bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined non‐pharmacological interventions for newborn pain relief in two degrees of pain procedures: A randomized clinical trial
Authors: Leng H.‐Y. , Zheng X.‐L. , Zhang X.‐H. , He H.‐Y. , Tu G.‐F. , Fu Q. , Shi S.‐N. , Yan L.
Published: December 2015

Background

Non‐pharmacological interventions are effective neonatal pain reduction strategies. We aimed to study the effects of non‐nutritive sucking (NNS) and swaddling on infants' behavioural and physiological parameters during shallow or deep heel stick procedures.

Method

In this prospective, multi‐centred, randomized controlled clinical trial, we enrolled 671 newborns. The infants undergoing shallow or deep heel stick procedures were randomized into four groups: oral sucrose (routine care, group S), oral sucrose combined with NNS (group NS), oral sucrose combined with swaddling (group SS) and oral sucrose combined with NNS and swaddling (group NSS). The behavioural responses were evaluated by the Revised Neonatal Facial Coding System and the physiological signals were monitored by electrocardiogram monitors.

Results

A significant synergistic analgesic effect was observed between the NS and SS groups in both the shallow (F = 5.952, p = 0.015) and deep heel stick (F = 7.452, p = 0.007) procedure. NSS group exhibited the lowest pain score. For the deep heel stick procedure, the NS group had a significantly lower increase in heart rate (HR)% and decrease in SPO2% than the S group (F = 17.540, p = 0.000, F = 10.472, p = 0.001), while this difference was not observed in the shallow heel stick procedure. No difference was found between the S and SS groups, in terms of different physiological parameters.

Conclusion

Non‐nutritive sucking and swaddling had synergistic effects on pain relief when used with oral sucrose. For the deep heel stick procedure, oral sucrose combined with NNS and swaddling provided the best pain relief effect. For the shallow heel stick procedure, addition of NNS and swaddling did not improve the effects.
Electrode Based on Nickel‐containing SBA‐15 for the Determination of Copper in Ethanol Biofuel
Authors: Neto Sakae Y. , Viégas Helmara D. C. , Almeida Joseany M. S. , Cavalheiro Eder T. G. , Araújo Antonio S. , Marques Edmar P. , Marques Aldaléa L. B.
Published: December 2015

A sensor based in a graphite–polyurethane composite electrode modified with the mesoporous nanostructured silica with hexagonal array of pores called Santa Barbara Amorphous type material (SBA‐15) containing nickel was built. The presence of Ni, incorporated during the synthesis of SBA‐15, resulted in an increase in sensitivity when compared to the other electrodes based on the unmodified SBA‐15. A procedure was proposed for the determination of Cu2+ in ethanol biofuel by square wave stripping voltammetry with linear response in concentration levels of 1.0×10−8 and 1.0×10−7 mol L−1, resulting in a limit of detection of 1.83×10−10 mol L−1 and precision (RSD) of 2.09 %.
Determination of DNA Hypermethylation Using Anti‐cancer Drug‐Temozolomide
Authors: Topkaya Seda Nur , Serindere Gokçe , Ozder Melike
Published: December 2015

An electrochemical drug‐DNA biosensor was developed for the detection of interaction between the anti‐cancer drug, Temozolomide (TMZ), and DNA sequences by using Differential Pulse Voltammetry at the graphite electrode surfaces. TMZ is a pro‐drug and an alkylating agent that crosses the blood‐brain barrier, so it is mainly used for brain cancers treatment. In this study, we aim to develop a‐proof‐of‐concept study to investigate the effect of TMZ on formerly methylated DNA sequences since TMZ shows its anti‐cancer activity by methylating the DNA. Interaction between TMZ and DNA causes localized distortion of DNA away from an idealized B‐form, resulting in a wider major groove and greater steric accessibility of functional groups in the base of the groove. According to the results, TMZ behaves as a ‘hybridization indicator’ because of its different electrochemical behavior to different strands of DNA. After interaction with TMZ, hybrid (double stranded DNA‐dsDNA) signals decreased dramatically whereas probe (single stranded DNA‐ssDNA) and control signals remain almost unchanged. The signal differences enabled us to distinguish ssDNA and dsDNA without using a label or tag. It is the first study to demonstrate the interaction between the TMZ and dsDNA created from probe and target. We use specific oligonucleotides sequences instead of using long dsDNA sequences.
Materials for Advanced Ultra‐Supercritical Fossil‐Fuel Power Plants: Materials Properties, Microstructure, and Component Behavior
Authors: Speicher Magdalena , Hueggenberg Daniel , Klenk Andreas , Zickler Stefan , Metzger Klaus
Published: December 2015

Piping and components made of nickel alloys under plant specific loading conditions were tested to ensure the feasibility of high‐efficiency ultra‐supercritical coal‐fired power plants by using the test loop HWT II system (Hochtemperatur‐Werkstoff‐Teststrecke) installed in the fossil power plant GKM in Mannheim, Germany. The performance of the materials and the applicability of advanced numerical simulations for the lifetime assessment of components were performed. The results of materials investigations on Alloy 617 mod., Alloy 263, and their welded joints as well as numerical simulations for selected components under static and cyclic loading are presented.
Antioxidant activity and phenolic profiles of the wild currantRibes magellanicumfrom Chilean and Argentinean Patagonia
Authors: Jiménez‐Aspee Felipe , Thomas‐Valdés Samanta , Schulz Ayla , Ladio Ana , Theoduloz Cristina , Schmeda‐Hirschmann Guillermo
Published: December 2015

