bluuebunny/crossref_metadata_2025 huggingface dataset:
Survey of 548 oncogenic fusion transcripts in thyroid tumors supports the importance of the already established thyroid fusions genes
Authors: Celestino Ricardo , Sigstad Eva , Løvf Marthe , Thomassen Gard O. S. , Grøholt Krystyna K. , Jørgensen Lars H. , Berner Aasmund , Castro Patrícia , Lothe Ragnhild A. , Bjøro Trine , Sobrinho‐Simões Manuel , Soares Paula , Skotheim Rolf I.
Published: September 2012

Neoplasms frequently present structural chromosomal aberrations that can alter the level of expression of a protein or to the expression of an aberrant chimeric protein. In the thyroid, the PAX8‐PPARG fusion is present in the neoplastic lesions that have a follicular architecture—follicular thyroid carcinoma (FTC) and follicular variant of papillary thyroid carcinoma (FVPTC), and less frequently in follicular thyroid adenoma (FTA), while the presence of RET/PTC fusions are largely restricted to papillary thyroid carcinoma (PTC). The ability to detect fusion genes is relevant for a correct diagnosis and for therapy. We have developed a new fusion gene microarray‐based approach for simultaneous analysis of all known and predicted fusion gene variants. We did a comprehensive screen for 548 known and putative fusion genes in 27 samples of thyroid tumors and three positive controls—one thyroid cancer cell line (TPC‐1) and two PTCs with known CCDC6‐RET (alias RET/PTC1) fusion gene, using this microarray. Within the thyroid tumors tested, only well known, previously reported fusion genes in thyroid oncology were identified. Our results reinforce the pathogenic role played by RET/PTC1, RET/PTC3, and PAX8‐PPARG fusion genes in thyroid tumorigenesis. © 2012 Wiley Periodicals, Inc.
SOCIETAL VIEWS ON NICE, CANCER DRUGS FUND AND VALUE‐BASED PRICING CRITERIA FOR PRIORITISING MEDICINES: A CROSS‐SECTIONAL SURVEY OF 4118 ADULTS IN GREAT BRITAIN
Authors: Linley Warren G. , Hughes Dyfrig A.
Published: September 2012

The criteria used by the National Institute for Health and Clinical Excellence (NICE) for accepting higher incremental cost‐effectiveness ratios for some medicines over others, and the recent introduction of the Cancer Drugs Fund (CDF) in England, are assumed to reflect societal preferences for National Health Service resource allocation. Robust empirical evidence to this effect is lacking. To explore societal preferences for these and other criteria, including those proposed for rewarding new medicines under the future value‐based pricing (VBP) system, we conducted a choice‐based experiment in 4118 UK adults via web‐based surveys. Preferences were determined by asking respondents to allocate fixed funds between different patient and disease types reflecting nine specific prioritisation criteria. Respondents supported the criteria proposed under the VBP system (for severe diseases, address unmet needs, are innovative—provided they offered substantial health benefits, and have wider societal benefits) but did not support the end‐of‐life premium or the prioritisation of children or disadvantaged populations as specified by NICE, nor the special funding status for treatments of rare diseases, nor the CDF. Policies introduced on the basis of perceived—and not actual—societal values may lead to inappropriate resource allocation decisions with the potential for significant population health and economic consequences. Copyright © 2012 John Wiley & Sons, Ltd.
Impairment of CD4+ cytotoxic T cells predicts poor survival and high recurrence rates in patients with hepatocellular carcinoma
Authors: Fu Junliang , Zhang Zheng , Zhou Lin , Qi Zhaorui , Xing Shaojun , Lv Jiyun , Shi Jianfei , Fu Baoyun , Liu Zhenwen , Zhang Ji-Yuan , Jin Lei , Zhao Yulai , Lau George K.K. , Zhao Jingmin , Wang Fu-Sheng
Published: September 2012

The role of CD4+ cytotoxic T cells (CTLs) in hepatocellular carcinoma (HCC) remains obscure. This study characterized CD4+ CTLs in HCC patients and further elucidated the associations between CD4+ CTLs and HCC disease progression. In all, 547 HCC patients, 44 chronic hepatitis B (CHB) patients, 86 liver cirrhosis (LC) patients, and 88 healthy individuals were enrolled in the study. CD4+ CTLs were defined by flow cytometry, immunohistochemistry, and lytic granule exocytosis assays. A multivariate analysis of prognostic factors for overall survival was performed using the Cox proportional hazards model. Circulating and liver-infiltrating CD4+ CTLs were found to be significantly increased in HCC patients during early stage disease, but decreased in progressive stages of HCC. This loss of CD4+ CTLs was significantly correlated with high mortality rates and reduced survival time of HCC patients. In addition, the proliferation, degranulation, and production of granzyme A, granzyme B, and perforin of CD4+ CTLs were inhibited by the increased forkhead/winged helix transcription factor (FoxP3+) regulatory T cells in these HCC patients. Further analysis showed that both circulating and tumor-infiltrating CD4+ CTLs were independent predictors of disease-free survival and overall survival after the resection of the HCC. Conclusion: The progressive deficit in CD4+ CTLs induced by increased FoxP3+ regulatory T cells was correlated with poor survival and high recurrence rates in HCC patients. These data suggest that CD4+ CTLs may represent both a potential prognostic marker and a therapeutic target for the treatment of HCC. (HEPATOLOGY 2013)
Single determination of C-reactive protein at the time of diagnosis predicts long-term outcome of patients with hepatocellular carcinoma
Authors: Sieghart Wolfgang , Pinter Matthias , Hucke Florian , Graziadei Ivo , Schöniger-Hekele Maximilian , Müller Christian , Vogel Wolfgang , Trauner Michael , Peck-Radosavljevic Markus
Published: September 2012

