bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surveillance biopsies after paediatric kidney transplantation: A review
Authors: Rose Edward M. , Kennedy Sean E. , Mackie Fiona E. 
Published: June 2016

AbstractKidney transplantation is the most effective means of treating children with end‐stage kidney disease, and yet, there continues to be a limited “life span” of transplanted kidneys in paediatric recipients. Early graft monitoring, using the surveillance biopsy, has the potential to extend renal allograft survival in paediatric recipients. The surveillance biopsy provides important and timely information about acute and chronic graft pathology, particularly SCR and calcineurin inhibitor‐induced nephrotoxicity, which can subsequently guide management decisions and improve long‐term graft survival. The ostensible value of the surveillance biopsy is furthered by the limitations of conventional renal functional studies. However, there is still much debate surrounding the surveillance biopsy in paediatric recipients, particularly in regard to its overall utility, safety and timing. This review discusses the current literature regarding the utility, safety, and potential predictive value of surveillance biopsies for guiding post‐transplant management in paediatric renal allograft recipients, as well as the viability of other potentially newer non‐invasive strategies for renal allograft monitoring.
Thomas F. Mayer (1951–2014) and the Roman Inquisition: A Review Essay
Authors: Pattenden Miles 
Published: June 2016

The Roman Inquisition: A Papal Bureaucracy and its Laws in the Age of Galileo, Thomas F. Mayer, University of Pennsylvania Press, 2013 (ISBN 978‐0‐8122‐4473‐1), 385 pp., hb £52The Roman Inquisition on the Stage of Italy, c. 1590‐1640, Thomas F. Mayer, University of Pennsylvania Press, 2014 (ISBN 978‐0‐8122‐4573‐8), 361 pp., hb £52The Roman Inquisition: Trying Galileo, Thomas F. Mayer, University of Pennsylvania Press, 2015 (ISBN: 978‐0‐8122‐4655‐1), 368 pp., hb £58.50AbstractThis review article appraises the recent trilogy of books on the Roman Inquisition written by the late Thomas F. Mayer. It explains the context in which Mayer came to write these works, the research questions which guided him and the nature of the outputs he delivered before his untimely death. Mayer's principal theme of the importance of process in guiding inquisitors' actions and activities, is traced through his three volumes: the first a general reconstruction of how the Holy Office operated, the second an application of his insights to specific cases of importance throughout late sixteenth‐ and early seventeenth‐century Italy, the third on the Galileo trial itself. Other scholars have received Mayer's work in a number of different ways, some favorable, others less so. Here, this essay summarizes parameters of the debate which Mayer catalyzed, in particular between scholars of Galileo and of the Inquisition; it also explains the further questions that has risen. Finally, it assesses how, as colleagues, we might extend Mayer's inquires and evaluates the wider impact his work deserves to have in historical studies and, indeed, in contemporary academic discourse. Mayer's insistance on the need to understand the methods and processes of censorship seems especially timely given the general assault on free speech which we currently face on many university campuses. On that basis, his scholarship should continue to resonate with all of us, perhaps in some uncomfortable ways.
ICT and Exporting: The Effects of Broadband on the Extensive Margin of Business Service Exports
Authors: Kneller Richard , Timmis Jonathan 
Published: June 2016

AbstractOver the last three decades the global economy has witnessed rapid growth of international trade in services. This has been particularly true of service‐intensive countries such as the UK. Developments in information and communication technologies are an obvious explanation for this. We provide empirical evidence for the effects of broadband use on the firm‐extensive margin of UK service exports. To deal with the issue of causality we build a novel instrument that exploits exogenous variation in access to broadband technologies owing to the historic telephone network. We find evidence for a causal effect from the Internet on trade in business services, but no evidence for an effect on trade in services more generally.
Phenotypic H-Antigen Typing by Mass Spectrometry Combined with Genetic Typing of H Antigens, O Antigens, and Toxins by Whole-Genome Sequencing Enhances Identification of Escherichia coli Isolates
Authors: Cheng Keding , Chui Huixia , Domish Larissa , Sloan Angela , Hernandez Drexler , McCorrister Stuart , Robinson Alyssia , Walker Matthew , Peterson Lorea A. M. , Majcher Miles , Ratnam Sam , Haldane David J. M. , Bekal Sadjia , Wylie John , Chui Linda , Tyler Shaun , Xu Bianli , Reimer Aleisha , Nadon Celine , Knox J. David , Wang Gehua 
Published: June 2016