The Patagonian currantRibes magellanicumis highly valued due to its pleasant flavor and sweet taste. The aim of this study was to characterize its constituents and to assess their antioxidant and cytoprotective properties. For the fruit phenolic‐enriched extract (PEE), total phenolics (TP), total flavonoids (TF), and antioxidant activity (DPPH, Ferric reducing antioxidant power (FRAP), and Trolox equivalent antioxidant activity (TEAC)) were determined. Argentinean samples presented better activity in theDPPHandFRAPassays. Best cytoprotection against oxidative stress induced by H2O2inAGScells was found in one Argentinean sample at 500 μg mL−1(65.7%).HPLC MS/MSanalysis allowed the tentative identification of 59 constituents, including eight anthocyanins, 11 conjugates of caffeic‐, ferulic‐, and coumaric acid, and 38 flavonoids, most of them quercetin and kaempferol derivatives. Argentinean samples showed a more complex pattern of anthocyanins, hydroxycinnamic acids (HCA), and flavonoids. Cyanidin rhamnoside hexoside and cyanidin hexoside were the main anthocyanins, accounting for 35 and 55% for the Argentinean and 60 and 27% for the ripe Chilean fruits.HCAcontent was about three times higher in Argentinean samples. The phenolic profiles of Chilean and ArgentineanRibes magellanicumshow remarkable differences in chemical composition with higherHCAand flavonoid content in Argentinean samples.
Estimation and Hedging Effectiveness of Time‐Varying Hedge Ratio: Nonparametric Approaches
Authors: Fan Rui , Li Haiqi , Park Sung Y.
Published: December 2015

Many studies have estimated the optimal time‐varying hedge ratio using futures, with most employing a bivariate generalized autoregressive conditional heteroscedasticity (BGARCH) model or a random coefficient model to estimate the time‐varying hedge ratio. However, it has been argued that when the variability of the estimated time‐varying hedge ratio is large, this ratio's hedging performance is not as good as that of the unconditional (constant) hedge ratio. This study proposes a nonparametric estimation approach to estimate and evaluate the optimal conditional hedge ratio. This method produces a time‐varying hedge ratio with less volatility than those obtained from the BGARCH and random coefficient models. We evaluate the hedging performance of the various models using soybean oil, corn, S&P 500, and Hang Seng futures indices. The empirical results support the proposed nonparametric approach in terms of both in‐sample and out‐of‐sample performance. © 2015 Wiley Periodicals, Inc. Jrl Fut Mark 36:968–991, 2016
Bone morphogenetic protein 4 regulates microRNA expression in breast cancer cell lines in diverse fashion
Authors: Alarmo Emma‐Leena , Havunen Riikka , Häyrynen Sergei , Penkki Sanna , Ketolainen Johanna , Nykter Matti , Kallioniemi Anne
Published: December 2015

Bone morphogenetic protein 4 (BMP4) is a remarkably powerful inhibitor of breast cancer cell proliferation, but it is also able to induce breast cancer cell migration in certain cellular contexts. Previous data demonstrate that BMP4 controls the transcription of a variety of protein‐coding genes, but not much is known about microRNAs (miRNA) regulated by BMP4. To address this question, miRNA expression profiles following BMP4 treatment were determined in one mammary epithelial and seven breast cancer cell lines using microarrays. While the analysis revealed an extensive variation in differentially expressed miRNA across cell lines, four miRNAs (miR‐16‐5p, miR‐106b‐5p, miR‐23a‐3p, and miR‐23b‐3p) were commonly induced in a subset of breast cancer cells upon BMP4 treatment. Inhibition of their expression demonstrated an increase in BT‐474 cell number, indicating that they possess tumor suppressive properties. However, with the exception of miR‐106b‐5p, these effects were independent of BMP4 treatment. Scratch assay with miR‐16‐5p and miR‐106b‐5p inhibitors on BMP4‐treated MDA‐MB‐231 cells resulted in enhanced cell migration, suggesting that these miRNAs are engaged in BMP4‐induced motility. Taken together, we have for the first time characterized the BMP4‐induced miRNA expression profiles in breast cancer cell lines, showing that induced miRNAs contribute to the fine‐tuning of proliferation and migration phenotypes. © 2015 Wiley Periodicals, Inc.
miR expression profiling at diagnosis predicts relapse in pediatric precursor B‐cell acute lymphoblastic leukemia
Authors: Avigad Smadar , Verly Iedan RN , Lebel Asaf , Kordi Oshrit , Shichrur Keren , Ohali Anat , Hameiri‐Grossman Michal , Kaspers Gertjan JL , Cloos Jacqueline , Fronkova Eva , Trka Jan , Luria Drorit , Kodman Yona , Mirsky Hadar , Gaash Dafna , Jeison Marta , Avrahami Galia , Elitzur Sarah , Gilad Gil , Stark Batia , Yaniv Isaac
Published: December 2015

Our aim was to identify miRNAs that can predict risk of relapse in pediatric patients with acute lymphoblastic leukemia (ALL). Following high‐throughput miRNA expression analysis (48 samples), five miRs were selected for further confirmation performed by real time quantitative PCR on a cohort of precursor B‐cell ALL patients (n = 138). The results were correlated with clinical parameters and outcome. Low expression of miR‐151‐5p, and miR‐451, and high expression of miR‐1290 or a combination of all three predicted inferior relapse free survival (P = 0.007, 0.042, 0.025, and <0.0001, respectively). Cox regression analysis identified aberrant expression of the three miRs as an independent prognostic marker with a 10.5‐fold increased risk of relapse (P = 0.041) in PCR‐MRD non‐high risk patients. Furthermore, following exclusion of patients harboring IKZF1 deletion, the aberrant expression of all three miRs could identify patients with a 24.5‐fold increased risk to relapse (P < 0.0001). The prognostic relevance of the three miRNAs was evaluated in a non‐BFM treated precursor B‐cell ALL cohort (n = 33). A significant correlation between an aberrant expression of at least one of the three miRs and poor outcome was maintained (P < 0.0001). Our results identify an expression profile of miR‐151‐5p, miR‐451, and miR‐1290 as a novel biomarker for outcome in pediatric precursor B‐cell ALL patients, regardless of treatment protocol. The use of these markers may lead to improved risk stratification at diagnosis and allow early therapeutic interventions in an attempt to improve survival of high risk patients. © 2015 Wiley Periodicals, Inc.
Aspartate β‐hydroxylase modulates cellular senescence through glycogen synthase kinase 3β in hepatocellular carcinoma
Authors: Iwagami Yoshifumi , Huang Chiung‐Kuei , Olsen Mark J. , Thomas John‐Michael , Jang Grace , Kim Miran , Lin Qiushi , Carlson Rolf I. , Wagner Carl E. , Dong Xiaoqun , Wands Jack R.
Published: December 2015

