bluuebunny/crossref_metadata_2025_split huggingface dataset:
Equine deep stromal abscesses (51 cases – 2004–2009) – Part 2: the histopathology and immunohistochemical aspect with attention to the histopathologic diagnosis, vascular response, and infectious agents
Authors: de Linde Henriksen Michala , Andersen Pia Haubro , Mietelka Kristy , Farina Lisa , Thomsen Preben D. , Plummer Caryn E , Mangan Brendan G , Heegaard Steffen , Coleman James K , Toft Nils , Brooks Dennis E. 
Published: October 2013

AbstractPurposeTo investigate histopathologic and immunohistochemical aspects of equine deep stromal abscesses (DSA) with a focus on the histopathologic diagnosis, presumptive etiology, and the immunohistochemical expression of three angiogenesis‐related factors: vascular endothelial growth factor‐A(VEGF‐A), pigment epithelium‐derived factor (PEDF), and interleukin‐1 receptor antagonist (IL‐1ra).Sample populationParaffin‐embedded biopsy samples from 51DSA. The biopsies were collected from full‐thickness penetrating keratoplasty or split‐thickness lamellar keratoplasty surgeries at theUniversity ofFlorida VeterinaryMedicalCenter in the period from 2004 to 2009.ProcedureThe histopathologic and immunohistochemical findings were tested for association between each other. Prevalence calculation and test for association with qualitative data analysis was used for data evaluation.ResultsFungal hyphae were found histologically in 47.1% (n = 24) of theDSAcases. Histopathologically, most fungalDSAshowed suppurative keratitis (n = 34; 66.7%) and little to no stromal vascularization infiltrating the abscess (negative association,P = 0.005). All three angiogenesis‐related factors were expressed to some degree inDSAtissue. A negative association betweenVEGF‐A andPEDFwhen compared to the presence of fungal hyphae (P < 0.001,P = 0.023) indicated that cases positive for these two factors will most probably not have fungal hyphae present.ConclusionAbnormally decreasedVEGF‐A expression is suggested as the reason for the slow vascularization and delayed resolution of fungalDSA, whereasPEDFandIL‐ra did not seem to have any influence on the vascularization process. Clinical and histopathologic characteristics ofDSAmake it possible to suggest an etiology for an equineDSAwith an unknown etiology.
Equine deep stromal abscesses (51 cases – 2004–2009) –Part 1: the clinical aspects with attention to the duration of the corneal disease, treatment history, clinical appearance, and microbiology results
Authors: de Linde Henriksen Michala , Andersen Pia H. , Thomsen Preben D. , Plummer Caryn E. , Mangan Brendan , Heegaard Steffen , Toft Nils , Brooks Dennis E. 
Published: October 2013

AbstractObjectiveTo study the equine deep stromal abscesses (DSA) with focus on the duration of the corneal disease, medical treatment, season of presentation, clinical appearance, and the degree of corneal vascularization.Material and MethodsEquineDSAdiagnosed, biopsied, and surgically treated at theUniversity ofFloridaVeterinaryMedicalCenter (UFVMC) from 2004 to 2009 were identified. The medical record, clinical photographic images, and microbiology results for each case were evaluated. Frequency and prevalence calculation as well as qualitative data analysis was performed for clinical and microbiological data.ResultsFifty‐one equineDSAwere included in the study. Spring (March,April,May; 33.4%) and winter (December,January,February; 31.4%) were the most common seasons forDSApresentation. The 51 cases were divided into four categories of focal opacity from their clinical appearance: focal yellow (45.2%), focal white (23.5%), diffuse yellow/white (23.5%), and focal pink (7.8%). 5.9% of theDSA(n = 3) were culture positive for fungal growth, whereas 17.6% were positive for bacterial growth (n = 9). No association between short‐/long‐term systemically administeredNSAIDtreatment and the corneal vascular response to the corneal lesion could be appreciated.ConclusionEquineDSAmost often present in the spring and winter in the subtropical environment of the state ofFlorida (USA). The clinical appearance may have a connection with the etiology and pathogenesis of the equineDSA. No connection between short‐ or long‐term systemically administeredNSAIDand the degree of corneal vascularization of theDSAwas noted.
Molecular Analysis and Clinical Significance of Lactobacillus spp. Recovered from Clinical Specimens Presumptively Associated with Disease
Authors: Martinez Raquel M. , Hulten Kristina G. , Bui Uyen , Clarridge Jill E. 
Published: October 2013

