bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quetiapine, QTc interval prolongation, and torsade de pointes: a review of case reports
Authors: Hasnain Mehrul , Vieweg W. Victor R. , Howland Robert H. , Kogut Christopher , Breden Crouse Ericka L. , Koneru Jayanthi N. , Hancox Jules C. , Digby Geneviève C. , Baranchuk Adrian , Deshmukh Anand , Pandurangi Ananda K. 
Published: November 2013

Recently, both the manufacturer of quetiapine and the US Food and Drug Administration warned healthcare providers and patients about quetiapine-induced QTc interval prolongation and torsade de pointes ( TdP) when using this drug within the approved labeling.  We reviewed the case-report literature and found 12 case reports of QTc interval prolongation in the setting of quetiapine administration. There were no cases of quetiapine-induced TdP or sudden cardiac death (SCD) among patients using quetiapine appropriately and free of additional risk factors for QTc interval prolongation and TdP. Among the 12 case reports risk factors included female sex (nine cases), coadministration of a drug associated with QTc interval prolongation (eight cases), hypokalemia or hypomagnesemia (six cases) quetiapine overdose (five cases), cardiac problems (four cases), and coadministration of cytochrome P450 3A4 inhibitors (two cases). There were four cases of TdP. As drug-induced TdP is a rare event, prospective studies to evaluate the risk factors associated with QTc prolongation and TdP are difficult to design, would be very costly, and would require very large samples to capture TdP rather than its surrogate markers. Furthermore, conventional statistical methods may not apply to studies of TdP, which is rare and an ‘outlier’ manifestation of QTc prolongation. We urge drug manufacturers and regulatory agencies to periodically publish full case reports of psychotropic drug-induced QTc interval prolongation, TdP, and SCD so that clinicians and investigators may better understand the clinical implications of prescribing such drugs as quetiapine.
An animal model of adult T-cell leukemia: humanized mice with HTLV-1–specific immunity
Authors: Tezuka Kenta , Xun Runze , Tei Mami , Ueno Takaharu , Tanaka Masakazu , Takenouchi Norihiro , Fujisawa Jun-ichi 
Published: November 2013

Key Points
Humanized mice, IBMI-huNOG, were generated by intra–bone marrow injection of human CD133+ hematopoietic stem cells. HTLV-1–infected IBMI-huNOG mice recapitulated distinct ATL-like symptoms as well as HTLV-1–specific adaptive immune responses.
Comparative transcriptome analysis of geographically distinct virulent and attenuated Babesia bovis strains reveals similar gene expression changes through attenuation
Authors: Pedroni Monica J , Sondgeroth Kerry S , Gallego-Lopez Gina M , Echaide Ignacio , Lau Audrey OT 
Published: November 2013

Abstract

Background
Loss of virulence is a phenotypic adaptation commonly seen in prokaryotic and eukaryotic pathogens. This mechanism is not well studied, especially in organisms with multiple host and life cycle stages such as Babesia, a tick-transmitted hemoparasite of humans and animals. B. bovis, which infects cattle, has naturally occurring virulent strains that can be reliably attenuated in vivo. Previous studies suggest the virulence loss mechanism may involve post-genomic modification. We investigated the transcriptome profiles of two geographically distinct B. bovis virulent and attenuated strain pairs to better understand virulence loss and to gain insight into pathogen adaptation strategies.

Results
Expression microarray and RNA-sequencing approaches were employed to compare transcriptome profiles of two B. bovis strain pairs, with each pair consisting of a virulent parental and its attenuated derivative strain. Differentially regulated transcripts were identified within each strain pair. These included genes encoding for VESA1, SmORFs, undefined membrane and hypothetical proteins. The majority of individual specific gene transcripts differentially regulated within a strain were not shared between the two strains. There was a disproportionately greater number of ves genes upregulated in the virulent parental strains. When compared with their attenuated derivatives, divergently oriented ves genes were included among the upregulated ves genes in the virulent strains, while none of the upregulated ves genes in the attenuated derivatives were oriented head to head. One gene family whose specific members were consistently and significantly upregulated in expression in both attenuated strains was spherical body protein (SBP) 2 encoding gene where SBP2 truncated copies 7, 9 and 11 transcripts were all upregulated.