ABSTRACTMass spectrometry-based phenotypic H-antigen typing (MS-H) combined with whole-genome-sequencing-based genetic identification of H antigens, O antigens, and toxins (WGS-HOT) was used to type 60 clinicalEscherichia coliisolates, 43 of which were previously identified as nonmotile, H type undetermined, or O rough by serotyping or having shown discordant MS-H and serotyping results. Whole-genome sequencing confirmed that MS-H was able to provide more accurate data regarding H antigen expression than serotyping. Further, enhanced and more confident O antigen identification resulted from gene cluster based typing in combination with conventional typing based on the gene pair comprisingwzxandwzyand that comprisingwzmandwzt. The O antigen was identified in 94.6% of the isolates when the two genetic O typing approaches (gene pair and gene cluster) were used in conjunction, in comparison to 78.6% when the gene pair database was used alone. In addition, 98.2% of the isolates showed the existence of genes for various toxins and/or virulence factors, among which verotoxins (Shiga toxin 1 and/or Shiga toxin 2) were 100% concordant with conventional PCR based testing results. With more applications of mass spectrometry and whole-genome sequencing in clinical microbiology laboratories, this combined phenotypic and genetic typing platform (MS-H plus WGS-HOT) should be ideal for pathogenicE. colityping.
The BD Onclarity HPV Assay on Samples Collected in SurePath Medium Meets the International Guidelines for Human Papillomavirus Test Requirements for Cervical Screening
Authors: Ejegod Ditte , Bottari Fabio , Pedersen Helle , Sandri Maria Teresa , Bonde Jesper 
Published: June 2016

ABSTRACT
This study describes a validation of the BD Onclarity HPV (Onclarity) assay using the international guidelines for HPV test requirements for cervical cancer screening of women 30 years old and older using Danish SurePath screening samples. The clinical specificity (0.90, 95% confidence interval [CI] = 0.88 to 0.91) and sensitivity (0.97, 95% CI = 0.87 to 1.0) of the Onclarity assay were shown to be not inferior to the reference assay (specificity, 0.90 [95% CI = 0.88 to 0.92]; sensitivity, 0.98 [95% CI = 0.91 to 1.0]). The intralaboratory reproducibility of Onclarity was 97%, with a lower confidence bound of 96% (kappa value, 0.93). The interlaboratory agreement was 97%, with a lower confidence bound of 95% (kappa value, 0.92). The BD Onclarity HPV assay fulfills all the international guidelines for a new HPV test to be used in primarily screening. This is the first clinical validation of a new HPV assay using SurePath screening samples, and thus the Onclarity HPV assay is the first HPV assay to hold an international validation for both SurePath and ThinPrep.
Mycoplasma genitalium Prevalence, Coinfection, and Macrolide Antibiotic Resistance Frequency in a Multicenter Clinical Study Cohort in the United States
Authors: Getman Damon , Jiang Alice , O'Donnell Meghan , Cohen Seth 
Published: June 2016

ABSTRACT

The prevalence rates of
Mycoplasma genitalium
infections and coinfections with other sexually transmitted organisms and the frequency of a macrolide antibiotic resistance phenotype were determined in urogenital specimens collected from female and male subjects enrolled in a multicenter clinical study in the United States. Specimens from 946 subjects seeking care from seven geographically diverse clinical sites were tested for
M. genitalium
and for
Chlamydia trachomatis
,
Neisseria gonorrhoeae
, and
Trichomonas vaginalis
. Sequencing was used to assess macrolide antibiotic resistance among
M. genitalium
-positive subjects.
M. genitalium
prevalence rates were 16.1% for females and 17.2% for males. Significant risk factors for
M. genitalium
infections were black race, younger age, non-Hispanic ethnicity, and female symptomatic status. Female
M. genitalium
infections were significantly more prevalent than
C. trachomatis
and
N. gonorrhoeae
infections, while the
M. genitalium
infection rate in males was significantly higher than the
N. gonorrhoeae
and
T. vaginalis
infection rates. The macrolide-resistant phenotype was found in 50.8% of females and 42% of males. These results show a high prevalence of
M. genitalium
single infections, a lower prevalence of coinfections with other sexually transmitted organisms, and high rates of macrolide antibiotic resistance in a diverse sample of subjects seeking care across a wide geographic area of the United States.
Commentary: The Future of Whole-Genome Sequencing for Public Health and the Clinic
Authors: Allard Marc W. 
Published: June 2016

