bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overcoming resistance to existing therapies in HIV‐infected patients: The role of new antiretroviral drugs
Authors: Perno Carlo‐Federico , Moyle Graeme , Tsoukas Chris , Ratanasuwan Winai , Gatell Jose , Schechter Mauro 
Published: February 2008

AbstractResistance to available antiretroviral (ARV) agents is of increasing concern, and development of novel agents that address this problem has been identified as a major public health priority. As ARV resistance becomes more prevalent with extended use of existing agents, individuals with HIV infection resistant to all three traditional classes of ARVs, nucleoside reverse transcriptase inhibitors (NRTIs), non‐nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs), find themselves increasingly limited with regard to effective treatment options. The need for tolerable new drug regimens that effectively suppress viral replication while being simple to adhere to is increasingly pressing. This article reviews the epidemiology of antiretroviral drug resistance, the factors that contribute to the emergence of resistance, and presents data that support the need for early detection of resistance and maximal virologic suppression in order to delay treatment failure and reduce mortality. Healthcare providers are encouraged to optimize therapy through the use of new agents from existing drug classes, which can minimize cross‐resistance, as well as agents with novel mechanisms of action, in order to realize the potential for greater viral containment and to forestall development of resistance mutations. This article evaluates several emerging therapies that are in late‐stage clinical development and promise to expand treatment options for highly treatment‐experienced patients with the goal of improving outcomes for HIV‐infected individuals whose options for sustained antiviral efficacy are increasingly limited. J. Med. Virol. 80:565–576, 2008. © 2008 Wiley‐Liss, Inc.
Incidence of respiratory viruses among travelers with a febrile syndrome returning from tropical and subtropical areas
Authors: Camps M. , Vilella A. , Marcos M.A. , Letang E. , Muñoz J. , Salvadó E. , González A. , Gascón J. , Jiménez de Anta M.T. , Pumarola T. 
Published: February 2008

AbstractFifty million people are estimated to travel from industrial countries to the tropics annually. In spite of exhaustive studies and widely different diagnosis among returned patients, some cases of febrile illnesses remain without an etiological diagnosis, suggesting that these cases could be due to viral respiratory tract infections. From August 2005 to October 2006, 118 febrile patients without a specific diagnosis in their first visit at the Center for International Health of the Hospital Clínic of Barcelona were included. In all of them, in order to study respiratory viruses, a nasopharyngeal swab was collected. Clinical and radiological features and epidemiological data, as well as other samples for microbiologic studies, were also collected during consultation. Based on the physician's judgment at the time of consultation, patients were classified into four groups: respiratory symptoms (62%), febrile syndrome with nonspecific symptoms (24%), digestive symptoms (10%), and patients presenting both respiratory and digestive symptoms (4%). A pathogen microorganism was detected in 61 patients (52%). Respiratory viruses were detected in 44 out of 118 (37%) travelers included in the study, representing 56% of the patients with respiratory symptoms. The most frequently viruses detected were influenza virus (38%), rhinovirus (23%), adenovirus (9%), and respiratory syncytial virus (9%). Respiratory viruses have been shown to play an important role in imported fever. In light of the fact that international tourism is an increasing phenomenon, new strategies to prevent the spread of respiratory viruses should be considered, specially for influenza when a vaccine is available. J. Med. Virol. 80:711–715, 2008. © 2008 Wiley‐Liss, Inc.
Quantitation of human herpes virus 6 genome in children with acute lymphoblastic leukemia
Authors: Seror Elisa , Coquerel Bérénice , Gautheret‐Dejean Agnès , Ballerini Paola , Landman‐Parker Judith , Leverger Guy , Schneider Pascale , Vannier Jean‐Pierre 
Published: February 2008