Conclusions
We conclude that ves heterodimer pair upregulation and overall higher frequency of ves gene expressions in the virulent strains is consistent with the involvement of this gene family in virulence. This is logical given the role of VESA1 proteins in cytoadherence of infected cells to endothelial cells. However, upregulation of some ves genes in the attenuated derivatives suggests that the consequence of upregulation is gene-specific. Furthermore, upregulation of the spherical body protein 2 gene family may play a role in the attenuated phenotype. Exactly how these two gene families may contribute to the loss or gain of virulence is discussed.
Visual pursuit response in the severe disorder of consciousness: modulation by the central autonomic system and a predictive model
Authors: Riganello Francesco , Cortese Maria D , Dolce Giuliano , Sannita Walter G 
Published: November 2013

Abstract

Background
A visual pursuit response is reportedly observed in ~20-30% of subjects in vegetative state (VS/UWS) and predicts better outcome; it is a key marker of evolution into the minimally conscious state (MCS). The probability of observing a positive response, however, has proven variable during the day, with comparable timing of the minima and maxima in VS/UWS and MCS. We verified if measures of sympathetic/parasympathetic balance are possible independent variables on which the occurrence of a pursuit response could depend and be predicted.

Methods
Fourteen subjects in VS/UWS and sixteen in MCS for more than one year were studied. A mirror was used to test the pursuit response for a total 231 useful trials. Non-invasive measures of the sympathetic/parasympathetic functional state (Heart rate variability descriptors nuLF and peakLF) used in the study of responsiveness in VS/UWS and MCS subjects were recorded and processed by descriptive statistics and advanced Support Vector Machine (SVM).

Results
A pursuit response was observed in 33% and 78.2% of subjects in VS or MCS, respectively. Incidence was higher at HRV nuLF values in the 20–60 range and peakLF values at 0.06-0.12 Hz (76.6%) and at nuLF values in the 10–60 range and peakLF values at 0.05-0.10 Hz (80.7%) in the VS and MCS, respectively. The SVM generated model confirmed the results in the training leave one out and 10 fold cross validation tests (81% and 81.4%).

Conclusion
The pursuit response incidence depends to a relevant extent on the sympathetic/parasympathetic balance and autonomic functional state. Extensive monitoring appears advisable.
Assessment of early changes in 3H-fluorothymidine uptake after treatment with gefitinib in human tumor xenograft in comparison with Ki-67 and phospho-EGFR expression
Authors: Zhao Songji , Kuge Yuji , Zhao Yan , Takeuchi Satoshi , Hirata Kenji , Takei Toshiki , Shiga Tohru , Dosaka-Akita Hirotoshi , Tamaki Nagara 
Published: November 2013

Abstract

Background
The purpose of this study was to evaluate whether early changes in 3′-deoxy-3′-3H-fluorothymidine (3H-FLT) uptake can reflect the antiproliferative effect of gefitinib in a human tumor xenograft, in comparison with the histopathological markers, Ki-67 and phosphorylated EGFR (phospho-EGFR).

Methods
An EGFR-dependent human tumor xenograft model (A431) was established in female BALB/c athymic mice, which were divided into three groups: one control group and two treatment groups. Mice in the treatment groups were orally administered a partial regression dose (100 mg/kg/day) or the maximum tolerated dose of gefitinib (200 mg/kg/day), once daily for 2 days. Mice in the control group were administered the vehicle (0.1% Tween 80). Tumor size was measured before and 3 days after the start of treatment. Biodistribution of 3H-FLT and 18F-FDG (%ID/g/kg) was examined 3 days after the start of the treatment. Tumor cell proliferative activity with Ki-67 was determined. Immunohistochemical staining of EGFR and measurement of phospho-EGFR were also performed.

Results
High expression levels of EGFR and Ki-67 were observed in the A431 tumor. After the treatment with 100 and 200 mg/kg gefitinib, the uptake levels of 3H-FLT in the tumor were significantly reduced to 67% and 61% of the control value, respectively (0.39 ± 0.09, 0.36 ± 0.06, 0.59 ± 0.11%ID/g/kg for 100 mg/kg, 200 mg/kg, and control groups, respectively; p < 0.01 vs. control), but those of 18F-FDG were not. After the treatment with 100 and 200 mg/kg gefitinib, the expression levels of Ki-67 in the tumor were markedly decreased (4.6 ± 2.4%, 6.2 ± 1.8%, and 10.4 ± 5.7% for 100 mg/kg, 200 mg/kg, and control groups, respectively, p < 0.01 vs. control). The expression levels of the phospho-EGFR protein also significantly decreased (29% and 21% of the control value for 100, and 200 mg/kg, respectively p < 0.01 vs. control). There was no statistically significant difference in tumor size between pre- and post-treatments in each group.

