bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic characterization and genotyping of hepatitis B virus (HBV) isolates from donors with an occult HBV infection
Authors: Chamni N. , Louisirirotchanakul S. , Oota S. , Sakuldamrongpanish T. , Saldanha J. , Chongkolwatana V. , Phikulsod S. 
Published: July 2014

Background and ObjectivesScreening of Thai blood donors has resulted in the detection of donors with an occult HBV infection (OBI), where HBsAg is undetectable, but hepatitis B virus (HBV) DNA is present in serum in low concentrations. This study was designed to determine whether the occurrence of OBI in donors was linked to the HBV genotype and possibly to mutations in the surface (S) and core (C) gene regions.Materials and MethodsMutations in the S and C gene regions in 48 Thai donors with OBI were mapped by sequencing. Genotyping was determined with the INNO‐LiPA test and by phylogenetic analysis of sequences from the S and C genes.ResultsThe majority of OBI samples were genotype C (81·3%) with 6·3% of samples being genotype B. In addition, two genotype I isolates were identified. Mutations in the S region (100%) were found especially in loop 1 of the major hydrophilic loop (MHL) at positions I110L, T114S, T126I and S113T, whereas mutations in the C region (65%) were within the basal core promoter region (position A1762T/G1764A) and precore region (position G1896A).ConclusionThe majority of OBI samples were HBV genotype C, although genotype I, which is newly emerging in Thailand, was also detected. The study demonstrated that OBI was probably not associated with a particular HBV genotype or with certain mutations in the S and C gene regions. However, mutations in the C gene region which could potentially impair viral replication and HBsAg production and potentially lead to OBI were identified.
Hyaluronan in wound healing: Rediscovering a major player
Authors: Aya Kessiena L. , Stern Robert 
Published: July 2014

AbstractWound healing involves a series of carefully modulated steps, from initial injury and blood clot to the final reconstituted tissue or scar. A dynamic reciprocity exists throughout between the wound, blood elements, extracellular matrix, and cells that participate in healing. Multiple cytokines and signal transduction pathways regulate these reactions. A major component throughout most of the process is hyaluronan, a straight‐chain carbohydrate extracellular matrix polymer. Hyaluronan occurs in multiple forms, chain length being the only distinguishing characteristic between them. Levels of hyaluronan in its high–molecular‐weight form are prominent in the earliest stages of wound repair. Progressively more fragmented forms occur in a manner not previously appreciated. We outline here steps in the wound healing cascade in which hyaluronan participates, as well as providing a review of its metabolism. Although described by necessity in a series of quantum steps, the healing process is constituted by a smooth continuum of overlapping reactions. The prevalence of hyaluronan in the wound (initially termed “hexosamine‐containing mucopolysaccharide”), particularly in its early stages, was pointed out over half a century ago by the Harvard surgeon J. Engelbert Dunphy. It appears we are now returning to where we started.
Stable maps and stable quotients
Authors: Manolache Cristina 
Published: July 2014

AbstractWe analyze the relationship between two compactifications of the moduli space of maps from curves to a Grassmannian: the Kontsevich moduli space of stable maps and the Marian–Oprea–Pandharipande moduli space of stable quotients. We construct a moduli space which dominates both the moduli space of stable maps to a Grassmannian and the moduli space of stable quotients, and equip our moduli space with a virtual fundamental class. We relate the virtual fundamental classes of all three moduli spaces using the virtual push-forward formula. This gives a new proof of a theorem of Marian–Oprea–Pandharipande: that enumerative invariants defined as intersection numbers in the stable quotient moduli space coincide with Gromov–Witten invariants.
Vanishing of negative -theory in positive characteristic
Authors: Kelly Shane 
Published: July 2014

AbstractWe show how a theorem of Gabber on alterations can be used to apply the work of Cisinski, Suslin, Voevodsky, and Weibel to prove that $K_n(X) \otimes \mathbb{Z}[{1}/{p}]= 0$ for$n < {-}\! \dim X$ where $X$ is a quasi-excellent noetherian scheme, $p$ is a prime that is nilpotent on $X$, and $K_n$ is the $K$-theory of Bass–Thomason–Trobaugh. This gives a partial answer to a question of Weibel.
Development of patient‐specific molecular imaging phantoms using a 3D printer
Authors: Gear J. I. , Long C. , Rushforth D. , Chittenden S. J. , Cummings C. , Flux G. D. 
Published: July 2014

