Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk of upper gastrointestinal bleeding in patients on oral anticoagulant and proton pump inhibitor co-therapy

Background Proton pump inhibitors (PPIs) are known to reduce the risk of upper gastrointestinal bleeding in patients on oral anticoagulants, and patients are increasingly on oral anticoagulants and PPI co-therapy. However, evidence is lacking on the safety and effectiveness of oral anticoagulants when co-administered with PPIs. Methods Among patients initiating oral anticoagulants (warfarin and non-vitamin K antagonist oral anticoagulants [NOACs], i.e. rivaroxaban, dabigatran, apixaban, and edoxaban) during 2013–2017, those concomitantly prescribed PPIs were identified (n = 19,851). The primary endpoint was hospitalization for major upper gastrointestinal bleeding, and secondary endpoints were death and ischemic stroke. Results During a mean 1.4 years of follow-up, the primary endpoint occurred in 512 (2.58%) patients. Overall, NOACs were associated with lower upper gastrointestinal bleeding risk after adjustment for age, sex, comorbidities and concomitant medications (adjusted hazard ratio 0.78, 95% confidence interval 0.65–0.94), compared to warfarin. There was no significant difference in upper gastrointestinal bleeding risk among the individual NOACs. This trend of reduced risk for upper gastrointestinal bleeding in NOACs compared to warfarin was consistent for both regular and reduced doses, throughout bleeding risk groups, and other subgroup analyses. NOACs were also associated with lower risk of death compared to warfarin. The risk for ischemic stroke was not significantly different among the oral anticoagulants in patients with atrial fibrillation. Conclusion In patients on oral anticoagulant and PPI co-therapy, NOACs were associated with lower risk of upper gastrointestinal bleeding and mortality compared to warfarin, while there was no difference among the oral anticoagulants for stroke prevention. In patients on PPI therapy, NOACs may preferred over warfarin for decreasing risk of upper gastrointestinal bleeding and mortality.
Timeliness of routine childhood vaccination in low- and middle-income countries, 1978–2021: Protocol for a scoping review to map methodologic gaps and determinants

The literature on the timeliness of childhood vaccination (i.e. vaccination at the earliest appropriate age) in low-and middle-income countries has important measurement and methodological issues that may limit their usefulness and cross comparison. We aim to conduct a comprehensive scoping review to map the existing literature with a key focus on how the literature on vaccination timeliness has evolved, how it has been defined or measured, and what determinants have been explored in the period spanning the last four decades. This scoping review protocol was developed based on the guidance for scoping reviews from the Joanna Briggs Institute. We will include English and French language peer-reviewed publications and grey literature on the timeliness of routine childhood vaccination in low-and middle-income countries published between January 1978 through to 2021. A three-step search strategy that involves an initial search of two databases to refine the keywords, a full search of all included electronic databases, and screening of references of previous studies for relevant articles missing from our full search will be employed. The search will be conducted in five electronic databases: MEDLINE, EMBASE, Global Health, CINAHL and Web of Science. Google search will also be conducted to identify relevant grey literature on vaccination timeliness. All retrieved titles from the search will be imported into Endnote X9.3. 3 (Clarivate Analytics) and deduplicated. Two reviewers will screen the titles, abstracts and full texts of publications for eligibility using Rayyan–the web based application for screening articles for systematic reviews. Using a tailored data extraction template, we will extract relevant information from eligible studies. The study team will analyse the extracted data using descriptive statistical methods and thematic analysis. The results will be presented using tables, while charts and maps will be used to aid the visualisation of the key findings and themes. The proposed review will generate evidence on key methodological gaps in the literature on timeliness of childhood vaccination. Such evidence would shape the direction of future research, and assist immunisation programme managers and country-level stakeholders to address the needs of their national immunisation system.
Physical outcomes of patients infected with HIV requiring intensive care unit admission for mechanical ventilation at one South African hospital: a pilot study

