bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiation dose measurements in a dental orthopantogram unit using indigenously developed optically stimulated luminescence dosimeters
Authors: Kumar Pradip , Dutt Sharma Sunil , Chandola Rakesh Mohan , Mishra Devesh Ramdhar , Dhabekar Bhushan , Rawat Narender Singh , Kadam Sonal , Agrawal Sadhana
Published: April 2019

Dental orthopantogram (OPG)/cone beam computed tomography (CBCT) scanners are gaining popularity due to their 3D imaging with multiplanar view that provides clinical benefits over conventional dental radiography systems. Dental OPG/CBCT provides optimal visualization of adjacent overlaying anatomical structures that will be superpositioned in any single projection. The characteristics of indigenously developed optically stimulated luminescence dosimeters, namely, aluminium oxide doped with carbon (Al2O3:C), lithium magnesium phosphate doped with terbium and boron (LiMgPO4:Tb,B) and lithium calcium aluminium fluoride doped with europium and yttrium (LiCaAlF6:Eu,Y) were evaluated for their use in dental dosimetry. The dose−response of these dosimeters was studied at X‐ray energies 60 kV, 70 kV and 81 kV. Radiation doses were also measured using Gafchromic film for comparison. Radiation dose was measured at eight different locations of a polymethyl methacrylate (PMMA) head phantom including eyes. The optically stimulated luminescence (OSL) sensitivity of LiMgPO4:Tb,B is about 1.5 times and LiCaAlF6:Eu, is about 20 times higher than the sensitivity of Al2O3:C. It was found that measured radiation doses by the three optically stimulated luminescence dosimeters (OSLDs) and Gafchromic film in the occipital region (back side) of a PMMA phantom, were consistent but variations in dose at other locations were significantly higher. The three OSLDs used in this study were found to be suitable for radiation dose measurement in dental units.
Comparative analysis of the methods used for finding surface energy to investigate protein interaction behavior on chromatographic supports
Authors: Aasim Muhammad , Khan Muhammad H. , Rahman Inam U. , Bibi Noor Shad , Ali Waqar , Khan Nadir Z. , Khan Abid A.
Published: April 2019

Hydrophobic interaction chromatography, an important and effective purification strategy, is generally used for the purification of variety of biomolecules. A basic understanding of the protein interaction behavior is required to effectively separate these biomolecules. A colloidal type extended Derjaguin, Landau, Verwey, and Overbeek calculations were utilized to study the interactions behavior of model proteins to commercially available hydrophobic chromatographic materials that is, Toyopearl Phenyl 650C and Toyopearl Butyl 650C. Physicochemical properties of selected model proteins were achieved by contact angle and zeta potential measurements. The contact angle of chromatographic materials used was achieved through sessile drop method on disrupted beads and capillary penetration method (CPM) on intact beads. The surface properties were further used to calculate the interactions of the proteins to chromatographic supports. The calculated secondary energy minimum of the proteins with the chromatographic materials (from the contact angle values determined through both methods can be correlated with the retention volumes from the real chromatography. The secondary energy minimum values are higher for each protein to the chromatographic materials calculated from the inputs derived through sessile drop method compared to CPM. For instance, immunoglobulin G has secondary energy minimum value of 0.17 kT compared to 0.11 kT, obtained through sessile drop method and CPM, respectively. Average relative values of the energy minimum calculated for all proteins are as 1.51 kT and 1.29 kT for Toyopearl Butyl 650C and Toyopearl Phenyl 650C, respectively, as a conversion factor for estimation of secondary energy minimum for both methods.
Targeted silencing of MYCL1 by RNA interference inhibits migration and invasion of MGC‐803 gastric cancer cells
Authors: Qin Pan , Wang Haiyan , Zhang Feng , Huang Yanmei , Chen Shuqin
Published: April 2019

MYCL1 protein expression encoded by a proto‐oncogene MYCL1, a member of the MYC family, is correlated with poor prognosis in gastric cancer patients. Nevertheless, the role of MYCL1 in gastric cancer cells remains unknown. In this study, the expression levels of MYCL1 mRNA and protein were downregulated by lentiviral‐mediated RNA interference (RNAi) in the MGC‐803 gastric cancer cell line. Then, the influence of MYCL1 on the biological behaviour of gastric cancer cells was investigated. Finally, a stable animal model of the MGC‐803 human gastric cancer tumour model in nude mice was made successfully. Functionally, silencing of MYCL1 inhibited migration and invasion of the MGC‐803 line in vitro and was accompanied with some ultrastructural changes. These results provide some evidences that lentiviral‐mediated MYCL1 silencing may be a novel therapeutic strategy for the treatment of gastric cancer.

Significance of the study

Gastric cancer is one of the most common malignant tumours worldwide and the second leading cause of cancer‐related death in China. Our previous study revealed that expression of MYCL1 in gastric cancer tissue was associated with poor prognosis of patients. However, the potential underlying mechanism is still unclear. In the current study, we displayed the influence of MYCL1 gene on invasion and migration phenotype of gastric cancer cells and provided a possible explanation from the aspect of structural alteration. Our results suggested that downregulation of MYCL1 may be a potential therapeutic strategy for gastric cancer.
Safety gaps in medical team communication: Results of quality improvement efforts in a cardiac catheterization laboratory
Authors: Doorey Andrew J. , Turi Zoltan G. , Lazzara Elizabeth H. , Mendoza Erika G. , Garratt Kirk N. , Weintraub William S.
Published: April 2019

Objectives

To assess closed‐loop communications (readback), a fundamental aspect of effective communication, among cardiovascular teams and assess improvement efforts.