ABSTRACT

Lactobacillus
spp. are part of the normal human flora and are generally assumed to be nonpathogenic. We determined the genotypic identification of >100
Lactobacillus
isolates from clinical specimens in the context of presumed pathogenic potential (e.g., recovered as the single/predominant isolate from a sterile site or at ≥10
5
CFU/ml from urine). This study assessed the clinical significance and the frequency of occurrence of each
Lactobacillus
sp. We identified 16 species of
Lactobacillus
by 16S rRNA gene sequence analysis, 10 of which could not be associated with disease. While
Lactobacillus rhamnosus
,
Lactobacillus gasseri
, and
Lactobacillus paracasei
were associated with infections,
L. gasseri
was also a common colonizing/contaminating species.
Lactobacillus casei
,
Lactobacillus johnsonii
, and
Lactobacillus delbrueckii
were associated with at least one infection. Species commonly used in probiotic products (e.g.,
L. rhamnosus
and
L. casei
) were identical, by 16S rRNA gene sequencing, to our isolates associated with disease. Human isolates of
Lactobacillus
spp. have differing site associations and levels of clinical significance. Knowing the niche and pathogenic potential of each
Lactobacillus
sp. can be of importance to both clinical microbiology and the food and probiotic supplement industry.
Molecular Characterization of a Catalase-Negative Methicillin-Susceptible Staphylococcus aureus subsp. aureus Strain Collected from a Patient with Cutaneous Abscess
Authors: Ellis Michael W. , Johnson Ryan C. , Crawford Katrina , Lanier Jeffrey B. , Merrell D. Scott 
Published: October 2013

ABSTRACT

We describe a cutaneous abscess caused by catalase-negative methicillin-susceptible
Staphylococcus aureus
subsp.
aureus
in a patient who was concomitantly colonized with virulent USA300 methicillin-resistant
S. aureus
(MRSA). Sequencing of the
katA
gene demonstrated a thymine insertion leading to a frameshift mutation and premature truncation of catalase to 21 amino acids.
Evaluation of the BioFire FilmArray Respiratory Panel and the GenMark eSensor Respiratory Viral Panel on Lower Respiratory Tract Specimens
Authors: Ruggiero Phyllis , McMillen Tracy , Tang Yi-Wei , Babady N. Esther 
Published: October 2013

ABSTRACTWe evaluated the performance characteristics of the FilmArray respiratory panel and the eSensor respiratory viral panel on clinical and spiked lower respiratory tract specimens (LRTS). The overall agreement between the two methods was 89.5% (51/57). The lower limit of detection of both assays for all targets in LRTS was comparable to that for nasopharyngeal swab specimens.
Rotavirus NSP1 Protein Inhibits Interferon-Mediated STAT1 Activation
Authors: Sen Adrish , Rott Lusijah , Phan Nguyen , Mukherjee Gourab , Greenberg Harry B. 
Published: October 2013

ABSTRACTRotavirus (RV) replicates efficiently in intestinal epithelial cells (IECs)in vivodespite the activation of a local host interferon (IFN) response. Previously, we demonstrated that homologous RV efficiently inhibits IFN induction in single infected and bystander villous IECsin vivo. Paradoxically, RV also induces significant type I IFN expression in the intestinal hematopoietic cell compartment in a relatively replication-independent manner. This suggests that RV replication and spread in IECs must occur despite exogenous stimulation of the STAT1-mediated IFN signaling pathway. Here we report that RV inhibits IFN-mediated STAT1 tyrosine 701 phosphorylation in human IECsin vitroand identify RV NSP1 as a direct inhibitor of the pathway. Infection of human HT29 IECs with simian (RRV) or porcine (SB1A or OSU) RV strains, which inhibit IFN induction by targeting either IFN regulatory factor 3 (IRF3) or NF-κB, respectively, resulted in similar regulation of IFN secretion. By flow cytometric analysis at early times during infection, neither RRV nor SB1A effectively inhibited the activation of Y701-STAT1 in response to exogenously added IFN. However, at later times during infection, both RV strains efficiently inhibited IFN-mediated STAT1 activation within virus-infected cells, indicating that RV encodes inhibitors of IFN signaling targeting STAT1 phosphorylation. Expression of RV NSP1 in the absence of other viral proteins resulted in blockage of exogenous IFN-mediated STAT1 phosphorylation, and this function was conserved in NSP1 from simian, bovine, and murine RV strains. Analysis of NSP1 determinants responsible for the inhibition of IFN induction and signaling pathways revealed that these determinants are encoded on discrete domains of NSP1. Finally, we observed that at later times during infection with SB1A, there was almost complete inhibition of IFN-mediated Y701-STAT1 in bystander cells staining negative for viral antigen. This property segregated with the NSP1 gene and was observed in a simian SA11 monoreassortant that encoded porcine OSU NSP1 but not in wild-type SA11 or a reassortant encoding simian RRV NSP1.
The Selection of Low Envelope Glycoprotein Reactivity to Soluble CD4 and Cold during Simian-Human Immunodeficiency Virus Infection of Rhesus Macaques
Authors: McGee Kathleen , Haim Hillel , Korioth-Schmitz Birgit , Espy Nicole , Javanbakht Hassan , Letvin Norman , Sodroski Joseph 
Published: October 2013