AbstractAcute lymphoblastic leukemia is the main type of leukemia in children. An infectious etiology has been suspected and the role of the Human herpesvirus‐6 (HHV‐6) has been suggested. Several studies have tried to establish a link between HHV‐6 infections and hematological malignancies, with discordant results. The potential role of HHV‐6 in the pathogenesis of pediatric acute lymphoblastic leukemia was investigated. HHV‐6 genome copy number was measured by quantitative real‐time PCR (RQ‐PCR) in bone marrow or peripheral blood samples obtained from 36 children (median age = 4 years) with B acute lymphoblastic leukemia (n = 31) and T acute lymphoblastic leukemia (n = 5) at diagnosis and during complete remission. Positive samples were further characterized to define viral variant, A or B. A total of 24.7% of samples were positive for HHV‐6 genome: 13.9% were leukemia samples and 34.1% were complete remission samples. Viral load was low with values lower at diagnosis (median viral copy number = 22.9) than at complete remission (median copy number = 60.1). Among the 17 patients with positive samples, 15 were typed as B‐variant whereas 2 could not be typed. These results argue against a role of HHV6 infection in the development of pediatric acute lymphoblastic leukemia. They also suggest that HHV‐6 may infect latently bone marrow progenitors but seems not able to infect leukemic cells, raising again the question of the mechanism of virus fusion and entry. This observation shows that a reactivation may be observed during complete remission supporting the possibility of virus reactivation in immunocompromised hosts. J. Med. Virol. 80:689–693, 2008. © 2008 Wiley‐Liss, Inc.
Molecular typing and epidemiology of non‐polio enteroviruses isolated from Yunnan Province, the People's Republic of China
Authors: Bingjun Tian , Yoshida Hiromu , Yan Wu , Lin Lu , Tsuji Takao , Shimizu Hiroyuki , Miyamura Tatsuo 
Published: February 2008

AbstractThis report presents an overview of human enteroviruses in Yunnan Province, the People's Republic of China. A total of 210 non‐polioviruses isolated under acute flaccid paralysis (AFP) surveillance during a total study period of 5 years—1997 to 2000 and 2004—were examined. Of the 210 non‐poliovirus isolates, 12 adenoviruses were serologically identified, and the remaining 198 isolates were used for molecular typing. The viral genomes of 195 non‐polio enteroviruses (NPEVs) on VP1 partial region of virus capsid were translated to the corresponding amino acid sequences; these were compared with those of prototype strains. Based on molecular typing, 5 isolates were classified into 5 serotypes of the human enterovirus A species, 158 isolates, into 35 serotypes of the human enterovirus B species; and 32 isolates, into 6 serotypes of the human enterovirus C species. Viruses belonging to the human enterovirus D species were not isolated. Thus, under AFP surveillance, the human enterovirus B species accounted for 75.2% of the 210 isolates, and it was considered the predominant species. This was followed by human enterovirus C (12.2%), adenovirus (5.7%), and human enterovirus A (2.4%). Further, molecular analysis suggested that several serotypes of human enteroviruses B and C that exhibited genetic polymorphism were indigenous. Molecular typing methods may aid in understanding the epidemiology of NPEVs in Yunnan Province. J. Med. Virol. 80:670–679, 2008. © 2008 Wiley‐Liss, Inc.
Possible molecular mechanism of the relationship between NS5B polymorphisms and early clearance of hepatitis C virus during interferon plus ribavirin treatment
Authors: Nakamura Mitsuyasu , Saito Hidetsugu , Ikeda Masanori , Tada Shinichiro , Kumagai Naoki , Kato Nobuyuki , Shimotohno Kunitada , Hibi Toshifumi 
Published: February 2008

AbstractWe previously reported the relationship between viral polymerase polymorphisms and the initial decline in viral load induced by interferon‐α and ribavirin therapy in genotype 1b‐related chronic hepatitis C patients. The presence of E124K and I85V of NS5B was closely associated with viral clearance at 8 weeks of treatment. The aim of this study was to investigate the mechanisms by which this polymorphism of NS5B protein affects early viral clearance. We used a replicon system derived from strain O, genotype 1b virus. Three mutants (V85I), (K124E), and (V85I/K124E) were introduced to the replicon. OR6c, a derivative of HuH7 cells, was transfected with the replicon including a luciferase reporter gene. Luciferase activities were measured 72 hr post‐transfection. All three mutants showed higher luciferase activity than that of the wild type, and the V85I mutant showed the highest activity. This result was also confirmed by neomycin gene‐containing replicons with same mutations. All replicons were down‐regulated by ribavirin, but the level of reduction in the V85I mutant was the lowest. Our results suggested that this mutation at least partly contributes to resistance to early viral clearance during interferon and ribavirin combination therapy. J. Med. Virol. 80:632–639, 2008. © 2008 Wiley‐Liss, Inc.
Molecular epidemiological analysis of a nosocomial outbreak of respiratory syncytial virus associated pneumonia in a kangaroo mother care unit in South Africa
Authors: Visser Adele , Delport Suzanne , Venter Marietjie 
Published: February 2008

