bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concomitant Oral and Intravenous Pharmacokinetics of Dabrafenib, a BRAF Inhibitor, in Patients with BRAF V600 Mutation‐Positive Solid Tumors
Authors: Denton Cathrine L. , Minthorn Elisabeth , Carson Stanley W. , Young Graeme C. , Richards‐Peterson Lauren E. , Botbyl Jeffrey , Han Chao , Morrison Royce A. , Blackman Samuel C. , Ouellet Daniele 
Published: July 2013

AbstractDabrafenib is an orally bioavailable, potent, and selective inhibitor of human wild‐type BRAF and CRAF kinases as well as mutant forms of BRAF kinase. The aim of this phase 1, single‐center, open‐label study in four patients with BRAF mutation‐positive solid tumors was to determine the absolute bioavailability of a 150 mg oral dose of dabrafenib. A microtracer study approach, in which a 50 µg radiolabeled intravenous (IV) microdose of dabrafenib was given concomitantly with a 150 mg oral dose, was used to simultaneously recover IV and oral pharmacokinetic parameters. The least squares mean (90% CI) absolute bioavailability of dabrafenib (HPMC capsules) was 94.5% (81.3%, 109.7%). Median Tmax after oral administration was 2.0 hours and the geometric mean terminal half‐life was 4.8 hours. The geometric mean clearance and volume of distribution after IV administration were 12.0 L/h and 45.5 L, respectively. Human clearance and volume of distribution at steady state were in agreement with predictions made using allometric scaling of pharmacokinetic parameters from four preclinical species. In conclusion, dabrafenib absolute bioavailability was high, whereas first‐pass metabolism was low. Furthermore, the microtracer approach provided an innovative and efficient method for assessing the absolute bioavailability of dabrafenib in patients with advanced cancer.
Environmental impact and seroepidemiology of HTLV in two communities in the eastern Brazilian amazon
Authors: Magno Falcão Luiz Fábio , Fuzii Hellen Thais , Feio Libonati Rosana Maria , de Souza Aarão Tinara Leila , Moura Guimarães André Gustavo , Martins Luisa Carício , Simões Quaresma Juarez Antônio 
Published: July 2013

AbstractThe objective of this study was to detect antibodies for human T lymphotropic virus (HTLV) in subjects residing in two communities located in the eastern Brazilian Amazon and on the shores of the Tucuruí hydroelectric power plant. A total of 657 serum samples were analysed using an enzyme‐linked immunosorbent assay with an anti‐HTLV antibody (Symbiosis™, São Paulo, Brazil), demonstrating a virus prevalence of 4.7%. Most individuals with HTLV were aged over 30 years (P = 0.013), were unmarried (P = 0.019), resided in the area for more than 10 years (P = 0.001), had a low level of education (P = 0.015), and had a family income of up to $305 (100%). In contrast, there was no significant association between infection and sex, city of birth, haemotransfusion, or previous surgery. The prevalence observed in these communities suggests that the residents should be concerned about HTLV infection, and that some areas may become endemic for HTLV. J. Med. Virol. 85:1585–1590, 2013. © 2013 Wiley Periodicals, Inc.
Impact of human cytomegalovirus (CMV) infection on immune response to pandemic 2009 H1N1 influenza vaccine in healthy adults
Authors: Wald Anna , Selke Stacy , Magaret Amalia , Boeckh Michael 
Published: July 2013

AbstractHuman cytomegalovirus (CMV) infection has been implicated in immunosenescence. To examine the influence of CMV on ability of healthy adults to respond to a novel influenza antigen, the rate of seroconversion and the magnitude of titers to pandemic 2009 H1N1 vaccine was assessed. The clinical trial was stratified by age; 52 persons aged 18–64 and 55 aged 65 and older were enrolled. Among the younger group, 33% had CMV antibody compared with 62% among the older group. No differences by CMV seropositivity in the proportion of participants achieving a seroprotective titer 21 days following the second immunization were noted. However, the geometric mean titer in hemagglutination inhibition assay was significantly higher among CMV seronegative younger participants compared with CMV seropositive younger participants (385 vs. 142, P = 0.013). In contrast, among the older group, CMV serostatus was not associated with differential antibody titers (53 vs. 63, P = 0.75). These data suggest that CMV may shape immune response to neoantigens among younger persons; these groups should be included in future studies of immunosenescence and CMV. J. Med. Virol. 85:1557–1560, 2013. © 2013 Wiley Periodicals, Inc.
Different norovirus genotypes in patients with gastroenteritis in Kuwait
Authors: Al‐Rashidi Amirah , Chehadeh Wassim , Szücs György G. , Albert M. John 
Published: July 2013

