bluuebunny/crossref_metadata_2025 huggingface dataset:
Energy Evolution Law of Ore-Bearing Rock during Unloading under High Static Stress and Frequent Disturbance
Authors: Wang Chun , Xie Mei-zhi , Xiong Zu-qiang , Wang Cheng , Cheng Lu-ping
Published: October 2020

Based on the complex engineering environment in deep rock engineering, preloaded high axial pressure, unloading of axial pressure, and impact loading were used to simulate high in situ stress, unloading of excavation, and blasting disturbance, respectively; the experimental study on frequent impact disturbances under unloading of high static load was carried out, which aimed at revealing the energy evolution law of rock. First, the equations of elastic property, plastic energy, and incident energy in the impact process are discussed by theoretical analysis. Then, it is found by further investigation that dynamic stress-strain curve and envelope curve of rock are with the same change tendency. The initial stage was short straight stage, and then linear stage appeared and was less influenced by unloading rate. The plastic energy, the ratio of reflected energy to incident energy, and the energy consumption per unit volume of rock increase during impact. The higher the preloaded axial pressure is, the greater the ratio of reflected energy to incident energy is, the smaller the ratio of transmitted energy to incident energy and the average energy dissipation per unit volume of rock are. When the unloading rate increased, the elastic energy generated by impact gradually increased, the plasticity gradually weakened, the ratio of transmitted energy to incident energy increased, and the ratio of reflection energy to incident energy decreased.
Coccoloba alnifoliaLeaf Extract as a Potential Antioxidant Molecule Using In Vitro and In Vivo Assays
Authors: de Melo Luciana Fentanes Moura , Gomes Dayanne Lopes , da Silva Lucas Felipe , Silva Larissa Marina Pereira , Machado Marina Lopes , Cadavid Cesar Orlando Muñoz , Zucolotto Silvana Maria , de Paula Oliveira Riva , dos Santos Deborah Yara Alves Cursino , Rocha Hugo Alexandre Oliveira , Scortecci Katia Castanho
Published: October 2020

The genusCoccolobais widely used in traditional folk medicine, but few scientific data exist for this genus. The goal of this study was to characterise the chemical composition and antioxidant activities ofC. alnifolialeaf extracts usingin vitroandin vivoassays. Six extracts were obtained: hexane (HE), chloroform (CE), ethanol (EE), methanol (ME), water end extract (WEE), and water extract (WE). Thin-layer chromatography (TLC) analysis showed the presence of phenols, saponins, terpenes, and flavonoids.In vitroassays demonstrated substantial antioxidant potential, especially for polar extracts (EE, ME, WEE, and WE). Moreover, no toxic effects were observed on mammalian cell lines for most of the extracts at the concentrations evaluated. The nematodeCaenorhabditis eleganswas also used as anin vivomodel for testing antioxidant potential. The EE and WE were chosen, based on previously obtained results. It was observed that neither the EE nor the WE had any toxic effect onC. elegansdevelopment. Additionally, the antioxidant potential was evaluated usingtert-butyl hydroperoxide as a stressor agent. The EE increased the life span ofC. elegansby 28% compared to that of the control, and the WE increased the range to 39.2-41.3%. High-performance liquid chromatography (HPLC-DAD) showed the presence of gallic acid,p-coumaric acid, and vitexin in the WE. Therefore,in vitroandin vivodata demonstrated the antioxidant potential ofC. alnifoliaextracts and their possible biotechnological applications.
Sodium Tanshinone IIA Silate Exerts Microcirculation Protective Effects against Spinal Cord Injury In Vitro and In Vivo
Authors: Li Xing , Luo Dan , Hou Yu , Hou Yonghui , Chen Shudong , Zhan Jiheng , Luan Jiyao , Wang Le , Lin Dingkun
Published: October 2020

Spinal cord microcirculation involves functioning endothelial cells at the blood spinal cord barrier (BSCB) and maintains normal functioning of spinal cord neurons, axons, and glial cells. Protection of both the function and integrity of endothelial cells as well as the prevention of BSCB disruption may be a strong strategy for the treatment of spinal cord injury (SCI) cases. Sodium Tanshinone IIA silate (STS) is used for the treatment of coronary heart disease and improves microcirculation. Whether STS exhibits protective effects for SCI microcirculation is not yet clear. The purpose of this study is to investigate the protective effects of STS on oxygen-glucose deprivation- (OGD-) induced injury of spinal cord endothelial cells (SCMECs) in vitro and to explore effects on BSCB and neurovascular protection in vivo. SCMECs were treated with various concentrations of STS (1 μM, 3 μM, and 10 μM) for 24 h with or without OGD-induction. Cell viability, tube formation, migration, and expression of Notch signaling pathway components were evaluated. Histopathological evaluation (H&E), Nissl staining, BSCB permeability, and the expression levels of von Willebrand Factor (vWF), CD31, NeuN, and Notch signaling pathway components were analyzed. STS was found to improve SCMEC functions and reduce inflammatory mediators after OGD. STS also relieved histopathological damage, increased zonula occludens-1 (ZO-1), inhibited BSCB permeability, rescued microvessels, protected motor neuromas, and improved functional recovery in a SCI model. Moreover, we uncovered that the Notch signaling pathway plays an important role during these processes. These results indicated that STS protects microcirculation in SCI, which may be used as a therapeutic strategy for SCI in the future.
Effectiveness and Safety of Trabeculectomy along with Amniotic Membrane Transplantation on Glaucoma: A Systematic Review
Authors: Shen Tian-yi , Hu Wei-nan , Cai Wen-ting , Jin Hui-zi , Yu Dong-hui , Sun Jing-hui , Yu Jing
Published: October 2020

