bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV-1 Tat C-mediated regulation of tumor necrosis factor receptor-associated factor-3 by microRNA 32 in human microglia
Authors: Mishra Ritu , Chhatbar Chintan , Singh Sunit Kumar 
Published: June 2012

Abstract

Background
HIV-1 Tat protein is known to be associated with neuroinflammation, a condition that develops in almost half of patients infected with HIV-1. HIV-1 Tat can alter glial neuroprotective functions, leading to neurotoxicity within the CNS. HIV-1 Tat is known to be secreted from productively infected cells and can affect neighboring uninfected cells by modulating cellular gene expression in a bystander fashion.

Methods
We were interested to study whether exogenous exposure to HIV-1 Tat-C protein perturbs the microRNA (miRNA) expression profile of human microglial cells, leading to altered protein expression. We used protein expression and purification, miRNA overexpression, miRNA knockdown, transfection, site-directed mutagenesis, real-time PCR, luciferase assay and western blotting techniques to perform our study.

Results
HIV-1 Tat-C treatment of human microglial cells resulted in a dose-dependent increase in miR-32 expression. We found that tumor necrosis factor-receptor–associated factor 3 TRAF3) is a direct target for miR-32, and overexpression of miR-32 in CHME3 cells decreased TRAF3 both at the mRNA and the protein level. Recovery of TRAF3 protein expression after transfection of anti-miR-32 and the results of the luciferase reporter assay provided direct evidence of TRAF3 regulation by miR-32. We found that the regulation of interferon regulatory factor 3 (IRF3) and IRF7 is controlled by cellular levels of TRAF3 protein in microglial cells, as after overexpression of miR-32 and application of anti-miR-32, expression levels of IRF3 and IRF7 were inversely regulated by expression levels of TRAF3. Thus, our results suggest a novel miRNA mediated mechanism for regulation of TRAF3 in human microglial cells exposed to HIV-1 Tat C protein. These results may help to elucidate the detrimental neuroinflammatory consequences of HIV-1 Tat C protein in bystander fashion.

Conclusion
HIV-1 Tat protein can modulate TRAF3 expression through miRNA mediated pathway and can change the downstream expression of IRF3 and IRF7. This study demonstrates a novel mechanism of HIV-1 Tat C protein-mediated perturbation of miRNA, resulting in dysregulation of cellular TRAF3.
Recovery of information from multiple imputation: a simulation study
Authors: Lee Katherine J , Carlin John B 
Published: June 2012

Abstract
Background
Multiple imputation is becoming increasingly popular for handling missing data. However, it is often implemented without adequate consideration of whether it offers any advantage over complete case analysis for the research question of interest, or whether potential gains may be offset by bias from a poorly fitting imputation model, particularly as the amount of missing data increases.

Methods
Simulated datasets (n = 1000) drawn from a synthetic population were used to explore information recovery from multiple imputation in estimating the coefficient of a binary exposure variable when various proportions of data (10-90%) were set missing at random in a highly-skewed continuous covariate or in the binary exposure. Imputation was performed using multivariate normal imputation (MVNI), with a simple or zero-skewness log transformation to manage non-normality. Bias, precision, mean-squared error and coverage for a set of regression parameter estimates were compared between multiple imputation and complete case analyses.

Results
For missingness in the continuous covariate, multiple imputation produced less bias and greater precision for the effect of the binary exposure variable, compared with complete case analysis, with larger gains in precision with more missing data. However, even with only moderate missingness, large bias and substantial under-coverage were apparent in estimating the continuous covariate’s effect when skewness was not adequately addressed. For missingness in the binary covariate, all estimates had negligible bias but gains in precision from multiple imputation were minimal, particularly for the coefficient of the binary exposure.

