With the rapid growth and development of sequencing technologies, genomes have become the new go-to for exploring solutions to some of the world’s biggest challenges such as searching for alternative energy sources and exploration of genomic dark matter. However, progress in sequencing has been accompanied by its share of errors that can occur during template or library preparation, sequencing, imaging or data analysis. In this study we screened over 18,000 publicly available microbial isolate genome sequences in the Integrated Microbial Genomes database and identified more than 1000 genomes that are contaminated with PhiX, a control frequently used during Illumina sequencing runs. Approximately 10% of these genomes have been published in literature and 129 contaminated genomes were sequenced under the Human Microbiome Project. Raw sequence reads are prone to contamination from various sources and are usually eliminated during downstream quality control steps. Detection of PhiX contaminated genomes indicates a lapse in either the application or effectiveness of proper quality control measures. The presence of PhiX contamination in several publicly available isolate genomes can result in additional errors when such data are used in comparative genomics analyses. Such contamination of public databases have far-reaching consequences in the form of erroneous data interpretation and analyses, and necessitates better measures to proofread raw sequences before releasing them to the broader scientific community.
Background: Little is known about invertebrate responses to DNA viruses. Here, we infect a commercially important pest moth species Plodia interpunctella with its naturally infecting DNA virus. We sequenced, assembled and annotated the complete transcriptome of the moth, and a partial transcriptome of the virus. We then tested for differential gene expression between moths that were exposed to the virus and controls. Results: We found 51 genes that were differentially expressed in moths exposed to a DNA baculovirus compared to controls. Gene set enrichment analysis revealed that cuticle proteins were significantly overrepresented in this group of genes. Interestingly, 6 of the 7 differentially expressed cuticle proteins were downregulated, suggesting that baculoviruses are able to manipulate its host’s response. In fact, an additional 29 of the 51 genes were also downregulated in exposed compared with control animals, including a gram-negative binding protein. In contrast, genes involved in transposable element movement were upregulated after infection. Conclusions: We present the first experiment to measure genome-wide gene expression in an insect after infection with a natural DNA virus. Our results indicate that cuticle proteins might be key genes underpinning the response to DNA viruses. Furthermore, the large proportion of genes that were downregulated after viral exposure suggests that this virus is actively manipulating the insect immune response. Finally, it appears that transposable element activity might increase during viral invasion. Combined, these results provide much needed host candidate genes that respond to DNA viral invaders.
Background: High-density genomic data is often analyzed by combining information over windows of adjacent markers. Interpretation of data grouped in windows versus at individual locations may increase statistical power, simplify computation, reduce sampling noise, and reduce the total number of tests performed. However, use of adjacent marker information can result in over- or under-smoothing, undesirable window boundary specifications, or highly correlated test statistics. We introduce a method for defining windows based on statistically guided breakpoints in the data, as a foundation for the analysis of multiple adjacent data points. This method involves first fitting a cubic smoothing spline to the data and then identifying the inflection points of the fitted spline, which serve as the boundaries of adjacent windows. This technique does not require prior knowledge of linkage disequilibrium, and therefore can be applied to data collected from individual or pooled sequencing experiments. Moreover, in contrast to existing methods, an arbitrary choice of window size is not necessary, since these are determined empirically and allowed to vary along the genome. Results: Simulations applying this method were performed to identify selection signatures from pooled sequencing F ST data, for which allele frequencies were estimated from a pool of individuals. The relative ratio of true to false positives was twice that generated by existing techniques. A comparison of the approach to a previous study that involved pooled sequencing F ST data from maize suggested that outlying windows were more clearly separated from their neighbors than when using a standard sliding window approach. Conclusions: We have developed a novel technique to identify window boundaries for subsequent analysis protocols. When applied to selection studies based on F ST data, this method provides a high discovery rate and minimizes false positives. The method is implemented in the R package GenWin, which is publicly available from CRAN.
Background: One of the usual problems psychologists and clinicians face in clinical practice is differential diagnostics of Alzheimer’s disease and depression. It has been reported that the ACE and ACE-R could discriminate the cognitive dysfunctions due to depression from that due to dementia, although this is not uniform in all studies. The current study aimed to evaluate the utility of the ACE-R to differentiate late-life onset depression (with severe episode) from mild-moderate Alzheimer’s Disease (AD). Methods: This study received approval from the Lithuanian Bioethics Committee. All participants were older than 50 years (mean age = 66.52 (±8.76) years). The study sample consisted of 295 individuals: 117 with severe depression, 85 with mild-moderate Alzheimer’s disease (AD), and 94 age, gender and education matched participants of control group. Results: The ACE-R had high sensitivity (100%) and specificity (81%) at detecting cognitive impairments related to AD. Patients with late-life onset depression (ACE-R mean 76.82, SD = 7.36) performed worse than controls (ACE-R mean 85.08, SD = 7.2), but better than the AD group (ACE-R mean 54.74, SD = 12.19). Participants with late-life onset depression were differentiated by mild impairment in the ACE-R total score with mild memory (13.79, SD = 6.29) and greater deficits in letter fluency (3.65, SD = 1.21) than in semantic fluency (4.68, SD = 1.23). Participants with AD were differentiated by severely impaired performance on attention and orientation (11.80, SD = 2.93), memory (8.25, SD = 3.47) and language subtests (17.21, SD = 4.04), and moderately impaired performance on verbal fluency (6.07, SD = 2.74). Conclusions: ACE-R has diagnostic accuracy in detecting people with AD and can be used in differential diagnostics of late-life onset depression (severe episode) and AD. Diagnostic accuracy may be improved by analyzing the neuropsychological profiles and using lower cutoffs for different age groups.