Purpose. To determine the effectiveness and safety of trabeculectomy along with amniotic membrane transplantation (AMT) for glaucoma. Methods. This systematic review was performed using RevMan 5.3. We searched PubMed, EMBASE, and the Cochrane Library and included studies published until September 2019. The treatment group included patients with AMT and trabeculectomy (group A), and the control group had only trabeculectomy (group B). We only included randomized controlled trials. The outcomes were intraocular pressure (IOP), complete success rate, number of antiglaucoma medications, and complications. Results. Five studies, including 174 eyes (87 eyes in the AMT group and 87 eyes in the control group), were eligible in this review. The parameters had no significant difference in heterogeneity between the AMT and control groups preoperatively. In the AMT group, the mean IOP was significantly lower at 3 and 12 months after operation (P < 0.0001 and P = 0.02, respectively), while the number of complete successes in the AMT group was significantly higher at 6 and 12 months (P = 0.02 and P = 0.003, respectively) compared with the control group. Complications, including a flat anterior chamber and hyphema, appeared to be decreased in the AMT group compared to the control group (P = 0.02 and P = 0.02, respectively). No differences were observed in the number of antiglaucoma medications, hypotony, encapsulated bleb, or choroidal detachment. Conclusion. Compared with only trabeculectomy, it is more efficient and safer to add AMT to trabeculectomy during glaucoma filtering surgery.
A Two-Stage Three-Machine Flow Shop Assembly Problem Mixed with a Controllable Number and Sum-of-Processing Times-Based Learning Effect by Simulated Annealing Algorithms
Authors: Liu Shang-Chia
Published: October 2020

The two-stage assembly scheduling problem is widely used in industrial and service industries. This study focuses on the two-stage three-machine flow shop assembly problem mixed with a controllable number and sum-of-processing times-based learning effect, in which the job processing time is considered to be a function of the control of the truncation parameters and learning based on the sum of the processing time. However, the truncation function is very limited in the two-stage flow shop assembly scheduling settings. Thus, this study explores a two-stage three-machine flow shop assembly problem with truncated learning to minimize the makespan criterion. To solve the proposed model, we derive several dominance rules, lemmas, and lower bounds applied in the branch-and-bound method. On the other hand, three simulated annealing algorithms are proposed for finding approximate solutions. In both the small and large size number of job situations, the SA algorithm is better than the JS algorithm in this study. All the experimental results of the proposed algorithm are presented on small and large job sizes, respectively.
On Janowski Analytic p,q-Starlike Functions in Symmetric Circular Domain
Authors: Khan Muhammad Ghaffar , Ahmad Bakhtiar , Frasin Basem Aref , Abdeljawad Thabet
Published: October 2020

The main object of the present paper is to apply the concepts of p,q-derivative by establishing a new subclass of analytic functions connected with symmetric circular domain. Further, we investigate necessary and sufficient conditions for functions belonging to this class. Convex combination, weighted mean, arithmetic mean, growth theorem, and convolution property are also determined.
Pharmacological Modulation of Smooth Muscles and Platelet Aggregation by Psidium cattleyanum
Authors: Rahman Hafiz Muhammad Abdur , Saghir Khaled Ahmed , Haider Muhammad Sajjad , Javaid Usman , Rasool Muhammad Fawad , Alqahtani Faleh , Imran Imran
Published: October 2020

Traditionally, in the Southern Asian countries, Psidium cattleyanum is a widely used plant for the management of various ailments such as gastrointestinal, respiratory, and cardiac disorders, but it lacks proof on a scientific basis, and therefore, this is the major emphasis of the current research work. Crude extract of Psidium cattleyanum (Pc.Cr) was preliminary analyzed for the presence of different classes of bioactive molecules. The aqueous and dichloromethane fractions of Pc.Cr were subjected to in vitro and in vivo studies. It was applied at variable concentrations (0.1–10 mg/ml) to isolated rabbit jejunum to investigate spasmolytic effect. Concentration dependent curves of calcium were constructed to check the calcium channel antagonistic activity. For the evaluation of tracheorelaxant activity, isolated tracheal tissue was treated with High‐K+ (80 mM) and carbachol (CCh) and then challenged cumulatively with Pc.Cr. To study the antidiarrheal effect of the plant extract, castor oil‐induced diarrhea model was adopted. For evaluation of the hypotensive effect of Pc.Cr, it was given intravenously to preanesthetized normotensive rats, and the response was recorded using pressure transducer. Platelet rich plasma was used for the assessment of the antiplatelet activity when challenged with purinergic and adrenergic agonists. Concentration‐dependent inhibition of spontaneous and High‐K+ mediated contractions in isolated jejunum was observed by the application of Pc.Cr. Contractions induced in isolated tracheal tissue by High‐K+ and CCh were inhibited by application of Pc.Cr to these tissues. Similarly, application of Pc.Cr to High‐K+ and phenylephrine (PE) treated aortic strips resulted in vasodilation. Platelet aggregation inhibition was shown by Pc.Cr against adenosine diphosphate (ADP) only. The antidiarrheal effect was observed as a reduction in the total number of feces in Pc.Cr‐treated mice when given castor oil. Dose‐dependent hypotension was seen in normotensive rats when treated with Pc.Cr intravenously. This study showed the spasmolytic, tracheorelaxant, vasodilator, platelet aggregation inhibitory, antidiarrheal, and hypotensive activities of P. cattleyanum which may be due to the blockage of calcium channels, but the involvement of any other pathway cannot be ignored.
Comprehensive Analysis of Differentially Expressed miRNAs and mRNAs Reveals That miR-181a-5p Plays a Key Role in Diabetic Dermal Fibroblasts
Authors: Liu Peng , Zhu Yi , Li Qin , Cheng Biao
Published: October 2020

