bluuebunny/crossref_metadata_2025 huggingface dataset:
How bilingualism protects the brain from aging: Insights from bimodal bilinguals
Authors: Li Le , Abutalebi Jubin , Emmorey Karen , Gong Gaolang , Yan Xin , Feng Xiaoxia , Zou Lijuan , Ding Guosheng
Published: May 2017

Bilingual experience can delay cognitive decline during aging. A general hypothesis is that the executive control system of bilinguals faces an increased load due to controlling two languages, and this increased load results in a more “tuned brain” that eventually creates a neural reserve. Here we explored whether such a neuroprotective effect is independent of language modality, i.e., not limited to bilinguals who speak two languages but also occurs for bilinguals who use a spoken and a signed language. We addressed this issue by comparing bimodal bilinguals to monolinguals in order to detect age‐induced structural brain changes and to determine whether we can detect the same beneficial effects on brain structure, in terms of preservation of gray matter volume (GMV), for bimodal bilinguals as has been reported for unimodal bilinguals. Our GMV analyses revealed a significant interaction effect of age × group in the bilateral anterior temporal lobes, left hippocampus/amygdala, and left insula where bimodal bilinguals showed slight GMV increases while monolinguals showed significant age‐induced GMV decreases. We further found through cortical surface‐based measurements that this effect was present for surface area and not for cortical thickness. Moreover, to further explore the hypothesis that overall bilingualism provides neuroprotection, we carried out a direct comparison of GMV, extracted from the brain regions reported above, between bimodal bilinguals, unimodal bilinguals, and monolinguals. Bilinguals, regardless of language modality, exhibited higher GMV compared to monolinguals. This finding highlights the general beneficial effects provided by experience handling two language systems, whether signed or spoken. Hum Brain Mapp 38:4109–4124, 2017. © 2017 Wiley Periodicals, Inc.
Efficacy and safety of ruxolitinib in intermediate‐1 IPSS risk myelofibrosis patients: Results from an independent study
Authors: Palandri Francesca , Tiribelli Mario , Benevolo Giulia , Tieghi Alessia , Cavazzini Francesco , Breccia Massimo , Bergamaschi Micaela , Sgherza Nicola , Polverelli Nicola , Crugnola Monica , Isidori Alessandro , Binotto Gianni , Heidel Florian H. , Buccisano Francesco , Martino Bruno , Latagliata Roberto , Spinsanti Marco , Kallenberg Lydia , Palumbo Giuseppe Alberto , Abruzzese Elisabetta , Scaffidi Luigi , Cuneo Antonio , Cavo Michele , Vianelli Nicola , Bonifacio Massimiliano
Published: May 2017

Patients with myelofibrosis at intermediate‐1 risk according to the International Prognostic Score System are projected to a relatively long survival; nonetheless, they may carry significant splenomegaly and/or systemic constitutional symptoms that hamper quality of life and require treatment. Since registrative COMFORT studies included only patients at intermediate‐2/high International Prognostic Score System risk, safety and efficacy data in intermediate‐1 patients are limited. We report on 70 intermediate‐1 patients treated with ruxolitinib according to standard clinical practice that were evaluated for response using the 2013 IWG‐MRT criteria. At 6 months, rates of spleen and symptoms response were 54.7% and 80% in 64 and 65 evaluable patients, respectively. At 3 months, ruxolitinib‐induced grade 3 anemia and thrombocytopenia occurred in 40.6% and 2.9% of evaluable patients, respectively. Notably, 11 (15.9%) patients experienced at least one infectious event ≥grade 2. Most (82.6%) patients were still on therapy after a median follow‐up of 27 months. These data support the need for standardized guidelines that may guide the decision to initiate ruxolitinib therapy in this risk category, balancing benefit expectations and potential adverse effects.
Effectively designed shell‐tube heat exchangers considering cost minimization and energy management
Authors: Tahery Amir Asgari , Khalilarya Shahram , Jafarmadar Samad
Published: May 2017

Cost optimization, which is expressed as a set of analytical variables, is a key objective in economic design approaches of shell‐and‐tube heat exchangers. This study has provided new design techniques based on tube bundle effect on the economic optimization design of shell‐and‐tube heat exchangers. Also the objective of this paper is to develop the cost estimating for the new modified shell‐and‐tube heat exchangers by introducing new objective functions. According to the results the best configuration choice will obviously be the one with the least irreversibility, that is, with the lowest exergy destruction rate and lower annual capital cost. Also, the combined reduction of annual capital investment and operating cost by the new design technique led to a decrease in the overall costs of about 10% to 24% in comparison with original design. So the proposed design technique shows potential for improvement and economic optimization of shell‐and‐tube heat exchangers.
Numerical investigation of the effects of geometric parameters of heaters on mixed covection in a lid‐driven cavity filled with different nanofluids
Authors: Salari Mahmoud , Mohammadtabar Ali , Mohammadtabar Mohammad
Published: May 2017

In this paper, the effects of the thicknesses and locations of two rectangular heaters, located on the bottom and one side of on an enclosure, on mixed convection of nanofluid flows in a lid‐driven cavity are numerically investigated. The enclosure is simultaneously heated partially by these two heaters which have similar or different thicknesses and also filled with different nanofluids containing nanoparticles of Cu, Ag, Al2O3, and TiO2 within the base fluid of water. A finite volume approach by the SIMPLE algorithm is used to solve the governing equations. The effects of different Rayleigh numbers (), Reynolds numbers (), solid volume fractions (), heater lengths (), heater locations () and heater thicknesses () on the streamlines, isotherms and the average Nusselt number along two heaters are studied accurately. Also, variations of average Nusselt number of two heaters are considered whenever one heater is fixed and the other heater moves along on the wall. Moreover, variations of the length of one heater on the average Nusselt number are also studied whenever the length of the other heater is fixed. In addition, variations of the thickness of one heater on the average Nusselt number are studied whenever the thickness of the other heater is fixed.
Exact, analytic temperature distributions of pin fins with constant thermal conductivity and power‐law type heat transfer coefficient
Authors: Shivanian Elyas , Campo Antonio
Published: May 2017