Background: To systematically review in- and outpatient costs in patients with coronary artery disease (CAD) and comorbid mental disorders. Methods: A comprehensive database search was conducted for studies investigating persons with CAD and comorbid mental disorders (Medline, EMBASE, PsycINFO, Psyndex, EconLit, IBSS). All studies were included which allowed a comparison of in- and outpatient health care costs (assessed either monetarily or in terms of health care utilization) of CAD patients with comorbid mental disorders (mood, anxiety, alcohol, eating, somatoform and personality disorders) and those without. Random effects meta-analyses were conducted and results reported using forest plots. Results: The literature search resulted in 7,275 potentially relevant studies, of which 52 met inclusion criteria. Hospital readmission rates were increased in CAD patients with any mental disorder (pooled standardized mean difference (SMD) = 0.34 [0.17;0.51]). Results for depression, anxiety and posttraumatic stress disorder pointed in the same direction with heterogeneous SMDs on a primary study level ranging from −0.44 to 1.26. Length of hospital stay was not increased in anxiety and any mental disorder, while studies on depression reported heterogeneous SMDs ranging from −0.08 to 0.82. Most studies reported increased overall and outpatient costs for patients with comorbid mental disorders. Results for invasive procedures were non-significant respectively inconclusive. Conclusions: Comorbid mental disorders in CAD patients are associated with an increased healthcare utilization in terms of higher hospital readmission rates and increased overall and outpatient health care costs. From a health care point of view, it is requisite to improve the diagnosis and treatment of comorbid mental disorders in patients with CAD to minimize incremental costs.
Background: Vaccination Week in the Americas (VWA) is an annual initiative in countries and territories of the Americas every April to highlight the work of national expanded programs on immunization (EPI) and increase access to vaccination services for high-risk population groups. In 2011, as part of VWA, Venezuela targeted children aged less than 6 years in 25 priority border municipalities using social mobilization to increase institution-based vaccination. Implementation of social communication activities was decentralized to the local level. We conducted a survey in one border municipality of Venezuela to evaluate the outcome of VWA 2011 and provide a snapshot of the overall performance of the routine EPI at that level. Methods: We conducted a coverage survey, using stratified cluster sampling, in the Venezuelan municipality of Bolivar (bordering Colombia) in August 2011. We collected information for children aged 85%, with a few exceptions. Conclusion: Low levels of VWA awareness among caregivers probably contributed to the limited vaccination of eligible children during the VWA activities in Bolivar in 2011. However, vaccine coverage for most EPI vaccines was high. Additionally, high vaccination card availability and high participation in VWA among those caregivers aware of it in 2011 suggest public trust in the EPI program in the municipality. Health authorities have used survey findings to inform changes to the routine EPI and better VWA implementation in subsequent years.
Background: Osteoarthritis (OA) is the most frequent articular disease and a leading cause of disability. There is a need for effective treatments able to slow the progression of disease. Some of the available treatments are dietary supplements providing natural components. Recent studies have shown that estrogen deficiency contributes to the pathophysiological events of OA progression. Methods: We have used the anterior cruciate ligament transection model of OA in ovariectomised rats to study the effects of BIS076, a new formulation of a natural porcine cartilage extract associated with hydroxyapatite (as a source of calcium) and vitamin D3. Cartilage degradation, proteoglycan depletion and synovitis were followed by histochemistry. Effects on bone microstructure were determined by μCT. The levels of biomarkers in serum and inflammatory mediators in knee homogenates were measured by luminex or ELISA. Results: Oral administration of BIS076 reduced articular cartilage damage and serum levels of cartilage degradation markers C-telopeptide of type II collagen and cartilage oligomeric matrix protein, as well as matrix metalloproteinase-3. The local inflammatory response was down-regulated by BIS076 with lower production of pro-inflammatory cytokines and prostaglandin E2 in joint tissues. In addition, BIS076 was effective on metaphyseal bone alterations as this formulation increased volumetric bone mineral density and improved bone micro-architecture. These effects were related to the modification of bone metabolism reflected by changes in bone biomarkers with reductions in the ratio receptor activator of nuclear factor κB ligand/osteoprotegerin and the levels of tartrate-resistant acid phosphatase-5b, suggesting an inhibitory activity of BIS076 on trabecular bone resorption. Conclusions: We have demonstrated the protective properties of a new formulation (BIS076) on joint lesion and bone alterations in an experimental model of OA in ovariectomised rats. This study supports the interest of BIS076 in OA treatments.
