bluuebunny/crossref_metadata_2025_split huggingface dataset:
Type-Specific Detection of 30 Oncogenic Human Papillomaviruses by Genotyping both E6 and L1 Genes
Authors: Peng Junping , Gao Lei , Guo Junhua , Wang Ting , Wang Ling , Yao Qing , Zhu Haijun , Jin Qi 
Published: November 2012

ABSTRACT
Human papillomavirus (HPV) is the principal cause of invasive cervical cancer and benign genital lesions. There are currently 30 HPV types linked to cervical cancer. HPV infection also leads to other types of cancer. We developed a 61-plex analysis of these 30 HPV types by examining two genes, E6 and L1, using MassARRAY matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) (PCR-MS). Two hundred samples from homosexual males (HM) were screened by PCR-MS and MY09/MY11 primer set-mediated PCR (MY-PCR) followed by sequencing. One hundred thirty-five formalin-fixed, paraffin-embedded (FFPE) cervical cancer samples were also analyzed by PCR-MS, and results were compared to those of the commercially available GenoArray (GA) assay. One or more HPV types were identified in 64.5% (129/200) of the samples from HM. Comprising all 30 HPV types, PCR-MS detected 51.9% (67/129) of samples with multiple HPV types, whereas MY-PCR detected only one single HPV type in these samples. All PCR-MS results were confirmed by MY-PCR. In the cervical cancer samples, PCR-MS and GA detected 97% (131/135) and 90.4% (122/135) of HPV-positive samples, respectively. PCR-MS and GA results were fully concordant for 122 positive and 4 negative samples. The sequencing results for the 9 samples that tested negative by GA were completely concordant with the positive PCR-MS results. Multiple HPV types were identified in 25.2% (34/135) and 55.6% (75/135) of the cervical cancer samples by GA and PCR-MS, respectively, and results were confirmed by sequencing. The new assay allows the genotyping of >1,000 samples per day. It provides a good alternative to current methods, especially for large-scale investigations of multiple HPV infections and degraded FFPE samples.
Clinical Spectrum of Exophiala Infections and a Novel Exophiala Species, Exophiala hongkongensis
Authors: Woo Patrick C. Y. , Ngan Antonio H. Y. , Tsang Chris C. C. , Ling Ian W. H. , Chan Jasper F. W. , Leung Shui-Yee , Yuen Kwok-Yung , Lau Susanna K. P. 
Published: November 2012

ABSTRACTWe characterized 12Exophialastrains isolated from patients over a 15-year period to the species level using phenotypic tests and internal transcribed spacer (ITS) andRpb1sequencing and described the clinical spectrum of the 12 patients. Eight patients had nail or skin infections, two had invasive infections, and two had colonization of the gastrointestinal tract. ITS andRpb1sequencing showed that 11 of the 12 strains were knownExophialaspecies (E. oligosperma[n= 3],E. jeanselmei[n= 2],E. lecanii-corni[n= 2],E. bergeri[n= 1],E. cancerae[n= 1],E. dermatitidis[n= 1], andE. xenobiotica[n= 1]), which included the first reported cases of onychomycosis caused byE. bergeriandE. oligosperma. The 12th strain (HKU32T), isolated from the nail clipping of the right big toe of a 68-year-old female patient with onychomycosis, possessed unique morphological characteristics distinct from otherExophialaspecies. It grew very slowly and had a velvety colony texture after 28 days, short conidiophores of the same olivaceous color as the supporting hyphae, numerous spores, and no chlamydospore-like cells. ITS,Rpb1, β-tubulin, and β-actin gene sequencing unambiguously showed that HKU32Twas clustered with but formed branches distinct from otherExophialaspecies in phylogenetic trees. We propose the new speciesExophiala hongkongensisto describe this novel fungus.
Multilocus Sequence Typing of Candida tropicalis Shows the Presence of Different Clonal Clusters and Fluconazole Susceptibility Profiles in Sequential Isolates from Candidemia Patients in São Paulo, Brazil
Authors: Magri Marcello Mihailenko Chaves , Gomes-Gouvêa Michele Soares , de Freitas Vera Lúcia Teixeira , Motta Adriana Lopes , Moretti Maria Luiza , Shikanai-Yasuda Maria Aparecida 
Published: November 2012