In this Technical Note, the problem of determining the temperature distribution in a pin fin with power‐law heat transfer coefficients is addressed. It is demonstrated that the governing fin equation, a nonlinear second‐order differential equation, is exactly solvable for the entire range of the exponent n in the power‐law heat transfer coefficients. The exact, closed‐form analytical solutions in implicit form are convenient for physical interpretation and optimization for maximum heat transfer. Furthermore, it is proved that the exact solutions have three different structures: (1) dual in the range of , (2) unique or dual in the range of , and (3) unique in the range of . Additionally, exact analytical expressions for the fin efficiency and the fin effectiveness are provided, both as a function of the dimensionless fin parameter for the gamma of n under study.
A numerical study of heat transfer charcteristics of a car radiator involved nanofluids
Authors: Kakavand Hossein , Molana Maysam
Published: May 2017

To investigate the heat transfer characteristics of a car radiator involved nanofluids, we used GAMBIT & FLUENT softwares and calculated the effective physical parameters using some famous models as a single‐phase mixture. Carbon nanotubes and boron nitride nanotubes have been used in less than 1% volume concentration in flat and twisted tubes. Our results show that nanofluids application in a twisted tube gives a great enhancement in the thermal performance in comparison of the flat tube.
Self‐assembled nanofiber coatings for controlling cell responses
Authors: Barros Raquel C. , Gelens Edith , Bulten Erna , Tuin Annemarie , de Jong Menno R. , Kuijer Roel , van Kooten Theo G.
Published: May 2017

Nanofibers are thought to enhance cell adhesion, growth, and function. We demonstrate that the choice of building blocks in self‐assembling nanofiber systems can be used to control cell behavior. The use of 2 D‐coated, self‐assembled nanofibers in controlling lens epithelial cells, fibroblasts, and mesenchymal stem cells was investigated, focusing on gene and protein expression related to the fibrotic response. To this end, three nanofibers with different characteristics (morphology, topography, and wettability) were compared with two standard materials frequently used in culturing cells, TCPS, and a collagen type I coating. Cell metabolic activity, cell morphology, and gene and protein expression were analyzed. The most hydrophilic nanofiber with more compact network consisting of small fibers proved to provide a beneficial 2 D environment for cell proliferation and matrix formation while decreasing the fibrotic/stress behavior in all cell lines when compared with TCPS and the collagen type I coating. This nanofiber demonstrates the potential to be used as a biomimetic coating to study the development of fibrosis through epithelial‐to‐mesenchymal transition. This study also shows that nanofiber structures do not enhance cell function by definition, because the physico‐chemical characteristics of the nanofibers influence cell behavior as well and actually can be used to regulate cell behavior toward suboptimal performance. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2252–2265, 2017.
Effect of silver‐loaded PMMA on Streptococcus mutans in a drip flow reactor
Authors: Williams Dustin L. , Epperson Richard Tyler , DeGrauw Jeffery P. , Nielsen Mattias B. , Taylor Nicholas B. , Jolley Ryan D.
Published: May 2017

Orthodontic retention has been proposed as a life‐long commitment for patients who desire to maintain straight teeth. However, the presence of foreign material increases risk of bacterial colonization and caries formation, of which Streptococcus mutans is a key contributor. Multiple studies have assessed the ability of silver to be added to base plate material and resist attachment of S. mutans. However, it does not appear that long‐term washout in connection with biofilm growth under physiologically relevant conditions has been taken into consideration. In this study, silver was added to base plate material and exposed to short‐ or long‐term washout periods. Materials were then assessed for their ability to resist biofilm formation of S. mutans using a drip flow reactor that modeled the human oral environment. Data indicated that silver was able to resist biofilm formation following short‐term washout, but long‐term washout periods resulted in a lack of ability to resist biofilm formation. These data will be important for future development of base plate materials to achieve long‐term antimicrobial efficacy to reduce risk of caries formation and benefit patients in the long term. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2632–2639, 2017.
Mapping intermediate degradation products of poly(lactic‐co‐glycolic acid) in vitro
Authors: Li Jian , Nemes Peter , Guo Ji
Published: May 2017

There is widespread interest in using absorbable polymers, such as poly(lactic‐co‐glycolic acid) (PLGA), as components in the design and manufacture of new‐generation drug eluting stents (DES). PLGA undergoes hydrolysis to progressively degrade through intermediate chemical entities to simple organic acids that are ultimately absorbed by the human body. Understanding the composition and structure of these intermediate degradation products is critical not only to elucidate polymer degradation pathways accurately, but also to assess the safety and performance of absorbable cardiovascular implants. However, analytical approaches to determining the intermediate degradation products have yet to be established and evaluated in a standard or regulatory setting. Hence, we developed a methodology using electrospray ionization mass spectrometry to qualitatively and quantitatively describe intermediate degradation products generated in vitro from two PLGA formulations commonly used in DES. Furthermore, we assessed the temporal evolution of these degradation products using time‐lapse experiments. Our data demonstrated that PLGA degradation products via heterogeneous cleavage of ester bonds are modulated by multiple intrinsic and environmental factors, including polymer chemical composition, degradants solubility in water, and polymer synthesis process. We anticipate the methodologies and outcomes presented in this work will elevate the mechanistic understanding of comprehensive degradation profiles of absorbable polymeric devices, and facilitate the design and regulation of cardiovascular implants by supporting the assessments of the associated biological response to degradation products. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1129–1137, 2018.
Pain, Quality of Life, and Safety Outcomes of Kyphoplasty for Vertebral Compression Fractures: Report of a Task Force of the American Society for Bone and Mineral Research
Authors: Rodriguez Alexander J , Fink Howard A , Mirigian Lynn , Guañabens Nuria , Eastell Richard , Akesson Kristina , Bauer Douglas C , Ebeling Peter R
Published: May 2017

