bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical value and safety of liver biopsies in patients transplanted for hepatitis C virus‐related end‐stage liver disease
Authors: Brauner C. , Lankisch T.O. , Fytili P. , Jaroszewicz J. , Lehner F. , Barg‐Hock H. , Klempnauer J. , Jaeckel E. , Manns M.P. , Wedemeyer H. , Negm A.A. 
Published: November 2014

AbstractBackgroundHepatitis C is the leading indication for liver transplantation. Differentiation between recurrent graft hepatitis C (RGH‐C) and graft rejection (GR) is challenging. Liver biopsy is standard to diagnose both conditions; however, little information is available regarding this procedure in hepatitis C virus (HCV)‐infected liver transplant recipients.MethodsLiver biopsies (n = 211) from all consecutive patients (n = 138) transplanted for hepatitis C at Hannover Medical School between January 2000 and October 2011 were screened, and a final cohort of 96 patients with 196 biopsies was included. Indications, histopathological findings, and biopsy‐related complications were documented. Modifications in the treatment based on the biopsy result and the biochemical outcome were analyzed.ResultsMost biopsies (196/211, 93%) were representative. Five patients (2.5%) developed non‐fatal biopsy‐related complications. Biopsy results were GR (35%), RGH‐C (31%), and other diagnoses (34%). GR was independently associated with lower albumin (P = 0.025) and higher bilirubin levels (P = 0.011). Treatment was modified based on the biopsy result in 25% of cases. Alanine aminotransferase (ALT), gamma‐glutamyl transferase (GGT), and bilirubin levels improved in 41%, 25%, and 31% of cases 4 weeks post biopsy respectively. ALT improvements were more significant in patients with GR than in those with RGH‐C.ConclusionLiver biopsy in HCV‐infected liver transplant recipients is safe and representative in >90% of cases. GR is independently associated with lower albumin and higher bilirubin levels.
Anti‐SSA antibodies are present in immunoglobulin preparations
Authors: van der Molen Renate G. , Hamann Dörte , Jacobs Joannes F.M. , van der Meer Arnold , de Jong Jan , Kramer Christine , Strengers Paul F.W. , van der Meer Jos W.M. 
Published: November 2014

BackgroundAnti‐SSA autoantibodies are among the most frequently detected autoantibodies and have traditionally been associated with Sjögren's syndrome (SjS) and systemic lupus erythematosus. The unexpected finding of anti‐SSA antibodies in a patient with common variable immunodeficiency disorder (CVID) treated with intravenous immunoglobulin (IVIG), who developed discoid lupus erythematosus, prompted us to investigate the presence of anti‐SSA antibodies in IVIG preparations. Since anti‐SSA antibodies may be present in apparently healthy individuals without overt autoimmune features, IVIG preparations may also contain anti‐SSA antibodies.Study Design and MethodsIVIG consists of polyclonal immunoglobulin G isolated from the plasma of more than 1000 blood donors. Several IVIG batches from different suppliers and serum samples of patients receiving these IVIG products were tested for the presence of anti‐nuclear antibodies (ANAs) and extractable nuclear antibodies (ENAs). In addition, we tested several plasma pools for the presence of anti‐SSA and subsequent serum samples of individual donors.ResultsSeveral CVID‐patients receiving IVIG tested positive for ANA and anti‐SSA. The IVIG products administered also contained clearly detectable concentrations of these antibodies. The frequency of apparently healthy blood donors with anti‐SSA positivity was 0.69% and one of 1894 donors (0.05%) showed a very high titer of anti‐SSA of more than 10,000 U/mL.ConclusionAnti‐SSA is present in IVIG products and in blood donors without clinical symptoms. IVIG replacement can interfere with ANA and ENA serology by passive transfer of autoantibodies. We hypothesize that such autoantibodies may be causally related to disease manifestations in some recipients.
Physical Activity and Sedentary Behavior Patterns of Singaporean Adolescents
Authors: Ting Jamie Lye Ching , Mukherjee Swarup , Hwa Michael Chia Yong 
Published: November 2014

