microscope. The MTT assay was carried out to evaluate chondrocyte viability. Hoechst 33258 staining and flow cytometry were adopted to assess chondrocyte apoptosis. The chondrocytes at passage 2 with the biological characteristics of chondrocytes were used for subsequent experiments. In IL‐1β‐treated chondrocytes, the growth rate of chondrocytes slowed down, the cells became narrow and long, the vacuoles were seen in the cells, and the morphology of the chondrocytes was irregular. The toluidine blue staining and the immunohistochemical staining of COL II became weaker. In response to IL‐1β induction, articular chondrocytes showed reduced MALAT‐1 expression; moreover, obvious cartilage injury was observed with decreased chondrocyte viability and Col II expression and elevated chondrocyte apoptosis, MMP‐13 expression, and p‐JNK expression. With the treatment of pcDNA‐MALAT‐1, the cartilage injury was alleviated with increased chondrocyte viability and type II collagen (Col II) expression and reduced chondrocyte apoptosis, MMP‐13 expression and p‐JNK expression. Taken together these results, lncRNA MALAT‐1 blocked the activation of the JNK signaling pathway; thereby, IL‐1β‐induced inflammation in articular chondrocytes was reduced with enhanced chondrocyte proliferation and suppressed chondrocyte apoptosis and extracellular matrix degradation.
Novel c.G630A TCIRG1 mutation causes aberrant splicing resulting in an unusually mild form of autosomal recessive osteopetrosis
Authors: Zirngibl Ralph A. , Wang Andrew , Yao Yeqi , Manolson Morris F. , Krueger Joerg , Dupuis Lucie , Mendoza‐Londono Roberto , Voronov Irina
Published: May 2019

Autosomal recessive osteopetrosis (ARO) is a severe genetic bone disease characterized by high bone density due to mutations that affect formation or function of osteoclasts. Mutations in the a3 subunit of the vacuolar‐type H+‐ATPase (encoded by T‐cell immune regulator 1 [TCIRG1]) are responsible for ~50% of all ARO cases. We identified a novel TCIRG1 (c.G630A) mutation responsible for an unusually mild form of the disease. To characterize this mutation, osteoclasts were differentiated using peripheral blood monocytes from the patient (c.G630A/c.G630A), male sibling (+/+), unaffected female sibling (+/c.G630A), and unaffected parent (+/c.G630A). Osteoclast formation, bone‐resorbing function, TCIRG1 protein, and mRNA expression levels were assessed. The c.G630A mutation did not affect osteoclast differentiation; however, bone‐resorbing function was decreased. Both TCIRG1 protein and full‐length TCIRG1 mRNA expression levels were also diminished in the affected patient's sample. The c.G630A mutation replaces the last nucleotide of exon 6 and may cause splicing defects. We analyzed the TCIRG1 splicing pattern between exons 4 to 8 and detected deletions of exons 5, 6, 7, and 5‐6 (ΔE56). These deletions were only observed in c.G630A/c.G630A and +/c.G630A samples, but not in +/+ controls. Among these deletions, only ΔE56 maintained the reading frame and was predicted to generate an 85 kDa protein. Exons 5‐6 encode an uncharacterized portion of the cytoplasmic N‐terminal domain of a3, a domain not involved in proton translocation. To investigate the effect of ΔE56 on V‐ATPase function, we transformed yeast with plasmids carrying full‐length or truncated Vph1p, the yeast ortholog of a3. Both proteins were expressed; however, ΔE56‐Vph1p transformed yeast failed to grow on Zn2+‐containing plates, a growth assay dependent on V‐ATPase‐mediated vacuolar acidification. In conclusion, our results show that the ΔE56 truncated protein is not functional, suggesting that the mild ARO phenotype observed in the patient is likely due to the residual full‐length protein expression.
B cell epitopes in the intrinsically disordered regions of neuraminidase and hemagglutinin proteins of H5N1 and H9N2 avian influenza viruses for peptide‐based vaccine development
Authors: Ramamurthy Mageshbabu , Sankar Sathish , Abraham Asha Mary , Nandagopal Balaji , Sridharan Gopalan
Published: May 2019