ABSTRACT
An American Society for Microbiology (ASM) conference titled the Conference on Rapid Next-Generation Sequencing and Bioinformatic Pipelines for Enhanced Molecular Epidemiological Investigation of Pathogens provided a venue for discussing how technologies surrounding whole-genome sequencing (WGS) are advancing microbiology. Several applications in microbial taxonomy, microbial forensics, and genomics for public health pathogen surveillance were presented at the meeting and are reviewed. All of these studies document that WGS is revolutionizing applications in microbiology and that the impact of these technologies will be profound. ASM is providing support mechanisms to promote discussions of WGS techniques to foster applications and interpretations.
Antiviral Activity of Myticin C Peptide from Mussel: an Ancient Defense against Herpesviruses
Authors: Novoa Beatriz , Romero Alejandro , Álvarez Ángel L. , Moreira Rebeca , Pereiro Patricia , Costa María M. , Dios Sonia , Estepa Amparo , Parra Francisco , Figueras Antonio 
Published: June 2016

ABSTRACT
Little is known about the antiviral response in mollusks. As in other invertebrates, the interferon signaling pathways have not been identified, and in fact, there is a debate about whether invertebrates possess antiviral immunity similar to that of vertebrates. In marine bivalves, due to their filtering activity, interaction with putative pathogens, including viruses, is very high, suggesting that they should have mechanisms to address these infections. In this study, we confirmed that constitutively expressed molecules in naive mussels confer resistance in oysters to ostreid herpesvirus 1 (OsHV-1) when oyster hemocytes are incubated with mussel hemolymph. Using a proteomic approach, myticin C peptides were identified in both mussel hemolymph and hemocytes. Myticins, antimicrobial peptides that have been previously characterized, were constitutively expressed in a fraction of mussel hemocytes and showed antiviral activity against OsHV-1, suggesting that these molecules could be responsible for the antiviral activity of mussel hemolymph. For the first time, a molecule from a bivalve has shown antiviral activity against a virus affecting mollusks. Moreover, myticin C peptides showed antiviral activity against human herpes simplex viruses 1 (HSV-1) and 2 (HSV-2). In summary, our work sheds light on the invertebrate antiviral immune response with the identification of a molecule with potential biotechnological applications.

IMPORTANCE
Several bioactive molecules that have potential pharmaceutical or industrial applications have been identified and isolated from marine invertebrates. Myticin C, an antimicrobial peptide from the Mediterranean mussel (
Mytilus galloprovincialis
) that was identified by proteomic techniques in both mussel hemolymph and hemocytes, showed potential as an antiviral agent against ostreid herpesvirus 1 (OsHV-1), which represents a major threat to the oyster-farming sector. Both hemolymph from mussels and a myticin C peptide inhibited OsHV-1 replication in oyster hemocytes. Additionally, a modified peptide derived from myticin C or the nanoencapsulated normal peptide also showed antiviral activity against the human herpesviruses HSV-1 and HSV-2. Therefore, myticin C is an example of the biotechnological and therapeutic potential of mollusks.
The K1 Protein of Kaposi's Sarcoma-Associated Herpesvirus Augments Viral Lytic Replication
Authors: Zhang Zhigang , Chen Wuguo , Sanders Marcia K. , Brulois Kevin F. , Dittmer Dirk P. , Damania Blossom 
Published: June 2016

ABSTRACT

The K1 gene product of Kaposi's sarcoma-associated herpesvirus (KSHV) is encoded by the first open reading frame (ORF) of the viral genome. To investigate the role of the K1 gene during the KSHV life cycle, we constructed a set of recombinant viruses that contained either wild-type (WT) K1, a deleted K1 ORF (KSHVΔK1), stop codons within the K1 ORF (KSHV-K1
5×STOP
), or a revertant K1 virus (KSHV-K1
REV
). We report that the recombinant viruses KSHVΔK1 and KSHV-K1
5×STOP
displayed significantly reduced lytic replication compared to WT KSHV and KSHV-K1
REV
upon reactivation from latency. Additionally, cells infected with the recombinant viruses KSHVΔK1 and KSHV-K1
5×STOP
also yielded smaller amounts of infectious progeny upon reactivation than did WT KSHV- and KSHV-K1
REV
-infected cells. Upon reactivation from latency, WT KSHV- and KSHV-K1
REV
-infected cells displayed activated Akt kinase, as evidenced by its phosphorylation, while cells infected with viruses deleted for K1 showed reduced phosphorylation and activation of Akt kinase. Overall, our results suggest that K1 plays an important role during the KSHV life cycle.