Aspartate β‐hydroxylase (ASPH) is an enzyme overexpressed in human hepatocellular carcinoma (HCC) tumors that participates in the malignant transformation process. We determined if ASPH was a therapeutic target by exerting effects on cellular senescence to retard HCC progression. ASPH knockdown or knockout was achieved by short hairpin RNAs or the CRISPR/Cas9 system, respectively, whereas enzymatic inhibition was rendered by a potent second‐generation small molecule inhibitor of ASPH. Alterations of cell proliferation, colony formation, and cellular senescence were evaluated in human HCC cell lines. The potential mechanisms for activating cellular senescence were explored using murine subcutaneous and orthotopic xenograft models. Inhibition of ASPH expression and enzymatic activity significantly reduced cell proliferation and colony formation but induced tumor cell senescence. Following inhibition of ASPH activity, phosphorylation of glycogen synthase kinase 3β and p16 expression were increased to promote senescence, whereas cyclin D1 and proliferating cell nuclear antigen were decreased to reduce cell proliferation. The mechanisms involved demonstrate that ASPH binds to glycogen synthase kinase 3β and inhibits its subsequent interactions with protein kinase B and p38 upstream kinases as shown by coimmunoprecipitation. In vivo experiments demonstrated that small molecule inhibitor treatment of HCC bearing mice resulted in significant dose‐dependent reduced tumor growth, induced phosphorylation of glycogen synthase kinase 3β, enhanced p16 expression in tumor cells, and promoted cellular senescence. Conclusions: We have identified a new mechanism that promotes HCC growth and progression by modulating senescence of tumor cells; these findings suggest that ASPH enzymatic activity is a novel therapeutic target for HCC. (Hepatology 2016;63:1213–1226)
Reproductive risk factors in relation to molecular subtypes of breast cancer: Results from the nurses' health studies
Authors: Sisti Julia S. , Collins Laura C. , Beck Andrew H. , Tamimi Rulla M. , Rosner Bernard A. , Eliassen A. Heather
Published: December 2015

Several intrinsic breast cancer subtypes, possibly representing unique etiologic processes, have been identified by gene expression profiles. Evidence suggests that associations with reproductive risk factors may vary by breast cancer subtype. In the Nurses' Health Studies, we prospectively examined associations of reproductive factors with breast cancer subtypes defined using immunohistochemical staining of tissue microarrays. Multivariate‐adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Over follow‐up, we identified 2,063 luminal A, 1,008 luminal B, 209 HER2‐enriched, 378 basal‐like and 110 unclassified tumors. Many factors appeared associated with luminal A tumors, including ages at menarche (pheterogeneity = 0.65) and menopause (pheterogeneity = 0.05), and current HT use (pheterogeneity = 0.33). Increasing parity was not associated with any subtype (pheterogeneity = 0.76), though age at first birth was associated with luminal A tumors only (per 1‐year increase HR = 1.03 95%CI (1.02–1.05), pheterogeneity = 0.04). Though heterogeneity was not observed, duration of lactation was inversely associated with risk of basal‐like tumors only (7+ months vs. never HR = 0.65 95%CI (0.49–0.87), ptrend = 0.02), pheterogeneity = 0.27). Years between menarche and first birth was strongly positively associated with luminal A and non‐luminal subtypes (e.g. 22‐year interval vs. nulliparous HR = 1.80, 95%CI (1.08–3.00) for basal‐like tumors; pheterogeneity = 0.003), and evidence of effect modification by breastfeeding was observed. In summary, many reproductive risk factors for breast cancer appeared most strongly associated with the luminal A subtype. Our results support previous reports that lactation is protective against basal‐like tumors, representing a potential modifiable risk factor for this aggressive subtype.
Soluble B‐cell activation marker of sCD27 and sCD30 and future risk of B‐cell lymphomas: A nested case‐control study and meta‐analyses
Authors: Hosnijeh Fatemeh Saberi , Portengen Lutzen , Späth Florentin , Bergdahl Ingvar A. , Melin Beatrice , Mattiello Amalia , Masala Giovanna , Sacerdote Carlotta , Naccarati Alessio , Krogh Vittorio , Tumino Rosario , Chadeau‐Hyam Marc , Vineis Paolo , Vermeulen Roel
Published: December 2015