ABSTRACT

The profiles of 61
Candida tropicalis
isolates from 43 patients (28 adults and 15 children) diagnosed with candidemia at two teaching hospitals in São Paulo, Brazil, were characterized by multilocus sequence typing (MLST). For the 14 patients who had bloodstream infections, 32 isolates were serially collected from their blood and/or catheters. Thirty-nine diploid sequence types (DSTs) were differentiated. According to the
C. tropicalis
MLST database (
http://pubmlst.org/ctropicalis/
), 36 DSTs and 23 genotypes identified from the 61 isolates had not previously been described. This report represents the first study to characterize sequential isolates of
C. tropicalis
from candidemia cases in South America. Microvariation in a single gene was found in the sequential isolates from 7 patients. The main polymorphisms occurred in the alleles of the
XYR1
gene, specifically at nucleotide positions 215, 242, and 344. Macrovariation in six gene fragments was detected in the isolates from 3 patients. eBURST analysis added two new groups to this study (groups 6 and 18). Additionally, susceptibility tests indicate that 3 isolates were resistant to fluconazole. No correlation was found between the DSTs and susceptibility to fluconazole and/or selective antifungal pressure. Two patients were sequentially infected with resistant and susceptible strains. MLST is an important tool for studying the genetic diversity of multiple/sequential isolates of patients with candidemia, allowing the comparison of our data with those from other regions of the world, as well as allowing an analysis of the genetic relationship among several clones in sequential isolates from the same or different candidemia patient sites (blood or catheter).
Felid Herpesvirus 1 as a Causative Agent of Severe Nonsuppurative Meningoencephalitis in a Domestic Cat
Authors: Hora Aline S. , Tonietti Paloma O. , Guerra Juliana M. , Leme Maiara C. , Pena Hilda F. J. , Maiorka Paulo C. , Brandão Paulo E. 
Published: November 2012

ABSTRACT
Felid herpesvirus 1 is an important respiratory pathogen of domestic cats. This report presents the first case of severe nonsuppurative meningoencephalitis caused by this virus in a cat.
Novel, Potentially Zoonotic Paramyxoviruses from the African Straw-Colored Fruit Bat Eidolon helvum
Authors: Baker Kate S. , Todd Shawn , Marsh Glenn A. , Crameri Gary , Barr Jennifer , Kamins Alexandra O. , Peel Alison J. , Yu Meng , Hayman David T. S. , Nadjm Behzad , Mtove George , Amos Benjamin , Reyburn Hugh , Nyarko Edward , Suu-Ire Richard , Murcia Pablo R. , Cunningham Andrew A. , Wood James L. N. , Wang Lin-Fa 
Published: November 2012

ABSTRACT

Bats carry a variety of paramyxoviruses that impact human and domestic animal health when spillover occurs. Recent studies have shown a great diversity of paramyxoviruses in an urban-roosting population of straw-colored fruit bats in Ghana. Here, we investigate this further through virus isolation and describe two novel rubulaviruses: Achimota virus 1 (AchPV1) and Achimota virus 2 (AchPV2). The viruses form a phylogenetic cluster with each other and other bat-derived rubulaviruses, such as Tuhoko viruses, Menangle virus, and Tioman virus. We developed AchPV1- and AchPV2-specific serological assays and found evidence of infection with both viruses in
Eidolon helvum
across sub-Saharan Africa and on islands in the Gulf of Guinea. Longitudinal sampling of
E. helvum
indicates virus persistence within fruit bat populations and suggests spread of AchPVs via horizontal transmission. We also detected possible serological evidence of human infection with AchPV2 in Ghana and Tanzania. It is likely that clinically significant zoonotic spillover of chiropteran paramyxoviruses could be missed throughout much of Africa where health surveillance and diagnostics are poor and comorbidities, such as infection with HIV or
Plasmodium
sp., are common.
Loss of a Tyrosine-Dependent Trafficking Motif in the Simian Immunodeficiency Virus Envelope Cytoplasmic Tail Spares Mucosal CD4 Cells but Does Not Prevent Disease Progression
Authors: Breed Matthew W. , Jordan Andrea P. O. , Aye Pyone P. , Lichtveld Cornelis F. , Midkiff Cecily C. , Schiro Faith R. , Haggarty Beth S. , Sugimoto Chie , Alvarez Xavier , Sandler Netanya G. , Douek Daniel C. , Kuroda Marcelo J. , Pahar Bapi , Piatak Michael , Lifson Jeffrey D. , Keele Brandon F. , Hoxie James A. , Lackner Andrew A. 
Published: November 2012

