bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amino acid differences in glycoproteins B (gB), C (gC), H (gH) and L(gL) are associated with enhanced herpes simplex virus type-1 (McKrae) entry via the paired immunoglobulin-like type-2 receptor α
Authors: Chowdhury Sona , Naderi Misagh , Chouljenko Vladimir N , Walker Jason D , Kousoulas Konstantin G 
Published: June 2012

Abstract

Background
Herpes simplex virus type-1 (HSV-1) enters into cells via membrane fusion of the viral envelope with plasma or endosomal membranes mediated by viral glycoproteins. HSV-1 virions attach to cell surfaces by binding of viral glycoproteins gC, gD and gB to specific cellular receptors. Here we show that the human ocular and highly neurovirulent HSV-1 strain McKrae enters substantially more efficiently into cells via the gB-specific human paired immunoglobulin-like type-2 receptor-α (hPILR-α). Comparison of the predicted amino acid sequences between HSV-1(F) and McKrae strains indicates that amino acid changes within gB, gC, gH and gL may cause increased entry via the hPILR- α receptor.

Results
HSV-1 (McKrae) entered substantially more efficiently than viral strain F in Chinese hamster ovary (CHO) cells expressing hPIRL-α but not within CHO-human nectin-1, -(CHO-hNectin-1), CHO-human HVEM (CHO-hHVEM) or Vero cells. The McKrae genes encoding viral glycoproteins gB, gC, gD, gH, gL, gK and the membrane protein UL20 were sequenced and their predicted amino acid (aa) sequences were compared with virulent strains F, H129, and the attenuated laboratory strain KOS. Most aa differences between McKrae and F were located at their gB amino termini known to bind with the PILRα receptor. These aa changes included a C10R change, also seen in the neurovirulent strain ANG, as well as redistribution and increase of proline residues. Comparison of gC aa sequences revealed multiple aa changes including an L132P change within the 129-247 aa region known to bind to heparan sulfate (HS) receptors. Two aa changes were located within the H1 domain of gH that binds gL. Multiple aa changes were located within the McKrae gL sequence, which were preserved in the H129 isolate, but differed for the F strain. Viral glycoproteins gD and gK and the membrane protein UL20 were conserved between McKrae and F strains.

Conclusions
The results indicate that the observed entry phenotype of the McKrae strain is most likely due to a combination of increased binding to heparan sulfate receptors and enhanced virus entry via gB-mediated fusion of the viral envelope with plasma membranes.
A type-specific nested PCR assay established and applied for investigation of HBV genotype and subgenotype in Chinese patients with chronic HBV infection
Authors: Nie Jing-Jing , Sun Kui-Xia , Li Jie , Wang Jie , Jin Hui , Wang Ling , Lu Feng-Min , Li Tong , Yan Ling , Yang Jing-Xian , Sun Mi-Shu , Zhuang Hui 
Published: June 2012

Abstract

Background
Many studies have suggested that hepatitis B virus (HBV) genotypes show not only geographical distribution and race specificity, but also are associated with disease progression and response to interferon treatment. The objective of this study was to develop a nested polymerase chain reaction (nPCR) assay for genotypes A-D and subgenotypes B1, B2, C1 and C2 of hepatitis B virus (HBV) and to investigate the distribution characteristics of HBV genotypes/subgenotype in China.

Methods
After redesigning the primers and optimizing the reaction conditions using common Taq polymerase, the sensitivity, specificity and reproducibility of the method were evaluated using plasmids and serum samples. In total, 642 serum samples from patients with chronic HBV infection were applied to investigate the distribution of HBV genotype and subgenotype in China.

Results
The genotype and subgenotype could be identified when the HBV DNA load of a sample was ≥102.3 IU/mL. For the 639 successfully genotyped samples, the sequencing results of 130 randomly selected samples (20.3%, 130/639) were consistent with those of the nPCR method. The present study showed that HBV genotype B (11.2%, 72/642), C (68.2%, 438/642) and D (7.2%, 46/642) were circulating in China, while genotype C was the dominant strain except for western region where genotype D was the prevalent strain. The main subgenotypes of genotypes B and C were B2 (87.5%, 63/72) and C2 (92.9%, 407/438), respectively.