We investigated the prognostic value of C-reactive protein (CRP) in patients with hepatocellular carcinoma (HCC) not amenable to surgery. A total of 615 patients diagnosed with HCC not amenable to surgery between April 1999 and December 2009 at the Department of Gastroenterology of the Medical Universities of Vienna and Innsbruck were included. We assessed the optimal CRP cutoff by regression spline analysis and tested its impact on median overall survival (OS) by the Kaplan-Meier method, univariate analysis (log-rank test), and multivariate analysis (Cox proportional hazard regression model) in a training cohort (n = 466, Vienna) and an independent validation cohort (n = 149, Innsbruck). We found a sigmoid-shaped association of CRP and the hazard ratio of death upon regression spline analysis and defined a CRP level <1/≥1 mg/dL as optimal cutoff for further survival assessments. Elevated CRP (≥1 mg/dL) at diagnosis was associated with poor OS (CRP-elevated versus CRP-normal; 4 versus 20 months;

P

< 0.001) and remained a significant negative predictor for OS upon multivariate analysis (hazard ratio, 1.7;

P

< 0.001), which was independent of age, Child-Pugh class, tumor characteristics, and treatment allocation. Analyses with respect to Barcelona Clinic Liver Cancer (BCLC) stage and Child-Pugh class supported the relevance of CRP (BCLC-stage C and Child-Pugh A: OS for CRP-elevated versus CRP-normal, 6 versus 14;

P

< 0.001; BCLC-stage C and Child-Pugh B: OS for CRP-elevated versus CRP-normal, 4 versus 15 months;

P

< 0.001). The prognostic significance of elevated CRP was reproducible at a second CRP determination timepoint and confirmed in the independent validation cohort.

Conclusion:

Elevated CRP is associated with a dismal prognosis in HCC patients and may become a useful marker for patient selection in HCC management.
Ammonia control and neurocognitive outcome among urea cycle disorder patients treated with glycerol phenylbutyrate
Authors: Diaz George A. , Krivitzky Lauren S. , Mokhtarani Masoud , Rhead William , Bartley James , Feigenbaum Annette , Longo Nicola , Berquist William , Berry Susan A. , Gallagher Renata , Lichter-Konecki Uta , Bartholomew Dennis , Harding Cary O. , Cederbaum Stephen , McCandless Shawn E. , Smith Wendy , Vockley Gerald , Bart Stephen A. , Korson Mark S. , Kronn David , Zori Roberto , Merritt Lawrence J. , Nagamani Sandesh C.S. , Mauney Joseph , LeMons Cynthia , Dickinson Klara , Moors Tristen L. , Coakley Dion F. , Scharschmidt Bruce F. , Lee Brendan
Published: September 2012

Glycerol phenylbutyrate is under development for treatment of urea cycle disorders (UCDs), rare inherited metabolic disorders manifested by hyperammonemia and neurological impairment. We report the results of a pivotal Phase 3, randomized, double-blind, crossover trial comparing ammonia control, assessed as 24-hour area under the curve (NH3-AUC0-24hr), and pharmacokinetics during treatment with glycerol phenylbutyrate versus sodium phenylbutyrate (NaPBA) in adult UCD patients and the combined results of four studies involving short- and long-term glycerol phenylbutyrate treatment of UCD patients ages 6 and above. Glycerol phenylbutyrate was noninferior to NaPBA with respect to ammonia control in the pivotal study, with mean (standard deviation, SD) NH3-AUC0-24hr of 866 (661) versus 977 (865) μmol·h/L for glycerol phenylbutyrate and NaPBA, respectively. Among 65 adult and pediatric patients completing three similarly designed short-term comparisons of glycerol phenylbutyrate versus NaPBA, NH3-AUC0-24hr was directionally lower on glycerol phenylbutyrate in each study, similar among all subgroups, and significantly lower (

P

< 0.05) in the pooled analysis, as was plasma glutamine. The 24-hour ammonia profiles were consistent with the slow-release behavior of glycerol phenylbutyrate and better overnight ammonia control. During 12 months of open-label glycerol phenylbutyrate treatment, average ammonia was normal in adult and pediatric patients and executive function among pediatric patients, including behavioral regulation, goal setting, planning, and self-monitoring, was significantly improved.

Conclusion:

Glycerol phenylbutyrate exhibits favorable pharmacokinetics and ammonia control relative to NaPBA in UCD patients, and long-term glycerol phenylbutyrate treatment in pediatric UCD patients was associated with improved executive function (ClinicalTrials.gov NCT00551200, NCT00947544, NCT00992459, NCT00947297).
Disruption of the histidine triad nucleotide-binding hint2 gene in mice affects glycemic control and mitochondrial function
Authors: Martin Juliette , Maurhofer Olivier , Bellance Nadège , Benard Giovanni , Graber Franziska , Hahn Dagmar , Galinier Anne , Hora Caroline , Gupta Anirudh , Ferrand Gisèle , Hoppeler Hans , Rossignol Rodrigue , Dufour Jean-François , St-Pierre Marie V.
Published: September 2012

The histidine triad nucleotide-binding (HINT2) protein is a mitochondrial adenosine phosphoramidase expressed in the liver and pancreas. Its physiological function is unknown. To elucidate the role of HINT2 in liver physiology, the mouse

Hint2

gene was deleted.