Background

Effective communication within teams is essential to assure safety and optimal outcomes. Readback of verbal physician orders is a hospital and national requirement.

Methods

Single‐center observational study, where the readback responses to physician verbal orders in the catheterization laboratory were characterized over three distinct time intervals from 2015 to 2017. Performance feedback and focused education on the value of readbacks was provided to the teams in two waves, with subsequent remeasurement. Responses to verbal orders were characterized as complete (all important parameters of the order repeated for verification), partial, acknowledgement only, or no response. Changes in readback performance after quality interventions were assessed.

Results

During the first‐observational period of 101 cases, complete readback occurred in 195 of 515 (38%) medication orders and 136 of 235 (58%) equipment orders. After initial quality improvement efforts, 102 cases were observed. In these, 298 of 480 (62%) medication orders had complete readback, and 210 of 420 (50%) equipment orders had complete readback. After additional quality improvement efforts, 168 cases were observed. In these, 506 of 723 (70%) medication orders had complete readback, and 630 of 1,061 (59%) equipment orders had complete readback. Overall, medication order readback improved over time (correlation = 0.26 [−0.30, −0.21]; p < 0.001), but equipment order readback did not (correlation = 0.02 [−0.07, 0.03]; p = 0.44).

Conclusions

Closed‐loop communication of physician verbal orders was used infrequently in this medical team setting and proved difficult to fully improve. This is an important safety gap.
Chronic total occlusions—Is true lumen wire passage preferred to subintimal dissection re‐entry?
Authors: Feldman Marc D. , Michalek Joel
Published: April 2019

Key Points

True lumen crossing is superior to subintimal crossing.

Subintimal versus true lumen crossing may only be apparent if IVUS is performed.

Newer techniques for true lumen crossing need to be developed.
Trifluoromethylation and Monofluoroalkenylation of Alkenes through Radical–Radical Cross‐Coupling
Authors: Wang Qiang , Qu Yi , Tian Hao , Liu Yuxiu , Song Hongjian , Wang Qingmin
Published: April 2019

The first visible‐light‐induced trifluoromethylation and monofluoroalkenylation of simple alkenes via a challenging radical–radical cross‐coupling step was achieved. This method provided a mild, step‐economical and redox‐neutral route to privileged two different fluorinated difunctionalized allyl compounds. The utility of this method is illustrated by late‐stage modification of medically important molecules.
Trace Metals Accumulation and Antioxidants Profiling in Two Maize Genotypes Against Sewage and Textile Wastewater Treatment
Authors: Zafar Zoya , Akhtar Javaid , Amjad Muhammad , Anwar‐ul‐Haq Muhammad , Saqib Zulfiqar Ahmed
Published: April 2019

Shortage of freshwater resources compels farmers to use sewage and textile effluents for irrigation, leading to accumulation of trace metals (Cr, Cu, Pb, Cd, Ni) to toxic levels and affecting plant growth and harming animals and humans. An experiment is conducted using raw (1:0) textile (TEX) and sewage (SWG) effluents and their dilution (1:1 and 1:3) by tap water (TAP) to assess the physiological changes against the trace metals accumulation in maize genotypes (999 and 984). Dilution of TEX and SWG effluents causes an increase in the uptake of trace metals in both genotypes, thereby decreasing metals accumulation in soil. Application of raw TEX and SWG effluents enhances lipid peroxidation (malondialdehyde, MDA) concentration and decreases by increasing dilution. The activities of antioxidants enzymes (superoxide dismutase, SOD; catalase, CAT; ascorbate peroxidase, APX; total antioxidants activity) are significantly higher in raw (1:0) treatment of TEX and SWG effluents compared to TAP treatment and decrease by increasing dilution. The activity of glutathione reductase (GR) increases by increasing dilution of effluents. The maize genotype “984” shows significantly higher values of measured antioxidant enzymes and lower MDA compared to “999.” The differential accumulation of trace metals in maize genotypes shows varied activities of the antioxidant enzymes responsible for their differences in growth and adaptability against trace metals toxicity. The plants' genotype tolerance against trace metals toxicity and effluents dilution is an effective measure to avoid entry of these metals into food chain.
Workflow scheduling using Jaya algorithm in cloud
Authors: Gupta Swati , Agarwal Isha , Singh Ravi Shankar
Published: April 2019

Cloud computing is an on‐demand service that can be accessed by a user according to his requirements through the Internet. Multiple users can request any amount of services, so scheduling of those services is a crucial task in cloud computing. Scheduling is a way of assigning the work to a computer resource. We have multiple tasks at a time that are waiting to be allotted to multiple computer resources. Various optimization algorithms have been used to do task scheduling so that total execution cost is minimized. In this paper, we have implemented Jaya optimization algorithm for workflow scheduling and have compared it with four nature‐inspired algorithms, namely, particle swarm optimization (PSO), genetic algorithm (GA), ant colony optimization (ACO), honey bee, and cat swarm optimization (CSO), keeping the fitness function same for all of them using CloudSim. Previously, work has been done on PSO, GA, ACO, honey bee, and CSO using different criteria. The results are compared on the basis of execution cost and makespan of the algorithm on both an independent set of tasks and a set of tasks that follow a workflow schedule. Benchmark functions such as Montage, CyberShake, Inspiral, and Sipht are used for workflow scheduling. It has been observed that Jaya outperforms the other algorithms as it produces similar results in the least amount of time as it converges very quickly.
Small Structural Changes in the Alkyl Substituents of Macrocyclic π‐Extended Thiophene Oligomers Causes a Key Effect on Their Stacking and Functional Properties
Authors: Fujiwara Toshihiro , Takashika Masataka , Hasegawa Masashi , Ie Yutaka , Aso Yoshio , Aoyagi Shinobu , Otani Hiroyuki , Iyoda Masahiko
Published: April 2019