Conclusions
The low-cost nPCR method would be a useful tool for clinical and epidemiological investigation in the regions where genotypes A-D are predominant.
Primary malignant melanoma of the duodenum without visible melanin pigment: a mimicker of lymphoma or carcinoma
Authors: Li Hongxia , Fan Qinhe , Wang Zhen , Xu Hai , Li Xiao , Zhang Weiming , Zhang Zhihong 
Published: June 2012

Abstract
Primary malignant melanoma of the duodenum is an unusual oncologic entity. Patients usually present the similar clinical symptoms like other common tumors in this site. And there are no specific radiological features either. The cases with only little melanin pigment or without notable melanin pigment are very misleading, especially in small biopsies or frozen sections. Definite diagnosis depends on both careful histologic examination and the use of proper immunohistochemical stains. Moreover, detailed history and thorough investigation should be made to exclude the preexistence or coexistence of a primary lesion elsewhere. Herein we report the case of a 60-year-old male patient with primary malignant melanoma of the duodenum, which was misdiagnosed as lymphoma or undifferentiated carcinoma in frozen consultation. The patient had achieved disease-free survival for more than 46 months without any evidence of recurrence after surgery.

Virtual slides

The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1221457317710561.
Gene interaction enrichment and network analysis to identify dysregulated pathways and their interactions in complex diseases
Authors: Liu Yu , Koyutürk Mehmet , Barnholtz-Sloan Jill S , Chance Mark R 
Published: June 2012

Abstract

Background
The molecular behavior of biological systems can be described in terms of three fundamental components: (i) the physical entities, (ii) the interactions among these entities, and (iii) the dynamics of these entities and interactions. The mechanisms that drive complex disease can be productively viewed in the context of the perturbations of these components. One challenge in this regard is to identify the pathways altered in specific diseases. To address this challenge, Gene Set Enrichment Analysis (GSEA) and others have been developed, which focus on alterations of individual properties of the entities (such as gene expression). However, the dynamics of the interactions with respect to disease have been less well studied (i.e., properties of components ii and iii).

Results
Here, we present a novel method called Gene Interaction Enrichment and Network Analysis (GIENA) to identify dysregulated gene interactions, i.e., pairs of genes whose relationships differ between disease and control. Four functions are defined to model the biologically relevant gene interactions of cooperation (sum of mRNA expression), competition (difference between mRNA expression), redundancy (maximum of expression), or dependency (minimum of expression) among the expression levels. The proposed framework identifies dysregulated interactions and pathways enriched in dysregulated interactions; points out interactions that are perturbed across pathways; and moreover, based on the biological annotation of each type of dysregulated interaction gives clues about the regulatory logic governing the systems level perturbation. We demonstrated the potential of GIENA using published datasets related to cancer.

Conclusions
We showed that GIENA identifies dysregulated pathways that are missed by traditional enrichment methods based on the individual gene properties and that use of traditional methods combined with GIENA provides coverage of the largest number of relevant pathways. In addition, using the interactions detected by GIENA, specific gene networks both within and across pathways associated with the relevant phenotypes are constructed and analyzed.
A framework to identify gene expression profiles in a model of inflammation induced by lipopolysaccharide after treatment with thalidomide
Authors: Paiva Renata T , Saliba Alessandra M , Fulco Tatiana O , de Souza Sales Jorgenilce , Serra de Carvalho Daniel , Sampaio Elizabeth P , Lopes Ulisses G , Sarno Euzenir N , Nobre Flavio F 
Published: June 2012

Abstract

Background
Thalidomide is an anti-inflammatory and anti-angiogenic drug currently used for the treatment of several diseases, including erythema nodosum leprosum, which occurs in patients with lepromatous leprosy. In this research, we use DNA microarray analysis to identify the impact of thalidomide on gene expression responses in human cells after lipopolysaccharide (LPS) stimulation. We employed a two-stage framework. Initially, we identified 1584 altered genes in response to LPS. Modulation of this set of genes was then analyzed in the LPS stimulated cells treated with thalidomide.