AbstractRespiratory syncytial virus (RSV) may cause severe lower respiratory tract disease in premature infants. Prolonged viral shedding has been reported in patients with underlying immunosuppressive disorders, such as human immunodeficiency virus 1 (HIV‐1) infection. During March to May 2006, 23 preterm pediatric patients developed nosocomial pneumonia in a district hospital in the Gauteng Province of South Africa due to RSV infection. The patients were identified using routine diagnostic testing. All had been admitted with their mothers to a Kangaroo Mother Care (KMC) ward from birth—a low care unit for the management of stable low birth weight infants. The HIV‐1 seroprevalence among the mothers to these infants was 52.6%, translating to a 52.6% perinatal exposure. A multiplex nested RT‐PCR was used to subtype RSV positive nasopharyngeal aspirates. Sequencing and phylogenetic analysis of part of the G‐protein gene was used for molecular epidemiological analysis of the outbreak. In total, 19 of the 23 RSV positive specimens could be PCR amplified and sequenced. The subtype A, GA5 genotype was identified in 14 specimens and the BA genotype, a new subtype B genotype not previously recognized in South Africa, in seven. One patient had an infection with both genotypes. Phylogenetic analysis demonstrated eight separate introductions. Two of the strains identified in this outbreak were identical to strains circulating in a general pediatric ward of this hospital during the preceding month. Inadequate infection control measures by health care providers and mothers to children in KMC units may increase potentially the risk of severe RSV infection in a population group with compounded risk factors. J. Med. Virol. 80:724–732, 2008. © 2008 Wiley‐Liss, Inc.
Improved detection of natural hepatitis B virus surface antigen (HBsAg) mutants by a new version of the VITROS® HBsAg assay
Authors: Echevarría José M. , Avellón Ana 
Published: February 2008

AbstractThe sensitivity of immunoassays for hepatitis B virus (HBV) surface antigen (HBsAg) detection may be hampered by the presence of mutants involving the major antigenic determinant of the protein. The performance of the VITROS® HBsAg Assay has been shown to be affected by mutations comprising amino acid changes at residues 143, 144, and 145 of the HBsAg molecule. Sixty‐seven serum samples from HBV carriers containing major populations of natural HBsAg mutants assayed previously by that assay were tested by the new VITROS® HBsAg ES Assay. Samples displayed either single or multiple amino acid substitutions between positions 112 and 145 of the HBsAg, including changes in relevant residues such as 118–120, 125–127, and 143–145. Testing of undiluted samples by the current assay gave rise to false negative results in two samples displaying the single substitutions 145A and 145R, and in one additional sample displaying a dual mutation 118A + 145A. Unusually weak reactivity (<25 S/CO units) was, in addition, recorded in samples containing mutants 143L (2 samples) and 115N + 120Q + 131K + 144A (1 sample). Testing samples at the 1/40 dilution by the modified assay did not produce, in contrast, false negative results, and reactivity below 25 S/CO units was recorded only in three cases. These results confirm that the capability of immunoassays to detect the presence of natural HBsAg mutants in clinical samples may be improved significantly by introducing changes in their design, and show that such improvement has been achieved successfully with the new VITROS® HBsAg ES Assay. J. Med. Virol. 80:598–602, 2008. © 2008 Wiley‐Liss, Inc.
Physiological Improvement to Enhance Escherichia coli Cell‐Surface Display via Reducing Extracytoplasmic Stress
Authors: Narayanan Niju , Chou C. Perry 
Published: February 2008