IMPORTANCE
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of three human malignancies, and KSHV K1 is a signaling protein that has been shown to be involved in cellular transformation and to activate the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway. In order to investigate the role of the K1 protein in the life cycle of KSHV, we constructed recombinant viruses that were deficient for K1. We found that K1 deletion viruses displayed reduced lytic replication compared to the WT virus and also yielded smaller numbers of infectious progeny. We report that K1 plays an important role in the life cycle of KSHV.
Klebsiella pneumoniae: Going on the Offense with a Strong Defense
Authors: Paczosa Michelle K. , Mecsas Joan 
Published: June 2016

SUMMARYKlebsiella pneumoniaecauses a wide range of infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Historically,K. pneumoniaehas caused serious infection primarily in immunocompromised individuals, but the recent emergence and spread of hypervirulent strains have broadened the number of people susceptible to infections to include those who are healthy and immunosufficient. Furthermore,K. pneumoniaestrains have become increasingly resistant to antibiotics, rendering infection by these strains very challenging to treat. The emergence of hypervirulent and antibiotic-resistant strains has driven a number of recent studies. Work has described the worldwide spread of one drug-resistant strain and a host defense axis, interleukin-17 (IL-17), that is important for controlling infection. Four factors, capsule, lipopolysaccharide, fimbriae, and siderophores, have been well studied and are important for virulence in at least one infection model. Several other factors have been less well characterized but are also important in at least one infection model. However, there is a significant amount of heterogeneity inK. pneumoniaestrains, and not every factor plays the same critical role in all virulentKlebsiellastrains. Recent studies have identified additionalK. pneumoniaevirulence factors and led to more insights about factors important for the growth of this pathogen at a variety of tissue sites. Many of these genes encode proteins that function in metabolism and the regulation of transcription. However, much work is left to be done in characterizing these newly discovered factors, understanding how infections differ between healthy and immunocompromised patients, and identifying attractive bacterial or host targets for treating these infections.
Bacterial Sphingomyelinases and Phospholipases as Virulence Factors
Authors: Flores-Díaz Marietta , Monturiol-Gross Laura , Naylor Claire , Alape-Girón Alberto , Flieger Antje 
Published: June 2016

SUMMARYBacterial sphingomyelinases and phospholipases are a heterogeneous group of esterases which are usually surface associated or secreted by a wide variety of Gram-positive and Gram-negative bacteria. These enzymes hydrolyze sphingomyelin and glycerophospholipids, respectively, generating products identical to the ones produced by eukaryotic enzymes which play crucial roles in distinct physiological processes, including membrane dynamics, cellular signaling, migration, growth, and death. Several bacterial sphingomyelinases and phospholipases are essential for virulence of extracellular, facultative, or obligate intracellular pathogens, as these enzymes contribute to phagosomal escape or phagosomal maturation avoidance, favoring tissue colonization, infection establishment and progression, or immune response evasion. This work presents a classification proposal for bacterial sphingomyelinases and phospholipases that considers not only their enzymatic activities but also their structural aspects. An overview of the main physiopathological activities is provided for each enzyme type, as are examples in which inactivation of a sphingomyelinase- or a phospholipase-encoding gene impairs the virulence of a pathogen. The identification of sphingomyelinases and phospholipases important for bacterial pathogenesis and the development of inhibitors for these enzymes could generate candidate vaccines and therapeutic agents, which will diminish the impacts of the associated human and animal diseases.
Insights into cyanobacterial fossilization in Ediacaran siliciclastic environments
Authors: Newman Sharon A. , Mariotti Giulio , Pruss Sara , Bosak Tanja 
Published: June 2016