Results
We identified 64 genes with altered expression induced by thalidomide using the rank product method. In addition, the lists of up-regulated and down-regulated genes were investigated by means of bioinformatics functional analysis, which allowed for the identification of biological processes affected by thalidomide. Confirmatory analysis was done in five of the identified genes using real time PCR.

Conclusions
The results showed some genes that can further our understanding of the biological mechanisms in the action of thalidomide. Of the five genes evaluated with real time PCR, three were down regulated and two were up regulated confirming the initial results of the microarray analysis.
Proteolytic profiling and comparative analyses of active trypsin-like serine peptidases in preimaginal stages of Culex quinquefasciatus
Authors: Borges-Veloso Andre , Saboia-Vahia Leonardo , Cuervo Patricia , Pires Renata C , Britto Constança , Fernandes Nilma , d’Avila-Levy Claudia M , De Jesus Jose B 
Published: June 2012

AbstractBackgroundThe mosquitoCulex quinquefasciatu s, a widespread insect in tropical and sub-tropical regions of the world, is a vector of multiple arboviruses and parasites, and is considered an important risk to human and veterinary health. Proteolytic enzymes play crucial roles in the insect physiology including the modulation of embryonic development and food digestion. Therefore, these enzymes represent important targets for the development of new control strategies. This study presents zymographic characterization and comparative analysis of the proteolytic activity found in eggs, larval instars and pupae ofCulex quinquefasciatus.MethodsThe proteolytic profiles of eggs, larvae and pupa ofCx. quinquefasciatuswere characterized by SDS-PAGE co-polymerized with 0.1% gelatin, according to the pH, temperature and peptidase inhibitor sensitivity. In addition, the proteolytic activities were characterized in solution using 100 μM of the fluorogenic substrate Z-Phe-Arg-AMC.ResultsComparison of the proteolytic profiles by substrate-SDS-PAGE from all preimaginal stages of the insect revealed qualitative and quantitative differences in the peptidase expression among eggs, larvae and pupae. Use of specific inhibitors revealed that the proteolytic activity from preimaginal stages is mostly due to trypsin-like serine peptidases that display optimal activity at alkaline pH. In-solution, proteolytic assays of the four larval instars using the fluorogenic substrate Z-Phe-Arg-AMC in the presence or absence of a trypsin-like serine peptidase inhibitor confirmed the results obtained by substrate-SDS-PAGE analysis. The trypsin-like serine peptidases of the four larval instars were functional over a wide range of temperatures, showing activities at 25°C and 65°C, with an optimal activity between 37°C and 50°C.ConclusionThe combined use of zymography and in-solution assays, as performed in this study, allowed for a more detailed analysis of the repertoire of proteolytic enzymes in preimaginal stages of the insect. Finally, differences in the trypsin-like serine peptidase profile of preimaginal stages were observed, suggesting that such enzymes exert specific functions during the different stages of the life cycle of the insect.
Are platinum agents, paclitaxel and irinotecan effective for clear cell carcinoma of the ovary? DNA damage detected with γH2AX induced by anticancer agents
Authors: Takatori Eriko , Shoji Tadahiro , Kumagai Seisuke , Sawai Takashi , Kurose Akira , Sugiyama Toru 
Published: June 2012

Abstract

Objectives
Differences in the incidences and types of DNA damage induced by antitumor agents for clear cell carcinoma (CCC) were determined in 2 ovarian CCC cell lines using γH2AX.

Material and methods
The antitumor activity of anticancer agents, CDDP, CBDCA, PTX and SN-38, was examined using ovarian clear cell carcinoma cultured cell lines (OVISE and RMG-I). After culture, each cell line was treated with each anticancer agent, the cells were collected, fixed, and then reacted with the anti-γH2AX antibody. γH2AX and nuclear DNA were then simultaneously detected by flow cytometry using FITC and propidium iodide, respectively, to determine γH2AX in each cell cycle phase.

