Miracle-dz/UniFAR-FTUs huggingface dataset:
Direct numerical simulations of laminar separation bubbles: investigation of absolute instability and active flow control of transition to turbulence

Abstract Laminar separation bubbles generated on a flat plate by an adverse pressure gradient are investigated using direct numerical simulations (DNSs). Two-dimensional periodic forcing is applied at a blowing/suction slot upstream of separation. Control of separation through forcing with various frequencies and amplitudes is examined. For the investigation of absolute instability mechanisms, baseflows provided by two-dimensional Navier–Stokes calculations are analysed by introducing pulse disturbances and computing the three-dimensional flow response using DNS. The primary instability of the time-averaged flow is investigated with a local linear stability analysis. Employing a steady flow solution as baseflow, the nonlinear and non-parallel effects on the self-sustained disturbance development are illustrated, and a feedback mechanism facilitated by the upstream flow deformation is identified. Secondary instability is investigated locally using spatially periodic baseflows. The flow response to pulsed forcing indicates the existence of an absolute secondary instability mechanism, and the results indicate that this mechanism is dependent on the periodic forcing. Results from three-dimensional DNS provide insight into the global instability mechanisms of separation bubbles and complement the local analysis. A forcing strategy was devised that suppresses the temporal growth of three-dimensional disturbances, and as a consequence, breakdown to turbulence does not occur. Even for a separation bubble that has transitioned to turbulence, the flow relaminarizes when applying two-dimensional periodic forcing with proper frequencies and amplitudes.
Materials for single-etch double patterning process: surface curing agent and thermal cure resist

Two different pattern curing techniques were developed to stabilize first lithographic images for the single-etch double patterning process. The first method uses a surface curing agent (SCA) that is coated on top of the patterned surface to form a protective coating layer during the curing bake process. It was found that the surface curing process with SCA offers minimum CD changes before and after the double patterning process. Virtually no CD change was observed with the first lithographic images at various curing bake temperatures ranging from 120 ~160°C indicating the curing reaction is limited on the patterned surface. The second method uses a thermal cure resist (TCR) that is a special 193nm photoresist with a crosslinkable functional group to form an insoluble network upon heating at higher temperature. A single-step curing process of the first lithographic images was achieved using TCR by baking the patterned images at 180°C for 60sec. A cross-line contact hole double patterning method was used to evaluate these two different curing techniques and both SCA and TCR successfully demonstrated their capability to print 45nm contact holes with excellent CD uniformity in immersion lithography (1.35NA) with a 45nm half pitch mask. It was also confirmed that both SCA and TCR can be extended to the top-coat free immersion double patterning process using an embedded barrier layer technique.
Multiple instance learning framework can facilitate explainability in murmur detection

Objective: Cardiovascular diseases (CVDs) account for a high fatality rate worldwide. Heart murmurs can be detected from phonocardiograms (PCGs) and may indicate CVDs. Still they are often overlooked as their detection and correct clinical interpretation requires expert skills. In this work, we aim to predict the presence of murmurs and clinical outcome from multiple PCG recordings employing an explainable multitask model. Approach: Our approach consists of a two-stage multitask model. In the first stage, we predict the murmur presence in single PCGs using a multiple instance learning (MIL) framework. MIL also allows us to derive sample-wise classifications (i.e. murmur locations) while only needing one annotation per recording ("weak label") during training. In the second stage, we fuse explainable hand-crafted features with features from a pooling-based artificial neural network (PANN) derived from the MIL framework. Finally, we predict the presence of murmurs as well as the clinical outcome for a single patient based on multiple recordings using a simple feed-forward neural network. Main results: We show qualitatively and quantitatively that the MIL approach yields useful features and can be used to detect murmurs on multiple time instances and may thus guide a practitioner through PCGs. We analyze the second stage of the model in terms of murmur classification and clinical outcome. We achieved a weighted accuracy of 0.714 and an outcome cost of 13612 when using PANN model and demographic features on the CirCor dataset (hidden testset of the George B. Moody PhysioNet challenge 2022, team "Heart2Beat", rank 12 / 40). Significance: To the best of our knowledge, we are the first to demonstrate the usefulness of MIL in PCG classification. Also, we showcase how the explainability of the model can be analyzed quantitatively, thus avoiding confirmation bias inherent to many post-hoc methods. Finally, our overall results demonstrate the merit of employing MIL combined with handcrafted features for the generation of explainable features as well as for a competitive classification performance.
Genetic modification of inflammation and clonal hematopoiesis-associated coronary artery disease