Prediagnostic serum/plasma concentrations of B‐cell activation markers have been associated with future risk of B‐cell lymphomas (BCL) in HIV‐infected patients and in the general population. Current evidence for the general population is however limited and relies on relatively small numbers of observations, especially for specific histologies. We carried out a nested case‐control study, including 218 BCL and 218 matched controls, within two prospective cohorts, to investigate the association between plasma levels of soluble (s)CD27 and sCD30 and future risk of BCL, and main histologic subtypes separately. To expand the evidence further, we performed meta‐analyses of the published data on these associations from prospective studies among the general population. Our study revealed a significant relationship between sCD30 concentration and BCL risk (OR = 0.86, 1.53, 1.76, for the 2nd–4th quartiles respectively, p trend = 0.01). Similar increased risks were observed for diffuse large B‐cell lymphoma and follicular lymphoma. Analyses of sCD27 blood concentrations did not show significant associations with BCL, (OR = 0.90, 1.26, 1.65 for the 2nd–4th quartiles, respectively, p trend = 0.17), but significant associations were observed for chronic lymphocytic leukaemia and for the group of “other BCL” subtypes. Our findings involving sCD30 were confirmed within our meta‐analyses of five prospective cohorts, while results were more heterogeneous for sCD27 with the exception of CLL which was found consistently in all studies. Data to date suggest that chronic B‐cell stimulation might be an important mechanism involved in B‐cell lymphomagenesis both in HIV‐infected and in the general population.
Progression of HPV infection to detectable cervical lesions or clearance in adult women: Analysis of the control arm of the VIVIANE study
Authors: Rachel Skinner S. , Wheeler Cosette M. , Romanowski Barbara , Castellsagué Xavier , Lazcano‐Ponce Eduardo , Rowena Del Rosario‐Raymundo M. , Vallejos Carlos , Minkina Galina , Pereira Da Silva Daniel , McNeil Shelly , Prilepskaya Vera , Gogotadze Irina , Money Deborah , Garland Suzanne M. , Romanenko Viktor , Harper Diane M. , Levin Myron J. , Chatterjee Archana , Geeraerts Brecht , Struyf Frank , Dubin Gary , Bozonnat Marie‐Cécile , Rosillon Dominique , Baril Laurence ,   for the VIVIANE study group
Published: December 2015

The control arm of the phase III VIVIANE (Human PapillomaVIrus: Vaccine Immunogenicity ANd Efficacy; NCT00294047) study in women >25 years was studied to assess risk of progression from cervical HPV infection to detectable cervical intraepithelial neoplasia (CIN). The risk of detecting CIN associated with the same HPV type as the reference infection was analysed using Kaplan–Meier and multivariable Cox models. Infections were categorised depending upon persistence as 6‐month persistent infection (6MPI) or infection of any duration. The 4‐year interim analysis included 2,838 women, of whom 1,073 (37.8%) experienced 2,615 infections of any duration and 708 (24.9%) experienced 1,130 6MPIs. Infection with oncogenic HPV types significantly increased the risk of detecting CIN grade 2 or greater (CIN2+) versus non‐oncogenic types. For 6MPI, the highest risk was associated with HPV‐33 (hazard ratio [HR]: 31.9 [8.3–122.2, p < 0.0001]). The next highest risk was with HPV‐16 (21.1 [6.3–70.0], p < 0.0001). Similar findings were seen for infections of any duration. Significant risk was also observed for HPV‐18, HPV‐31, and HPV‐45. Concomitant HPV infection or CIN grade 1 or greater associated with a different oncogenic HPV type increased risk. Most women (79.3%) with an HPV infection at baseline cleared detectable infections of any duration, and 69.9% cleared a 6MPI. The risk of progression of HPV infection to CIN2+ in women >25 years in this study was similar to that in women 15–25 years in PATRICIA.
Associations between unprocessed red and processed meat, poultry, seafood and egg intake and the risk of prostate cancer: A pooled analysis of 15 prospective cohort studies
Authors: Wu Kana , Spiegelman Donna , Hou Tao , Albanes Demetrius , Allen Naomi E. , Berndt Sonja I. , van den Brandt Piet A. , Giles Graham G. , Giovannucci Edward , Alexandra Goldbohm R. , Goodman Gary G. , Goodman Phyllis J. , Håkansson Niclas , Inoue Manami , Key Timothy J. , Kolonel Laurence N. , Männistö Satu , McCullough Marjorie L. , Neuhouser Marian L. , Park Yikyung , Platz Elizabeth A. , Schenk Jeannette M. , Sinha Rashmi , Stampfer Meir J. , Stevens Victoria L. , Tsugane Shoichiro , Visvanathan Kala , Wilkens Lynne R. , Wolk Alicja , Ziegler Regina G. , Smith‐Warner Stephanie A.
Published: December 2015

Reports relating meat intake to prostate cancer risk are inconsistent. Associations between these dietary factors and prostate cancer were examined in a consortium of 15 cohort studies. During follow‐up, 52,683 incident prostate cancer cases, including 4,924 advanced cases, were identified among 842,149 men. Cox proportional hazard models were used to calculate study‐specific relative risks (RR) and then pooled using random effects models. Results do not support a substantial effect of total red, unprocessed red and processed meat for all prostate cancer outcomes, except for a modest positive association for tumors identified as advanced stage at diagnosis (advanced(r)). For seafood, no substantial effect was observed for prostate cancer regardless of stage or grade. Poultry intake was inversely associated with risk of advanced and fatal cancers (pooled multivariable RR [MVRR], 95% confidence interval, comparing ≥45vs. <5 g/day: advanced 0.83, 0.70–0.99; trend testpvalue 0.29), fatal, 0.69, 0.59–0.82, trend testpvalue 0.16). Participants who ate ≥25versus<5 g/day of eggs (1 egg ∼ 50 g) had a significant 14% increased risk of advanced and fatal cancers (advanced 1.14, 1.01–1.28, trend testpvalue 0.01; fatal 1.14, 1.00–1.30, trend testpvalue 0.01). When associations were analyzed separately by geographical region (North Americavs. other continents), positive associations between unprocessed red meat and egg intake, and inverse associations between poultry intake and advanced, advanced(r) and fatal cancers were limited to North American studies. However, differences were only statistically significant for eggs. Observed differences in associations by geographical region warrant further investigation.
Vandetanib as a potential new treatment for estrogen receptor‐negative breast cancers
Authors: Hatem Rana , Labiod Dalila , Château‐Joubert Sophie , de Plater Ludmilla , El Botty Rania , Vacher Sophie , Bonin Florian , Servely Jean‐Luc , Dieras Véronique , Bièche Ivan , Marangoni Elisabetta
Published: December 2015

