Miracle-dz/UniFAR-FTUs huggingface dataset:
NCBI’s Virus Discovery Hackathon: Engaging Research Communities to Identify Cloud Infrastructure Requirements

A wealth of viral data sits untapped in publicly available metagenomic data sets when it might be extracted to create a usable index for the virological research community. We hypothesized that work of this complexity and scale could be done in a hackathon setting. Ten teams comprised of over 40 participants from six countries, assembled to create a crowd-sourced set of analysis and processing pipelines for a complex biological data set in a three-day event on the San Diego State University campus starting 9 January 2019. Prior to the hackathon, 141,676 metagenomic data sets from the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA) were pre-assembled into contiguous assemblies (contigs) by NCBI staff. During the hackathon, a subset consisting of 2953 SRA data sets (approximately 55 million contigs) was selected, which were further filtered for a minimal length of 1 kb. This resulted in 4.2 million (Mio) contigs, which were aligned using BLAST against all known virus genomes, phylogenetically clustered and assigned metadata. Out of the 4.2 Mio contigs, 360,000 contigs were labeled with domains and an additional subset containing 4400 contigs was screened for virus or virus-like genes. The work yielded valuable insights into both SRA data and the cloud infrastructure required to support such efforts, revealing analysis bottlenecks and possible workarounds thereof. Mainly: (i) Conservative assemblies of SRA data improves initial analysis steps; (ii) existing bioinformatic software with weak multithreading/multicore support can be elevated by wrapper scripts to use all cores within a computing node; (iii) redesigning existing bioinformatic algorithms for a cloud infrastructure to facilitate its use for a wider audience; and (iv) a cloud infrastructure allows a diverse group of researchers to collaborate effectively. The scientific findings will be extended during a follow-up event. Here, we present the applied workflows, initial results, and lessons learned from the hackathon.
Expression of FGF8, FGF18, and FGFR4 in Gastroesophageal Adenocarcinomas

Even though distinctive advances in the field of esophageal cancer therapy have occurred over the last few years, patients’ survival rates remain poor. FGF8, FGF18, and FGFR4 have been identified as promising biomarkers in a number of cancers; however no data exist on expression of FGF8, FGF18, and FGFR4 in adenocarcinomas of the esophago-gastric junction (AEG). A preliminary analysis of the Cancer Genome Atlas (TCGA) database on FGF8, FGF18, and FGFR4 mRNA expression data of patients with AEG was performed. Furthermore, protein levels of FGF8, FGF18, and FGFR4 in diagnostic biopsies and post-operative specimens in neoadjuvantly treated and primarily resected patients using immunohistochemistry were investigated. A total of 242 patients was analyzed in this study: 87 patients were investigated in the TCGA data set analysis and 155 patients in the analysis of protein expression using immunohistochemistry. High protein levels of FGF8, FGF18, and FGFR4 were detected in 94 (60.7%), 49 (31.6%) and 84 (54.2%) patients, respectively. Multivariable Cox proportional hazard regression models revealed that high expression of FGF8 was an independent prognostic factor for diminished overall survival for all patients and for neoadjuvantly treated patients. By contrast, FGF18 overexpression was significantly associated with longer survival rates in neoadjuvantly treated patients. In addition, FGF8 protein level correlated with Mandard regression due to neoadjuvant therapy, indicating potential as a predictive marker. In summary, FGF8 and FGF18 are promising candidates for prognostic factors in adenocarcinomas of the esophago-gastric junction and new potential targets for new anti-cancer therapies.
Bacteriophages as Adjuvant to Antibiotics for the Treatment of Periprosthetic Joint Infection Caused by Multidrug-Resistant Pseudomonas aeruginosa