Results
After administration of CDDP, DNA damage was frequent in S-phase cells, while cell-cycle arrest occurred in the G1 and G2/M phases and γH2AX did not increase in CDDP-resistant cells. Sensitivities to CDDP and CBDCA differed between the two cell lines. The antitumor effect of PTX is induced by G2/M arrest, and combination treatment with CBDCA, inducing DNA damage in G2/M-phase cells, might be effective.

Conclusions
This is the first study in Japan to evaluate the antitumor activity of anticancer agents by focusing on the relationship between the cell cycle and DNA damage using γH2AX as an indicator. The immunocytochemical method used in this study detects γH2AX, which indicates DNA damage even at very low concentrations and with high sensitivity. Therefore, a promising method of easily and rapidly identifying agents potentially effective against CCC.
Enhanced patient reported outcome measurement suitable for head and neck cancer follow-up clinics
Authors: Ghazali Naseem , Lowe Derek , Rogers Simon N 
Published: June 2012

Abstract

Background
The ‘Worse-Stable-Better’ (W-S-B) question was introduced to capture patient-perceived change in University of Washington Quality of Life (UW-QOL) domains.

Methods
202 head and neck cancer patients in remission prospectively completed UW-QOL and Patients Concerns Inventory (PCI). For each UW-QOL domain, patients indicated whether over the last month things had worsened (W), remained stable (S) or were better (B).

Results
202 patients at 448 attendances selected 1752 PCI items they wanted to discuss in consultation, and 58% (1024/1752) of these were not covered by the UW-QOL. UW-QOL algorithms highlighted another 440 significant problems that the patient did not want to discuss (i.e. the corresponding items on the PCI were not selected).
After making allowance for UW-QOL algorithms to identify 'significant problems' and PCI selection of corresponding issues for discussion there remained clear residual and notable variation in W-S-B responses, in particular to identify patients with significant problems that were getting worse, and patients without significant problems that wanted to discuss issues that were getting worse. Changes in mean UW-QOL scores were notably lower for those getting worse on the W-S-B question, typically by 10 or more units a magnitude that suggests clinically important changes in score.

Conclusions
The W-S-B question adds little questionnaire burden and could help to better identify patients who might benefit from intervention. The results of this study suggest that the UW-QOL with the W-S-B modification should be used together with the PCI to allow optimal identification of issues for patient-clinician discussion during routine outpatient clinics.
Prevalance of BRCA1 and BRCA2 mutations in familial breast cancer patients in Lebanon
Authors: Jalkh Nadine , Nassar-Slaba Jinane , Chouery Eliane , Salem Nabiha , Uhrchammer Nancy , Golmard Lisa , Stoppa-Lyonnet Domique , Bignon Yves-Jean , Mégarbané André 
Published: June 2012

Abstract
Breast cancer is the most prevalent malignancy in women in Western countries, currently accounting for one third of all female cancers. Familial aggregation is thought to account for 5–10 % of all BC cases, and germline mutations in BRCA1 and BRCA2 account for less of the half of these inherited cases. In Lebanon, breast cancer represents the principal death-causing malignancy among women, with 50 % of the cases diagnosed before the age of 50 years.
In order to study BRCA1/2 mutation spectra in the Lebanese population, 72 unrelated patients with a reported family history of breast and/or ovarian cancers or with an early onset breast cancer were tested. Fluorescent direct sequencing of the entire coding region and intronic sequences flanking each exon was performed.
A total of 38 BRCA1 and 40 BRCA2 sequence variants were found. Seventeen of them were novel. Seven confirmed deleterious mutations were identified in 9 subjects providing a frequency of mutations of 12.5 %. Fifteen variants were considered of unknown clinical significance according to BIC and UMD-BRCA1/BRCA2 databases.
In conclusion, this study represents the first evaluation of the deleterious and unclassified genetic variants in the BRCA1/2 genes found in a Lebanese population with a relatively high risk of breast cancer.
Esophageal impedance baseline according to different time intervals
Authors: Ummarino Dario , Salvatore Silvia , Hauser Bruno , Staiano Annamaria , Vandenplas Yvan 
Published: June 2012

Abstract

Background
The impedance baseline has been shown to reflect esophageal integrity, and to be decreased in patients with esophagitis. However, different methods for the determination of the impedance baseline have not been compared.