Three new macrocyclic π‐extended thiophene hexamers composed of four thienylene‐ethynylene and two thienylene‐vinylene units with or without four alkyl substituents have been synthesized. Despite similar shape‐persistent structures in solution, the alkyl substituents control the solid‐state structures and morphologies. The unsubstituted hexamer exhibited a planar conformation with a theoretically predicted structure in the solid state; however, the planar hexamer with four ethyl substituents formed a closely stacked columnar crystal structure to exhibit π‐π interactions. Interestingly, the hexamer with four butyl substituents adopted both planar and twisted conformations in the solid state, exhibiting polymorphism based on induced‐fit stacking of molecules. Thus, the butyl‐substituted hexamer produces a mixture of yellow, orange, and red single crystals from toluene/acetone, and X‐ray analysis revealed six different conformations. Consequently, the small structural difference in the macrocycles causes a key effect on their functional properties in the solid state, and their morphology governs electrical conductivity and organic field‐effect‐transistor activity. The polymorphism of the hexamers was applied to the switching of film morphology.
Bit error probability of the M‐QAM scheme under η‐μ fading and impulsive noise in a communication system using spatial diversity
Authors: Silva Hugerles S. , Alencar Marcelo S. , Queiroz Wamberto J. L. , Almeida Danilo B. T. , Madeiro Francisco
Published: April 2019

This paper presents a new and exact expression for the bit error probability (BEP) of the square M‐ary quadrature amplitude modulation (M‐QAM) scheme, with the channel under double gated additive white Gaussian noise (G2AWGN) and η‐μ fading in a communication system using the spatial diversity technique. The expression for the BEP is written in terms of the Appell function. The BEP curves are presented under different values of the number of branches of the maximum ratio combining (MRC) receiver, order of the constellation M, and parameters that characterize mathematically the channel, corroborated by simulations performed with Monte Carlo method.
Chemical defense of toad tadpoles under risk by four predator species
Authors: Üveges Bálint , Szederkényi Márk , Mahr Katharina , Móricz Ágnes M. , Krüzselyi Dániel , Bókony Veronika , Hoi Herbert , Hettyey Attila
Published: April 2019

Many organisms use inducible defenses as protection against predators. In animals, inducible defenses may manifest as changes in behavior, morphology, physiology, or life history, and prey species can adjust their defensive responses based on the dangerousness of predators. Analogously, prey may also change the composition and quantity of defensive chemicals when they coexist with different predators, but such predator‐induced plasticity in chemical defenses remains elusive in vertebrates. In this study, we investigated whether tadpoles of the common toad (Bufo bufo) adjust their chemical defenses to predation risk in general and specifically to the presence of different predator species; furthermore, we assessed the adaptive value of the induced defense. We reared tadpoles in the presence or absence of one of four caged predator species in a mesocosm experiment, analyzed the composition and quantity of their bufadienolide toxins, and exposed them to free‐ranging predators. We found that toad tadpoles did not respond to predation risk by upregulating their bufadienolide synthesis. Fishes and newts consumed only a small percentage of toad tadpoles, suggesting that bufadienolides provided protection against vertebrate predators, irrespective of the rearing environment. Backswimmers consumed toad tadpoles regardless of treatment. Dragonfly larvae were the most voracious predators and consumed more predator‐naïve toad tadpoles than tadpoles raised in the presence of dragonfly cues. These results suggest that tadpoles in our experiment had high enough toxin levels for an effective defense against vertebrate predators even in the absence of predator cues. The lack of predator‐induced phenotypic plasticity in bufadienolide synthesis may be due to local adaptation for constantly high chemical defense against fishes in the study population and/or due to the high density of conspecifics.
Learned helplessness reveals a population at risk for depressive‐like behaviour after myocardial infarction in mice
Authors: Bruns Bastian , Schmitz Thomas , Diemert Nathalie , Schwale Chrysovalandis , Werhahn Stefanie Maria , Weyrauther Friederike , Gass Peter , Vogt Miriam Annika , Katus Hugo , Herzog Wolfgang , Backs Johannes , Schultz Jobst‐Hendrik
Published: April 2019

Aims

Myocardial infarction (MI) and heart failure (HF) are risk factors for the development of depression, additionally worsening the quality of life and patient outcome. How HF causes depression and how depression promotes HF remain mechanistically unclear, which is at least partly caused by the difficulty of in vivo modelling of psychosomatic co‐morbidity. We aimed to study the potential sequence of events with respect to different depression aspects upon HF.

Methods and results

Male C57BL6 mice underwent MI, followed by behavioural and echocardiographic characterization. Motility, exploration, and anxiety‐like behaviour were unaffected in mice after MI. We did not observe increased depressive‐like behaviour in the sucrose preference, tail suspension, or Porsolt forced swim test. Mice did not display signs of learned helplessness (LH) when compared to sham. Accordingly, cluster analysis revealed only a slightly higher quota of LH in HF (38%) vs. sham mice (32%). But strikingly, three‐group cluster analysis revealed an additional intermediate subpopulation at risk for LH after HF (29%). Interestingly, this population featured elevated cardiac expression of nr4a1.