The relative efficacy and harms of balloon kyphoplasty (BK) for treating vertebral compression fractures (VCF) are uncertain. We searched multiple electronic databases to March 2016 for randomized and quasi-randomized controlled trials comparing BK with control treatment (nonsurgical management [NSM], percutaneous vertebroplasty [PV], KIVA VCF treatment system [Benvenue Medical, Inc., Santa Clara, CA, USA], vertebral body stenting, or other) in adults with VCF. Outcomes included back pain, back disability, quality of life, new VCF, and adverse events (AEs). One reviewer extracted data, a second checked accuracy, and two rated risk of bias (ROB). Mean differences and 95% confidence intervals (CIs) were calculated using inverse-variance models. Risk ratios of new VCF and AE were calculated using Mantel-Haenszel models. Ten unique trials enrolled 1837 participants (age range, 61 to 76 years; 74% female), all rated as having high or uncertain ROB. Versus NSM, BK was associated with greater reductions in pain, back-related disability, and better quality of life (k = 1 trial) that appeared to lessen over time, but were less than minimally clinically important differences. Risk of new VCF at 3 and 12 months was not significantly different (k = 2 trials). Risk of any AE was increased at 1 month (RR = 1.73; 95% CI, 1.36 to 2.21). There were no significant differences between BK and PV in back pain, back disability, quality of life, risk of new VCF, or any AE (k = 1 to 3 trials). Limitations included lack of a BK versus sham comparison, availability of only one RCT of BK versus NSM, and lack of study blinding. Individuals with painful VCF experienced symptomatic improvement compared with baseline with all interventions. The clinical importance of the greater improvements with BK versus NSM is unclear, may be due to placebo effect, and may not counterbalance short-term AE risks. Outcomes appeared similar between BK and other surgical interventions. Well-conducted randomized trials comparing BK with sham would help resolve remaining uncertainty about the relative benefits and harms of BK. © 2017 American Society for Bone and Mineral Research.
Nucleophosmin Regulates Intracellular Oxidative Stress Homeostasis via Antioxidant PRDX6
Authors: Liu Guo‐Yan , Shi Jing‐Xian , Shi Song‐Lin , Liu Fan , Rui Gang , Li Xiao , Gao Li‐Bin , Deng Xiao‐Ling , Li Qi‐Fu
Published: May 2017

Reactive oxygen species (ROS) play both deleterious and beneficial roles in cancer cells. Nucleophosmin (NPM) is heavily implicated in cancers of diverse origins, being its gene over‐expression in solid tumors or frequent mutations in hematological malignancies. However, the role and regulatory mechanism of NPM in oxidative stress are unclear. Here, we found that NPM regulated the expression of peroxiredoxin 6 (PRDX6), a member of thiol‐specific antioxidant protein family, consequently affected the level and distribution of ROS. Our data indicated that NPM knockdown caused the increase of ROS and its relocation from cytoplasm to nucleoplasm. In contrast, overexpression or cytoplasmic localization of NPM upregulated PRDX6, and decreased ROS. In addition, NPM knockdown decreased peroxiredoxin family proteins, including PRDX1, PRDX4, and PRDX6. Co‐immunoprecipitation further confirmed the interaction between PRDX6 and NPM. Moreover, NSC348884, an inhibitor specifically targeting NPM oligomerization, decreased PRDX6 and significantly upregulated ROS. These observations demonstrated that the expression and localization of NPM affected the homeostatic balance of oxidative stress in tumor cells via PRDX6 protein. The regulation axis of NPM/PRDX/ROS may provide a novel therapeutic target for cancer treatment. J. Cell. Biochem. 118: 4697–4707, 2017. © 2017 Wiley Periodicals, Inc.
The Therapeutic Potential of PI3K/Akt/mTOR Inhibitors in Breast Cancer: Rational and Progress
Authors: Bahrami Afsane , Khazaei Majid , Shahidsales Soodabeh , Hassanian Seyed Mahdi , Hasanzadeh Malihe , Maftouh Mina , Ferns Gordon A. , Avan Amir
Published: May 2017

Breast cancer (BC) is the most commonly diagnosed cancer in women. The PI3K/AKT/mTOR pathway is among the most frequently dysregulated pathways in patients with BC. The activation of this pathway is associated with increased cell growth and clinical outcome, and its overexpression is associated with a poor prognosis. It has been proposed that it may be of importance as a potential therapeutic target in the treatment of BC. The aim of current review is to provide an overview of the potential utility of PI3K/Akt/mTOR inhibitors in patients with BC, with particular emphasis on recent preclinical and clinical studies. J. Cell. Biochem. 119: 213–222, 2018. © 2017 Wiley Periodicals, Inc.
Gingerenone A Attenuates Monocyte‐Endothelial Adhesion via Suppression of I Kappa B Kinase Phosphorylation
Authors: Kim Hee Joo , Son Joe Eun , Kim Jae Hwan , Lee Charles C. , Yang Hee , Yaghmoor Soonham Sami , Ahmed Youssri , Yousef Jehad Mustafa , Abualnaja Khalid Omer , Al‐Malki Abdulrahman Labeed , Kumosani Taha Abdullah , Kim Jong Hun , Yoon Park Jung Han , Lee Chang Yong , Kim Jong‐Eun , Lee Ki Won
Published: May 2017

