Miracle-dz/UniFAR-FTUs huggingface dataset:
Unicycler: Resolving bacterial genome assemblies from short and long sequencing reads

The Illumina DNA sequencing platform generates accurate but short reads, which can be used to produce accurate but fragmented genome assemblies. Pacific Biosciences and Oxford Nanopore Technologies DNA sequencing platforms generate long reads that can produce more complete genome assemblies, but the sequencing is more expensive and error prone. There is significant interest in combining data from these complementary sequencing technologies to generate more accurate “hybrid” assemblies. However, few tools exist that truly leverage the benefits of both types of data, namely the accuracy of short reads and the structural resolving power of long reads. Here we present Unicycler, a new tool for assembling bacterial genomes from a combination of short and long reads, which produces assemblies that are accurate, complete and cost-effective. Unicycler builds an initial assembly graph from short reads using the de novo assembler SPAdes and then simplifies the graph using information from short and long reads. Unicycler utilises a novel semi-global aligner, which is used to align long reads to the assembly graph. Tests on both synthetic and real reads show Unicycler can assemble larger contigs with fewer misassemblies than other hybrid assemblers, even when long read depth and accuracy are low. Unicycler is open source (GPLv3) and available at github.com/rrwick/Unicycler.
Socioeconomic Position and Health-Seeking Behavior for Hearing Loss Among Older Adults in England

Objective. To examine whether socioeconomic position (SEP) is associated with progression in the health-seeking process for hearing loss. Method. Logistic regression of data from a cross-sectional survey representative of noninstitutionalized, 50 years and older population of England (ELSA wave 2, 2004). Using self-reported hearing difficulty as starting point, we examined the association between SEP and health-seeking behaviors in 6 stages leading to hearing aid acquisition and use. Results. Higher SEP was associated with lower odds of self-reported hearing difficulty, adjusted odds ratio [OR] = 0.87 (95% confidence interval [CI] 0.83–0.91, p < .001). There was marginal negative association between higher SEP and receiving hearing aid recommendation (adjusted OR = 0.88, 95% CI 0.78–0.99, p = .05). SEP was not associated with any other stage of health-seeking behavior. Discussion. Among the noninstitutionalized older population of England, SEP-related inequalities exist in the prevalence of self-reported hearing loss. However, SEP is not strongly associated with progression in the remaining stages of health-seeking process during and after an individual’s contact with the health system.
The landscape of genetic susceptibility correlations among diseases and traits

Objective The aim of the study was to comprehensively explore the genetic susceptibility correlations among diseases and traits from large-scale individual genotype data. Materials and Methods Based on a knowledge base of genetic variants significantly (P < 5 × 10 -8 ) linked with human phenotypes, genetic risk scores (GRSs) of diseases or traits were calculated for 2504 individuals with whole-genome sequencing data from the 1000 Genomes Project. Associations between diseases/traits were statistically evaluated by pairwise correlation analysis of GRSs. Overlaps between the genetic susceptibility correlations and disease comorbidity associations from hospital claims data in more than 30 million patients in United States were assessed. Results Correlation analysis of GRSs revealed 823 significant correlations among 78 diseases and 89 traits (false discovery rate adjusted P -value or Q -value < 0.01). It is noticeable that GRSs were correlated in 464 associations (56.4%) even if they were combinations of distinct sets of risk variants without chromosomal linkage, suggesting the presence of genetic interactions beyond chromosome position. When 312 significant genetic susceptibility correlations between diseases were compared to nationwide disease comorbidity correlations obtained from data from 32 million Medicare claims in the United States, 108 overlaps (34.6%) were found that had both genetic susceptibility and epidemiologic comorbid correlations. Conclusion The study suggests that common genetic background exists between diseases and traits with epidemiologic associations. The GRS correlation approach provides a rich source of candidate associations among diseases and traits from the genetic perspective, warranting further epidemiologic studies.
Factors associated with postoperative costs following anatomic lung resections without major complications