Conclusions

The LH paradigm uncovered a subtle predisposition to depressive‐like behaviour after MI, whereas testing for anhedonia and despair was insufficient to show a behavioural shift in mice. Therefore, we suggest an accumulating risk profile and a multiple‐hits hypothesis regarding the pathogenesis of co‐morbid depression after MI. Symptoms of LH may present a marker of subclinical depression after MI, the impact of which remains to be investigated. The proposed sequence of behavioural testing enables the mechanistic dissection of cardio‐psychogenic signalling in the future.
Synthesis and Characterization of Ag‐Delafossites AgBO2 (B: Al, Ga, In) from a Rapid Hydrothermal Process
Authors: Zwiener Leon , Jones Travis , Wolf Elisabeth Hannah , Girgsdies Frank , Plodinec Milivoj , Klyushin Alexander Yu. , Willinger Elena , Rosowski Frank , Schlögl Robert , Frei Elias
Published: April 2019

Invited for the cover of this issue are Dr. Elias Frei and co‐workers from the Inorganic Chemistry Department of the Fritz‐Haber‐Institute of the Max‐Planck‐Gesellschaft, Berlin, and Dr. Frank Rosowski from BasCat/BASF, Ludwigshafen, Germany. The cover image shows three different hourglasses underlining the importance of the reaction time for the hydrothermal preparation of the metastable delafossites AgBO2 (B: Al, Ga, In).
Garlic Supplementation Modified Enzymatic Omega‐6 Polyunsaturated Fatty Acid Oxidation in Mild Hypercholesterolemia
Authors: Leung Ho Hang , Yau Yu Fung , Leung Kin Sum , Lee Yiu Yiu , Oger Camille , Durand Thierry , Galano Jean‐Marie , Loke Wai Mun , Lee Jetty Chung‐Yung
Published: April 2019

Dietary garlic has been shown to alleviate hypercholesterolemia, a condition associated with the development of cardiovascular disease. Reactive oxygen species take part in the disease progression, but it is unknown if antioxidant rich garlic arrests lipid and cholesterol oxidation in hypercholesterolemia. This study provides fermented garlic or non‐fermented garlic to mild hypercholesterolemia (total cholesterol: 5.2–6.2 mmol L−1) and determines its ability to relieve in vivo oxidative stress by measuring multiple oxidized lipid products of polyunsaturated fatty acid (PUFA) and cholesterol oxidation products (COPs) in plasma. Plasma fatty acids levels are also analyzed. After 13 weeks supplementation, both groups show a significant increase in α‐linolenic acid level (p < 0.05). Levels of arachidic acid increase and palmitoleic acid decreases in the group supplemented with non‐fermented garlic. Of the oxidized PUFA products, notably those derived from enzymatic oxidation of arachidonic acid, namely hydroxyeicosatetraenoic acid (HETE), show a significant difference. Levels of lipoxygenase mediate 5‐HETE and 12‐HETE, and CYP‐P450 mediates 9‐HETE and 11‐HETE decreases after non‐fermented garlic supplementation only (p < 0.05). Non‐enzymatic PUFA oxidation and COPs are not altered by garlic supplementation. Overall, only non‐fermented garlic intake shows selective antioxidant properties in mild hypercholesterolemia where limited effect is found in reducing lipid oxidation.

Practical Applications: Current research provides a new insight for the use of garlic extract as a nutraceutical to reduce in vivo oxidative stress. The modified enzymatic oxidation of arachidonic acid in mild hypercholesterolemia after non‐fermented garlic extract intake potentially preventes the progression of chronic inflammation that can lead to complicated pathologies such as arthritis, cardiovascular diseases, and non‐alcoholic fatty liver disease.

Garlic is a claimed functional food. The fermented form is proposed to have stronger antioxidant properties. Analysis of mild hypercholesterolemia plasma before and after fermented or non‐fermented garlic extract intake for 13 weeks revealed augmented α‐linolenic acid. Garlic appeared to be selective in the antioxidant property. Pro‐inflammatory lipid mediators (5‐, 9‐, 11‐, and 12‐HETE) released via enzymatic polyunsaturated fatty acid (PUFA) oxidation reduced after non‐fermented garlic extract intake only. However, intake of both garlic types did not reduce non‐enzymatic PUFA oxidation status.
Computationally efficient nonstationary nearest‐neighbor Gaussian process models using data‐driven techniques
Authors: Konomi B. A. , Hanandeh A. A. , Ma P. , Kang E. L.
Published: April 2019

Due to the increased availability of measurements of various geophysical processes, a need has arisen for statistical methods suitable for the analysis of very large nonstationary spatial data sets. The nearest‐neighbor Gaussian process (NNGP) models are one of the latest and most popular Gaussian process‐based models, which reduce computational complexity and memory storage. The Bayesian inference is based on the assumption of a parametric covariance function that is often assumed stationary or known. Given that NNGP models are sensitive in the stationary assumption in comparison to other reduction methods, there is a need to build nonstationary covariance functions within the NNGP models. However, the construction of a nonstationary covariance function and/or matrix may be computationally expensive by itself in the presence of big data. In this paper, we develop an efficient two‐stage approach that deals with nonstationarity and the computational complexity in the presence of a big spatial data set. We propose a new low‐cost data‐driven tree‐structured partitioning technique to divide the spatial region into distinct subregions. Given the partitions, we construct computationally efficient nonstationary covariance functions for NNGP models. We demonstrate the performance of our approach through simulation experiments and an application to the global Total Ozone Matrix Spectrometer (TOMS) data set, in which the proposed approach performs well in terms of both prediction accuracy and computational complexity.
Determinants of self‐ and carer‐rated quality of life and caregiver burden in Alzheimer disease
Authors: Schumann Christin , Alexopoulos Panagiotis , Perneczky Robert
Published: April 2019

Objective

We aimed to investigate factors associated with self‐ and carer‐rated quality of life (QoL) and caregiver burden related to very mild to severe clinical Alzheimer disease (AD).