Conclusions
Although multiple imputation can be useful if covariates required for confounding adjustment are missing, benefits are likely to be minimal when data are missing in the exposure variable of interest. Furthermore, when there are large amounts of missingness, multiple imputation can become unreliable and introduce bias not present in a complete case analysis if the imputation model is not appropriate. Epidemiologists dealing with missing data should keep in mind the potential limitations as well as the potential benefits of multiple imputation. Further work is needed to provide clearer guidelines on effective application of this method.
Prediction and identification of mouse cytotoxic T lymphocyte epitopes in Ebola virus glycoproteins
Authors: Wu Shipo , Yu Ting , Song Xiaohong , Yi Shaoqiong , Hou Lihua , Chen Wei 
Published: June 2012

Abstract

Background
Ebola viruses (EBOVs) cause severe hemorrhagic fever with a high mortality rate. At present, there are no licensed vaccines or efficient therapies to combat EBOV infection. Previous studies have shown that both humoral and cellular immune responses are crucial for controlling Ebola infection. CD8+ T cells play an important role in mediating vaccine-induced protective immunity. The objective of this study was to identify H-2d-specific T cell epitopes in EBOV glycoproteins (GPs).

Results
Computer-assisted algorithms were used to predict H-2d-specific T cell epitopes in two species of EBOV (Sudan and Zaire) GP. The predicted peptides were synthesized and identified in BALB/c mice immunized with replication-deficient adenovirus vectors expressing the EBOV GP. Enzyme-linked immunospot assays and intracellular cytokine staining showed that the peptides RPHTPQFLF (Sudan EBOV), GPCAGDFAF and LYDRLASTV (Zaire EBOV) could stimulate splenoctyes in immunized mice to produce large amounts of interferon-gamma.

Conclusion
Three peptides within the GPs of two EBOV strains were identified as T cell epitopes. The identification of these epitopes should facilitate the evaluation of vaccines based on the Ebola virus glycoprotein in a BALB/c mouse model.
Rescue of virulent class I Newcastle disease virus variant 9a5b-D5C1
Authors: Yu Yang , Qiu Xusheng , Xu Dan , Zhan Yuan , Meng Chunchun , Wei Nana , Chen Hongjun , Tan Lei , Yu Shengqing , Liu Xiufan , Qin Aijian , Ding Chan 
Published: June 2012

Abstract

Background
The virulent class I Newcastle disease virus (NDV) variant 9a5b was generated from a nonvirulent NDV isolate Goose/Alaska/415/91 via nine consecutive passages in the chicken air sac, followed by five passages in the chick brain. The evolutionary mechanism of virulence in the class I NDV isolate is not fully understood. To elucidate this evolutionary mechanism, a reverse genetics manipulation specific for class I NDV is indispensable.

Results
A full-length cDNA clone of 9a5b and the helper plasmids pCI-NP, pCI-P, and pCI-L were constructed from segments of cDNA. After these plasmids were co-transfected into BSR T7/5 cells, infectious viral particles were obtained. The rescued viruses were genetically and biologically identical to the parental strain and showed similar pathogenicity in chickens.

Conclusion
A stable recovery method for class I NDV was established. Reverse genetics of the class I NDV variant 9a5b allowed for the generation of genetically altered and virulent NDV, and can be used as a foundation for research on the evolution of virulence in class I NDV isolates.
Effects of Peripheral Inflammation on the Blood-Spinal Cord Barrier
Authors: Xanthos Dimitris N , Püngel Isabella , Wunderbaldinger Gabriele , Sandkühler Jürgen 
Published: June 2012