OBJECTIVES To detect factors associated with costs of anatomic lung resection without major complications. METHODS Two hundred and fifty consecutive patients submitted to anatomic lung resection (185 by VATS) in 1 fiscal year (1 April 2014–31 March 2015) were included. Thoracic Morbidity and Mortality (TMM) system was used to grade the severity of complications. Two hundred and ten patients who did not develop major complications (TMM < 3) were analysed. Postoperative costs were retrieved from the Financial Department through a Patient Level Information and Costing System. Multivariable regression and bootstrap analyses were used to test the association of several baseline patient characteristics with costs and obtain an aggregate scoring system to estimate postoperative costs. RESULTS Among the 210 patients, 117 (56%) did not develop any complication and 93 (44%) had minor complications. Their average postoperative cost was 4040€, significantly lower than the one observed in patients with major complications (13 156€, P < 0.0001). Multivariable regression revealed that open thoracotomy (P = 0.01), carbon monoxide lung diffusion capacity (DLCO) < 60% (P = 0.001) and coronary artery disease (CAD) (P = 0.009) were associated with postoperative costs. Open thoracotomy would increase the cost by 648€, DLCO < 60% by 935€ and CAD by 1043€. If all three factors were present, they would cause an increase of postoperative costs from 3592€ to 6219€. CONCLUSION We were able to identify clinical factors associated with postoperative costs in patients without major complications. Recognizing groups of increased cost may lead to specific process analyses aimed at optimising their pathways of care and ultimately saving money. Moreover, these findings may help administrators to tailor future individualized lung resection reimbursement tariffs based on patient characteristics.
High expression of stromal PDGFRβ is associated with reduced benefit of tamoxifen in breast cancer

Cancer‐associated fibroblasts (CAFs) regulate tumour growth, metastasis and response to treatment. Recent studies indicate the existence of functionally distinct CAF subsets. Suggested mechanisms whereby CAFs can impact on treatment response include paracrine signalling affecting cancer cell drug sensitivity and effects on tumour drug uptake. PDGFRβ is an important regulator of fibroblasts. Experimental studies have linked PDGFRβ‐positive fibroblasts to metastasis and also to reduced tumour drug uptake. This study has investigated the potential role of PDGFRβ‐positive fibroblasts in response to adjuvant tamoxifen treatment of breast cancer. Analyses of two breast cancer collections from randomised studies analysing adjuvant tamoxifen treatment in early breast cancer demonstrated significant benefit of tamoxifen in the group with low stromal PDGFRβ, which was not observed in the group with high stromal PDGFRβ. In general terms these findings provide novel evidence, derived from analyses of randomised clinical studies, of response‐predictive capacity of a marker‐defined subset of CAFs and, more specifically, identify stromal PDGFRβ as a marker related to tamoxifen benefit in early breast cancer.
Preoperative inspiratory muscle training prevents pulmonary complications after cardiac surgery - a systematic review.

INTRODUCTION Post-operative pulmonary complications are a common cause of morbidity and mortality in patients undergoing heart surgery. The aim of this systematic review was to determine if preoperative inspiratory muscle training could prevent the development of pneumonia and atelectasis in patients undergoing coronary artery bypass grafting (CABG) or heart valve surgery. METHODS Systematic searches were performed in MEDLINE, Embase and the Cochrane Library. The included studies compared the development of pneumonia and atelectasis in CABG patients or heart valve surgery patients who were prescribed either preoperative inspiratory muscle training or usual care. The quality of the studies was assessed using the Cochrane Risk of Bias Tool. RESULTS The search yielded 2,479 records. The inclusion criteria were fulfilled by five studies. All the studies were randomised controlled trials. We found that the development of both pneumonia and atelectasis was significantly reduced among patients who received inspiratory muscle training preoperatively compared with patients treated with usual care. CONCLUSIONS Preoperative inspiratory muscle training may reduce the risk of developing pneumonia and atelectasis. However, more trials are needed to support and strengthen the evidence found in this systematic review before routine implementation of this kind of training preoperatively.
Reproducibility of quantitative indices of lung function and microstructure from 129Xe chemical shift saturation recovery (CSSR) MR spectroscopy

