bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges to mapping the health risk of hepatitis A virus infection
Authors: Mohd Hanafiah Khayriyyah , Jacobsen Kathryn H , Wiersma Steven T 
Published: November 2011

Abstract

Background
World maps are among the most effective ways to convey public health messages such as recommended vaccinations, but creating a useful and valid map requires careful deliberation. The changing epidemiology of hepatitis A virus (HAV) in many world regions heightens the need for up-to-date risk maps. HAV infection is usually asymptomatic in children, so low-income areas with high incidence rates usually have a low burden of disease. In higher-income areas, many adults remain susceptible to the virus and, if infected, often experience severe disease.

Results
Several challenges associated with presenting hepatitis A risk using maps were identified, including the need to decide whether prior infection or continued susceptibility more aptly indicates risk, whether to display incidence or prevalence, how to distinguish between different levels of risk, how to display changes in risk over time, how to present complex information to target audiences, and how to handle missing or obsolete data.

Conclusion
For future maps to be comparable across place and time, we propose the use of the age at midpoint of population susceptibility as a standard indicator for the level of hepatitis A endemicity within a world region. We also call for the creation of an accessible active database for population-based age-specific HAV seroprevalence and incidence studies. Health risk maps for other conditions with rapidly changing epidemiology would benefit from similar strategies.
Retinoic acid pathway activity in wilms tumors and characterization of biological responses in vitro
Authors: Wegert Jenny , Bausenwein Sabrina , Kneitz Susanne , Roth Sabine , Graf Norbert , Geissinger Eva , Gessler Manfred 
Published: November 2011

Abstract

Background
Wilms tumor (WT) is one of the most common malignancies in childhood. With current therapy protocols up to 90% of patients can be cured, but there is still a need to improve therapy for patients with aggressive WT and to reduce treatment intensity where possible. Prior data suggested a deregulation of the retinoic acid (RA) signaling pathway in high-risk WT, but its mode of action remained unclear.

Results
The association of retinoid signaling and clinical parameters could be validated in a large independent tumor set, but its relevance in primary nephrectomy tumors from very young children may be different. Reduced RA pathway activity and MYCN overexpression were found in high risk tumors as opposed to tumors with low/intermediate risk, suggesting a beneficial impact of RA especially on advanced WT. To search for possible modes of action of retinoids as novel therapeutic options, primary tumor cell cultures were treated in vitro with all-trans-RA (ATRA), 9cis- RA, fenretinide and combinations of retinoids and a histone deacetylase (HDAC) inhibitor. Genes deregulated in high risk tumors showed opposite changes upon treatment suggesting a positive effect of retinoids. 6/7 primary cultures tested reduced proliferation, irrespective of prior RA signaling levels. The only variant culture was derived from mesoblastic nephroma, a distinct childhood kidney neoplasm. Retinoid/HDAC inhibitor combinations provided no synergistic effect. ATRA and 9cis- RA induced morphological changes suggestive of differentiation, while fenretinide induced apoptosis in several cultures tested. Microarray analysis of ATRA treated WT cells revealed differential expression of many genes involved in extracellular matrix formation and osteogenic, neuronal or muscle differentiation. The effects documented appear to be reversible upon drug withdrawal, however.

Conclusions
Altered retinoic acid signaling has been validated especially in high risk Wilms tumors. In vitro testing of primary tumor cultures provided clear evidence of a potential utility of retinoids in Wilms tumor treatment based on the analysis of gene expression, proliferation, differentiation and apoptosis.
Mobile multimedia sensor networks: architecture and routing
Authors: Chen Min , Lai Chin-Feng , Wang Honggang 
Published: November 2011