Avian influenza viruses (AIV) are very active in several parts of the globe and are the cause of huge economic loss for the poultry industry and also human fatalities. Three dimensional modeling was carried out for neuraminidase (NA) and hemagglutinin (HA) proteins of AIV. The C‐score, estimated TM‐Score, and estimated root‐mean‐square deviation (RMSD) score for NA of H5N1 were −1.18, 0.57 ± 0.15, and 9.8 ± 7.6, respectively. The C‐score, estimated TM‐Score, and estimated RMSD score for NA of H9N2 were −1.43, 0.54 ± 0.15, and 10.5 ± 4.6, respectively. The C‐score, estimated TM‐Score, and estimated RMSD score for HA of H5N1 were −0.03, 0.71 ± 0.12, and 7.7 ± 4.3, respectively. The C‐score, estimated TM‐Score, and estimated RMSD score for HA of H9N2 were −0.57, 0.64 ± 0.13, and 8.9 ± 4.6, respectively.

Intrinsically disordered regions were identified for the NA and HA proteins of H5N1 and H9N2 with the use of PONDR program. Linear B cell epitope was predicted using BepiPred 2 program for NA and HA of H5N1 and H9N2 avian influenza strains. Discontinuous epitopes were predicted by Discotope 2 program. The linear epitopes that were considered likely to be immunogenic and within the intrinsically disordered region for the NA of H5N1 was TKSTNSRSGFEMIWDPNGWTGTDSSFSVK, and for H9N2 it was VGDTPRNDDSSSSSNCRDPNNERGAP. In the case of HA of H5N1, it was QRLVPKIATRSKVNGQSG and ATGLRNSPQRERRRKK; for H9N2 it was INRTFKPLIGPRPLVNGLQG and SLKLAVGLRNVPARSSR. The discontinuous epitopes of NA of H5N1 and H9N2 were identified at various regions of the protein structure spanning from amino acid residue positions 90 to 449 and 107 to 469, respectively. Similarly, the discontinuous epitopes of HA of H5N1 and H9N2 were identified in the amino acid residue positions 27 to 517 and 136 to 521, respectively.

This study has identified potential and highly immunogenic linear and conformational B‐cell epitopes towards developing a vaccine against AIV both for human and poultry use.
The effect of combined miR‐200c replacement and cisplatin on apoptosis induction and inhibition of gastric cancer cell line migration
Authors: Ghasabi Mehri , Majidi Jafar , Mansoori Behzad , Mohammadi Ali , Shomali Navid , Shirafkan Naghmeh , Baghbani Elham , Kazemi Tohid , Baradaran Behzad
Published: May 2019

One of the major obstacles in the treatment of cancer is resistance to standard chemotherapeutic drugs. According to the numerous reports, miR‐200c is involved in many cancers, especially gastric cancer, and also miR‐200c has been known as an effective factor in the elimination of chemotherapy resistance. The purpose of this study was to explore the potential function and mechanism of miR‐200c and cisplatin in the inhibition of migration and induction of apoptosis in gastric cancer cells. In this study, first, miR‐200c mimics and LNA‐anti‐miR‐200c were transfected into KATOIII cells. Moreover, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay results revealed that increased miR‐200c expression and cisplatin can more inhibited the proliferation of KATOIII cells. MiR‐200c overexpression inhibited the movement of KATOIII cells in wound healing assay. Subsequently, miR‐200c/cisplatin could suppress colony formation in KATOIII cells. To identify a potential miR‐200c target, we investigated the effect of miR‐200c modulation on RhoE, PTEN, VEGFR, and MMP9 expression levels. Increased miR‐200c expression caused a reduction in VEGFR and MMP9 mRNA and protein, suggesting that VEGFR and MMP9 are targets of miR‐200c. In addition, reverse‐transcription polymerase chain reaction assays showed that RhoE is target gene of miR‐200c and LNA‐anti‐miR‐200c suppressed the expression of PTEN. Flow cytometry and 4′,6‐diamidino‐2‐phenylindole staining analysis indicated that miR‐200c increased the cisplatin‐induced apoptosis which may be associated with suppression of RhoE expression in KATOIII cells, also cell‐cycle analysis showed the arrest of cell‐cycle progression at the G2 phase. These data demonstrated that miR‐200c functioned as a suppressor gene in KATOIII cells. Also, miR‐200c can be a potential therapeutic approach to overcome chemoresistance during cisplatin chemotherapy.
Enrichment of cancer stem‐like cells by the induction of epithelial‐mesenchymal transition using lentiviral vector carrying E‐cadherin shRNA in HT29 cell line
Authors: Saltanatpour Zohreh , Johari Behrooz , Alizadeh Akram , Lotfinia Majid , Majidzadeh‐A Keivan , Nikbin Behrooz , Kadivar Mehdi
Published: May 2019