To evaluate the reproducibility of indices of lung microstructure and function derived from 129Xe chemical shift saturation recovery (CSSR) spectroscopy in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD), and to study the sensitivity of CSSR‐derived parameters to pulse sequence design and lung inflation level.
Generation of Induced Pluripotent Stem Cells from the Prairie Vole

The vast majority of animals mate more or less promiscuously. A few mammals, including humans, utilize more restrained mating strategies that entail a longer term affiliation with a single mating partner. Such pair bonding mating strategies have been resistant to genetic analysis because of a lack of suitable model organisms. Prairie voles are small mouse-like rodents that form enduring pair bonds in the wild as well as in the laboratory, and consequently they have been used widely to study social bonding behavior. The lack of targeted genetic approaches in this species however has restricted the study of the molecular and neural circuit basis of pair bonds. As a first step in rendering the prairie vole amenable to reverse genetics, we have generated induced pluripotent stem cell (IPSC) lines from prairie vole fibroblasts using retroviral transduction of reprogramming factors. These IPSC lines display the cellular and molecular hallmarks of IPSC cells from other organisms, including mice and humans. Moreover, the prairie vole IPSC lines have pluripotent differentiation potential since they can give rise to all three germ layers in tissue culture and in vivo. These IPSC lines can now be used to develop conditions that facilitate homologous recombination and eventually the generation of prairie voles bearing targeted genetic modifications to study the molecular and neural basis of pair bond formation.
Trend of CD4+ Cell Counts at Diagnosis and Initiation of Highly Active Antiretroviral Therapy (HAART): Korea HIV/AIDS Cohort Study, 1992-2015

Background CD4+ cell counts reflect immunologic status of human immunodeficiency virus (HIV) patients. Recommended CD4+ cell counts for the initiation of highly active antiretroviral therapy (HAART) has increased over the past several years in various HIV treatment guidelines. We investigated the trend of CD4+ cell counts at diagnosis and treatment start using data from the Korea HIV/acquired immune deficiency syndrome (AIDS) Cohort Study. Materials and Methods The Korea HIV/AIDS Cohort Study started in 2006 and enrolled HIV patients from 21 tertiary and secondary hospitals in South Korea. The data for CD4+ cell counts at diagnosis and HAART initiation from these HIV patients were analyzed by three-year time intervals and presented by number of CD4+ cells (≤100, 101-200, 201-350, 351-500 and >500 cells/mm3). The HIV-RNA titer at diagnosis and HAART initiation were presented by 3-year intervals by groups ≤50,000, 50,001-100,000, 100,001-200,000, 200,001-1,000,000, and >1,000,000 copies/mL. Results Median values of CD4+ cell count and HIV-RNA titer at initial HIV diagnosis were 247 cells/mm3 and 394,955 copies/mL, respectively. At time of initiating HAART, median values of CD4+ cell count and HIV-RNA were 181 cells/mm3 and 83,500 copies/mL, respectively. Patients with low CD4+ cell count (CD4+ cell count ≤200 cells/mm3) at diagnosis (31-51%) and initiation of HAART accounted for the largest proportion (30-65%) over the three-year time intervals. This proportion increased until 2010-2012. Conclusion CD4+ cell count at initiation of HAART was found to be very low, and the increase in late initiation of HAART in recent years is of concern. We think that this increase is primarily due to an increasing proportion of late presenters. We recommend early detection of HIV patients and earlier start of HAART in order to treat and prevent spread of HIV infection.
Occurrence and characterization of mcr-1-harbouring Escherichia coli isolated from pigs in Great Britain from 2013 to 2015