We documented the adjunctive bacteriophage therapy to treat a chronic relapsing periprosthetic joint infection of the knee and chronic osteomyelitis of the femur caused by multidrug-resistant Pseudomonas aeruginosa. The combined antibiotic-phage treatment eradicated the infection, and no side effects to phages were observed. ABSTRACT We documented the adjunctive bacteriophage therapy to treat a chronic relapsing periprosthetic joint infection of the knee and chronic osteomyelitis of the femur caused by multidrug-resistant Pseudomonas aeruginosa. The combined antibiotic-phage treatment eradicated the infection, and no side effects to phages were observed.
Biomarkers for Detecting Resilience against Mycobacterial Disease in Animals

Paratuberculosis and bovine tuberculosis are two mycobacterial diseases of ruminants which have a considerable impact on livestock health, welfare, and production. These are chronic “iceberg” diseases which take years to manifest and in which many subclinical cases remain undetected. Suggested biomarkers to detect infected or diseased animals are numerous and include cytokines, peptides, and expression of specific genes; however, these do not provide a strong correlation to disease. ABSTRACT Paratuberculosis and bovine tuberculosis are two mycobacterial diseases of ruminants which have a considerable impact on livestock health, welfare, and production. These are chronic “iceberg” diseases which take years to manifest and in which many subclinical cases remain undetected. Suggested biomarkers to detect infected or diseased animals are numerous and include cytokines, peptides, and expression of specific genes; however, these do not provide a strong correlation to disease. Despite these advances, disease detection still relies heavily on dated methods such as detection of pathogen shedding, skin tests, or serology. Here we review the evidence for suitable biomarkers and their mechanisms of action, with a focus on identifying animals that are resilient to disease. A better understanding of these factors will help establish new strategies to control the spread of these diseases.
Subtype-specific transcriptional regulators in breast tumors subjected to genetic and epigenetic alterations

Abstract Motivation Breast cancer consists of multiple distinct tumor subtypes, and results from epigenetic and genetic aberrations that give rise to distinct transcriptional profiles. Despite previous efforts to understand transcriptional deregulation through transcription factor networks, the transcriptional mechanisms leading to subtypes of the disease remain poorly understood. Results We used a sophisticated computational search of thousands of expression datasets to define extended signatures of distinct breast cancer subtypes. Using ENCODE ChIP-seq data of surrogate cell lines and motif analysis we observed that these subtypes are determined by a distinct repertoire of lineage-specific transcription factors. Furthermore, specific pattern and abundance of copy number and DNA methylation changes at these TFs and targets, compared to other genes and to normal cells were observed. Overall, distinct transcriptional profiles are linked to genetic and epigenetic alterations at lineage-specific transcriptional regulators in breast cancer subtypes. Availability and implementation The analysis code and data are deposited at https://bitbucket.org/qzhu/breast.cancer. tf/. Supplementary information Supplementary data are available at Bioinformatics online.
Nimodipine-Dependent Protection of Schwann Cells, Astrocytes and Neuronal Cells from Osmotic, Oxidative and Heat Stress Is Associated with the Activation of AKT and CREB

Clinical and experimental data assumed a neuroprotective effect of the calcium channel blocker nimodipine. However, it has not been proven which neuronal or glial cell types are affected by nimodipine and which mechanisms underlie these neuroprotective effects. Therefore, the aim of this study was to investigate the influence of nimodipine treatment on the in vitro neurotoxicity of different cell types in various stress models and to identify the associated molecular mechanisms. Therefore, cell lines from Schwann cells, neuronal cells and astrocytes were pretreated for 24 h with nimodipine and incubated under stress conditions such as osmotic, oxidative and heat stress. The cytotoxicity was measured via the lactate dehydrogenase (LDH) activity of cell culture supernatant. As a result, the nimodipine treatment led to a statistically significantly reduced cytotoxicity in Schwann cells and neurons during osmotic (p ≤ 0.01), oxidative (p ≤ 0.001) and heat stress (p ≤ 0.05), when compared to the vehicle. The cytotoxicity of astrocytes was nimodipine-dependently reduced during osmotic (p ≤ 0.01), oxidative (p ≤ 0.001) and heat stress (not significant). Moreover, a decreased caspase activity as well as an increased proteinkinase B (AKT) and cyclic adenosine monophosphate response element-binding protein (CREB) phosphorylation could be observed after the nimodipine treatment under different stress conditions. These results demonstrate a cell type-independent neuroprotective effect of the prophylactic nimodipine treatment, which is associated with the prevention of stress-dependent apoptosis through the activation of CREB and AKT signaling pathways and the reduction of caspase 3 activity.
Nautical Collision Avoidance