ABSTRACT Patients with life-threatening illnesses in intensive care receive management that improves their chances for survival. The physical outcomes of individuals infected with HIV who survive an intensive care unit (ICU) stay are not well known. The purpose was to describe the physical outcomes of ICU survivors in a high HIV prevalent area and highlight challenges as it relates to study feasibility. A pilot study at a tertiary-care university-affiliated hospital was done. Participants were assessed at ICU and ward admission, hospital discharge, three and six months following discharge. The profile and physical function, assessed with the ICU Mobility Scale, Karnofsky Performance Status Scale and six-minute walk test, of participants was determined. The EQ-5D-3 L provides information on participants’ health-related quality of life (HRQOL). The pilot study consists of five patients (n = 173 screened). All were independently mobile and on antiretroviral therapy prior to hospital admission. Respiratory and peripheral muscle weakness were present with variable performance in physical function across participants. Improvement in function occurred over time but participants still had physical dysfunction at six months. Pain/physical discomfort and anxiety/depression were common complaints influencing HRQOL. ICU survivors, who are HIV-positive, present with significant physical dysfunction who require rehabilitation to reduce disability.
Early career doctors' experiences of psychiatry placements: A qualitative study

Abstract Introduction On completion of a medical degree, junior doctors in the UK undergo a 2 year Foundation Programme. Since 2016, 45% of Foundation Programme doctors are required to undertake a psychiatry placement during foundation training. During this time, recruitment to Core Psychiatry Training has fluctuated, dropping to a 69% fill rate in 2017. Methods With the support of the Royal College of Psychiatrists, Health Education England and the UK Foundation Programme Office, a large-scale study was formulated utilising semi-structured focus groups. These exploring participant experiences help to understand how and if the psychiatry foundation placements are valuable, and their potential influence on a trainee choosing psychiatry as a career. A framework analysis was used to analyse data. Results Seventy-four participants across 10 foundation schools in England participated. Experiences and perceptions were split into three broad themes; pre-placement, during placement, and post-placement. Within these, 12 sub-themes emerged. Doctors valued independence and responsibility especially if accompanied by a level of support from seniors. They also enjoyed working as part of a multi-disciplinary team. However, there were clear issues around staffing levels, stigma attached to psychiatry, and out of hours working. Discussion The pre-placement perceptions of psychiatry as a specialty as well as the trainees’ personal priorities for career selection were influenced by psychiatry placement experiences. The results have important implications for the recruitment to the specialty and need to be considered when designing and constructing placement aims.
A Convolutional Neural Network for Improved Anomaly-Based Network Intrusion Detection

Cybersecurity protects and recovers computer systems and networks from cyber attacks. The importance of cybersecurity is growing commensurately with people's increasing reliance on technology. An anomaly detection-based network intrusion detection system is essential to any security framework within a computer network. In this article, we propose two models based on deep learning to address the binary and multiclass classification of network attacks. We use a convolutional neural network architecture for our models. In addition, a hybrid two-step preprocessing approach is proposed to generate meaningful features. The proposed approach combines dimensionality reduction and feature engineering using deep feature synthesis. The performance of our models is evaluated using two benchmark data sets, namely the network security laboratory-knowledge discovery in databases data set and the University of New South Wales Network Based 2015 data set. The performance is compared with similar deep learning approaches in the literature, as well as state-of-the-art classification models. Experimental results show that our models achieve good performance in terms of accuracy and recall, outperforming similar models in the literature.
Breast-Specific Molecular Clocks Comprised of ELF5 Expression and Promoter Methylation Identify Individuals Susceptible to Cancer Initiation