A diabetic nonhealing wound causes heavy economic burden and compromised quality of life in patients. The human dermal fibroblast (HDF), which is an important kind of effector cell in the wound healing process, represents different biological behaviors in the normal and diabetic skins. Given this, we attempt to explore functional changes in diabetic skin-derived HDFs and try to find out the “hub” genes that modulate diabetic HDFs and may be the potential therapeutic targets of diabetic wound healing. We searched the GEO database for related miRNA (GSE68185, GSE84971) and mRNA (GSE49566, GSE78891) profiles. After eliminating batch effects and identifying differentially expressed genes (DEGs), we applied enrichment analyses and found that 3 miRNAs and 30 mRNAs were differentially expressed in diabetic HDFs. Enrichment analyses showed that these genes are closely related to wound healing, for example, extracellular matrix (ECM) organization, angiogenesis, cell proliferation, and migration. Subsequently, we constructed the gene correlation network of DEGs to identify hub genes by merging the protein-protein interaction network, weighted gene coexpression network, and predicted miRNA-mRNA regulatory network. Based on the gene correlation network, we identified the top 3 hub genes: miR-181a-5p, POSTN, and CDH11. Among these, POSTN is a predicted target of miR-181a-5p and is supposed to work together with CDH11 as a functional group. Finally, we verified the expression pattern of the hub genes by in vitro quantification experiments in glucose-cultured HDFs. Our study suggested that miR-181a-5p possibly plays a key role in modulation of HDF behaviors during the diabetic state. However, the effects and mechanisms of miR-181a-5p in high glucose-cultured HDFs remain to be explored in the future.
The Complexity Analysis and Control of Time-Delay OEM Supply Chain considering R&D Efforts and Marketing Level
Authors: Dai Daoming , Wu Xuanyu , Si Fengshan
Published: October 2020

In this paper, we investigate a supply chain consisting of an OEM (i.e., original equipment manufacturer) and a CM (contract manufacturer), in which the OEM decides design effort level and marketing level, and the CM makes decision on product manufacturing effort level. We establish a three-dimensional discrete dynamic model with time delay. Firstly, the sufficient conditions for Neimark–Sacker bifurcation are obtained by using different combinations of decision delay periods as bifurcation parameters, and the effect of the adjustment speeds of decision variables on the system stability and impact of time delay on the system stability are discussed, respectively. Secondly, we perform numerical simulation of this model from the perspective of entropy theory. Finally, we propose two methods to control chaos. Results show that when the time delay or the adjustment speed of decision variable exceed a certain threshold, the system will be led into a chaotic state and the entropy of the system will increase. For alleviating the negative effects of chaotic systems, we introduce control parameters to make efficient control on the chaos. At the critical point, the critical value of the adjustment speed of design effort level (or marketing level) of OEM increases as the adjustment speed of the manufacturing effort level of CM decreases, and vice versa.
Mutations Associated with Rifampicin Resistance in Mycobacterium tuberculosis Isolates from Moroccan Patients: Systematic Review
Authors: Eddabra Rkia , Neffa Mounsef
Published: October 2020

Background. In recent years, the treatment of tuberculosis has been threatened by the increasing number of patients with drug resistance, especially rifampicin resistance, which is the most effective first-line antibiotic against Mycobacterium tuberculosis. Methods. We performed a systematic review of the literature by searching the PubMed database for studies of rifampicin-resistant Mycobacterium tuberculosis (MTB) isolates from Moroccan patients, published between 2010 and 2020. The aim of this review was to quantify the frequency of the most common mutations associated with rifampicin resistance, to describe the frequency at which these mutations co-occur. Identified studies were critically appraised according to the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Results. 6 studies met our inclusion criteria. Results show that 99.36% of MTB isolates had a single-point mutation, and the most commonly mutated codon of rpoB gene is 531 with 70.33% of phenotypically resistant strains. However, 10.38% of MTB strains phenotypically resistant to RIF did not exhibit any mutation in the rpoB gene. Conclusion. Identification of a resistance-associated mutation to rifampicin can be a good marker of drug-resistant TB, but lack of a mutation in the target sequence must be interpreted with caution.
Preparation and Characterization of Liposomal Everolimus by Thin-Film Hydration Technique
Authors: Torres-Flores Gabriela , Gonzalez-Horta Azucena , Vega-Cantu Yadira I. , Rodriguez Ciro , Rodriguez-Garcia Aida
Published: October 2020

In 10% to 40% of the cases of coronary stent implantation, patients face in-stent restenosis due to an inflammatory response, which induces artery thickening. Everolimus, a drug that inhibits growth factor-stimulated cell proliferation of endothelial cells, represents a promising alternative to prevent in-stent restenosis. In this study, everolimus was encapsulated by a film hydration technique in liposomes by using phosphatidylcholine and cholesterol at different ratios. As the ratio of cholesterol increases, it modulates the rigidity of the structure which can affect the encapsulation efficiency of the drug due to steric hindrance. Moreover, various lipid : drug ratios were tested, and it was found that as the lipid : drug ratio increases, the encapsulation efficiency also increases. This behavior is observed because everolimus is a hydrophobic drug; therefore, if the lipidic region increases, more drug can be entrapped into the liposomes. In addition, stability of the encapsulated drug was tested for 4 weeks at 4°C. Our results demonstrate that it is possible to prepare liposomal everolimus by film hydration technique followed by extrusion with high entrapment efficiency as a viable drug delivery system.
Efficacy and Safety of Stem Cell Therapy for T1DM: An Updated Systematic Review and Meta-Analysis
Authors: Sun Shi-Yi , Gao Yun , Liu Guan-Jian , Li Yong-Kun , Gao Wei , Ran Xing-Wu
Published: October 2020