Background: Changes in the blood-central nervous system barriers occur under pathological conditions including inflammation and contribute to central manifestations of various diseases. After short-lasting peripheral and neurogenic inflammation, the evidence is mixed whether there are consistent blood-spinal cord changes. In the current study, we examine changes in the blood-spinal cord barrier after intraplantar capsaicin and λ-carrageenan using several methods: changes in occludin protein, immunoglobulin G accumulation, and fluorescent dye penetration. We also examine potential sex differences in male and female adult rats. Results: After peripheral carrageenan inflammation, but not capsaicin inflammation, immunohistochemistry shows occludin protein in lumbar spinal cord to be significantly altered at 72 hours post-injection. In addition, there is also significant immunoglobulin G detected in lumbar and thoracic spinal cord at this timepoint in both male and female rats. However, acute administration of sodium fluorescein or Evans Blue dyes is not detected in the parenchyma at this timepoint. Conclusions: Our results show that carrageenan inflammation induces changes in tight junction protein and immunoglobulin G accumulation, but these may not be indicative of a blood-spinal cord barrier breakdown. These changes appear transiently after peak nociception and may be indicative of reversible pathology that resolves together with inflammation.
Developed-developing country partnerships: Benefits to developed countries?
Authors: Syed Shamsuzzoha B , Dadwal Viva , Rutter Paul , Storr Julie , Hightower Joyce D , Gooden Rachel , Carlet Jean , Nejad Sepideh Bagheri , Kelley Edward T , Donaldson Liam , Pittet Didier 
Published: June 2012

Abstract
Developing countries can generate effective solutions for today’s global health challenges. This paper reviews relevant literature to construct the case for international cooperation, and in particular, developed-developing country partnerships. Standard database and web-based searches were conducted for publications in English between 1990 and 2010. Studies containing full or partial data relating to international cooperation between developed and developing countries were retained for further analysis. Of 227 articles retained through initial screening, 65 were included in the final analysis. The results were two-fold: some articles pointed to intangible benefits accrued by developed country partners, but the majority of information pointed to developing country innovations that can potentially inform health systems in developed countries. This information spanned all six WHO health system components. Ten key health areas where developed countries have the most to learn from the developing world were identified and include, rural health service delivery; skills substitution; decentralisation of management; creative problem-solving; education in communicable disease control; innovation in mobile phone use; low technology simulation training; local product manufacture; health financing; and social entrepreneurship. While there are no guarantees that innovations from developing country experiences can effectively transfer to developed countries, combined developed-developing country learning processes can potentially generate effective solutions for global health systems. However, the global pool of knowledge in this area is virgin and further work needs to be undertaken to advance understanding of health innovation diffusion. Even more urgently, a standardized method for reporting partnership benefits is needed—this is perhaps the single most immediate need in planning for, and realizing, the full potential of international cooperation between developed and developing countries.
Prediction of pathological and oncological outcomes based on extended prostate biopsy results in patients with prostate cancer receiving radical prostatectomy: a single institution study
Authors: Ishizaki Fumio , Hara Noboru , Koike Hiroshi , Kawaguchi Makoto , Tadokoro Akira , Takizawa Itsuhiro , Nishiyama Tsutomu , Takahashi Kota , Hohenfellner Rudolf 
Published: June 2012

Abstract

Background
The prediction of pathological outcomes prior to surgery remains a challenging problem for the appropriate surgical indication of prostate cancer. This study was performed to identify preoperative values predictive of pathological and oncological outcomes based on standardized extended prostate biopsies with core histological results diagrammed/mapped in patients receiving radical prostatectomy for prostate cancer clinically diagnosed as localized or locally advanced disease.

Methods
In 124 patients with clinically localized or locally advanced prostate cancer (cT1c–cT3a) without prior treatment, pathological outcomes on the surgical specimen including seminal vesicle involvement (SVI), positive surgical margin (PSM), and perineural invasion (PNI) were studied in comparison with clinical parameters based on the results of 14-core prostate biopsies comprising sextant, laterally-directed sextant, and bilateral transition zone (TZ) sampling.

Results
Concerning the association of pathological outcomes with oncological outcomes, patients with PSM and PNI on surgical specimens had poorer biochemical-progression-free survival than those without PSM (logrank p = 0.002) and PNI (p = 0.003); it was also poorer concerning SVI, although the difference was not significant (p = 0.120). Concerning the impact of clinical parameters on these pathological outcomes, positive TZ and multiple positive biopsy cores in the prostatic middle were independent values predictive of SVI with multivariate analyses (p = 0.020 and p = 0.025, respectively); both positive TZ and multiple positive prostatic middle biopsies were associated with larger tumor volume (p < 0.001 in both). The percentage of positive biopsy cores (%positive cores) and biopsy Gleason score were independent values predictive of PSM (p = 0.001) and PNI (p = 0.001), respectively. Multiple positive cores in the prostatic base were associated with proximal/bladder-side PSM (p < 0.001), and also linked to poorer biochemical-progression-free survival (p = 0.004). Clinical T stage had no association with these pathological outcomes.

