bluuebunny/crossref_metadata_2025_split huggingface dataset:
Susceptibility to myocardial ischemia reperfusion injury at early stage of type 1 diabetes in rats
Authors: Li Haobo , Liu Zipeng , Wang Junwen , Wong Gordon T , Cheung Chi-Wai , Zhang Liangqing , Chen Can , Xia Zhengyuan , Irwin Michael G 
Published: September 2013

Abstract

Background
Large body of evidences accumulated in clinical and epidemiological studies indicate that hearts of diabetic subjects are more sensitive to ischemia reperfusion injury (IRI), which results in a higher rate of mortality at post-operation than that of non-diabetes. However, experimental results are equivocal and point to either increased or decreased susceptibility of the diabetic hearts to IRI, especially at the early stage of the disease. The present study was designed to test the hypothesis that the duration/severity of the indexed ischemia is a major determinant of the vulnerability to myocardial IRI at early stage of diabetes.

Methods
Four weeks streptozotocin (STZ)-induced diabetic (D) and non-diabetic (C) Sprague–Dawley rats were randomly assigned to receive 30 or 45 min of left anterior descending artery ligation followed by 2 or 3 hours of reperfusion, respectively. Cardiac function was recorded by using Pressure-Volume (PV) conduction system. Myocardial infarct size was determined with triphenyltetrazolium chloride staining. Plasma Creatine kinase-MB (CK-MB), Lactate dehydrogenase (LDH) release, myocardial nitric oxide(NO) content and nitrotyrosine formation, 15-F2t-Isoprostane and plasma superoxide dismutase (SOD) were measured with colorimetric assays. Cardiomyocyte apoptosis was assessed by TUNEL staining. Myocardial TNFα, Caspase-3, STAT3, Akt, and GSK-3β were determined by Western blotting.

Results
Prolongation of ischemia but not reperfusion from 30 min to 45 min significantly increased infarct size in D compared to C rats (P < 0.05), accompanied with significantly increased plasma CK-MB (P < 0.05). Prolongation of the duration of either ischemia or reperfusion significantly increased plasma LDH release and myocardial 15-F2t-Isoprostane and reduced plasma SOD activity, with concomitant reduction of myocardial NO and increase of nitrotyrosine formation in D relative to C (P < 0.05). Prolongation of ischemia and reperfusion significantly reduced left ventricular ejection fraction and increased the peak rate of pressure, accompanied with increased end systolic pressure in D relative to C rats (P < 0.05) but reduced phosphorylations of myocardial STAT3 at site Ser727 and Akt at site Ser473 as well as GSK-3β at Ser 9 (P < 0.05).

Conclusions
Diabetic hearts, even at early stage of the disease are more sensitive to IRI, and this increased severity of post-ischemic myocardial injury depends more on the duration of ischemia than that of reperfusion.
Lipid peroxidation and antioxidant enzymes activity in Plasmodium vivax malaria patients evolving with cholestatic jaundice
Authors: Fabbri Camila , de Cássia Mascarenhas-Netto Rita , Lalwani Pritesh , Melo Gisely C , Magalhães Belisa ML , Alexandre Márcia AA , Lacerda Marcus VG , Lima Emerson S 
Published: September 2013

Abstract

Background

Plasmodium vivax infection has been considered a benign and self-limiting disease, however, recent studies highlight the association between vivax malaria and life-threatening manifestations. Increase in reactive oxygen species has already been described in vivax malaria, as a result of the increased metabolic rate triggered by the multiplying parasite, and large quantities of toxic redox-active byproducts generated. The present study aimed to study the oxidative stress responses in patients infected with P. vivax, who developed jaundice (hyperbilirubinaemia) in the course of the disease, a common clinical complication related to this species.

Methods
An evaluation of the lipid peroxidation and antioxidant enzymes profile was performed in 28 healthy individuals and compared with P. vivax infected patients with jaundice, i.e., bilirubin < 51.3 μmol/L (8 patients) or without jaundice (34 patients), on day 1 (D1) and day 14 (D14) after anti-malarial therapy.