ABSTRACTA hallmark of pathogenic simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) infections is the rapid and near-complete depletion of mucosal CD4+T lymphocytes from the gastrointestinal tract. Loss of these cells and disruption of epithelial barrier function are associated with microbial translocation, which has been proposed to drive chronic systemic immune activation and disease progression. Here, we evaluate in rhesus macaques a novel attenuated variant of pathogenic SIVmac239, termed ΔGY, which contains a deletion of a Tyr and a proximal Gly from a highly conserved YxxØ trafficking motif in the envelope cytoplasmic tail. Compared to SIVmac239, ΔGY established a comparable acute peak of viremia but only transiently infected lamina propria and caused little or no acute depletion of mucosal CD4+T cells and no detectable microbial translocation. Nonetheless, these animals developed T-cell activation and declining peripheral blood CD4+T cells and ultimately progressed with clinical or pathological features of AIDS. ΔGY-infected animals also showed no infection of macrophages or central nervous system tissues even in late-stage disease. Although the ΔGY mutation persisted, novel mutations evolved, including the formation of new YxxØ motifs in two of four animals. These findings indicate that disruption of this trafficking motif by the ΔGY mutation leads to a striking alteration in anatomic distribution of virus with sparing of lamina propria and a lack of microbial translocation. Because these animals exhibited wild-type levels of acute viremia and immune activation, our findings indicate that these pathological events are dissociable and that immune activation unrelated to gut damage can be sufficient for the development of AIDS.
Role of Transmembrane Domains of Hepatitis B Virus Small Surface Proteins in Subviral-Particle Biogenesis
Authors: Siegler Vera D. , Bruss Volker 
Published: November 2012

ABSTRACT
The hepatitis B virus (HBV) surface proteins not only are incorporated into the virion envelope but in addition form subviral particles (SVP) consisting solely of surface proteins and lipids. Heterologous expression of the small HBV envelope protein S produces secreted spherical SVP 20 nm in diameter, with approximately 100 S molecules per particle. The pathway leading from the initial S translation product as a multispanning transmembrane protein to the final SVP is largely unknown. To investigate the role of the four transmembrane domains (TM) of S in this process, we introduced mutations in these regions and characterized their effects on SVP formation in transfected Huh7 cells. We found that the insertion of one amino acid in the center of the α-helix of TM1 or the exchange of TM1 with a heterologous TM blocked SVP release and SVP formation by coexpressed wild-type S chains in a transdominant negative fashion. Surprisingly, this effect was partially neutralized when the mutations were expressed in the background of the HBV surface protein M, suggesting that mutations in TM1 could partially be complemented by the pre-S2 domain. The exchange of TM2 with heterologous TMs that form α-helices of the same lengths was also incompatible with SVP formation. However, these mutants no longer blocked SVP formation by coexpressed wild-type S. We conclude that TM2 is essential for the stable assembly of S chains by establishing intramembrane interactions.
Epstein-Barr Virus LMP1 Modulates Lipid Raft Microdomains and the Vimentin Cytoskeleton for Signal Transduction and Transformation
Authors: Meckes David G. , Menaker Nathan F. , Raab-Traub Nancy 
Published: November 2012

ABSTRACT
The Epstein-Barr virus (EBV) is an important human pathogen that is associated with multiple cancers. The major oncoprotein of the virus, latent membrane protein 1 (LMP1), is essential for EBV B-cell immortalization and is sufficient to transform rodent fibroblasts. This viral transmembrane protein activates multiple cellular signaling pathways by engaging critical effector molecules and thus acts as a ligand-independent growth factor receptor. LMP1 is thought to signal from internal lipid raft containing membranes; however, the mechanisms through which these events occur remain largely unknown. Lipid rafts are microdomains within membranes that are rich in cholesterol and sphingolipids. Lipid rafts act as organization centers for biological processes, including signal transduction, protein trafficking, and pathogen entry and egress. In this study, the recruitment of key signaling components to lipid raft microdomains by LMP1 was analyzed. LMP1 increased the localization of phosphatidylinositol 3-kinase (PI3K) and its activated downstream target, Akt, to lipid rafts. In addition, mass spectrometry analyses identified elevated vimentin in rafts isolated from LMP1 expressing NPC cells. Disruption of lipid rafts through cholesterol depletion inhibited PI3K localization to membranes and decreased both Akt and ERK activation. Reduction of vimentin levels or disruption of its organization also decreased LMP1-mediated Akt and ERK activation and inhibited transformation of rodent fibroblasts. These findings indicate that LMP1 reorganizes membrane and cytoskeleton microdomains to modulate signal transduction.
A Bovine Herpesvirus 1 Protein Expressed in Latently Infected Neurons (ORF2) Promotes Neurite Sprouting in the Presence of Activated Notch1 or Notch3
Authors: Sinani Devis , Frizzo da Silva Leticia , Jones Clinton 
Published: November 2012

