Miracle-dz/UniFAR-FTUs huggingface dataset:
Predictive Utility of an Objective Measure of Situation Awareness

Situation awareness (SA) can generally be defined as the pilot's mental model of the world around him. The ability of the pilot to maintain situation awareness has been recognized in the pilot community as crucial to mission success and survivability. Little empirical work has been done to explore this construct, however, as measurement techniques have been lacking. The Situation Awareness Global Assessment Technique (SAGAT) was developed and validated as an objective measure of a pilot's situation awareness to meet this need. An investigation of the relationship between situation awareness and performance was conducted using SAGAT. The study evaluated the utility of situation awareness in a manned fighter sweep tactical mission using experienced pilot subjects. A total of 90 trials were conducted. The results support the importance of situation awareness for mission effectiveness. Blue Team subjects were almost twice as likely to later kill an aircraft when they had SA of that aircraft, as measured by SAGAT, than when they did not. The effect of rules of engagement, mission scenario, aircraft and weapons systems on the relationship between SA and performance is discussed.
Fiducial markers and their impact on ablation outcome for patients treated with MR-guided transurethral ablation (TULSA): a retrospective technical analysis

Abstract Objectives Fiducial markers improve accuracy in external beam radiation therapy (EBRT) for treatment of prostate cancer (PCa). However, many patients recur after EBRT necessitating additional treatment, such as MR-guided transurethral ultrasound ablation (TULSA). Residual markers may compromise TULSA through ultrasound field distortions and generation of local susceptibility artifacts. The objective was to investigate how markers affect the ablation outcome during clinical TULSA treatments. Subjects and methods A retrospective analysis was performed on nine patients with radiorecurrent PCa and residual markers who received TULSA. The MR susceptibility artifact was quantified as a function of marker type, size and orientation, in particular for thermometry. The spatial distribution of markers inside the prostate was recorded, and the resulting impact on the thermal dose was measured. The thermal dose measurements were directly compared to the residual enhancing prostatic tissue observed on the immediate and control post-TULSA contrast enhanced (CE) image. Results Successful thermal dose accumulation to the target boundary occurred for 14/20 (70%) of markers, confirmed with CE imaging. Gold markers situated simultaneously close to the urethra (≤12 mm) and far from the target boundary (≥13 mm) reduced the ultrasound depth of heating. Nitinol markers produced large, hypointense artifacts that disrupted thermometry and compromised treatment. Artifacts from gold markers were less pronounced, but when located near the target boundary, also affected treatment. Conclusion Marker composition, orientation and location inside the prostate can all potentially impact treatment outcome. Proper patient selection through detailed MRI screening is critical to ensure successful radiorecurrent PCa treatment outcomes with TULSA.
Resourcing resilience: educational considerations for supporting well-being and preventing violent extremism amongst Finnish youth

ABSTRACT Resilience has been highlighted in educational policies internationally as one of the key elements that may prevent negative developmental trajectories, such as radicalization into violent extremism. To examine the factors that contribute to resilience at adolescence and to understand how resilience relates to wellbeing this study investigates the resilience resources of Finnish youth (n=2837). Furthermore, we examined the relationship between resilience and the youth’s self-reported levels of empathy and beneficence (pro-social orientation), life satisfaction and meaning in life (contentment with life), and their intention for non-violent action (activism), and intention for violent actions (radicalism). The results of the latent profile analysis suggest that high resilience resources are related to higher levels of pro-social orientation and contentment with life, while the opposite is true for low resilience resources. However, the findings do not indicate any significant connection between low resilience resources and an increased intent for activism or radicalism.
Enhancing Type 2 diabetes risk communication with message framing and tailored risk feedback: an online randomised controlled trial