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with an increased risk of cardiovascular diseases (CVD), putatively via inflammasome activation. We pursued an inflammatory gene modifier scan for CHIP-associated CVD risk among 424,651 UK Biobank participants. CHIP was identified using whole exome sequencing data of blood DNA and modeled both as a composite and for common drivers (DNMT3A, TET2, ASXL1, and JAK2) separately. We developed predicted gene expression scores for 26 inflammasome-related genes and assessed how they modify CHIP-associated CVD risk. We identify IL1RAP as a potential key molecule for CHIP-associated CVD risk across genes and increased AIM2 gene expression leading to heightened JAK2- and ASXL1-associated CVD risks. We show that CRISPR-induced Asxl1 mutated murine macrophages have a particularly heightened inflammatory response to AIM2 agonism. Our study provides new evidence to support gene-specific strategies to address CHIP-associated CVD risk.
Integrated bioinformatics analysis shows integrin alpha 3 is a prognostic biomarker for pancreatic cancer

Abstract Integrin subunit alpha 3 (ITGA3) expression correlates with the development and prognosis of human cancers. This study aimed to investigate the association of ITGA3 expression with pancreatic cancer (PCa) prognosis. The ITGA3 gene expression data were extracted from The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) cohort and 14 Gene Expression Omnibus microarray datasets. The differences in ITGA3 expression levels between tumor and non-tumor tissues were compared using the Mann–Whitney U test. Cox regression analysis and meta-analysis were performed to detect the association of ITGA3 expression with PCa prognosis. ITGA3 expression was higher in tumors than in controls. Tumors with advanced grades (3/4) had higher ITGA3 levels compared with early-grade tumors (1/2). The meta-analysis of the TCGA PAAD cohort and seven microarray datasets (GSE28735, GSE62452, GSE79668, GSE71729, GSE57495, GSE78229, and GSE21501) showed that ITGA3 was a prognostic biomarker in PCa (hazard ratio (HR) = 1.38, 95% confidence interval (CI) 1.26–1.51, p < 0.00001). Five ITGA3-related genes, including ITGB1 (HR = 1.6), ITGB5 (HR = 1.6), ITGB6 (HR = 1.6), LAMA3 (HR = 2.1), and CD9 (HR = 2.3), correlated with PCa prognosis significantly (p < 0.05). Functional enrichment analysis showed that ITGA3 was related to “hsa04151: PI3K-Akt signaling pathway” and “hsa04510: Focal adhesion. ” We concluded that high ITGA3 expression was a potential prognostic biomarker in PCa.
Enhancing Packet Tracing of Microservices in Container Overlay Networks using eBPF

The microservices architecture has been rapidly adopted to latency-sensitive applications. The architecture of these applications and the container overlay networks on servers are also complex. Distributed tracing is widely adopted in microservice applications; it suffers from the drawback of only focusing on service discovery and latency-based monitoring at an application layer, making it still challenging to monitor container overlay networks using distributed tracing. In this paper, we present an extended Berkeley Packet Filter (eBPF)-based packet tracing method using distributed tracing for latency measurement in the container overlay network. To efficiently detect the trace context on a HTTP payload, we moved the trace context position just behind the HTTP request line using sidecar proxy. Our tracing method gathered the HTTP packets that had the trace context and measured the latency using eBPF. Our evaluation was conducted using open-source benchmarks on Kubernetes; the results showed that the proposed tracing header format reduced the HTTP payload search space by up to approximately 80, and there was no significant change in end-to-end latency. Moreover, our eBPF-based tracing method presented similar latency characteristics on the overlay network in comparison with the characteristics of the packet-level traces obtained under tcpdump.
Prediction of intermediate and high risk factors based on MRI imaging radiomics before neoadjuvant therapy for cervical cancer

