bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virus and Host Factors Affecting the Clinical Outcome of Bluetongue Virus Infection
Authors: Caporale Marco , Di Gialleonorado Luigina , Janowicz Anna , Wilkie Gavin , Shaw Andrew , Savini Giovanni , Van Rijn Piet A. , Mertens Peter , Di Ventura Mauro , Palmarini Massimo 
Published: July 2014

ABSTRACTBluetongue is a major infectious disease of ruminants caused by bluetongue virus (BTV), an arbovirus transmitted byCulicoides. Here, we assessed virus and host factors influencing the clinical outcome of BTV infection using a single experimental framework. We investigated how mammalian host species, breed, age, BTV serotypes, and strains within a serotype affect the clinical course of bluetongue. Results obtained indicate that in small ruminants, there is a marked difference in the susceptibility to clinical disease induced by BTV at the host species level but less so at the breed level. No major differences in virulence were found between divergent serotypes (BTV-8 and BTV-2). However, we observed striking differences in virulence between closely related strains of the same serotype collected toward the beginning and the end of the European BTV-8 outbreak. As observed previously, differences in disease severity were also observed when animals were infected with either blood from a BTV-infected animal or from the same virus isolated in cell culture. Interestingly, with the exception of two silent mutations, full viral genome sequencing showed identical consensus sequences of the virus before and after cell culture isolation. However, deep sequencing analysis revealed a marked decrease in the genetic diversity of the viral population after passaging in mammalian cells. In contrast, passaging inCulicoidescells increased the overall number of low-frequency variants compared to virus never passaged in cell culture. Thus,Culicoidesmight be a source of new viral variants, and viral population diversity can be another factor influencing BTV virulence.IMPORTANCEBluetongue is one of the major infectious diseases of ruminants. It is caused by an arbovirus known as bluetongue virus (BTV). The clinical outcome of BTV infection is extremely variable. We show that there are clear links between the severity of bluetongue and the mammalian host species infected, while at the breed level differences were less evident. No differences were observed in the virulence of two different BTV serotypes (BTV-8 and BTV-2). In contrast, we show that the European BTV-8 strain isolated at the beginning of the bluetongue outbreak in 2006 was more virulent than a strain isolated toward the end of the outbreak. In addition, we show that there is a link between the variability of the BTV population as a whole and virulence, and our data also suggest thatCulicoidescells might function as an “incubator” of viral variants.
Legislative, educational, policy and other interventions targeting physicians’ interaction with pharmaceutical companies: a systematic review
Authors: Alkhaled Lina , Kahale Lara , Nass Hala , Brax Hneine , Fadlallah Racha , Badr Kamal , Akl Elie A 
Published: July 2014

BackgroundPharmaceutical company representatives likely influence the prescribing habits and professional behaviour of physicians.ObjectiveThe objective of this study was to systematically review the effects of interventions targeting practising physicians’ interactions with pharmaceutical companies.Eligibility criteriaWe included observational studies, non-randomised controlled trials (non-RCTs) and RCTs evaluating legislative, educational, policy or other interventions targeting the interactions between physicians and pharmaceutical companies.Data sourcesThe search strategy included an electronic search of MEDLINE and EMBASE. Two reviewers performed duplicate and independent study selection, data abstraction and assessment of risk of bias.Appraisal and synthesis methodsWe assessed the risk of bias in each included study. We summarised the findings narratively because the nature of the data did not allow a meta-analysis to be conducted. We assessed the quality of evidence by outcome using the GRADE methodology.ResultsOf 11 189 identified citations, one RCT and three observational studies met the eligibility criteria. All four studies specifically targeted one type of interaction with pharmaceutical companies, that is, interactions with drug representatives. The RCT provided moderate quality evidence of no effect of a ‘collaborative approach’ between the pharmaceutical industry and a health authority. The three observational studies provided low quality evidence suggesting a positive effect of policies aiming to reduce interaction between physicians and pharmaceutical companies (by restricting free samples, promotional material, and meetings with pharmaceutical company representatives) on prescription behaviour.LimitationsWe identified too few studies to allow strong conclusions.ConclusionsAvailable evidence suggests a potential impact of policies aiming to reduce interaction between physicians and drug representatives on physicians’ prescription behaviour. We found no evidence concerning interventions affecting other types of interaction with pharmaceutical companies.
Temporal relationship between hospital admissions for pneumonia and weather conditions in Shanghai, China: a time-series analysis
Authors: Liu Yuan , Kan Haidong , Xu Jianming , Rogers David , Peng Li , Ye Xiaofang , Chen Renjie , Zhang Yue , Wang Weibing 
Published: July 2014