Background:Adolescents require at least 60 minutes of daily moderate to vigorous intensity physical activity (PA) for optimum health benefits. Reduced active and increased sedentary time can adversely affect health independently. This study investigated the sedentary behavior and physical activity patterns of Singaporean adolescents.Methods:233 adolescents aged 13 to 15 years participated in the study. Accelerometry was used to assess the daily PA patterns for 3 weekdays and 2 weekend days consecutively. Height, weight, BMI, waist circumference and waist-hip ratio were determined as surrogate measures of health.Results:None of the participants achieved the recommended 60 minutes of daily moderate-to-vigorous physical activity (MVPA) on all 5 days. Significantly more time was spent engaging in sedentary activity compared with MVPA on both weekdays and weekends. MVPA and sedentary time were positively associated on weekdays after controlling for gender (P < .001). Weekday MVPA was positively associated with waist circumference (P < .001) and waist-hip ratio (P < .001).Conclusion:Singaporean adolescents fall substantially short of meeting the daily PA recommendations. Separate strategies to promote PA may be necessary for adolescents of differing weight status and gender. Pragmatic rather than idealistic targets to promote PA need to be set based on population-specific baseline data.
Bartonella clarridgeiae Bacteremia Detected in an Asymptomatic Blood Donor
Authors: Vieira-Damiani Gislaine , Diniz Pedro Paulo Vissotto de Paiva , Pitassi Luiza Helena Urso , Sowy Stanley , Scorpio Diana Gerardi , Lania Bruno Grosselli , Drummond Marina Rovani , Soares Tânia Cristina Benetti , Barjas-Castro Maria de Lourdes , Breitschwerdt Edward B. , Nicholson William L. , Velho Paulo Eduardo Neves Ferreira 
Published: November 2014

ABSTRACT

Human exposure to
Bartonella clarridgeiae
has been reported only on the basis of antibody detection. We report for the first time an asymptomatic human blood donor infected with
B. clarridgeiae
, as documented by enrichment blood culture, PCR, and DNA sequencing.
Development of an Immunochromatographic Assay Kit Using Fluorescent Silica Nanoparticles for Rapid Diagnosis of Acanthamoeba Keratitis
Authors: Toriyama Koji , Suzuki Takashi , Inoue Tomoyuki , Eguchi Hiroshi , Hoshi Saichi , Inoue Yoshitsugu , Aizawa Hideki , Miyoshi Kazutomi , Ohkubo Michio , Hiwatashi Eiji , Tachibana Hiroshi , Ohashi Yuichi 
Published: November 2014

ABSTRACT

We developed an immunochromatographic assay kit that uses fluorescent silica nanoparticles bound to anti-
Acanthamoeba
antibodies (fluorescent immunochromatographic assay [FICGA]) and evaluated its efficacy for the detection of
Acanthamoeba
and diagnosis of
Acanthamoeba
keratitis (AK). The sensitivity of the FICGA kit was evaluated using samples of
Acanthamoeba
trophozoites and cysts diluted to various concentrations. A conventional immunochromatographic assay kit with latex labels (LICGA) was also evaluated to determine its sensitivity in detecting
Acanthamoeba
trophozoites. To check for cross-reactivity, the FICGA was performed by using samples of other common causative pathogens of infectious keratitis, such as
Pseudomonas aeruginosa
,
Staphylococcus aureus
,
Staphylococcus epidermidis
, and
Candida albicans
. Corneal scrapings from patients with suspected AK were tested with the FICGA kit to detect the presence of
Acanthamoeba
, and the results were compared with those of real-time PCR. The FICGA kit detected organisms at concentrations as low as 5 trophozoites or 40 cysts per sample. There were no cross-reactivities with other pathogens. The FICGA was approximately 20 times more sensitive than the LICGA for the detection of
Acanthamoeba
trophozoites. The FICGA kit yielded positive results for all 10 patients, which corresponded well with the real-time PCR results. The FICGA kit demonstrated high sensitivity for the detection of
Acanthamoeba
and may be useful for the diagnosis of AK.
JC Virus Quasispecies Analysis Reveals a Complex Viral Population Underlying Progressive Multifocal Leukoencephalopathy and Supports Viral Dissemination via the Hematogenous Route
Authors: Van Loy Tom , Thys Kim , Ryschkewitsch Caroline , Lagatie Ole , Monaco Maria C. , Major Eugene O. , Tritsmans Luc , Stuyver Lieven J. 
Published: November 2014