Background. The long-term insulin therapy for type 1 diabetes mellitus (T1DM) fails to achieve optimal glycemic control and avoid adverse events simultaneously. Stem cells have unique immunomodulatory capacities and have been considered as a promising interventional strategy for T1DM. Stem cell therapy in T1DM has been tried in many studies. However, the results were controversial. We thus performed a meta-analysis to update the efficacy and safety of stem cell therapy in patients with T1DM. Methods. We systematically searched the Medline, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Web of Science, Wan Fang Data, China National Knowledge Infrastructure, VIP database, and the Chinese Biomedical Literature Database (SinoMed) for relevant studies published before March 19, 2019. The outcomes included parameters for glycemic control (i.e., glycosylated hemoglobin (HbA1c) levels and insulin dosages), β cell function (i.e., fasting C-peptide levels and area-under-curve of C-peptide concentration (AUCC)), and relative risk of adverse events. Statistical analysis was conducted by using RevMan 5.3 and Stata 12.0. Results. Five randomized controlled trials (RCTs) and eight nonrandomized concurrent control trials (NRCCTs) with a total of 396 individuals were finally included into the meta-analysis. Among RCTs, stem cell therapy could significantly reduce HbA1c levels (MD=−1.20, 95% CI -1.91 to -0.49, P=0.0009) and increase fasting C-peptide levels (MD=0.25, 95% CI 0.04 to 0.45, P=0.02) and AUCC (SMD=0.66, 95% CI 0.13 to 1.18, P=0.01). Stem cell therapy could also reduce insulin dosages (SMD=−2.65, 95% CI -4.86 to -0.45, P=0.02) at 6 months after treatment. NRCCTs also had consistent results. Furthermore, RCTs showed stem cell therapy did not increase relative risk of gastrointestinal symptom (RR = 0.69, 95% CI 0.14 to 3.28, P=0.64) and infection (RR = 0.97, 95% CI 0.40 to 2.34, P=0.95). However, NRCCTs showed stem cell therapy increased relative risk of gastrointestinal symptom (RR = 44.49, 95% CI 9.20 to 215.18, P<0.00001). Conclusion. Stem cell therapy for T1DM may improve glycemic control and β cell function without increasing the risk of serious adverse events. Stem cell therapy may also have a short-term (3-6 months) effect on reducing insulin dosages.
Association of Genetic Variants of KCNJ11 and KCNQ1 Genes with Risk of Type 2 Diabetes Mellitus (T2DM) in the Indian Population: A Case-Control Study
Authors: Khan Vasiuddin , Verma Amit Kumar , Bhatt Deepti , Khan Shahbaz , Hasan Rameez , Goyal Yamini , Ramachandran Sowmya , Alsahli Mohammed A. , Rahmani Arshad Husain , Almatroudi Ahmad , Shareef M. Y. , Meena Babita , Dev Kapil
Published: October 2020

Type 2 diabetes mellitus (T2DM) is a polygenic metabolic disease described by hyperglycemia, which is caused by insulin resistance or reduced insulin secretion. The interaction between various genetic variants and environmental factors triggers T2DM. The aim of this study was to find risk associated with genetic variants rs5210 and rs2237895 of KCNJ11 and KCNQ1 genes, respectively, in the development of T2DM in the Indian population. A total number of 300 cases of T2DM and 100 control samples were studied to find the polymorphism in KCNJ11 and KCNQ1 through PCR-RFLP. The genotype and allele frequencies in T2DM cases were significantly different compared to the control population. KCNJ11 rs5210 and KCNQ1 rs2237895 variants were found to be significantly associated with risk of T2DM in dominant (KCNJ11: OR, 2.07; 95% CI, 1.30–3.27; p−0.001; KCNQ1: OR, 2.33; 95% CI, 1.46–3.70; p−0.0003) and codominant models (KCNJ11: OR, 1.76; 95% CI, 1.09–2.84; p−0.020; KCNQ1: OR, 1.85; 95% CI, 1.16–2.95; p−0.009). We also compared clinicopathological characteristics between cases and control and observed a significant difference in all the parameters except HDL, gender, and family history. In this study, clinicopathological data with a carrier of a variant allele of both KCNJ11 and KCNQ1 genes were also analysed, and a significant association was found between the carrier of a variant allele with gender and PPG in KCNJ11 and with triglyceride in KCNQ1. We confirm the significant association of KCNJ11 (rs5210) and KCNQ1 (rs2237895) gene polymorphism with T2DM, indicating the role of these variants in developing risk for T2DM in Indian population.
Exact Traveling Wave Solutions of the Gardner Equation by the Improved tanΘϑ-Expansion Method and the Wave Ansatz Method
Authors: Günerhan Hatıra
Published: October 2020

Nonlinear partial differential equations (NLPDEs) are an inevitable mathematical tool to explore a large variety of engineering and physical phenomena. Due to this importance, many mathematical approaches have been established to seek their traveling wave solutions. In this study, the researchers examine the Gardner equation via two well-known analytical approaches, namely, the improved tanΘϑ-expansion method and the wave ansatz method. We derive the exact bright, dark, singular, and W-shaped soliton solutions of the Gardner equation. One can see that the methods are relatively easy and efficient to use. To better understand the characteristics of the theoretical results, several numerical simulations are carried out.
Tilianin Protects against Ischemia/Reperfusion‐Induced Myocardial Injury through the Inhibition of the Ca2+/Calmodulin‐Dependent Protein Kinase II‐Dependent Apoptotic and Inflammatory Signaling Pathways
Authors: Jiang Hailun , Xing Jianguo , Fang Jiansong , Wang Linlin , Wang Yu , Zeng Li , Li Zhuorong , Liu Rui
Published: October 2020