During the early stages of atherosclerosis, monocytes bind and migrate into the endothelial layer, promoting inflammation within the aorta. In order to prevent the development of atherosclerosis, it is critical to inhibit such inflammation. The therapeutic effects of ginger have been investigated in several models of cardiovascular disease. However, although a number of previous studies have focused on specific compounds, the mechanisms of action responsible remain unclear. Here, we investigated five major compounds present in ginger, and observed that gingerenone A exhibited the strongest inhibitory effects against tumor necrosis factor (TNF)‐α and lipopolysaccharide (LPS) induced monocyte‐endothelial adhesion. Furthermore, gingerenone A significantly suppressed the expression of TNF‐α and LPS‐induced vascular cell adhesion molecule‐1 (VCAM‐1) and chemokine (C‐C motif) ligand 2 (CCL2), key mediators of the interaction between monocytes, and endothelial cells. Transactivation of nuclear factor‐κB (NF‐κB), which is a key transcription factor of VCAM‐1 and CCL2, was induced by TNF‐α and LPS, and inhibited by treatment of gingerenone A. Gingerenone A also inhibited the phosphorylation of NF‐κB inhibitor (IκB) α and IκB Kinase. Taken together, these results demonstrate that gingerenone A attenuates TNF‐α and LPS‐induced monocyte adhesion and the expression of adhesion factors in endothelial cells via the suppression of NF‐κB signaling. J. Cell. Biochem. 119: 260–268, 2018. © 2017 Wiley Periodicals, Inc.
Pleiotropic Effects of Chronic Phorbol Ester Treatment to Improve Glucose Transport in Insulin‐Resistant Cardiomyocytes
Authors: Viglino Christelle , Khoramdin Bahareh , Praplan Guillaume , Montessuit Christophe
Published: May 2017

Stimulation of glucose transport is an important determinant of myocardial susceptibility to ischemia and reperfusion. Stimulation of glucose transport is markedly impaired in cardiomyocytes exposed to free fatty acids (FFA). Deactivation of the Focal Adhesion Kinase (FAK) by FFA contributes to glucose transport impairment, and could be corrected by chronic treatment with the phorbol ester TPA. However, TPA must have effects in addition to FAK reactivation to restore stimulated glucose transport. Chronic treatment with TPA improved basal and stimulated glucose transport in FFA‐exposed, but not in control cardiomyocytes. Chronic FFA exposure induced the activation of PKCδ and PKCϵ. TPA markedly downregulated the expression of PKCα, PKCδ, and PKCϵ, suggesting that PKCδ or PKCϵ activation could contribute to inhibition of glucose transport by FFA. Rottlerin, a specific PKCδ inhibitor, improved glucose transport in FFA‐exposed cardiomyocytes; and PKCδ was reduced in the particulate fraction of FFA + TPA‐exposed cardiomyocytes. TPA also activated Protein Kinase D 1(PKD1) in FFA‐exposed cardiomyocytes, as assessed by autophosphorylation of PKD1 on Y916. Pharmaceutical inhibition of PKD1 only partially prevented the improvement of glucose transport by TPA. Chronic TPA treatment also increased basal and stimulated glycolysis and favored accumulation of lipid droplets in FFA‐exposed cardiomyocytes. In conclusion, basal and stimulated glucose transport in cardiomyocytes is reduced by chronic FFA exposure, but restored by concomitant treatment with a phorbol ester. The mechanism of action of phorbol esters may involve downregulation of PKCδ, activation of PKD1 and a general switch from fatty acid to glucose metabolism. J. Cell. Biochem. 9999: 4716–4727, 2017. © 2017 Wiley Periodicals, Inc.
Retracted: Potential Role of Long Non‐Coding RNA ANRIL in Pediatric Medulloblastoma Through Promotion on Proliferation and Migration by Targeting miR‐323
Authors: Zhang Hong , Wang Xiuli , Chen Xinxin
Published: May 2017

Medulloblastoma (MB) is a common primary tumor of the central nervous system diagnosed in pediatric patients. Survivors of MB are frequently accompanied by severe side effects, thus it is urgent to explore novel therapeutic target. First of all, the level of antisense non‐coding RNA in the INK4 locus (ANRIL) in normal cerebellum and DAOY cells were evaluated. Then, the effect of ANRIL on DAOY cell proliferation, migration, and apoptosis were tested. Then, qRT‐PCR was performed to explore whether ANRIL acted as a sponge of miR‐323. The effects of miR‐323 inhibition on ANRIL silence‐induced alterations of cell proliferation, migration, and apoptosis were estimated. Predicted by TargetScan, the possible target gene of miR‐323 was screened, followed by validation with luciferase assay. The abnormally expressed BRI3 on cell proliferation, migration, apoptosis, and signaling pathways were all evaluated. ANRIL was up‐regulated in MB and its silence significantly lowered cell viability and migration but promoted cell apoptosis. ANRIL acted as a sponge of miR‐323 and its silence functioned through up‐regulating miR‐323. BRI3 and CDK6 were target genes of miR‐323 and the effect of BRI3 on DAOY cells was the same as ANRIL. Moreover, ANRIL suppression could reduce phosphorylated levels of p38 MAPK, ERK and AKT, and inhibit Wnt signaling pathway through positively regulating BRI3. ANRIL inhibition repressed cell proliferation and migration but promoted cell apoptosis through miR‐323‐mediated regulation of BRI3, which could activate p38 MAPK, ERK, and AKT as well as Wnt signaling pathway. J. Cell. Biochem. 118: 4735–4744, 2017. © 2017 Wiley Periodicals, Inc.
β3‐Adrenergic Regulation of EPC Features Through Manipulation of the Bone Marrow MSC Niche
Authors: Vafaei Rana , Nassiri Seyed Mahdi , Siavashi Vahid
Published: May 2017