Objective: A fusion model based on axial LAVA+C sequence images and clinical characteristics on preoperative MRI before neoadjuvant therapy is discussed for identifying intermediate and high risk factors in cervical cancer patients. Methods: In a retrospective analysis of 145 cervical cancer patients treated at Fujian Cancer Hospital between January 2013 and July 2018, cases with more than two intermediate risk factors or more than one high-risk factor were classified as positive based on pathological findings, while cases with fewer than two intermediate risk factors and no high-risk factors were classified as negative based on pathological findings. Using an entirely random process, the cases were split into 116 cases for the training set and 29 cases for the test set, based on the Ax-LAVA+C sequence to extract radiomics features. dimensionality reduction for features LASSO and spearman correlation coefficient are used to select the most advantageous radiomics features. The best radiomics models may be filtered out using seven machine learning techniques. To create a composite radiomics model, combine the imaging radiomics model and the clinical model. And assess the model's effectiveness using the ROC, decision curves, and calibration curves. Results: The AUC of the validation set in the clinical- radiomics model was 0.823, the accuracy was 0.793, the sensitivity was 0.667, and the specificity was 0.972, which were higher than the clinical model and comparable to the radiomics model. Conclusion: Before beginning neoadjuvant therapy, the MRI radiomics model based on the Ax-LAVA+C sequence is effective in identifying intermediate- and high-risk variables for postoperative cervical cancer.
The Effect of Tanshinone IIA on Suppressing the Development of APL Through Inhibiting PI3K/AKT Signaling Pathway and Inducing Apoptosis or Triggering Differentiation of NB4 Cells

Acute promyelocytic leukemia, a hematologic malignancy that predominantly affects young adults, has a relatively high mortality rate. Although the application of all-trans retinoic acid (ATRA) therapy over the last decades has significantly improved the long-term survival rate of APL patients, this method of treatment is often accompanied by severe complications such as RAS. This study investigates the effect of using milder traditional Chinese herbal medicine Salvia Miltiorrhiza Bunge, containing tanshinone IIA as an active compound, to treat APL with minor adverse reactions. This experiment will use a known human acute promyelocytic leukemia cell line (NB-4). After treatment with tanshinone, measure phospho-AKT and AKT by western blot, indicating activity of apoptosis. The positive control is taxol, and the negative control is PBS/DMSO. Differentiation of NB4 will be measured by FACS for CD11b and CD11c. The positive control is ATRA, and negative control is no treatment of tanshinone IIA.
Clostridium Perfringens Alpha Toxin Inhibits Granulocyte Colony-Stimulating Factor

Clostridium perfringens is a gram-positive spore-forming anaerobic bacteria. C. perfringens is one of the most common causes of food poisoning illness and has a high mortality rate. As a growth factor, granulocyte colony-stimulating factor helps immune system maintain the balanced numbers of neutrophils when we are infected by pathogens. Clostridium perfringens alpha toxin promotes the formation of G-CSF. During the bacterial infection, lipopolysaccharide (LPS) is sensed through a Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88)-dependent pathway. This leads to the increased secretion of G-CSF into the systemic circulation which accelerated the proliferation and differentiation of neutrophils. However, Clostridium perfringens impairs the granulopoiesis by decreasing the surface expression of neutrophil Ly6G+. The study will use mice, which were separate into positive control groups with C. perfringens injection and negative control group with phosphate-buffered saline. Employing a variety of procedures and methods, in vivo, such as FACS and ELISA, the paper investigates whether C. perfringens alpha toxin would inhibit granulocyte colony-stimulating factor, impairing granulopoiesis and inhibiting G-CSF-mediated cell proliferation of Ly6G+ neutrophils in a productive and effective way.
X-Ray and Optical Emission from Radio Hot Spots of Powerful Quasars

