bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical procedure for colon carcinoma tissue sampling directly affects the cancer marker-capacity of VEGF family members
Authors: Pringels Sarah , Van Damme Nancy , De Craene Bram , Pattyn Piet , Ceelen Wim , Peeters Marc , Grooten Johan 
Published: November 2012

Abstract

Background
mRNA levels of members of the Vascular Endothelial Growth Factor family (VEGF-A, -B, -C, -D, Placental Growth Factor/PlGF) have been investigated as tissue-based markers of colon cancer. These studies, which used specimens obtained by surgical resection or colonoscopic biopsy, yielded contradictory results. We studied the effect of the sampling method on the marker accuracy of VEGF family members.

Methods
Comparative RT-qPCR analysis was performed on healthy colon and colon carcinoma samples obtained by biopsy (n = 38) or resection (n = 39) to measure mRNA expression levels of individual VEGF family members. mRNA levels of genes encoding the eicosanoid enzymes cyclooxygenase 2 (COX2) and 5-lipoxygenase (5-LOX) and of genes encoding the hypoxia markers glucose transporter 1 (GLUT-1) and carbonic anhydrase IX (CAIX) were included as markers for cellular stress and hypoxia.

Results
Expression levels of COX2, 5-LOX, GLUT-1 and CAIX revealed the occurrence in healthy colon resection samples of hypoxic cellular stress and a concurrent increment of basal expression levels of VEGF family members. This increment abolished differential expression of VEGF-B and VEGF-C in matched carcinoma resection samples and created a surgery-induced underexpression of VEGF-D. VEGF-A and PlGF showed strong overexpression in carcinoma samples regardless of the sampling method.

Conclusions
Sampling-induced hypoxia in resection samples but not in biopsy samples affects the marker-reliability of VEGF family members. Therefore, biopsy samples provide a more accurate report on VEGF family mRNA levels. Furthermore, this limited expression analysis proposes VEGF-A and PlGF as reliable, sampling procedure insensitive mRNA-markers for molecular diagnosis of colon cancer.
The growth and composition of primary and community-based care services. Metrics and evidence from the Italian National Health Service
Authors: Longo Francesco , Salvatore Domenico , Tasselli Stefano 
Published: November 2012

Abstract

Background
Over the past few decades, in OECD countries there has been a general growing trend in the prevalence of out-of-hospital healthcare services, but there is a general lack of data on the use of these services.

Methods
We defined a list of 303 indicators related to primary and community healthcare services in collaboration with 13 Italian Local Health Authorities (LHAs). Then, for each LHA, we collected and analyzed these indicators for two different years (2003 and 2007).

Results
Out-of-hospital care absorbs 56% of all costs in our sample of LHAs. Expenditure on outpatients’ visits to specialists and on diagnostic examinations accounts for 13% of the costs, while spending on primary care (including prevention and public health) accounts for 9%, and for intermediate structures (including those related to rehabilitation, elderly people, disabled people, and mental health) the figure is 11%. Different Italian LHAs have made different strategic choices with respect to primary and community-based care (PCC).

Conclusions
Two distinct strategic orientations in the adoption of PCC services by LHAs has emerged from our study. The first has been an investment mainly in ambulatory and home-based primary care services in order to increase the number of low-complexity settings. A second strategy has prioritized the allocation of resources to intermediate inpatient structures for specific types of patients, namely elderly and disabled people, post-acute patients in need of rehabilitation and long-term care, and patients in hospices.
Unique functions of CHK1 and WEE1 underlie synergistic anti-tumor activity upon pharmacologic inhibition
Authors: Guertin Amy D , Martin Melissa M , Roberts Brian , Hurd Melissa , Qu Xianlu , Miselis Nathan R , Liu Yaping , Li Jing , Feldman Igor , Benita Yair , Bloecher Andrew , Toniatti Carlo , Shumway Stuart D 
Published: November 2012

Abstract

Background
Inhibition of kinases involved in the DNA damage response sensitizes cells to genotoxic agents by abrogating checkpoint-induced cell cycle arrest. CHK1 and WEE1 act in a pathway upstream of CDK1 to inhibit cell cycle progression in response to damaged DNA. Therapeutic targeting of either CHK1 or WEE1, in combination with chemotherapy, is under clinical evaluation. These studies examine the overlap and potential for synergy when CHK1 and WEE1 are inhibited in cancer cell models.

Methods
Small molecules MK-8776 and MK-1775 were used to selectively and potently inhibit CHK1 and WEE1, respectively.