Mesenchymal stem cells (MSCs) reside in a specific niche in the bone marrow, however, biological features of this niche are still not fully understood. Given the interactions of MSCs with endothelial cells in different tissues, bone marrow MSC niche may influence the biological features of endothelial progenitor cells (EPCs). To understand the role of the sympathetic nervous system in regulation of the MSC niche, we examined whether the manipulation of the MSC niche via β3‐adrenergic signals will affect EPC features. A selective β3 agonist (BRL37344) or a β3 antagonist (SR59230A) was administered in mice for 2 weeks to determine the potential effects of these regimens on the population of CD133+ stem cells in the bone marrow. Then, bone marrow‐derived MSCs and EPCs were harvested and expanded from the mice to examine the effect of changes in the MSC niche on EPC features. Improved MSC colony forming potency with increased bone marrow stromal cell‐derived factor 1 (SDF‐1) (also known as C‐X‐C motif chemokine 12 [CXCL12]) expression was shown as a result of intensification of the bone marrow adrenergic signals through BRL37344 injection. On the other hand, the blockage of these signals limited the expression level of SDF‐1 and resulted in bone marrow enrichment of CD133+ cells. Manipulation of the MSC niche and decreased SDF‐1 expression via SR59230A injection also prompted EPCs to form more colonies with augmented proliferation and differentiation capacity. Overall, our results indicate that the β3‐adrenergic signals regulate the MSC niche, thereby resulting in modulation of EPC biological features. J. Cell. Biochem. 118: 4753–4761, 2017. © 2017 Wiley Periodicals, Inc.
Excited‐state minima and emission energies of retinal chromophore analogues: Performance of CASSCF and CC2 methods as compared with CASPT2
Authors: Szefczyk Borys , Grabarek Dawid , Walczak Elżbieta , Andruniów Tadeusz
Published: May 2017

This study provides gas‐phase S1 excited‐state geometries along with emission and adiabatic energies for methylated/demethylated and ring‐locked analogues of protonated Schiff base retinal models comprising system of five conjugated double bonds (PSB5), using second order multiconfiguration perturbation theory (CASPT2). CASPT2 results serve as reference data to assess the performance of CC2 (second‐order approximate coupled cluster singles and doubles) and a commonly used CASSCF/CASPT2 protocol, that is, complete active space self‐consistent field (CASSCF) geometry optimization followed by CASPT2 energy calculation. We find that the CASSCF methodology fails to locate planar S1 minimum energy structures for four out of five investigated planar models in contrast to CC2 and CASPT2 methods. However, for those which were found: one planar and two twisted minima, there is an excellent agreement between CASSCF and CASPT2 results in terms of geometrical parameters, one‐electron properties, as well as emission and adiabatic energies. CC2 performs well for in‐plane S1 minima and their spectroscopic and electronic properties. However, this picture deteriorates for twisted minima. As expected, the CC2 description of the S2 electronic state, with strong multireference and significant double excitation character, is very poor, exhibiting errors in transition energies exceeding 1 eV. They may be substantially diminished by recalculating transition energies with CASPT2 method. Our work shows that CASSCF/CASPT2 and CC2 shortcomings may influence gas‐phase retinal analogues' excited state description in a dramatic way. © 2017 Wiley Periodicals, Inc.
Rapid diagnosis of sepsis with TaqMan‐Based multiplex real‐time PCR
Authors: Liu Chang‐Feng , Shi Xin‐Ping , Chen Yun , Jin Ye , Zhang Bing
Published: May 2017

Background

The survival rate of septic patients mainly depends on a rapid and reliable diagnosis. A rapid, broad range, specific and sensitive quantitative diagnostic test is the urgent need. Thus, we developed a TaqMan‐Based Multiplex real‐time PCR assays to identify bloodstream pathogens within a few hours.

Methods

Primers and TaqMan probes were designed to be complementary to conserved regions in the 16S rDNA gene of different kinds of bacteria. To evaluate accurately, sensitively, and specifically, the known bacteria samples (Standard strains, whole blood samples) are determined by TaqMan‐Based Multiplex real‐time PCR. In addition, 30 blood samples taken from patients with clinical symptoms of sepsis were tested by TaqMan‐Based Multiplex real‐time PCR and blood culture.

Results

The mean frequency of positive for Multiplex real‐time PCR was 96% at a concentration of 100 CFU/mL, and it was 100% at a concentration greater than 1000 CFU/mL. All the known blood samples and Standard strains were detected positively by TaqMan‐Based Multiplex PCR, no PCR products were detected when DNAs from other bacterium were used in the multiplex assay. Among the 30 patients with clinical symptoms of sepsis, 18 patients were confirmed positive by Multiplex real‐time PCR and seven patients were confirmed positive by blood culture.