Background: Although cavernous hemangioma is one of the most frequently encountered benign hepatic neoplasms, hepatic sclerosed hemangioma is very rare. We report a case of hepatic sclerosed hemangioma that was difficult to distinguish from an intrahepatic cholangiocarcinoma by imaging studies.Case presentationA 76-year-old male patient with right hypochondralgia was referred to our hospital. Abdominal ultrasonography revealed a heterogeneously hyperechoic tumor that was 59 mm in diameter in segment 7 of the liver. Dynamic computed tomography showed a low-density tumor with delayed ring enhancement. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) demonstrated a low-signal intensity mass with ring enhancement on T1-weighted images. The mass had several high-signal intensity lesions on T2-weighted images. EOB-MRI revealed a hypointense nodule on the hepatobiliary phase. From these imaging studies, the tumor was diagnosed as intrahepatic cholangiocarcinoma, and we performed laparoscopy-assisted posterior sectionectomy of the liver with lymph node dissection in the hepatoduodenal ligament. Histopathological examination revealed a hepatic sclerosed hemangioma with hyalinized tissue and collagen fibers. Conclusion: Hepatic sclerosed hemangioma is difficult to diagnose preoperatively because of its various imaging findings. We report a case of hepatic sclerosed hemangioma and review the literatures, especially those concerning imaging findings.
Background: Three decades of research findings have documented the health effects of handling hazardous drugs. Oncology nurses are vulnerable due to frequent administration of antineoplastics, low adherence to equipment use, reported barriers to use, and perceived low risk of health effects. No interventions have been tested in a controlled, multi-site trial to increase nurses’ use of protective equipment when handling hazardous drugs. The Drug Exposure Feedback and Education for Nurses’ Safety (DEFENS) study will compare the efficacy of education (control) versus an audit and feedback intervention (treatment) on nurses’ self-reported use of personal protective equipment when handling hazardous drugs. The treatment intervention will include tailored messages based on nurses’ reported barriers to protective equipment use.Methods/DesignThe DEFENS Study is a cluster randomized controlled trial. We are enrolling cancer centers and will recruit nurse participants in April 2015. Eligible cancer centers employ at least 20 eligible registered nurses in the chemotherapy infusion setting and have on-site phlebotomy resources. Eligible participants are nurses who work at least 0.40 full-time equivalent hours in the chemotherapy infusion setting and have not received an antineoplastic drug for a health problem in the past year. An encrypted, user-authenticated website will administer surveys and deliver control and treatment interventions. The primary endpoint is the change in score on nurses’ reports of the Revised Hazardous Drug Handling Questionnaire between baseline and approximately 18 months later. A baseline survey is completed after informed consent and is repeated 18 months later. Nurses in all sites who experience a drug spill will also report incidents as they occur; these reports inform the treatment intervention. Plasma will be obtained at baseline, approximately 18 months later (the primary endpoint), and with drug spill occurrences to measure hazardous drugs levels and to inform the treatment intervention. Potential mediators include knowledge of hazardous drug handling and perceived risk of drug exposure. We will examine whether personal factors and organizational factors moderate the intervention effects.Trial registrationClinicaltrials.gov NCT02283164, registered 31 October 2014.
IntroductionA still not well defined proportion of patients with multiple myeloma (MM) and eligible for autologous stem cell transplantation (AuSCT) fails to mobilize CD34+ peripheral blood stem cells (PBSC) at all or to collect an adequate number for a safe procedure or sufficient for multiple transplants. These so-called “poor-mobilizers” are difficult to be predicted, due to marked difference across previous heterogeneous studies. Methods: We aimed to develop a method based on simple clinical parameters for predicting unsuccessful (<2 × 106/kg) or sub-optimal (<5 × 106/kg) collections of CD34+ PBSC in newly diagnosed MM patients eligible for AuSCT, treated with novel agents and receiving an homogeneous mobilizing therapy with cyclophosphamide and granulocyte-colony stimulating factor (G-CSF). To this purpose, 1.348 patients enrolled in five consecutive Italian clinical trials were retrospectively analysed. Age, baseline low peripheral blood cell counts, use of lenalidomide, and haematological toxicity developed during induction were taken into account as possible factors associated with poor mobilization. Results: Overall, 280 patients (20.8%) showed either sub-optimal (167 patients, 12.4%) or unsuccessful (113 patients, 8.4%) collections. All analysed parameters negatively influenced the procedure, but only age and haematological toxicity during induction maintained their significance at multivariate analysis. Based on ordinal logistic regression model, we constructed a risk heat-map where the four parameters were pooled and weighted according to their relevance as single or combined variables. This model was predictive for different probabilities of failure, suboptimal or optimal outcomes. Conclusions: We found that about one fifth of newly diagnosed MM fails to collect an adequate number of PBSC. Our model, based on a large group of patients treated frontline with novel agents and receiving the most popular mobilizing approach currently employed in Europe, is applicable in individual subjects and may contribute to the early identification of “poor mobilizer” phenotypes.