Objective Experimentally investigate maneuver decision preferences in navigating ships to avoid a collision. How is safety (collision avoidance) balanced against efficiency (deviation from path and delay) and rules of the road under conditions of both trajectory certainty and uncertainty. Background Human decision error is a prominent factor in nautical collisions, but the multiple factors of geometry of collisions and role of uncertainty have been little studied in empirical human factors literature. Approach Eighty-seven Mechanical Turk participants performed in a lower fidelity ship control simulation, depicting ownship and a cargo ship hazard on collision or near-collision trajectories of various conflict geometries, while controlling heading and speed with the sluggish relative dynamics. Experiment 1 involved the hazard on a straight trajectory. In Experiment 2, the hazard could turn on unpredictable trials. Participants were rewarded for efficiency and penalized for collisions or close passes. Results Participants made few collisions, but did so more often when on a collision path. They sometimes violated the instructed rules of the road by maneuvering in front of the hazard ship’s path. They preferred speed control to heading control. Performance degraded in conditions of uncertainty. Conclusion Data reveal an understanding of maneuver decisions and conditions that affect the balance between safety and efficiency. Application The simulation and data highlight the degrading role of uncertainty and provide a foundation upon which more complex questions can be asked, asked of more trained navigators, and decision support tools examined.
Can clinical audits be enhanced by pathway simulation and machine learning? An example from the acute stroke pathway

Objective To evaluate the application of clinical pathway simulation in machine learning, using clinical audit data, in order to identify key drivers for improving use and speed of thrombolysis at individual hospitals. Design Computer simulation modelling and machine learning. Setting Seven acute stroke units. Participants Anonymised clinical audit data for 7864 patients. Results Three factors were pivotal in governing thrombolysis use: (1) the proportion of patients with a known stroke onset time (range 44%–73%), (2) pathway speed (for patients arriving within 4 hours of onset: per-hospital median arrival-to-scan ranged from 11 to 56 min; median scan-to-thrombolysis ranged from 21 to 44 min) and (3) predisposition to use thrombolysis (thrombolysis use ranged from 31% to 52% for patients with stroke scanned with 30 min left to administer thrombolysis). A pathway simulation model could predict the potential benefit of improving individual stages of the clinical pathway speed, whereas a machine learning model could predict the benefit of ‘exporting’ clinical decision making from one hospital to another, while allowing for differences in patient population between hospitals. By applying pathway simulation and machine learning together, we found a realistic ceiling of 15%–25% use of thrombolysis across different hospitals and, in the seven hospitals studied, a realistic opportunity to double the number of patients with no significant disability that may be attributed to thrombolysis. Conclusions National clinical audit may be enhanced by a combination of pathway simulation and machine learning, which best allows for an understanding of key levers for improvement in hyperacute stroke pathways, allowing for differences between local patient populations. These models, based on standard clinical audit data, may be applied at scale while providing results at individual hospital level. The models facilitate understanding of variation and levers for improvement in stroke pathways, and help set realistic targets tailored to local populations.
Outcome prediction for patients with obstructive lung disease considered for admission to critical care units in England, Wales and Northern Ireland.