Conclusion

TaqMan‐Based Multiplex real‐time PCR assay with highly sensitivity, specificity and broad detection range, is a rapid and accurate method in the detection of bacterial pathogens of sepsis and should have a promising usage in the diagnosis of sepsis.
Histomorphology and innate immunity during the progression of osteoarthritis: Does synovitis affect cartilage degradation?
Authors: Wang Huan , Wang Qingguo , Yang Meijuan , Yang Lili , Wang Weili , Ding Haobin , Zhang Dong , Xu Jing , Tang Xuezhang , Ding Haitao , Wang Qingfu
Published: May 2017

Osteoarthritis (OA) is a common chronic degenerative disease that affects all joints. At present, the pathological processes and mechanisms of OA are still unclear. Innate immunity, a key player in damage to the structure of the joint and the mechanism by which the host attempts to repair OA, affects all pathological stages of the disease. In the present study, our aim was to assess changes in innate immunity during the pathological processes of OA in articular cartilage (AC) and the synovial membrane (SM), which are the major structures in joints, and to systematically examine the histological changes in AC and SM in mild, moderate and severe cases of OA, in order to further speculate about the manner in which the interactions of AC and SM are facilitated by innate immunity. Histological methods (including HE and Safranin O‐fast green staining), immunofluorescent double staining, TUNEL stain, and Western blots were used to assess the morphological changes within AC and SM tissues in healthy and mild, moderate, or severe OA rats. Our results showed that the damage to AC and SM within the joints progressively worsened in different degrees during the course of the disease, and that the innate immune system was closely involved in the AC and SM during each stage of OA. These findings also confirmed that SM may affect the pathological changes in AC through the innate immune system, and therefore affect the progress of OA.
The emerging role of NPNT in tissue injury repair and bone homeostasis
Authors: Sun Youqiang , Kuek Vincent , Qiu Heng , Tickner Jennifer , Chen Leilei , Wang Haibin , He Wei , Xu Jiake
Published: May 2017

Nephronectin (NPNT), a highly conserved extracellular matrix protein, plays an important role in regulating cell adhesion, differentiation, spreading, and survival. NPNT protein belongs to the epidermal growth factor (EGF)‐like superfamily and exhibits several common structural determinants; including EGF‐like repeat domains, MAM domain (Meprin, A5 Protein, and Receptor Protein‐Tyrosine Phosphatase µ), RGD motif (Arg‐Gly‐Asp) and a coiled‐coil domain. It regulates integrins‐mediated signaling pathways via the interaction of its RGD motif with integrin α8β1. Recent studies revealed that NPNT is involved in kidney development, renal injury repair, atrioventricular canal differentiation, pulmonary function, and muscle cell niche maintenance. Moreover, NPNT regulates osteoblast differentiation and mineralization, as well as osteogenic angiogenesis. Altered expression of NPNT has been linked with the progression of certain types of cancers, such as spontaneous breast tumor metastasis and malignant melanoma. Interestingly, NPNT gene expression can be regulated by a range of external factors such as tumor necrosis factor alpha (TNF‐α), transforming growth factor beta (TGF‐β), oncostatin M (OSM), bone morphogenic protein 2 (BMP2), Wnt3a, Vitamin D3, and microRNA‐378 (miR378). Further understanding the cellular and molecular mechanisms by which NPNT regulates tissue homeostasis in an organ‐specific manner is critical in exploring NPNT as a therapeutic target for tissue regeneration and tissue engineering.
The Utility of a Population Approach in Drug–Drug Interaction Assessments: A Simulation Evaluation
Authors: Wang Diane D. , Yu Yanke , Kassir Nastya , Zhu Min , Hanley William D. , Earp Justin C. , Chow Andrew T. , Gupta Manish , Hu Chuanpu
Published: May 2017

This study aims at evaluating the utility of the population pharmacokinetics approach in therapeutic protein drug‐drug‐interaction (DDI) assessment. Simulations were conducted for 2 representative victim drugs, methotrexate and trastuzumab, using a parallel‐group design with and without the interaction drug. The effect of a perpetrator on the exposure of the victim drug is described as the ratio of clearance/apparent clearance of the victim drug given with or without the perpetrator. The power of DDI assessment was calculated as the percentage of runs with 90% confidence interval of the estimated DDI effect within 80% to 125% for the scenarios of no DDI, benchmarked with the noncompartmental approach with intensive sampling. The impact of the number of subjects, the number of sampling points per subject, sampling time error, and model misspecification on the power of DDI determination were evaluated. Results showed that with equal numbers of subjects in each arm, the population pharmacokinetics approach with sparse sampling may need about the same or a higher number of subjects compared to a noncompartmental approach in order to achieve similar power. Increasing the number of subjects, even if only in the study drug alone arm, can increase the power. Sampling or dosing time error had notable impacts on the power for methotrexate but not for trastuzumab. Model misspecification had no notable impacts on the power for trastuzumab. Overall, the population pharmacokinetics approach with sparse sampling built in phase 2/3 studies allows appropriate DDI assessment with adequate study design and analysis and can be considered as an alternative to dedicated DDI studies.
Effect of Pentoxifylline in Ameliorating Myocardial Injury in Patients With Myocardial Infarction Undergoing Thrombolytic Therapy: A Pilot Randomized Clinical Trial
Authors: Namdar Hossein , Zohori Rasoul , Aslanabadi Naser , Entezari‐Maleki Taher
Published: May 2017