AbstractCell physiology was impaired when enhanced yellow fluorescence protein (EYFP) was displayed on the Escherichia coli cell surface, resulting in growth arrest and poor display performance. Coexpression of Skp, a periplasmic chaperone known to interact with several outer membrane proteins for their transport and insertion in the outer membrane, was demonstrated to be effective to restore cell physiology. When Skp was coexpressed with EYFP display, host cells became less sensitive to ethylenediaminetetraacetic acid and sodium dodecyl sulfate, implying that cell physiology was improved. Most importantly, the display performance was highly enhanced as a result of the increased specific fluorescence intensity without growth arrest. The results of transmission electron microscopy indicate that the density of surface‐displayed EYFP was highly increased upon Skp coexpression. Cells with EYFP display experienced extracytoplasmic stress, as reflected by the induced promoter activities of three stress‐responsive genes, degP, cpxP, and rpoH. The extracytoplasmic stress reflected by the degP promoter activity appears to be consistent with the cell physiology observed phenotypically under various culture conditions for cell‐surface display. Therefore, the PdegP:: lacZ allele was proposed to be a suitable “sensor” for monitoring the extracytoplasmic stress and cell physiology during the course of E. coli cell‐surface display.
Periodically Discontinuous Induction of Bone Marrow Stem Cells toward Osteogenic Differentiation in Vitro
Authors: Wang Zhen , Peng Rong , Ding Jiandong 
Published: February 2008

AbstractThis paper reveals that a discontinuous in vitro induction, namely, the periodic presence and absence of foreign induction factors, might be, under a certain condition, more effective to stimulate stem cells' differentiation than a continuous induction. Bone marrow stem cells (BMSCs) derived from Sprague Dawley rats were employed to examine the effects of discontinuous additions of osteogenic supplements with a series of alternate frequency in contrast to those with continuous induction or no induction. The results demonstrated that a suitable discontinuous induction was more able to achieve osteogenesis than not only no induction but also the associated continuous induction. Additionally, the osteogenic supplements were confirmed to enhance cell differentiation but suppress cell proliferation. So, the combination of differentiation extent per cell and cell number accounts for the “unexpected” good osteogenic effect of the discontinuous induction. The induction effect was found to be dependent upon alternate frequency, and the optimum alternate period in our experimental systems was determined to be around 4 days. Since it is very common to change culture medium every 2–4 days, such a strategy of discontinuous induction does not bring any extra manual work but reduces the consumption of foreign induction factors and significantly enhances the global differentiation efficacy. Our work thus affords a convenient and practical approach to achieve differentiation of BMSCs, which might be useful for potential large‐scale culture and differentiation of stem cells. Meanwhile, the existence of optimum frequency implies some unknown inherent rhythms of cell proliferation and differentiation.
fdrMotif: identifyingcis-elements by an EM algorithm coupled with false discovery rate control
Authors: Li Leping , Bass Robert L. , Liang Yu 
Published: February 2008

AbstractMotivation: Most de novo motif identification methods optimize the motif model first and then separately test the statistical significance of the motif score. In the first stage, a motif abundance parameter needs to be specified or modeled. In the second stage, a Z-score or P-value is used as the test statistic. Error rates under multiple comparisons are not fully considered.Methodology: We propose a simple but novel approach, fdrMotif, that selects as many binding sites as possible while controlling a user-specified false discovery rate (FDR). Unlike existing iterative methods, fdrMotif combines model optimization [e.g. position weight matrix (PWM)] and significance testing at each step. By monitoring the proportion of binding sites selected in many sets of background sequences, fdrMotif controls the FDR in the original data. The model is then updated using an expectation (E)- and maximization (M)-like procedure. We propose a new normalization procedure in the E-step for updating the model. This process is repeated until either the model converges or the number of iterations exceeds a maximum.Results: Simulation studies suggest that our normalization procedure assigns larger weights to the binding sites than do two other commonly used normalization procedures. Furthermore, fdrMotif requires only a user-specified FDR and an initial PWM. When tested on 542 high confidence experimental p53 binding loci, fdrMotif identified 569 p53 binding sites in 505 (93.2%) sequences. In comparison, MEME identified more binding sites but in fewer ChIP sequences than fdrMotif. When tested on 500 sets of simulated ‘ChIP’ sequences with embedded known p53 binding sites, fdrMotif, compared to MEME, has higher sensitivity with similar positive predictive value. Furthermore, fdrMotif is robust to noise: it selected nearly identical binding sites in data adulterated with 50% added background sequences and the unadulterated data. We suggest that fdrMotif represents an improvement over MEME.Availability: C code can be found at: http://www.niehs.nih.gov/research/resources/software/fdrMotif/Contact: li3@niehs.nih.govSupplementary information: Supplementary data are available at http://www.niehs.nih.gov/research/resources/software/fdrMotif/
CGHweb: a tool for comparing DNA copy number segmentations from multiple algorithms
Authors: Lai Weil , Choudhary Vidhu , Park Peter J. 
Published: February 2008