Tilianin is a naturally occurring phenolic compound with a cardioprotective effect against myocardial ischemia/reperfusion injury (MIRI). The aim of our study was to determine the potential targets and mechanism of action of tilianin against cardiac injury induced by MIRI. An in silico docking model was used in this study for binding mode analysis between tilianin and Ca2+/calmodulin‐dependent protein kinase II (CaMKII). Oxygen‐glucose deprivation/reperfusion‐ (OGD/R‐) injured H9c2 cardiomyocytes and ischemia/reperfusion‐ (I/R‐) injured isolated rat hearts were developed as in vitro and ex vivo models, respectively, which were both treated with tilianin in the absence or presence of a specific CaMKII inhibitor KN93 for target verification and mechanistic exploration. Results demonstrated the ability of tilianin to facilitater the recovery of OGD/R‐induced cardiomyocyte injury and the maintenance of cardiac function in I/R‐injured hearts. Tilianin interacted with CaMKIIδ with an efficient binding performance, a favorable binding score, and restraining p‐CaMKII and ox‐CaMKII expression in cardiomyocytes injured by MIRI. Importantly, inhibition of CaMKII abolished tilianin‐mediated recovery of OGD/R‐induced cardiomyocyte injury and maintenance of cardiac function in I/R‐injured hearts, accompanied by the disability to protect mitochondrial function. Furthermore, the protective effects of tilianin towards mitochondrion‐associated proapoptotic and antiapoptotic protein counterbalance and c‐Jun N‐terminal kinase (JNK)/nuclear factor‐ (NF‐) κB‐related inflammation suppression were both abolished after pharmacological inhibition of CaMKII. Our investigation indicated that the inhibition of CaMKII‐mediated mitochondrial apoptosis and JNK/NF‐κB inflammation might be considered as a pivotal mechanism used by tilianin to exert its protective effects on MIRI cardiac damage.
Stability-Indicating High-Performance Liquid Chromatographic Determination of Levamisole Hydrochloride in Bulk and Dosage Forms
Authors: Abdalraheem Amal , Shantier Shaza , Abureid Imad , Gadkariem Elrasheed A.
Published: October 2020

A selective, accurate, and precise stability-indicating HPLC method for analysis of levamisole hydrochloride in bulk and in their injection and oral solution formulations has been developed and validated in accordance with ICH guidelines. The chromatographic separation was carried out on a C8 column (250 × 4.6 mm with a particle size of 5 micrometer) using a mixture of phosphate buffer pH 8.0 and acetonitrile (70 : 30 v/v) as the mobile phase pumped at a flow rate of 1.5 ml/min with UV detection at 215 nm. The calibration curve was linear over the 10–50 μg/ml concentration range with a correlation coefficient of 1.0000. The limit of detection (LOD) and the limit of quantitation (LOQ) were 0.29 μg/ml and 0.89 μg/ml, respectively. The accuracy and the precision of the developed method were significantly good (RSD < 2%). The validity of the proposed method was further confirmed through the statistical comparison of the obtained data with those of the official method.
Clinical Characteristics of Colorectal Cancer Patients in terms of Selected Platelet Indices
Authors: Copija Angelika , Nowakowska-Zajdel Ewa , Janion Karolina , Walkiewicz Katarzyna
Published: October 2020

Mounting evidence suggests that inflammation, immune response, and coagulation status determine many processes during the carcinogenesis pathway in colorectal cancer (CRC). Inflammation strongly promotes tumor formation, progression, and metastasis. The systemic inflammatory response (SIR) may be reflected by simple indicators evaluated on the basis of peripheral blood morphology parameters. The indices are easily obtained by the peripheral blood test and could be promising biomarkers for CRC. We present the results of the retrospective study evaluating the potential relation between the platelet indices (platelet count (PC), platelet-to-lymphocyte ratio (PLR), neutrophil platelet score (NPS), mean platelet volume (MPV), and MPV/PC ratio) and the clinicopathological features of CRC patients. The study included 247 patients (104 males and 143 females) aged 39-87 years with CRC stages II-IV. The complete blood counts with the automated differential counts were performed prior to the qualification to systemic treatment. High PC, high PLR, and NPS 0 were associated with older age and higher BMI of the patients. No link between the analyzed platelet indices and histological grade of the tumor, primary tumor location, and gender was noted. The patients aged ≥65 years were characterized by the higher MPV/PC ratio than the younger population. We observed a trend to the higher MPV/PC ratio among the patients with excessive body weight defined by BMI compared to BMI within normal limits. A higher frequency of PC>400, NPS 1 and 2, and a trend to more frequent PLR≥150 were observed in the subgroup with metastatic disease compared to individuals with CRC stages II and III. The presented results expand the knowledge on potential association between SIR parameters and other clinicopathological factors that should be considered during interpreting the prognostic and predictive value of the inflammation parameters.
Accidental Explantation of a Cochlear Implant in a Child Who Developed Cholesteatoma as a Late Complication of Cochlear Implantation
Authors: Low Wong Kein , Pok Wan Ni , Ng Win Nie , Tan Judy
Published: October 2020

