bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges to surface water quality in mid‐sized African cities: conclusions from Awetu‐Kito Rivers in Jimma, south‐west Ethiopia
Authors: Haddis Alemayehu , Getahun Tadesse , Mengistie Embialle , Jemal Amana , Smets Ilse , van der Bruggen Bart 
Published: December 2012

AbstractRapid urbanization and industrialization, uncontrolled population growth, indiscriminate waste discharge and poor infrastructure are problems that African cities are facing. This paper describes an exemplary case study from Jimma, south‐west Ethiopia. A cross‐sectional study was conducted along the Awetu‐Kito drainage system in Jimma town to assess the level of pollution from urban dwellers and related activities. The study indicates that the Environmental Protection Agency (EPA) norms for biochemical oxygen demand (BOD), dissolved oxygen (DO) and orthophosphates are not met downstream of the major industrial and institutional activities. Small‐scale industries, Jimma University and residential areas contributed 50, 15 and 23% pollution load on the river, respectively. It can be concluded that the pollution effect in Jimma town is mainly as a result of the growing (uncontrolled) industrial activities and not to discharge of household wastewater. Given the same trends of urbanization and population growth, similar development (socio‐economic) indicators and similar climatic conditions, the key findings for Jimma are transferable to other mid‐sized African cities.
Impact of variable RBE on proton fractionation
Authors: Dasu Alexandru , Toma‐Dasu Iuliana 
Published: December 2012

Purpose:To explore the impact of variable proton relative biological effectiveness (RBE) on dose fractionation for clinically relevant situations. A generic RBE = 1.1 is generally used for isoeffect calculations, while experimental studies showed that proton RBE varies with tissue type, dose, and linear energy transfer (LET).Methods:An analytical expression for the LET and α/β dependence of the linear‐quadratic (LQ) model has been used for proton simulations in parallel with the assumption of a generic RBE = 1.1. Calculations have been performed for ranges of LET values and fractionation sensitivities to describe clinically relevant cases, such as the treatment of head and neck and prostate tumors. Isoeffect calculations were compared with predictions from a generic RBE value and reported clinical results.Results:The generic RBE = 1.1 appears to be a reasonable estimate for the proton RBE of rapidly growing tissues irradiated with low LET radiation. However, the use of a variable RBE predicts larger differences for tissues with low α/β (both tumor and normal) and at low doses per fraction. In some situations these differences may appear in contrast to the findings from photon studies highlighting the importance of accurate accounting for the radiobiological effectiveness of protons. Furthermore, the use of variable RBE leads to closer predictions to clinical results.Conclusions:The LET dependence of the RBE has a strong impact on the predicted effectiveness of fractionated proton radiotherapy. The magnitude of the effect is modulated by the fractionation sensitivity and the fractional dose indicating the need for accurate analyses both in the target and around it. Care should therefore be employed for changing clinical fractionation patterns or when analyzing results from clinical studies for this type of radiation.
Tissue Distribution of Neospora caninum in Experimentally Infected Cattle
Authors: Nishimura Maki , Kohara Junko , Hiasa Jun , Muroi Yoshikage , Yokoyama Naoaki , Kida Katsuya , Xuan Xuenan , Furuoka Hidefumi , Nishikawa Yoshifumi 
Published: December 2012

ABSTRACTHistopathology and quantitative PCR (qPCR) were used to determine the tissue distribution ofNeospora caninumin calves at 80 days postinfection. Our findings revealed that the most appropriate brain areas for researchingN. caninumpathogenesis were the amygdala and hippocampus for qPCR and the corpus striatum and diencephalon for histopathology.
In VivoDifferences in the Virulence, Pathogenicity, and Induced Protective Immunity ofwboAMutants from Genetically Different Parent Brucella spp
Authors: Wang Zhen , Niu Jianrui , Wang Shuangshan , Lv Yanli , Wu Qingmin 
Published: December 2012