A better understanding of cancer stem cells (CSCs) may facilitate the prevention and treatment of cancers. Epithelial‐mesenchymal transition (EMT) is a process activated during invasion and metastasis of tumors. EMT induction in normal and tumor cells makes them more resistant to chemotherapy. E‐cadherin is a membrane protein and plays a role in tumor invasion, metastasis, and prognosis. Downregulation of E‐cadherin is a hallmark of EMT. Here, we created a model of cancer stem‐like cells enrichment via EMT induction using E‐cadherin downregulation in HT29 cell line using a lentiviral vector carrying shRNA. We aimed to evaluate cancer and anti‐CSC chemotherapeutics screening. The markers of EMT and CSCs were assessed and compared with control cells using flow cytometry, real‐time PCR, immunocytochemistry, western blot, migration assay, invasion assay, and colony formation assay. The transduced cells showed a mesenchymal morphology. High levels of EMT‐related proteins were also expressed. These results confirmed that the transduced cells underwent EMT. In addition, we observed an increased population of E‐cadherin‐downregulated HT29 cell line among the cells expressing colon CSC markers (CD133+ and CD44+) after EMT induction. E‐cadherin‐downregulated cells were morphologically like mesenchymal cells, and the number of CD133+‐ and CD44+‐cells (CSC‐like cells) increased. These cells can be used as stable models to study cancer cells and screening of antitumor therapeutics.
Factors responsible for estivation in spotted stem borer, Chilo partellus (Swinhoe)
Authors: Dhillon Mukesh K. , Hasan Fazil , Tanwar Aditya K. , Bhadauriya Amarpal S.
Published: May 2019

Diapause is an important adaptive trait in certain groups of insects at a particular stage, which contribute in controlling insect ecology, phenology, and physiology. Considering the importance of various factors in appropriate combinations, we studied effects of different temperature and photoperiod conditions on larval morphometrics, development, induction, and termination of estivation, and overall mortality due to estivation in Chilo partellus (Swinhoe). Weight, length, and head capsule width of C. partellus larvae significantly increased with increase in temperature and photoperiod treatments upto certain age and duration of exposure. According to Dyar's ratio, overall head capsule width progressed geometrically with minimum constant ratio of 1.20, and second‐degree polynomial regression equations were best fitted to all the test treatment conditions. The mortality of diapausing C. partellus individuals varied between 7.0% and 37.3% under different constant and varying temperature and photoperiod regimes, which at 38°C + 14L:10D reached upto 100.0%. However, the exposure to 30°C + 12.5L:11.5D and 32°C + 13L:11D along with dry food accelerated the process of estivation, wherein the diapause larval survival was significantly higher and overall mortality of individuals due to diapause was lower suggesting these conditions appropriate for induction of estivation in C. partellus. These studies have implications for better understanding the bioecology and population regulation system under varying climatic conditions and devising novel strategies for management of C. partellus.
Bis‐thiourea Derivatives and Their Utility in Synthesis of Mono‐heterocyclic, Bis‐heterocyclic, and Fused Heterocyclic Systems
Authors: Dawood Kamal M.
Published: May 2019