ABSTRACT
Opportunistic infection of oligodendrocytes by human JC polyomavirus may result in the development of progressive multifocal encephalopathy in immunocompromised individuals. Neurotropic JC virus generally harbors reorganized noncoding control region (NCCR) DNA interspersed on the viral genome between early and late coding genes. By applying 454 sequencing on NCCR DNA amplified from body fluid samples (urine, plasma, and cerebrospinal fluid [CSF]) from 19 progressive multifocal leukoencephalopathy (PML) patients, we attempted to reveal the composition of the JC polyomavirus population (the quasispecies, i.e., the whole of the consensus population and minor viral variants) contained in different body compartments and to better understand intrapatient viral dissemination. Our data demonstrate that in the CSF of PML patients, the JC viral population is often a complex mixture composed of multiple viral variants that contribute to the quasispecies. In contrast, urinary JC virus highly resembled the archetype virus, and urine most often did not contain minor viral variants. It also appeared that archetype JC virus could sporadically be identified in PML patient brain, although selection of rearranged JC virus DNA was favored. Comparison of the quasispecies from different body compartments within a given patient suggested a strong correlation between the viral population in plasma and CSF, whereas the viral population shed in urine appeared to be unrelated. In conclusion, it is shown that the representation of viral DNA in the CSF following the high-level DNA replication in the brain underlying PML has hitherto been much underestimated. Our data also underscore that the hematogenous route might play a pivotal role in viral dissemination from or toward the brain.

IMPORTANCE
For the first time, the JC polyomavirus population contained in different body compartments of patients diagnosed with progressive multifocal encephalopathy has been studied by deep sequencing. Two main findings came out of this work. First, it became apparent that the complexity of the viral population associated with PML has been highly underestimated so far, suggestive of a highly dynamic process of reorganization of the noncoding control region of JC polyomavirus
in vivo
, mainly in CSF and blood. Second, evidence showing viral dissemination from and/or toward the brain via the hematogenous route was provided, confirming a hypothesis that was recently put forward in the field.
Two Distinct Sets of NS2A Molecules Are Responsible for Dengue Virus RNA Synthesis and Virion Assembly
Authors: Xie Xuping , Zou Jing , Puttikhunt Chunya , Yuan Zhiming , Shi Pei-Yong 
Published: November 2014

ABSTRACT

Flavivirus nonstructural protein 2A (NS2A) plays important roles in both viral RNA synthesis and virion assembly. The molecular details of how the NS2A protein modulates the two distinct events have not been defined. To address this question, we have performed a systematic mutagenesis of NS2A using dengue virus (DENV) serotype 2 (DENV-2) as a model. We identified two sets of NS2A mutations with distinct defects during a viral infection cycle. One set of NS2A mutations (D125A and G200A) selectively abolished viral RNA synthesis. Mechanistically, the D125A mutation abolished viral RNA synthesis through blocking the N-terminal cleavage of the NS2A protein, leading to an unprocessed NS1-NS2A protein; this result suggests that amino acid D125 (far downstream of the N terminus of NS2A) may contribute to the recognition of host protease at the NS1-NS2A junction. The other set of NS2A mutations (G11A, E20A, E100A, Q187A, and K188A) specifically impaired virion assembly without significantly affecting viral RNA synthesis. Remarkably, mutants defective in virion assembly could be rescued by supplying in
trans
wild-type NS2A molecules expressed from a replicative replicon, by wild-type NS2A protein expressed alone, by a mutant NS2A (G200A) that is lethal for viral RNA synthesis, or by a different mutant NS2A that is defective in virion assembly. In contrast, none of the mutants defective in viral RNA synthesis could be rescued by
trans
-complementation. Collectively, the results indicate that two distinct sets of NS2A molecules are responsible for DENV RNA synthesis and virion assembly.

IMPORTANCE
Dengue virus (DENV) represents the most prevalent mosquito-borne human pathogen. Understanding the replication of DENV is essential for development of vaccines and therapeutics. Here we characterized the function of DENV-2 NS2A using a systematic mutagenesis approach. The mutagenesis results revealed two distinct sets of NS2A mutations: one set of mutations that result in defects in viral RNA synthesis and another set of mutations that result in defects in virion assembly.
trans
-Complementation analysis showed that mutants defective in viral RNA synthesis could not be rescued by wild-type NS2A; in contrast, mutants defective in virion assembly could be successfully rescued by wild-type NS2A or even by a mutant NS2A that is incompetent to support viral RNA synthesis. These results support a model in which two distinct sets of NS2A molecules are responsible for DENV RNA synthesis (located in the viral replication complex) and virion assembly (located in the virion assembly/budding site). The study confirms and extends our understanding of the two critical roles of flavivirus NS2A in viral RNA synthesis and virion assembly.
Electron Cryotomography Studies of Maturing HIV-1 Particles Reveal the Assembly Pathway of the Viral Core
Authors: Woodward Cora L. , Cheng Sarah N. , Jensen Grant J. 
Published: November 2014

