bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacodynamics of oxytetracycline administered alone and in combination with carprofen in calves
Authors: Brentnall C. , Cheng Z. , McKellar Q. A. , Lees P. 
Published: July 2012

The pharmacodynamics (PD) of oxytetracycline was investigated against a strain of Mannheimia haemolytica. In vitro measurements, comprising minimum inhibitory concentration (MIC), minimum bactericidal concentration and time‐kill curves, were conducted in five matrices; Mueller Hinton Broth (MHB), cation‐adjusted MHB (CAMHB) and calf serum, exudate and transudate. MICs were much higher in the biological fluids than in MHB and CAMHB. Ratios of MIC were, serum: CAMHB 19 : 1; exudate:CAMHB 16.1; transudate:CAMHB 14 : 1. Ex vivo data, generated in the tissue cage model of inflammation, demonstrated that oxytetracycline, administered to calves intramuscularly at a dose rate of 20 mg/kg, did not inhibit the growth of M haemolytica in serum, exudate and transudate, even at peak concentration. However, using in vitro susceptibility in CAMHB and in vivo‐determined pharmacokinetic (PK) variables, average and minimum oxytetracycline concentrations relative to MIC (Cav /MIC and Cmin /MIC) predicted achievement of efficacy for approximately 48 hours after dosing. Similar Cav /MIC and Cmin /MIC data were obtained when oxytetracycline was administered in the presence of carprofen. PK‐PD integration of data for oxytetracycline, based on MICs determined in the three biological fluids, suggests that it possesses, at most, limited direct killing activity against M haemolytica. These data raise questions concerning the mechanism(s) of action of oxytetracycline, when administered at clinically recommended dose rates.
Mechanisms of BRCA1 Tumor Suppression
Authors: Silver Daniel P. , Livingston David M. 
Published: July 2012

Abstract
The p220 BRCA1 tumor suppressor protein has been implicated in multiple biochemical and biologic functions since its molecular cloning 18 years ago. Here, we discuss those functions most relevant for its tumor-suppressing activities with an emphasis on new findings. In particular, this review focuses on what is known of the activities of those BRCA1-binding partners that have tumor suppressor functions, on the reversion of mutant BRCA1 alleles concomitant with therapy resistance, on insights gained from studies of BRCA1 structure–function relationships, recent findings from animal models, and the potential role of BRCA1 in some nonhereditary tumors. From this information, a more detailed and refined picture of BRCA1 tumor suppression is beginning to emerge. Although key mysteries remain—such as why BRCA1 tumor suppression is focused on carcinomas of the breast and ovary—the pace of discovery is increasing.
Significance: BRCA1 functions as a clinically important classical tumor suppressor in hereditary breast and ovarian cancer; here, we review progress in understanding how BRCA1 operates to suppress tumor formation. Cancer Discov; 2(8); 679–84. ©2012 AACR.
Patterns and architecture of genomic islands in marine bacteria
Authors: Fernández-Gómez Beatriz , Fernàndez-Guerra Antonio , Casamayor Emilio O , González José M , Pedrós-Alió Carlos , Acinas Silvia G 
Published: July 2012

AbstractBackgroundGenomic Islands (GIs) have key roles since they modulate the structure and size of bacterial genomes displaying a diverse set of laterally transferred genes. Despite their importance, GIs in marine bacterial genomes have not been explored systematically to uncover possible trends and to analyze their putative ecological significance.ResultsWe carried out a comprehensive analysis of GIs in 70 selected marine bacterial genomes detected with IslandViewer to explore the distribution, patterns and functional gene content in these genomic regions. We detected 438 GIs containing a total of 8152 genes. GI number per genome was strongly and positively correlated with the total GI size. In 50% of the genomes analyzed the GIs accounted for approximately 3% of the genome length, with a maximum of 12%. Interestingly, we found transposases particularly enriched within Alphaproteobacteria GIs, and site-specific recombinases in Gammaproteobacteria GIs. We described specific Homologous Recombination GIs (HR-GIs) in several genera of marine Bacteroidetes and inShewanellastrains among others. In these HR-GIs, we recurrently found conserved genes such as the β-subunit of DNA-directed RNA polymerase, regulatory sigma factors, the elongation factor Tu and ribosomal protein genes typically associated with the core genome.ConclusionsOur results indicate that horizontal gene transfer mediated by phages, plasmids and other mobile genetic elements, and HR by site-specific recombinases play important roles in the mobility of clusters of genes between taxa and within closely related genomes, modulating the flexible pool of the genome. Our findings suggest that GIs may increase bacterial fitness under environmental changing conditions by acquiring novel foreign genes and/or modifying gene transcription and/or transduction.
Global transcriptome analysis reveals distinct expression among duplicated genes during sorghum-Bipolaris sorghicolainteraction
Authors: Mizuno Hiroshi , Kawahigashi Hiroyuki , Kawahara Yoshihiro , Kanamori Hiroyuki , Ogata Jun , Minami Hiroshi , Itoh Takeshi , Matsumoto Takashi 
Published: July 2012