Bis‐thiourea derivatives have distinguished synthetic potentialities. They are interesting substrates for construction of various classes of heterocycles, such as thiazoles, thiadiazoles, imidazoles, bis‐thiazoles, bis‐thiadiazoles, and fused heterocyclic systems. The current review is concerned on disclosing the synthetic and research applications of bis‐thioureas that were reported in the literature during the last decade.
Low catalytic activity is insufficient to induce disease pathology in triosephosphate isomerase deficiency
Authors: Segal Joanna , Mülleder Michael , Krüger Antje , Adler Thure , Scholze‐Wittler Manuela , Becker Lore , Calzada‐Wack Julia , Garrett Lillian , Hölter Sabine M. , Rathkolb Birgit , Rozman Jan , Racz Ildiko , Fischer Ralf , Busch Dirk H. , Neff Frauke , Klingenspor Martin , Klopstock Thomas , Grüning Nana‐Maria , Michel Steve , Lukaszewska‐McGreal Beata , Voigt Ingo , Hartmann Ludger , Timmermann Bernd , Lehrach Hans , Wolf Eckhard , Wurst Wolfgang , Gailus‐Durner Valérie , Fuchs Helmut , H. de Angelis Martin , Schrewe Heinrich , Yuneva Mariia , Ralser Markus
Published: May 2019

Triosephosphate isomerase (TPI) deficiency is a fatal genetic disorder characterized by hemolytic anemia and neurological dysfunction. Although the enzyme defect in TPI was discovered in the 1960s, the exact etiology of the disease is still debated. Some aspects indicate the disease could be caused by insufficient enzyme activity, whereas other observations indicate it could be a protein misfolding disease with tissue‐specific differences in TPI activity. We generated a mouse model in which exchange of a conserved catalytic amino acid residue (isoleucine to valine, Ile170Val) reduces TPI specific activity without affecting the stability of the protein dimer. TPIIle170Val/Ile170Val mice exhibit an approximately 85% reduction in TPI activity consistently across all examined tissues, which is a stronger average, but more consistent, activity decline than observed in patients or symptomatic mouse models that carry structural defect mutant alleles. While monitoring protein expression levels revealed no evidence for protein instability, metabolite quantification indicated that glycolysis is affected by the active site mutation. TPIIle170Val/Ile170Val mice develop normally and show none of the disease symptoms associated with TPI deficiency. Therefore, without the stability defect that affects TPI activity in a tissue‐specific manner, a strong decline in TPI catalytic activity is not sufficient to explain the pathological onset of TPI deficiency.
A new justification of the Hartung‐Knapp method for random‐effects meta‐analysis based on weighted least squares regression
Authors: van Aert Robbie C. M. , Jackson Dan
Published: May 2019

The Hartung‐Knapp method for random‐effects meta‐analysis, that was also independently proposed by Sidik and Jonkman, is becoming advocated for general use. This method has previously been justified by taking all estimated variances as known and using a different pivotal quantity to the more conventional one when making inferences about the average effect. We provide a new conceptual framework for, and justification of, the Hartung‐Knapp method. Specifically, we show that inferences from fitted random‐effects models, using both the conventional and the Hartung‐Knapp method, are equivalent to those from closely related intercept only weighted least squares regression models. This observation provides a new link between Hartung and Knapp's methodology for meta‐analysis and standard linear models, where it can be seen that the Hartung‐Knapp method can be justified by a linear model that makes a slightly weaker assumption than taking all variances as known. This provides intuition for why the Hartung‐Knapp method has been found to perform better than the conventional one in simulation studies. Furthermore, our new findings give more credence to ad hoc adjustments of confidence intervals from the Hartung‐Knapp method that ensure these are at least as wide as more conventional confidence intervals. The conceptual basis for the Hartung‐Knapp method that we present here should replace the established one because it more clearly illustrates the potential benefit of using it.
Cochlear implant failures and reimplantation: A 30‐year analysis and literature review
Authors: Lane Ciaran , Zimmerman Kim , Agrawal Sumit , Parnes Lorne
Published: May 2019

Objectives/Hypothesis

The objectives of the study were to present an institutional experience with device failures and cochlear reimplantation rates over a 30‐year period and to perform a detailed literature review.