Results
Hyperbilirubinaemia was more frequent among women and patients experiencing their first malarial infection, and lower haemoglobin and higher lactate dehydrogenase levels were observed in this group. Malondialdehyde levels and activity of celuroplasmin and glutathione reductase were increased in the plasma from patients with P. vivax with jaundice compared to the control group on D1. However, the activity of thioredoxin reductase was decreased. The enzymes glutathione reductase, thioredoxin reductase, thiols and malondialdehyde also differed between jaundiced versus non-jaundiced patients. On D14 jaundice and parasitaemia had resolved and oxidative stress biomarkers were very similar to the control group.

Conclusion
Cholestatic hyperbilirubinaemia in vivax malaria cannot be totally disassociated from malaria-related haemolysis. However, significant increase of lipid peroxidation markers and changes in antioxidant enzymes in patients with P. vivax-related jaundice was observed. These results suggest oxidative processes contributing to malaria pathogenesis, what may be useful information for future anti-oxidant therapeutical interventions in these patients.
Molecular-guided therapy predictions reveal drug resistance phenotypes and treatment alternatives in malignant peripheral nerve sheath tumors
Authors: Peacock Jacqueline D , Cherba David , Kampfschulte Kevin , Smith Mallory K , Monks Noel R , Webb Craig P , Steensma Matthew 
Published: September 2013

Abstract

Background
Malignant peripheral nerve sheath tumors (MPNST) are rare highly aggressive sarcomas that affect 8-13% of people with neurofibromatosis type 1. The prognosis for patients with MPNST is very poor. Despite TOP2A overexpression in these tumors, doxorubicin resistance is common, and the mechanisms of chemotherapy resistance in MPNST are poorly understood. Molecular-guided therapy prediction is an emerging strategy for treatment refractory sarcomas that involves identification of therapy response and resistance mechanisms in individual tumors. Here, we report the results from a personalized, molecular-guided therapy analysis of MPNST samples.

Methods
Established molecular-guided therapy prediction software algorithms were used to analyze published microarray data from human MPNST samples and cell lines, with benign neurofibroma tissue controls. MPNST and benign neurofibroma-derived cell lines were used for confirmatory in vitro experimentation using quantitative real-time PCR and growth inhibition assays. Microarray data was analyzed using Affymetrix expression console MAS 5.0 method. Significance was calculated with Welch’s t-test with non-corrected p-value < 0.05 and validated using permutation testing across samples. Paired Student’s t-tests were used to compare relative EC50 values from independent growth inhibition experiments.

Results
Molecular guided therapy predictions highlight substantial variability amongst human MPNST samples in expression of drug target and drug resistance pathways, as well as some similarities amongst samples, including common up-regulation of DNA repair mechanisms. In a subset of MPNSTs, high expression of ABCC1 is observed, serving as a predicted contra-indication for doxorubicin and related therapeutics in these patients. These microarray-based results are confirmed with quantitative, real-time PCR and immunofluorescence. The functional effect of drug efflux in MPNST-derived cells is confirmed using in vitro growth inhibition assays. Alternative therapeutics supported by the molecular-guided therapy predictions are reported and tested in MPNST-derived cells.

Conclusions
These results confirm the substantial molecular heterogeneity of MPNSTs and validate molecular-guided therapy predictions in vitro. The observed molecular heterogeneity in MPNSTs influences therapy prediction. Also, mechanisms involving drug transport and DNA damage repair are primary mediators of MPNST chemotherapy resistance. Together, these findings support the utility of individualized therapy in MPNST as in other sarcomas, and provide initial proof-of concept that individualized therapy prediction can be accomplished.
Are morphological criteria sufficient for the identification of circulating tumor cells in renal cancer?
Authors: El-Heliebi Amin , Kroneis Thomas , Zöhrer Evelyn , Haybaeck Johannes , Fischereder Katja , Kampel-Kettner Karin , Zigeuner Richard , Pock Hannelore , Riedl Regina , Stauber Rudolf , Geigl Jochen Bernd , Huppertz Berthold , Sedlmayr Peter , Lackner Carolin 
Published: September 2013

Abstract

Background
Single circulating tumor cells (CTCs) or circulating tumor microemboli (CTMs) are potential biomarkers of renal cell cancer (RCC), however studies of CTCs/CTMs in RCC are limited. In this pilot study we aimed to evaluate a novel blood filtration technique suited for cytomorphological classification, immunocytochemical and molecular characterization of filtered, so called circulating non-hematologic cells (CNHCs) - putative CTCs/CTMs - in patients with RCC.