Purpose:The aim of the study was to investigate rapid prototyping technology for the production of patient‐specific, cost‐effective liquid fillable phantoms directly from patient CT data.Methods:Liver, spleen, and kidney volumes were segmented from patient CT data. Each organ was converted to a shell and filling holes and leg supports were added using computer aided design software and prepared for printing. Additional fixtures were added to the liver to allow lesion inserts to be fixed within the structure. Phantoms were printed from an ultraviolet curable photopolymer using polyjet technology on an Objet EDEN 500V 3D printer.Results:The final print material is a clear solid acrylic plastic which is watertight, rigid, and sufficiently durable to withstand multiple assembly and scanning protocols. Initial scans of the phantoms have been performed with Tc‐99m SPECT and F‐18 PET/CT.Conclusions:The organ geometry showed good correspondence with anatomical references. The methodology developed can be generally applied to other anatomical or geometrical phantoms for molecular imaging.
Verification of a novel method for tube voltage constancy measurement of orthovoltage x‐ray irradiators
Authors: Wang Chu , Belley Matthew D. , Chao Nelson J. , Dewhirst Mark W. , Yoshizumi Terry 
Published: July 2014

Purpose:For orthovoltage x‐ray irradiators, the tube voltage is one of the most fundamental system parameters as this directly relates to the dosimetry in radiation biology studies; however, to the best of our knowledge, there is no commercial portable quality assurance (QA) tool to directly test the constancy of the tube voltage greater than 160 kV. The purpose of this study is to establish the Beam Quality Index (BQI), a quantity strongly correlated to the tube voltage, as an alternative parameter for the verification of the tube voltage as part of the QA program of orthovoltage x‐ray irradiators.Methods:A multipurpose QA meter and its associated data acquisition software were used to customize the measurement parameters to measure the BQI and collect its time‐plot. BQI measurements were performed at 320 kV with four filtration levels on three orthovoltage x‐ray irradiators of the same model, one of which had been recently energy‐calibrated at the factory.Results:For each of the four filtration levels, the measured BQI values were in good agreement (<5%) between the three irradiators. BQI showed filtration‐specificity, possibly due to the difference in beam quality.Conclusions:The BQI has been verified as a feasible alternative for monitoring the constancy of the tube voltage for orthovoltage irradiators. The time‐plot of BQI offers information on the behavior of beam energy at different phases of the irradiation time line. In addition, this would provide power supply performance characteristics from initial ramp‐up to plateau, and finally, the sharp drop‐off at the end of the exposure.
Organogenesis in a dish: Modeling development and disease using organoid technologies
Authors: Lancaster Madeline A. , Knoblich Juergen A. 
Published: July 2014

The making of bodies part by part
Mention of organoids—organlike structure growing in a Petri dish—might conjure up images of science fiction. However, the generation of organoids is very real, as is the increased understanding of organ form and function that comes from studying them. Lancaster and Knoblich review organoids as structures that include more than one cell type of an organ that exhibit structural and functional features of the natural counterpart. Knowledge of normal organ developmental pathways guides the formation of these structures. Organoids show great promise for modeling human development and disease and for biomedical research and regenerative medicine.

Science
, this issue
10.1126/science.1247125
Commercially Available Complement Component-Depleted Sera Are Unexpectedly Codepleted of Ficolin-2
Authors: Brady Allison M. , Geno K. Aaron , Dalecki Alex G. , Cheng Xiaogang , Nahm Moon H. 
Published: July 2014

ABSTRACTThe ficolins are a family of innate pattern recognition molecules that are known to bind acetylated compounds and activate complement through the association of mannose binding lectin (MBL)/ficolin-associated serine proteases (MASPs). Their importance has more recently become appreciated, as they have been shown to play a role in a variety of disease processes from infection to autoimmunity. While studying ficolin-2-mediated complement deposition onStreptococcus pneumoniae, we found that sera depleted of C1q or other complement components were also codepleted of ficolin-2 but not ficolin-1, ficolin-3, or MBL. MBL present in C1q-depleted sera was able to mediate complement deposition onSaccharomyces cerevisiae, suggesting the presence of MASPs. We found that complement was activated on pneumococci in C1q-depleted serum only after opsonization with exogenous recombinant ficolin-2 (rFicolin-2). Also, no complement deposition was observed in C1q-depleted serum when pneumococci were opsonized with rFicolin-2 mutated at its lysine-57 residue, where MASPs are known to associate. Thus, these depleted sera are a unique tool to study ficolin-2-mediated complement pathways; however, one should be aware that ficolin-2 is absent from complement component-depleted sera.
First Isolate of KPC-2-Producing Klebsiella pneumonaie Sequence Type 23 from the Americas
Authors: Cejas Daniela , Fernández Canigia Liliana , Rincón Cruz Giovanna , Elena Alan X. , Maldonado Ivana , Gutkind Gabriel O. , Radice Marcela A. 
Published: July 2014