Study Design

Retrospective institutional experience and literature review.

Methods

A review of cochlear implant failures over a period of 30 years, between January 1988 and March 2017, at a single institution was conducted. Cochlear implant failures were calculated based on manufacturer, type of failure, and overall failure rate. Survival analysis was performed using Kaplan‐Meier curves. An electronic search of the PubMed, Web of Science, and EMBASE databases revealed 24 articles on the topic of cochlear device failure. Data on reimplantation and device failure rates were extracted from this literature review and analyzed.

Results

A total of 804 cochlear implantations were reviewed from three manufacturers. The institutional reimplantation rate was 2.9% compared to the pooled rate of 6.0% calculated from the literature review. Medical failures accounted for 0.5% of the overall failures, device failures accounted for 1.6%, and inconclusive failures account for 0.7%. Survival analysis revealed a significant difference among manufacturers. An improved device failure rate was noted in the adult population (0.8%) as compared to the pediatric population (2.8%).

Conclusions

This 30‐year review represents one of the longest series in the literature examining reimplantation, device failure, and medical failure rates. Cochlear implant survival varied by manufacturer and was significantly better in adult compared to pediatric patients.

Level of Evidence

NA

Laryngoscope, 130:782–789, 2020
Intraoperative cone‐beam CT‐guided osteotomy navigation in mandible and maxilla surgery
Authors: Hasan Wael , Daly Michael J. , Chan Harley H. L , Qiu Jimmy , Irish Jonathan C.
Published: May 2019

Objectives

Surgical navigation systems based on preoperative imaging are now increasingly used for guidance of head and neck resection and reconstruction. The primary aim of this study was to quantify osteotomy cutting accuracy using an image‐guidance system for intraoperative cone‐beam computed tomography (CBCT) imaging and surgical saw navigation. To enable clinical translation of this CBCT‐guided navigation system, a secondary aim of the study was to design and fabricate a patient reference tracker suitable for clinical use on a mobile mandible.

Methods

First, a preclinical cadaveric study was performed to quantify navigation accuracy with the use of clinically suitable patient reference trackers. Second, a proof‐of‐principle patient study was conducted to evaluate this technique under clinical conditions.

Results

In both preclinical (5 cadavers) and clinical (5 patients) experiments, the mean cutting accuracy was less than 2 mm. In all preclinical specimens, bilateral mandibulectomies and bilateral maxillectomies were performed, for a total of 20 cut planes for analysis. The mean (standard deviation [SD]) values for distance, pitch, and roll were 1.4 mm (1.1 mm), 4.2° (3.5°), and 2.9° (2.5°) mm, respectively. Five mandibulectomies were performed on five patients, for a total of 10 cut planes for analysis. The mean (SD) values for distance, pitch, and roll were 1.7 mm (0.8 mm), 5.4° (1.5°), and 6.7° (4.6°) mm, respectively.

Conclusions

The overall performance in comparison to alternative approaches warrants further consideration. In terms of accuracy, the results presented here are comparable to recent systematic reviews assessing CAD‐CAM cutting guides that cite accuracies of ~2 to 2.5 mm.

