bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hygiene intervention reduces contamination of weaning food in Bangladesh
Authors: Islam Mohammad Sirajul , Mahmud Zahid Hayat , Gope Partha Sarathi , Zaman Rokon Uz , Hossain Zakir , Islam Mohammad Shafiqul , Mondal Dinesh , Sharker Mohammad Abu Yushuf , Islam Khairul , Jahan Hasin , Bhuiya Abbas , Endtz Hubert P. , Cravioto Alejandro , Curtis Valerie , Touré Ousmane , Cairncross Sandy 
Published: December 2012

AbstractObjectiveThis study was conducted to measure the impact of a hygiene intervention on the contamination of weaning food in Bangladesh.MethodsSixty households were selected: 30 study and 30 control households. Samples of weaning food were collected from all the 60 households at baseline and examined for faecal coliforms (FC), faecal streptococci (FS) and Clostridium perfringens (CP) following standard procedures. After cooking, food samples were collected on three occasions before feeding. Following Hazard Analysis Critical Control Point (HACCP) procedures, critical control points were determined. The mothers in the 30 study households were then trained for 4 weeks in how to attain the control point conditions. Then, again the food samples were collected and analysed.ResultsAt baseline, weaning foods from study and control households were heavily contaminated with FC and FS. The FC and FS counts were 1.84 log10 and 1.92 log10 colony‐forming unit (cfu)/g, respectively, in the study households, and 0.86 log10 and 1.33 log10 cfu/g, respectively, in the control households in the first feeding. After the intervention, the FC and FS counts in study households had dropped to 0.10 log10 and 0.09 log10 cfu/g, respectively, a statistically significant reduction (P < 0.001). Monitoring the sustainability of the behaviour change after 3 months showed that the mothers were maintaining food hygiene.ConclusionsA hygiene intervention following the HACCP approach reduced the weaning food contamination significantly. Awareness building among mothers about weaning food hygiene could be an important intervention for preventing weaning food–related diarrhoea in Bangladesh.
Observed changes in soyabean growth and seed yield from Abutilon theophrasti competition as a function of carbon dioxide concentration
Authors: Ziska L 
Published: December 2012

SummarySoyabean (Glycine max) was grown at ambient and projected levels of atmospheric carbon dioxide (+250 μmol mol−1 above ambient) over two field seasons with and without the presence of a weed, Abutilon theophrasti, to quantify the potential effect of rising atmospheric carbon dioxide concentration on weed–crop interactions and potential yield loss in soyabean. Under weed‐free conditions, elevated CO2 resulted in stimulations in soyabean seed yield and associated components, including pod number. At an approximate density of 6 plants m−2, A. theophrasti competition resulted in a significant reduction (−40%) in soyabean seed yield. Although differences in seed yield reduction by A. theophrasti were observed as a function of year, the relative decrease in seed yield with A. theophrasti biomass did not differ in response to CO2. Although careful weed management will be necessary if CO2‐induced increases in seed yield for soyabean are to be achieved, these data suggest that soyabean seed yield may be more resilient in competition with A. theophrasti as a function of rising atmospheric levels of carbon dioxide.
Factors Associated with Dog Rabies Vaccination in Bhol, Philippines: Results of a Cross‐Sectional Cluster Survey Conducted Following the Island‐Wide Rabies Elimination Campaign
Authors: Davlin S. , Lapiz S. M. , Miranda M. E. , Murray K. 
Published: December 2012

SummaryThe Philippines has a long history of rabies control efforts in their dog populations; however, long‐term success of such programmes and the goal of rabies elimination have not yet been realized. The Bohol Rabies Prevention and Elimination Program was developed as an innovative approach to canine rabies control in 2007. The objective of this study was to assess canine rabies vaccination coverage in the owned‐dog population in Bohol and to describe factors associated with rabies vaccination 2 years after implementation of the programme. We utilized a cross‐sectional cluster survey based on the World Health Organization’s Expanded Programme on Immunization coverage survey technique. We sampled 460 households and collected data on 539 dogs residing within these households. Seventy‐seven per cent of surveyed households reported owning at least one dog. The human‐to‐dog ratio was approximately 4 : 1, and the mean number of dogs owned per household was 1.6. Based on this ratio, we calculated an owned‐dog population of almost 300 000. Overall, 71% of dogs were reported as having been vaccinated for rabies at some time in their lives; however, only 64% of dogs were reported as having been recently vaccinated. Dogs in our study were young (median age = 24 months). The odds of vaccination increased with increasing age. Dogs aged 12–23 months had 4.6 times the odds of vaccination compared to dogs aged 3–11 months (95% CI 1.8–12.0; P = 0.002). Confinement of the dog both day and night was also associated with increased odds of vaccination (OR = 2.1; 95% CI 0.9–4.9; P = 0.07), and this result approached statistical significance. While the programme is on track to meet its goal of 80% vaccination coverage, educational efforts should focus on the need to confine dogs and vaccinate young dogs.
A Survey of Canadian Public Health Personnel Regarding Knowledge, Practice and Education of Zoonotic Diseases
Authors: Snedeker K. G. , Anderson M. E. C. , Sargeant J. M. , Weese J. S. 
Published: December 2012