ABSTRACT Objective Type 2 diabetes (T2D) risk communication may help individuals better understand their risk and motivate behavioural changes. There is a wealth of research in health risk communication which suggest the effectiveness of message framing and tailored risk feedback; however, little is known about their potential utility when used concurrently and in high-risk population approaches to T2D prevention. Methods This study evaluated the effects of message framing and tailored risk feedback on T2D risk perception and behavioural intentions, and if these effects were varied by level of alcohol consumption. Three hundred and forty-seven online participants were stratified by levels of alcohol consumption and subsequently randomised to receive T2D information, risk estimates, and lifestyle recommendations that were subjected to four different message framing and tailoring manipulations. Results No significant differences were observed in T2D risk perceptions or behavioural intentions by study arm. However, T2D risk perception scores and accuracies, and behavioural intentions significantly increased post-intervention across all conditions. Conclusions Despite the lack of impact of message framing or message tailoring, this study suggests that a brief online T2D risk communication can help to correct risk perceptions and increase behavioural intentions. These preliminary findings are encouraging and support the continued development of online risk assessment and communication to help combat the current T2D epidemic. KEY POINTS What is already known about this topic: (1) Most individuals at risk of Type 2 diabetes do not engage in risk-reducing behaviours. (2) Risk communication may help to correct Type 2 diabetes risk perception and lead to healthy behavioural changes. (3) Message framing and tailored risk feedback have been shown to be effective ways of communication, though no studies have examined them in combination. What this topic adds: (1) Preliminary support for the brief online Type 2 diabetes risk communication intervention in correcting risk perceptions and increasing behavioural intentions. (2) Effectiveness of manipulation did not differ based on message manipulation. (3) Preliminary support for the use of the risk communication intervention in high-risk populations.
Optimization techniques for orbit estimation and determination to control the satellite motion

This paper analyzes the methods of accurate orbit estimation and determination, which are the first and the most important phases in preparation of the satellite-control-maneuver. The paper specifically addresses the algorithmic implementation of the Least Mean Squares (LMS) and Kalman filters for the spacecraft orbit determination problem. The inherent advantages, disadvantages and trade-off, which are required to select the suitable method, have been analyzed. This approach has been refined using multi layer Adaptive Neural Network (ANN) with a nonlinear function. The three different approaches have been compared with regard to efficiency, performance, accuracy and running time in order to analyze the inherent characteristics of the used techniques. ANN has shown a good agreement with the definitive solution in case of the availability of old cycles data of the geostationary satellite. Depending on the application and available data one should carefully choose among these methods in orbit determination.
New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data

Tetratricopeptide repeat and ankyrin repeat containing 1 (TRANK1) is a robust risk gene of bipolar disorder (BD). However, little is known on the role of TRANK1 in the pathogenesis of BD and whether the gut microbiota is capable of regulating TRANK1 expression. In this study, we first investigated the serum mRNA level of TRANK1 in medication-free patients with a depressive episode of BD, then a mice model was constructed by fecal microbiota transplantation (FMT) to explore the effects of gut microbiota on brain TRANK1 expression and neuroinflammation, which was further verified by in vitro Lipopolysaccharide (LPS) treatment in BV-2 microglial cells and neurons. 22 patients with a depressive episode and 28 healthy individuals were recruited. Serum level of TRANK1 mRNA was higher in depressed patients than that of healthy controls. Mice harboring ‘BD microbiota’ following FMT presented depression-like phenotype. mRNA levels of inflammatory cytokines and TRANK1 were elevated in mice hippocampus and prefrontal cortex. In vitro, LPS treatment activated the secretion of pro-inflammatory factors in BV-2 cells, which was capable of upregulating the neuronal expression of TRANK1 mRNA. Moreover, primary cortical neurons transfected with plasmid Cytomegalovirus DNA (pcDNA3.1(+)) vector encoding human TRANK1 showed decreased dendritic spine density. Together, these findings add new evidence to the microbiota-gut-brain regulation in BD, indicating that microbiota is possibly involved in the neuropathogenesis of BD by modulating the expression of TRANK1.
Efficacy and Benefit of Postoperative Chemotherapy in Micropapillray or Solid Predominant Pattern in Stage IB Lung Adenocarcinoma: A Systematic Review and Meta-Analysis