Conclusions
%positive cores and Gleason score in extended biopsies were independent values predictive of PSM and PNI in prostate cancer clinically diagnosed as localized or locally advanced disease, respectively, which were associated with poorer oncological outcomes. When diagramming biopsy-core results, extended biopsy may provide additional information for predicting oncological and pathological outcomes including SVI in patients clinically diagnosed as having localized or locally advanced disease.

Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8790262771042628
A serological and bacteriological survey of brucellosis in wild boar (Sus scrofa) in Belgium
Authors: Grégoire Fabien , Mousset Bénédicte , Hanrez David , Michaux Charles , Walravens Karl , Linden Annick 
Published: June 2012

Abstract

Background
Brucellosis is frequently reported among wild boar populations in Europe. The aim of the study was to assess the epidemiological situation in Belgium, regarding the steady increase of wild boar populations over the last decades. Several serological tests were used and compared with culture and IS711 polymerase chain reaction (PCR), to determine the most suitable combination of diagnostic tools for conducting a successful prevalence study in wildlife.

Results
An indirect enzyme-linked immunosorbent assay (iELISA) was used on 1168 sera from hunter-killed wild boar sampled between 2003 and 2007 in 4 natural regions of southern Belgium. Results gave an apparent prevalence of 54.88% (95% CI 52.03-57.73). Prevalence was significantly affected by age and by the year of study, but not by sex nor by the region of sampling. The relative sensitivities of the complement fixation test (CFT), the Rose Bengal test (RBT), and the slow agglutination test (SAT) versus the iELISA differed widely between tests, reaching 62.67%, 46.68%, and 34.77%, respectively. The relative specificities of the CFT, RBT and SAT versus the iELISA were respectively 99.01%, 92.49%, and 99.1%. From seropositive animals (iELISA), 9% were positive by culture and 24% by PCR when testing spleen and/or tonsils. Sensitivity of the PCR was higher on tonsils than on spleen. All bacterial isolates were identified as Brucella suis biovar 2.

Conclusions
Brucellosis is widespread among wild boar in southern Belgium, with seroprevalences having increased over ten years, and constitutes a growing risk of spillback to outdoor-farmed pig herds. The iELISA showed a better sensitivity than the CFT, RBT and SAT. Serological tests must be associated with direct diagnosis and PCR proved more sensitive than culture under wildlife sampling conditions. Spleen and tonsils are lymphoid tissues usually sampled in multi-disease monitoring programs. They remain top-grade organs for direct diagnosis of brucellosis, with a preference for tonsils.
A seroepidemiologic study of Reston ebolavirus in swine in the Philippines
Authors: Sayama Yusuke , Demetria Catalino , Saito Mariko , Azul Rachel R , Taniguchi Satoshi , Fukushi Shuetsu , Yoshikawa Tomoki , Iizuka Itoe , Mizutani Tetsuya , Kurane Ichiro , Malbas Fidelino F , Lupisan Socorro , Catbagan Davinio P , Animas Samuel B , Morales Rieldrin G , Lopez Emelinda L , Dazo Karen Rose C , Cruz Magdalena S , Olveda Remigio , Saijo Masayuki , Oshitani Hitoshi , Morikawa Shigeru 
Published: June 2012

Abstract

Background
Ebola viruses cause viral hemorrhagic fever in humans and non-human primates and are endemic in Africa. Reston ebolavirus (REBOV) has caused several epizootics in cynomolgus monkeys (Macaca fascicularis) but is not associated with any human disease. In late 2008, REBOV infections were identified in swine for the first time in the Philippines.