Conclusion
In our animal model, 3H-FLT uptake levels significantly decreased after the treatment with two different doses of gefitinib before a significant change in tumor size was observed. These results were confirmed by the immunohistochemical staining of Ki-67 and phospho-EGFR protein immunoassay. Thus, it was indicated that early changes in 3H-FLT uptake may reflect the antiproliferative effect of gefitinib in a mouse model of a human epidermoid cancer.
Relationships between self-rated oral health, subjective symptoms, oral health behavior and clinical conditions in Japanese university students: a cross-sectional survey at Okayama University
Authors: Kojima Azusa , Ekuni Daisuke , Mizutani Shinsuke , Furuta Michiko , Irie Koichiro , Azuma Tetsuji , Tomofuji Takaaki , Iwasaki Yoshiaki , Morita Manabu 
Published: November 2013

Abstract

Background
Self-rated oral health is a valid and useful summary indicator of overall oral health status and quality of life. However, few studies on perception of oral health have been conducted among Japanese young adults. This study investigated whether oral health behavior, subjective oral symptoms, or clinical oral status were associated with self-rated oral health in Japanese young adults.

Methods
This cross-sectional survey included 2,087 students (1,183 males, 904 females), aged 18 and 19 years, at Okayama University, Japan. A self-administered questionnaire was distributed and an oral examination was performed.

Results
In a structural equation modeling analysis, the score of decayed, missing and filled teeth (DMFT) significantly affected self-rated oral health (p <0.05) and the effect size was highest. Malocclusion, subjective symptoms of temporomandibular disorders (TMD) and stomatitis, and poor oral health behavior significantly induced self-rated poor oral health with small effect sizes (p <0.05). Clinical periodontal conditions and Oral Hygiene Index-simplified were not related to self-rated oral health.

Conclusion
Self-rated oral health was influenced by subjective symptoms of TMD and stomatitis, oral health behavior, the score of DMFT, and malocclusion. The evaluation of these parameters may be a useful approach in routine dental examination to improve self-rated oral health in university students.
Effects of coenzyme Q10 supplementation (300 mg/day) on antioxidation and anti-inflammation in coronary artery disease patients during statins therapy: a randomized, placebo-controlled trial
Authors: Lee Bor-Jen , Tseng Yu-Fen , Yen Chi-Hua , Lin Ping-Ting 
Published: November 2013

Abstract

Background
High oxidative stress and chronic inflammation can contribute to the pathogenesis of coronary artery disease (CAD). Coenzyme Q10 is an endogenous lipid-soluble antioxidant. Statins therapy can reduce the biosynthesis of coenzyme Q10. The purpose of this study was to investigate the effects of a coenzyme Q10 supplement (300 mg/d; 150 mg/b.i.d) on antioxidation and anti-inflammation in patients who have CAD during statins therapy.

Methods
Patients who were identified by cardiac catheterization as having at least 50% stenosis of one major coronary artery and who were treated with statins for at least one month were enrolled in this study. The subjects (n = 51) were randomly assigned to the placebo (n = 24) and coenzyme Q10 groups (Q10-300 group, n = 27). The intervention was administered for 12 weeks. The concentrations of coenzyme Q10, vitamin E, antioxidant enzymes activities (superoxide dismutase, catalase, and glutathione peroxidase), and inflammatory markers [C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6)] were measured in the 42 subjects (placebo, n = 19; Q10-300, n = 23) who completed the study.

Results
The levels of the plasma coenzyme Q10 (P < 0.001) and antioxidant enzymes activities (P < 0.05) were significantly higher after coenzyme Q10 supplementation. The levels of inflammatory markers (TNF-α, P = 0.039) were significantly lower after coenzyme Q10 supplementation. The subjects in the Q10-300 group had significantly higher vitamin E (P = 0.043) and the antioxidant enzymes activities (P < 0.05) than the placebo group at week 12. The level of plasma coenzyme Q10 was significantly positively correlated with vitamin E (P = 0.008) and antioxidant enzymes activities (P < 0.05) and was negatively correlated with TNF-α (P = 0.034) and IL-6 (P = 0.027) after coenzyme Q10 supplementation.

Conclusion
Coenzyme Q10 supplementation at 300 mg/d significantly enhances antioxidant enzymes activities and lowers inflammation in patients who have CAD during statins therapy.