Hint2

−/− and

Hint2

+/+ mice were generated in a mixed C57Bl6/J × 129Sv background. At 20 weeks, the phenotypic changes in

Hint2

−/− relative to

Hint2

+/+ mice were an accumulation of hepatic triglycerides, decreased tolerance to glucose, a defective counter-regulatory response to insulin-provoked hypoglycemia, and an increase in plasma interprandial insulin but a decrease in glucose-stimulated insulin secretion and defective thermoregulation upon fasting. Leptin messenger RNA (mRNA) in adipose tissue and plasma leptin were elevated. In mitochondria from

Hint2

−/− hepatocytes, state 3 respiration was decreased, a finding confirmed in HepG2 cells where

HINT2

mRNA was silenced. The linked complex II-III electron transfer was decreased in

Hint2

−/− mitochondria, which was accompanied by a lower content of coenzyme Q. Hypoxia-inducible factor-2α expression and the generation of reactive oxygen species were increased. Electron microscopy of mitochondria in

Hint2

−/− mice aged 12 months revealed clustered, fused organelles. The hepatic activities of 3-hydroxyacyl-coenzyme A dehydrogenase short chain and glutamate dehydrogenase (GDH) were decreased by 68% and 60%, respectively, without a change in protein expression. GDH activity was similarly decreased in HINT2-silenced HepG2 cells. When measured in the presence of purified sirtuin 3, latent GDH activity was recovered (126% in

Hint2

−/− versus 83% in

Hint2

+/+). This suggests a greater extent of acetylation in

Hint2

−/− than in

Hint2

+/+.

Conclusion :

Hint2/HINT2 positively regulates mitochondrial lipid metabolism and respiration and glucose homeostasis. The absence of Hint2 provokes mitochondrial deformities and a change in the pattern of acetylation of selected proteins.
Nigerian resident doctors on strike: insights from and policy implications of job satisfaction among resident doctors in a Nigerian teaching hospital
Authors: Akinyemi Oluwaseun , Atilola Olayinka
Published: September 2012

Objectives

The Nigerian health system has been engulfed in a crisis occasioned by a deluge of strike actions by resident doctors in recent times. Dissatisfaction with conditions of service has been cited as the bone of contention. Job satisfaction studies among doctors have provided insights into the contributory factors to recurrent industrial disputes in other climes. This study aims to determine the predictors of job satisfaction among resident doctors in a tertiary healthcare centre in Nigeria. This is with a view to gain some insights into the possible contributory factors to industrial disputes and to discuss the policy implications of such findings.

Methods

A semi‐structured questionnaire was used to obtain socio‐demographic characteristics and job‐related determinants of job satisfaction among resident doctors. Logistic regression analysis was carried out to determine predictors of job satisfaction.

Findings

A total of 163 resident doctors completed the study. Overall, 90 (55.2%) of the resident doctors were satisfied with their jobs. Lower age, career advancement opportunities, autonomy of practice, alignment of job with core personal and professional values, and working environment predicted job satisfaction.

Conclusions

To restore satisfaction and possibly stem industrial disputes by resident doctors, government of Nigeria needs to sustain current wages while introducing non‐financial benefits. There is a need to adopt policies geared towards increasing government spending on health especially in the area of human capacity and infrastructural development, so as to afford resident doctors opportunities for skill acquisition and career development. Copyright © 2012 John Wiley & Sons, Ltd.
Hydrologic impact of regional climate change for the snowfed and glacierfed river basins in the Republic of Tajikistan: hydrological response of flow to climate change
Authors: Kure S. , Jang S. , Ohara N. , Kavvas M. L. , Chen Z. Q.
Published: September 2012

The warming of the Earth's atmosphere system is likely to change temperature and precipitation, which may affect the climate, hydrology and water resources at the river basins over the world. The importance of temperature change becomes even greater in snow or glacier dominated basins where it controls the snowmelt processes during the late‐winter, spring and summer months. In this study hydrologic responses of streamflow in the Pyanj and Vaksh River basins to climate change are analysed with a watershed hydrology model, based on the downscaled atmospheric data as input, in order to assess the regional climate change impact for the snowfed and glacierfed river basins in the Republic of Tajikistan. As a result of this analysis, it was found that the annual mean river discharge is increasing in the future at snow and glacier dominated areas due to the air temperature increase and the consequent increase in snow/ice melt rates until about 2060. Then the annual mean flow discharge starts to decrease from about 2080 onward because the small glaciers start to disappear in the glacier areas. It was also found that there is a gradual change in the hydrologic flow regime throughout a year, with the high flows occuring earlier in the hydrologic year, due to the warmer climate in the future. Furthermore, significant increases in annual maximum daily flows, including the 100‐year return period flows, at the Pyanj and Vaksh River basins toward the end of the 21st century can be inferred from flood frequency analysis results. Copyright © 2012 John Wiley & Sons, Ltd.
Spatial delineation of groundwater–surface water interactions through intensive in‐stream profiling
Authors: Haria Atul H. , Shand Paul , Soulsby Chris , Noorduijn Saskia
Published: September 2012