Methods
A total of 215 swine sera collected at two REBOV-affected farms in 2008, in Pangasinan and Bulacan, were tested for the presence of REBOV-specific antibodies using multiple serodiagnosis systems. A total of 98 swine sera collected in a non-epizootic region, Tarlac, were also tested to clarify the prevalence of REBOV infection in the general swine population in the Philippines.

Results
Some 70 % of swine sera at the affected farms were positive for REBOV antibodies in the multiple serodiagnosis systems. On the other hand, none of the swine sera collected in Tarlac showed positive reactions in any of the diagnosis systems.

Conclusions
The high prevalence of REBOV infection in swine in the affected farms in 2008 suggests that swine is susceptible for REBOV infection. The multiple serological assays used in the study are thought to be useful for future surveillance of REOBV infection in swine in the Philippines.
A simple theoretical framework for understanding heterogeneous differentiation of CD4+ T cells
Authors: Hong Tian , Xing Jianhua , Li Liwu , Tyson John J 
Published: June 2012

Abstract

Background
CD4+ T cells have several subsets of functional phenotypes, which play critical yet diverse roles in the immune system. Pathogen-driven differentiation of these subsets of cells is often heterogeneous in terms of the induced phenotypic diversity. In vitro recapitulation of heterogeneous differentiation under homogeneous experimental conditions indicates some highly regulated mechanisms by which multiple phenotypes of CD4+ T cells can be generated from a single population of naïve CD4+ T cells. Therefore, conceptual understanding of induced heterogeneous differentiation will shed light on the mechanisms controlling the response of populations of CD4+ T cells under physiological conditions.

Results
We present a simple theoretical framework to show how heterogeneous differentiation in a two-master-regulator paradigm can be governed by a signaling network motif common to all subsets of CD4+ T cells. With this motif, a population of naïve CD4+ T cells can integrate the signals from their environment to generate a functionally diverse population with robust commitment of individual cells. Notably, two positive feedback loops in this network motif govern three bistable switches, which in turn, give rise to three types of heterogeneous differentiated states, depending upon particular combinations of input signals. We provide three prototype models illustrating how to use this framework to explain experimental observations and make specific testable predictions.

Conclusions
The process in which several types of T helper cells are generated simultaneously to mount complex immune responses upon pathogenic challenges can be highly regulated, and a simple signaling network motif can be responsible for generating all possible types of heterogeneous populations with respect to a pair of master regulators controlling CD4+ T cell differentiation. The framework provides a mathematical basis for understanding the decision-making mechanisms of CD4+ T cells, and it can be helpful for interpreting experimental results. Mathematical models based on the framework make specific testable predictions that may improve our understanding of this differentiation system.
Incidental renal cell carcinoma presenting in a renal transplant recipient with autosomal dominant polycystic kidney disease: a case report
Authors: Misumi Toshihiro , Ide Kentaro , Onoe Takashi , Banshodani Masataka , Tazawa Hirofumi , Teraoka Yoshifumi , Hotta Ryuichi , Yamashita Masahiro , Tashiro Hirotaka , Ohdan Hideki 
Published: June 2012

Abstract

Introduction
We report an instructive case of incidental renal cell carcinoma in a patient with autosomal dominant polycystic kidney disease who underwent simultaneous bilateral native nephrectomy and living donor renal transplantation.

Case presentation
A 57-year-old Asian man with end-stage kidney disease due to autosomal dominant polycystic kidney disease received a living kidney graft from his brother. Because of recurrent infection, chronic pain and enlarged kidneys, he underwent a bilateral nephrectomy with concomitant renal transplantation. The total weight of the removed kidneys was 6kg; the maximal diameter of the larger kidney was 28cm. His left kidney had a 1cm diameter tumor. Pathology indicated papillary renal cell carcinoma. At the time of this report, the transplant kidney function was normal with no evidence of local recurrence or distant metastasis.

Conclusion
This case shows and reinforces the importance of considering the possibility of an occult malignancy in the native kidneys of patients with autosomal dominant polycystic kidney disease. Simultaneous bilateral native nephrectomy should be considered in these renal transplant recipients not only for preventing the development of adverse symptoms but also for detecting an occult malignancy.