Trial registration
Clinical Trials.gov Identifier: NCT01424761.
Quantitative assessment of carotid plaque surface irregularities and correlation to cerebrovascular symptoms
Authors: Kanber Baris , Hartshorne Timothy C , Horsfield Mark A , Naylor A Ross , Robinson Thompson G , Ramnarine Kumar V 
Published: November 2013

Abstract

Background
The purpose of this study was to determine whether surface irregularities measured from ultrasound images of carotid artery plaques and quantified using a novel method, correlate with the presence of ipsilateral hemispheric cerebrovascular symptoms.

Methods
A plaque surface irregularity index (SII) was measured in 47 carotid artery plaques (32 subjects, stenosis range 10% -95%, 49% symptomatic) using ultrasound image sequences spanning several cardiac cycles. The differences in the distribution of SII in plaques with ipsilateral hemispheric symptoms versus those without symptoms and the correlation between the SII of plaques and the degrees of stenosis of the corresponding arteries were assessed. Diagnostic performance of plaque SII was evaluated on its own and in combination with the degree of stenosis.

Results
The mean SII was significantly greater for plaques with ipsilateral hemispheric symptoms (1.89 radians/mm) than for asymptomatic plaques (1.67 radians/mm, p = 0.03). There was no statistically significant association between the SII and the degree of stenosis (p = 0.30). SII predicted the presence of cerebrovascular symptoms with an accuracy of 66% (sensitivity 65%, specificity 67%) on its own and with an accuracy of 83% (sensitivity 96%, specificity 71%) in combination with the degree of stenosis.

Conclusions
Quantitative assessment of carotid plaque surface irregularities using a novel SII parameter correlates with the presence ipsilateral hemispheric cerebrovascular symptoms and may increase diagnostic performance beyond that provided by the degree of stenosis.
Cytogenetic analysis of quinoa chromosomes using nanoscale imaging and spectroscopy techniques
Authors: Yangquanwei Zhong , Neethirajan Suresh , Karunakaran Chithra 
Published: November 2013

Abstract
Here we present a high-resolution chromosomal spectral map derived from synchrotron-based soft X-ray spectromicroscopy applied to quinoa species. The label-free characterization of quinoa metaphase chromosomes shows that it consists of organized substructures of DNA-protein complex. The analysis of spectra of chromosomes using the scanning transmission X-ray microscope (STXM) and its superposition of the pattern with the atomic force microscopy (AFM) and scanning electron microscopy (SEM) images proves that it is possible to precisely locate the gene loci and the DNA packaging inside the chromosomes. STXM has been successfully used to distinguish and quantify the DNA and protein components inside the quinoa chromosomes by visualizing the interphase at up to 30-nm spatial resolution. Our study represents the successful attempt of non-intrusive interrogation and integrating imaging techniques of chromosomes using synchrotron STXM and AFM techniques. The methodology developed for 3-D imaging of chromosomes with chemical specificity and temporal resolution will allow the nanoscale imaging tools to emerge from scientific research and development into broad practical applications such as gene loci tools and biomarker libraries.
Integrating multiple ‘omics’ analyses identifies serological protein biomarkers for preeclampsia
Authors: Liu Linda Y , Yang Ting , Ji Jun , Wen Qiaojun , Morgan Alexander A , Jin Bo , Chen Gongxing , Lyell Deirdre J , Stevenson David K , Ling Xuefeng B , Butte Atul J 
Published: November 2013

Abstract

Background
Preeclampsia (PE) is a pregnancy-related vascular disorder which is the leading cause of maternal morbidity and mortality. We sought to identify novel serological protein markers to diagnose PE with a multi-’omics’ based discovery approach.

Methods
Seven previous placental expression studies were combined for a multiplex analysis, and in parallel, two-dimensional gel electrophoresis was performed to compare serum proteomes in PE and control subjects. The combined biomarker candidates were validated with available ELISA assays using gestational age-matched PE (n=32) and control (n=32) samples. With the validated biomarkers, a genetic algorithm was then used to construct and optimize biomarker panels in PE assessment.

Results
In addition to the previously identified biomarkers, the angiogenic and antiangiogenic factors (soluble fms-like tyrosine kinase (sFlt-1) and placental growth factor (PIGF)), we found 3 up-regulated and 6 down-regulated biomakers in PE sera. Two optimal biomarker panels were developed for early and late onset PE assessment, respectively.