Abstract
Ediacaran sedimentary successions are noted for the preservation of microbes and microbial textures on the surfaces of sandstones and siltstones. Although microorganisms have been preserved in coarse-grained siliciclastic sand throughout geologic history, the exceptional preservation of microbes in Ediacaran sediments suggests the potential for a unique taphonomic window. Here, we identify conditions conducive to the fossilization of filamentous cyanobacteria growing in the presence of siliciclastic sand and demonstrate that the sheaths of filamentous cyanobacteria can become coated by clay minerals within days under oxic conditions. Smooth, extensive mineral coatings develop in the presence of 5.6 to 55.6 mg/L of suspended clay and 0.1 mM or greater concentrations of dissolved silica. Thus, elevated concentrations of seawater silica and the delivery of suspended clays promote microbial preservation on sandy and silty surfaces. These factors likely facilitated microbial fossilization in coarse-grained siliciclastic sand throughout the Ediacaran Period and may have also contributed to microbial fossilization in siliciclastic deposits at other times throughout Earth’s history.
The value of emergency medicine placements for postgraduate doctors: views of Foundation Year 2 doctors and training leads in the emergency department (ED)
Authors: O’Keeffe Colin , Carter Angela , Mason Suzanne 
Published: June 2016

ABSTRACTObjectivesTo examine the delivery of postgraduate training in the emergency medicine setting and its impact on postgraduate doctor (Foundation Year 2) performance and competence.MethodsA national study in four emergency departments (EDs) in England between 2009 and 2010 was undertaken. Semistructured interviews with ED training leads (TLs) and focus groups with Foundation Year 2 (F2) doctors were carried out in each ED. Interviews and focus group data were analysed to compare the perspectives of F2 doctors and TLs on the delivery of training and performance and confidence of F2 doctors.ResultsInterviews were carried out with eight TLs and focus groups with 30 F2s. F2 doctors and EDTLs agreed that ED was a valuable environment for F2 doctors to develop their competence, with exposure to a broad range of patients and the opportunity to make decisions about clinical care. Diverging views existed around competence and performance of F2s. F2 doctors had anxieties about decision-making (particularly discharging patients) and required regular feedback to feel confident in their care. TLs recognised a need for more supervision and support for F2 doctors but this was challenging in a busy, performance-led service.ConclusionsEmergency medicine placements were important in the development of confident and competent F2 doctors, particularly in the context of less clinical exposure in other specialty placements. However, there are competing tensions between elements of postgraduate learning and service delivery within emergency medicine that require addressing to enable trainees to optimally develop knowledge and skills in this environment.
BMI-1 Targeting Interferes with Patient-Derived Tumor-Initiating Cell Survival and Tumor Growth in Prostate Cancer
Authors: Bansal Nitu , Bartucci Monica , Yusuff Shamila , Davis Stephani , Flaherty Kathleen , Huselid Eric , Patrizii Michele , Jones Daniel , Cao Liangxian , Sydorenko Nadiya , Moon Young-Choon , Zhong Hua , Medina Daniel , Kerrigan John , Stein Mark N. , Kim Isaac Y. , Davis Thomas W. , DiPaola Robert S. , Bertino Joseph , Sabaawy Hatem E. 
Published: June 2016

Abstract
Purpose: Current prostate cancer management calls for identifying novel and more effective therapies. Self-renewing tumor-initiating cells (TICs) hold intrinsic therapy resistance and account for tumor relapse and progression. As BMI-1 regulates stem cell self-renewal, impairing BMI-1 function for TIC-tailored therapies appears to be a promising approach.
Experimental Design: We have previously developed a combined immunophenotypic and time-of-adherence assay to identify CD49bhiCD29hiCD44hi cells as human prostate TICs. We utilized this assay with patient-derived prostate cancer cells and xenograft models to characterize the effects of pharmacologic inhibitors of BMI-1.
Results: We demonstrate that in cell lines and patient-derived TICs, BMI-1 expression is upregulated and associated with stem cell–like traits. From a screened library, we identified a number of post-transcriptional small molecules that target BMI-1 in prostate TICs. Pharmacologic inhibition of BMI-1 in patient-derived cells significantly decreased colony formation in vitro and attenuated tumor initiation in vivo, thereby functionally diminishing the frequency of TICs, particularly in cells resistant to proliferation- and androgen receptor–directed therapies, without toxic effects on normal tissues.
Conclusions: Our data offer a paradigm for targeting TICs and support the development of BMI-1–targeting therapy for a more effective prostate cancer treatment. Clin Cancer Res; 22(24); 6176–91. ©2016 AACR.