Abstract
Recent advances in the fields of wireless technology and multimedia systems have exhibited a strong potential and tendency on improving human life by enabling smart services in ubiquitous computing environments. This paper investigates a mobile multimedia system through combining various technologies, such as wireless sensor networks, embedded multimedia system and node mobility. In particular, we will employ some powerful sensor node with both mobility and multimedia functionalities, which can be controlled by contextual information collected by other systems to enable interactive multimedia services. The new architecture is called mobile multimedia sensor network (MMSN) in this paper. A routing scheme named mobile multimedia geographic routing (MGR) is specially designed to minimize energy consumption and satisfy constraints on the average end-to-end delay of specific applications in MMSNs. Simulations verify the MGR's performance to satisfy QoS requirement while saving energy for MMSNs.
Human brain endothelial cells endeavor to immunoregulate CD8 T cells via PD-1 ligand expression in multiple sclerosis
Authors: Pittet Camille L , Newcombe Jia , Prat Alexandre , Arbour Nathalie 
Published: November 2011

Abstract

Background
Multiple sclerosis (MS), an inflammatory disease of the central nervous system (CNS), is characterized by blood-brain barrier (BBB) disruption and massive infiltration of activated immune cells. Engagement of programmed cell death-1 (PD-1) expressed on activated T cells with its ligands (PD-L1 and PD-L2) suppresses T cell responses. We recently demonstrated in MS lesions elevated PD-L1 expression by glial cells and absence of PD-1 on many infiltrating CD8 T cells. We have now investigated whether human brain endothelial cells (HBECs), which maintain the BBB, can express PD-L1 or PD-L2 and thereby modulate T cells.

Methods
We used primary cultures of HBECs isolated from non-tumoral CNS tissue either under basal or inflamed conditions. We assessed the expression of PD-L1 and PD-L2 using qPCR and flow cytometry. Human CD8 T cells were isolated from peripheral blood of healthy donors and co-cultured with HBECs. Following co-culture with HBECs, proliferation and cytokine production by human CD8 T cells were measured by flow cytometry whereas transmigration was determined using a well established in vitro model of the BBB. The functional impact of PD-L1 and PD-L2 provided by HBECs was determined using blocking antibodies. We performed immunohistochemistry for the detection of PD-L1 or PD-L2 concurrently with caveolin-1 (a cell specific marker for endothelial cells) on post-mortem human brain tissues obtained from MS patients and normal controls.

Results
Under basal culture conditions, PD-L2 is expressed on HBECs, whilst PD-L1 is not detected. Both ligands are up-regulated under inflammatory conditions. Blocking PD-L1 and PD-L2 leads to increased transmigration and enhanced responses by human CD8 T cells in co-culture assays. Similarly, PD-L1 and PD-L2 blockade significantly increases CD4 T cell transmigration. Brain endothelium in normal tissues and MS lesions does not express detectable PD-L1; in contrast, all blood vessels in normal brain tissues are PD-L2-positive, while only about 50% express PD-L2 in MS lesions.

Conclusions
Our observations suggest that brain endothelial cells contribute to control T cell transmigration into the CNS and immune responses via PD-L2 expression. However, such impact is impaired in MS lesions due to downregulation of endothelium PD-L2 levels.
Plasma proteome analysis in HTLV-1-associated myelopathy/tropical spastic paraparesis
Authors: Kirk Paul DW , Witkover Aviva , Courtney Alan , Lewin Alexandra M , Wait Robin , Stumpf Michael PH , Richardson Sylvia , Taylor Graham P , Bangham Charles RM 
Published: November 2011

Abstract

Background
Human T lymphotropic virus Type 1 (HTLV-1) causes a chronic inflammatory disease of the central nervous system known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM) which resembles chronic spinal forms of multiple sclerosis (MS). The pathogenesis of HAM remains uncertain. To aid in the differential diagnosis of HAM and to identify pathogenetic mechanisms, we analysed the plasma proteome in asymptomatic HTLV-1 carriers (ACs), patients with HAM, uninfected controls, and patients with MS. We used surface-enhanced laser desorption-ionization (SELDI) mass spectrometry to analyse the plasma proteome in 68 HTLV-1-infected individuals (in two non-overlapping sets, each comprising 17 patients with HAM and 17 ACs), 16 uninfected controls, and 11 patients with secondary progressive MS. Candidate biomarkers were identified by tandem Q-TOF mass spectrometry.