Objective. To develop an outcome prediction score for patients with obstructive lung disease considered for admission to critical care. Design. Prospective cohort study using multivariate logistic regression for model building followed by score development and bootstrapping to adjust for over fitting. Setting. Critical care and respiratory high dependency units in England Wales and Northern Ireland. Participants. Patients aged 45 years and older with a clinical diagnosis of breathlessness, respiratory failure or change in mental status due to an exacerbation of COPD, asthma or a combination of COPD and asthma. Main outcome measures. The primary outcome was survival at 180 days and the model was constructed to predict this. The secondary outcomes were the accuracy of clinicians' predictions at the time of critical care admission and 180-day health-related quality of life Results. Ninety two critical care units and three respiratory high dependency units took part. Eight hundred and thirty two patients were recruited and the 651 patients without treatment limitations were used to develop the outcome score. Of the 651 patients 450 were intubated and 107 (16.4%) died in critical care, another 66 (10.1%) died in hospital and a further 47 (7.2%) had died by 180 days follow-up, giving a cumulative 180-day mortality of 33.8% (220 deaths). 420 of 518 (81.1%) survivors provided quality of life data and 400 (96.4%) would want ICU again under similar circumstances. A score using length of stay, age, sex, acute physiology, functional capacity, mid-arm circumference, atrial fibrillation, intubation status and diagnosis had an area under the receiver operating characteristic curve of 0.75 after bootstrapping and was well calibrated. Clinicians' predictions had an ROC area of 0.71 and were less well calibrated with a tendency towards pessimism. Conclusions. This study has produced an outpome prediction score with reasonable discrimination and good calibration that has the potential to support clinicians in understanding the prognosis of patients with obstructive lung disease considered for critical care
Electronic Devices: Content Use and Health Effects in Saudi Female Nursing Students

This is a cross sectional study assessing ownership, time spent and content use of electronic devices and their association with health symptoms, sleeping habits, dependence and sociability. Results showed portable devices and mobile phones were owned by 92.4% and 95.9% of students respectively. Computers and mobile phones use of 1 - 3 hours/ day was reported by 43.3% and 31.6% of students respectively. Audio, interactive and visual content use was reported by 90%, 67.8% and 56.6% of students respectively. Mild headache and poor sleeping quality was reported by 39.2% and 52% of students respectively. Dependence and sociability was reported by 77.2 % and 86 % of students respectively. Results show correlation between visual content use and headaches (p=0.02), between interactive use and ear symptoms (p= 0.03) also between dependence and audio use (p= 0.039). Significant correlation between the time spent using a mobile phone and sociability (p=0.01).
Dynamic predictive model for postoperative nausea and vomiting for intravenous fentanyl patient‐controlled analgesia

Postoperative nausea and vomiting is the most common side‐effect of opioid‐based intravenous patient‐controlled analgesia. Apfel's simplified risk score is popular but it has some limitations. We developed and validated a dynamic predictive model for nausea or vomiting up to 48 postoperative hours, available as an online web application. Fentanyl was used by 22,144 adult patients for analgesia after non‐cardiac surgery under general anaesthesia: we randomly divided them into development (80%) and validation (20%) cohorts, repeated 100 times. We used linear discriminant analysis to select variables for multivariate logistic regression. The incidences of postoperative nausea or vomiting were: 0–48 h, 5691/22,144 (26%); 0–6 h, 2749/22,144 (12%); 6–12 h, 2687/22,144 (12%); 12–18 h, 2624/22,144 (12%); 18–24 h, 1884/22,144 (9%); and 24–48 h, 1082/22,144 (5%). The median (95%CI) area under the receiver operating characteristic curve was 0.72 (0.71–0.73) up to 48 postoperative hours compared with 0.65 (0.64–0.66) for the Apfel model, p < 0.001. The equivalent areas for 0–6 h, 6–12 h, 12–18 h, 18–24 h and 24–48 h were: 0.70 (0.69–0.72); 0.71 (0.69–0.73); 0.69 (0.68–0.71); 0.70 (0.67–0.72); and 0.69 (0.66–0.71), respectively. Our web application allows clinicians to calculate incidences of nausea and vomiting in patients receiving intravenous fentanyl for patient‐controlled analgesia.
Occupational stress and cognitive failure of nurses and associations with on self-reported adverse events: a national cross-sectional survey.