ABSTRACTTo explore the effects of the genetic background on the characteristics ofwboAgene deletion rough mutants generated from different parentBrucellasp. strains, we constructed the rough-mutant strainsBrucella melitensis16 M-MB6,B. abortus2308-SB6,B. abortusS19-RB6, andB. melitensisNI-NB6 and evaluated their survival, pathogenicity, and induced protective immunity in mice and sheep. In mice, the survival times of the four mutants were very different in the virulence assay, from less than 6 weeks forB. abortusS19-RB6 to 11 weeks forB. abortus2308-SB6 andB. melitensisNI-NB6. However,B. abortusS19-RB6 andB. melitensis16 M-MB6, with a shorter survival time in mice, offered better protection against challenges withB. abortus2308 in protection tests thanB. abortus2308-SB6 andB. melitensisNI-NB6. It seems that the induced protective immunity of each mutant might not be associated with its survival timein vivo. In the cross-protection assay, bothB. melitensis16 M-MB6 andB. abortusS19-RB6 induced greater protection against homologous challenges than heterologous challenges. When pregnant sheep were inoculated withB. abortusS19-RB6 andB. melitensis16 M-MB6,B. abortusS19-RB6 did not induce abortion, whereasB. melitensis16 M-MB6 did. These results demonstrated the differences in virulence, pathogenicity, and protective immunityin vivoin thewboAdeletion mutants from genetically different parentBrucellaspp. and also indicated that future rough vaccine strain development could be promising if suitable parentBrucellastrains and/or genes were selected.
Host Cell Autophagy Modulates Early Stages of Adenovirus Infections in Airway Epithelial Cells
Authors: Zeng Xuehuo , Carlin Cathleen R. 
Published: December 2012

ABSTRACT
Human adenoviruses typically cause mild infections in the upper or lower respiratory tract, gastrointestinal tract, or ocular epithelium. However, adenoviruses may be life-threatening in patients with impaired immunity and some serotypes cause epidemic outbreaks. Attachment to host cell receptors activates cell signaling and virus uptake by endocytosis. At present, it is unclear how vital cellular homeostatic mechanisms affect these early steps in the adenovirus life cycle. Autophagy is a lysosomal degradation pathway for recycling intracellular components that is upregulated during periods of cell stress. Autophagic cargo is sequestered in double-membrane structures called autophagosomes that fuse with endosomes to form amphisomes which then deliver their content to lysosomes. Autophagy is an important adaptive response in airway epithelial cells targeted by many common adenovirus serotypes. Using two established tissue culture models, we demonstrate here that adaptive autophagy enhances expression of the early region 1 adenovirus protein, induction of mitogen-activated protein kinase signaling, and production of new viral progeny in airway epithelial cells infected with adenovirus type 2. We have also discovered that adenovirus infections are tightly regulated by endosome maturation, a process characterized by abrupt exchange of Rab5 and Rab7 GTPases, associated with early and late endosomes, respectively. Moreover, endosome maturation appears to control a pool of early endosomes capable of fusing with autophagosomes which enhance adenovirus infection. Many viruses have evolved mechanisms to induce autophagy in order to aid their own replication. Our studies reveal a novel role for host cell autophagy that could have a significant impact on the outcome of respiratory infections.
Sequencing, Annotation, and Characterization of the Influenza Ferret Infectome
Authors: León Alberto J. , Banner David , Xu Luoling , Ran Longsi , Peng Zhiyu , Yi Kang , Chen Chao , Xu Fengping , Huang Jinrong , Zhao Zhen , Lin Zhen , Huang Stephen H. S. , Fang Yuan , Kelvin Alyson A. , Ross Ted M. , Farooqui Amber , Kelvin David J. 
Published: December 2012

ABSTRACT

Ferrets have become an indispensable tool in the understanding of influenza virus virulence and pathogenesis. Furthermore, ferrets are the preferred preclinical model for influenza vaccine and therapeutic testing. Here we characterized the influenza infectome during the different stages of the infectious process in ferrets with and without prior specific immunity to influenza. RNA from lung tissue and lymph nodes from infected and naïve animals was subjected to next-generation sequencing, followed by
de novo
data assembly and annotation of the resulting sequences; this process generated a library comprising 13,202 ferret mRNAs. Gene expression profiles during pandemic H1N1 (pdmH1N1) influenza virus infection were analyzed by digital gene expression and solid support microarrays. As expected during primary infection, innate immune responses were triggered in the lung tissue; meanwhile, in the lymphoid tissue, genes encoding antigen presentation and maturation of effector cells of adaptive immunity increased dramatically. After 5 days postinfection, the innate immune gene expression was replaced by the adaptive immune response, which correlates with viral clearance. Reinfection with homologous pandemic influenza virus resulted in a diminished innate immune response, early adaptive immune gene regulation, and a reduction in clinical severity. The fully annotated ferret infectome will be a critical aid to the understanding of the molecular events that regulate disease severity and host-influenza virus interactions among seasonal, pandemic, and highly pathogenic avian influenzas.
Respiratory Syncytial Virus Modified by Deletions of the NS2 Gene and Amino Acid S1313 of the L Polymerase Protein Is a Temperature-Sensitive, Live-Attenuated Vaccine Candidate That Is Phenotypically Stable at Physiological Temperature
Authors: Luongo Cindy , Winter Christine C. , Collins Peter L. , Buchholz Ursula J. 
Published: December 2012