The receptor tyrosine kinase RET is implicated in the progression of luminal breast cancers (BC) but its role in estrogen receptor (ER) negative tumors is unknown. Here we investigated the expression of RET in breast cancer patients tumors and patient‐derived xenografts (PDX) and evaluated the therapeutic potential of Vandetanib, a tyrosin kinase inhibitor with strong activity against RET, EGFR and VEGFR2, in ER negative breast cancer PDX. The RT‐PCR analysis of RET expression in breast tumors of 446 patients and 57 PDX, showed elevated levels of RET in ER+ and HER2+ subtypes and in a small subgroup of triple‐negative breast cancers (TNBC). The activity of Vandetanib was tested in vivo in three PDX models of TNBC and one model of HER2+ BC with different expression levels of RET and EGFR. Vandetanib induced tumor regression in PDX models with high expression of RET or EGFR. The effect was associated with inhibition of RET/EGFR phosphorylation and MAP kinase pathway and increased necrosis. In a PDX model with no expression of RET nor EGFR, Vandetanib slowed tumor growth without inducing tumor regression. In addition, treatment by Vandetanib decreased expression of murine Vegf receptors and the endothelial marker Cd31 in the four PDX models tested, suggesting inhibition of tumor vascularization. In summary, these preclinical results suggest that Vandetanib treatment could be useful for patients with ER negative breast cancers overexpressing Vandetanib's main targets.
Biomedical Sciences From a New Perspective
Authors: Lady Grace
Published: December 2015

This column features essays written by current middle school and high school teachers, media specialists, librarians, literacy coaches, curriculum specialists, administrators, preservice teachers, teacher educators, and adolescent and adult learners. They highlight diverse perspectives on teaching and/or learning with literacies to inspire reader reflection.
Long‐term exposure to high levels of decabrominated diphenyl ether inhibits CD4 T‐cell functions in C57Bl/6 mice
Authors: Feng Yan , Zeng Weihong , Wang Ying , Shen Hao , Wang Yan
Published: December 2015

In recent years, the adverse health effects of decabrominated diphenyl ether (BDE‐209) have raised more concerns as a growing number of studies reported its persistence in the environment and abundance in the human population, especially in occupational environmental compartments and exposed personnel. This study applies our previous animal model simulating occupational exposure to BDE‐209 to investigate its potential adverse effects on CD4 T cells. Female C57Bl/6 mice were orally gavaged with BDE‐209 at a dose of 800 mg kg−1 every 2 days for 10 months and the blood of each mouse was collected for analysis. Kinetic changes of the peripheral immune system were investigated from 1 to 5 months of exposure. The chronic effects on cytokine production, proliferation and the antigen‐specific responses of CD4 T cells were evaluated at 7, 9 and 10 months, respectively. The results have shown that impaired proliferation and cytokine (IFN‐γ, IL‐2 or TNF‐α) production of CD4 T cells were observed in BDE‐209‐exposed mice, accompanied by increased T regulatory cells in the blood. BDE‐209 exposure in vitro also suppressed the reactivity of CD4 T cells at concentrations of 0.01, 0.1, 1 and 10 μM. Furthermore, we observed weaker antigen‐specific CD4 T‐cell responses to Listeria monocytogenes infection in the mice exposed to BDE‐209, suggesting decreased resistance to exogenous pathogens. Taken together, these observations indicate an impaired cellular immunity after long‐term and relative high‐dose exposure to BDE‐209 in adult mice. Copyright © 2015 John Wiley & Sons, Ltd.
Dihydroartemisinin, an Anti-Malaria Drug, Suppresses Estrogen Deficiency-Induced Osteoporosis, Osteoclast Formation, and RANKL-Induced Signaling Pathways
Authors: Zhou Lin , Liu Qian , Yang Mingli , Wang Tao , Yao Jun , Cheng Jianwen , Yuan Jinbo , Lin Xixi , Zhao Jinmin , Tickner Jennifer , Xu Jiake
Published: December 2015

Osteoporosis is an osteolytic disease that features enhanced osteoclast formation and bone resorption. Identification of agents that can inhibit osteoclast formation and function is important for the treatment of osteoporosis. Dihydroartemisinin is a natural compound used to treat malaria but its role in osteoporosis is not known. Here, we found that dihydroartemisinin can suppress RANKL-induced osteoclastogenesis and bone resorption in a dose-dependent manner. Dihydroartemisinin inhibited the expression of osteoclast marker genes such as cathepsin K, calcitonin receptor, and tartrate-resistant acid phosphatase (TRAcP). Furthermore, dihydroartemisinin inhibited RANKL-induced NF-κB and NFAT activity. In addition, using an in vivo ovariectomized mouse model, we show that dihydroartemisinin is able to reverse the bone loss caused by ovariectomy. Together, this study shows that dihydroartemisinin attenuates bone loss in ovariectomized mice through inhibiting RANKL-induced osteoclast formation and function. This indicates that dihydroartemisinin, the first physiology or medicine nobel prize discovery of China, is a potential treatment option against osteolytic bone disease. © 2015 American Society for Bone and Mineral Research.
Expression of cFLIPL Determines the Basal Interaction of Bcl‐2 With Beclin‐1 and Regulates p53 Dependent Ubiquitination of Beclin‐1 During Autophagic Stress
Authors: Ranjan Kishu , Pathak Chandramani
Published: December 2015