Methods
The median impedance baseline was calculated in 10 consecutive multichannel intraluminal impedance recordings in children with non-erosive reflux disease. All children underwent an endoscopy with a biopsy as part of the clinical work-up to exclude esophagitis. The impedance baseline was obtained both by including and excluding all impedance episodes (IE; reflux, swallows and gas episodes) during the full recording, and during the first 1-minute period without an IE every hour (method 1), every 2 hours (method 2) or every 4 hours (method 3). The impedance baseline obtained during the full recording was set at 100%, and the variation (difference in impedance baseline for the different methods) and variability (difference in impedance baseline during one analysis period) were assessed.

Results
None of the participants had esophagitis. The mean difference over the six channels between the impedance baseline over the total recording with and without IE was approximately 2.5%, and comparable for each channel (range 0.47% to 5.55%). A mean of 1,028 IEs were excluded in each tracing, and it took between 4 and 24 hours to delete all events in one tracing. The difference in the impedance baseline obtained with and without IEs was mainly caused by the gas episodes in the upper channels and swallows in the lower channels. The median impedance baseline according to the three one-minute analysis methods was comparable to the median impedance baseline according to the 24 hour analysis.

Conclusions
The automatic determination of the median impedance baseline over the total tracing including IEs is an adequate method. In isolated tracings with numerous IEs, the calculation of the median impedance baseline over one minute every 4 hours is an alternative option. Companies should develop software to calculate the median impedance baseline during the whole registration deleting all IEs for the analysis.
N-terminal pro-brain natriuretic peptide in a novel screening algorithm for pulmonary arterial hypertension in systemic sclerosis: a case-control study
Authors: Thakkar Vivek , Stevens Wendy M , Prior David , Moore Owen A , Byron Jillian , Liew Danny , Patterson Karen , Hissaria Pravin , Roddy Janet , Zochling Jane , Sahhar Joanne , Nash Peter , Tymms Kathleen , Celermajer David , Gabbay Eli , Youssef Peter , Proudman Susanna M , Nikpour Mandana 
Published: June 2012

Abstract
Introduction
Pulmonary arterial hypertension is a major cause of mortality in systemic sclerosis. N-terminal pro-brain natriuretic peptide (NT-proBNP) has emerged as a candidate biomarker that may enable the early detection of systemic sclerosis-related pulmonary arterial hypertension (SSc-PAH). The objective of our study was to incorporate NT-proBNP into a screening algorithm for SSc-PAH that could potentially replace transthoracic echocardiography (TTE) as a more convenient and less costly "first tier" test.

Methods
NT-proBNP levels were measured in patients from four clinical groups: a group with right heart catheter (RHC)-diagnosed SSc-PAH before commencement of therapy for PAH; a group at high risk of SSc-PAH based on TTE; a group with interstitial lung disease; and systemic sclerosis (SSc) controls with no cardiopulmonary complications. NT-proBNP levels were compared by using ANOVA and correlated with other clinical variables by using simple and multiple linear regression. ROC curve analyses were performed to determine the optimal cut point for NT-proBNP and other clinical variables in prediction of PAH.

Results
NT-proBNP was highest in the PAH group compared with other groups (P < 0.0001), and higher in the risk group compared with controls (P < 0.0001). NT-proBNP was positively correlated with systolic pulmonary artery pressure (PAP) on TTE (P < 0.0001), and mean PAP (P = 0.013), pulmonary vascular resistance (P = 0.005), and mean right atrial pressure (P = 0.006) on RHC. A composite model wherein patients screened positive if NT-proBNP was ≥ 209.8 pg/ml, and/or DLCOcorr was < 70.3% with FVC/DLCOcorr ≥ 1.82, had a sensitivity of 100% and specificity of 77.8% for SSc-PAH.

Conclusion
We have proposed a screening algorithm for SSc-PAH, incorporating NT-proBNP level and PFTs. This model has high sensitivity and specificity for SSc-PAH and, if positive, should lead to TTE and confirmatory testing for PAH. This screening algorithm must be validated prospectively.