Cell death following acute myocardial infarction (MI) is the hallmark pathology of cardiovascular disease, leading to considerable mortality and morbidity. Platelet and neutrophil activation and inflammatory cytokines, prominently TNF‐α, play an important role in the development of cell death. Because pentoxifylline inhibits platelet and neutrophil activation and reduces TNF‐α, this study was performed to assess the potential benefit of pentoxifylline in the reduction of myocardial injury following acute MI. In this randomized clinical trial, 98 patients with acute MI were randomly divided into 2 groups. The intervention group received an oral dose of 1200 mg of pentoxifylline immediately before thrombolytic therapy (TLT). All patients received the same standard protocol for treatment of MI. Cardiac enzymes were checked over 48 hours. ST resolution was measured over 90 minutes. Then all patients were followed up for a 1‐month period to assess major adverse cardiac effects (MACEs). There were no significant differences in peak levels of CPK (P = .18) and CK‐MB (P = .33) between the 2 groups, whereas peak level of troponin I was significantly lower in the pentoxifylline group (16.8 ± 10.4 vs 21.3 ± 11.6; P = .048). No significant change between the groups was observed in biomarkers levels, ST segment resolution, cardiac ejection fraction, and MACEs. The results showed that pentoxifylline significantly reduced the peak value of troponin I in patients with acute MI receiving TLT. No significant change was observed in the other studied parameters. Further outcome‐based studies are needed to show the clinical relevance of differences between the groups in troponin peak.
Milk pancreatitis with hypertriglyceridemia and diabetic ketoacidosis
Authors: Shinotsuka Manami , Tokuda Yasuharu
Published: May 2017

Excessive milk intake may lead to diabetic ketoacidosis and acute pancreatitis. A 55‐year‐old milk salesperson with diabetes and dyslipidemia presented with a 5‐day history of fatigue and thirst. The patient had drunk a large amount of milk for 2 months prior to the admission. Laboratory data showed metabolic acidosis, hyperglycemia, ketonuria, hypertriglyceridemia, and elevated serum amylase. Abdominal CT with contrast material revealed the swelling of the pancreas. The patient received medical treatment for diabetic ketoacidosis and acute pancreatitis and was discharged uneventfully on day 18. Dietary advice for diabetics should include the avoidance of excessive amount of milk.
Natural history of intraductal papillary mucinous neoplasm and non‐neoplastic cyst: long‐term imaging follow‐up study
Authors: Hisada Yuya , Nagata Naoyoshi , Imbe Koh , Takasaki Yusuke , Sekine Katsunori , Tajima Tsuyoshi , Yanase Mikio , Fujimoto Kazuma , Akiyama Junichi , Uemura Naomi
Published: May 2017

Background

To identify differences in incidence and mortality of pancreatic cancer (PC) between intraductal papillary mucinous neoplasm (IPMN) and non‐neoplastic cyst.

Methods

Patients with pancreatic cyst (n = 526; 263 with IPMN and 263 with non‐neoplastic cyst matched for age, sex, and diagnosis year) were periodically followed‐up with imaging. Hazard ratio (HR), standardized incidence ratio (SIR), and standardized mortality ratio (SMR) for PC and PC‐related mortality were estimated.

Results

During a mean follow‐up of 57.5 months with 3,376 computed tomography scans and 1,079 magnetic resonance imaging scans, 5‐year cumulative PC incidence was 4.0% for IPMN and 0% for non‐neoplastic cyst, respectively (HR 5.2; P = 0.031). During a mean follow‐up of 73.1 months, 5‐year cumulative PC‐related mortality was 2.6% for IPMN and 0% for non‐neoplastic cyst, respectively (HR 4.5; P = 0.05). Compared with the general population in Japan, patients with IPMN, but not those with non‐neoplastic cyst, had significantly increased risks of PC incidence (SIR 22.03) and related mortality (SMR 15.9).

Conclusions

During long‐term imaging follow‐up, patients with IPMN developed PC over time, whereas none of the patients with non‐neoplastic cyst developed it within 5 years. Compared with the general population, patients with IPMN, but not those with non‐neoplastic cyst, were at risk of PC and related mortality.
Cytomegalovirus infection and atherosclerosis risk: A meta‐analysis
Authors: Jia Yang‐jie , Liu Jun , Han Fei‐fei , Wan Zi‐rui , Gong Li‐li , Liu He , Zhang Wen , Wardell Thomas , Lv Ya‐li , Liu Li‐hong
Published: May 2017

Human cytomegalovirus (HCMV) infection is an important risk factor for atherosclerosis (AS). Numerous studies have been conducted to analyze the association between HCMV infection and risk of AS, but no clear consensus has been reached. So the objective of this paper was aimed to demonstrate the relationship between HCMV and AS by doing a meta‐analysis. Relative literature was searched through the electronic databases PubMed, Embase, and CNKI. Data were accurately assessed and analyzed independently by two investigators. Ultimately, the 30 studies, involving 3328 cases and 2090 controls were included in our meta‐analysis. The positive ratio of HCMV IgG, IgM, DNA and pp65 were, respectively, 63.26% (923/1459), 25.46% (69/271), 33.69% (381/1131), and 50.32% (158/314) in case patients. Meanwhile the positive ratio of HCMV IgG, IgM, DNA, and pp65 were, respectively, 52.12% (541/1038), 1.55% (3/194), 13.72% (79/576), and 12.26% (28/229) in control subjects. The positive ratio of HCMV infection was higher in atherosclerosis group than that in non‐atherosclerosis group. Especially in Asian group, calculated odds ratios for the presence of HCMV infection in IgG‐based HCMV tests, IgM‐based tests, PCR‐based tests, and pp65‐based tests, expressed as OR (95% confidence intervals, 95%CI), were 3.07(95%CI 2.09‐4.51), 8.92(95%CI 3.17‐25.11), 6.75 (95%CI 3.50‐13.02), and 5.72(95%CI 1.51‐21.58), respectively. The meta‐analysis results showed that HCMV infection is significant connected with an increased risk for AS.
Impact of “a” determinant mutations on detection of hepatitis B surface antigen (HBsAg) in HBV strains from Chinese patients with occult hepatitis B
Authors: Huang Xiangyan , Ma Chenyun , Zhang Qiang , Shi Qingfen , Huang Tao , Liu Chao , Li Jie , Hollinger F. Blaine
Published: May 2017