Level of Evidence

2

Laryngoscope, 130:1122–1127, 2020
Smoothable zero dimensional schemes and special projections of algebraic varieties
Authors: Jelisiejew Joachim , Kapustka Grzegorz , Kapustka Michał
Published: May 2019

We study the degrees of generators of the ideal of a projected Veronese variety to depending on the center of projection. This is related to the geometry of zero dimensional schemes of length 8 in , Cremona transforms of , and the geometry of Tonoli Calabi‐Yau threefolds of degree 17 in .
Halogen‐Bond‐Mediated Self‐Assembly of Polymer–Resorcinarene Complexes
Authors: Välimäki Salla , Gustavsson Lotta , Beyeh Ngong Kodiah , Linko Veikko , Kostiainen Mauri A.
Published: May 2019

A new supramolecular system based on halogen‐bonded macromolecular substances is presented. Binding and complex formation between a halogen bond acceptor N‐benzyl ammonium resorcinarene bromide and a library of polymeric halogen bond donors based on iodotetrafluorophenoxy functionality is shown. The complex formation was confirmed in liquid state by dynamic light scattering and transmission electron microscopy. Spectroscopic measurements in the solid state verify the halogen bonding. In particular, the study shows that both homopolymers and polyethylene glycol block copolymers act as effective halogen bond donors leading to polymer‐architecture‐dependent complex morphologies.
Evidence that peroxisome proliferator‐activated receptor γ suppresses squamous carcinogenesis through anti‐inflammatory signaling and regulation of the immune response
Authors: Ren Lu , Konger Raymond L.
Published: May 2019

A variety of evidence suggests that peroxisome proliferator‐activated receptor (PPAR)γ agonists may represent a potential pharmacologic target in the prevention or treatment of skin cancer. In particular, recent reports suggest that PPARγ activation may exert at least some of its anti‐neoplastic effects through the suppression of tumor promoting chronic inflammation as well as by strengthening antitumor immune responses. This activity is thought to occur through a distinct mode of ligand interaction with PPARγ that causes transrepression of transcription factors that are involved in inflammatory and immunomodulatory signaling. However, current thiazolidinedione (TZD)‐type PPARγ agonists have significant safety concerns that limit their usefulness as a preventive or therapeutic option. Due to the relatively large ligand binding pocket of PPARγ, a diverse group of ligands can be seen to interact with distinct modes of binding to PPARγ, leading to the phenomenon of partial agonist activity and selective PPARγ modulators (SPPARγM). This has led to the development of ligands that are tailored to deliver desired pharmacologic activity, but lack some of the negative side effects associated with full agonists, such as the currently utilized TZD‐type PPARγ agonists. In addition, there is evidence that a number of phytochemicals that are currently being touted as antineoplastic nutraceuticals also possess PPARγ activity that may partially explain their pharmacologic activity. We propose that one or more of these partial agonists, SPPARγMs, or putative phytochemical PPARγ ligands could presumably be used as a starting point to design more efficacious anti‐neoplastic PPARγ ligands that lack adverse pharmacological effects.
Influence of glutathione S‐transferases (GSTM1, GSTT1, and GSTP1) genetic polymorphisms and smoking on susceptibility risk of chronic myeloid leukemia and treatment response
Authors: Rostami Golale , Assad Dlnya , Ghadyani Fatemeh , Hamid Mohammad , Karami Amirhossien , Jalaeikhoo Hasan , Kalahroodi Ramezan Ali
Published: May 2019

Background

Glutathione S‐transferases (GSTs) polymorphisms may impact on chronic myeloid leukemia (CML) risk or heterogeneous responses to Imatinib mesylate (IM). The aim of this study was to evaluate the correlation between GSTs polymorphisms and CML risk, treatment response.

Methods

We genotyped GSTM1, GSTT1 null deletion polymorphisms, and GSTP1 Ile105Val polymorphism by PCR methods and BCR‐ABL transcripts were analyzed by qRT‐PCR in 104 CML patients and 104 sex‐ and age‐matched healthy individuals.