ABSTRACT

KPC-2-producing
Klebsiella pneumoniae
isolates mainly correspond to clonal complex 258 (CC258); however, we describe KPC-2-producing
K. pneumoniae
isolates belonging to invasive sequence type 23 (ST23). KPC-2 has scarcely been reported to occur in ST23, and this report describes the first isolation of this pathogen in the Americas. Acquisition of resistant markers in virulent clones could mark an evolutionary step toward the establishment of these clones as major nosocomial pathogens.
Bacteriophage-Based Latex Agglutination Test for Rapid Identification of Staphylococcus aureus
Authors: Idelevich Evgeny A. , Walther Thomas , Molinaro Sonja , Li Xuehua , Xia Guoqing , Wieser Andreas , Peters Georg , Peschel Andreas , Becker Karsten 
Published: July 2014

ABSTRACTRapid diagnosis is essential for the management ofStaphylococcus aureusinfections. A host recognition protein fromS. aureusbacteriophage phiSLT was recombinantly produced and used to coat streptavidin latex beads to develop a latex agglutination test (LAT). The diagnostic accuracy of this bacteriophage-based test was compared with that of a conventional LAT, Pastorex Staph-Plus, by investigating a clinical collection of 86S. aureusisolates and 128 coagulase-negative staphylococci (CoNS) from deep tissue infections. All of the clinicalS. aureusisolates were correctly identified by the bacteriophage-based test. While most of the CoNS were correctly identified as non-S. aureusisolates, 7.9% of the CoNS caused agglutination. Thus, the sensitivity of the bacteriophage-based LAT for identification ofS. aureusamong clinical isolates was 100%, its specificity was 92.1%, its positive predictive value (PPV) was 89.6%, and its negative predictive value (NPV) was 100%. The sensitivity, specificity, PPV, and NPV of the Pastorex LAT for the identification ofS. aureuswere 100%, 99.2%, 98.9%, and 100%, respectively. Among the additionally tested 35S. aureusand 91 non-S. aureusstaphylococcal reference and type strains, 1 isolate was false negative by each system; 13 and 8 isolates were false positive by the bacteriophage-based and Pastorex LATs, respectively. The ability of the phiSLT protein to detectS. aureuswas dependent on the presence of wall teichoic acid (WTA) and corresponded to the production of ribitol phosphate WTA, which is found in mostS. aureusclones but only a small minority of CoNS. Bacteriophage-based LAT identification is a promising strategy for rapid pathogen identification. Finding more specific bacteriophage proteins would increase the specificity of this novel diagnostic approach.
Expression of Porcine Fusion Protein IRF7/3(5D) Efficiently Controls Foot-and-Mouth Disease Virus Replication
Authors: Ramírez-Carvajal Lisbeth , Díaz-San Segundo Fayna , Hickman Danielle , Long Charles R. , Zhu James , Rodríguez Luis L. , de los Santos Teresa 
Published: July 2014

ABSTRACT

Several studies have demonstrated that the delivery of type I, II, or III interferons (IFNs) by inoculation of a replication-defective human adenovirus 5 (Ad5) vector expressing IFNs can effectively control foot-and-mouth disease (FMD) in cattle and swine during experimental infections. However, relatively high doses are required to achieve protection. In this study, we identified the functional properties of a porcine fusion protein, poIRF7/3(5D), as a biotherapeutic and enhancer of IFN activity against FMD virus (FMDV). We showed that poIRF7/3(5D) is a potent inducer of type I IFNs, including alpha IFN (IFN-α), IFN-β, and IFN-ω but not type III IFN (interleukin-28B), without inducing cytotoxicity. Expression of poIRF7/3(5D) significantly and steadily reduced FMDV titers by up to 6 log
10
units in swine and bovine cell lines. Treatment with an IFN receptor inhibitor (B18R) combined with an anti-IFN-α antibody neutralized the antiviral activity in the supernatants of cells transduced with an Ad5 vector expressing poIRF7/3(5D) [Ad5-poIRF7/3(5D)]. However, several transcripts with known antiviral function, including type I IFNs, were still highly upregulated (range of increase, 8-fold to over 500-fold) by poIRF7/3(5D) in the presence of B18R. Furthermore, the sera of mice treated with Ad5-poIRF7/3(5D) showed antiviral activity that was associated with the induction of high levels of IFN-α and resulted in complete protection against FMDV challenge at 6, 24, or 48 h posttreatment. This study highlights for the first time the antiviral potential of Ad5-poIRF7/3(5D)
in vitro
and
in vivo
against FMDV.