The dominance of ‘old’ pre‐event water in headwater storm runoff has been recorded in numerous upland catchment studies; however, the mechanisms by which this pre‐event water enters the stream channel are poorly understood. Understanding these processes is fundamental to determining the controls on surface water quality and associated impacts on stream ecology. Previous studies in the upland forested catchment of the Afon Hafren (River Severn) at Plynlimon, mid‐Wales, identified an active bedrock groundwater system that was discharging into the stream channel during storm response. Detailed analysis showed that these discharges were small and could not account for the majority of pre‐event storm water response identified at this site; pre‐event storm runoff had to be sourced predominantly from further upstream. An intensive stream survey was used to determine the spatial nature of groundwater–surface water (GW–SW) interactions in the Hafren Catchment. Detailed physico‐chemical in‐stream profiling identified a marked change in water quality indicating a significant discrete point of bedrock groundwater discharge upstream of the Hafren Transect study site. The in‐stream profiling showed the importance of high spatial resolution sampling as a key to understanding processes of GW–SW interaction and how quick and cost‐effective measurements of specific electrical conductance of stream waters could be used to highlight in‐stream heterogeneity. This approach is recommended for use in headwater catchments for initial characterisation of the stream channel in order to better locate instrumentation and to determine more effective targeted sampling protocols in upland catchment research. Copyright © 2012 John Wiley & Sons, Ltd.
Russian nesting dolls effect – Using wavelet analysis to reveal non‐stationary and nested stationary signals in water yield from catchments on a northern forested landscape
Authors: Mengistu Samson G. , Creed Irena F. , Kulperger Reg J. , Quick Christopher G.
Published: September 2012

Determining catchment responses to climate signals gives insight into the potential effects of climate change. This study tested the hypothesis that a 28‐year time series of water yields from four headwater catchments in the Turkey Lakes Watershed (TLW), Ontario contains signals of non‐stationary climate change and naturally occurring stationary climate oscillations and that the effects of these signals are greater in catchments with lower rates of change in water loading and lower water storage capacity (small wetlands). Non‐stationary trends explained 0%, 18%, 44%, and 52% of the variance in the water yields of the four catchments. Wavelet analysis using Morlet wavelets identified stationary responses at multiple temporal scales, increasing the amount of variance explained to 56%, 63%, 76%, and 81% when combining stationary and non‐stationary models. The catchment with low water loading and low water storage was most sensitive to non‐stationary and stationary signals, suggesting that these catchments act as sentinels to detect climatic signals. Wavelet coherence analysis revealed correlations between global climate oscillation indices and water yield. The Atlantic Multidecadal Oscillation (AMO) index was strongly correlated with both temperature and precipitation (R2 = 0.46, P < 0.001 and R2 of 0.34, P < 0.001, respectively). Temperature in the TLW increased by 0.067 °C per year from 1981 to 2008, but approximately 0.037 °C of this increase can be explained by the AMO index. While it is likely that anthropogenic climate change impacts water yields, it is important to account for multiple nested climate oscillations to avoid exaggerating its effects. Copyright © 2012 John Wiley & Sons, Ltd.
How Do Career Centers Use Social Networking Sites?
Authors: Osborn Debra S. , LoFrisco Barbara M.
Published: September 2012

The popularity and growth of social networking sites (SNSs), particularly among the college‐aged demographic, makes them logical tools for university career centers to use to connect with students. The authors surveyed 78 university career centers to determine how they use SNSs, the benefits and drawbacks, and the advice they would give to a career center considering using SNSs. The most commonly used SNSs by this sample include Facebook, LinkedIn, and Twitter, mainly to provide career information. Benefits included students’ responsivity to the SNS posts and increased visibility and attendance at events; the main drawback was time required. The most common recommendation was to determine goals and plan implementation.
Midlife Career Transitions of Men Who Are Scientists and Engineers: A Narrative Study
Authors: Liu Yosen , Englar‐Carlson Matt , Minichiello Victor
Published: September 2012

This article summarizes the results of a qualitative study of career transition experiences of middle‐aged male scientists and engineers in the current socioeconomic environment in the United States. The study addresses the effects of the transitions from psychosocial perspectives. The authors selected participants from research organizations, industry, and academic fields. The authors used a narrative approach to collect data and analyzed the data using a grounded theory approach. The results suggest that the major factors that describe the dynamics in the career transition experiences are personhood, relationships, lifestyle, and workplace environment. The findings and their implications in developing coping skills and counseling strategies are discussed.
Serine/threonine‐protein phosphatase 2A physically interacts with human telomerase reverse transcriptase hTERT and regulates its subcellular distribution
Authors: Xi Peng , Zhou Lili , Wang Miao , Liu Jun‐Ping , Cong Yu‐Sheng
Published: September 2012

Telomerase plays fundamental roles in bypassing cellular aging and promoting cancer progression by maintaining telomere homeostasis and telomere‐independent activities. However, the molecular mechanisms by which telomerase provokes aging and cancer are far from being fully understood. In a search for proteins interacting with human telomerase reverse transcriptase hTERT by the yeast two‐hybrid screen using hTERT T‐motif as bait, we identified PP2A scaffolding subunit PR65 alpha isoform as an hTERT interacting partner. We showed that both PP2A catalytic subunit PP2AC and scaffolding subunit PR65 interacted with hTERT in vivo and in vitro and inhibited telomerase activity. In addition, we found that PP2A prevented the interaction of hTERT with 14‐3‐3θ signaling protein, an hTERT binding partner that is required for nuclear localization of hTERT. Activation of PP2A by overexpression of PP2AC or PR65 led to cytoplasmic accumulation of hTERT, which was reversed by treatment with PP2A inhibitor okadaic acid. Together, these observations suggest that PP2A regulates hTERT subcellular localization, in addition to its inhibitory effects on telomerase activity. J. Cell. Biochem. 114: 409–417, 2013. © 2012 Wiley Periodicals, Inc.
Tezosentan increases nitric oxide signaling via enhanced hydrogen peroxide generation in lambs with surgically induced acute increases in pulmonary blood flow
Authors: Kumar Sanjiv , Oishi Peter E. , Rafikov Ruslan , Aggarwal Saurabh , Hou Yali , Datar Sanjeev A. , Sharma Shruti , Azakie Anthony , Fineman Jeffrey R. , Black Stephen M.
Published: September 2012