Abstract

Background
Sorghum (Sorghum bicolor L. Moench) is a rich source of natural phytochemicals. We performed massive parallel sequencing of mRNA to identify differentially expressed genes after sorghum BTx623 had been infected with Bipolaris sorghicola, a necrotrophic fungus causing a sorghum disease called target leaf spot.

Result
Seventy-six-base-pair reads from mRNAs of mock- or pathogen-infected leaves were sequenced. Unannotated transcripts were predicted on the basis of the piling-up of mapped short reads. Differentially expressed genes were identified statistically; particular genes in tandemly duplicated putative paralogs were highly upregulated. Pathogen infection activated the glyoxylate shunt in the TCA cycle; this changes the role of the TCA cycle from energy production to synthesis of cell components. The secondary metabolic pathways of phytoalexin synthesis and of sulfur-dependent detoxification were activated by upregulation of the genes encoding amino acid metabolizing enzymes located at the branch point between primary and secondary metabolism. Coordinated gene expression could guide the metabolic pathway for accumulation of the sorghum-specific phytochemicals 3-deoxyanthocyanidin and dhurrin. Key enzymes for synthesizing these sorghum-specific phytochemicals were not found in the corresponding region of the rice genome.

Conclusion
Pathogen infection dramatically changed the expression of particular paralogs that putatively encode enzymes involved in the sorghum-specific metabolic network.
Net financial benefits of averting HIV infections among people who inject drugs in Urumqi, Xinjiang, Peoples Republic of China (2005–2010)
Authors: Ni Mingjian J , Fu Li Ping , Chen Xue Ling , Hu Xiao Yuan , Wheeler Kim 
Published: July 2012

Abstract

Background
To quantify the contribution of locally implemented prevention programmes in contributing to reductions in treatment and care costs by averting HIV infections among those who inject drugs this study calculates net financial benefit of providing harm reduction programmes using information from services being implemented in Urumqi, Xinjiang Uighur Autonomous Region of China ( between 2005 and 2010).

Methods
Information was collected to assess cost of providing methadone treatment (MMT) and needle and syringe programmes (NSP). HIV incidence was estimated among people who inject drugs (PWID). HIV infections averted were calculated. Net benefit was assessed by estimating costs of providing prevention programmes and comparing these to the costs of providing care.

Results
An estimated 5678 (range 3982–7599) HIV infections were averted between 2005 and 2010 and the net financial benefit of providing harm reduction programmes compared to treatment and care costs for HIV infections averted was USD 4.383 million during the same time period.

Conclusion
These results demonstrate the net and accumulating benefit of investing in harm reduction programmes for PWID in Urumqi. The return on investment progressively increased during the time period studied and it is clear that these cost savings will continue to accrue with the continued implementation of HIV prevention interventions in the community that include harm reduction programmes targeted at PWID.
Computational challenges and human factors influencing the design and use of clinical research participant eligibility pre-screening tools
Authors: Pressler Taylor R , Yen Po-Yin , Ding Jing , Liu Jianhua , Embi Peter J , Payne Philip R O 
Published: July 2012

Abstract

Background
Clinical trials are the primary mechanism for advancing clinical care and evidenced-based practice, yet challenges with the recruitment of participants for such trials are widely recognized as a major barrier to these types of studies. Data warehouses (DW) store large amounts of heterogenous clinical data that can be used to enhance recruitment practices, but multiple challenges exist when using a data warehouse for such activities, due to the manner of collection, management, integration, analysis, and dissemination of the data. A critical step in leveraging the DW for recruitment purposes is being able to match trial eligibility criteria to discrete and semi-structured data types in the data warehouse, though trial eligibility criteria tend to be written without concern for their computability. We present the multi-modal evaluation of a web-based tool that can be used for pre-screening patients for clinical trial eligibility and assess the ability of this tool to be practically used for clinical research pre-screening and recruitment.