Objectives: To determine the occurrence of mcr-1-harbouring Escherichia coli in archived pig material originating in Great Britain (GB) from 2013 to 2015 and characterize mcr-1 plasmids. Methods: Enrichment and selective culture of 387 archived porcine caecal contents and recovery from archive of 1109 E. coli isolates to identify colistin-resistant bacteria by testing for the presence of mcr-1 by PCR and RT–PCR. mcr-1-harbouring E. coli were characterized by WGS and compared with other available mcr-1 WGS. Results: Using selective isolation following enrichment, the occurrence of mcr-1 E. coli in caeca from healthy pigs at slaughter from unique farms in GB was 0.6% (95% CI 0%–1.5%) in 2015. mcr-1 E. coli were also detected in isolates from two porcine veterinary diagnostic submissions in 2015. All isolates prior to 2015 were negative. WGS analysis of the four mcr-1-positive E. coli indicated no other antimicrobial resistance (AMR) genes were linked to mcr-1-plasmid-bearing contigs, despite all harbouring multiple AMR genes. The sequence similarity between mcr-1-plasmid-bearing contigs identified and those found in GB, Chinese and South African human isolates and Danish, French and Estonian livestock-associated isolates was 90%–99%. Conclusions: mcr-1-harbouring plasmids were diverse, implying transposable elements are involved in mcr-1 transmission in GB. The low number of mcr-1-positive E. coli isolates identified suggested mcr-1 is currently uncommon in E. coli from pigs within GB. The high sequence similarity between mcr-1 plasmid draft genomes identified in pig E. coli and plasmids found in human and livestock-associated isolates globally requires further investigation to understand the full implications.
Serious adverse events of cell therapy for respiratory diseases: a systematic review and meta-analysis

Background Cell therapy holds the most promising for acute and chronic deleterious respiratory diseases. However, the safety and tolerance for lung disorders are controversy. Methods We undertook a systematic review and meta-analyses of all 23 clinical studies of cell therapy. The outcomes were odds ratio (OR), risk difference (RD), Peto OR, relative risk, and mean difference of serious adverse events. Results 342 systemic infusions and 57 bronchial instillations (204 recipients) of cells were analyzed for acute respiratory distress syndrome (ARDS), bronchopulmonary dysplasia, pulmonary arterial hypertension, silicosis, sarcoidosis, extensively drug-resistant tuberculosis, chronic obstructive pulmonary diseases (COPD), and idiopathic pulmonary fibrosis. The frequency of death in adults from any causes was 71 and 177 per 1,000 for cell therapy and controls, respectively, with an OR of 0.31 (95% CI: 0.03, 3.76) and RD of -0.22 (95% CI: -0.53, 0.09). No significant difference was found for ARDS and COPD. The frequency of deaths and non-fatal serious adverse events of 17 open studies were similar to those of randomized controlled trials. Moreover, serious adverse events of allogenic cells were greater than autologous preparations, as shown by frequency, OR and RD. Conclusions We conclude that either infusion or instillation of mesenchymal stem stromal or progenitor cells are well tolerated without serious adverse events causally related to cell treatment. Cell therapy has not been associated with significant changes in spirometry, immune function, cardiovascular activity, and the quality of life.
Effects of Mobility and Multimorbidity on Inpatient and Postacute Health Care Utilization

Background This study examines effects of mobility and multimorbidity on hospitalization and inpatient and postacute care (PAC) facility days among older men. Methods Prospective study of 1,701 men (mean age 79.3 years) participating in Osteoporotic Fractures in Men (MrOS) Study Year 7 (Y7) examination (2007-2008) linked with their Medicare claims. At Y7, mobility ascertained by usual gait speed and categorized as poor, intermediate, or good. Multimorbidity quantified by applying Elixhauser algorithm to inpatient and outpatient claims and categorized as none, mild-moderate, or high. Hospitalizations and PAC facility stays ascertained during 12 months following Y7. Results Reduced mobility and greater multimorbidity burden were independently associated with a higher risk of inpatient and PAC facility utilization, after accounting for each other and traditional indicators. Adjusted mean total facility days per year were 1.13 (95% confidence interval [CI] = 0.74-1.40) among men with good mobility increasing to 2.43 (95% CI = 1.17-3.84) among men with poor mobility, and 0.67 (95% CI = 0.38-0.91) among men without multimorbidity increasing to 2.70 (95% CI = 1.58-3.77) among men with high multimorbidity. Men with poor mobility and high multimorbidity had a ninefold increase in mean total facility days per year (5.50, 95% CI = 2.78-10.87) compared with men with good mobility without multimorbidity (0.59, 95% CI = 0.37-0.95). Conclusions Among older men, mobility limitations and multimorbidity were independent predictors of higher inpatient and PAC utilization after considering each other and conventional predictors. Marked combined effects of reduced mobility and multimorbidity burden may be important to consider in clinical decision-making and planning health care delivery strategies for the growing aged population.
Cytosolic NADH-NAD(+) Redox Visualized in Brain Slices by Two-Photon Fluorescence Lifetime Biosensor Imaging.