ABSTRACT

Human respiratory syncytial virus (RSV) is the leading viral cause of lower respiratory tract disease in infants and children worldwide. In previous work to develop point mutations in RSV with improved genetic stability, we observed that an attenuating mutation at amino acid position 1321 in the L polymerase protein was subject to deattenuation by a spontaneous second-site compensatory mutation at position 1313 (C. Luongo, C. C. Winter, P. L. Collins, and U. J. Buchholz, J. Virol. 86:10792–10804, 2012). In the present study, we found that deletion of position 1313 (Δ1313), irrespective of the presence of an attenuating mutation at position 1321, provided a new attenuating mutation. RSV bearing Δ1313 replicated in cell culture as efficiently as wild-type virus at 32°C, was restricted for replication at 37°C, and was restricted 50-fold and 150-fold in the upper and lower respiratory tracts, respectively, of mice. We combined the Δ1313 deletion with the previously described, attenuating NS2 gene deletion (ΔNS2) to produce the recombinant live-attenuated RSV vaccine candidate ΔNS2/Δ1313. During
in vitro
stress tests involving serial passage at incrementally increasing temperatures, a second-site compensatory mutation was detected in close proximity of Δ1313, namely, I1314T. This site was genetically and phenotypically stabilized by an I1314L substitution. Combination of I1314L with ΔNS2/Δ1313 yielded a virus, ΔNS2/Δ1313/1314L, with genetic stability at physiological temperature. This stabilized vaccine candidate was moderately temperature sensitive and had a level of restriction in chimpanzees comparable to that of MEDI-559, a promising RSV vaccine candidate that presently is in clinical trials but lacks stabilized attenuating mutations. The level of attenuation and genetic stability identify ΔNS2/Δ1313/1314L as a promising candidate for evaluation in pediatric phase I studies.
Does transition into parenthood lead to changes in mental health? Findings from three waves of a population based panel study
Authors: Mckenzie Sarah K , Carter Kristie 
Published: December 2012

BackgroundLongitudinal studies specifically looking at the transition into parenthood and changes in mental health in the general population are scarce. This study aimed to investigate the impact of transition into parenthood on mental health and psychological distress using longitudinal survey data.MethodsThe analysis used three waves from the longitudinal Survey of Family, Income and Employment. Parenthood was classified as first time parent (first and only child <12 months at interview date), subsequent parent (child <12 months and other children in the family), existing parent (no children <12 months but other existing children in the family) and not a parent. We used fixed effects generalised linear modelling, controlling for all time-invariant and time-varying sources of confounding in a sample of 6670 adults within families.ResultsAfter adjusting for confounding from time-varying partner status, area deprivation, labour force status and household income, those who became first time parents reported an increase in mental health (β 1.22, 95% CI −0.06 to 2.50; mean=83.8, SD=14.1) and a decrease in psychological distress (β −0.70 95% CI −1.10 to −0.29; mean=13.4, SD=5.0). Subsequent parents reported a decrease in psychological distress (β −0.60 95% CI −0.95 to −0.24).ConclusionsOur findings suggest that a transition into parenthood for the first time leads to changes in mental health and psychological distress. Understanding the relationship between becoming a parent and mental health outcomes is important given that parental mental health is integral to effective parenting.
Impact of Tumor Microenvironment and Epithelial Phenotypes on Metabolism in Breast Cancer
Authors: Brauer Heather Ann , Makowski Liza , Hoadley Katherine A. , Casbas-Hernandez Patricia , Lang Lindsay J. , Romàn-Pèrez Erick , D'Arcy Monica , Freemerman Alex J. , Perou Charles M. , Troester Melissa A. 
Published: December 2012