Methods

One hundred patient‐carer dyads were recruited, and assessments of relevant outcomes were performed, including sociodemographic characteristics, QoL, activities of daily living (ADL), cognitive performance, behavioural and psychological symptoms of dementia (BPSD), caregiver burden, and health resource utilisation.

Results

There was a strong correlation between carer‐ and self‐rated QoL, with patients consistently rating their QoL higher than caregivers. Duration of illness did not affect the QoL ratings. There was an inverse association between both self‐ and carer‐rated QoL with age, age at symptom onset, impairment of ADL, time spent on assisting the patient, and depression. Both self‐ and carer‐rated QoL ratings were higher if the caregiver was a spouse vs a child. Carer‐rated QoL was inversely associated with severity of dementia, BPSD, caregiver burden, and requirement to supervise the patient. The variables age at symptom onset, ADL, and living together with the primary caregiver explained 34.50% of the variance in self‐rated QoL, whereas age at symptom onset, ADL, and BPSD explained 48.20% of the variance in carer‐rated QoL. For caregiver burden, 26% of the variance was explained by the variables ADL, living together with the primary caregiver, and agitation.

Conclusion

Our study highlights the need for a stronger focus on QoL in clinical AD research by providing further pieces of evidence on the key determinants, including the important aspect of caregiver burden.
Recategorization of tumor stage in patients with node‐negative oral tongue cancer: Impact of the eighth edition American Joint Committee staging system
Authors: Dang Rushil R. , Qureshi Muhammad M. , Caldroney Steven J. , Salama Andrew R. , Truong Minh Tam
Published: April 2019

Background

To evaluate recategorization of pT1‐3N0 oral tongue cancer, from seventh to eighth editions of the American Joint Committee on Cancer (AJCC) staging classification, and impact on overall survival (OS).

Methods

Using the National Cancer Database, 1277 patients were categorized using tumor size and depth of invasion with seventh and eighth AJCC staging systems and evaluated for OS.

Results

Tumor‐category was unchanged in 82.9% and upstaged in 17.1% patients with eighth AJCC. The 3‐year OS was 85.3%, 76.6%, and 77.0% with seventh AJCC compared to 87.1%, 75.1%, and 81% with eighth AJCC, for patients with pT1N0, pT2N0, and pT3N0 disease, respectively. Improved discrimination of pT1N0 vs pT2N0 for OS on multivariate analysis was seen for eighth AJCC (hazard ratio [HR] = 1.43, 95% confidence interval [CI]: 1.03‐1.98, P = .03) but not for patients with pT3N0, with seventh AJCC (HR = 1.02, 95% CI:0.53‐1.98, P = .95), and eighth AJCC (HR = 0.86, 95% CI: 0.52‐1.42, P = .55).

Conclusion

Eighth edition AJCC staging leads to improved discrimination of OS between pT1N0 and pT2N0 but not for patients with pT3N0.
Genetic variants of genes in the NER pathway associated with risk of breast cancer: A large‐scale analysis of 14 published GWAS datasets in the DRIVE study
Authors: Ge Jie , Liu Hongliang , Qian Danwen , Wang Xiaomeng , Moorman Patricia G. , Luo Sheng , Hwang Shelley , Wei Qingyi
Published: April 2019

A recent hypothesis‐free pathway‐level analysis of genome‐wide association study (GWAS) datasets suggested that the overall genetic variation measured by single nucleotide polymorphisms (SNPs) in the nucleotide excision repair (NER) pathway genes was associated with breast cancer (BC) risk, but no detailed SNP information was provided. To substantiate this finding, we performed a larger meta‐analysis of 14 previously published GWAS datasets in the Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) study with 53,107 subjects of European descent. Using a hypothesis‐driven approach, we selected 138 candidate genes from the NER pathway using the “Molecular Signatures Database (MsigDB)” and “PathCards”. All SNPs were imputed using IMPUTE2 with the 1000 Genomes Project Phase 3. Logistic regression was used to estimate BC risk, and pooled ORs for each SNP were obtained from the meta‐analysis using the false discovery rate for multiple test correction. RegulomeDB, HaploReg, SNPinfo and expression quantitative trait loci (eQTL) analysis were used to assess the SNP functionality. We identified four independent SNPs associated with BC risk, BIVM‐ERCC5 rs1323697_C (OR = 1.06, 95% CI = 1.03–1.10), GTF2H4 rs1264308_T (OR = 0.93, 95% CI = 0.89–0.97), COPS2 rs141308737_C deletion (OR = 1.06, 95% CI = 1.03–1.09) and ELL rs1469412_C (OR = 0.93, 95% CI = 0.90–0.96). Their combined genetic score was also associated with BC risk (OR = 1.12, 95% CI = 1.08–1.16, ptrend < 0.0001). The eQTL analysis revealed that BIVM‐ERCC5 rs1323697 C and ELL rs1469412 C alleles were correlated with increased mRNA expression levels of their genes in 373 lymphoblastoid cell lines (p = 0.022 and 2.67 × 10−22, respectively). These SNPs might have roles in the BC etiology, likely through modulating their corresponding gene expression.
Enhanced phosphorylation of AMPK by lutein and oxidised lutein that lead to mitochondrial biogenesis in hyperglycemic HepG2 cells
Authors: Nanjaiah Hemalatha , Vallikannan Baskaran
Published: April 2019