We have previously shown that acute increases in pulmonary blood flow (PBF) are limited by a compensatory increase in pulmonary vascular resistance (PVR) via an endothelin‐1 (ET‐1) dependent decrease in nitric oxide synthase (NOS) activity. The mechanisms underlying the reduction in NO signaling are unresolved. Thus, the purpose of this study was to elucidate mechanisms of this ET‐1–NO interaction. Pulmonary arterial endothelial cells were acutely exposed to shear stress in the presence or absence of tezosentan, a combined ETA/ETB receptor antagonist. Shear increased NOx, eNOS phospho‐Ser1177, and H2O2 and decreased catalase activity; tezosentan enhanced, while ET‐1 attenuated all of these changes. In addition, ET‐1 increased eNOS phospho‐Thr495 levels. In lambs, 4 h of increased PBF decreased H2O2, eNOS phospho‐Ser1177, and NOX levels, and increased eNOS phospho‐Thr495, phospho‐catalase, and catalase activity. These changes were reversed by tezosentan. PEG‐catalase reversed the positive effects of tezosentan on NO signaling. In all groups, opening the shunt resulted in a rapid increase in PBF by 30 min. In vehicle‐ and tezosentan/PEG‐catalase lambs, PBF did not change further over the 4 h study period. PVR fell by 30 min in vehicle‐ and tezosentan‐treated lambs, and by 60 min in tezosentan/PEG‐catalase‐treated lambs. In vehicle‐ and tezosentan/PEG‐catalase lambs, PVR did not change further over the 4 h study period. In tezosentan‐treated lambs, PBF continued to increase and LPVR to decrease over the 4 h study period. We conclude that acute increases in PBF are limited by an ET‐1 dependent decrease in NO production via alterations in catalase activity, H2O2 levels, and eNOS phosphorylation. J. Cell. Biochem. 114: 435–447, 2013. © 2012 Wiley Periodicals, Inc.
Serum proteomic profiling for the early diagnosis of colorectal cancer
Authors: Zhu Dexiang , Wang Jie , Ren Li , Li Yan , Xu Bin , Wei Ye , Zhong Yunshi , Yu Xinzhe , Zhai Shenyong , Xu Jianmin , Qin Xinyu
Published: September 2012

No ideal serum biomarker currently exists for the early diagnosis of colorectal cancer (CRC). Magnetic bead‐based fractionation coupled with MALDI‐TOF MS was used to screen serum samples from CRC patients, healthy controls, and other cancer patients. A diagnostic model with five proteomic features (m/z 1778.97, 1866.16, 1934.65, 2022.46, and 4588.53) was generated using Fisher algorithm with best performance. The Fisher‐based model could discriminate CRC patients from the controls with 100% (46/46) sensitivity and 100% (35/35) specificity in the training set, 95.6% (43/45) sensitivity and 83.3% (35/42) specificity in the test set. We further validated the model with 94.4% (254/269) sensitivity and 75.5% (83/110) specificity in the external independent group. In other cancers group, the Fisher‐based model classified 25 of 46 samples (54.3%) as positive and the other 21 as negative. With FT‐ICR‐MS, the proteomic features of m/z 1778.97, 1866.16, 1934.65, and 2022.46, of which intensities decreased significantly in CRC, were identified as fragments of complement C3f. Therefore, the Fisher‐based model containing five proteomic features was able to effectively differentiate CRC patients from healthy controls and other cancers with a high sensitivity and specificity, and may be CRC‐specific. Serum complement C3f, which was significantly decreased in CRC group, may be relevant to the incidence of CRC. J. Cell. Biochem. 114: 448–455, 2013. © 2012 Wiley Periodicals, Inc.
Retinoic acid and the transcription factor MafB act together and differentially to regulate aggrecan and matrix metalloproteinase gene expression in neonatal chondrocytes
Authors: Zhang Yao , Ross A. Catharine
Published: September 2012

Vitamin A (VA) and its active form, retinoic acid (RA), are regulators of skeletal development and chondrogenesis. MafB, a transcription factor, has been identified as an important mediator in monocyte and osteoclast differentiation. However, the presence and function of MafB in chondrocytes is not clear. In this study, MafB gene expression was regulated by both the VA status of the mother (VA‐marginal, adequate, and supplemented diets) and by direct oral supplementation of the neonates with VARA (VA mixed with 10% RA). Expression was highest in neonates of VA‐supplemented versus VA‐marginal dams (P < 0.05), and in VARA‐treated versus placebo‐treated neonates across all diet groups (P < 0.05). To examine cellular changes, primary chondrocytes derived from neonatal rat ribs were cultured in the presence of RA for up to 48 h. MafB mRNA exhibited a time‐ and dose‐dependent increase in response to RA, while the induction of MafB mRNA was attenuated by BMS‐493, a pan‐RAR inverse agonist, implicating RAR signaling in the regulation of MafB. The genetic knockdown of MafB in chondrocytes using siRNA (MafBSI chondrocytes) abrogated the RA‐induced increase in MafB expression. MafBSI chondrocytes expressed higher levels of aggrecan mRNA. Additionally, the increased matrix metalloproteinase (MMP)3 and MMP13 gene expression due to RA was attenuated in MafBSI chondrocytes, while total extracellular matrix staining was increased. These results support a role for MafB as a regulator of chondrocyte gene expression and matrix formation via control of aggrecan, MMP3 and MMP13 expression, and indicate an important role for RA in the regulation of MafB. J. Cell. Biochem. 114: 471–479, 2013. © 2012 Wiley Periodicals, Inc.
Efficient differentiation of human iPSC‐derived mesenchymal stem cells to chondroprogenitor cells
Authors: Guzzo Rosa M. , Gibson Jason , Xu Ren‐He , Lee Francis Y. , Drissi Hicham
Published: September 2012