Methods
The study used a validation study, usability testing, and a heuristic evaluation to evaluate and characterize the operational characteristics of the software as well as human factors affecting its use.

Results
Clinical trials from the Division of Cardiology and the Department of Family Medicine were used for this multi-modal evaluation, which included a validation study, usability study, and a heuristic evaluation. From the results of the validation study, the software demonstrated a positive predictive value (PPV) of 54.12% and 0.7%, respectively, and a negative predictive value (NPV) of 73.3% and 87.5%, respectively, for two types of clinical trials. Heuristic principles concerning error prevention and documentation were characterized as the major usability issues during the heuristic evaluation.

Conclusions
This software is intended to provide an initial list of eligible patients to a clinical study coordinators, which provides a starting point for further eligibility screening by the coordinator. Because this software has a high “rule in” ability, meaning that it is able to remove patients who are not eligible for the study, the use of an automated tool built to leverage an existing enterprise DW can be beneficial to determining eligibility and facilitating clinical trial recruitment through pre-screening. While the results of this study are promising, further refinement and study of this and related approaches to automated eligibility screening, including comparison to other approaches and stakeholder perceptions, are needed and future studies are planned to address these needs.
Artemisinin resistance containment project in Thailand. (I): Implementation of electronic-based malaria information system for early case detection and individual case management in provinces along the Thai-Cambodian border
Authors: Khamsiriwatchara Amnat , Sudathip Prayuth , Sawang Surasak , Vijakadge Saowanit , Potithavoranan Thanapon , Sangvichean Aumnuyphan , Satimai Wichai , Delacollette Charles , Singhasivanon Pratap , Lawpoolsri Saranath , Kaewkungwal Jaranit 
Published: July 2012

Abstract

Background
The Bureau of Vector-borne Diseases, Ministry of Public Health, Thailand, has implemented an electronic Malaria Information System (eMIS) as part of a strategy to contain artemisinin resistance. The attempt corresponds to the WHO initiative, funded by the Bill & Melinda Gates Foundation, to contain anti-malarial drug resistance in Southeast Asia. The main objective of this study was to demonstrate the eMIS’ functionality and outputs after implementation for use in the Thailand artemisinin-resistance containment project.

Methods
The eMIS had been functioning since 2009 in seven Thai-Cambodian border provinces. The eMIS has covered 61 malaria posts/clinics, 27 Vector-borne Disease Units covering 12,508 hamlets at risk of malaria infections. The eMIS was designed as an evidence-based and near real-time system to capture data for early case detection, intensive case investigation, monitoring drug compliance and on/off-site tracking of malarial patients, as well as collecting data indicating potential drug resistance among patients. Data captured by the eMIS in 2008–2011 were extracted and presented.

Results
The core functionalities of the eMIS have been utilized by malaria staff at all levels, from local operational units to ministerial management. The eMIS case detection module suggested decreasing trends during 2009–2011; the number of malaria cases detected in the project areas over the years studied were 3818, 2695, and 2566, with sero-positive rates of 1.24, 0.98, and 1.16%, respectively. The eMIS case investigation module revealed different trends in weekly Plasmodium falciparum case numbers, when classified by responsible operational unit, local and migrant status, and case-detection type. It was shown that most Thai patients were infected within their own residential district, while migrants were infected either at their working village or from across the border. The data mapped in the system suggested that P. falciparum-infected cases and potential drug-resistant cases were scattered mostly along the border villages. The mobile technology application has detected different follow-up rates, with particularly low rates among seasonal and cross-border migrants.

Conclusion
The eMIS demonstrated that it could capture essential data from individual malaria cases at local operational units, while effectively being used for situation and trend analysis at upper-management levels. The system provides evidence-based information that could contribute to the control and containment of resistant parasites. Currently, the eMIS is expanding beyond the Thai-Cambodian project areas to the provinces that lie along the Thai-Myanmar border.
Silencing of Apoptosis-Inducing factor and poly (ADP-ribose) glycohydrolase reveals novel roles in breast cancer cell death after chemotherapy
Authors: Feng Xiaoxing , Zhou Yiran , Proctor Alicia M , Hopkins Mandi M , Liu Mengwei , Koh David W 
Published: July 2012

Abstract

Background
Cell death induced by poly(ADP-ribose) (PAR) and mediated by apoptosis-inducing factor (AIF) is well-characterized in models of ischemic tissue injury, but their roles in cancer cell death after chemotherapy are less understood.