Introduction. Although rare, cholesteatoma can develop as a late complication of cochlear implantation. The electrode array may then be exposed in the external auditory canal surrounded by cholesteatoma debris. Case Report. The cochlear implant of a child was inadvertently explanted by a clinician during a routine aural toilet procedure. The child had previously reported recurrent ear infections, pain, and unexplained implant function degradation. Reimplantation was carried out 2 days later with good postoperative hearing results. Part of the electrode array was observed to be embedded in cholesteatoma. Postreimplantation recovery was complicated by a breakdown of the blind-sac. Discussion. Clinical indicators that could alert the clinician to the possibility of this late complication include recurrent infections, presence of keratotic debris in the external auditory canal, unexplained implant function degradation, and nonauditory stimulation. Although this patient managed to achieve excellent postreimplantation hearing outcomes, a delay in reimplantation surgery following explantation could possibly compromise successful reinsertion of the electrode array. External ear canal overclosure without mastoid cavity obliteration has merit in facilitating CT scan surveillance, but it may increase the risk of the blind-sac breaking down. This case also illustrated how the electrode array could have facilitated propagation of the cholesteatoma from the middle ear to the mastoid. Conclusion. If aural toilet is required in the implanted ear of a cochlear implant recipient, any complaint of hearing change, pain, or discharge should alert the clinician of the possibility of cholesteatoma developing. It warrants prompt evaluation by an experienced otologist in order to prevent accidental explantation. Keywords. Cochlear implant, cochlear implant complications, chronic suppurative otitis media, cholesteatoma, reimplantation, blind-sac, external auditory canal overclosure, mastoid cavity obliteration.
Diagnosis Test Meta-Analysis for Apolipoprotein E in Alzheimer’s Disease
Authors: Xiong Xuan , Xiao Hongtao , Zhang Yuan , Yu Dongke , Chuan Junlan , Zhong Lei , Yin Qinan , Tong Rongsheng
Published: October 2020

Objective. To evaluate the diagnostic value of apolipoprotein E (APOE) gene in Alzheimer’s disease (AD). Methods. Databases including PubMed, EMBASE, Google Scholar, Wanfang Med online, China National Knowledge Infrastructure (CNKI), and China Biomedical Literature Database (CBM) were searched for literatures in English or Chinese. No limitations on the date. The sensitivity, specificity, likelihood ratio, and diagnostic odds ratio were pooled for meta-analysis. The symmetric receiver operator characteristic curve (SROC) and Fagan’s Nomogram were drawn, and metaregression and subgroup analysis were used to explore the source of heterogeneity. Results. A total of 13 studies, including 2662 cases and 8843 controls, were analyzed. The combined sensitivity (SEN) was 0.62 (95% CI (0.58-0.66)), specificity (SPE) was 0.84 (95% CI (0.81-0.86)), the positive likelihood ratio was 3.8 (95% CI (3.3-4.3)), and the negative likelihood ratio was 0.45 (95% CI (0.41-0.49)). The area under the ROC curve was 0.80, and the diagnostic ratio (DOR) was 8. Neither publication bias was detected in Deeks’ funnel plot, nor threshold effect was shown in the SROC. Metaregression analysis showed that the diagnostic methods, experimental design, and sample size contributed to the heterogeneity in SEN, while the diagnostic methods, experimental design, blind evaluation on test results, and sample size contributed to the heterogeneity in SPE. When the pretest probability was set as 50%, the posterior probability in Fagan’s Nomogram was 79%, the positive likelihood ratio (LRP) was 5, and the negative likelihood ratio (LRN) was 0.42. Conclusions. AD could neither be confirmed nor excluded by the APOE genotype test. The sensitivity and specificity of the APOE gene test were relatively low in the diagnosis of AD. The diagnostic value of APOE ε4 gene in AD was moderate; it might play an important role in the prevention of AD.
The Model of PPARγ-Downregulated Signaling in Psoriasis
Authors: Sobolev Vladimir , Nesterova Anastasia , Soboleva Anna , Dvoriankova Evgenia , Piruzyan Anastas , Mildzikhova Dzerassa , Korsunskaya Irina , Svitich Oxana
Published: October 2020

Interactions of genes in intersecting signaling pathways, as well as environmental influences, are required for the development of psoriasis. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and transcription factor which inhibits the expression of many proinflammatory genes. We tested the hypothesis that low levels of PPARγ expression promote the development of psoriatic lesions. We combined experimental results and network functional analysis to reconstruct the model of PPARγ-downregulated signaling in psoriasis. We hypothesize that the expression of IL17, STAT3, FOXP3, and RORC and FOSL1 genes in psoriatic skin is correlated with the level of PPARγ expression, and they belong to the same signaling pathway that regulates the development of psoriasis lesion.
A Study of Impact Response and Its Numerical Study of Hybrid Polypropylene Fiber‐Reinforced Concrete with Different Sizes
Authors: Liang Ninghui , Yan Ru , Liu Xinrong , Yang Peng , Zhong Zuliang
Published: October 2020

Compressive properties of hybrid polypropylene fiber‐reinforced concrete (HPFRC) with different sizes of polypropylene fibers (PPFs) under the impact load (101∼102/s) were tested by using a 74 mm diameter various cross‐section split‐Hopkinson pressure bar (SHPB), in which the fiber content of fine PPFs was 0.9 kg/m3 and that of coarse PPFs was 6.0 kg/m3. The effect of strain rate and PPF hybridization on the impact characteristics of HPFRC was analyzed. It is found that dynamic compressive properties, including dynamic compressive strength, dynamic compressive strength increase factor (DCF), ultimate strain, and impact toughness, increased with the increase of strain rate. Meanwhile, both fine PPFs and coarse PPFs can enhance the impact strength of concrete, and an appropriate hybridization of two sizes of PPFs in concrete was more effective than the concrete reinforced with one size of PPF. Moreover, a modified constitutive model for HPFRC was proposed based on the Holmquist–Johnson–Cook (HJC) constitutive model. Then, the numerical study of SHPB tests for HPFRC was conducted based on the modified model, which showed that the modified HJC constitutive model could well describe the dynamic stress‐strain relationship of HPFRC.
The Effect of Different Thawing Rates on Cryopreserved Human Iliac Arteries Allograft’s Structural Damage and Mechanical Properties
Authors: Novotny Robert , Mericka Pavel , Chlupac Jaroslav , Matejka Roman , Kristek Jakub , Marada Tomas , Konarik Miroslav , Ivak Peter , Sterba Lubomir , Hlubocky Jaroslav , Pirk Jan , Janousek Libor , Fronek Jiri
Published: October 2020