Background: The benefit of postoperative chemotherapy remains controversial for patients with either a micropapillary or solid pattern in stage IB non-small cell lung cancer. This study is designed to explore the significance of postoperative chemotherapy in patients with either a micropapillary or solid pattern in stage IB lung adenocarcinoma. Method: To conduct the meta-analysis, PubMed, Cochrane Library, Embase and Medline were used to collect literature on long-term follow-up studies published before March, 2021, involving postoperative chemotherapy for patients with both a micropapillary or solid pattern in stage IB lung adenocarcinoma as compared to non-postoperative chemotherapy. Survival data was extracted from the literature, including the overall survival and disease-free survival. Based on overall survival and disease-free survival, hazard ratios and their 95% of confidence intervals were applied to assess the prognostic effect of postoperative chemotherapy. Review Manager software was used to merge the effect size for the meta-analysis. Result: In total, 6 papers with 956 patients were included. In terms of the prognosis of patients suffering from lung cancer when receiving postoperative chemotherapy, this study comprehensively reviews and evaluates the available evidence of micropapillary or solid patterns. After excluding the heterogeneity between the studies, we found that the pooled results from 6 studies report that postoperative chemotherapy was associated with a better overall survival rate when compared with non-postoperative chemotherapy (hazard ratio = 0.58, 95% confidence interval, 0.44–0.77; P = 0.0002). Postoperative chemotherapy also significantly improved the disease-free survival in patients with either a micropapillary or a solid pattern in stage IB lung adenocarcinoma (postoperative chemotherapy vs. non-postoperative chemotherapy, hazard ratio = 0.51, 95% confidence interval, 0.40–0.64; P < 0.001). However, a subgroup analysis showed that compared with non-postoperative chemotherapy, tumor size was unrelated to the prognosis of patients in stage IB undergoing postoperative chemotherapy (hazard ratio = 0.98, 95% confidence interval, 0.94–1.02; P = 0.27). Conclusion: Postoperative chemotherapy results in a better long-term survival rate for patients with either a solid or a micropapillary pattern in stage IB lung adenocarcinoma. Multi-center, prospective, clinical trials are needed to validate our findings.
Comparison of Intraocular Cytokine Levels of Choroidal Neovascularization Secondary to Different Retinopathies

Purpose: To investigate and compare the aqueous concentrations of vascular endothelial growth factor (VEGF) and other inflammatory cytokines in various choroidal neovascularization (CNV) diseases and types. Methods: This observational study included 127 naive eyes with CNV and 43 control eyes with cataracts. Aqueous humor (AH) samples were obtained prior to intravitreal anti-VEGF injection or cataract surgery. Multiple inflammatory cytokines, including VEGF, interleukin (IL) 6, IL-8, IL-10, interferon-inducible protein 10 (IP-10), and monocyte chemotactic protein 1 (MCP-1) levels, were measured using a multiplex bead assay. The angiogenesis index was defined as the ratio of IP-10 to MCP-1. In addition, the relationship among AH cytokine levels, central macular thickness (CMT), and CNV size on optical coherence tomography angiography (OCTA) was evaluated. Results: Except in the myopic CNV group (P = 0.452), the AH concentration of VEGF was significantly higher in all other CNV groups than in the control group (P < 0.05 for all comparisons). IL-8, IL-10, IP-10, and MCP-1 levels (P < 0.05 for all groups) were significantly higher in all CNV diseases except those with neovascular central serous chorioretinopathy. The angiogenesis index was significantly higher in all CNV diseases (P < 0.05 for all comparisons). The VEGF level may be associated with the size of the CNV on OCTA (p = 0.043). Conclusions: The level of intraocular inflammatory cytokines varied among different CNV diseases and CNV types. Therefore, the angiogenesis index may be a more sensitive indicator of angiogenesis.
On the Effect of Soft Molecularly Imprinted Nanoparticles Receptors Combined to Nanoplasmonic Probes for Biomedical Applications