IMPORTANCE
FMD remains one of the most devastating diseases that affect livestock worldwide. Effective vaccine formulations are available but are serotype specific and require approximately 7 days before they are able to elicit protective immunity. We have shown that vector-delivered IFN is an option to protect animals against many FMDV serotypes as soon as 24 h and for about 4 days postadministration. Here we demonstrate that delivery of a constitutively active transcription factor that induces the production of endogenous IFNs and potentially other antiviral genes is a viable strategy to protect against FMD.
A Substitution in the Transmembrane Region of the Glycoprotein Leads to an Unstable Attenuation of Machupo Virus
Authors: Patterson Michael , Koma Takaaki , Seregin Alexey , Huang Cheng , Miller Milagros , Smith Jennifer , Yun Nadezhda , Smith Jeanon , Paessler Slobodan 
Published: July 2014

ABSTRACT
Machupo virus (MACV) is the etiologic agent of Bolivian hemorrhagic fever (BHF). Utilizing a reverse-genetics system recently developed, we report the rescue of a rationally modified recombinant MACV containing a single mutation in the transmembrane region of the glycoprotein. Following challenge of susceptible mice, we identified a significant reduction in virulence in the novel virus. We also identified an instability leading to reversion of the single mutation to a wild-type genotype.
Epstein-Barr Virus EBNA1 Protein Regulates Viral Latency through Effects on let-7 MicroRNA and Dicer
Authors: Mansouri Sheila , Pan Qun , Blencowe Benjamin J. , Claycomb Julie M. , Frappier Lori 
Published: July 2014

ABSTRACT
The EBNA1 protein of Epstein-Barr virus (EBV) plays multiple roles in EBV latent infection, including altering cellular pathways relevant for cancer. Here we used microRNA (miRNA) cloning coupled with high-throughput sequencing to identify the effects of EBNA1 on cellular miRNAs in two nasopharyngeal carcinoma cell lines. EBNA1 affected a small percentage of cellular miRNAs in both cell lines, in particular, upregulating multiple let-7 family miRNAs, including let-7a. The effects of EBNA1 on let-7a were verified by demonstrating that EBNA1 silencing in multiple EBV-positive carcinomas downregulated let-7a. Accordingly, the let-7a target, Dicer, was found to be partially downregulated by EBNA1 expression (at the mRNA and protein levels) and upregulated by EBNA1 silencing in EBV-positive cells. Reporter assays based on the Dicer 3′ untranslated region with and without let-7a target sites indicated that the effects of EBNA1 on Dicer were mediated by let-7a. EBNA1 was also found to induce the expression of let-7a primary RNAs in a manner dependent on the EBNA1 transcriptional activation region, suggesting that EBNA1 induces let-7a by transactivating the expression of its primary transcripts. Consistent with previous reports that Dicer promotes EBV reactivation, we found that a let-7a mimic inhibited EBV reactivation to the lytic cycle, while a let-7 sponge increased reactivation. The results provide a mechanism by which EBNA1 could promote EBV latency by inducing let-7 miRNAs.

IMPORTANCE
The EBNA1 protein of Epstein-Barr virus (EBV) contributes in multiple ways to the latent mode of EBV infection that leads to lifelong infection. In this study, we identify a mechanism by which EBNA1 helps to maintain EBV infection in a latent state. This involves induction of a family of microRNAs (let-7 miRNAs) that in turn decreases the level of the cellular protein Dicer. We demonstrate that let-7 miRNAs inhibit the reactivation of latent EBV, providing an explanation for our previous observation that EBNA1 promotes latency. In addition, since decreased levels of Dicer have been associated with metastatic potential, EBNA1 may increase metastases by downregulating Dicer.
Automated clinical trial eligibility prescreening: increasing the efficiency of patient identification for clinical trials in the emergency department
Authors: Ni Yizhao , Kennebeck Stephanie , Dexheimer Judith W , McAneney Constance M , Tang Huaxiu , Lingren Todd , Li Qi , Zhai Haijun , Solti Imre 
Published: July 2014