AbstractNorovirus is a leading cause of acute gastroenteritis worldwide. The importance of this virus infection in Kuwait is not known. Eight out of 100 stool samples (8.0%) from children up to 5 years of age with gastroenteritis studied during 2006–2007 from one hospital, and 6 out of 70 stool samples (8.5%) from similar children studied from another hospital during 2010–2011 were positive for norovirus by RT‐PCR. Out of these 170 samples studied from both hospitals, 10 samples were positive for norovirus when tested by ELISA. Phylogenetic tree analysis of norovirus strains showed that 50% of the norovirus strains belonged to genotype GII.4, and the predominant strain was GII.4 2006b. Other detected genotypes were GII.12, GII.b, GII.3, GII.8, and GII.7. This study highlights the importance of screening for norovirus infection in acute gastroenteritis and having a reporting system to understand better the epidemiology of norovirus infection in Kuwait. J. Med. Virol. 85:1611–1618, 2013. © 2013 Wiley Periodicals, Inc.
The prevalence of neutralizing antibodies against AAV serotype 1 in healthy subjects in China: Implications for gene therapy and vaccines using AAV1 vector
Authors: Liu Qiang , Huang Weijin , Zhao Chenyan , Zhang Li , Meng Shufang , Gao Dongying , Wang Youchun 
Published: July 2013

ABSTRACTRecombinant adeno‐associated virus serotype 1 (AAV1) has attracted tremendous interest as a promising vector for gene therapy and vaccine applications. However, the presence of AAV1 neutralizing antibodies as a consequence of exposure to wild type AAV1 can limit significantly effective gene transfer for biologics based AAV1 vector. Prior studies have reported that a prevalence of AAV1 neutralizing antibodies ranged from 10% to 50% in different countries around the world, and up to 79% in Dutch subjects. However, few studies have reported on the AAV1 neutralizing antibody prevalence in Chinese subjects. In this study, a high‐throughput luciferase‐based virus neutralization assay was established and standardized for critical parameters, including the appropriate cell line, and the optimal viral infection dose, and the infection time with homologous AAV1 vaccinated mice and guinea pig sera. Then, a total of 500 healthy individual serum samples from two separate regions of China were screened for the AAV1 neutralizing antibodies by conducting a non‐randomized, cross‐sectional analysis. Interestingly, a high prevalence of AAV1 neutralizing antibody (69.8%) was found in all individuals. There was significant difference observed for prevalence by gender (P = 0.042), age range (P = 0.011) and geographic origin (P < 0.001). The percentage of positive AAV1 neutralizing antibodies (NT50 > 10) in teenagers (year <18, as of 2012) was significant lower than that of adults (19–56, as of 2012) (P = 0.011), indicating the optimal vaccination period of childhood. The current study provides a useful insight for the future development of AAV1‐based vaccination and gene therapy strategies in Beijing and Anhui provinces of China. J. Med. Virol. 85:1550–1556, 2013. © 2013 Wiley Periodicals, Inc.
Intratypic variants of human papillomavirus type 16 and risk of cervical Neoplasia in Taiwan
Authors: Chang Ya‐Ju , Chen Hui‐Chi , Pan Mei‐Hung , Lee Bor‐Heng , You San‐Lin , Lin Ching‐Yu , Chou Yi‐Chun , Hsieh Chang‐Yao , Cheng Yu‐Juen , Liaw Kai‐Li , Hsing Ann W. , Schiffman Mark , Chen Chien‐Jen ,   for the CBCSP‐HPV Study Group
Published: July 2013