Autophagy and apoptosis are two different physiological processes, which is required for the maintenance of cellular homeostasis. The apoptosis associated proteins such as Bcl‐2 and p53 have a close association with autophagic proteins HMGB1 and Beclin‐1 to modulate autophagic signaling. We demonstrate here the involvement of anti‐apoptotic protein cFLIPL in the regulation of autophagy during cellular stress. We found that ectopic expression of cFLIPL decreases the sensitivity of HEK 293T cells against rapamycin and H2O2 induced autophagic stress. Notably, the selective knockdown of cFLIPL augments autophagic stress in the cells accompanied with JNK1 activation and p53 dependent ubiquitination of Beclin‐1. However, re‐expression of cFLIPL in cFLIP knockdown cells restores autophagic equilibrium collectively with reversible effects on JNK1 and Beclin‐1 integrity. The co‐immunoprecipitation analysis suggests that cFLIPL is essential to maintain the canonical interaction of Bcl‐2 with Beclin‐1 to regulate autophagic stress and cell death. Altogether, our findings suggest that expression of cFLIPL regulates the basal interaction of Bcl‐2 with Beclin‐1 and substantiates p53 dependent ubiquitination of Beclin‐1 during autophagic stress to determine the fate of cell death or survival. J. Cell. Biochem. 117: 1757–1768, 2016. © 2015 Wiley Periodicals, Inc.
microRNA‐16 Is Downregulated During Insulin Resistance and Controls Skeletal Muscle Protein Accretion
Authors: Lee David E. , Brown Jacob L. , Rosa Megan E. , Brown Lemuel A. , Perry Richard A. , Wiggs Michael P. , Nilsson Mats I. , Crouse Stephen F. , Fluckey James D. , Washington Tyrone A. , Greene Nicholas P.
Published: December 2015

Insulin resistant diabetes, currently at epidemic levels in developed countries, begins in the skeletal muscle and is linked to altered protein turnover. microRNAs downregulate targeted mRNA translation decreasing the amount of translated protein, thereby regulating many cellular processes. Regulation of miRNAs and their function in skeletal muscle insulin resistance is largely unexplored. The purpose of this study was to identify the effects of insulin resistance on contents of skeletal muscle miRNAs with potential functions in protein turnover. We examined miRs ‐1, ‐16, ‐23, ‐27, ‐133a, ‐133b, and ‐206 in muscles of Zucker rats. miR‐1 was 5‐ to 10‐fold greater in obesity, whereas miRs‐16 and ‐133b were repressed ∼50% in obese compared to lean rats, with no other alterations in miRNA contents. miR‐16 correlated to protein synthesis in lean, but not obese rats. miR‐16 reduction by lipid overload was verified in‐vivo by diet‐induced obesity and in‐vitro using a diacylglycerol analog. A role for miR‐16 in protein turnover of skeletal myocytes was established using transient overexpression and anti‐miR inhibition. miR‐16 overexpression resulted in lower protein synthesis (puromycin incorporation, ∼25–50%), mTOR (∼25%), and p70S6K1 (∼40%) in starved and insulin stimulated myoblasts. Conversely, anti‐miR‐16 increased basal protein synthesis (puromycin incorporation, ∼75%), mTOR (∼100%), and p70S6K1 (∼100%). Autophagy was enhanced by miR‐16 overexpression (∼50% less BCL‐2, ∼100% greater LC3II/I, ∼50% less p62) and impaired with miR‐16 inhibition (∼45% greater BCL‐2, ∼25% less total LC3, ∼50% greater p62). This study demonstrates reduced miR‐16 during insulin resistance and establishes miR‐16 control of protein accretion in skeletal muscle. J. Cell. Biochem. 117: 1775–1787, 2016. © 2015 Wiley Periodicals, Inc.
Epidemics of GI.2 sapovirus in gastroenteritis outbreaks during 2012−2013 in Osaka City, Japan
Authors: Iritani Nobuhiro , Yamamoto Seiji P. , Abe Niichiro , Kubo Hideyuki , Oka Tomoichiro , Kaida Atsushi
Published: December 2015

Sapovirus (SaV) is a causative agent of gastroenteritis in humans in both sporadic cases and outbreaks. During the period from January 2005 to August 2014, SaV was detected in 30 (5.9%) of 510 gastroenteritis outbreaks in Osaka City, Japan using real‐time RT‐PCR. Seasonal distribution of SaV‐associated outbreaks revealed an increase during the 2011–2012 season and the highest frequency of outbreaks during the 2012–2013 season. Genotyping analysis based on the capsid region demonstrated that the most common genotype was GI.2 (36.7%), in which the strains were closely related. The comparison of complete capsid gene sequences with 18 GI.2 strains (7 strains in this study and 11 from GenBank) between 1990 and 2013 showed that GI.2 strains were classified into at least three genetic clusters (1990–2000, 2004–2007, and 2008–2013) with chronologically unique amino acid residues and accumulation of mutations in the predicted P domain, suggesting the one of the causes of emergence and spread of GI.2 strains. This study will also be helpful for understanding the evolutionary mechanism of the SaV genome. J. Med. Virol. 88:1187–1193, 2016. © 2015 Wiley Periodicals, Inc.
Clinical and biological significance of PIM1 kinase in osteosarcoma
Authors: Liao Yunfei , Feng Yong , Shen Jacson , Gao Yan , Cote Gregory , Choy Edwin , Harmon David , Mankin Henry , Hornicek Francis , Duan Zhenfeng
Published: December 2015