In a survey with Chandra and HST of a sample of 17 radio sources with bright radio jets (16 powerful FR II and one nearby FR I), we detected X-ray and optical emission from a number of radio hot spots and lobes. Six hot spots on the near sides of powerful FR II galaxies (as determined from the jet asymmetry) were detected at X-rays, while none were detected on the far side, suggesting that high-energy emission from hot spots is anisotropic. In the nearby FR I galaxy 0836+299 (the only FR I in our sample) both hot spots are detected in X-rays, in agreement with the symmetric radio morphology. In the latter case the spectral energy distributions (SEDs) of both hot spots can be modeled from radio to X-rays with synchrotron emission from a single power-law energy distribution of electrons with Lorentz factors up to ~2 × 107. For the six hot spots of powerful FR II galaxies the X-ray flux lies above the extrapolation from the radio-to-optical continuum. Modeling the SEDs with a one-zone synchrotron self-Compton model, we find that equipartition is strongly violated, with the particle energy density dominating over the magnetic field one by 1-2 orders of magnitude. We discuss alternatives to this simple model, concluding that a viable alternative is that the X-ray emission is produced in the still-relativistic (Doppler factor δ = 3-6) terminal part of the jet by inverse Compton (IC) scattering on the CMB or synchrotron photons emitted by plasma flowing with a small velocity. X-ray emission from some of the lobes is detected on the side opposite to the jet, suggesting the possible relevance of back-scattered central radiation in providing seed photons for the IC process.
Improving nutrition through biofortification–A systematic review

Nutritious foods are essential for human health and development. However, malnutrition and hidden hunger continue to be a challenge globally. In most developing countries, access to adequate and nutritious food continues to be a challenge. Although hidden hunger is less prevalent in developed countries compared to developing countries where iron (Fe) and zinc (Zn) deficiencies are common. The United Nations (UN) 2nd Sustainable Development Goal was set to eradicate malnutrition and hidden hunger. Hidden hunger has led to numerous cases of infant and maternal mortalities, and has greatly impacted growth, development, cognitive ability, and physical working capacity. This has influenced several countries to develop interventions that could help combat malnutrition and hidden hunger. Interventions such as dietary diversification and food supplementation are being adopted. However, fortification but mainly biofortification has been projected to be the most sustainable solution to malnutrition and hidden hunger. Plant-based foods (PBFs) form a greater proportion of diets in certain populations; hence, fortification of PBFs is relevant in combating malnutrition and hidden hunger. Agronomic biofortification, plant breeding, and transgenic approaches are some currently used strategies in food crops. Crops such as cereals, legumes, oilseeds, vegetables, and fruits have been biofortified through all these three strategies. The transgenic approach is sustainable, efficient, and rapid, making it suitable for biofortification programs. Omics technology has also been introduced to improve the efficiency of the transgenic approach.
Meaning in life, meaning-making and posttraumatic growth in cancer patients: Systematic review and meta-analysis

Introduction The purpose of this systematic review and meta-analysis is to assess the association between meaning in life (MiL), meaning-making and posttraumatic growth (PTG) in the context of cancer. Methods A systematic search was conducted in eighteen electronic databases. The screening and selection process followed the PRISMA guidelines. For the purpose of the meta-analysis, the correlation coefficients between meaning in life and posttraumatic growth were extracted from the included studies. The effect size (r) was calculated using the restricted maximum-likelihood estimator, a random-effects model. Heterogeneity was assessed through the Q statistic, I2 index and forest plot, while publication bias was analyzed with the use of the funnel plot and Egger’s test. Results 889 records were considered according to the inclusion criteria. A total of nine articles, published between 2006 and 2021, were included in the systematic review. More than half were published in the last five years. The sample was mostly diagnosed with breast cancer. The meta-analysis included five articles (N = 844) and the results indicate a significant moderate correlation between meaning in life and posttraumatic growth (r = 0.43, 95% IC [0.36, 0.50]). Discussion In conclusion, there is a clear association between meaning in life and posttraumatic growth in cancer patients. Future research should explore this relationship further, in order to better assist and guide meaning centered interventions that can potentiate a positive adjustment and possibly growth from the cancer experience.
Does the practice of mindfulness reduce somatic symptoms and COVID-19-related anxiety? A community-based survey