Results
The concentrations of three plasma proteins - high [β2-microglobulin], high [Calgranulin B], and low [apolipoprotein A2] - were specifically associated with HAM, independently of proviral load. The plasma [β2-microglobulin] was positively correlated with disease severity.

Conclusions
The results indicate that monocytes are activated by contact with activated endothelium in HAM. Using β2-microglobulin and Calgranulin B alone we derive a diagnostic algorithm that correctly classified the disease status (presence or absence of HAM) in 81% of HTLV-1-infected subjects in the cohort.
Incidence and risk factors of antiretroviral treatment failure in treatment-naïve HIV-infected patients at Chiang Mai University Hospital, Thailand
Authors: Khienprasit Nitta , Chaiwarith Romanee , Sirisanthana Thira , Supparatpinyo Khuanchai 
Published: November 2011

Abstract

Background
The use of combination antiretroviral therapy (cART) has become a standard of care for the treatment of HIV infection. However, cost and resistance to cART are major obstacles for access to treatment especially in resource-limited settings. In this study, we aimed to determine the incidence and risk factors of treatment failure in a cohort of treatment-naïve Thai HIV-infected patients.

Methods
A retrospective cohort study was conducted among HIV-infected patients initiating their first cART at Chiang Mai University Hospital, Thailand.

Results
From January 2002 to December 2008, 788 patients were enrolled; 365 were male (46.3%), and the mean age was 37.9 ± 8.6 years. The median baseline CD4 count was 57.7 cells/mm3 (IQR 22, 127). GPO-VIR® (a fixed-dose combination of lamivudine, stavudine, and nevirapine) was the most common prescribed cART (657 patients, 83.4%). Seventy-six patients developed virological failure given the cumulative incidence of 9.6%. The incidence of virological failure was 2.79 (95% CI 2.47, 3.14) cases per 100 person years. Poor adherence was the strongest predictor for virological failure. Of 535 immunologically evaluable patients, 179 (33.5%) patients developed immunological failure. A low CD4 cell count at baseline (< 100 cells/mm3) and the increment of CD4 cell count of < 50 cell/mm3 after 6 months of cART were the predictors for immunological failure (p < 0.001).

Conclusions
This study demonstrated that even in resource-limited settings, the high rate of success could be expected in the cohort with good and sustainable drug adherence. Poor adherence, older age, and low baseline CD4 cell count are the predictors for unfavorable outcome of cART.
Constructing stochastic models from deterministic process equations by propensity adjustment
Authors: Wu Jialiang , Vidakovic Brani , Voit Eberhard O 
Published: November 2011

Abstract

Background
Gillespie's stochastic simulation algorithm (SSA) for chemical reactions admits three kinds of elementary processes, namely, mass action reactions of 0th, 1st or 2nd order. All other types of reaction processes, for instance those containing non-integer kinetic orders or following other types of kinetic laws, are assumed to be convertible to one of the three elementary kinds, so that SSA can validly be applied. However, the conversion to elementary reactions is often difficult, if not impossible. Within deterministic contexts, a strategy of model reduction is often used. Such a reduction simplifies the actual system of reactions by merging or approximating intermediate steps and omitting reactants such as transient complexes. It would be valuable to adopt a similar reduction strategy to stochastic modelling. Indeed, efforts have been devoted to manipulating the chemical master equation (CME) in order to achieve a proper propensity function for a reduced stochastic system. However, manipulations of CME are almost always complicated, and successes have been limited to relative simple cases.

Results
We propose a rather general strategy for converting a deterministic process model into a corresponding stochastic model and characterize the mathematical connections between the two. The deterministic framework is assumed to be a generalized mass action system and the stochastic analogue is in the format of the chemical master equation. The analysis identifies situations: where a direct conversion is valid; where internal noise affecting the system needs to be taken into account; and where the propensity function must be mathematically adjusted. The conversion from deterministic to stochastic models is illustrated with several representative examples, including reversible reactions with feedback controls, Michaelis-Menten enzyme kinetics, a genetic regulatory motif, and stochastic focusing.