ABSTRACT

Bovine herpesvirus 1 (BHV-1) infection induces clinical symptoms in the upper respiratory tract, inhibits immune responses, and can lead to life-threatening secondary bacterial infections. Following acute infection, BHV-1 establishes latency in sensory neurons within trigeminal ganglia, but stress can induce reactivation from latency. The latency-related (LR) RNA is the only viral transcript abundantly expressed in latently infected sensory neurons. An LR mutant virus with stop codons at the amino terminus of the first open reading frame (ORF) in the LR gene (ORF2) is not reactivated from latency, in part because it induces higher levels of apoptosis in infected neurons. ORF2 inhibits apoptosis in transiently transfected cells, suggesting that it plays a crucial role in the latency-reactivation cycle. ORF2 also interacts with Notch1 or Notch3 and inhibits its ability to
trans
activate certain viral promoters. Notch3 RNA and protein levels are increased during reactivation from latency, suggesting that Notch may promote reactivation. Activated Notch signaling interferes with neuronal differentiation, in part because neurite and axon generation is blocked. In this study, we demonstrated that ORF2 promotes neurite formation in mouse neuroblastoma cells overexpressing Notch1 or Notch3. ORF2 also interfered with Notch-mediated
trans
activation of the promoter that regulates the expression of Hairy Enhancer of Split 5, an inhibitor of neurite formation. Additional studies provided evidence that ORF2 promotes the degradation of Notch3, but not that of Notch1, in a proteasome-dependent manner. In summary, these studies suggest that ORF2 promotes a mature neuronal phenotype that enhances the survival of infected neurons and consequently increases the pool of latently infected neurons.
Amantadine and the Place of Acupuncture in the Treatment of Fatigue in Patients with Multiple Sclerosis: An Observational Study
Authors: Foroughipour Mohsen , Bahrami Taghanaki Hamid Reza , Saeidi Morteza , Khazaei Mojtaba , Sasannezhad Payam , Shoeibi Ali 
Published: November 2012

Background Fatigue is a common symptom in patients with multiple sclerosis (MS). It has significant negative effects on the quality of life of patients with the condition. There are few therapeutic modalities for fatigue, which are also usually not sufficiently effective. The aim of this study was to evaluate the efficacy of acupuncture on this common symptom of patients with MS. Methods In this before-and-after clinical trial, 40 patients with definite diagnoses of MS, according to the ‘McDonald’ criteria, were studied. Patients who had Expanded Disability Status Scale (EDSS) scores greater than 4, or who had another disease that could be potentially responsible for their fatigue, were excluded from the study. In all, 20 patients with fatigue refractory to amantadine underwent 12 sessions of acupuncture. Fatigue was scored according to the Fatigue Severity Scale (FSS). Results A total of 15 (37.5%) patients with MS with fatigue responded to amantadine. The mean FSS score reduction after 2 months of treatment was 8±4, which was statistically significant (p<0.001). Of the 20 patients who were resistant to amantadine, 5 (25%) responded to acupuncture combined with amantadine treatment. The FSS scores of the 20 patients who were refractory were significantly reduced after this treatment (mean: 13±6, p<0.001). Conclusions Acupuncture appears to be associated with benefits for a proportion of patients with fatigue who are resistant to conventional drugs such as amantadine, and this finding justifies further research.
De Novo Design of a Tumor-Penetrating Peptide
Authors: Alberici Luca , Roth Lise , Sugahara Kazuki N. , Agemy Lilach , Kotamraju Venkata R. , Teesalu Tambet , Bordignon Claudio , Traversari Catia , Rizzardi Gian-Paolo , Ruoslahti Erkki 
Published: November 2012