ABSTRACTEnvelope glycoprotein (Env) reactivity (ER) describes the propensity of human immunodeficiency virus type 1 (HIV-1) Env to change conformation from the metastable unliganded state in response to the binding of ligands (antibodies and soluble CD4 [sCD4]) or incubation in the cold. To investigate Env properties that favorin vivopersistence, we inoculated rhesus macaques with three closely related CCR5-tropic simian-human immunodeficiency viruses (SHIVs) that differ in ER to cold (ERcold) and ER to sCD4 (ERsCD4); these SHIVs were neutralized by antibodies equivalently and thus were similar in ERantibody. All three SHIVs achieved high levels of acute viremia in the monkeys without alteration of their Env sequences, indicating that neither ERcoldnor ERsCD4significantly influences the establishment of infection. Between 14 and 100 days following infection, viruses with high ERcoldand ERsCD4were counterselected. Remarkably, the virus variant with low ERcoldand low ERsCD4did not elicit a neutralizing antibody response against the infecting virus, despite the generation of high levels of anti-Env antibodies in the infected monkeys. All viruses that achieved persistent viremia escaped from any autologous neutralizing antibodies and exhibited low ERcoldand low ERsCD4. One set of gp120 changes determined the decrease in ERcoldand ERsCD4, and a different set of gp120 changes determined resistance to autologous neutralizing antibodies. Each set of changes contributed to a reduction in Env-mediated entry. During infection of monkeys, any Env replication fitness costs associated with decreases in ERcoldand ERsCD4may be offset by minimizing the elicitation of autologous neutralizing antibodies.
Functional Characterization of Bovine Viral Diarrhea Virus Nonstructural Protein 5A by Reverse Genetic Analysis and Live Cell Imaging
Authors: Isken Olaf , Langerwisch Ulrike , Schönherr Robert , Lamp Benjamin , Schröder Kristin , Duden Rainer , Rümenapf Tillmann H. , Tautz Norbert 
Published: October 2013

ABSTRACTNonstructural protein 5A (NS5A) of bovine viral diarrhea virus (BVDV) is a hydrophilic phosphoprotein with RNA binding activity and a critical component of the viral replicase.In silicoanalysis suggests that NS5A encompasses three domains interconnected by two low-complexity sequences (LCSs). While domain I harbors two functional determinants, an N-terminal amphipathic helix important for membrane association, and a Zn-binding site essential for RNA replication, the structure and function of the C-terminal half of NS5A are still ill defined. In this study, we introduced a panel of 10 amino acid deletions covering the C-terminal half of NS5A. In the context of a highly efficient monocistronic replicon, deletions in LCS I and the N-terminal part of domain II, as well as in domain III, were tolerated with regard to RNA replication. When introduced into a bicistronic replicon, only deletions in LCS I and the N-terminal part of domain II were tolerated. In the context of the viral full-length genome, these mutations allowed residual virion morphogenesis. Based on these data, a functional monocistronic BVDV replicon coding for an NS5A variant with an insertion of the fluorescent protein mCherry was constructed. Live cell imaging demonstrated that a fraction of NS5A-mCherry localizes to the surface of lipid droplets. Taken together, this study provides novel insights into the functions of BVDV NS5A. Moreover, we established the first pestiviral replicon expressing fluorescent NS5A-mCherry to directly visualize functional viral replication complexes by live cell imaging.
Crystal Structures of Beta- and Gammaretrovirus Fusion Proteins Reveal a Role for Electrostatic Stapling in Viral Entry
Authors: Aydin Halil , Cook Jonathan D. , Lee Jeffrey E. 
Published: October 2013