SummaryZoonoses, diseases that can spread under natural conditions between humans and other animals, are become a major public health concern in many countries including Canada. In Canada, investigations of zoonotic disease incidents are often conducted by public health inspectors (PHIs). However, little is known about PHIs' knowledge of transmission of zoonotic pathogens, their perceptions of zoonotic disease importance or their education regarding zoonotic diseases. The objective of this study was therefore to assess the knowledge, perceptions and education of Canadian PHIs regarding zoonotic diseases. Data were collected from December 2008–January 2009 using an internet‐based survey distributed to members of the Canadian Institute of Public Health Inspectors national listserv. Responses were received from 229 PHIs in four provinces, with a response rate of approximately 20%. The majority of respondents reported at least 10 years of experience in the public health sector, 80% (181/225) were in frontline positions, and 62% (137/222) were routinely involved in investigations of infectious diseases. Two‐thirds believed that the importance of zoonotic diseases with regards to public health would increase in the next 5 years. Whilst most respondents were able to correctly identify animals capable of directly transmitting common zoonotic pathogens, there were gaps in knowledge, particularly with regard to rabies and transmission of gastrointestinal pathogens by companion animals. PHIs tended to feel that their training on zoonotic diseases prior to working as PHIs was deficient in some areas, or left some room for improvement. Their responses also suggested that there is a need for improvement in both the quantity and the quality of continuing education on zoonotic diseases. In particular, less than one‐third of PHIs received ongoing continuing education regarding zoonotic diseases, and of those that did, nearly two‐thirds rated the quantity and quality as only fair.
Risk of HIV or second syphilis infection in Danish men with newly acquired syphilis in the period 2000–2010
Authors: Salado-Rasmussen Kirsten , Katzenstein Terese Lea , Gerstoft Jan , Cowan Susan Alice , Knudsen Troels Bygum , Mathiesen Lars , Hoffmann Steen , Obel Niels 
Published: December 2012

ObjectivesRisk of subsequent diagnosis of HIV in persons diagnosed with newly acquired syphilis, and syphilis in HIV-infected persons, are of interest as these infections are markers of unsafe sex.MethodsFrom a nationwide register, all Danish men aged >16 years diagnosed with syphilis in the period 2000–2010 (n=1217) were identified, and subsequently data on HIV status was extracted from the Danish HIV Cohort Study. We used Kaplan–Meier analysis to estimate the 5-year risk of HIV and second syphilis infection, and Cox regression to determine incidence rate ratios (IRR).ResultsThe 5-year risk of HIV diagnosis was 9.8% (95% CI 7.0% to 12.6%). Those with a second diagnosis of syphilis had a higher risk of being diagnosed with HIV (IRR=3.1, 95% CI 1.2 to 8.0). The 5-year risk for a second diagnosis of syphilis was 14.8% (95% CI 12.1% to 17.4%) and HIV-infected persons had a higher risk of a second syphilis diagnosis (IRR=4.0, 95% CI 2.8 to 5.9). Sixty-five percent of the persons were men having sex with men (MSM). Thirty-four percent of the HIV-infected persons had viral load >1000 copies/ml at time of syphilis diagnosis.ConclusionsThe substantial risks of syphilis and HIV infection in men diagnosed with one of these sexually transmitted diseases indicate a high frequency of unsafe sex in the Danish MSM population. As one-third of the HIV-infected persons diagnosed with syphilis had high viral loads, our data support initiation of antiretroviral therapy in all HIV-infected MSM to reduce HIV transmission.
Chromothripsis and Focal Copy Number Alterations Determine Poor Outcome in Malignant Melanoma
Authors: Hirsch Daniela , Kemmerling Ralf , Davis Sean , Camps Jordi , Meltzer Paul S. , Ried Thomas , Gaiser Timo 
Published: December 2012