Induced pluripotent stem cells (iPSC) hold tremendous potential for personalized cell‐based repair strategies to treat musculoskeletal disorders. To establish human iPSCs as a potential source of viable chondroprogenitors for articular cartilage repair, we assessed the in vitro chondrogenic potential of the pluripotent population versus an iPSC‐derived mesenchymal‐like progenitor population. We found the direct plating of undifferentiated iPSCs into high‐density micromass cultures in the presence of BMP‐2 promoted chondrogenic differentiation, however these conditions resulted in a mixed population of cells resembling the phenotype of articular cartilage, transient cartilage, and fibrocartilage. The progenitor cells derived from human iPSCs exhibited immunophenotypic features of mesenchymal stem cells (MSCs) and developed along multiple mesenchymal lineages, including osteoblasts, adipocytes, and chondrocytes in vitro. The data indicate the derivation of a mesenchymal stem cell population from human iPSCs is necessary to limit culture heterogeneity as well as chondrocyte maturation in the differentiated progeny. Moreover, as compared to pellet culture differentiation, BMP‐2 treatment of iPSC‐derived MSC‐like (iPSC–MSC) micromass cultures resulted in a phenotype more typical of articular chondrocytes, characterized by the enrichment of cartilage‐specific type II collagen (Col2a1), decreased expression of type I collagen (Col1a1) as well as lack of chondrocyte hypertrophy. These studies represent a first step toward identifying the most suitable iPSC progeny for developing cell‐based approaches to repair joint cartilage damage. J. Cell. Biochem. 114: 480–490, 2013. © 2012 Wiley Periodicals, Inc.
Recent agents targeting HIF‐1α for cancer therapy
Authors: Hu Yaozhong , Liu Jing , Huang He
Published: September 2012

The discovery of hypoxia‐inducible factor‐1 (HIF‐1) has led to an increasing understanding of the mechanism of tumor hypoxia in the past two decades. As a key transcriptional regulator, HIF‐1 plays a central role in the adaptation of tumor cells to hypoxia by activating the transcription of targeting genes, which regulate several biological processes including angiogenesis, cell proliferation, survival, glucose metabolism and migration. The inhibitors of HIF‐1 in cancer have provided us a new clue for the targeting cancer therapy. This review will introduce the general knowledge of the biology characteristic of HIF‐1 and mechanism of O2‐dependent regulation. Moreover, a number of chemical inhibitors plus protein and nucleic acid inhibitors are included and classified mainly based on their different mechanism of inhibiting action. We also prefer to discuss the advantages of protein and nucleic acid inhibitors compared with chemical inhibitors. J. Cell. Biochem. 114: 498–509, 2013. © 2012 Wiley Periodicals, Inc.
Perioperative processes and outcomes after implementation of a hospitalist‐run preoperative clinic
Authors: Vazirani Sondra , Lankarani‐Fard Azadeh , Liang Li‐Jung , Stelzner Matthias , Asch Steven M.
Published: September 2012

BACKGROUND:

A structured, medical preoperative evaluation may positively impact the perioperative course of medically complex patients. Hospitalists are in a unique position to assist in preoperative evaluations, given their expertise with inpatient medicine and postoperative surgical consultation.

OBJECTIVE:

To evaluate specific outcomes after addition of a Hospitalist‐run, medical Preoperative clinic to the standard Anesthesia preoperative evaluation.

DESIGN, SETTING, PATIENTS:

A pre/post retrospective, comparative review of outcomes of 5223 noncardiac surgical patients at a tertiary care Veterans Administration (VA) medical center.

RESULTS:

Length of stay was reduced for inpatients with an American Society of Anesthesia (ASA) score of 3 or higher (P < 0.0001). There was a trend towards a reduction in same‐day, medically avoidable surgical cancellations (8.5% vs 4.9%, P = 0.065). More perioperative beta blockers were used (P < 0.0001) and more stress tests were ordered (P = 0.012). Inpatient mortality rates were reduced (1.27% vs 0.36%, P = 0.0158).

CONCLUSION:

A structured medical preoperative evaluation may benefit medically complex patients and improve perioperative processes and outcomes. Journal of Hospital Medicine 2012. © 2012 Society of Hospital Medicine
Synthesis of deuterium‐labeled olmesartan and candesartan
Authors: Zhang Chi , Shen Zucheng , Tian Lei , Chen Liqin
Published: September 2012

This paper describes the synthesis of deuterium‐labeled olmesartan and candesartan. The two desired compounds both used [2H4] 2‐cyano‐4′‐methyl‐biphenyl as deuterium‐labeled reagent, which was synthesized beforehand in two steps. [2H4] olmesartan was synthesized in six steps further with 17% overall yield, and [2H4] candesartan was synthesized in seven steps further with 13% overall yield. Copyright © 2012 John Wiley & Sons, Ltd.
Using elemental profiles and stable isotopes to trace the origin of green coffee beans on the global market
Authors: Santato Alessandro , Bertoldi Daniela , Perini Matteo , Camin Federica , Larcher Roberto
Published: September 2012