Osteosarcoma is the most prevalent histological form of primary malignant bone tumor. The majority of osteosarcoma patients have limited alternative therapeutic options and metastatic patients generally have a poor prognosis. Proto‐oncogene serine/threonine‐protein kinase PIM1 is associated with growth and survival of many kinds of tumor cells. However, the role of PIM1 in osteosarcoma remains largely unknown. In this study, we investigated the functional and therapeutic relevance of PIM1 as a putative target in osteosarcoma. We found PIM1 was highly expressed in various osteosarcoma cell lines and in tumor tissues from osteosarcoma patients. Tissue microarray and immunohistochemistry analysis showed that the overall and disease‐free survival rate of patients with high levels of PIM1 protein expression were significantly shorter than patients with low levels. High levels of PIM1 were also associated with present metastasis and can be considered as an independent prognostic factor in osteosarcoma patients. Knockdown of PIM1 expression by synthetic siRNA or shRNA greatly inhibited cell growth, migration, and invasion. Moreover, these changes accompanied with down‐regulation of anti‐apoptotic protein Bcl‐2. The similar results were obtained in osteosarcoma cells treated with PIM1 specific inhibitor (SMI‐4a). These results suggest that PIM1 kinase is critical for the growth and metastasis of osteosarcoma cells and can be a potential therapeutic target for osteosarcoma treatment. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1185–1194, 2016.
Nontumoral portal vein thrombosis in patients awaiting liver transplantation
Authors: Chen Hui , Turon Fanny , Hernández‐Gea Virginia , Fuster Josep , Garcia‐Criado Angeles , Barrufet Marta , Darnell Anna , Fondevila Constantino , Garcia‐Valdecasas Juan Carlos , Garcia‐Pagán Juan Carlos
Published: December 2015

Portal vein thrombosis (PVT) occurs in approximately 2%‐26% of the patients awaiting liver transplantation (LT) and is no longer an absolute contraindication for LT. Nearly half of PVT cases are accidentally found during the LT procedure. The most important risk factor for PVT development in cirrhosis may be the severity of liver disease and reduced portal blood flow. Whether other inherited or acquired coagulation disorders also play a role is not yet clear. The development of PVT may have no effect on the liver disease progression, especially when it is nonocclusive. PVT may not increase the risk of wait‐list mortality, but it is a risk factor for poor early post‐LT mortality. Anticoagulation and transjugular intrahepatic portosystemic shunt (TIPS) are 2 major treatment strategies for patients with PVT on the waiting list. The complete recanalization rate after anticoagulation is approximately 40%. The role of TIPS to maintain PV patency for LT as the primary indication has been reported, but the safety and efficacy should be further evaluated. PVT extension and degree may determine the surgical technique to be used during LT. If a “conventional” end‐to‐end portal anastomotic technique is used, there is not a major impact on post‐LT survival. Post‐LT PVT can significantly reduce both graft and patient survival after LT and can preclude future options for re‐LT. Liver Transpl 22:352‐365, 2016. © 2015 AASLD.
Minimum graft size calculated from preoperative recipient status in living donor liver transplantation
Authors: Marubashi Shigeru , Nagano Hiroaki , Eguchi Hidetoshi , Wada Hiroshi , Asaoka Tadafumi , Tomimaru Yoshito , Tomokuni Akira , Umeshita Koji , Doki Yuichiro , Mori Masaki
Published: December 2015

Small‐for‐size graft syndrome is an inevitable complication in living donor liver transplantation (LDLT). We hypothesized that graft weight (GW) measured after graft procurement is one of the variables predicting postoperative graft function. A total of 138 consecutive recipients of adult‐to‐adult LDLT between March 1999 and October 2014 were included in this study. We investigated the factors associated with small‐for‐size–associated graft loss (SAGL) to determine the GW required for each patient. Both preoperatively assessed and postoperatively obtained risk factors for SAGL were analyzed in univariate and multivariate logistic regression analysis. Twelve (8.8%) of the transplant recipients had SAGL. In multivariate logistic regression analyses using preoperatively assessed variables, the preoperative Model for End‐Stage Liver Disease (MELD) score (P < 0.001) and actual GW/recipient standard liver volume (SLV) ratio (P = 0.008) were independent predictors of SAGL. The recommended graft volume by preoperative computed tomography volumetry was calculated as SLV × (1.616 × MELD + 0.344)/100/0.85 (mL) [MELD ≥ 18.2], or SLV × 0.35 (mL) [MELD < 18.2]. The required allograft volume in LDLT can be determined by the preoperative MELD score of the recipient, and patients with higher MELD scores require larger grafts or deceased donor whole liver transplant to avoid SAGL. Liver Transplantation 22 599‐606 2016 AASLD.
Substantia Nigra Echogenicity Predicts Response to Drug Withdrawal in Suspected Drug‐Induced Parkinsonism
Authors: López‐Sendón Moreno Jose L. , Alonso‐Cánovas Araceli , Buisán Catevilla Javier , García Barragán Nuria , Corral Corral Iñigo , de Felipe Mimbrera Alicia , Matute Lozano María Consuelo , Masjuan Vallejo Jaime , Martínez‐Castrillo Juan Carlos
Published: December 2015

Introduction

Response to drug withdrawal in patients with suspected drug‐induced parkinsonism (DIP) is of prognostic and therapeutic importance, but cannot be predicted solely on clinical information. The aim of this study was to validate SN hyperechogenicity (SN+) assessed by transcranial sonography as a predictor of response to drug withdrawal in this group of patients.

Methods

Patients were diagnosed according to previously published criteria and prospectively included in the study. All patients were followed until complete recovery of parkinsonian symptoms or at least for 6 months after discontinuation of the offending drug and then diagnosed as DIP or parkinsonism following neuroleptic exposure (PFNE). Transcranial sonography (TCS) findings were compared with the clinical diagnosis.

Results

Sixty patients comprised the group for the final analysis. Sixteen patients were classified as PFNE and 44 as DIP. The area of SN echogenicity was significantly increased in the PFNE group (0.23 cm2; standard deviation [SD]: 0.04), compared to the DIP group (0.14 cm2; SD, 0.05; one‐way analysis of variance; P < 0.001). Normal SN was significantly associated with complete recovery after withdrawal of the parkinsonism‐inducing drug (P < 0.0005). Accuracy of SN+ to distinguish PFNE from DIP was: sensitivity 81.2%; specificity 84.1%; positive predictive value 47.4%; and negative predictive value 96.2%.