Introduction. The rate of thawing of cryopreserved human iliac arteries allografts (CHIAA) directly affects the severeness of structural changes that occur during this process. Method. The experiment was performed on ten CHIAA. The 10% dimethylsulphoxide in 6% hydroxyethyl starch solution was used as the cryoprotectant; all CHIAA were cooled at a controlled rate and stored in the vapor phase of liquid nitrogen (‐194°C). Two thawing protocols were tested: (1) placing the CHIAA in a water bath at 37°C, and (2) the CHIAA were thawed in a controlled environment at 5°C. All samples underwent analysis under a scanning electron microscope. Testing of the mechanical properties of the CHIAA was evaluated on a custom‐built single axis strain testing machine. Longitudinal and circumferential samples were prepared from each tested CHIAA. Results. Ultrastructural analysis revealed that all five CHIAA thawed during the thawing protocol 1 which showed significantly more damage to the subendothelial structures when compared to the samples thawed in protocol 2. Mechanical properties: Thawing protocol 1—longitudinal UTS 2, 53 ± 0, 47 MPa at relative strain 1, 27 ± 0, 12 and circumferential UTS 1, 94 ± 0, 27 MPa at relative strain 1, 33 ± 0, 09. Thawing protocol 2—longitudinal ultimate tensile strain (UTS) 2, 42 ± 0, 34 MPa at relative strain 1, 32 ± 0, 09 and circumferential UTS 1, 98 ± 0, 26 MPa at relative strain 1, 29 ± 0, 07. Comparing UTS showed no statistical difference between thawing methods. Conclusion. Despite the significant differences in structural changes of presented thawing protocols, the ultimate tensile strain showed no statistical difference between thawing methods.
Inference for the Difference of Two Independent KS Sharpe Ratios under Lognormal Returns
Authors: Qi J. , Rekkas M. , Wong A.
Published: October 2020

A higher-order likelihood-based asymptotic method to obtain inference for the difference between two KS Sharpe ratios when gross returns of an investment are assumed to be lognormally distributed is proposed. Theoretically, our proposed method has

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distributional accuracy, whereas conventional methods for inference have

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distributional accuracy. Using an example, we show how discordant confidence interval results can be depending on the methodology used. We are able to demonstrate the accuracy of our proposed method through simulation studies.
Rh-CSF1 Attenuates Oxidative Stress and Neuronal Apoptosis via the CSF1R/PLCG2/PKA/UCP2 Signaling Pathway in a Rat Model of Neonatal HIE
Authors: Hu Xiao , Li Shirong , Doycheva Desislava Met , Huang Lei , Lenahan Cameron , Liu Rui , Huang Juan , Gao Ling , Tang Jiping , Zuo Gang , Zhang John H.
Published: October 2020

Oxidative stress (OS) and neuronal apoptosis are major pathological processes after hypoxic-ischemic encephalopathy (HIE). Colony stimulating factor 1 (CSF1), binding to CSF1 receptor (CSF1R), has been shown to reduce neuronal loss after hypoxic-ischemia- (HI-) induced brain injury. In the present study, we hypothesized that CSF1 could alleviate OS-induced neuronal degeneration and apoptosis through the CSF1R/PLCG2/PKA/UCP2 signaling pathway in a rat model of HI. A total of 127 ten-day old Sprague Dawley rat pups were used. HI was induced by right common carotid artery ligation with subsequent exposure to hypoxia for 2.5 h. Exogenous recombinant human CSF1 (rh-CSF1) was administered intranasally at 1 h and 24 h after HI. The CSF1R inhibitor, BLZ945, or phospholipase C-gamma 2 (PLCG2) inhibitor, U73122, was injected intraperitoneally at 1 h before HI induction. Brain infarct volume measurement, cliff avoidance test, righting reflex test, double immunofluorescence staining, western blot assessment, 8-OHdG and MitoSOX staining, Fluoro-Jade C staining, and TUNEL staining were used. Our results indicated that the expressions of endogenous CSF1, CSF1R, p-CSF1R, p-PLCG2, p-PKA, and uncoupling protein2 (UCP2) were increased after HI. CSF1 and CSF1R were expressed in neurons and astrocytes. Rh-CSF1 treatment significantly attenuated neurological deficits, infarct volume, OS, neuronal apoptosis, and degeneration at 48 h after HI. Moreover, activation of CSF1R by rh-CSF1 significantly increased the brain tissue expressions of p-PLCG2, p-PKA, UCP2, and Bcl2/Bax ratio, but reduced the expression of cleaved caspase-3. The neuroprotective effects of rh-CSF1 were abolished by BLZ945 or U73122. These results suggested that rh-CSF1 treatment attenuated OS-induced neuronal degeneration and apoptosis after HI, at least in part, through the CSF1R/PLCG2/PKA/UCP2 signaling pathway. Rh-CSF1 may serve as therapeutic strategy against brain damage in patients with HIE.
Ephrin‐A5 Is Involved in Retinal Neovascularization in a Mouse Model of Oxygen‐Induced Retinopathy
Authors: Du Wei , Huang Lvzhen , Tang Xin , Li Jiarui , Li Xiaoxin
Published: October 2020