Conclusions
Both early and late onset PE diagnostic panels, constructed with our PE biomarkers, were superior over sFlt-1/PIGF ratio in PE discrimination. The functional significance of these PE biomarkers and their associated pathways were analyzed which may provide new insights into the pathogenesis of PE.
Construction of a full-length infectious bacterial artificial chromosome clone of duck enteritis virus vaccine strain
Authors: Chen Liu , Yu Bin , Hua Jionggang , Ye Weicheng , Ni Zheng , Yun Tao , Deng Xiaohui , Zhang Cun 
Published: November 2013

AbstractBackgroundDuck enteritis virus(DEV) is the causative agent of duck viral enteritis, which causes an acute, contagious and lethal disease of many species of waterfowl within the orderAnseriformes. In recent years, two laboratories have reported on the successful construction of DEV infectious clones in viral vectors to express exogenous genes. The clones obtained were either created with deletion of viral genes and based on highly virulent strains or were constructed using a traditional overlapping fosmid DNA system. Here, we report the construction of a full-length infectious clone of DEV vaccine strain that was cloned into a bacterial artificial chromosome (BAC).MethodsA mini-F vector as a BAC that allows the maintenance of large circular DNA inE. coliwas introduced into the intergenic region between UL15B and UL18 of a DEV vaccine strain by homologous recombination in chicken embryoblasts (CEFs). Then, the full-length DEV clone pDEV-vac was obtained by electroporating circular viral replication intermediates containing the mini-F sequence intoE. coliDH10B and identified by enzyme digestion and sequencing. The infectivity of the pDEV-vac was validated by DEV reconstitution from CEFs transfected with pDEV-vac. The reconstructed virus without mini-F vector sequence was also rescued by co-transfecting the Cre recombinase expression plasmid pCAGGS-NLS/Cre and pDEV-vac into CEF cultures. Finally, thein vitrogrowth properties and immunoprotection capacity in ducks of the reconstructed viruses were also determined and compared with the parental virus.ResultsThe full genome of the DEV vaccine strain was successfully cloned into the BAC, and this BAC clone was infectious. Thein vitrogrowth properties of these reconstructions were very similar to parental DEV, and ducks immunized with these viruses acquired protection against virulent DEV challenge.ConclusionsDEV vaccine virus was cloned as an infectious bacterial artificial chromosome maintaining full-length genome without any deletions or destruction of the viral coding sequence, and the viruses rescued from the DEV-BAC clone exhibited wild-type phenotypes bothin vitroandin vivo. The generated infectious clone will greatly facilitate studies on the individual genes of DEV and applications in gene deletion or live vector vaccines.
Lack of P2Y13 in mice fed a high cholesterol diet results in decreased hepatic cholesterol content, biliary lipid secretion and reverse cholesterol transport
Authors: Lichtenstein Laeticia , Serhan Nizar , Annema Wijtske , Combes Guillaume , Robaye Bernard , Boeynaems Jean-Marie , Perret Bertrand , Tietge Uwe J F , Laffargue Muriel , Martinez Laurent O 
Published: November 2013

Abstract

Background
The protective effect of HDL is mostly attributed to their metabolic function in reverse cholesterol transport (RCT), a process whereby excess cellular cholesterol is taken up from peripheral cells, processed in HDL particles, and later delivered to the liver for further metabolism and biliary secretion. Mechanistically, the purinergic P2Y13 ADP-receptor is involved in hepatic HDL endocytosis (i.e., uptake of both HDL protein + lipid moieties), which is considered an important step of RCT. Accordingly, chow-fed P2Y13 knockout (P2Y13
-/-) mice exhibit lower hepatic HDL uptake, which translates into a decrease of hepatic free cholesterol content and biliary cholesterol and phospholipid secretion.

Findings
The aim of this study was to determine the effect of high cholesterol diet (HCD) in P2Y13
-/- mice, in order to mimic high dietary cholesterol intake, which is a major cause of dyslipidemia in humans. As previously reported with chow-diet, HCD did not affect plasma lipid levels in P2Y13
-/- compared with control mice but decreased hepatic free and esterified cholesterol content (p < 0.05, P2Y13
-/- versus control). Interestingly, biliary lipid secretion and macrophages-to-feces RCT were more dramatically impaired in P2Y13
-/- mice fed a HCD than chow-diet. HCD did not enhance atherosclerosis in P2Y13
-/- compared with control mice.

Conclusion
This study demonstrates that high dietary cholesterol intake accentuated the metabolic phenotype of P2Y13
-/- mice, with impaired hepatobiliary RCT. Although other animal models might be required to further evaluate the role of P2Y13 receptor in atherosclerosis, P2Y13 appears a promising target for therapeutic intervention aiming to stimulate RCT, particularly in individuals with lipid-rich diet.