The stimulation of adenosine monophosphate‐activated protein kinase (AMPK) is a prime target to decrease the hyperglycemic condition, hence it is a lutein (L) and oxidised lutein (OXL) is a target molecule for the treatment of type II diabetes. In the current study, a plausible interaction of L and OXL with AMPK was investigated by molecular docking. In addition, the effect of L and OXL for the activation of AMPK that triggers the downstream regulator peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α), TFAM expression, mitochondrial DNA (mtDNA), mitochondrial biogenesis and superoxide dismutase 2 (SOD2) in high glucose treated HepG2 cells were investigated by quantitative polymerase chain reaction and Western blot analysis. Molecular docking reveals higher binding affinity of L (ΔG = −6.3 kcal/mol) and OXL (ΔG = −15.5 kcal/mol) with AMPK, compared with metformin (ΔG = −5.0 kcal/mol). The phosphorylation of AMPK increased by 1.3‐ and 1.5‐fold with L and OXL treatment, respectively, in high glucose induced HepG2 cells. The activation of PGC‐1α is significant (P < 0.05) in OXL group than L. Similarly, TFAM expression is increased with L and OXL compared with the high glucose group. Further increase in SOD2 and mtDNA, confirms the efficacy of L and OXL in restoring the mitochondrial biogenesis in high glucose induced cells through AMPK, PGC‐1α, and TFAM.
EphA8 acts as an oncogene and contributes to poor prognosis in gastric cancer via regulation of ADAM10
Authors: Wang Yingjing , Zhou Nan , Li Peng , Wu Han , Wang Qingqing , Gao Xiaodong , Wang Xudong , Huang Jianfei
Published: April 2019

EphA8 is a member of the erythropoietin‐producing hepatocellular receptor (Eph) family of receptor tyrosine kinases. Ephs and their ephrins ligands play crucial roles in many cellular processed by mediating intracellular signaling resulting from cell–cell interactions. But the underlying mechanisms of EphA8 in gastric cancer (GC) remains unclearly. 298 clinical specimens in tissues microarray, and was found to be significantly higher in GC tissues compared with nontumor tissues (p < 0.001). EphA8 expression was also strongly associated with differentiation level (p = 0.025), tumor‐node‐metastasis stage (p = 0.019), and poor 5 years survival (p < 0.001). A panel of GC cell lines showed reduced proliferation, invasion, and migration capacities after RNA‐mediated knockdown of EphA8, concomitant with downregulation of the proliferation‐related proteins (cyclin A, cyclin D1, and cyclin‐dependent kinase 4) and the metastasis‐related (matrix metalloproteinases MMP2, and MMP9). EphA8 knockdown also decreased expression of the protease ADAM10 (a disintegrin and metalloproteinase domain‐containing protein 10) and ADAM10‐related protein AKT, suggesting an interaction between EphA8 and ADAM10. In conclusion, we found that EphA8, which is highly expressed in GC tissues, stimulates proliferation, invasion, and migration of cancer cells, and is an independent risk factor for poor prognosis of GC. These dates suggest that EphA8 could be new diagnostic and/or therapeutic targets for GC.
Sclerostin inhibits odontogenic differentiation of human pulp‐derived odontoblast‐like cells under mechanical stress
Authors: Liao Chufang , Ou Yanjing , Wu Yun , Zhou Yi , Liang Shanshan , Wang Yining
Published: April 2019

Sclerotic dentin is a natural self‐protective barrier beneath non‐carious cervical lesions (NCCLs), which are mainly induced by mechanical stress. Sclerostin is a mechanosensory protein and serves as an inhibitor of dentinogenesis. However, its function on mechanotransduction in dentine–pulp complex has not been elucidated yet. In this study, decreased sclerostin expression was detected in odontoblasts beneath NCCL‐affected sclerotic dentin. Then human pulp‐derived odontoblast‐like cells (hOBs) were subjected to mechanical strain (MS) in vitro: the results showed that MS‐induced upregulation of odontogenic differentiation markers (dentin sialophosphoprotein, osteopontin, osteocalcin, and runt‐related transcription factor 2) in hOBs with downregulated sclerostin expression, and this inductive differentiation was attenuated when sclerostin was overexpressed. Additionally, MS activated ERK1/2 pathway and ERK1/2 inhibition restored MS‐induced downregulation of sclerostin. Proteasome inhibitor MG132 could also rescue MS‐induced decrease of sclerostin. Furthermore, MS suppressed STAT3 pathway, which could be reversed by sclerostin overexpression. STAT3 inhibition was shown to ameliorate the reduction of odontogenic markers induced by sclerostin overexpression. Taken together, we conclude that MS downregulates sclerostin expression via the ERK1/2 and proteasome signaling pathways to promote odontogenic differentiation of hOBs through the STAT3 signaling pathway. It can therefore be inferred that under mechanical stress, sclerostin inhibition promotes reactive dentin formation by enhancing odontogenic differentiation of odontoblasts, which might be one of potential forming mechanisms of sclerotic dentin beneath NCCLs.
GRP94 promotes muscle differentiation by inhibiting the PI3K/AKT/mTOR signaling pathway
Authors: Li Shuang , Fu Yuying , Pang Yusheng , Tong Huili , Li Shufeng , Yan Yunqin
Published: April 2019

The glucose‐regulated endoplasmic reticulum chaperone protein 94 (GRP94) is required for many biological processes, such as secretion of immune factors and mesoderm induction. Here, we demonstrated that GRP94 promotes muscle differentiation in vitro and in vivo. Moreover, GRP94 inhibited the PI3K/AKT/mTOR signaling pathway. Using both in vitro and in vivo approaches, in myoblasts, we found that this inhibition resulted in reduced proliferation and increased differentiation. To further investigate the mechanism of GRP94‐induced muscle differentiation, we used co‐immunoprecipitation and proximity ligation assays and found that GRP94 interacted with PI3K‐interacting protein 1 (Pik3ip1). The latter protein promoted muscle differentiation by inhibiting the PI3K/AKT/mTOR pathway. Furthermore, GRP94 was found to regulate Pik3ip1 expression. Finally, when Pik3ip1 expression was inhibited, GRP94‐induced promotion of muscle differentiation was diminished. Taken together, our data demonstrated that GRP94 promoted muscle differentiation, mediated by Pik3ip1‐dependent inhibition of the PI3K/AKT/mTOR signaling pathway.
The role of inflammation and its related microRNAs in breast cancer: A narrative review
Authors: Bahiraee Alireza , Ebrahimi Reyhane , Halabian Raheleh , Aghabozorgi Amirsaeed Sabeti , Amani Jafar
Published: April 2019