A broad elemental profile incorporating 54 elements (Li, Be, B, Na, Mg, Al, P, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, Ge, As, Se, Rb, Sr, Y, Mo, Pd, Ag, Cd, Sn, Sb, Te, Cs, Ba, La, Ce, Pr, Nd, Sm, Eu, Gd, Dy, Er, Tm, Yb, Re, Ir, Pt, Au, Hg, Tl, Pb, Bi and U) in combination with δ2H, δ13C, δ15N and δ18O was used to characterise the composition of 62 green arabica (Coffea arabica) and robusta (Coffea canephora) coffee beans grown in South and Central America, Africa and Asia, the four most internationally renowned areas of production. The δ2H, Mg, Fe, Co and Ni content made it possible to correctly assign 95% of green coffee beans to the appropriate variety. Canonical discriminant analysis, performed using δ13C, δ15N, δ18O, Li, Mg, P, K, Mn, Co, Cu, Se, Y, Mo, Cd, La and Ce correctly traced the origin of 98% of coffee beans. Copyright © 2012 John Wiley & Sons, Ltd.
Free and bound aroma compounds characterization by GC‐MS of Negroamaro wine as affected by soil management
Authors: Toci Aline T. , Crupi Pasquale , Gambacorta Giuseppe , Dipalmo Tiziana , Antonacci Donato , Coletta Antonio
Published: September 2012

Negroamaro is an autochthonous wine grape variety of Southern Italy, which is becoming very important for the Italian wine market. The wine aroma is primary affected by the chemical composition of grapes, which can be influenced also by agronomic practices such as soil management. In this study, the free and bound aroma characterization was performed by gas chromatography–mass spectrometry analyses, and the influence of two soil managements (cover cropping and soil tillage) was evaluated. A total of 40 volatile compounds were observed in the wine samples. Alcohols (55.7 mg/L), fatty acids (7.0 mg/L) and esters (6.6 mg/L) were found as the main classes in Negroamaro wine. The results showed that the aroma composition of Negroamaro wine was positively affected by soil tillage probably because of the higher water stress (ψs) recorded in the vines from this treatment. Indeed, among the free volatile compounds, higher contents of esters, carboxylic acids, alcohols, phenolics and acetamides together with lower contents of sulfurs compounds were found in soil tillage wine. Conversely, no difference was observed in glycoside volatile compounds. Copyright © 2012 John Wiley & Sons, Ltd.
Occurrence of arbuscular mycorrhizas and dark septate endophytes in pteridophytes from a patagonian rainforest, Argentina
Authors: Fernández Natalia Verónica , Messuti María Inés , Fontenla Sonia Beatriz
Published: September 2012

Arbuscular mycorrhizas (AM) are one of the most widespread types of symbiotic associations. Pteridophytes occupy an important position in the evolution of vascular plants. However, their mycorrhizal state remains poorly understood. The aim of this work was to describe the general mycorrhizal status and the occurrence of dark septate endophytes (DSE) in the pteridophytic flora of a Valdivian temperate forest in Patagonia, Argentina. First, the roots of nine terrestrial species representing six families were examined, and this information was then compared with other surveys concerning the occurrence of AM in other pteridophytic species within the same Valdivian temperate forest. AM were recorded in 98.6% of the samples analyzed in this work and all of them corresponded to the Paris‐type morphology. DSEs were also present within the roots of all terrestrial species. A comparison to published results in other ferns and lycophytes that have been studied in this Valdivian temperate forest (161 sporophytes, 21 species and 10 families) was made. Clear differences in colonization patterns between eusporangiate/leptosporangiate and epiphytic/terrestrial species became evident and are discussed.
Genetic diversity of internalin genes in the ascB‐dapE locus among Listeria monocytogenes lineages III and IV strains
Authors: Chen Jianshun , Cheng Changyong , Lv Yonghui , Fang Weihuan
Published: September 2012

Listeria monocytogenes is an important foodborne pathogen encompassing four phylogenetic lineages. Lineages III and IV are rare, but have been reported to show considerable biodiversity, providing important clues for the evolutionary history in Listeria. In this study, analysis of the ascB‐dapE locus reveals genetic diversity in lineages III and IV, and is consistent with the classification of sublineages. Four of the six genetic patterns (two of sublineage IIIC and two of lineage IV) are specific to these two lineages. The ascB‐dapE locus suggests a hot spot for genome diversification, and serves as an attractive molecular marker for better understanding of the biodiversity and population structure of lineages III and IV strains.
Characterization of Bombyx mori nucleopolyhedrovirus Bm17
Authors: Shen Hongxing , Wang Rudu , Han Qinggong , Zhang Wen , Nin Bin , Zhou Yang , Shao Shihe , Yao Qin , Chen Keping , Liu Xiaoyong
Published: September 2012

Open reading frame17 (Bm17) of Bombyx mori nucleopolyhedrovirus is a highly conserved gene in lepidopteran nucleopolyhedroviruses, suggesting that it performs an important role in the virus life cycle whose function is unknown. In this report, we describe the characterization of Bm17. Reversed transcriptive‐PCR (RT‐PCR) and Western blot analysis demonstrated that Bm17 was expressed as a late gen. Immunofluorescence analysis by confocal microscopy showed that BM17 protein was localized on cytoplasm and nucleus of infected cells. These results show that BM17 was a late protein localized in cytoplasm and nucleus.
Evidence for a vast peptide overlap between West Nile virus and human proteomes
Authors: Capone Giovanni , Pagoni Maria , Delfino Antonella Pesce , Kanduc Darja
Published: September 2012

The primary amino acid sequence of West Nile virus (WNV) polyprotein, GenBank accession number M12294, was analyzed by computional biology. WNV is a mosquito‐borne neurotropic flavivirus that has emerged globally as a significant cause of viral encephalitis in humans. Using pentapeptides as scanning units and the perfect peptide match program from PIR International Protein Sequence Database, we compared the WNV polyprotein and the human proteome. WNV polyprotein showed significant sequence similarities to a number of human proteins. Several of these proteins are involved in embryogenesis, neurite outgrowth, cortical neuron branching, formation of mature synapses, semaphorin interactions, and voltage dependent L‐type calcium channel subunits. The biocomputional study suggest that common amino acid segments might represent a potential platform for further studies on the neurological pathophysiology of WNV infections.
Real time visualization of femoroacetabular impingement and subluxation using 320‐slice computed tomography
Authors: Wassilew Georgi I. , Janz Viktor , Heller Markus O. , Tohtz Stephan , Rogalla Patrik , Hein Patrick , Perka Carsten
Published: September 2012