Objective Since the beginning of COVID-19 pandemic, several studies have shown an increase of psychological distress in the general population. Previous research demonstrated that high levels of anxiety are associated with reporting more somatic symptoms. The ability to adaptively regulate emotions is essential to deal with stressful situations, and it is one of the main components of mindfulness practice. The aim of the present study was to document the effect of mindfulness practice on somatic symptoms and psychological distress in the context of COVID-19 pandemic. Methods The study has a descriptive cross-sectional design. During the second wave of COVID-19 pandemic, between November 2020 and January 2021 participants living in France responded to an online survey on the impact of COVID-19 on psychological distress and physical health. The questionnaire included the assessment of COVID-19-related anxiety, mindfulness practice and experience, dispositional mindfulness, somatization, depression, generalized anxiety, and emotion regulation. Results A total of 569 people (mean age = 39.8 years, 90% women) were included in the study. COVID-19 related anxiety was associated with higher levels of somatic symptoms, generalized anxiety, and depression. About half of the sample (n = 318, 56%) reported moderate to severe somatic symptoms that were associated with higher levels of depression and anxiety, lower levels of dispositional mindfulness and to the use of maladaptive emotion regulation strategies. Overall, 164 subjects (28.8%) reported practicing meditation. No differences were found in dispositional mindfulness (MAAS score) between beginners and advanced practitioners, regardless of the type, years, frequency, and length of practice. Participants with less experience in mindfulness practice reported a significant higher number of somatic symptoms than non-practitioners and a higher use of rumination. Moreover, mindfulness experience was associated with the use of more adaptive emotion regulation strategies. Conclusion Mindfulness meditation has been promoted as a practice enhancing well-being and helping to cope with the psychological impact of stressful events. However, in a distressing situation as COVID-19 pandemic, a limited experience in mindfulness practices might result in the development or endurance of somatic symptoms. Adequate training and a focus on mindful acceptance, may contribute to enhance the effectiveness of mindfulness practice.
Implementation of systematic safety checklists in a neurocritical care unit: a quality improvement study

Background and objectives Structured and systematised checklists have been shown to prevent complications and improve patient care. We evaluated the implementation of systematic safety checklists in our neurocritical care unit (NCCU) and assessed its effect on patient outcomes. Design/methods This quality improvement project followed a Plan–Do–Study–Act (PDSA) methodology. A checklist for medication reconciliation, thromboembolic prophylaxis, glycaemic control, daily spontaneous awakening, breathing trial, diet, catheter/lines duration monitoring and antibiotics de-escalation was implemented during daily patient rounds. Main outcomes included the rate of new infections, mortality and NCCU-length of stay (LOS). Intervened patients were compared with historical controls after propensity score and Euclidean distance matching to balance baseline covariates. Results After several PDSA iterations, we applied checklists to 411 patients; the overall average age was 61.34 (17.39). The main reason for admission included tumour resection (31.39%), ischaemic stroke (26.76%) and intracerebral haemorrhage (10.95%); the mean Sequential Organ Failure Assessment (SOFA) score was 2.58 (2.68). At the end of the study, the checklist compliance rate throughout the full NCCU stays reached 97.11%. After controlling for SOFA score, age, sex and primary admitting diagnosis, the implementation of systematic checklists significantly correlated with a reduced LOS (ß=−0.15, 95% CI −0.24 to −0.06), reduced rate of any new infections (OR 0.59, 95% CI 0.40 to 0.87) and reduced urinary tract infections (UTIs) (OR 0.23, 95% CI 0.09 to 0.55). Propensity score and Euclidean distance matching yielded 382 and 338 pairs with excellent covariate balance. After matching, outcomes remained significant. Discussion The implementation of safety checklists in the NCCU proved feasible, easy to incorporate into the NCCU workflow, and a helpful tool to improve adherence to practice guidelines and quality of care measurements. Furthermore, our intervention resulted in a reduced NCCU-LOS, rate of new infections and rate of UTIs compared with propensity score and Euclidean distance matched historical controls.