ObjectivesTo explore the association between weather conditions and hospital admissions for pneumonia in Shanghai.DesignA time-series analysis was performed for a period of 4 years (January 2008–December 2011). A generalised additive model was used to calculate the relative risks.SettingShanghai, China.ParticipantsAll daily hospital admissions for pneumonia were obtained from the Shanghai health insurance system between 1 January 2008 and 31 December 2011 (n=99 403).ResultsThe relationship between the mean temperature and pneumonia hospital admissions followed a V-shaped curve, with an optimum temperature (OT) at 13°C. When the mean temperature was below the OT, a 1°C decrease corresponded to a 4.88% (95% CI 2.71% to 7.09%) and 5.34% (95% CI 2.04% to 8.74%) increase in pneumonia hospital admissions in lag 4 using a single-day lag structure and lag 0–7 using a multiday lag structure. When the mean temperature ≥OT, no adverse effects from the temperature on pneumonia hospital admissions were found. The magnitude of the effects of temperature varied across gender and age groups. Hospitalisations for pneumonia increased by 15.99% (95% CI 0.06% to 34.46%) in the cold period.ConclusionsCold temperature may be one of the important risk factors for pneumonia hospitalisations. Prevention programmes are needed to reduce the impact of cold temperature on pneumonia hospitalisations such as developing a weather warning system within a wide public health context.
The impact of chronic obstructive pulmonary disease on intensive care unit admission and 30-day mortality in patients undergoing colorectal cancer surgery: a Danish population-based cohort study
Authors: Platon Anna Maria , Erichsen Rune , Christiansen Christian Fynbo , Andersen Lea Kjær , Sværke Claus , Montomoli Jonathan , Sørensen Henrik Toft 
Published: July 2014

Background and purposeChronic obstructive pulmonary disease (COPD) may increase the risk of postoperative complications and thus mortality after colorectal cancer (CRC) surgery, but the evidence is sparse.MethodsWe conducted this nationwide population-based cohort study in Denmark, including all patients undergoing CRC surgery in the period 2005–2011, identified through medical databases. We categorised the patients according to the history of COPD.We assessed the rate of complications within 30 days. We computed 30-day mortality among patients with/without COPD using the Kaplan-Meier method. We used Cox regression to compute HRs for death, controlling for age, gender, type of admission, cancer stage, hospital volume, alcohol-related diseases, obesity and Charlson comorbidity score.ResultsWe identified 18 302 CRC surgery patients. Of these, 7.9% had a prior diagnosis of COPD. Among patients with COPD, 16.1% were admitted postoperatively to the intensive care unit, 1.9% were treated with mechanical ventilation, and 3.6% were treated with non-invasive ventilation. In patients without COPD, the corresponding proportions were 9.7%, 1.1% and 1.1%. The reoperation rate was 10.6% among patients with COPD and 8% among patients with cancer without COPD. 30-day mortality was 13% (95% CI 11.4% to 14.9%) among patients with COPD and 5.3% (95% CI 5.0% to 5.7%) among patients without COPD, corresponding to an adjusted HR of 1.7 (95% CI 1.5 to 2.0).ConclusionsCOPD is a strong predictor for intensive care unit admission and mortality after CRC surgery.
The syndrome of inappropriate antidiuresis is associated with excess long-term mortality: a retrospective cohort analyses
Authors: Basu Ansu , Ryder Robert E J 
Published: July 2014

IntroductionThe syndrome of inappropriate antidiuresis (SIAD) is the commonest cause of euvolaemic hyponatraemia in patients admitted to hospital. The mortality after discharge from hospital has not been previously studied in patients with SIAD.AimsTo compare mortality in patients with SIAD and those with kidney injury (KI). To identify underlying diagnoses associated with deaths due to SIAD.MethodsSingle-centre retrospective cohort analyses of 804 patients with severe hyponatraemia over a 3-year period. Five-year survival data in patients with SIAD and those with KI were compared. The underlying diagnoses that contributed to SIAD in this cohort were analysed using ICD-10 codes.Results202 patients had SIAD using biochemical cut-off parameters; 248 patients had KI. Patient with KI had a statistically significant (log-rank p<0.0001) shorter median survival time (2.24 months (95% CI 1.3 to 4.3)) compared with those with SIAD (31.0 months (95% CI 21.6 to 54.8)). 53.8% (n=78) of patients with hyponatraemia due to SIAD died within the first year after admission; the corresponding figure for those presenting with KI was 74.1% (n=166). Five years after admission, 80.8% (n=117) of those with SIAD had died; the corresponding figure for those with KI was 88.4% (n=200). In those patients with SIAD that died within the first year, malignancy appeared to be the most common cause (25.4%) followed by infection (23.8%).ConclusionsSevere hyponatraemia in SIAD carries a high mortality after discharge, and although this seems often to be attributable to the underlying cause, the extent to which treatment with V2-recptor antagonists may help to correct the hyponatraemia associated with SIAD and influence the medium-to-long-term outcome in such patients is worthy of further study.
Web based pathology assessment in RTOG 98-04
Authors: Woodward Wendy A , Sneige Nour , Winter Kathryn , Kuerer Henry Mark , Hudis Clifford , Rakovitch Eileen , Smith Barbara L , Pierce Lori J , Germano Isabelle , Pu Anthony T , Walker Eleanor M , Grisell David Lawrence , White Julia R , McCormick Beryl 
Published: July 2014