Conclusions
The construction of a stochastic model for a biochemical network requires the utilization of information associated with an equation-based model. The conversion strategy proposed here guides a model design process that ensures a valid transition between deterministic and stochastic models.
Pyosalpinx as a sequela of labial fusion in a post-menopausal woman: a case report
Authors: Tsianos George I , Papatheodorou Stefania I , Michos George M , Koliopoulos George , Stefos Theodor 
Published: November 2011

Abstract

Introduction
Complete labia fusion is a rare clinical entity in post-menopausal women. The most common complications of this presentation are infections of the urinary tract and retention of urine in the vagina. We present the case of a post-menopausal woman with adnexal mass and abdominal pain due to fusion of the labia majora. To the best of our knowledge this is the first report in the literature of this complication.

Case presentation
A 78-year-old Caucasian woman was admitted to our hospital due to abdominal pain and urination difficulty, along with fever and leucocytosis. On examination the labial majora were fused. Computed tomography of the abdomen revealed a cystic formation in the anatomical area of the right adnexa. Our patient had developed a pyosalpinx as a Sequela of labial fusion. At laparoscopy the right pyosalpinx was identified and resected, whereas the labia majora were reconstructed via dissection and separation.

Conclusions
Labial fusion is a rare clinical entity in post-menopausal women and can have serious and unexpected complications. Though this presentation is rare, a clinical examination must be performed in detail in order to gain valuable information for an accurate diagnosis. Post-operational instruction must be given to patients in order to prevent the re-occurrence of the fusion and its complications.
Proliferating cell nuclear antigen is required for loading of the SMCX/KMD5C histone demethylase onto chromatin
Authors: Liang Zhihui , Diamond Marc , Smith Johanna A , Schnell Matthias , Daniel René 
Published: November 2011

Abstract

Background
Histone methylation is regulated by a large number of histone methyltransferases and demethylases. The recently discovered SMCX/KMD5C demethylase has been shown to remove methyl residues from lysine 4 of histone H3 (H3K4), and constitutes an important component of the regulatory element-1-silencing transcription factor (REST) protein complex. However, little is known about the cellular mechanisms that control SMCX activity and intracellular trafficking.

Results
In this study, we found that small interfering RNA-mediated knockdown of proliferating cell nuclear antigen (PCNA) resulted in the reduction of the chromatin-bound SMCX fraction. We identified a PCNA-interaction protein motif (PIP box) in the SMCX protein. Using site-directed mutagenesis, we found that the amino acids of the SMCX PIP box are involved in the association of SMCX with PCNA and its interaction with chromatin.

Conclusions
Our data indicate that the intracellular trafficking of SMCX is controlled by its association with PCNA.
Peptide immunotherapy for childhood allergy ‐ addressing translational challenges
Authors: Mackenzie Karen J , Anderton Stephen M , Schwarze Jürgen 
Published: November 2011

AbstractAllergic sensitisation usually begins early in life. The number of allergens a patient is sensitised to can increase over time and the development of additional allergic conditions is increasingly recognised. Targeting allergic disease in childhood is thus likely to be the most efficacious means of reducing the overall burden of allergic disease. Specific immunotherapy involves administering protein allergen to tolerise allergen reactive CD4+ T cells, thought key in driving allergic responses. Yet specific immunotherapy risks allergic reactions including anaphylaxis as a consequence of preformed allergen‐specific IgE antibodies binding to the protein, subsequent cross‐linking and mast cell degranulation. CD4+ T cells direct their responses to short “immunodominant” peptides within the allergen. Such peptides can be given therapeutically to induce T cell tolerance without facilitating IgE cross‐linking. Peptide immunotherapy (PIT) offers attractive treatment potential for allergic disease. However, PIT has not yet been shown to be effective in children. This review discusses the immunological mechanisms implicated in PIT and briefly covers outcomes from adult PIT trials. This provides a context for discussion of the challenges for the application of PIT, both generally and more specifically in relation to children.
Production optimization of cyanophycinase ChpEal from Pseudomonas alcaligenes DIP1
Authors: Sallam Ahmed , Kalkandzhiev Dimitar , Steinbüchel Alexander 
Published: November 2011