This study was designed to detect mutations that occur within the “a” determinant in the S gene of the hepatitis B virus (HBV) in patients with occult hepatitis B (OHB), and to analyze the influence of these mutations on expression and reactivity of the hepatitis B surface antigen (HBsAg). Twenty‐three certified OHB samples were compared to 32 HBsAg positive samples from patients with chronic hepatitis B. The median HBV DNA levels in the OHB group were significantly lower than those in the control group (P < 0.0001). Mutations within the “a” determinant were analyzed by gene amplification and sequencing. This revealed mixed infections in which clones within a sample displayed either different mutations or mutations in association with clones that exhibited wild type amino acid patterns. Sequencing analysis also showed a significant difference between the proportions of amino acid mutations observed in the OHB and control groups. Seven recombinant S (rS) proteins with corresponding OHB mutations and three wild type alleles were expressed and purified in the Pichia pastoris expression system to preserve conformational attributes, and their reactivity analyzed using six commercial HBsAg assays. The OHB sera were HBsAg nonreactive while the rS proteins with corresponding OHB mutations were universally reactive. Thus, we postulate that the reduced binding affinity between mutated HBsAg and its antibody may not be as important in defining OHB as is the effect of specific mutations in the preS/S region of the genome that affect the synthesis and secretion of the S protein and/or the virion.
ZL006 promotes migration and differentiation of transplanted neural stem cells in male rats after stroke
Authors: Wang Dong‐Liang , Qian Xiao‐Dan , Lin Yu‐Hui , Tian Bin‐Bin , Liang Hai‐Ying , Chang Lei , Wu Hai‐Yin , Zhu Dong‐Ya , Luo Chun‐Xia
Published: May 2017

New strategies must be developed to resolve the problems of stroke treatment. In recent years, stem cell–based therapy after stroke has come into the public and academic lens. Previously we have shown that uncoupling neuronal nitric oxide synthase (nNOS) from the postsynaptic density protein‐95 (PSD‐95) by ZL006, a small molecular compound, can ameliorate ischemic damage and promote neuronal differentiation of endogenous neural stem cells (NSCs) in focal cerebral ischemic male rats. In this study, we transplanted exogenous NSCs into the ipsilateral hemisphere of male rats in combination with ZL006 treatment after ischemic stroke. We show that ZL006 treatment facilitates the migration of transplanted NSCs into the ischemia‐injured area and promotes neuronal differentiation of these cells, which is not due to a direct effect of ZL006 on exogenous NSCs but is associated with increased phosphorylation of cAMP response element–binding protein (CREB) in neurons and favorable microenvironment. Moreover, improved functional outcome in the ZL006‐treated group was also found. Taken together, our data indicate that ZL006, uncoupling nNOS–PSD‐95 in neurons, positively regulates the fate of transplanted NSCs and benefits the functional outcome after stroke in male rats.
Biomechanical function of a balloon nucleus pulposus replacement system: A human cadaveric spine study
Authors: Lee Taekyeong , Lim Tae‐Hong , Lee Sang‐Heon , Kim Joo‐Han , Hong Junghwa
Published: May 2017

With recent advances in motion‐sparing techniques in spine surgery, disc nucleus replacement (DNR) has been introduced as a viable method to restore the biomechanical functions of the spine. Several methods of DNR have been proposed in the literature. However, the risk of device migration or extrusion is a major issue that should be addressed for a successful DNR. DNR using a balloon nucleus (BN) filled with pressurized fluid may be capable of reducing such risks while preserving the advantages of DNR. The objective of this study was to investigate the biomechanical functionalities of the human cadaveric lumbar motion segments with a custom made BN filled with saline at internal fluid pressure of 0.3 or 0.6 MPa in terms of axial and rotational flexibilities of the L4‐L5 motion segment. Axial flexibility was quantified by the axial displacement resulting from an axial compressive force of 400 N while the rotational flexibility by the range of motions determined as the rotational angles in response to a pure moment of 6.0 Nm in flexion, extension, and right‐ and left‐lateral bending directions. These tests were performed successively on the motion segment in the following conditions: intact, post nucleotomy, implanting BN with 0.3 MPa, and BN with 0.6 MPa. The nucleotomy was found to significantly increase both the axial and rotational flexibilities while the implantation of the BN reduced the axial and rotational flexibilities to those of the intact segment. The axial and rotational flexibilities of the segment with the BN with 0.3 MPa were greater than those of the segment with the BN with 0.6 MPa. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:167–173, 2018.
The changing model of Free Economic Zones in China: To what extent will this further foster economic growth and entrepreneurship?
Authors: Floyd David , Sun Dabu , Barnes Ian
Published: May 2017

Free trade zones play an important part in China’s economic development. More improved methods of organization are leading to higher levels of technology transfer. Research, skills, entrepreneurship, and employment are being applied through foreign investments into free trade zones. Cultural benefits arising from such investments should not be underestimated, while benefits for the service sector are playing an increasingly important role.
Establishing a viable institutional environment for entrepreneurship in China: A case study of Zhejiang province
Authors: Millman Cindy , Li Zhengwei
Published: May 2017

New ways of helping graduates in China to become more entrepreneurial are being established. Innovation and entrepreneurship are crucial for China to move up the value chain. Entrepreneurship in some provinces has more drawbacks due to varying levels of infrastructure provision. Much can be learnt from current experiments taking place across the country that have often been linked to various forms of taxation incentive.