AimsRadiation Therapy Oncology Group 98-04 sought to identify women with ‘good risk’ ductal carcinoma in situ (DCIS) who receive no significant benefit from radiation. Enrolment criteria excluded close or positive margins and grade 3 disease. To ensure reproducibility in identifying good risk pathology, an optional web based teaching tool was developed and a random sampling of 10% of submitted slides were reviewed by a central pathologist.MethodsSubmitting pathologists were asked to use the web based teaching tool and submit an assessment of the tool along with the pathology specimen form and DCIS H&E stained slide. Per protocol pathology was centrally reviewed for 10% of the cases.ResultsOf the 55 DCIS cases reviewed, three had close or positive margins and three were assessed to include grade 3 DCIS, therefore 95% of DCIS cases reviewed were correctly graded, and 89% reviewed were pathologically appropriate for enrolment. Regarding the teaching tool, 13% of DCIS cases included forms that indicated the website was used. One of these seven who used the website submitted DCIS of grade 3.ConclusionsCentral review demonstrates high pathological concordance with enrolment eligibility, particularly with regard to accurate grading. The teaching tool appeared to be underused.
Suitability of Becton Dickinson Vacutainer rapid serum tube for collecting and storing blood samples for antibiotic and anticonvulsant drug monitoring
Authors: Yan Ronald , Colantonio David , Wong Pui-Yuen , Chen Yu 
Published: July 2014

AimsTo investigate the suitability of newly developed Becton Dickinson Vacutainer rapid serum tube (RST) for therapeutic drug monitoring of antibiotics and anticonvulsants.MethodsTwo pools of citrated whole blood were created by spiking high and low concentrations of gentamicin, vancomycin, phenytoin, lamotrigine and carbamazepine. After recalcification with 15 mmol/L calcium chloride, spiked whole blood was added into four different Becton Dickinson blood collection tubes: RST, serum separator tube, red top tube and polyethylene plain tube. Serum aliquots were collected at baseline (0 h), 2 h, 24 h, day 3 and day 7. Drug concentrations were measured in batch by HPLC and the Architect c8000.ResultsGentamicin and vancomycin concentrations were stable up to 7 days in all 4 blood collection tubes. Anticonvulsants results for the RST were stable and did not deviate substantially from those of the red top and plain tubes, and demonstrated better performance than the serum separator tubes that showed significant (≥10% bias, p<0.05) decrease in phenytoin and carbamazepine levels after 3 days of storage.ConclusionsThe RST provides acceptable drug stability over the course of 7 days for gentamicin, vancomycin, phenytoin and lamotrigine and over 3 days for carbamazepine.
Evaluation of sedation and clinical effects of midazolam with ketamine or dexmedetomidine in pet rabbits
Authors: Bellini L. , Banzato T. , Contiero B. , Zotti A. 
Published: July 2014