Abstract
Objectives (1) To develop an automated eligibility screening (ES) approach for clinical trials in an urban tertiary care pediatric emergency department (ED); (2) to assess the effectiveness of natural language processing (NLP), information extraction (IE), and machine learning (ML) techniques on real-world clinical data and trials.
Data and methods We collected eligibility criteria for 13 randomly selected, disease-specific clinical trials actively enrolling patients between January 1, 2010 and August 31, 2012. In parallel, we retrospectively selected data fields including demographics, laboratory data, and clinical notes from the electronic health record (EHR) to represent profiles of all 202795 patients visiting the ED during the same period. Leveraging NLP, IE, and ML technologies, the automated ES algorithms identified patients whose profiles matched the trial criteria to reduce the pool of candidates for staff screening. The performance was validated on both a physician-generated gold standard of trial–patient matches and a reference standard of historical trial–patient enrollment decisions, where workload, mean average precision (MAP), and recall were assessed.
Results Compared with the case without automation, the workload with automated ES was reduced by 92% on the gold standard set, with a MAP of 62.9%. The automated ES achieved a 450% increase in trial screening efficiency. The findings on the gold standard set were confirmed by large-scale evaluation on the reference set of trial–patient matches.
Discussion and conclusion By exploiting the text of trial criteria and the content of EHRs, we demonstrated that NLP-, IE-, and ML-based automated ES could successfully identify patients for clinical trials.
Stem cell transplantation of matched sibling donors compared with immunosuppressive therapy for acquired severe aplastic anaemia: a Cochrane systematic review
Authors: Peinemann Frank , Labeit Alexander Michael 
Published: July 2014

ObjectivesAcquired severe aplastic anaemia is a rare and potentially fatal disease. The aim of this Cochrane review was to evaluate the effectiveness and adverse events of first-line allogeneic haematopoietic stem cell transplantation of human leucocyte antigen (HLA)-matched sibling donors compared with first-line immunosuppressive therapy.SettingSpecialised stem cell transplantations units in primary care hospitals.ParticipantsWe included 302 participants with newly diagnosed acquired severe aplastic anaemia. The age ranged from early childhood to young adulthood. We excluded studies on participants with secondary aplastic anaemia.InterventionsWe included allogeneic haematopoietic stem cell transplantation as the test intervention harvested from any source of matched sibling donor and serving as a first-line therapy. We included immunosuppressive therapy as comparator with either antithymocyte/antilymphocyte globulin or ciclosporin or a combination of the two.Primary and secondary outcome measures planned and finally measuredThe primary outcome was overall mortality. Secondary outcomes were treatment-related mortality, graft failure, graft-versus-host disease, no response to immunosuppressive therapy, relapse after initial successful treatment, secondary clonal disease or malignancies, health-related quality of life and performance scores.ResultsWe identified three prospective non-randomised controlled trials with a study design that was consistent with the principle of ‘Mendelian randomisation’ in allocating patients to treatment groups. All studies had a high risk of bias due to the study design and were conducted more than 15 years. The pooled HR for overall mortality for the donor group versus the no donor group was 0.95 (95% CI 0.43 to 2.12, p=0.90).ConclusionsThere are insufficient and biased data that do not allow any firm conclusions to be made about the comparative effectiveness of first-line allogeneic haematopoietic stem cell transplantation of HLA-matched sibling donors and first-line immunosuppressive therapy of patients with acquired severe aplastic anaemia.
Follow‐up fiasco
Authors: Green Richard 
Published: July 2014

THIS series gives readers the opportunity to consider and contribute to discussion of some of the ethical dilemmas that can arise in veterinary practice. Each month, a case scenario is presented, followed by discussion of some of the issues involved.In addition, a possible way forward is suggested; however, there is rarely a cut‐and‐dried answer in such cases, and readers may wish to suggest an alternative approach. This month's dilemma, ‘Follow‐up fiasco’, was submitted and is discussed by Richard Green. Readers with comments to contribute are invited to send them as soon as possible, so that they can be considered for publication in the next issue. Discussion of the dilemma ‘A stitch in time. . . ’, which was published in the June issue of In Practice, appears on page 375.The series is being coordinated by Siobhan Mullan, of the University of Bristol. It is hoped it will provide a framework that will help practices find solutions when facing similar dilemmas.