Soft, deformable, molecularly imprinted nanoparticles (nanoMIPs) were combined to nano-plasmonic sensor chips realized on poly (methyl methacrylate) (PMMA) substrates to develop highly sensitive bio/chemical sensors. NanoMIPs (dmean < 50 nm), which are tailor-made nanoreceptors prepared by a template assisted synthesis, were made selective to bind Bovine Serum Albumin (BSA), and were herein used to functionalize gold optical nanostructures placed on a PMMA substrate, this latter acting as a slab waveguide. We compared nanoMIP-functionalized non-optimized gold nanogratings based on periodic nano-stripes to optimized nanogratings with a deposited ultra-thin MIP layer (<100 nm). The sensors performances were tested by the detection of BSA using the same setup, in which both chips were considered as slab waveguides, with the periodic nano-stripes allocated in a longitudinal orientation with respect to the direction of the input light. Result demonstrated the nanoMIP-non optimized nanogratings showed superior performance with respect to the ultra-thin MIP-optimized nanogratings. The peculiar deformable character of the nano-MIPs enabled to significantly enhance the limit of detection (LOD) of the plasmonic bio/sensor, allowing the detection of the low femtomolar concentration of analyte (LOD ∼ 3 fM), thus outpassing of four orders of magnitude the sensitivies achieved so far on optimized nano-patterned plasmonic platforms functionalized with ultra-thin MIP layers. Thus, deformable nanoMIPs onto non-optimized plasmonic probes permit to attain ultralow detections, down to the quasi-single molecule. As a general consideration, the combination of more plasmonic transducers to different kinds of MIP receptors is discussed as a mean to attain the detection range for the selected application field.
Iron Rims in Patients With Multiple Sclerosis as Neurodegenerative Marker? A 7-Tesla Magnetic Resonance Study

Introduction: Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system, characterized by inflammatory-driven demyelination. Symptoms in MS manifest as both physical and neuropsychological deficits. With time, inflammation is accompanied by neurodegeneration, indicated by brain volume loss on an MRI. Here, we combined clinical, imaging, and serum biomarkers in patients with iron rim lesions (IRLs), which lead to severe tissue destruction and thus contribute to the accumulation of clinical disability. Objectives: Subcortical atrophy and ventricular enlargement using an automatic segmentation pipeline for 7 Tesla (T) MRI, serum neurofilament light chain (sNfL) levels, and neuropsychological performance in patients with MS with IRLs and non-IRLs were assessed. Methods: In total 29 patients with MS [15 women, 24 relapsing-remitting multiple sclerosis (RRMS), and five secondary-progressive multiple sclerosis (SPMS)] aged 38 (22–69) years with an Expanded Disability Status Score of 2 (0–8) and a disease duration of 11 (5–40) years underwent neurological and neuropsychological examinations. Volumes of lesions, subcortical structures, and lateral ventricles on 7-T MRI (SWI, FLAIR, and MP2RAGE, 3D Segmentation Software) and sNfL concentrations using the Simoa SR-X Analyzer in IRL and non-IRL patients were assessed. Results: (1) Iron rim lesions patients had a higher FLAIR lesion count (p = 0.047). Patients with higher MP2Rage lesion volume exhibited more IRLs (p <0.014) and showed poorer performance in the information processing speed tested within 1 year using the Symbol Digit Modalities Test (SDMT) (p <0.047). (2) Within 3 years, patients showed atrophy of the thalamus (p = 0.021) and putamen (p = 0.043) and enlargement of the lateral ventricles (p = 0.012). At baseline and after 3 years, thalamic volumes were lower in IRLs than in non-IRL patients (p = 0.045). (3) At baseline, IRL patients had higher sNfL concentrations (p = 0.028). Higher sNfL concentrations were associated with poorer SDMT (p = 0.004), regardless of IRL presence. (4) IRL and non-IRL patients showed no significant difference in the neuropsychological performance within 1 year. Conclusions: Compared with non-IRL patients, IRL patients had higher FLAIR lesion counts, smaller thalamic volumes, and higher sNfL concentrations. Our pilot study combines IRL and sNfL, two biomarkers considered indicative for neurodegenerative processes. Our preliminary data underscore the reported destructive nature of IRLs.
A Microphysiological Cell-Culturing System for Pharmacokinetic Drug Exposure and High-Resolution Imaging of Arrays of 3D Microtissues