Results
In vitro, the combination of MK-8776 and MK-1775 induces up to 50-fold more DNA damage than either MK-8776 or MK-1775 alone at a fixed concentration. This requires aberrant cyclin-dependent kinase activity but does not appear to be dependent on p53 status alone. Furthermore, DNA damage takes place primarily in S-phase cells, implying disrupted DNA replication. When dosed together, the combination of MK-8776 and MK-1775 induced more intense and more durable DNA damage as well as anti-tumor efficacy than either MK-8776 or MK-1775 dosed alone. DNA damage induced by the combination was detected in up to 40% of cells in a treated xenograft tumor model.

Conclusions
These results highlight the roles of WEE1 and CHK1 in maintaining genomic integrity. Importantly, the strong synergy observed upon inhibition of both kinases suggests unique yet complimentary anti-tumor effects of WEE1 and CHK1 inhibition. This demonstration of DNA double strand breaks in the absence of a DNA damaging chemotherapeutic provides preclinical rationale for combining WEE1 and CHK1 inhibitors as a cancer treatment regimen.
3D modeling of dual-gate FinFET
Authors: Mil’shtein Samson , Devarakonda Lalitha , Zanchi Brian , Palma John 
Published: November 2012

Abstract
The tendency to have better control of the flow of electrons in a channel of field-effect transistors (FETs) did lead to the design of two gates in junction field-effect transistors, field plates in a variety of metal semiconductor field-effect transistors and high electron mobility transistors, and finally a gate wrapping around three sides of a narrow fin-shaped channel in a FinFET. With the enhanced control, performance trends of all FETs are still challenged by carrier mobility dependence on the strengths of the electrical field along the channel. However, in cases when the ratio of FinFET volume to its surface dramatically decreases, one should carefully consider the surface boundary conditions of the device. Moreover, the inherent non-planar nature of a FinFET demands 3D modeling for accurate analysis of the device performance. Using the Silvaco modeling tool with quantization effects, we modeled a physical FinFET described in the work of Hisamoto et al. (IEEE Tran. Elec. Devices 47:12, 2000) in 3D. We compared it with a 2D model of the same device. We demonstrated that 3D modeling produces more accurate results. As 3D modeling results came close to experimental measurements, we made the next step of the study by designing a dual-gate FinFET biased at V
g1 > V
g2. It is shown that the dual-gate FinFET carries higher transconductance than the single-gate device.
Identification of a new cell line permissive to porcine reproductive and respiratory syndrome virus infection and replication which is phenotypically distinct from MARC-145 cell line
Authors: Provost Chantale , Jia Jian Jun , Music Nedzad , Lévesque Cynthia , Lebel Marie-Ève , del Castillo Jérôme RE , Jacques Mario , Gagnon Carl A 
Published: November 2012

Abstract

Background
Airborne transmitted pathogens, such as porcine reproductive and respiratory syndrome virus (PRRSV), need to interact with host cells of the respiratory tract in order to be able to enter and disseminate in the host organism. Pulmonary alveolar macrophages (PAM) and MA104 derived monkey kidney MARC-145 cells are known to be permissive to PRRSV infection and replication and are the most studied cells in the literature. More recently, new cell lines developed to study PRRSV have been genetically modified to make them permissive to the virus. The SJPL cell line origin was initially reported to be epithelial cells of the respiratory tract of swine. Thus, the goal of this study was to determine if SJPL cells could support PRRSV infection and replication in vitro.

Results
The SJPL cell growth was significantly slower than MARC-145 cell growth. The SJPL cells were found to express the CD151 protein but not the CD163 and neither the sialoadhesin PRRSV receptors. During the course of the present study, the SJPL cells have been reported to be of monkey origin. Nevertheless, SJPL cells were found to be permissive to PRRSV infection and replication even if the development of the cytopathic effect was delayed compared to PRRSV-infected MARC-145 cells. Following PRRSV replication, the amount of infectious viral particles produced in SJPL and MARC-145 infected cells was similar. The SJPL cells allowed the replication of several PRRSV North American strains and were almost efficient as MARC-145 cells for virus isolation. Interestingly, PRRSV is 8 to 16 times more sensitive to IFNα antiviral effect in SJPL cell in comparison to that in MARC-145 cells. PRRSV induced an increase in IFNβ mRNA and no up regulation of IFNα mRNA in both infected cell types. In addition, PRRSV induced an up regulation of IFNγ and TNF-α mRNAs only in infected MARC-145 cells.