Results

Individual analysis showed significant association of GSTM1 (p = 0.008; OR = 0.46; 95% CI: 0.26–0.82) and GSTP1 genes (p = 0.04; OR = 1.56; 95% CI: 1.016–2.423) with CML risk. The combined analysis indicated that GSTM1 null/GSTT1 present, GSTM1‐null/GSTP1M*(AG/GG) as well as GSTT1 present/ GSTP1M* genotype were associated with CML risk (ORg(‐):2.28; 95% CI: 1.29–4.04; ORgg: 2.85; 95% CI: 1.36–5.97; OR(‐)g: 1.75; 95% CI: 0.99–3.06, respectively). The proportion of CML cancer attributable to the interaction of smoking and GSTM1 null, GSTT1null, and GSTP1 M* was 42%, 39%, and 13%, respectively. Patients with GSTM1‐null and GSTP1 AG/GG genotype had significantly a lower rate of MMR achievement (p = 0.00; p = 0.009 respectively). Event‐free survival (EFS) percentage was similar between GSTM1 null and GSTM1 present patients (p = 0.21).

Conclusion

Our study suggests the influence of GSTM1 and GSTP1 polymorphisms on CML risk and treatment response. The interaction between GSTs polymorphisms and smoking plays a significant role on CML susceptibility.
Association of glypican‐6 polymorphisms with lumbar disk herniation risk in the Han Chinese population
Authors: Hu Baoyang , Xing Wenhua , Li Feng , Huang Zhi , Zheng Wenkai , Ji Demin , Niu Fanglin , Zhu Yong , Yang Xuejun
Published: May 2019

Background

Lumbar disk herniation (LDH) is a degenerative disorder, which partly results from complex genetic factors. The aim of the study was to investigate the potential associations between glypican‐6 (GPC6) variants and LDH risk in Han Chinese population.

Methods

A total of 508 Han Chinese LDH patients and 508 healthy controls were recruited in this study. Six single‐nucleotide polymorphisms (SNPs) in GPC6 were selected and genotyped using an Agena MassARRAY platform. We used logistic regression method to evaluate the linkage between GPC6 variants and LDH risk by calculating the odds ratio (OR) and 95% confidence intervals (CIs) in multiple genetic models. HaploReg database was used for SNP functional annotation.

Results

Our result revealed GPC6 rs4773724 was associated with a decreased risk of LDH in allele model (OR = 0.82, 95% CI: 0.68–0.98, p = 0.026), whereas rs1008993 increased the LDH risk (OR = 1.34, 95% CI: 1.05–1.71, p = 0.020). Besides, we also found rs4773724 and rs9523981 were associated with susceptibility of LDH among individuals whose age are less than 45. And rs1008993 was associated with increased LDH risk in males. Furthermore, Haplotype analysis showed that the TT (rs4773724, rs1008993) haplotype and GC (rs4773724, rs1008993) haplotype had the opposite effects on the susceptibility of LDH.

Conclusions

For the first time, we suggest that rs4773724 and rs1008993 in GPC6 were considered as a protective factor and a risk factor for LDH in Han Chinese population, respectively. These results provide new ideas for the treatment and prevention of LDH in Han Chinese population.
Panelists tout CCBHCs, engage in timely talk on mental health
Authors: Canady Valerie A.
Published: May 2019

As legislation to expand the Certified Community Behavioral Health Clinic (CCBHC) model that would bring CCBHCs to 11 new states that have invested time planning for the program and add two more years to the current eight states participating in the initiative is pending, lawmakers and advocates gathered together last week to discuss mental illness and the need for the expansion.
A fast numerical algorithm based on the Taylor wavelets for solving the fractional integro‐differential equations with weakly singular kernels
Authors: Keshavarz Elham , Ordokhani Yadollah
Published: May 2019

In this paper, a fast numerical algorithm based on the Taylor wavelets is proposed for finding the numerical solutions of the fractional integro‐differential equations with weakly singular kernels. The properties of Taylor wavelets are given, and the operational matrix of fractional integration is constructed. These wavelets are utilized to reduce the solution of the given fractional integro‐differential equation to the solution of a linear system of algebraic equations. Also, convergence of the proposed method is studied. Illustrative examples are included to demonstrate the validity and applicability of the technique.
Stabilization criteria of a class of switched systems
Authors: Carapito Ana C.
Published: May 2019