Understanding the pharmacokinetic/pharmacodynamic (PK/PD)-relationship of a drug candidate is key to determine effective, yet safe treatment regimens for patients. However, current testing strategies are inefficient in characterizing in vivo responses to fluctuating drug concentrations during multi-day treatment cycles. Methods based on animal models are resource-intensive and require time, while traditional in vitro cell-culturing methods usually do not provide temporally-resolved information on the effects of in vivo–like drug exposure scenarios. To address this issue, we developed a microfluidic system to 1) culture arrays of three-dimensional spheroids in vitro, to 2) apply specific dynamic drug exposure profiles, and to 3) in-situ analyze spheroid growth and the invoked drug effects in 3D by means of 2-photon microscopy at tissue and single-cell level. Spheroids of fluorescently-labeled T-47D breast cancer cells were monitored under perfusion-culture conditions at short time intervals over three days and exposed to either three 24 h-PK-cycles or a dose-matched constant concentration of the phosphatidylinositol 3-kinase inhibitor BYL719. While the overall efficacy of the two treatment regimens was similar, spheroids exposed to the PK profile displayed cycle-dependent oscillations between regression and regrowth. Spheroids treated with a constant BYL719 concentration regressed at a steady, albeit slower rate. At a single-cell level, the cell density in BYL719-treated spheroids oscillated in a concentration-dependent manner. Our system represents a versatile tool for in-depth preclinical characterization of PK/PD parameters, as it enables an evaluation of drug efficacy and/or toxicity under realistic exposure conditions.
Lacosamide Inhibition of NaV1.7 Channels Depends on its Interaction With the Voltage Sensor Domain and the Channel Pore

Lacosamide, developed as an anti-epileptic drug, has been used for the treatment of pain. Unlike typical anticonvulsants and local anesthetics which enhance fast-inactivation and bind within the pore of sodium channels, lacosamide enhances slow-inactivation of these channels, suggesting different binding mechanisms and mode of action. It has been reported that lacosamide’s effect on NaV1.5 is sensitive to a mutation in the local anesthetic binding site, and that it binds with slow kinetics to the fast-inactivated state of NaV1.7. We recently showed that the NaV1.7-W1538R mutation in the voltage-sensing domain 4 completely abolishes NaV1.7 inhibition by clinically-achievable concentration of lacosamide. Our molecular docking analysis suggests a role for W1538 and pore residues as high affinity binding sites for lacosamide. Aryl sulfonamide sodium channel blockers are also sensitive to substitutions of the W1538 residue but not of pore residues. To elucidate the mechanism by which lacosamide exerts its effects, we used voltage-clamp recordings and show that lacosamide requires an intact local anesthetic binding site to inhibit NaV1.7 channels. Additionally, the W1538R mutation does not abrogate local anesthetic lidocaine-induced blockade. We also show that the naturally occurring arginine in NaV1.3 (NaV1.3-R1560), which corresponds to NaV1.7-W1538R, is not sufficient to explain the resistance of NaV1.3 to clinically-relevant concentrations of lacosamide. However, the NaV1.7-W1538R mutation conferred sensitivity to the NaV1.3-selective aryl-sulfonamide blocker ICA-121431. Together, the W1538 residue and an intact local anesthetic site are required for lacosamide’s block of NaV1.7 at a clinically-achievable concentration. Moreover, the contribution of W1538 to lacosamide inhibitory effects appears to be isoform-specific.