Breast cancer is recognized as the most common type of cancer among women with a high rate of mortality all over the world. Over the past years, growing attention has been regarded to realize more about the mechanisms underlying the disease process. It is revealed that the progression of breast cancer may be strongly linked to chronic inflammation owing to the role of inflammatory factors in genetic instability and subsequent cancer predisposition. Although the association between breast cancer and inflammatory pathways has been well‐defined now, only recent evidence pointed towards the inflammation‐related microRNAs (miRNAs) as potential biomarkers and therapeutic targets involved in the crosstalk of multiple pathways during breast cancer development. Moreover, the practical interactions between these miRNAs and inflammatory factors are also a little characterized. In this review, we intended to describe the effects of predominant inflammatory pathways such as cytokines, phosphoinositide 3‐kinase/protein kinase B, and nuclear factor kappa B in association with tumor promoting and tumor suppressing miRNAs on breast cancer progression. Providing new studies in the field of combining biomarkers for early diagnosis, prognosis, and monitoring breast cancer are very important. Notably, understanding the underlying mechanisms of miRNAs as a possible link between inflammation and tumorigenesis may offer a novel insight for combating this epidemic.
Retracted: Long noncoding RNA CHRF exacerbates IL‐6‐induced inflammatory damages by downregulating microRNA‐146a in ATDC5 cells
Authors: Yu Chuandong , Shi Donglei , Li Zhilin , Wan Guang , Shi Xuefeng
Published: April 2019

Osteoarthritis (OA) is a frequent chronic musculoskeletal disorder which lacks applicably effective therapeutic strategy. In this study, we attempted to investigate whether long noncoding RNA (lncRNA) cardiac hypertrophy‐related factor (CHRF) participated in mediating interleukin‐6 (IL‐6)‐induced in vitro inflammatory damages as well as the regulatory mechanisms. ATDC5 cells were stimulated with IL‐6, and then cellular damages were evaluated on the basis of cell viability by CCK‐8, apoptotic cells by observation with flow cytometry, apoptosis‐associated proteins by western blot analysis, and accumulation of inflammatory factors by quantitative reverse transcription polymerase chain reaction (RT‐qPCR), enzyme‐linked immunosorbent assay (ELISA), and western blot analysis. Then, effects of lncRNA CHRF on IL‐6‐treated cells were evaluated. We further explored the downstream factor of lncRNA CHRF and demonstrated whether lncRNA CHRF functioned through the downstream factor. Afterwards, crucial signaling cascades were anatomized. We found that IL‐6 reduced cell viability, elevated apoptosis, induced upregulation of inflammatory factors, as well as upregulated lncRNA CHRF and down‐regulated miR‐146a expression. Then, we found lncRNA CHRF overexpression aggravated IL‐6‐induced alterations, and lncRNA CHRF knockdown showed the opposite effects. Furthermore, miR‐146a was identified to be negatively regulated by lncRNA CHRF, and its overexpression abrogated the roles of lncRNA CHRF in IL‐6‐treated cells. IL‐6‐induced the accumulation of IκBα, p65, JAK1, and STAT3 at phosphorylated level was further facilitated by lncRNA CHRF whereas repressed by miR‐146a. In conclusion, lncRNA CHRF aggravated the IL‐6‐induced inflammatory damages in ATDC5 cells. We further outlined a possible mechanism that through downregulating miR‐146a, lncRNA CHRF evoked the activation of NF‐κB and JAK1/STAT3 signaling cascades.
n‐3 Docosapentaenoic Acid Intake and Relationship with Plasma Long‐Chain n‐3 Fatty Acid Concentrations in the United States: NHANES 2003–2014
Authors: Richter Chesney K. , Bisselou Karl Stessy , Nordgren Tara M. , Smith Lynette , Appiah Adams Kusi , Hein Nicholas , Anderson‐Berry Ann , Kris‐Etherton Penny , Hanson Corrine , Skulas‐Ray Ann C.
Published: April 2019

The long‐chain n‐3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play a crucial role in health, but previous National Health and Nutrition Examination Survey (NHANES) analyses have shown that EPA and DHA intake in the United States is far below recommendations (~250–500 mg/day EPA + DHA). Less is known about docosapentaenoic acid (DPA), the metabolic intermediate of EPA and DHA; however, evidence suggests DPA may be an important contributor to long‐chain n‐3 fatty acid intake and impart unique benefits. We used NHANES 2003–2014 data (n = 45,347) to assess DPA intake and plasma concentrations, as well as the relationship between intake and plasma concentrations of EPA, DPA, and DHA. Mean DPA intake was 22.3 ± 0.8 mg/day from 2013 to 2014, and increased significantly over time (p < 0.001), with the lowest values from 2003 to 2004 (16.2 ± 1.2 mg/day). DPA intake was higher in adults (20–55 years) and seniors (55+ years) compared to younger individuals. In regression analyses, DPA intake was a significant predictor of plasma EPA (β = 138.5; p < 0.001) and DHA (β = 318.9; p < 0.001). Plasma DPA was predicted by EPA and DHA intake (β = 13.15; p = 0.001 and β = 7.4; p = 0.002), but not dietary DPA (p = 0.3). This indicates that DPA intake is not a good marker of plasma DPA status (or vice versa), and further research is needed to understand the factors that affect the interconversion of EPA and DPA. These findings have implications for future long‐chain n‐3 fatty acids dietary recommendations.
Advantages of large medical record database for outcomes research: Insights into post‐menopausal hormone therapy
Authors: Tannen Richard L. , Barnhart Kurt T. , Rubin Joshua C.
Published: April 2019