Retinal neovascularization (RNV) is an important pathological feature of vitreoretinopathy that can lead to severe vision loss. The purpose of this study was to identify the role of ephrin‐A5 (Efna5) in RNV and to explore its mechanism. The expression pattern and biological significance of Efna5 were investigated in a mouse model of oxygen‐induced retinopathy (OIR). The expression of Efna5 and downstream signaling pathway members was determined by RT‐PCR, immunofluorescence, immunohistochemistry, and western blot analyses. shRNA was used to knockdown Efna5 in the retina of the OIR mouse model. Retinal flat mounts were performed to evaluate the impact of Efna5 silencing on the RNV process. We found that the Efna5 was greatly upregulated in the retina of OIR mice. Elevated Efna5 mainly colocalized with the retinal vessels and endothelial cells. We then showed that knockdown of Efna5 in OIR mouse retinas using lentivirus‐mediated shRNA markedly decreased the expression of Efna5 and reduced the retinal neovascularization and avascular retina area. We further showed hypoxia stimulation dramatically increased both total and phosphorylation levels of ERK1/2 and the phosphorylation levels of Akt in OIR mice. More importantly, knockdown of Efna5 could inhibit the p‐Akt and p‐ERK signaling pathways. Our results suggested that Efna5 may regulate the RNV. This study suggests that Efna5 was significantly upregulated in the retina of OIR mice and closely involved in the pathological retinal angiogenesis.
Association of VPREB1 Gene Copy Number Variation and Rheumatoid Arthritis Susceptibility
Authors: Aslam Muhammad Muaaz , John Peter , Fan Kang-Hsien , Bhatti Attya , Feingold Eleanor , Demirci F. Yesim , Kamboh M. Ilyas
Published: October 2020

Objective. Copy number variation (CNV) is a structural variation in the human genome that has been associated with multiple clinical phenotypes. B cells are important components of rheumatoid arthritis- (RA-) mediated immune response; hence, CNV in the regulators of B cells (such as VPREB1) can influence RA susceptibility. In this study, we aimed to explore the association of CNV in the VPREB1 gene with RA susceptibility in the Pakistani population. Methods. A total of 1,106 subjects (616 RA cases, 490 healthy controls) were selected from three rheumatology centers in Pakistan. VPREB1 CNV was determined using the TaqMan® CN assay (Hs02879734_cn, Applied Biosystems, Foster City, CA, USA), and CNV was estimated by using CopyCaller® (version 2.1; Applied Biosystems, USA) software. Odds ratio (OR) was calculated by logistic regression with sex and age as covariates in R. Results. A significant association between >2 VPREB1 CNV and RA risk was observed with an OR of 3.92 (95% CI: 1.27 - 12.12; p=0.01746) in the total sample. Whereas <2 CNV showed a significantly protective effect against RA risk in women with an OR of 0.48 (95% CI: 0.29-0.79; p=0.00381). Conclusion. CNV>2 of VPREB1 is a risk factor for RA in the total Pakistani population, while CNV<2 is protective in women.
Distant Metastases in Patients with Intrahepatic Cholangiocarcinoma: Does Location Matter? A Retrospective Analysis of 370 Patients
Authors: Hahn Felix , Müller Lukas , Mähringer-Kunz Aline , Tanyildizi Yasemin , Santos Daniel Pinto dos , Düber Christoph , Galle Peter R. , Weinmann Arndt , Kloeckner Roman
Published: October 2020

Background. Intrahepatic cholangiocarcinoma (ICC) is an aggressive tumor entity, and distant metastases are common. However, studies investigating patterns and clinical relevance of distant metastases are rare. Therefore, we aimed to analyze occurrence, location, and prognostic impact of distant metastases on overall survival (OS). Methods. Between 1997 and 2018, 417 patients with ICC were treated at our tertiary care center. Distant metastases and intrahepatic tumor burden were retrospectively evaluated in a longitudinal approach using volumetric assessment of cross-sectional imaging studies and all available medical/histopathological reports. Results. Finally, 370 patients with histopathologically confirmed ICC were included. Of these, 186 showed distant metastases, either initially (n = 59) or during follow-up (n = 127). The most common metastatic sites were the lung (n = 105), peritoneum (n = 81), and bone (n = 50). After detection of lung metastases, the residual median OS was 5.3 months; followed by peritoneal metastases, 4.5 months, and bone metastases, 4.4 months (P=0.17). At the time of first metastatic occurrence, residual OS according to intrahepatic tumor burden of <25%, 25–50%, and >50% was 6.5 months, 4.9 months, and 1.2 months, respectively (P<0.001). In multivariate hazard regression, hepatic tumor burden, liver function, and subsequent treatment were significant predictors of survival. Conclusions. During the disease course, every second patient developed extrahepatic metastases. While the presence of distant metastases was associated with poor patient outcomes, there was no significant difference between metastatic sites. However, hepatic tumor burden was the life-limiting risk factor in a majority of patients at the time of distant metastatic disease.
The Effects of Load Location on Dropper Stress in a Catenary System for a High-Speed Railway
Authors: He Fan , Guo Dandan
Published: October 2020

In this paper, the effects of load location on dropper stress are studied. We treat contact wire as a beam element and derive its response equation and then deduce the stress equation of dropper. A computer code based on MATLAB is written to calculate dropper stress using the finite difference method. The results show that there are three stages during the period of the stress changes of dropper, including instant rebound, damped sinusoidal vibration, and bending compression. The shorter the distance away from a load is, the larger the vertical displacement of the dropper is, which results in the corresponding increases of its stress amplitude and the maximum tensile stress. The load location has a significant impact on the stress changes of dropper. Compared to the condition of the load in the middle, the load acting on the edge of contact wire could induce the larger tensile stress when both ends of contact wire are considered as free boundaries. Therefore, it is necessary to add supports at both ends.