ABSTRACT
To better characterize the assembly of the HIV-1 core, we have used electron cryotomography (ECT) to image infected cells and the viral particles cryopreserved next to them. We observed progressive stages of virus assembly and egress, including flower-like flat Gag lattice assemblies, hemispherical budding profiles, and virus buds linked to the plasma membrane via a thin membrane neck. The population of budded viral particles contains immature, maturation-intermediate, and mature core morphologies. Structural characteristics of the maturation intermediates suggest that the core assembly pathway involves the formation of a CA sheet that associates with the condensed ribonucleoprotein (RNP) complex. Our analysis also reveals a correlation between RNP localization within the viral particle and the formation of conical cores, suggesting that the RNP helps drive conical core assembly. Our findings support an assembly pathway for the HIV-1 core that begins with a small CA sheet that associates with the RNP to form the core base, followed by polymerization of the CA sheet along one side of the conical core toward the tip, and then closure around the body of the cone.

IMPORTANCE
During HIV-1 assembly and release, the Gag polyprotein is organized into a signature hexagonal lattice, termed the immature lattice. To become infectious, the newly budded virus must disassemble the immature lattice by proteolyzing Gag and then reassemble the key proteolytic product, the structural protein p24 (CA), into a distinct, mature hexagonal lattice during a process termed maturation. The mature HIV-1 virus contains a conical capsid that encloses the condensed viral genome at its wide base. Mutations or small molecules that interfere with viral maturation also disrupt viral infectivity. Little is known about the assembly pathway that results in the conical core and genome encapsidation. Here, we have used electron cryotomography to structurally characterize HIV-1 particles that are actively maturing. Based on the morphologies of core assembly intermediates, we propose that CA forms a sheet-like structure that associates with the condensed viral genome to produce the mature infectious conical core.
Isotretinoin exposure during pregnancy: a population-based study in The Netherlands
Authors: Zomerdijk Ingeborg M , Ruiter Rikje , Houweling Leanne M A , Herings Ron M C , Sturkenboom Miriam C J M , Straus Sabine M J M , Stricker Bruno H 
Published: November 2014

ObjectiveTo estimate isotretinoin exposure in Dutch pregnant women despite the implemented pregnancy prevention programme (PPP) and second, to analyse the occurrence of adverse fetal or neonatal outcomes in these isotretinoin exposed pregnancies.DesignPopulation-based study.SettingThe Netherlands.ParticipantsA cohort of 203 962 pregnancies with onset between 1 January 1999 and 1 September 2007 consisting of 208 161 fetuses or neonates.Main outcome measuresIsotretinoin exposure in the 30 days before or during pregnancy. Proportions of adverse fetal or neonatal outcomes, defined as intrauterine deaths ≥16 week of gestation and neonates with major congenital anomalies. ORs with 95% CIs adjusted for maternal age were calculated to estimate the risk of adverse fetal or neonatal outcome after maternal isotretinoin exposure.Results51 pregnancies, 2.5 (95% CI 1.9 to 3.3) per 10 000 pregnancies, were exposed to isotretinoin despite the pregnancy prevention programme. Forty-five of these pregnancies, 2.2 (95% CI 1.6 to 2.9) per 10 000 pregnancies, were exposed to isotretinoin during pregnancy and six additional women became pregnant within 30 days after isotretinoin discontinuation. In 60% of isotretinoin exposed pregnancies, women started isotretinoin while already pregnant. In five out of the 51 isotretinoin exposed pregnancies (53 fetuses), 9.4% (95% CI 1.3% to 17.6%), had an adverse fetal or neonatal outcome. The OR for adverse fetal or neonatal outcomes after isotretinoin exposure in 30 days before or during pregnancy was 2.3 (95% CI 0.9 to 5.7) after adjustment for maternal age.ConclusionsAlthough a PPP was already implemented in 1988, we showed that isotretinoin exposed pregnancies and adverse fetal and neonatal events potentially related to the exposure still occur. These findings from the Netherlands add to the evidence that there is no full compliance to the isotretinoin PPP in many Western countries. Given the limited success of iPLEDGE, the question is which further measures are able to improve compliance.
Development and validation of an administrative data algorithm to estimate the disease burden and epidemiology of multiple sclerosis in Ontario, Canada
Authors: Widdifield Jessica , Ivers Noah M , Young Jacqueline , Green Diane , Jaakkimainen Liisa , Butt Debra A. , O’Connor Paul , Hollands Simon , Tu Karen 
Published: November 2014