The effects of two sedation protocols combining midazolam with ketamine (ketamine group) or dexmedetomidine (dexmedetomidine group) were studied in dwarf companion rabbits undergoing abdominal ultrasound scan. The onset of sedation was faster in the ketamine group; a few rabbits in the dexmedetomidine group required additional doses to lose the righting reflex, although sedation time was not different between groups. A semi‐quantitative scale was used to score sedation quality, which was higher in rabbits that received dexmedetomidine rather than ketamine. Pulse rate was lower in the dexmedetomidine group (206 vs 240 bpm), although Doppler blood pressure was higher than in the ketamine group (109 vs 89 mm Hg). Respiratory rate decreased in relation to the baseline values with both protocols but arterial haemoglobin saturation with oxygen was maintained similar to the pre‐sedation values throughout the entire procedure, regardless of protocol used and without oxygen supplementation. Both protocols allowed performance of ultrasound scanning, although dexmedetomidine may be preferred if a deep sedation level is required.
Association Studies of Fcγ Receptor Polymorphisms with Outcome in HER2+ Breast Cancer Patients Treated with Trastuzumab in NCCTG (Alliance) Trial N9831
Authors: Norton Nadine , Olson Rebecca M. , Pegram Mark , Tenner Kathleen , Ballman Karla V. , Clynes Raphael , Knutson Keith L. , Perez Edith A. 
Published: July 2014

AbstractPatients with HER2+ breast cancer treated with trastuzumab and chemotherapy have superior survival compared with patients treated with chemotherapy alone. Polymorphisms within FCGR2A and FCGR3A are associated with binding affinity of natural killer cells to the IgG1 portion of trastuzumab, and a polymorphism in FCGR2B (I232T) is associated with impaired regulatory activity. The association of these polymorphisms with clinical response among trastuzumab-treated patients is equivocal, with both positive and negative associations. We performed genotyping analysis on the FCGR3A V158F, FCGR2A R131H, and FCGR2B I232T polymorphisms in 1,325 patients from the N9831 clinical trial. Patients in arm A (N = 419) received chemotherapy only. Patients in arms B (N = 469) and C (N = 437) were treated with chemotherapy and trastuzumab (sequentially in arm B and concurrently in arm C). Using log-rank test and Cox proportional hazard models, we compared disease-free survival (DFS) among genotypic groups within pooled arms B/C. We found no differences in DFS between trastuzumab-treated patients who had the FCGR3A 158 V/V and/or FCGR2A 131 H/H high-affinity genotypes and patients without those genotypes. Furthermore, there was no significant interaction between FCGR3A and FCGR2A and treatment. However, there was a difference in DFS for FCGR2B I232T, with I/I patients deriving benefit from trastuzumab (P &lt; 0.001), compared with the T carriers who did not (P = 0.81). The interaction between FCGR2B genotype and treatment was statistically significant (P = 0.03). Our analysis did not reveal an association between FcγR high-affinity genotypes and outcomes. However, it seems that the FCGR2B inhibitory gene may be predictive of adjuvant trastuzumab benefit. Cancer Immunol Res; 2(10); 962–9. ©2014 AACR.
Combining mutations that modulate inter-subunit interactions and proteolytic inactivation enhance the stability of factor VIIIa
Authors: Wakabayashi Hironao , Wintermute Jennifer M. , Fay Philip J. 
Published: July 2014

SummaryFVIIIa is labile due to the dissociation of A2 subunit. Previously, we introduced hydrophobic mutations at select A1/A2/A3 subunit interfaces yielding more stable FVIII(a) variants. Separately we showed that altering the sequence flanking the primary FXa cleavage site in FVIIIa (Arg336) yielded reduced rates of proteolytic inactivation of FVIIIa. In this study we prepared the FXa-cleavage resistant mutant (336(P4-P3’)562) combined with mutations of Ala108Ile, Asp519Val/ Glu665Val or Ala108Ile/Asp519Val/Glu665Val and examined the effects of these combinations relative to FVIII thermal stability, rates of FVIIIa decay and proteolytic inactivation of FVIIIa by FXa. Thermal decay rates for 336(P4-P3’)562/Ala108Ile, 336(P4-P3’)562/Asp519Val/ Glu665Val, and 336(P4-P3’)562/Ala108Ile/Asp519Val/Glu665Val variants were reduced by ∼2– to 5-fold as compared with wild-type (WT) primarily reflecting the effects of the A domain interface mutations. FVIIIa decay rates for 336(P4-P3’)562/Asp519Val/Glu665Val and 336(P4-P3’)562/Ala108Ile/Asp519Val/Glu665Val variants were reduced by ∼25 fold, indicating greater stability than the control Asp519Val/Glu665Val variant (∼14-fold). Interestingly, 336(P4-P3’)562/Asp519Val/Glu665Val and 336(P4-P3’)562/Ala108Ile/ Asp519Val/Glu665Val variants showed reduced FXa-inactivation rates compared with the 336(P4-P3’)562 control (∼4-fold), suggesting A2 subunit destabilisation is a component of proteolytic inactivation. Thrombin generation assays using the combination variants were similar to the Asp519Val/Glu665Val control. These results indicate that combining multiple gain-of-function FVIII mutations yields FVIII variants with increased stability relative to a single type of mutation.
Contribution of Homeostatic Chemokines CCL19 and CCL21 and Their Receptor CCR7 to Coronary Artery Disease
Authors: Cai Wenzhi , Tao Jie , Zhang Xiaolin , Tian Xiaoxiang , Liu Tengfei , Feng Xueyao , Bai Jing , Yan Chenghui , Han Yaling 
Published: July 2014