ELF5 expression or DNA methylation level at the ELF5 promoter region can be used as breast-specific biological clocks to identify women at higher than average risk of breast cancer. A robust breast cancer prevention strategy requires risk assessment biomarkers for early detection. We show that expression of ELF5, a transcription factor critical for normal mammary development, is downregulated in mammary luminal epithelia with age. DNA methylation of the ELF5 promoter is negatively correlated with expression in an age-dependent manner. Both ELF5 methylation and gene expression were used to build biological clocks to estimate chronological ages of mammary epithelia. ELF5 clock-based estimates of biological age in luminal epithelia from average-risk women were within three years of chronological age. Biological ages of breast epithelia from BRCA1 or BRCA2 mutation carriers, who were high risk for developing breast cancer, suggested they were accelerated by two decades relative to chronological age. The ELF5 DNA methylation clock had better performance at predicting biological age in luminal epithelial cells as compared with two other epigenetic clocks based on whole tissues. We propose that the changes in ELF5 expression or ELF5-proximal DNA methylation in luminal epithelia are emergent properties of at-risk breast tissue and constitute breast-specific biological clocks. Prevention Relevance: ELF5 expression or DNA methylation level at the ELF5 promoter region can be used as breast-specific biological clocks to identify women at higher than average risk of breast cancer.
Knowledge Exchange Between Domain-Adversarial and Private Networks Improves Open Set Image Classification

Both target-specific and domain-invariant features can facilitate Open Set Domain Adaptation (OSDA). To exploit these features, we propose a Knowledge Exchange (KnowEx) model which jointly trains two complementary constituent networks: (1) a Domain-Adversarial Network (DAdvNet) learning the domain-invariant representation, through which the supervision in source domain can be exploited to infer the class information of unlabeled target data; (2) a Private Network (PrivNet) exclusive for target domain, which is beneficial for discriminating between instances from known and unknown classes. The two constituent networks exchange training experience in the learning process. Toward this end, we exploit an adversarial perturbation process against DAdvNet to regularize PrivNet. This enhances the complementarity between the two networks. At the same time, we incorporate an adaptation layer into DAdvNet to address the unreliability of the PrivNet’s experience. Therefore, DAdvNet and PrivNet are able to mutually reinforce each other during training. We have conducted thorough experiments on multiple standard benchmarks to verify the effectiveness and superiority of KnowEx in OSDA.
Vocal Music Listening Enhances Poststroke Language Network Reorganization

Abstract Listening to vocal music has been recently shown to improve language recovery in stroke survivors. The neuroplasticity mechanisms supporting this effect are, however, still unknown. Using data from a three-arm, single-blind, randomized controlled trial including acute stroke patients (N = 38) and a 3 month follow-up, we set out to compare the neuroplasticity effects of daily listening to self-selected vocal music, instrumental music, and audiobooks on both brain activity and structural connectivity of the language network. Using deterministic tractography, we show that the 3 month intervention induced an enhancement of the microstructural properties of the left frontal aslant tract (FAT) for the vocal music group compared with the audiobook group. Importantly, this increase in the strength of the structural connectivity of the left FAT correlated with improved language skills. Analyses of stimulus-specific activation changes showed that the vocal music group exhibited increased activations in the frontal termination points of the left FAT during vocal music listening compared with the audiobook group from acute to 3 month poststroke stage. The increased activity correlated with the structural neuroplasticity changes in the left FAT. These results suggest that the beneficial effects of vocal music listening on poststroke language recovery are underpinned by structural neuroplasticity changes within the language network and extend our understanding of music-based interventions in stroke rehabilitation.
Natural Products from Nocardia and Their Role in Pathogenicity

Nocardia spp. are filamentous Actinobacteria of the order Corynebacteriales and mostly known for their ability to cause localized and systemic infections in humans. However, the onset and progression of nocardiosis is only poorly understood, in particular the mechanisms of strain-specific presentations. Recent genome sequencing has revealed an extraordinary capacity for the production of specialized small molecules. Such secondary metabolites are often crucial for the producing microbe to survive the challenges of different environmental conditions. An interesting question thus concerns the role of these natural products in Nocardia-associated pathogenicity and immune evasion in a human host. In this review, a summary and discussion of Nocardia metabolites is presented, which may play a part in nocardiosis because of their cytotoxic, immunosuppressive and metal-chelating properties or otherwise vitally important functions. This review also contains so far unpublished data concerning the biosynthesis of these molecules that were obtained by detailed bioinformatic analyses.
Early development of the cortical layers in the human brain