Conclusions
In conclusion, the SJPL cells are permissive to PRRSV. In addition, they are phenotypically different from MARC-145 cells and are an additional tool that could be used to study PRRSV pathogenesis mechanisms in vitro.
Molecular portrait-based correlation between primary canine mammary tumor and its lymph node metastasis: possible prognostic-predictive models and/or stronghold for specific treatments?
Authors: Beha Germana , Brunetti Barbara , Asproni Pietro , Muscatello Luisa Vera , Millanta Francesca , Poli Alessandro , Sarli Giuseppe , Benazzi Cinzia 
Published: November 2012

Abstract

Background
This study aimed to evaluate the relationship between the molecular phenotype of the primary mammary tumor and its related lymph node metastasis in the dog to develop prognostic-predictive models and targeted therapeutic options.

Results
Twenty mammary tumor samples and their lymph node metastases were selected and stained by immunohistochemistry with anti-estrogen receptor (ER), -progesterone receptor (PR), -human epidermal growth factor receptor 2 (c-erbB-2), -cytokeratin 5/6 (CK 5/6), -cytokeratin 14 (CK14), -cytokeratin 19 (CK 19) and -protein 63 (p63) antibodies. Four phenotypes (luminal A, luminal B, c-erbB2 overexpressing and basal-like) were diagnosed in primary tumors and five (luminal A, luminal B, c-erbB-2 overexpressing, basal-like and normal-like) in the lymph node metastases. Phenotypic concordance was found in 13 of the 20 cases (65%), and seven cases (35%) showed discordance with different lymph node phenotypic profile from the primary tumor.

Conclusions
The phenotype of the primary tumor assumes a predictive-therapeutic role only in concordant cases, meaning that both the primary tumor and its lymph node metastasis should be evaluated at the same time. A treatment plan based only on the primary tumor phenotype could lead to therapeutic failures if the phenotype of the lymph node metastasis differs from that of the primary tumor.
NaHSO4-SiO2 as an efficient and chemoselective catalyst, for the synthesis of acylal from aldehydes under, solvent-free conditions
Authors: Kannasani Ravi Kumar , Peruri V V Satyanarayana , Battula Srinivasa Reddy 
Published: November 2012

Abstract

Background
Structurally diverse aldehydes are successfully converted into acylals (1,1-diacetates) with acetic anhydride using NaHSO4-SiO2 as a mild, convenient and inexpensive catalyst under solvent-free conditions. The noteworthy features of the present system are shorter reaction times, and mild and solvent-free conditions. Furthermore, it offers chemoselective protection of aldehydes.

Results
Both aromatic and aliphatic aldehydes reacts smoothly with acetic anhydride in presence of silica supported sodium hydrogen sulphate to afford the corresponding 1,1-diacetates in good to excellent yields. We studied competitive reactions for the acylation of aldehydes in the presence of ketones using silica supported sodium hydrogen sulphate as a catalyst. Using this catalytic system, the highly selective conversion of an aldehyde in the presence of ketone was observed.

Conclusions
NaHSO4-SiO2 is a chemoselective and highly efficient catalyst for acylal formation from aldehydes. The advantages of this methodology over the reported methods is the availability of the starting materials, simplicity of acylation procedure, a clean work-up, a short reaction time, high yields and reusability.
Population genetic analysis and sub-structuring of Theileria parva in the northern and eastern parts of Zambia
Authors: Muleya Walter , Namangala Boniface , Simuunza Martin , Nakao Ryo , Inoue Noboru , Kimura Takashi , Ito Kimihito , Sugimoto Chihiro , Sawa Hirofumi 
Published: November 2012

Abstract

Background
Theileriosis, caused by Theileria parva, is an economically important disease in Africa. It is a major constraint to the development of the livestock industry in some parts of eastern, central and southern Africa. In Zambia, theileriosis causes losses of up to 10,000 cattle annually.

Methods
Cattle blood samples were collected for genetic analysis of Theileria parva from Isoka and Petauke districts in Zambia. Microsatellite analysis was then performed on all Theileria parva positive samples for PCR using a panel of 9 microsatellite markers. Microsatellite data was analyzed using microsatellite toolkit, GenAlEx ver. 6, Fstat ver. 2.9.3.2, and LIAN computer softwares.