Abstract
Purpose: Cancer cells have altered metabolism, with increased glucose uptake, glycolysis, and biomass production. This study conducted genomic and metabolomic analyses to elucidate how tumor and stromal genomic characteristics influence tumor metabolism.
Experimental Design: Thirty-three breast tumors and six normal breast tissues were analyzed by gene expression microarray and by mass spectrometry for metabolites. Gene expression data and clinical characteristics were evaluated in association with metabolic phenotype. To evaluate the role of stromal interactions in altered metabolism, cocultures were conducted using breast cancer cells and primary cancer-associated fibroblasts (CAF).
Results: Across all metabolites, unsupervised clustering resulted in two main sample clusters. Normal breast tissue and a subset of tumors with less aggressive clinical characteristics had lower levels of nucleic and amino acids and glycolysis byproducts, whereas more aggressive tumors had higher levels of these Warburg-associated metabolites. While tumor-intrinsic subtype did not predict metabolic phenotype, metabolic cluster was significantly associated with expression of a wound response signature. In cocultures, CAFs from basal-like breast cancers increased glucose uptake and basal-like epithelial cells increased glucose oxidation and glycogen synthesis, suggesting interplay of stromal and epithelial phenotypes on metabolism. Cytokine arrays identified hepatocyte growth factor (HGF) as a potential mediator of stromal–epithelial interaction and antibody neutralization of HGF resulted in reduced expression of glucose transporter 1 (GLUT1) and decreased glucose uptake by epithelium.
Conclusions: Both tumor/epithelial and stromal characteristics play important roles in metabolism. Warburg-like metabolism is influenced by changes in stromal–epithelial interactions, including altered expression of HGF/Met pathway and GLUT1 expression. Clin Cancer Res; 19(3); 571–85. ©2012 AACR.
Cardiac autonomic function in healthy young smokers
Authors: Erdem Alim , Ayhan Suzi Selim , Öztürk Serkan , Özlü Mehmet Fatih , Alcelik Aytekin , Sahin Safak , Tosun Mehmet , Erdem Fatma Hizal , Gumustekin Kenan , Yazici Mehmet 
Published: December 2012

The present study examined the heart rate turbulence (HRT) and heart rate variability (HRV) parameters in healthy young smokers (<40 years) to assess the effects of smoking on cardiac autonomic function. The study included 75 smokers with a history of habitual smoking for at least 1 year (41 males and 34 females; mean age, 29.3 ± 7.3 years) and 30 nonsmokers (hospital staff; 16 males and 14 females; mean age, 29.0 ± 6.1 years). Addiction to smoking was evaluated using the modified Fagerström test for nicotine-dependence index (NDI). HRT, HRV, basic clinical and echocardiographic, and Holter test parameters were compared between groups. No significant differences between the two groups were found in the basic clinical and echocardiographic variables. Turbulence onset (TO) was significantly higher in the smoking group than in the controls, and turbulence slope was significantly lower in the smokers, than in the controls ( p < 0.05). Standard deviation of all normal-to-normal (NN) interval index (SDNNI) was the only HRV parameter that was significantly different between the smoking and control groups ( p < 0.05). The NDI was positively correlated with the TO ( p < 0.05). Smoking impairs the baroregulatory function in healthy young smokers, particularly the HRT parameters and SDNNI. Our findings highlight the importance of complete smoking cessation.
Partnerships for community mental health in the Asia-Pacific: principles and best-practice models across different sectors
Authors: Ng Chee , Fraser Julia , Goding Margaret , Paroissien David , Ryan Brigid ,   on behalf of the Editorial Group of the Asia-Pacific Community Mental Health Development Project Stage 2 (listed in the Appendix*)
Published: December 2012

Objectives: Stage Two of the Asia-Pacific Community Mental Health Development Project was established to document successful partnership models in community mental health care in the region. This paper summarizes the best-practice examples and principles of partnerships in community mental health across 17 Asia-Pacific countries. Conclusions: A series of consensus workshops between countries identified best-practice exemplars that promote or advance community mental health care in collaboration with a range of community stakeholders. These prototypes highlighted a broad range of partnerships across government, non-government and community agencies, as well as service users and family carers. From practice-based evidence, a set of 10 key principles was developed that can be applied in building partnerships for community mental health care consistent with the local cultures, communities and systems in the region. Such practical guidance can be useful to minimize fragmentation of community resources and promote effective partnerships to extend community mental health services in the region.
Evaluation of sources to document extended shelf lives of compounded cytostatics
Authors: Larsson Iben , Kart Trine 
Published: December 2012