AIM To determine correlations for nurse self-reported occupational stress, prevalence of cognitive failure and adverse events. DESIGN Cross-sectional nationwide survey. METHODS Tertiary-level public hospitals (N=115) from 13 provinces in Iran were recruited and 2895 nurses surveyed (August 2016 - December 2017). Participants' self-reported demographic information, occupational stress, cognitive failure and frequency of adverse events were analysed using chi-square, t tests and binary logistic regression. RESULTS This study showed that 29.1% of nurses had experienced adverse events in the past six months. Significant predictors for reported adverse events from logistic regression were 'Role stressors' 'Interpersonal relations stressors' and 'Action', while 'Working environment stressors' was protective for reported adverse events. Demographic predictors of adverse events were longer work hours and male gender, while those working in critical care units, general wards and other wards had higher reported adverse events than for emergency wards. CONCLUSIONS Occupational stress and cognitive failure are associated with the reporting of adverse events. Further research is needed to assess interventions to address occupational stress and cognitive failure to reduce adverse events. IMPACT Adverse events compromise patient safety, lead to increased health care costs and impact nursing staff. Higher self-reported adverse events were associated with higher reported stressors and cognitive failure. Understanding the factors that influence occupational stress, cognitive failure and adverse events will support quality patient care and safety.
Nanomaterials as Delivery Vehicles and Components of New Strategies to Combat Bacterial Infections: Advantages and Limitations

Life-threatening bacterial infections have been well-controlled by antibiotic therapies and this approach has greatly improved the health and lifespan of human beings. However, the rapid and worldwide emergence of multidrug resistant (MDR) bacteria has forced researchers to find alternative treatments for MDR infections as MDR bacteria can sometimes resist all the present day antibiotic therapies. In this respect, nanomaterials have emerged as innovative antimicrobial agents that can be a potential solution against MDR bacteria. The present review discusses the advantages of nanomaterials as potential medical means and carriers of antibacterial activity, the types of nanomaterials used for antibacterial agents, strategies to tackle toxicity of nanomaterials for clinical applications, and limitations which need extensive studies to overcome. The current progress of using different types of nanomaterials, including new emerging strategies for the single purpose of combating bacterial infections, is also discussed in detail.
Retinal exams requested at Primary Care Unit: indications, results and alternative strategies of evaluation

ABSTRACT Objective To evaluate indications, results and strategy of retinal exams requested at Primary Care Units. Methods A retrospective study that analyzed the indications and results of retinal exams, in the modalities clinical dilated fundus exams and color fundus photographs. In the following situations, patients were considered eligible for color fundus photographs if visual acuity was normal and ocular symptoms were absent: diabetes mellitus and/or hypertension, in use of drugs with potential retinal toxicity, diagnosis or suspicion of glaucoma, stable and asymptomatic retinopathies, except myopia greater than -3.00 diopters. Results A total of 1,729 patients were evaluated (66% female, age 63.5±15.5 years), and 1,190 underwent clinical dilated fundus exam and 539 underwent color fundus photographs. Diabetes was present in 32.2%. The main indications were diabetes (23.7%) and glaucoma evaluation (23.5%). In 3.4% of patients there was no apparent indication. The main results were a large cup/disc ratio (30.7%) and diabetic retinopathy (13.2%). Exam was normal in 9.6%, detected peripheral changes in 7% and could not be performed in 1%. Considering patients eligible for fundus photographs (22.4%), more than half underwent clinical dilated fundus exams. Conclusion Regarding exam modality, there were no important differences in the distribution of indications or diagnosis. Color fundus photograph is compatible with telemedicine and more cost-effective, and could be considered the strategy of choice in some scenarios. Since there are no clear guidelines for retinal exams indications or the modality of choice, this study may contribute to such standardization, in order to optimize public health resources.