AbstractThe associations between variants of human papillomavirus (HPV) 16 and risk of cervical neoplasia have been reported, but nucleotide variations of HPV 16 in Asian populations and their association with cervical neoplasia have not been evaluated extensively. During 1991–1992, 11,923 women from seven townships in Taiwan were enrolled. The HPV DNA in cervical cells was detected and genotyped using EasyChip HPV blot. Nucleotide variations in the long control region (LCR), E6, and E7 genes were determined using DNA sequencing for 170 HPV 16‐positive cervical samples. The Asian variant was the most prevalent variant (81.8%) of HPV 16 in Taiwan, and was also associated with increased prevalence of histologically confirmed cervical intraepithelial neoplasia grade 3 or worse, showing an age‐adjusted odds ratio (exact confidence limits) of 10.70 (1.62–451.05; P = 0.0049) compared to the HPV 16 European variant. Similar significant associations with cervical intraepithelial neoplasia grade 3 or worse were also observed for distinct nucleotide substitutions, including T178A/G, A647G, A7730C/G, T7781C, G7842A, and C24T/G. These results demonstrate that non‐European variants (non‐E) of HPV 16, predominantly Asian variants, are associated with increased risk for severe cervical neoplasia, compared with European variants. Molecular mechanisms accounting for varied cervical neoplasia risk among different HPV 16 variants warrant further investigation. J. Med. Virol. 85:1567–1576, 2013. © 2013 Wiley Periodicals, Inc.
Prevalence of human papillomavirus infection in women in some cities and regions of Bulgaria
Authors: Kovachev Stefan , Slavov Victor , Slavova Kremena 
Published: July 2013

ABSTRACTThis aim of this study was to evaluate the prevalence of human papillomavirus (HPV) infections among women (aged 15–55 years) in four of the biggest cities and regions in Bulgaria (viz., Sofia, Plovdiv, Varna, and Burgas), as well as in two other smaller cities (viz., Pleven and Vidin). Furthermore, study aimed to identify the prevalence of the 12 high‐risk HPV (HR‐HPV) genotypes in 2012, and to predict the benefits of a future national vaccination campaign for 12‐year‐old girls in Bulgaria. This HPV genotypes prevalence study covered 2,331,341 women from these cities and regions, representing 61.7% of the female population of Bulgaria. DNA‐sorb‐AM nucleic acid extraction kit was used to analyze the HPV status in cervical samples collected during a 4‐year period (2008–2011) from 1,120 women aged 15–55 years (divided into four age groups) who had visited 47 gynecological clinics across the study sites. HR‐HPV infections were confirmed in 435 (38.8%) of the women examined. The remaining 685 (61.2%) women were found to be HR‐HPV negative. The most common genotype in all 435 infected women was HPV16, which was found in 200 women (46%), followed by HPV56 in 86 women (19.8%), HPV31 in 53 women (12.2%), and HPV33 in 50 women (11.5%). This is the first study to have established the prevalence of HR‐HPV infections in the larger Bulgarian regions and cities (including the capital), and to have drawn attention to the unusually high proportion of the different HR‐HPV genotypes. J. Med. Virol. 85:1577–1584, 2013. © 2013 Wiley Periodicals, Inc.
Coinfection of hepatitis B and hepatitis delta virus in Belgium: A multicenter BASL study. Prospective epidemiology and comparison with HBV mono‐infection
Authors: Ho E. , Deltenre P. , Nkuize M. , Delwaide J. , Colle I. , Michielsen P. ,   Belgian Association for the Study of the Liver
Published: July 2013

ABSTRACTEpidemiological data on hepatitis delta virus (HDV) infection in Belgium are lacking. A multicenter questionnaire‐based registry on HDV infection was collated between March 1, 2008 and February 28, 2009. It consisted of patients coinfected with hepatitis B virus (HBV) and HDV. The data samples were compared to those of a concurrent registry on HBV infection. Prospective data of patients with HBV–HDV coinfection were collected. Active HBV replication is defined as HBeAg positivity or HBV DNA > 2,000 IU/ml. Forty‐four patients from 15 centers were registered. A comparison of 29 patients infected with HDV (registered in the concurrent HBV registry) was made against 785 HBV mono‐infected patients. The seroprevalence of patients coinfected with HBV and HDV in Belgium is reported to be 3.7% (29/785), consisting solely of the HBV–HDV coinfected patients in the HBV registry. This rises to 5.5% (44/800) if all patients infected with HDV from the two registries combined are included. The patients coinfected with HBV and HDV had higher (P < 0.05) ALT values and more advanced liver disease (Metavir score ≥F2), but had less active HBV replication and lower HBV DNA titers when compared with the patients infected only with HBV. Additionally, the majority of HBV–HDV coinfected patient was male, and 13.6% (6/44) of the patients that were coinfected HBV and HDV were also infected with HCV. In conclusion, this study provided much needed epidemiological data on the current state of HDV infection in Belgium. J. Med. Virol. 85:1513–1517, 2013. © 2013 Wiley Periodicals, Inc.
Long‐term efficacy of the hepatitis B Vaccine in a high‐risk group
Authors: Al Ghamdi Sarah S. , Fallatah Hind I. , Fetyani Dina M. , Al‐Mughales Jamil A. , Gelaidan Abdulhadi T. 
Published: July 2013