Abstract

Pseudomonas alcaligenes DIP1 produces an extracellular cyanophycinase (CphEal). The corresponding gene (cphE

al
) was identified from subclones of a genomic DNA gene library by heterologously expressing the functionally active enzyme in Escherichia coli. The nucleotide sequence of the gene (1260 base pairs) was determined indicating a theoretical mass of 43.6 kDa (mature CphEal) plus a leader peptide of 2,6 kDa which corresponds well to the apparent molecular mass of 45 kDa as revealed by SDS-PAGE. The enzyme exhibited a high sequence identity of 91% with the extracellular cyanophycinase from P. anguilliseptica strain BI and carried an N-terminal Sec secretion signal peptide. Analysis of the amino acid sequence of cph E revealed a putative catalytic triad consisting of the serine motif GXSXG plus a histidine and a glutamate residue, suggesting a catalytic mechanism similar to serine-type proteases. The cyanophycinase (CphEal) was heterologously produced in two different E. coli strains (Top10 and BL21(DE3)) from two plasmid vectors (pBBR1MCS-4 and pET-23a(+)). The signal peptide of CphEal was cleaved in E. coli, suggesting active export of the protein at least to the periplasm. Substantial enzyme activity was also present in the culture supernatants. The extracellular cyanophycinase activities in E. coli were higher than activities in the wild type P. alcaligenes DIP1 in complex LB medium. Highest extracellular enzyme production was achieved with E. coli BL21(DE3) expressing CphEal from pBBR1MCS-4. Using M9 minimal medium was less effective, but the relatively low cost of mineral salt media makes these results important for the industrial-scale production of dipeptides from cyanophycin.
Nomogram for Predicting the Benefit of Adjuvant Chemoradiotherapy for Resected Gallbladder Cancer
Authors: Wang Samuel J. , Lemieux Andrew , Kalpathy-Cramer Jayashree , Ord Celine B. , Walker Gary V. , Fuller C. David , Kim Jong-Sung , Thomas Charles R. 
Published: November 2011

Purpose Although adjuvant chemoradiotherapy for resected gallbladder cancer may improve survival for some patients, identifying which patients will benefit remains challenging because of the rarity of this disease. The specific aim of this study was to create a decision aid to help make individualized estimates of the potential survival benefit of adjuvant chemoradiotherapy for patients with resected gallbladder cancer. Methods Patients with resected gallbladder cancer were selected from the Surveillance, Epidemiology, and End Results (SEER) –Medicare database who were diagnosed between 1995 and 2005. Covariates included age, race, sex, stage, and receipt of adjuvant chemotherapy or chemoradiotherapy (CRT). Propensity score weighting was used to balance covariates between treated and untreated groups. Several types of multivariate survival regression models were constructed and compared, including Cox proportional hazards, Weibull, exponential, log-logistic, and lognormal models. Model performance was compared using the Akaike information criterion. The primary end point was overall survival with or without adjuvant chemotherapy or CRT. Results A total of 1,137 patients met the inclusion criteria for the study. The lognormal survival model showed the best performance. A Web browser–based nomogram was built from this model to make individualized estimates of survival. The model predicts that certain subsets of patients with at least T2 or N1 disease will gain a survival benefit from adjuvant CRT, and the magnitude of benefit for an individual patient can vary. Conclusion A nomogram built from a parametric survival model from the SEER-Medicare database can be used as a decision aid to predict which gallbladder patients may benefit from adjuvant CRT.