Abstract
Summary: Accurate estimation of DNA copy numbers from array comparative genomic hybridization (CGH) data is important for characterizing the cancer genome. An important part of this process is the segmentation of the log-ratios between the sample and control DNA along the chromosome into regions of different copy numbers. However, multiple algorithms are available in the literature for this procedure and the results can vary substantially among these. Thus, a visualization tool that can display the segmented profiles from a number of methods can be helpful to the biologist or the clinician to ascertain that a feature of interest did not arise as an artifact of the algorithm. Such a tool also allows the methodologist to easily contrast his method against others.
We developed a web-based tool that applies a number of popular algorithms to a single array CGH profile entered by the user. It generates a heatmap panel of the segmented profiles for each method as well as a consensus profile. The clickable heatmap can be moved along the chromosome and zoomed in or out. It also displays the time that each algorithm took and provides numerical values of the segmented profiles for download. The web interface calls algorithms written in the statistical language R. We encourage developers of new algorithms to submit their routines to be incorporated into the website.
Availability: http://compbio.med.harvard.edu/CGHweb
Contact: peter_park@harvard.edu
A comprehensive assessment of sequence-based and template-based methods for protein contact prediction
Authors: Wu Sitao , Zhang Yang 
Published: February 2008

Abstract
Motivation: Pair-wise residue-residue contacts in proteins can be predicted from both threading templates and sequence-based machine learning. However, most structure modeling approaches only use the template-based contact predictions in guiding the simulations; this is partly because the sequence-based contact predictions are usually considered to be less accurate than that by threading. With the rapid progress in sequence databases and machine-learning techniques, it is necessary to have a detailed and comprehensive assessment of the contact-prediction methods in different template conditions.
Results: We develop two methods for protein-contact predictions: SVM-SEQ is a sequence-based machine learning approach which trains a variety of sequence-derived features on contact maps; SVM-LOMETS collects consensus contact predictions from multiple threading templates. We test both methods on the same set of 554 proteins which are categorized into ‘Easy’, ‘Medium’, ‘Hard’ and ‘Very Hard’ targets based on the evolutionary and structural distance between templates and targets. For the Easy and Medium targets, SVM-LOMETS obviously outperforms SVM-SEQ; but for the Hard and Very Hard targets, the accuracy of the SVM-SEQ predictions is higher than that of SVM-LOMETS by 12–25%. If we combine the SVM-SEQ and SVM-LOMETS predictions together, the total number of correctly predicted contacts in the Hard proteins will increase by more than 60% (or 70% for the long-range contact with a sequence separation ≥24), compared with SVM-LOMETS alone. The advantage of SVM-SEQ is also shown in the CASP7 free modeling targets where the SVM-SEQ is around four times more accurate than SVM-LOMETS in the long-range contact prediction. These data demonstrate that the state-of-the-art sequence-based contact prediction has reached a level which may be helpful in assisting tertiary structure modeling for the targets which do not have close structure templates. The maximum yield should be obtained by the combination of both sequence- and template-based predictions.
Contact: yzhang@ku.edu
Supplementary information: Supplementary data are available at Bioinformatics online.