The cortical plate (CP) first appears at seven postconceptional weeks (pcw), when it splits the preexisting preplate into two layers, the marginal zone and the presubplate (pSP). Although three‐dimensional (3D) analysis using fetal magnetic resonance imaging and two‐dimensional tissue observations have been reported, there have been no studies analyzing the early development of the layer structure corresponding to the pSP stage in 3D. Here, we reconstructed 3‐D models of the brain with a focus on the cortical layers in pSP stage. To achieve this, we digitized serial tissue sections of embryos between CS20 and CS23 from the Kyoto Collection (n = 7, approximately 7–8.5 pcw), and specimens at early fetal phase from the Blechschmidt Collection (n = 2, approximately 9.5–12 pcw, crown rump length [CRL] 39 and 64 mm). We observed tissue sections and 3D images and performed quantitative analysis of the thickness, surface area, and volume. Because the boundary between pSP and the intermediate zone (IZ) could not be distinguished in hematoxylin and eosin‐stained sections, the two layers were analyzed together as a single layer in this study. The histology of the layers was observed from CS21 and became distinct at CS22. Subsequently, we observed the 3‐D models; pSP‐IZ was present in a midlateral region of the cerebral wall at CS21, and an expansion centered around this region was observed after CS22. We observed it over the entire cerebral hemisphere at early fetal phase (CRL 39 mm). The thickness of pSP‐IZ was visible in 3D and was greater in the midlateral region. At the end of the pSP stage (CRL 64 mm), the thick region expanded to lateral, superior, and posterior regions around the primordium of the insula. While, the region near the basal ganglia was not included in the thickest 10% of the pSP‐IZ area. Middle cerebral artery was found in the midlateral region of the cerebral wall, near the area where pSP‐IZ was observed. Feature of layer structure growth was revealed by quantitative assessment as thickness, surface area, and volume. The maximum thickness value of pSP‐IZ and CP increased significantly according to CRL, whereas the median value increased slightly. The layer structure appeared to grow and spread thin, rather than thickening during early development, which is characteristic during pSP stages. The surface area of the cerebral total tissue, CP, and pSP‐IZ increased in proportion to the square of CRL. The surface area of CP and pSP‐IZ approached that of the total tissue at the end of the pSP stage. Volume of each layer increased in proportion to the cube of CRL. pSP‐IZ and CP constituted over 50% of the total tissue in volume at the end of the pSP stages. We could visualize the growth of pSP‐IZ in 3D and quantify it during pSP stage. Our approach allowed us to observe the process of rapid expansion of pSP‐IZ from the midlateral regions of the cerebral wall, which subsequently becomes the insula.
Perform Thermodynamics Measurements on Fuel Cycle Case Study Systems

This document was prepared to meet FCR&D level 3 milestone M3FT-14IN0304022, “Perform Thermodynamics Measurements on Fuel Cycle Case Study Systems. ” This work was carried out under the auspices of the Thermodynamics and Kinetics FCR&D work package. This document reports preliminary work in support of determining the thermodynamic parameters for the ALSEP process. The ALSEP process is a mixed extractant system comprised of a cation exchanger 2-ethylhexyl-phosphonic acid mono-2-ethylhexyl ester (HEH[EHP]) and a neutral solvating extractant N,N,N’,N’-tetraoctyldiglycolamide (TODGA). The extractant combination produces complex organic phase chemistry that is challenging for traditional measurement techniques. To neutralize the complexity, temperature dependent solvent extraction experiments were conducted with neat TODGA and scaled down concentrations of the ALSEP formulation to determine the enthalpies of extraction for the two conditions. A full set of thermodynamic data for Eu, Am, and Cm extraction by TODGA from 3.0 M HNO3 is reported. These data are compared to previous extraction results from a 1.0 M HNO3 aqueous medium, and a short discussion of the mixed HEH[EHP]/TODGA system results is offered.
Randomized, Single-Blind, Multicenter Phase II Study of Two Doses of Imetelstat in Relapsed or Refractory Myelofibrosis