Methods
Blood of 40 patients with renal tumors was subjected to ScreenCell® filtration. CNHCs were classified according to cytomorphological criteria. Immunocytochemical analysis was performed with antibodies against CD45, CD31 and carbonic anhydrase IX (CAIX, a RCC marker). DNA of selected CNHCs and respective primary tumors was analysed by array-CGH.

Results
CNHC-clusters with malignant or uncertain malignant cytomorphological features - putative CTMs - were negative for CD45, positive for CD31, while only 6% were CAIX positive. Array-CGH revealed that 83% of malignant and uncertain malignant cells did represent with a balanced genome whereas 17% presented genomic DNA imbalances which did not match the aberrations of the primary tumors. Putative single CTCs were negative for CD45, 33% were positive for CD31 and 56% were positive for CAIX.

Conclusions
The majority of CNHC-clusters, putative CTMs, retrieved by ScreenCell® filtration may be of endothelial origin. Morphological criteria seem to be insufficient to distinguish malignant from non-malignant cells in renal cancer.
Regional consensus opinion for the management of Beta thalassemia major in the Arabian Gulf area
Authors: Qari Mohamad H , Wali Yasser , Albagshi Muneer H , Alshahrani Mohammad , Alzahrani Azzah , Alhijji Ibrahim A , Almomen Abdulkareem , Aljefri Abdullah , Al Saeed Hussain H , Abdullah Shaker , Al Rustumani Ahmad , Mahour Khoutir , Mousa Shaker A 
Published: September 2013

AbstractThalassemia syndrome has diverse clinical presentations and a global spread that has far exceeded the classical Mediterranean basin where the mutations arose. The mutations that give rise to either alpha or beta thalassemia are numerous, resulting in a wide spectrum of clinical severity ranging from carrier state to life-threatening, inherited hemolytic anemia that requires regular blood transfusion. Beta thalassemia major constitutes a remarkable challenge to health care providers. The complications arising due to the anemia, transfusional iron overload, as well as other therapy-related complications add to the complexity of this condition. To produce this consensus opinion manuscript, a PubMed search was performed to gather evidence-based original articles, review articles, as well as published work reflecting the experience of physicians and scientists in the Arabian Gulf region in an effort to standardize the management protocol.
Female physicians: trends and likely impacts on healthcare in Israel
Authors: Haklai Ziona , Applbaum Yael , Tal Orna , Aburbeh Myriam , Goldberger Nehama F 
Published: September 2013

Abstract

Background
Female physicians have become an increasing proportion of the medical workforce in Israel. This study investigates this trend and discusses its likely impact on the quantity and quality of medical care available.

Method
Data on licensed physicians and new licenses issued to physicians were taken from a Ministry of Health database, and analyzed by gender, age, academic origin (Israeli graduates, immigrants, Israeli-born who studied abroad), and specialty for the years 1999–2011.
Data on employed physicians, their population group, and work hours were taken from the Central Bureau of Statistics (CBS) annual Labour Force Survey for the years 2009–2011.

Results
The proportion of women amongst physicians aged under 65 rose from 38% in 1999 to 42% in 2011, and was even higher for younger physicians. The highest proportion of females is found amongst new immigrant physicians who studied abroad. The corresponding proportion has been rising steadily amongst Israeli-educated physicians, and is lowest amongst Israeli-born physicians who studied abroad.
Similarly, among newly licensed physicians, the proportion of females has traditionally been highest among immigrants who studied abroad and lowest among Israeli-born graduates who studied abroad. Among newly-licensed physicians who studied in Israel, the proportion of females has historically been intermediate between the other two groups, but it has recently risen to 54% and now parallels the proportion of females among immigrants who studied abroad. In recent years, the mix of academic origins among newly licensed physicians has changed dramatically, with important implications for the proportion of women among newly licensed physicians.
The highest percentage of females was found in family medicine followed by oncology, pediatrics and psychiatry. The greatest increase over the years in this percentage was for gynecology and internal medicine.
Female physicians worked shorter hours than males, particularly at younger ages. The proportion of females among employed Arab physicians is much lower than among Jewish physicians.