Methods
Here we investigated the roles of PAR and AIF by RNA interference (RNAi) in MDA-MB-231 and MCF-7 breast adenocarcinoma cells after chemotherapy. Differences in effects were statistically tested by analysis-of-variance and unpaired student’s t-test.

Results
Silencing of AIF by RNAi led to decreased MDA-MB-231 and MCF-7 breast cancer cell death after chemotherapy, which demonstrates a critical role for AIF. RNAi silencing of PAR glycohydrolase (PARG), the primary enzyme that catalyzes the hydrolysis of PAR, led to increased PAR levels but decreased cell death. Further investigation into the possible role of PAR in apoptosis revealed decreased caspase-3/7/8/9 activity in PARG-null cells. Interestingly, the pharmacologic inhibition of caspase activity in PARG-silenced breast cancer cells led to increased cell death after chemotherapy, which indicates that an alternative cell death pathway is activated due to elevated PAR levels and caspase inhibition. AIF silencing in these cells led to profound protection from chemotherapy, which demonstrates that the increased cell death after PARG silencing and caspase inhibition was mediated by AIF.

Conclusions
The results show a role for AIF in breast cancer cell death after chemotherapy, the ability of PAR to regulate caspase activity, and the ability of AIF to substitute as a primary mediator of breast cancer cell death in the absence of caspases. Thus, the induction of cell death by PAR/AIF may represent a novel strategy to optimize the eradication of breast tumors by activating an alternative cell death pathway.
Neural Mobilization Reverses Behavioral and Cellular Changes That Characterize Neuropathic Pain in Rats
Authors: Santos Fabio M , Silva Joyce T , Giardini Aline C , Rocha Priscila A , Achermann Arnold PP , Alves Adilson S , Britto Luiz RG , Chacur Marucia 
Published: July 2012

Background: The neural mobilization technique is a noninvasive method that has proved clinically effective in reducing pain sensitivity and consequently in improving quality of life after neuropathic pain. The present study examined the effects of neural mobilization (NM) on pain sensitivity induced by chronic constriction injury (CCI) in rats. The CCI was performed on adult male rats, submitted thereafter to 10 sessions of NM, each other day, starting 14 days after the CCI injury. Over the treatment period, animals were evaluated for nociception using behavioral tests, such as tests for allodynia and thermal and mechanical hyperalgesia. At the end of the sessions, the dorsal root ganglion (DRG) and spinal cord were analyzed using immunohistochemistry and Western blot assays for neural growth factor (NGF) and glial fibrillary acidic protein (GFAP). Results: The NM treatment induced an early reduction (from the second session) of the hyperalgesia and allodynia in CCI-injured rats, which persisted until the end of the treatment. On the other hand, only after the 4th session we observed a blockade of thermal sensitivity. Regarding cellular changes, we observed a decrease of GFAP and NGF expression after NM in the ipsilateral DRG (68% and 111%, respectively) and the decrease of only GFAP expression after NM in the lumbar spinal cord (L3-L6) (108%). Conclusions: These data provide evidence that NM treatment reverses pain symptoms in CCI-injured rats and suggest the involvement of glial cells and NGF in such an effect.
Constitutive phosphorylation of the mTORC2/Akt/4E-BP1 pathway in newly derived canine hemangiosarcoma cell lines
Authors: Murai Atsuko , Asa Samah Abou , Kodama Atsushi , Hirata Akihiro , Yanai Tokuma , Sakai Hiroki 
Published: July 2012

Abstract

Background
Canine hemangiosarcoma (HSA) is a malignant tumor with poor long-term prognosis due to development of metastasis despite aggressive treatment. The phosphatidyl-inositol-3 kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is involved in its endothelial pathologies; however, it remains unknown how this pathway plays a role in canine HSA. Here, we characterized new canine HSA cell lines derived from nude mice-xenografted canine HSAs and investigated the deregulation of the signaling pathways in these cell lines.