AIM Cytosolic NADH-NAD(+) redox state is central to cellular metabolism and a valuable indicator of glucose and lactate metabolism in living cells. Here we sought to quantitatively determine NADH-NAD(+) redox in live cells and brain tissue using a fluorescence lifetime imaging of the genetically-encoded single-fluorophore biosensor Peredox. RESULTS We show that Peredox exhibits a substantial change in its fluorescence lifetime over its sensing range of NADH-NAD(+) ratio. This allows changes in cytosolic NADH redox to be visualized in living cells using a two-photon scanning microscope with fluorescence lifetime imaging capabilities (2p-FLIM), using time-correlated single photon counting. INNOVATION Because the lifetime readout is absolutely calibrated (in nanoseconds) and is independent of sensor concentration, we demonstrate that quantitative assessment of NADH redox is possible using a single fluorophore biosensor. CONCLUSION Imaging of the sensor in mouse hippocampal brain slices reveals that astrocytes are typically much more reduced (with higher NADH:NAD(+) ratio) than neurons under basal conditions, consistent with the hypothesis that astrocytes are more glycolytic than neurons. Antioxid. Redox Signal. 25, 553-563.
E-Cigarette Social Media Messages: A Text Mining Analysis of Marketing and Consumer Conversations on Twitter

Background As the use of electronic cigarettes (e-cigarettes) rises, social media likely influences public awareness and perception of this emerging tobacco product. Objective This study examined the public conversation on Twitter to determine overarching themes and insights for trending topics from commercial and consumer users. Methods Text mining uncovered key patterns and important topics for e-cigarettes on Twitter. SAS Text Miner 12.1 software (SAS Institute Inc) was used for descriptive text mining to reveal the primary topics from tweets collected from March 24, 2015, to July 3, 2015, using a Python script in conjunction with Twitter’s streaming application programming interface. A total of 18 keywords related to e-cigarettes were used and resulted in a total of 872,544 tweets that were sorted into overarching themes through a text topic node for tweets (126,127) and retweets (114,451) that represented more than 1% of the conversation. Results While some of the final themes were marketing-focused, many topics represented diverse proponent and user conversations that included discussion of policies, personal experiences, and the differentiation of e-cigarettes from traditional tobacco, often by pointing to the lack of evidence for the harm or risks of e-cigarettes or taking the position that e-cigarettes should be promoted as smoking cessation devices. Conclusions These findings reveal that unique, large-scale public conversations are occurring on Twitter alongside e-cigarette advertising and promotion. Proponents and users are turning to social media to share knowledge, experience, and questions about e-cigarette use. Future research should focus on these unique conversations to understand how they influence attitudes towards and use of e-cigarettes.
Model‐based dose finding under model uncertainty using general parametric models

The statistical methodology for the design and analysis of clinical Phase II dose‐response studies, with related software implementation, is well developed for the case of a normally distributed, homoscedastic response considered for a single timepoint in parallel group study designs. In practice, however, binary, count, or time‐to‐event endpoints are encountered, typically measured repeatedly over time and sometimes in more complex settings like crossover study designs. In this paper, we develop an overarching methodology to perform efficient multiple comparisons and modeling for dose finding, under uncertainty about the dose‐response shape, using general parametric models. The framework described here is quite broad and can be utilized in situations involving for example generalized nonlinear models, linear and nonlinear mixed effects models, Cox proportional hazards models, with the main restriction being that a univariate dose‐response relationship is modeled, that is, both dose and response correspond to univariate measurements. In addition to the core framework, we also develop a general purpose methodology to fit dose‐response data in a computationally and statistically efficient way. Several examples illustrate the breadth of applicability of the results. For the analyses, we developed the R add‐on package DoseFinding, which provides a convenient interface to the general approach adopted here. Copyright © 2013 John Wiley & Sons, Ltd.