Background: Due to the increasing demand for compounded cytostatics, future compounding of these drugs has to include automated production and improved logistics, and in both cases batch production for stockholding is needed. This set-up would also meet future staff shortages. Stockholding requires documentation of extended shelf lives in the range of minimum 1–3 months. Documentation is often provided by summary of product characteristics, data provided by the industry which is not included in the summary of product characteristics and data from literature. Objective: To evaluate the quality of the three main stability data sources used by hospital pharmacies when assessing extended shelf lives of compounded cytostatics. Methods: A total of 150 summary of product characteristics for fluorouracil, cyclophosphamid, oxaliplatin, cisplatin, doxorubicin, paclitaxel, vincristin, irinotecan, epirubicin, gemcitabin, docetaxel, carboplatin and cytarabin were examined regarding available information on how to handle the compounded product. A survey of literature for shelf lives for cyclophosphamide, fluorouracil, oxaliplatin and gemcitabine has been made. Dialogues with 14 suppliers of cytostatica have been conducted to clarify the possibility of expanding the fluorouracil information on shelf lives to include information on extended shelf lives of compounded products. Results: The analysis showed that often the information on shelf life stated in the summary of product characteristic is very short and sparse in basic information regarding the compounded product. The dialogues with the companies revealed that longer shelf lives will probably not be stated in the summary of product characteristic, and the literature review revealed very different stability data and uncertainty on the validity of the obtained data. Conclusion: None of these data sources can be applied as documentation for extended shelf lives and it is crucial to document the extended stability yourself.
Effects of early treatment with glatiramer acetate in patients with clinically isolated syndrome
Authors: Comi Giancarlo , Martinelli Vittorio , Rodegher Mariaemma , Moiola Lucia , Leocani Letizia , Bajenaru Ovidiu , Carra Adriana , Elovaara Irina , Fazekas Franz , Hartung Hans-Peter , Hillert Jan , King John , Komoly Samuel , Lubetzki Catherine , Montalban Xavier , Myhr Kjell-Morten , Preziosa Paolo , Ravnborg Mads , Rieckmann Peter , Rocca Maria A , Wynn Daniel , Young Carolyn , Filippi Massimo 
Published: December 2012

Background: The placebo-controlled phase of the PreCISe study showed that glatiramer acetate delayed onset of clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome and brain lesions on MRI. Objective: To compare the effects of early versus delayed glatiramer acetate treatment in the open-label phase of PreCISe. Methods: Patients with a clinically isolated syndrome suggestive of MS with unifocal manifestation and ≥2 T2-weighted brain lesions were randomized to receive glatiramer acetate 20 mg/d (early-treatment, n=198) or placebo (delayed-treatment, n=211) for 36 months or until conversion to CDMS, followed by open-label glatiramer acetate treatment for two years. Results: Early glatiramer acetate treatment reduced CDMS conversion risk by 41% (hazard ratio 0.59, 95% confidence interval 0.44–0.80; p=0.0005) versus delayed-treatment, and was associated with a 972-day delay (185%) in conversion to CDMS, less brain atrophy (−28%, p=0.0209), fewer new T2 lesions/year (−42%, <0.0001) and lower T2 lesion volume (−22%, p=0.0005) versus delayed treatment. Adverse events were consistent with the established safety profile of glatiramer acetate. Conclusions: Effects of early glatiramer acetate treatment on the rate of conversion to CDMS and on MRI measures of disease activity and lesion burden support initiating glatiramer acetate treatment soon after the first clinical symptoms suggestive of MS and continuing treatment to sustain benefits.
Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia
Authors: Rossi Davide , Rasi Silvia , Spina Valeria , Bruscaggin Alessio , Monti Sara , Ciardullo Carmela , Deambrogi Clara , Khiabanian Hossein , Serra Roberto , Bertoni Francesco , Forconi Francesco , Laurenti Luca , Marasca Roberto , Dal-Bo Michele , Rossi Francesca Maria , Bulian Pietro , Nomdedeu Josep , Del Poeta Giovanni , Gattei Valter , Pasqualucci Laura , Rabadan Raul , Foà Robin , Dalla-Favera Riccardo , Gaidano Gianluca 
Published: December 2012

Key Points
The integration of mutations and cytogenetic lesions improves the accuracy of survival prediction in chronic lymphocytic leukemia.