Results
Seven canine HSA cell lines were established from 3 xenograft canine HSAs and showed characteristics of endothelial cells (ECs), that is, uptake of acetylated low-density lipoprotein and expression of canine-specific CD31 mRNA. They showed varied morphologies and mRNA expression levels for VEGF-A, bFGF, HGF, IGF-I, EGF, PDGF-B, and their receptors. Cell proliferation was stimulated by these growth factors and fetal bovine serum (FBS) in 1 cell line and by FBS alone in 3 cell lines. However, cell proliferation was not stimulated by growth factors and FBS in the remaining 3 cell lines. Phosphorylated p44/42 Erk1/2 was increased by FBS stimulation in 4 cell lines. In contrast, phosphorylation of Akt at Ser473, mTOR complex 1 (mTORC1) at Ser2448, and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) at Ser65 was high in serum-starved condition and not altered by FBS stimulation in 6 cell lines, despite increased phosphorylation of these residues in normal canine ECs. This suggested that the mTORC2/Akt/4E-BP1 pathway was constitutively activated in these 6 canine HSA cell lines. After cell inoculation into nude mice, canine HSA tumors were formed from 4 cell lines and showed Akt and 4E-BP1 phosphorylation identical to the parental cell lines.

Conclusions
Our findings suggest that the present cell lines may be useful tools for investigating the role of the mTORC2/Akt/4E-BP1 pathway in canine HSA formation both in vivo and in vitro.
The saw-tooth sign as a clinical clue for intrathoracic central airway obstruction
Authors: Nakajima Akira , Saraya Takeshi , Takata Saori , Ishii Haruyuki , Nakazato Yoko , Takei Hidefumi , Takizawa Hajime , Goto Hajime 
Published: July 2012

Abstract

Background
The saw-tooth sign was first described by Sanders et al in patients with obstructive sleep apnea syndrome as one cause of extrathoracic central airway obstruction. The mechanism of the saw-tooth sign has not been conclusively clarified. The sign has also been described in various extrathoracic central airway diseases, such as in burn victims with thermal injury to the upper airways, Parkinson’s disease, tracheobronchomalacia, laryngeal dyskinesia, and pedunculated tumors of the upper airway.

Case presentation
A 61-year-old man was referred to our hospital with a two-month history of persistent dry cough and dyspnea. He was diagnosed with lung cancer located in an intrathoracic central airway, which was accompanied by the saw-tooth sign on flow-volume loops. This peculiar sign repeatedly improved and deteriorated, in accordance with the waxing and waning of central airway stenosis by anti-cancer treatments.

Conclusion
This report suggests that the so-called saw-tooth sign may be found even in intrathoracic central airway obstruction due to lung cancer.
Genome-wide DNA methylation profiling of non-small cell lung carcinomas
Authors: Carvalho Rejane Hughes , Haberle Vanja , Hou Jun , van Gent Teus , Thongjuea Supat , van IJcken Wilfred , Kockx Christel , Brouwer Rutger , Rijkers Erikjan , Sieuwerts Anieta , Foekens John , van Vroonhoven Mirjam , Aerts Joachim , Grosveld Frank , Lenhard Boris , Philipsen Sjaak 
Published: July 2012

Abstract

Background
Non-small cell lung carcinoma (NSCLC) is a complex malignancy that owing to its heterogeneity and poor prognosis poses many challenges to diagnosis, prognosis and patient treatment. DNA methylation is an important mechanism of epigenetic regulation involved in normal development and cancer. It is a very stable and specific modification and therefore in principle a very suitable marker for epigenetic phenotyping of tumors. Here we present a genome-wide DNA methylation analysis of NSCLC samples and paired lung tissues, where we combine MethylCap and next generation sequencing (MethylCap-seq) to provide comprehensive DNA methylation maps of the tumor and paired lung samples. The MethylCap-seq data were validated by bisulfite sequencing and methyl-specific polymerase chain reaction of selected regions.

Results
Analysis of the MethylCap-seq data revealed a strong positive correlation between replicate experiments and between paired tumor/lung samples. We identified 57 differentially methylated regions (DMRs) present in all NSCLC tumors analyzed by MethylCap-seq. While hypomethylated DMRs did not correlate to any particular functional category of genes, the hypermethylated DMRs were strongly associated with genes encoding transcriptional regulators. Furthermore, subtelomeric regions and satellite repeats were hypomethylated in the NSCLC samples. We also identified DMRs that were specific to two of the major subtypes of NSCLC, adenocarcinomas and squamous cell carcinomas.

Conclusions
Collectively, we provide a resource containing genome-wide DNA methylation maps of NSCLC and their paired lung tissues, and comprehensive lists of known and novel DMRs and associated genes in NSCLC.