AbstractChronic infection with hepatitis B virus (HBV) is a global health problem. In an attempt to control infection, worldwide HBV vaccination programs have been established. Saudi Arabia, an endemic area for HBV infection, established an HBV immunization program in 1989. This cross‐sectional study evaluates the long‐term protection of HBV vaccination 14–24 years after primary immunization in a high‐risk group (clinical year medical students) at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. All participants had complete HBV immunization at birth or in early childhood. Hepatitis B surface antibody (anti‐HBs) levels were obtained. An anti‐HBs titer of <10 mIU/ml indicated no protection, while a titer of >10 mIU/ml was considered to represent protective immune status. A total of 238 students were included; they were predominantly females (n = 182, 76.5%). Mean age was 22.2 ± 1.1 years. Duration since primary vaccination was 19.8 ± 2.3 years. Female students were more likely to maintain long‐term protection compared to males (62.1% and 58.8%, respectively). Anti‐HBs levels were significantly low in many students after primary immunization. Testing medical students for anti‐HBs levels may be warranted as they represent a high‐risk population. The higher rate of vaccine failure in males than females requires further investigation as it may explain the higher prevalence of HBV in the male population. J. Med. Virol. 85:1518–1522, 2013. © 2013 Wiley Periodicals, Inc.
Evaluation of the automated multianalyte point‐of‐care mariPOC® test for the detection of influenza A virus and respiratory syncytial virus
Authors: Tuuminen Tamara , Suomala Päivi , Koskinen Janne O. 
Published: July 2013

AbstractThe aim of the study was to evaluate the performance of the new mariPOC® method against the direct fluorescent antibody assay (DFA) as the primary reference method for rapid virus detection from nasopharyngeal aspirates and swab samples. The study was an open prospective evaluation during the seasonal winter epidemics in the Mikkeli Central Hospital, Finland. Altogether, 283 samples were analyzed; 124 (43.8%) were from young children (<5 years old). Discrepant samples were resolved by PCR. With nasopharyngeal aspirate samples, the sensitivity and clinical specificity of the mariPOC® assay for influenza A virus and respiratory syncytial virus, were 85.7% (CI 69.7–95.2) and 90% (CI 52.0–80.5), and 100% and 99.5%, respectively. The mariPOC® performed less well with swab samples having sensitivities at 77.3% (CI 54.6–92.2) and 67.4% (CI 52–80.5), respectively. The specificities were as for nasopharyngeal aspirates. Importantly, similar performance was observed regardless of the cohort age group. In conclusion, the mariPOC® test system has a high potential and utility in duty units because it is fast, simple, and multianalyte. The importance of personnel training for proper sample collection should be emphasized. J. Med. Virol. 85:1598–1601, 2013. © 2013 Wiley Periodicals, Inc.
Prevalence and quantitation of adenovirus DNA from human tonsil and adenoid tissues
Authors: Alkhalaf Moustafa Alissa , Guiver Malcolm , Cooper Robert J 
Published: July 2013

AbstractIn this study, real‐time PCR was used to quantify adenovirus DNA in cell suspensions prepared from 106 right and left tonsils and 10 adenoids obtained from 57 patients who underwent routine tonsillectomies and/or adenoidectomies. Eighty‐four (72.4%) tonsils and adenoids samples were positive for HAdV by real‐time PCR. The viral load ranged from 2.8 × 102 to 2.6 × 106 copies/107 cells and varied up to sixfold between the right and left tonsils. In some cases, only one tonsil was positive and the viral load was lower in older children. Seventy‐eight of 84 positive samples could be typed by sequencing of the hexon L1 region. Species C (types 1, 2, and 5) were detected in 84.1% of the patients followed by types 3 and 7 of species B (6.8%), HAdV‐E4 (6.8%), and HAdV‐F41 (2.3%). In one patient adenovirus C2 was found in the left tonsil and adenovirus C5 in the right tonsil. No DNA methylation was detected in either the E1A promoter or the major late promoter region of adenovirus DNA from six tonsils and adenoids samples and two clinical isolates. J Med. Virol. 85:1947–1954, 2013.. © 2013 Wiley Periodicals, Inc.
Evidence of ljungan virus specific antibodies in humans and rodents, Finland
Authors: Jääskeläinen Anne J. , Kolehmainen Pekka , Voutilainen Liina , Hauffe Heidi C. , Kallio‐Kokko Hannimari , Lappalainen Maija , Tolf Conny , Lindberg A. Michael , Henttonen Heikki , Vaheri Antti , Tauriainen Sisko , Vapalahti Olli 
Published: July 2013