Conclusions
The proportion of female physicians has been steadily rising, although in recent years the increase has leveled off. This has been due, in part, to the decline in the flow of immigrant physicians and the increase in the number of Israelis studying abroad. Future developments in medical education options and immigration will determine whether their proportion will continue rising. Planning for future medical personnel must take these results into consideration.
Recruitment and functionality traits as bioindicators of ecological restoration success in the Lurg Hills district, Victoria, Australia
Authors: Monie Kristin , Florentine Singarayer , Palmer Grant 
Published: September 2013

Abstract

Introduction
The Regent Honeyeater Project commenced ecological restoration in the Lurg district in 1994, with an aim to restore habitats for the critically endangered Regent Honeyeater Anthochaera phrygia and a range of other threatened and declining species. Within this context, our study aimed to explore whether plant reproduction can be an effective measure of ecological restoration success.

Methods
Evaluation involved comparing attributes at unrestored, restored and remnant sites to establish whether sites displayed evidence of a clear restoration trajectory. Five age classes (unrestored, 4–6 years old, 8–10 years old, 12–14 years old and remnant areas) and two landforms (upper hills and lower hills) were considered. The diversity of woody plant species—which have easily recognisable reproductive material and which all recruit seedlings—provides easily measured parameters that have the potential to allow the determination of early establishment success and long-term ecological development of restored ecosystems.

Results
Restoration plantings developed in a hybrid state towards a benchmark in the lower hills; seedling species composition differed significantly among age classes, increasing in similarity with time since restoration, with some divergence from the target pathway. Composition of functional groups with reproductive outputs was also significantly different among age classes; however, a restoration trajectory was only evident in the upper hills where sites converged towards the target goal.

Conclusions
Divergence or deviation from the restoration trajectory was not deemed to be a restoration failure, as the variety of functional groups with fruits and diversity of seedlings recruiting indicated a potential increase in resilience in the future due to greater variability across the landscape. Plant recruitment was effective in detecting development trends towards a restoration target in this study and therefore may be a useful measure that contributes to determining ecological restoration success.
Dynamic pressurization induces transition of notochordal cells to a mature phenotype while retaining production of important patterning ligands from development
Authors: Purmessur Devina , Guterl Clare C , Cho Samuel K , Cornejo Marisa C , Lam Ying W , Ballif Bryan A , Laudier Damien M , Iatridis James C 
Published: September 2013

Abstract
Introduction
Notochordal cells (NCs) pattern aneural and avascular intervertebral discs (IVDs), and their disappearance, is associated with onset of IVD degeneration. This study induced and characterized the maturation of nucleus pulposus (NP) tissue from a gelatinous NC-rich structure to a matrix-rich structure populated by small NP cells using dynamic pressurization in an ex vivo culture model, and also identified soluble factors from NCs with therapeutic potential.

Methods
Porcine NC-rich NP tissue was cultured and loaded with hydrostatic pressure (0.5 to 2 MPa at 0.1 Hz for 2 hours) either Daily, for 1 Dose, or Control (no pressurization) groups for up to eight days. Cell phenotype and tissue maturation was characterized with measurements of cell viability, cytomorphology, nitric oxide, metabolic activity, matrix composition, gene expression, and proteomics.

Results
Daily pressurization induced transition of NCs to small NP cells with 73.8%, 44%, and 28% NCs for Control, 1 Dose and Daily groups, respectively (P < 0.0002) and no relevant cell death. Dynamic loading matured NP tissue by significantly increasing metabolic activity and accumulating Safranin-O-stained matrix. Load-induced maturation was also apparent from the significantly decreased glycolytic, cytoskeletal (Vimentin) and stress-inducible (HSP70) proteins assessed with proteomics. Loading increased the production of bioactive proteins Sonic Hedgehog (SHH) and Noggin, and maintained Semaphorin3A (Sema3A).

Discussion
NP tissue maturation was induced from dynamic hydrostatic pressurization in a controlled ex vivo environment without influence from systemic effects or surrounding structures. NCs transitioned into small nonvacuolated NP cells probably via differentiation as evidenced by high cell viability, lack of nitric oxide and downregulation of stress-inducible and cytoskeletal proteins. SHH, Sema3A, and Noggin, which have patterning and neurovascular-inhibiting properties, were produced in both notochordal and matured porcine NP. Results therefore provide an important piece of evidence suggesting the transition of NCs to small NP cells is a natural part of aging and not the initiation of degeneration. Bioactive candidates identified from young porcine IVDs may be isolated and harnessed for therapies to target discogenic back pain.
Prediction of Survival by [18F]Fluorodeoxyglucose Positron Emission Tomography in Patients With Locally Advanced Non–Small-Cell Lung Cancer Undergoing Definitive Chemoradiation Therapy: Results of the ACRIN 6668/RTOG 0235 Trial
Authors: Machtay Mitchell , Duan Fenghai , Siegel Barry A. , Snyder Bradley S. , Gorelick Jeremy J. , Reddin Janet S. , Munden Reginald , Johnson Douglas W. , Wilf Larry H. , DeNittis Albert , Sherwin Nancy , Cho Kwan Ho , Kim Seok-ki , Videtic Gregory , Neumann Donald R. , Komaki Ritsuko , Macapinlac Homer , Bradley Jeffrey D. , Alavi Abass 
Published: September 2013