Results
The combined percentage of positive samples in both districts determined by PCR using the p104 gene primers was 54.9% (95% CI: 46.7 – 63.1%, 78/142), while in each district, it was 44.8% (95% CI: 34.8 – 54.8%) and 76.1% (95% CI = 63.9 – 88.4%) for Isoka and Petauke districts, respectively. We analyzed the population genetic structure of Theileria parva from a total of 61 samples (33 from Isoka and 28 from Petauke) using a panel of 9 microsatellite markers encompassing the 4 chromosomes of Theileria parva. Wright’s F index (FST = 0.178) showed significant differentiation between the Isoka and Petauke populations. Linkage disequilibrium was observed when populations from both districts were treated as a single population. When analyzed separately, linkage disequilibrium was observed in Kanyelele and Kalembe areas in Isoka district, Isoka district overall and in Petauke district. Petauke district had a higher multiplicity of infection than Isoka district.

Conclusion
Population genetic analyses of Theileria parva from Isoka and Petauke districts showed a low level of genotype exchange between the districts, but a high level of genetic diversity within each district population, implying genetic and geographic sub-structuring between the districts. The sub-structuring observed, along with the lack of panmixia in the populations, could have been due to low transmission levels at the time of sampling. However, the Isoka population was less diverse than the Petauke population.
Successful treatment of thyrotoxicosis is accompanied by a decrease in serum sclerostin levels
Authors: Skowrońska-Jóźwiak Elżbieta , Krawczyk-Rusiecka Kinga , Lewandowski Krzysztof C , Adamczewski Zbigniew , Lewiński Andrzej 
Published: November 2012

Abstract
Sclerostin, a product of a SOST gene, is a protein expressed by osteocytes that inhibits osteoblastic bone formation. Several hormones, including PTH and glucocorticosteroids, have been suggested to be possible regulators of sclerostin production. The influence of thyroid hormones on sclerostin synthesis has not been investigated, so far. The aim of the study was to evaluate sclerostin concentrations in patients before and after treatment of thyrotoxicosis.

Patients and methods

The study involved 15 patients (4 men), mean age 51.8±15.3 years, mean BMI value - 24.7±3.5, with thyrotoxicosis due to Graves’ disease or toxic multinodular goitre. Serum sclerostin was measured by immunoassay at diagnosis of thyrotoxicosis and after 6–10 weeks of treatment with thiamazole. The data were analysed by means of simple descriptive statistics of location and dispersion and Mann–Whitney U test for pairs of results, before and after thiamazole therapy. Association between variables was evaluated with use of Spearman`s correlation coefficient.

Results

There was a significant decrease in free T3 (FT3) and free T4 (FT4) concentrations (from 8.74±4.79 pg/ml to 3.54±2.40 pg/ml, and from 4.48±2.21 ng/ml to 1.02±1.07 ng/ml, respectively, p<0.001). This was accompanied by a marked decrease of serum sclerostin levels from 55.46±20.90 pmol/l to 35.73±15.70 pmol/l, p<0.0015). Interestingly, enough, sclerostin levels did not correlate with serum FT3 or FT4 concentrations.

Conclusions

Restoration of a euthyroid state in patients with thyrotoxicosis results in a significant decrease in serum sclerostin concentrations. The above mentioned phenomenon may reflect lowering of bone metabolism, but a possible direct influence of thyroid hormones on SOST gene needs to be investigated.
Identification of stable normalization genes for quantitative real-time PCR in porcine articular cartilage
Authors: McCulloch Ryan S , Ashwell Melissa S , O’Nan Audrey T , Mente Peter L 
Published: November 2012

Abstract

Background
Expression levels for genes of interest must be normalized with an appropriate reference, or housekeeping gene, to make accurate comparisons of quantitative real-time PCR results. The purpose of this study was to identify the most stable housekeeping genes in porcine articular cartilage subjected to a mechanical injury from a panel of 10 candidate genes.

Results
Ten candidate housekeeping genes were evaluated in three different treatment groups of mechanically impacted porcine articular cartilage. The genes evaluated were: beta actin, beta-2-microglobulin, glyceraldehyde-3-phosphate dehydrogenase, hydroxymethylbilane synthase, hypoxanthine phosphoribosyl transferase, peptidylprolyl isomerase A (cyclophilin A), ribosomal protein L4, succinate dehydrogenase flavoprotein subunit A, TATA box binding protein, and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein—zeta polypeptide. The stability of the genes was measured using geNorm, BestKeeper, and NormFinder software. The four most stable genes measured via geNorm were (most to least stable) succinate dehydrogenase flavoprotein, subunit A, peptidylprolyl isomerase A, glyceraldehyde-3-phosphate dehydrogenase, beta actin; the four most stable genes measured via BestKeeper were glyceraldehyde-3-phosphate dehydrogenase, peptidylprolyl isomerase A, beta actin, succinate dehydrogenase flavoprotein, subunit A; and the four most stable genes measured via NormFinder were peptidylprolyl isomerase A, succinate dehydrogenase flavoprotein, subunit A, glyceraldehyde-3-phosphate dehydrogenase, beta actin.