Abstract
Poor penetration of antitumor drugs into the extravascular tumor tissue is often a major factor limiting the efficacy of cancer treatments. Our group has recently described a strategy to enhance tumor penetration of chemotherapeutic drugs through use of iRGD peptide (CRGDK/RGPDC). This peptide comprises two sequence motifs: RGD, which binds to αvβ3/5 integrins on tumor endothelia and tumor cells, and a cryptic CendR motif (R/KXXR/K-OH). Once integrin binding has brought iRGD to the tumor, the peptide is proteolytically cleaved to expose the cryptic CendR motif. The truncated peptide loses affinity for its primary receptor and binds to neuropilin-1, activating a tissue penetration pathway that delivers the peptide along with attached or co-administered payload into the tumor mass. Here, we describe the design of a new tumor-penetrating peptide based on the current knowledge of homing sequences and internalizing receptors. The tumor-homing motif in the new peptide is the NGR sequence, which binds to endothelial CD13. The NGR sequence was placed in the context of a CendR motif (RNGR), and this sequence was embedded in the iRGD framework. The resulting peptide (CRNGRGPDC, iNGR) homed to tumor vessels and penetrated into tumor tissue more effectively than the standard NGR peptide. iNGR induced greater tumor penetration of coupled nanoparticles and co-administered compounds than NGR. Doxorubicin given together with iNGR was significantly more efficacious than the drug alone. These results show that a tumor-specific, tissue-penetrating peptide can be constructed from known sequence elements. This principle may be useful in designing tissue-penetrating peptides for other diseases. Cancer Res; 73(2); 804–12. ©2012 AACR.
A Candidate Molecular Biomarker Panel for the Detection of Bladder Cancer
Authors: Urquidi Virginia , Goodison Steve , Cai Yunpeng , Sun Yijun , Rosser Charles J. 
Published: November 2012

Abstract
Background: Bladder cancer is among the five most common malignancies worldwide, and due to high rates of recurrence, one of the most prevalent. Improvements in noninvasive urine-based assays to detect bladder cancer would benefit both patients and health care systems. In this study, the goal was to identify urothelial cell transcriptomic signatures associated with bladder cancer.
Methods: Gene expression profiling (Affymetrix U133 Plus 2.0 arrays) was applied to exfoliated urothelia obtained from a cohort of 92 subjects with known bladder disease status. Computational analyses identified candidate biomarkers of bladder cancer and an optimal predictive model was derived. Selected targets from the profiling analyses were monitored in an independent cohort of 81 subjects using quantitative real-time PCR (RT-PCR).
Results: Transcriptome profiling data analysis identified 52 genes associated with bladder cancer (P ≤ 0.001) and gene models that optimally predicted class label were derived. RT-PCR analysis of 48 selected targets in an independent cohort identified a 14-gene diagnostic signature that predicted the presence of bladder cancer with high accuracy.
Conclusions: Exfoliated urothelia sampling provides a robust analyte for the evaluation of patients with suspected bladder cancer. The refinement and validation of the multigene urothelial cell signatures identified in this preliminary study may lead to accurate, noninvasive assays for the detection of bladder cancer.
Impact: The development of an accurate, noninvasive bladder cancer detection assay would benefit both the patient and health care systems through better detection, monitoring, and control of disease. Cancer Epidemiol Biomarkers Prev; 21(12); 2149–58. ©2012 AACR.
A Randomized Controlled Trial of a Tailored Navigation and a Standard Intervention in Colorectal Cancer Screening
Authors: Myers Ronald E. , Bittner-Fagan Heather , Daskalakis Constantine , Sifri Randa , Vernon Sally W. , Cocroft James , DiCarlo Melissa , Katurakes Nora , Andrel Jocelyn 
Published: November 2012

Abstract
Background: This randomized, controlled trial assessed the impact of a tailored navigation intervention versus a standard mailed intervention on colorectal cancer screening adherence and screening decision stage (SDS).
Methods: Primary care patients (n = 945) were surveyed and randomized to a Tailored Navigation Intervention (TNI) Group (n = 312), Standard Intervention (SI) Group (n = 316), or usual care Control Group (n = 317). TNI Group participants were sent colonoscopy instructions and/or stool blood tests according to reported test preference, and received a navigation call. The SI Group was sent both colonoscopy instructions and stool blood tests. Multivariable analyses assessed intervention impact on adherence and change in SDS at 6 months.
Results: The primary outcome, screening adherence (TNI Group: 38%, SI Group: 33%, Control Group: 12%), was higher for intervention recipients than controls (P = 0.001 and P = 0.001, respectively), but the two intervention groups did not differ significantly (P = 0.201). Positive SDS change (TNI Group: +45%, SI Group: +37%, and Control Group: +23%) was significantly greater among intervention recipients than controls (P = 0.001 and P = 0.001, respectively), and the intervention group difference approached significance (P = 0.053). Secondary analyses indicate that tailored navigation boosted preferred test use, and suggest that intervention impact on adherence and SDS was attenuated by limited access to screening options.
Conclusions: Both interventions had significant, positive effects on outcomes compared with usual care. TNI versus SI impact had a modest positive impact on adherence and a pronounced effect on SDS.
Impact: Mailed screening tests can boost adherence. Research is needed to determine how preference, access, and navigation affect screening outcomes. Cancer Epidemiol Biomarkers Prev; 22(1); 109–17. ©2012 AACR.