ABSTRACT
Membrane fusion is a key step in the life cycle of all envelope viruses, but this process is energetically unfavorable; the transmembrane fusion subunit (TM) of the virion-attached glycoprotein actively catalyzes the membrane merger process. Retroviral glycoproteins are the prototypical system to study pH-independent viral entry. In this study, we determined crystal structures of extramembrane regions of the TMs from Mason-Pfizer monkey virus (MPMV) and xenotropic murine leukemia virus-related virus (XMRV) at 1.7-Å and 2.2-Å resolution, respectively. The structures are comprised of a trimer of hairpins that is characteristic of class I viral fusion proteins and now completes a structural library of retroviral fusion proteins. Our results allowed us to identify a series of intra- and interchain electrostatic interactions in the heptad repeat and chain reversal regions. Mutagenesis reveals that charge-neutralizing salt bridge mutations significantly destabilize the postfusion six-helix bundle and abrogate retroviral infection, demonstrating that electrostatic stapling of the fusion subunit is essential for viral entry. Our data indicate that salt bridges are a major stabilizing force on the MPMV and XMRV retroviral TMs and likely provide the key energetics for viral and host membrane fusion.
Murine Cytomegalovirus Protein pM92 Is a Conserved Regulator of Viral Late Gene Expression
Authors: Chapa Travis J. , Perng Yi-Cheih , French Anthony R. , Yu Dong 
Published: October 2013

ABSTRACT

In this study, we report that murine cytomegalovirus (MCMV) protein pM92 regulates viral late gene expression during virus infection. Previously, we have shown that MCMV protein pM79 and its human cytomegalovirus (HCMV) homologue pUL79 are required for late viral gene transcription. Identification of additional factors involved is critical to dissecting the mechanism of this regulation. We show here that pM92 accumulated abundantly at late times of infection in a DNA synthesis-dependent manner and localized to nuclear viral replication compartments. To investigate the role of pM92, we constructed a recombinant virus SM
in
92, in which pM92 expression was disrupted by an insertional/frameshift mutation. During infection, SM
in
92 accumulated representative viral immediate-early gene products, early gene products, and viral DNA sufficiently but had severe reduction in the accumulation of late gene products and was thus unable to produce infectious progeny. Coimmunoprecipitation and mass spectrometry analysis revealed an interaction between pM92 and pM79, as well as between their HCMV homologues pUL92 and pUL79. Importantly, we showed that the growth defect of pUL92-deficient HCMV could be rescued in
trans
by pM92. This study indicates that pM92 is an additional viral regulator of late gene expression, that these regulators (represented by pM92 and pM79) may need to complex with each other for their activity, and that pM92 and pUL92 share a conserved function in CMV infection. pM92 represents a potential new target for therapeutic intervention in CMV disease, and a gateway into studying a largely uncharted viral process that is critical to the viral life cycle.
Association of inorganic arsenic exposure with type 2 diabetes mellitus: a meta-analysis
Authors: Wang Weijing , Xie Zhutian , Lin Yan , Zhang Dongfeng 
Published: October 2013

BackgroundThe association of long-term effects of inorganic arsenic (iAs) exposure with type 2 diabetes mellitus (T2DM) risk remains controversial.MethodsA literature search was performed in PubMed, China National Knowledge Infrastructure and Web of Knowledge for relevant available articles published in English or Chinese from 1 January 1990 to 5 June 2013. Case-control, cohort or cross-sectional studies evaluating iAs and T2DM were included. The DerSimonian and Laird random effect model was adopted as the pooling method. Dose-response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression.ResultsOf the 569 articles identified through searching databases, 17 published articles with 2 243 745 participants for iAs in drinking water and 21 083 participants for total arsenic (tAs) in urine were included for this meta-analysis. The pooled relative risk with 95% CI of T2DM for the highest versus lowest category of iAs exposure level in drinking water was 1.75 (1.20 to 2.54). After removing three studies that had a strong effect on heterogeneity, the pooled relative risk was 1.23 (1.12 to 1.36). Dose–response analysis suggested T2DM risk increased by 13% (1.13 (1.00 to 1.27)) for every 100 µg/L increment of iAs in drinking water. Significant association of T2DM risk with tAs in urine was also found 1.28 (1.14 to 1.44).ConclusionsThis meta-analysis indicates that long-term iAs exposure might be positively associated with T2DM risk.
Phase I Trial of Preoperative Chemoradiation plus Sorafenib for High-Risk Extremity Soft Tissue Sarcomas with Dynamic Contrast-Enhanced MRI Correlates
Authors: Meyer Janelle M. , Perlewitz Kelly S. , Hayden James B. , Doung Yee-Cheen , Hung Arthur Y. , Vetto John T. , Pommier Rodney F. , Mansoor Atiya , Beckett Brooke R. , Tudorica Alina , Mori Motomi , Holtorf Megan L. , Afzal Aneela , Woodward William J. , Rodler Eve T. , Jones Robin L. , Huang Wei , Ryan Christopher W. 
Published: October 2013