In this paper, stabilizability property for a switched system under arbitrary switching is considered from an algebraic point of view by means of the existence of a set of block‐diagonal Lyapunov solutions with common Schur complement of certain order—or, equivalently, with common block (1,1)—for the matrix bank. It is shown that the existence of that set is equivalent to the existence of solutions for some Riccati inequalities done in terms of the blocks of matrices of the bank. In addition, we conclude that a particular class of systems with matrix bank constituted by Metzler matrices—Positive Switched Systems—are stabilizable by partial state reset.
Experimental and Theoretical Approaches in the Study of Phenanthroline‐Tetrahydroquinolines for Alzheimer's Disease
Authors: Duarte Yorley , Gutierrez Margarita , Álvarez Rocío , Alzate‐Morales Jans H. , Soto‐Delgado Jorge
Published: May 2019

The imino‐Diels‐Alder reaction is one of the most common strategies in organic chemistry and is an important tool for providing a broad spectrum of biologically active heterocyclic systems. A combined theoretical and experimental study of the imino‐Diels‐Alder reaction is described. The new phenanthroline‐tetrahydroquinolines were evaluated as cholinesterase inhibitors. Their cytotoxicity in human neuroblastoma SH‐SY5Y cells was also evaluated. The theoretical results suggest that compounds formation in stages can be explained by endo cycloadducts under the established reaction conditions, thereby confirming experimental results obtained for percentage yield. These results allowed us to establish that pyridine substituent remarkably influences activation energy and reaction yield, as well as in acetylcholinesterase (AChE) activity. Among these derivatives, compounds with 4‐pyridyl and 4‐nitrophenyl showed favorable AChE activity and proved to be non‐cytotoxic.
So far so good? Tracking the poverty eradication goal of SDGs in Kenya, Nigeria, and South Africa
Authors: Mubecua Mandla A. , David Ojochenemi James
Published: May 2019

This paper tracks the progress of the Sustainable Development Goals in selected countries in sub‐Saharan Africa, namely, Kenya, Nigeria, and South Africa. The study assesses economic indices such as GDP growth, employment, and poverty rate of each country to understand the present performance of these countries and the feasibility of it attaining the first goal of the Sustainable Development Goals. Considering the current economic outlook and trajectory of these countries, eradicating poverty in 2030 is highly unlikely, unless drastic measures are taken. GDP growth in Kenya is currently low, whereas the poverty and the unemployment rate are very high. Nigeria still battles with economic recovery following the recession since 2016 and a soaring poverty level. Equally, South Africa is saddled with the problem of rising poverty, unemployment, and corruption. The study recommends that cooperation between government, civil society, and the private sector needs to be drastically improved and promptly to meet the poverty eradication goal by 2030.
Injectable poloxamer/graphene oxide hydrogels with well‐controlled mechanical and rheological properties
Authors: Rohani Rad Elaheh , Vahabi Henri , Formela Krzysztof , Saeb Mohammad Reza , Thomas Sabu
Published: May 2019

Although significant progress has been made in the design and application of injectable hydrogels for biomedical applications, concurrent control of rheological and mechanical properties of injectable hydrogels has remained as an open challenge to the researchers. In this work, we introduce and put into practice a photo‐curable poloxamer (also known as Pluronic)/graphene oxide (Plu/GO) injectable hydrogel with well‐controlled rheological and mechanical properties. Acrylate group was anchored to hydrogel structure to endow photo‐crosslinking ability through decelerating degradation rate of poloxamer hydrogels after injection. It was found that the modified Plu remains stable in biological media for a long‐term period without significant weight loss. Rheological properties of hydrogels were also carried out as essential prerequisite for an ideal injectability via frequency sweep, flow curve, recovery, and yield stress before and after modification, signifying shear‐thinning behavior of Plu/GO hydrogels with high recoverability. The viscosity of shear‐thinning‐like hydrogels dropped at higher shear stress, which facilitated injection process. Moreover, mechanical behavior of Plu was optimized by manipulating the content of Plu, degree of modification with reactive precursor, curing, and particularly incorporation of GO without deteriorating effects on rheological behavior of Plu.