Abstract
Genetic changes during tumorigenesis are usually acquired sequentially. However, a recent study showed that in 2% to 3% of all cancers a single catastrophic event, termed chromothripsis, can lead to massive genomic rearrangements confined to one or a few chromosomes. To explore whether the degree of genomic instability and chromothripsis influences prognosis in cancer, we retrospectively applied array-comparative genomic hybridization (aCGH) to 20 malignant melanomas that showed, despite comparable conventional clinical and pathologic parameters, a profoundly different clinical course. We compared 10 patients who died of malignant melanoma 3.7 years (median, range 0.9–7.6 years) after diagnosis with 10 patients who survived malignant melanoma and had a median disease-free survival of 14.8 years (range 12.5–16.7 years; P = 0.00001). We observed a striking association between the degree of chromosomal instability, both numerical and structural, and outcome. Malignant melanomas associated with good prognosis showed only few chromosomal imbalances (mean 1.6 alterations per case), predominantly whole chromosome or chromosome arm gains and losses, whereas malignant melanomas with poor prognosis harbored significantly more chromosomal aberrations (13.9 per case; P = 0.008). Array-based CGH showed that these aberrations were mostly focal events, culminating in two cases in a pattern consistent with the phenomenon of chromothripsis, which was confirmed by paired-end sequencing. This is the first description of chromothripsis in primary malignant melanomas. Our study therefore links focal copy number alterations and chromothripsis with poor outcome in patients with malignant melanomas (P = 0.0002) and provides a genetic approach to predict outcome in malignant melanomas. Cancer Res; 73(5); 1454–60. ©2012 AACR.
p38α Inhibits Liver Fibrogenesis and Consequent Hepatocarcinogenesis by Curtailing Accumulation of Reactive Oxygen Species
Authors: Sakurai Toshiharu , Kudo Masatoshi , Umemura Atsushi , He Guobin , Elsharkawy Ahmed M. , Seki Ekihiro , Karin Michael 
Published: December 2012

Abstract
Most hepatocellular carcinomas (HCC) develop in the context of severe liver fibrosis and cirrhosis caused by chronic liver inflammation, which also results in accumulation of reactive oxygen species (ROS). In this study, we examined whether the stress-activated protein kinase p38α (Mapk14) controls ROS metabolism and development of fibrosis and cancer in mice given thioacetamide to induce chronic liver injury. Liver-specific p38α ablation was found to enhance ROS accumulation, which appears to be exerted through the reduced expression of antioxidant protein HSP25 (Hspb1), a mouse homolog of HSP27. Its reexpression in p38α-deficient liver prevents ROS accumulation and thioacetamide-induced fibrosis. p38α deficiency increased expression of SOX2, a marker for cancer stem cells and the liver oncoproteins c-Jun (Jun) and Gankyrin (Psmd10) and led to enhanced thioacetamide-induced hepatocarcinogenesis. The upregulation of SOX2 and c-Jun was prevented by administration of the antioxidant butylated hydroxyanisole. Intriguingly, the risk of human HCC recurrence is positively correlated with ROS accumulation in liver. Thus, p38α and its target HSP25/HSP27 appear to play a conserved and critical hepatoprotective function by curtailing ROS accumulation in liver parenchymal cells engaged in oxidative metabolism of exogenous chemicals. Augmented oxidative stress of liver parenchymal cells may explain the close relationship between liver fibrosis and hepatocarcinogenesis. Cancer Res; 73(1); 215–24. ©2012 AACR.
Interstitial Flow in a 3D Microenvironment Increases Glioma Invasion by a CXCR4-Dependent Mechanism
Authors: Munson Jennifer M. , Bellamkonda Ravi V. , Swartz Melody A. 
Published: December 2012