Abstract
Purpose: We conducted a phase I trial of the addition of sorafenib to a chemoradiotherapy regimen in patients with high-risk (intermediate/high grade, &gt;5 cm) extremity soft tissue sarcoma undergoing limb salvage surgery. We conducted a correlative study of quantitative dynamic contrast-enhanced MRI (DCE-MRI) to assess response to treatment.
Experimental Design: Patients were treated at increasing dose levels of sorafenib (200 mg daily, 400 mg daily, 400 mg twice daily) initiated 14 days before three preoperative and three postoperative cycles of epirubicin/ifosfamide. Radiation (28 Gy) was administered during cycle 2 with epirubicin omitted. The primary objective was to determine the maximum tolerated dose (MTD) of sorafenib. DCE-MRI was conducted at baseline, after 2 weeks of sorafenib, and before surgery. The imaging data were subjected to quantitative pharmacokinetic analyses.
Results: Eighteen subjects were enrolled, of which 16 were evaluable. The MTD of sorafenib was 400 mg daily. Common grade 3–4 adverse events included neutropenia (94%), hypophosphatemia (75%), anemia (69%), thrombocytopenia (50%), and neutropenic fever/infection (50%). Of note, 38% developed wound complications requiring surgical intervention. The rate of ≥95% histopathologic tumor necrosis was 44%. Changes in DCE-MRI biomarker ΔKtrans after 2 weeks of sorafenib correlated with histologic response (R2 = 0.67, P = 0.012) at surgery.
Conclusion: The addition of sorafenib to preoperative chemoradiotherapy is feasible and warrants further investigation in a larger trial. DCE-MRI detected changes in tumor perfusion after 2 weeks of sorafenib and may be a minimally invasive tool for rapid assessment of drug effect in soft tissue sarcoma. Clin Cancer Res; 19(24); 6902–11. ©2013 AACR.
Discrete Molecular Classes of Ovarian Cancer Suggestive of Unique Mechanisms of Transformation and Metastases
Authors: Gardi Nilesh L. , Deshpande Tejaswini U. , Kamble Swapnil C. , Budhe Sagar R. , Bapat Sharmila A. 
Published: October 2013

Abstract
Purpose: Tumor heterogeneity and subsistence of high-grade serous ovarian adenocarcinoma (HGSC) classes can be speculated from clinical incidences suggesting passive tumor dissemination versus active invasion and metastases.
Experimental Design: We explored this theme toward tumor classification through two approaches of gene expression pattern clustering: (i) derivation of a core set of metastases-associated genes and (ii) resolution of independent weighted correlation networks. Further identification of appropriate cell and xenograft models was carried out for resolution of class-specific biologic functions.
Results: Both clustering approaches achieved resolution of three distinct tumor classes, two of which validated in other datasets. Networks of enriched gene modules defined biologic functions of quiescence, cell division-differentiation-lineage commitment, immune evasion, and cross-talk with niche factors. Although deviant from normal homeostatic mechanisms, these class-specific profiles are not totally random. Preliminary validation of these suggests that Class 1 tumors survive, metastasize in an epithelial–mesenchymal transition (EMT)-independent manner, and are associated with a p53 signature, aberrant differentiation, DNA damage, and genetic instability. These features supported by association of cell-specific markers, including PAX8, PEG3, and TCF21, led to the speculation of their origin being the fimbrial fallopian tube epithelium. On the other hand, Class 2 tumors activate extracellular matrix–EMT–driven invasion programs (Slug, SPARC, FN1, THBS2 expression), IFN signaling, and immune evasion, which are prospectively suggestive of ovarian surface epithelium associated wound healing mechanisms. Further validation of these etiologies could define a new therapeutic framework for disease management. Clin Cancer Res; 20(1); 87–99. ©2013 AACR.