Conclusions

We believe that SN+ assessed with TCS is a valid prognostic marker in the setting of suspected DIP. It is a nonexpensive, feasible technique that can be implemented for proper counseling and guidance of treatment decisions.
Ritz–Galerkin method for solving a parabolic equation with non‐local and time‐dependent boundary conditions
Authors: Zhou Jian‐Rong , Li Heng , Xu Yongzhi
Published: December 2015

The paper is devoted to the investigation of a parabolic partial differential equation with non‐local and time‐dependent boundary conditions arising from ductal carcinoma in situ model. Approximation solution of the present problem is implemented by the Ritz–Galerkin method, which is a first attempt at tackling parabolic equation with such non‐classical boundary conditions. In the process of dealing with the difficulty caused by integral term in non‐local boundary condition, we use a trick of introducing the transition function G(x,t) to convert non‐local boundary to another non‐classical boundary, which can be handled with the Ritz–Galerkin method. Illustrative examples are included to demonstrate the validity and applicability of the technique in this paper. Copyright © 2015 John Wiley & Sons, Ltd.
Local well‐posedness of critical nonlinear Schrödinger equation on Zoll manifolds of odd‐growth
Authors: Zhao Tengfei
Published: December 2015

In this paper, we study the nonlinear Schrödinger equation on Zoll manifolds with odd order nonlinearities. We will obtain the local well‐poesdness in the critical space
. This extends the recent results in the literature to the Zoll manifolds of dimension d≥2 with general odd order nonlinearities and also partially improves the previous results in the subcritical spaces of Yang to the critical cases. Copyright © 2015 John Wiley & Sons, Ltd.
Concentrated terms and varying domains in elliptic equations: Lipschitz case
Authors: Aragão Gleiciane S. , Bruschi Simone M.
Published: December 2015

In this paper, we analyze the behavior of a family of solutions of a nonlinear elliptic equation with nonlinear boundary conditions, when the boundary of the domain presents a highly oscillatory behavior, which is uniformly Lipschitz and nonlinear terms, are concentrated in a region, which neighbors the boundary of domain. We prove that this family of solutions converges to the solutions of a limit problem inH1an elliptic equation with nonlinear boundary conditions which captures the oscillatory behavior of the boundary and whose nonlinear terms are transformed into a flux condition on the boundary. Indeed, we show the upper semicontinuity of this family of solutions.Copyright © 2015 John Wiley & Sons, Ltd.
A sufficient condition for blowup of solutions to a class of pseudo‐parabolic equations with a nonlocal term
Authors: Zhu Xiaoli , Li Fuyi , Liang Zhanping , Rong Ting
Published: December 2015

A sufficient condition for blowup of solutions to a class of pseudo‐parabolic equations with a nonlocal term is established in this paper. In virtue of the potential wells method, we first extend the results obtained by Xu and Su in [J. Funct. Anal., 264 (12): 2732‐2763, 2013] to the nonlocal case and describe successfully the behavior of solutions by using the energy functional, Nehari functional, and the ground state energy of the stationary equation. Sequently, we study the boundedness and convergency of any global solution. Finally, we achieve a criterion to guarantee the blowup of solutions without any limit of the initial energy.Copyright © 2015 John Wiley & Sons, Ltd.
Globalexponential stability of an epidemic model with saturated and periodic incidence rate
Authors: Xu Yanli , Li Lingwei
Published: December 2015

This paper is concerned with a SIR model with saturated and periodic incidence rate and saturated treatment function. By using differential inequality technique, we employ a novel argument to show that the disease‐free equilibrium is globally exponentially stable. The obtained results improve and supplement existing ones. We also use numerical simulations to demonstrate our theoretical results. Copyright © 2015 John Wiley & Sons, Ltd.
Application of intravoxel incoherent motion perfusion imaging to shoulder muscles after a lift‐off test of varying duration
Authors: Nguyen Audrey , Ledoux Jean‐Baptiste , Omoumi Patrick , Becce Fabio , Forget Joachim , Federau Christian
Published: December 2015

Intravoxel incoherent motion (IVIM) MRI is a method to extract microvascular blood flow information out of diffusion‐weighted images acquired at multiple b‐values. We hypothesized that IVIM can identify the muscles selectively involved in a specific task, by measuring changes in activity‐induced local muscular perfusion after exercise. We tested this hypothesis using a widely used clinical maneuver, the lift‐off test, which is known to assess specifically the subscapularis muscle functional integrity. Twelve shoulders from six healthy male volunteers were imaged at 3 T, at rest, as well as after a lift‐off test hold against resistance for 30 s, 1 and 2 min respectively, in three independent sessions. IVIM parameters, consisting of perfusion fraction (f), diffusion coefficient (D), pseudo‐diffusion coefficient D* and blood flow‐related fD*, were estimated within outlined muscles of the rotator cuff and the deltoid bundles. The mean values at rest and after the lift‐off tests were compared in each muscle using a one‐way ANOVA. A statistically significant increase in fD* was measured in the subscapularis, after a lift‐off test of any duration, as well as in D. A fD* increase was the most marked (30 s, +103%; 1 min, +130%; 2 min, +156%) and was gradual with the duration of the test (in 10‐3 mm2/s: rest, 1.41 ± 0.50; 30 s, 2.86 ± 1.17; 1 min, 3.23 ± 1.22; 2 min, 3.60 ± 1.21). A significant increase in fD* and D was also visible in the posterior bundle of the deltoid. No significant change was consistently visible in the other investigated muscles of the rotator cuff and the other bundles of the deltoid. In conclusion, IVIM fD* allows the demonstration of a task‐related microvascular perfusion increase after a specific task and suggests a direct relationship between microvascular perfusion and the duration of the effort. It is a promising method to investigate non‐invasively skeletal muscle physiology and clinical perfusion‐related muscular disorders. Copyright © 2015 John Wiley & Sons, Ltd.