Abstract
Brain tumor invasion leads to recurrence and resistance to treatment. Glioma cells invade in distinct patterns, possibly determined by microenvironmental cues including chemokines, structural heterogeneity, and fluid flow. We hypothesized that flow originating from pressure differentials between the brain and tumor is active in glioma invasion. Using in vitro models, we show that interstitial flow promotes cell invasion in multiple glioma cell lines. Flow effects were CXCR4-dependent, because they were abrogated by CXCR4 inhibition. Furthermore, CXCR4 was activated in response to flow, which could be responsible for enhanced cell motility. Flow was seen to enhance cell polarization in the flow direction, and this flow-induced polarization could be blocked by CXCR4 inhibition or CXCL12 oversaturation in the matrix. Furthermore, using live imaging techniques in a three-dimensional flow chamber, there were more cells migrating and more cells migrating in the direction of flow. This study shows that interstitial flow is an active regulator of glioma invasion. The new mechanisms of glioma invasion that we identify here—namely, interstitial flow-enhanced motility, activation of CXCR4, and CXCL12-driven autologous chemotaxis—are significant in therapy to prevent or treat brain cancer invasion. Current treatment strategies can lead to edema and altered flow in the brain, and one popular experimental treatment in clinical trials, convection enhanced delivery, involves enhancement of flow in and around the tumor. A better understanding of how interstitial flow at the tumor margin can alter chemokine distributions, cell motility, and directed invasion offers a better understanding of treatment failure. Cancer Res; 73(5); 1536–46. ©2012 AACR.
Biologic Challenges in the Detection of Circulating Tumor Cells
Authors: Joosse Simon A. , Pantel Klaus 
Published: December 2012

Abstract
Carcinoma cells found in the blood of cancer patients are predictors of metastatic progression and may guide treatment decisions. Most of the current strategies for detecting circulating tumor cells (CTC) are based on the epithelial markers epithelial cell adhesion molecule and keratin; however, evidence is accumulating that in certain tumor types, these epithelial markers are downregulated during tumor cell dissemination, hampering the detection of CTCs. This short review discusses the implications of the cellular changes of tumor cells during the metastatic cascade on CTC diagnostics. Cancer Res; 73(1); 8–11. ©2012 AACR.
Molecular Pathways: Toll-like Receptors in the Tumor Microenvironment—Poor Prognosis or New Therapeutic Opportunity
Authors: Ridnour Lisa A. , Cheng Robert Y.S. , Switzer Christopher H. , Heinecke Julie L. , Ambs Stefan , Glynn Sharon , Young Howard A. , Trinchieri Giorgio , Wink David A. 
Published: December 2012

Abstract
Numerous reports have described Toll-like receptor (TLR) expression in the tumor microenvironment as it relates to cancer progression, as well as their involvement in inflammation. While TLRs mediate immune surveillance, clinical studies have associated TLR expression in the tumor with poor patient survival, indicating that TLR expression may affect cancer treatment and survival. This review will examine mechanisms in which TLR activation upregulates protumorigenic pathways, including the induction of inducible nitric oxide synthase (iNOS2) and COX2, which in turn increase TLR expression and promote a feed-forward loop leading to tumor progression and the development of more aggressive tumor phenotypes. These propagating loops involve cancer cell, stroma, and/or immune cell TLR expression. Because of abundant TLR expression in many human tumors, several TLR agonists are now in clinical and preclinical trials and some have shown enhanced efficacy when used as adjuvant with radiation, chemotherapy, or cancer vaccines. These findings suggest that TLR expression influences cancer biology and therapeutic response, which may involve specific interactions within the tumor microenvironment, including mediators of inflammation such as nitric oxide and the arachidonic acid signaling pathways. Clin Cancer Res; 19(6); 1340–6. ©2012 AACR.
VS-5584, a Novel and Highly Selective PI3K/mTOR Kinase Inhibitor for the Treatment of Cancer
Authors: Hart Stefan , Novotny-Diermayr Veronica , Goh Kee Chuan , Williams Meredith , Tan Yong Cheng , Ong Lai Chun , Cheong Albert , Ng Bee Kheng , Amalini Chithra , Madan Babita , Nagaraj Harish , Jayaraman Ramesh , Pasha Khalid M. , Ethirajulu Kantharaj , Chng Wee Joo , Mustafa Nurulhuda , Goh Boon Cher , Benes Cyril , McDermott Ultan , Garnett Mathew , Dymock Brian , Wood Jeanette M. 
Published: December 2012