AbstractLjungan virus (LV, genus Parechovirus, family Picornaviridae) is considered currently to be a rodent‐borne virus. Despite suggested human disease associations, its zoonotic potential remains unclear. To date, LV antibody prevalence in both humans and rodents has not been studied. In this study, two different LV immunofluorescence assays (LV IFAs) were developed with LV genotypes 1 (LV strain 87‐012G) and 2 (LV strain 145SLG), and cross‐neutralization and ‐reaction studies were carried out with LV strain 145SLG. Finally, a panel of 37 Finnish sera was screened for anti‐LV antibodies using two different LV IFAs (LV 145SLG and LV 87‐012G) and a neutralization (NT) assay (LV 145SLG), and 50 samples from Myodes glareolus by LV IFA (LV 145SLG). The LV seroprevalence study showed 38% and 18% positivity in humans and M. glareolus, respectively. LV IFAs and NT assays were compared, and the results were in good agreement. The data are the first evidence of humans and rodents coming into contact with LV in Finland. Additional studies are required in order to acquire a better understanding of the prevalence, epidemiological patterns and possible disease association of LV infections. J Med. Virol. 85:2001–2008, 2013. © 2013 Wiley Periodicals, Inc.
An attenuated temperature‐sensitive strain of cytomegalovirus (tsm5) establishes immunity without development of CD8+ T cell memory inflation
Authors: Beswick Mark , Pachnio Annette , Al‐Ali Abdulaziz , Sweet Clive , Moss Paul A. 
Published: July 2013

AbstractCytomegalovirus (CMV) is a widely prevalent herpesvirus that is well tolerated by an immune competent host yet establishes a state of chronic infection. The virus is thought to undergo frequent subclinical episodes of reactivation which leads to an unusually large accumulation of CMV‐specific CD8+ T lymphocytes in the peripheral blood, a phenomenon termed “memory inflation.” The high magnitude of the CMV T cell response has been implicated in impaired immunity to heterologous pathogens such as EBV, influenza and West Nile virus. Here, using murine CMV (MCMV), we show that memory inflation of virus‐specific CD8+ T cells is avoided if mice are infected with a replication defective virus called temperature‐sensitive mutant 5 (tsm5), which carries an attenuating mutation within the DNA primase gene. Mice infected with tsm5 do generate primary T cell responses towards viral proteins but these do not amass to skew the memory repertoire of CD8+ T cells. Therefore, attenuation of the virus replication machinery may be valuable in future CMV vaccine designs because the virus remains immunogenic but does not contribute to CMV associated T cell immune senescence. J Med. Virol. 85:1968–1974, 2013. © 2013 Wiley Periodicals, Inc.
High cardiovascular risk profile in patients with sleep apnea
Authors: Herrscher Tobias E. , Overland Britt , Sandvik Leiv , Westheim Arne S. , Akre Harriet 
Published: July 2013

Objectives/HypothesisSleep apnea is associated with hypertension and diabetes, putting these patients at high risk for developing cardiovascular disease. The goal of this study was to identify the individual cardiovascular risk profile and to detect premature and undiagnosed disease in patients with various degrees of sleep apnea.Study DesignCross‐sectional.MethodsOver a 6‐month period, we consecutively characterized all patients referred to our sleep laboratory for an initial evaluation of sleep apnea. Clinical history; blood tests with oral glucose tolerance test, when appropriate; test for microalbuminuria; and an electrocardiogram (ECG) were performed. The Framingham general cardiovascular risk score was assessed in each patient.ResultsA total of 255 patients were evaluated. Of those, 190 (75%) were diagnosed with sleep apnea. Patients with sleep apnea had a significantly higher Framingham risk score than patients without sleep apnea. Adjusted for age and gender, severe sleep apnea was associated with a 60% increased cardiovascular risk compared with not having sleep apnea. In sleep apnea patients without previously diagnosed hypertension, an additional 45% had significant elevated blood pressure. Among sleep apnea patients without known diabetes, we tested 48% with a pathological glucose disposal. Twenty percent of sleep apnea patients without known heart disease had significant ECG changes.ConclusionsHigh Framingham score, undiagnosed hypertension, and pathological glucose disposal were highly prevalent in patients with sleep apnea. Appropriate screening routines are important to detect cardiovascular risk factors in patients with sleep apnea.Level of Evidence2b. Laryngoscope, 124:306–310, 2014