PURPOSE Patients with myelofibrosis who are relapsed or refractory (R/R) to Janus-associated kinase inhibitors (JAKis) have poor clinical outcomes including dismal overall survival (OS) that ranges between 13 and 16 months. Imetelstat, a telomerase inhibitor, was evaluated in patients with intermediate-2 or high-risk myelofibrosis R/R to JAKi in a phase II multicenter study (ClinicalTrials.gov identifier: NCT02426086). PATIENTS AND METHODS Patients were randomly assigned to receive either imetelstat 9.4 mg/kg or 4.7 mg/kg intravenous once every 3 weeks. Spleen response (≥ 35% spleen volume reduction) and symptom response (≥ 50% reduction in total symptom score) rates at week 24 were coprimary end points. Secondary end points included OS and safety. RESULTS Study enrollment was closed early, and patients treated with 4.7 mg/kg were permitted to continue treatment with 9.4 mg/kg. At week 24, spleen and symptom response rates were 10.2% and 32.2% in the 9.4-mg/kg arm and 0% and 6.3% in the 4.7-mg/kg arm. Treatment with imetelstat 9.4 mg/kg led to a median OS of 29.9 months and bone marrow fibrosis improvement in 40.5% and variant allele frequency reduction of driver mutations in 42.1% of evaluable patients. Fibrosis improvement and variant allele frequency reduction correlated with OS. Target inhibition was demonstrated by reduction of telomerase activity and human telomerase reverse transcriptase level and correlated with spleen response, symptom response, and OS. Most common adverse events on both arms were grade 3 or 4 reversible cytopenias. CONCLUSION In this phase II study of two imetelstat doses, 9.4 mg/kg once every 3 weeks demonstrated clinical benefits in symptom response rate, with an acceptable safety profile for this poor-risk JAKi R/R population. Biomarker and bone marrow fibrosis assessments suggested selective effects on the malignant clone. A confirmatory phase III study is currently underway.
Patient-Specific Computational Fluid Dynamics Reveal Localized Flow Patterns Predictive of Post–Left Ventricular Assist Device Aortic Incompetence

Background: Progressive aortic valve disease has remained a persistent cause of concern in patients with left ventricular assist devices. Aortic incompetence (AI) is a known predictor of both mortality and readmissions in this patient population and remains a challenging clinical problem. Methods: Ten left ventricular assist device patients with de novo aortic regurgitation and 19 control left ventricular assist device patients were identified. Three-dimensional models of patients’ aortas were created from their computed tomography scans, following which large-scale patient-specific computational fluid dynamics simulations were performed with physiologically accurate boundary conditions using the SimVascular flow solver. Results: The spatial distributions of time-averaged wall shear stress and oscillatory shear index show no significant differences in the aortic root in patients with and without AI (mean difference, 0.67 dyne/cm2 [95% CI, −0.51 to 1.85]; P=0.23). Oscillatory shear index was also not significantly different between both groups of patients (mean difference, 0.03 [95% CI, −0.07 to 0.019]; P=0.22). The localized wall shear stress on the leaflet tips was significantly higher in the AI group than the non-AI group (1.62 versus 1.35 dyne/cm2; mean difference [95% CI, 0.15–0.39]; P<0.001), whereas oscillatory shear index was not significantly different between both groups (95% CI, −0.009 to 0.001; P=0.17). Conclusions: Computational fluid dynamics serves a unique role in studying the hemodynamic features in left ventricular assist device patients where 4-dimensional magnetic resonance imaging remains unfeasible. Contrary to the widely accepted notions of highly disturbed flow, in this study, we demonstrate that the aortic root is a region of relatively stagnant flow. We further identified localized hemodynamic features in the aortic root that challenge our understanding of how AI develops in this patient population.