Purpose In this prospective National Cancer Institute–funded American College of Radiology Imaging Network/Radiation Therapy Oncology Group cooperative group trial, we hypothesized that standardized uptake value (SUV) on post-treatment [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) correlates with survival in stage III non–small-cell lung cancer (NSCLC). Patients and Methods Patients received conventional concurrent platinum-based chemoradiotherapy without surgery; postradiotherapy consolidation chemotherapy was allowed. Post-treatment FDG-PET was performed at approximately 14 weeks after radiotherapy. SUVs were analyzed both as peak SUV (SUVpeak) and maximum SUV (SUVmax; both institutional and central review readings), with institutional SUVpeak as the primary end point. Relationships between the continuous and categorical (cutoff) SUVs and survival were analyzed using Cox proportional hazards multivariate models. Results Of 250 enrolled patients (226 were evaluable for pretreatment SUV), 173 patients were evaluable for post-treatment SUV analyses. The 2-year survival rate for the entire population was 42.5%. Pretreatment SUVpeak and SUVmax (mean, 10.3 and 13.1, respectively) were not associated with survival. Mean post-treatment SUVpeak and SUVmax were 3.2 and 4.0, respectively. Post-treatment SUVpeak was associated with survival in a continuous variable model (hazard ratio, 1.087; 95% CI, 1.014 to 1.166; P = .020). When analyzed as a prespecified binary value (≤ v > 3.5), there was no association with survival. However, in exploratory analyses, significant results for survival were found using an SUVpeak cutoff of 5.0 (P = .041) or 7.0 (P < .001). All results were similar when SUVmax was used in univariate and multivariate models in place of SUVpeak. Conclusion Higher post-treatment tumor SUV (SUVpeak or SUVmax) is associated with worse survival in stage III NSCLC, although a clear cutoff value for routine clinical use as a prognostic factor is uncertain at this time.
Economic Burden of Cancer Survivorship Among Adults in the United States
Authors: Guy Gery P. , Ekwueme Donatus U. , Yabroff K. Robin , Dowling Emily C. , Li Chunyu , Rodriguez Juan L. , de Moor Janet S. , Virgo Katherine S. 
Published: September 2013

Purpose To present nationally representative estimates of the impact of cancer survivorship on medical expenditures and lost productivity among adults in the United States. Methods Using the 2008 to 2010 Medical Expenditure Panel Survey, we identified 4,960 cancer survivors and 64,431 individuals without a history of cancer age ≥ 18 years. Direct medical costs were measured using annual health care expenditures and examined by source of payment and service type. Indirect morbidity costs were estimated from lost productivity as a result of employment disability, missed work days, and lost household productivity. We evaluated the economic burden of cancer survivorship by estimating excess costs among cancer survivors, stratified by time since diagnosis (recently diagnosed [≤ 1 year] and previously diagnosed [> 1 year]), compared with individuals without a history of cancer using multivariable regression models stratified by age (18 to 64 and ≥ 65 years), controlling for age, sex, race/ethnicity, education, and comorbidities. Results In 2008 to 2010, the annual excess economic burden of cancer survivorship among recently diagnosed cancer survivors was $16,213 per survivor age 18 to 64 years and $16,441 per survivor age ≥ 65 years. Among previously diagnosed cancer survivors, the annual excess burden was $4,427 per survivor age 18 to 64 years and $4,519 per survivor age ≥ 65 years. Excess medical expenditures composed the largest share of the economic burden among cancer survivors, particularly among those recently diagnosed. Conclusion The economic impact of cancer survivorship is considerable and is also high years after a cancer diagnosis. Efforts to reduce the economic burden caused by cancer will be increasingly important given the growing population of cancer survivors.