Background: Few studies have assessed the accuracy of administrative data for identifying multiple sclerosis (MS) patients. Objectives: To validate administrative data algorithms for MS, and describe the burden and epidemiology over time in Ontario, Canada. Methods: We employed a validated search strategy to identify all MS patients within electronic medical records, to identify patients with and without MS (reference standard). We then developed and validated different combinations of administrative data for algorithms. The most accurate algorithm was used to estimate the burden and epidemiology of MS over time. Results: The accuracy of the algorithm of one hospitalisation or five physician billings over 2 years provided both high sensitivity (84%) and positive predictive value (86%). Application of this algorithm to provincial data demonstrated an increasing cumulative burden of MS, from 13,326 patients (0.14%) in 2000 to 24,647 patients in 2010 (0.22%). Age-and-sex standardised prevalence increased from 133.9 to 207.3 MS patients per 100,000 persons in the population, from 2000 – 2010. During this same period, age-and-sex-standardised incidence varied from 17.9 to 19.4 patients per 100,000 persons. Conclusions: MS patients can be accurately identified from administrative data. Our findings illustrated a rising prevalence of MS over time. MS incidence rates also appear to be rising since 2009.
Knowledge, attitudes, experience and behaviour of frontline health care workers during the early phase of 2009 influenza A(H1N1) pandemic, Birmingham, UK
Authors: Edeghere Obaghe , Fowler Tom , Wilson Fay , Caspa Richard , Raichand Smitri , Kara Edna , Janmohamed Rampling Sumi , Olowokure Babatunde 
Published: November 2014

Objectives During the early (‘containment’) phase of the influenza A(H1N1) pandemic, when the severity of the pandemic was unclear, health care workers (HCWs) across the UK were deployed to swab and prescribe antiviral drugs to suspected cases. This study describes the knowledge, attitudes, experience and behaviour of frontline HCWs in Birmingham, West Midlands, during this period. Methods During June 2009, a 25-item semi-structured questionnaire was used to survey HCWs who undertook defined clinical duties as part of the public health response during the early phase of the pandemic. Participants were clinical staff based in a primary care out-of-hours service provider. Results The response rate was 50% ( n = 20). All respondents provided direct clinical care that necessitated prolonged close contact with potentially infectious cases. Knowledge and use of personal protective equipment and infection control procedures was consistently high. However, the main source of infection control advice was local guidance. Uptake of, and attitude towards, vaccination as a preventive measure and antiviral prophylaxis was poor. Conclusions HCWs were prepared to provide an essential health care response during the pandemic even when the severity of disease was unclear. However, more needs to be done to change health care workers’ negative attitudes towards taking antivirals and receiving influenza vaccination.
Laparoscopic Complete Mesocolic Excision with Central Vascular Ligation in right colon cancer: long-term oncologic outcome between mesocolic and non-mesocolic planes of surgery
Authors: Siani L. M. , Pulica C. 
Published: November 2014

Aim: To analyze our experience in translating the concept of total mesorectal excision to “no-touch” complete removal of an intact mesocolonic envelope (complete mesocolic excision), along with central vascular ligation and apical node dissection, in the surgical treatment of right-sided colonic cancers, comparing “mesocolic” to less radical “non-mesocolic” planes of surgery in respect to quality of the surgical specimen and long-term oncologic outcome. Method: A total of 115 patients with right-sided colonic cancers were retrospectively enrolled from 2008 to 2013 and operated on following the intent of minimally invasive complete mesocolic excision with central vascular ligation. Results: Morbidity and mortality were 22.6% and 1.7%, respectively. Mesocolic, intramesocolic, and muscularis propria planes of resection were achieved in 65.2%, 21.7%, and 13% of cases, respectively, with significant impact for mesenteric plane of surgery on R0 resection rate (97.3%), circumferential resection margin <1 mm (2.6%), and consequent survival advantage (82.6% at 5 years) when compared to muscularis propria plane of surgery, with R0 resection rate and overall survival falling to 72% and 60%, respectively, and with circumferential resection margin <1 mm raising to 33.3%, all being statistically significant. Stratifying patients for stage of disease, laparoscopic complete mesocolic excision with central vascular ligation significantly impacted survival in patients with stage II, IIIA/B, and in a subgroup of IIIC patients with negative apical nodes. Conclusion: In our experience, minimally invasive complete mesocolic excision with central vascular ligation allows for both safety and higher quality of surgical specimens when compared to less radical intramesocolic or muscularis propria planes of “standard” surgery, significantly impacting loco-regional control and thus overall survival.