We visualized extreme ranges of motion of the hip and located femoroacetabular impingement (FAI) and subluxations using 4dimensional (D) volume computed tomography (CT). In dynamic 4D CT, 30 patients with hip pain (>3 months) and positive clinical and radiological signs of impingement were prospectively analyzed. The investigations were performed in flexion, abduction, and external rotation. The accuracy of the CT visualization of FAI was compared with the intraoperative findings during surgical dislocation, which served as the gold standard. Compared to the intraoperative visualization of FAI, the dynamic CT images showed a high degree of accuracy. 4D CT is a suitable method to dynamically visualize the functional consequences of anatomical FAI pathologies. The location of impingement can be accurately determined, and when combined with information about possible labral tears and chondral damage supplied by magnetic resonance arthrography, allows the surgeon to select the optimal surgical access and plan the required operation for minimal invasiveness. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 275–281, 2013
Non‐invasive micro Raman, SERS and visible reflectance analyses of coloring materials in ancient Moroccan Islamic manuscripts
Authors: El Bakkali A. , Lamhasni T. , Haddad M. , Ait Lyazidi S. , Sanchez‐Cortes S. , del Puerto Nevado E.
Published: September 2012

For the first time, a thorough study of a variety of ancient Islamic manuscripts of Morocco was performed with the aim of identifying the coloring materials and recipes used by ancient scribes and illustrators in the western Mediterranean region. Six manuscripts collected from the old cities of Fez, Meknes and Zerhoune were chosen to cover a wide historical period and belonging to different scribal schools. They have been analyzed by Raman microscopy, surface enhanced Raman scattering and UV–visible diffuse reflectance measurements. The analyzed writings and illuminations include black, bright red, pink crimson, blue, green, dark brown and pale brown–orange inks. The identification of the observed wide range of the pigments leads to the statement that the coloring materials and recipes, used by ancient scribes and illuminators over centuries, remained the same in the western Mediterranean region. Copyright © 2012 John Wiley & Sons, Ltd.
Synthesis and application of vinylpyridine containing ion‐imprinted copolymer gel microbeads for Cu(II) solid‐phase extraction
Authors: Dakova Ivanka , Karadjova Irina , Georgieva Ventsislava , Georgiev George
Published: September 2012

The influence of polymer matrix on the extraction efficiency for Cu(II) and selectivity against metal ions such as Ni(II), Cd(II), Pb(II) of Cu(II) imprinted copolymer gels was described. The functional monomers investigated include the weakly basic 4‐vinylpyridine (4‐VP) and its mixure with the acidic and hydrogen binding methacrylic acid. Copolymer gels were prepared by dispersion cross‐linking copolymerization using Cu(II)–4‐(2‐pyridylazo)resorcinol complex, Cu(II), or 4‐(2‐pyridylazo)resorcinol as templates. The chemical structure and morphology of the Cu(II)‐imprinted microbeads are defined using elemental analysis, Fourier transform infrared spectroscopy, and scanning electron microscopy. Extraction efficiencies of newly synthesized sorbents were studied by batch procedure. The prepared copolymer gel with 4‐VP as monomer and Cu(II)–4‐(2‐pyridylazo)resorcinol complex has higher capacity and selectivity toward Cu(II) than the copolymer gels prepared using the mixture of methacrylic acid and 4‐VP. This new sorbent can be used as an effective SPE material for the highly selective preconcentration and separation of Cu(II) in sea water samples. It shows high mechanical and chemical stability.
A comparison of two methods of endoscopic dilation of acute subglottic stenosis using a ferret model
Authors: Tubbs Kyle J. , Silva Rodrigo C. , Ramirez Harvey E. , Castleman William L. , Collins William O.
Published: September 2012

Objectives/Hypothesis:

Balloon dilation is accepted as a first line treatment of acute subglottic stenosis, but its effects on the subglottic tissue remain largely unknown. We aimed to develop an animal model of acute subglottic stenosis using endoscopic techniques. Once developed, this model was used to compare the immediate effects of balloon dilation and endotracheal tube dilation on subglottic tissue.

Study Design:

Prospective randomized animal study.

Methods:

Acute subglottic injury was induced in 10 ferrets by endoscopic cauterization with silver nitrate. After 48–72 hours of observation, eight animals were randomized to undergo subglottic dilation with either a 5‐mm balloon or endotracheal tubes of increasing diameter. These eight ferrets were euthanized within 10 minutes after dilation. The other two ferrets served as controls and were euthanized following observation only. The larynx from each ferret was harvested, and the subglottis was examined histologically by a pathologist blinded to the treatment arms.

Results:

Acute subglottic stenosis was induced in all 10 ferrets using the endoscopic technique. Both balloon and endotracheal tube dilation resulted in comparable improvement in the subglottic airway diameter. A decreased thickness of submucosa/lamina propria was seen in the balloon dilation group.

Conclusions:

Acute subglottic stenosis can be reliably induced in ferrets using endoscopic techniques. Multiple dilation methods can be used to relieve acute obstruction. Balloon dilators seem to improve airway patency, in part, by decreasing the thickness of the submucosa and lamina propria. Further research is needed to determine how this impacts later stages of wound healing and final outcomes. Laryngoscope, 2013