Objective—

Our aim was to identify the role of the homeostatic chemokines CCL19 and CCL21 and their common receptor CCR7 in atherogenesis and to study the relationships between
CCL19
,
CCL21
, and
CCR7
gene variants and coronary artery disease in a Chinese Han population.

Approach and Results—

Immunohistochemical analysis of samples with atherosclerosis of various stages showed increased CCL19, CCL21, and CCR7 expression in atherosclerotic coronary plaques compared with nonatherosclerotic controls. Expression levels increased in positive correlation with coronary lesion stage. Cell adhesion assays confirmed that CCL19 promoted monocyte adhesion, which was induced by CCR7, to human umbilical vein endothelial cells, an effect partially antagonized by atorvastatin. After the human umbilical vein endothelial cells were treated with CCR7-neutralizing antibody, both CCL19- and CCL21-induced monocyte to human umbilical vein endothelial cell migration and CCL19-induced monocyte to human umbilical vein endothelial cell adhesion were abolished. The associations between genetic variants of
CCL19
,
CCL21
,
CCR7
, and coronary artery disease in a Chinese Han population were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The following single nucleotide polymorphisms were associated with coronary artery disease:
CCL19
rs2227302,
CCL21
rs2812377, and
CCR7
rs588019. Individuals with the
CCL19
rs2227302 T allele or
CCL21
rs2812377 G allele had higher plasma CCL19 levels than those with C/C genotype and higher CCL21 levels than those with T/T genotype in both case and control subjects.

Conclusion—
CCL19/CCL21–CCR7 is a novel homeostatic chemokine system that modulates human monocyte adhesion and migration, promoting atherogenesis. It is associated with coronary artery disease risk in Chinese Han individuals. These data suggest that the CCL19/CCL21–CCR7 axis plays an important role in atherosclerosis progression.
MicroRNA-24 Regulates Macrophage Behavior and Retards Atherosclerosis
Authors: Di Gregoli Karina , Jenkins Nicholas , Salter Rebecca , White Stephen , Newby Andrew C. , Johnson Jason L. 
Published: July 2014

Objective—
Our recent studies have highlighted membrane type-1 matrix metalloproteinase (MMP)-14 as a selective marker for an invasive subset of macrophages potentially related to atherosclerotic plaque progression. Moreover, colony stimulating factors (CSF) may exert divergent effects on macrophage MMP expression, possibly through microRNAs. We, therefore, aim to identify and test the pathophysiological role of microRNAs, which modulate macrophage MMP-14 expression in atherosclerotic plaque progression.

Approach and Results—
Compared with macrophage CSF–differentiated macrophages, granulocyte/macrophage CSF–matured macrophages exhibited reduced MMP-14 mRNA levels but increased protein expression and activity, which resulted in heightened macrophage invasion. MicroRNA-24, identified to target MMP-14, was accordingly increased in macrophage CSF compared with granulocyte/macrophage CSF macrophages. Silencing microRNA-24 in macrophage CSF macrophages significantly increased MMP-14 expression and enhanced their invasive capacity, mimicking granulocyte/macrophage CSF macrophages, and suggesting that granulocyte/macrophage CSF modulates MMP-14 protein expression and subsequent macrophage invasion in a microRNA-24–dependent manner. In human coronary atherosclerotic plaques, increased MMP-14 protein expression in foam cell macrophages was associated with lesions exhibiting histological characteristics associated with an unstable phenotype. Furthermore, microRNA-24 expression in these atherosclerotic plaques was inversely related to MMP-14 protein expression. Moreover, stable plaques contained higher microRNA-24 levels than unstable plaques, and microRNA-24 colocalized with foam cell macrophages that exhibited low MMP-14 protein expression. Finally, in atherosclerotic mice (apolipoprotein E-deficient), microRNA-24 inhibition increased plaque size and macrophage MMP-14 expression.

Conclusions—
Taken together, our data demonstrates that downregulation of microRNA-24 promotes an invasive macrophage subset and plays a novel regulatory role in MMP-14 proteolytic activity and, therefore, plaque stability, highlighting its therapeutic potential.