Abstract
Dysregulation of the PI3K/mTOR pathway, either through amplifications, deletions, or as a direct result of mutations, has been closely linked to the development and progression of a wide range of cancers. Moreover, this pathway activation is a poor prognostic marker for many tumor types and confers resistance to various cancer therapies. Here, we describe VS-5584, a novel, low-molecular weight compound with equivalent potent activity against mTOR (IC50 = 37 nmol/L) and all class I phosphoinositide 3-kinase (PI3K) isoforms IC50: PI3Kα = 16 nmol/L; PI3Kβ = 68 nmol/L; PI3Kγ = 25 nmol/L; PI3Kδ = 42 nmol/L, without relevant activity on 400 lipid and protein kinases. VS-5584 shows robust modulation of cellular PI3K/mTOR pathways, inhibiting phosphorylation of substrates downstream of PI3K and mTORC1/2. A large human cancer cell line panel screen (436 lines) revealed broad antiproliferative sensitivity and that cells harboring mutations in PI3KCA are generally more sensitive toward VS-5584 treatment. VS-5584 exhibits favorable pharmacokinetic properties after oral dosing in mice and is well tolerated. VS-5584 induces long-lasting and dose-dependent inhibition of PI3K/mTOR signaling in tumor tissue, leading to tumor growth inhibition in various rapalog-sensitive and -resistant human xenograft models. Furthermore, VS-5584 is synergistic with an EGF receptor inhibitor in a gastric tumor model. The unique selectivity profile and favorable pharmacologic and pharmaceutical properties of VS-5584 and its efficacy in a wide range of human tumor models supports further investigations of VS-5584 in clinical trials. Mol Cancer Ther; 12(2); 151–61. ©2012 AACR.
WEE1 Kinase Inhibition Enhances the Radiation Response of Diffuse Intrinsic Pontine Gliomas
Authors: Caretti Viola , Hiddingh Lotte , Lagerweij Tonny , Schellen Pepijn , Koken Phil W. , Hulleman Esther , van Vuurden Dannis G. , Vandertop W. Peter , Kaspers Gertjan J.L. , Noske David P. , Wurdinger Thomas 
Published: December 2012

Abstract
Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric disease. Thus far, no therapeutic agent has proven beneficial in the treatment of this malignancy. Therefore, conventional DNA-damaging radiotherapy remains the standard treatment, providing transient neurologic improvement without improving the probability of overall survival. During radiotherapy, WEE1 kinase controls the G2 cell-cycle checkpoint, allowing for repair of irradiation (IR)-induced DNA damage. Here, we show that WEE1 kinase is one of the highest overexpressed kinases in primary DIPG tissues compared with matching non-neoplastic brain tissues. Inhibition of WEE1 by MK-1775 treatment of DIPG cells inhibited the IR-induced WEE1-mediated phosphorylation of CDC2, resulting in reduced G2–M arrest and decreased cell viability. Finally, we show that MK-1775 enhances the radiation response of E98-Fluc-mCherry DIPG mouse xenografts. Altogether, these results show that inhibition of WEE1 kinase in conjunction with radiotherapy holds potential as a therapeutic approach for the treatment of DIPG. Mol Cancer Ther; 12(2); 141–50. ©2012 AACR.
Selective Photodetection and Photodynamic Therapy for Prostate Cancer through Targeting of Proteolytic Activity
Authors: Zuluaga Maria-Fernanda , Sekkat Nawal , Gabriel Doris , van den Bergh Hubert , Lange Norbert 
Published: December 2012

AbstractFrequent side effects of radical treatment modalities and the availability of novel diagnostics have raised the interest in focal therapies for localized prostate cancer. To improve the selectivity and therapeutic efficacy of such therapies, we developed a minimally invasive procedure based on a novel polymeric photosensitizer prodrug sensitive to urokinase-type plasminogen activator (uPA). The compound is inactive in its prodrug form and accumulates passively at the tumor site by the enhanced permeability and retention effect. There, the prodrug is selectively converted to its photoactive form by uPA, which is overexpressed by prostate cancer cells. Irradiation of the activated photosensitizer exerts a tumor-selective phototoxic effect. The prodrug alone (8 μmol/L) showed no toxic effect on PC-3 cells, but upon irradiation the cell viability was reduced by 90%. In vivo, after systemic administration of the prodrug, PC-3 xenografts became selectively fluorescent. This is indicative of the prodrug accumulation in the tumor and selective local enzymatic activation. Qualitative analysis of the activated compound confirmed that the enzymatic cleavage occurred selectively in the tumor, with only trace amounts in the neighboring skin or muscle. Subsequent photodynamic therapy studies showed complete tumor eradication of animals treated with light (150 J/cm2 at 665 nm) 16 hours after the injection of the prodrug (7.5 mg/kg). These promising results evidence the excellent selectivity of our prodrug with the potential to be used for both imaging and therapy for localized prostate cancer. Mol Cancer Ther; 12(3); 306–13. ©2012 AACR.