Conclusions
BestKeeper, geNorm, and NormFinder all generated similar results for the most stable genes in porcine articular cartilage. The use of these appropriate reference genes will facilitate accurate gene expression studies of porcine articular cartilage and suggest appropriate housekeeping genes for articular cartilage studies in other species.
A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilator-associated pneumonia
Authors: Kollef Marin H , Chastre Jean , Clavel Marc , Restrepo Marcos I , Michiels Bart , Kaniga Koné , Cirillo Iolanda , Kimko Holly , Redman Rebecca 
Published: November 2012

Abstract
Introduction
The aim of this study was to compare a 7-day course of doripenem to a 10-day course of imipenem-cilastatin for ventilator-associated pneumonia (VAP) due to Gram-negative bacteria.

Methods
This was a prospective, double-blinded, randomized trial comparing a fixed 7-day course of doripenem one gram as a four-hour infusion every eight hours with a fixed 10-day course of imipenem-cilastatin one gram as a one-hour infusion every eight hours (April 2008 through June 2011).

Results
The study was stopped prematurely at the recommendation of the Independent Data Monitoring Committee that was blinded to treatment arm assignment and performed a scheduled review of data which showed signals that were close to the pre-specified stopping limits. The final analyses included 274 randomized patients. The clinical cure rate at the end of therapy (EOT) in the microbiological intent-to-treat (MITT) population was numerically lower for patients in the doripenem arm compared to the imipenem-cilastatin arm (45.6% versus 56.8%; 95% CI, -26.3% to 3.8%). Similarly, the clinical cure rate at EOT was numerically lower for patients with Pseudomonas aeruginosa VAP, the most common Gram-negative pathogen, in the doripenem arm compared to the imipenem-cilastatin arm (41.2% versus 60.0%; 95% CI, -57.2 to 19.5). All cause 28-day mortality in the MITT group was numerically greater for patients in the doripenem arm compared to the imipenem-cilastatin arm (21.5% versus 14.8%; 95% CI, -5.0 to 18.5) and for patients with P. aeruginosa VAP (35.3% versus 0.0%; 95% CI, 12.6 to 58.0).

Conclusions
Among patients with microbiologically confirmed late-onset VAP, a fixed 7-day course of doripenem was found to have non-significant higher rates of clinical failure and mortality compared to a fixed 10-day course of imipenem-cilastatin. Consideration should be given to treating patients with VAP for more than seven days to optimize clinical outcome.

Trial Registration
ClinicalTrials.gov: NCT00589693
Optimizing EM data acquisition for continental shelf exploration
Authors: Barker N. D. , Morten J. P. , Shantsev D. V. 
Published: November 2012

The controlled-source electromagnetic (CSEM) method has been applied to oil and gas exploration and production for more than 10 years. During this time, most of the focus has been on derisking deep- and ultradeep-water drilling decisions. In this article, we will consider how EM methods can be optimized for continental shelf applications, which represent approximately 80% of offshore discoveries.Historically, applications of EM on the continental shelf have been limited for two principal reasons:
Blood concentrations of lactate, glucose and corticosterone in dispersing hatchling sea turtles
Authors: Pereira Carla M. , Booth David T. , Bradley Adrian J. , Limpus Colin J. 
Published: November 2012

Summary
Natal dispersal of sea turtles is an energetically demanding activity that is fuelled primarily by aerobic metabolism. However, during intense exercise reptiles can use anaerobic metabolism to supplement their energy requirements. We assessed anaerobic metabolism in dispersing hatchling loggerhead and flatback turtles by measuring the concentrations of blood lactate during crawling and at different times during the first four hours of their frenzy swim. We also measured concentrations of blood glucose and corticosterone. Blood lactate (12.13 to 2.03 mmol/L), glucose (6.25 to 3.8 mmol/L) and corticosterone (8.13 to 2.01 ng/mL) concentrations decreased significantly over time in both loggerhead and flatback hatchlings and no significant differences were found between the species. These results indicate that anaerobic metabolism makes a significant contribution to the dispersal phase of hatchling sea turtles during the beach crawl and the first few hours of the frenzy swim.