Approximately 25 years ago, our team initiated studies to determine whether outcome results from a large medical record database would yield valid results. We utilized the data in the United Kingdom (UK) General Practice Research Database (GPRD) to replicate the randomized controlled trial (RCT) study result and compared them to confirm the database results. The initial studies compared favorably, but some subsequent studies did not. This prompted development of a new strategy to determine and correct for unrecognized confounding in the database. This strategy divided outcome rates prior to initiation of therapy in the database study (which should include both identified and unidentified confounders) into the outcome rates during the treatment interval. When they differed from Cox‐adjusted results, it reflected unrecognized confounding. We called this strategy Prior Event Rate Ratio (PERR)–adjusted outcome.

One of our previously published observational studies replicated the Women's Health Initiative (WHI) RCT study of hormone therapy in post‐menopausal women. Our study results replicated the WHI RCT results except it did not exhibit an increase in heart attack in contrast to the RCT. Furthermore, we could not evaluate death reliably since our analytic approach to overcome unrecognized confounding does not work for this outcome. In Volume 1, Issue 1 of the Learning Health Systems open access journal, we published a new study (titled “A new method to address unmeasured confounding of mortality in observational studies”) that reported a novel death method, based on our prior methodology, that could analyze unrecognized confounding of the death outcome. This new methodology, termed Post Treatment Event Rate Ratio (PTERR), permitted a reliable examination of mortality in post‐menopausal women undergoing hormone therapy. These results are reported in this manuscript. The study used the data from our previous observational study. It demonstrates that estrogen therapy markedly reduced death in post‐menopausal women.

This work also illuminates principles of database construction and correspondingly demonstrates the use of novel methodologies for obtaining valid results, which can be applied to enable learning from such databases. Work to advance such methodologies is essential to advancing the scientific integrity Core Value underpinning learning health systems (LHSs). Indeed, in the absence of such efforts to develop and refine methodologies for learning trustworthy lessons from real‐world data, we risk inadvertently creating mis‐learning systems.
Distal and non‐distal behavior in pairs
Authors: Nell Travis
Published: April 2019

The aim of this work is an analysis of distal and non‐distal behavior in dense pairs of o‐minimal structures. A characterization of distal types is given through orthogonality to a generic type in , non‐distality is geometrically analyzed through Keisler measures, and a distal expansion for the case of pairs of ordered vector spaces is computed.
Random sampling technique to predict the molecular weight distribution in nonlinear polymerization
Authors: Tobita Hidetaka
Published: April 2019

Comprehensive accounts for the newly proposed concept of the random sampling technique are given in detail. This techniques involves random sampling of polymer molecules from an infinite number of polymeric species in the reaction mixture, and can provide a deeper insight into the complex molecular buildup processes such as those involving branching, crosslinking, and degradation reactions. For simpler cases, the analytical solutions for the molecular weight distribution can be obtained. By combining this technique with the Monte Carlo method, one obtains a very powerful simulator that can be applied to virtually any type of nonlinear polymer formation (or degradation) irrespective of the reactor types used, as long as the chain‐length and structural dependences of the reaction kinetics can be neglected. In the Monte Carlo simulations, we can observe the structure of each polymer molecule directly so that very detailed structural information, including the spatial distribution of polymer chains, can be obtained in a straightforward manner. Several types of nonlinear polymerization schemes are used to illustrate the fundamentals of the presented technique.
Balance impairment in pediatric charcot–marie–tooth disease
Authors: Estilow Timothy , Glanzman Allan M. , Burns Joshua , Harrington Ann , Cornett Kayla , Menezes Manoj P. , Shy Rosemary , Moroni Isabella , Pagliano Emanuela , Pareyson Davide , Bhandari Trupti , Muntoni Francesco , Laurá Matilde , Reilly Mary M. , Finkel Richard S. , Eichinger Kate J. , Herrmann David N. , Troutman Gregory , Bray Paula , Halaki Mark , Shy Michael E. , Yum Sabrina W. ,   for the CMTPedS STUDY GROUP
Published: April 2019

Introduction: Balance impairment contributes to gait dysfunction, falls, and reduced quality of life in adults with Charcot–Marie–Tooth disease (CMT) but has been minimally examined in pediatric CMT. Methods: The CMT Pediatric Scale (CMTPedS) was administered to 520 children with CMT. Associations between balance function (Bruininks–Oseretsky Test of Motor Proficiency [BOT‐2]) and sensorimotor and gait impairments were investigated. Results: Daily trips/falls were reported by 42.3% of participants. Balance (BOT‐2) varied by CMT subtype, was impaired in 42% of 4‐year‐olds, and declined with age (P < 0.001). Vibration (P < 0.001), pinprick (P < 0.004), ankle dorsiflexion strength (P < 0.001), and foot alignment (P < 0.004) were associated with BOT‐2 balance (adjusted R2 = 0.28). The visual dependence of balance increased with age. Discussion: Balance impairment occurs from a young age in children with CMT. Balance intervention studies are required in pediatric CMT and should consider the degree of sensorimotor impairment, foot malalignment, and visual dependence. Muscle Nerve, 2019