Miracle-dz/UniFAR-FTUs huggingface dataset:
Cost-Effectiveness of Virtual Reality Cognitive Behavioral Therapy for Psychosis: Health-Economic Evaluation Within a Randomized Controlled Trial

Background Evidence was found for the effectiveness of virtual reality-based cognitive behavioral therapy (VR-CBT) for treating paranoia in psychosis, but health-economic evaluations are lacking. Objective This study aimed to determine the short-term cost-effectiveness of VR-CBT. Methods The health-economic evaluation was embedded in a randomized controlled trial evaluating VR-CBT in 116 patients with a psychotic disorder suffering from paranoid ideation. The control group (n=58) received treatment as usual (TAU) for psychotic disorders in accordance with the clinical guidelines. The experimental group (n=58) received TAU complemented with add-on VR-CBT to reduce paranoid ideation and social avoidance. Data were collected at baseline and at 3 and 6 months postbaseline. Treatment response was defined as a pre-post improvement of symptoms of at least 20% in social participation measures. Change in quality-adjusted life years (QALYs) was estimated by using Sanderson et al’s conversion factor to map a change in the standardized mean difference of Green’s Paranoid Thoughts Scale score on a corresponding change in utility. The incremental cost-effectiveness ratios were calculated using 5000 bootstraps of seemingly unrelated regression equations of costs and effects. The cost-effectiveness acceptability curves were graphed for the costs per treatment responder gained and per QALY gained. Results The average mean incremental costs for a treatment responder on social participation ranged between €8079 and €19,525, with 90.74%-99.74% showing improvement. The average incremental cost per QALY was €48,868 over the 6 months of follow-up, with 99.98% showing improved QALYs. Sensitivity analyses show costs to be lower when relevant baseline differences were included in the analysis. Average costs per treatment responder now ranged between €6800 and €16,597, while the average cost per QALY gained was €42,030. Conclusions This study demonstrates that offering VR-CBT to patients with paranoid delusions is an economically viable approach toward improving patients’ health in a cost-effective manner. Long-term effects need further research. Trial Registration International Standard Randomised Controlled Trial Number (ISRCTN) 12929657; http://www.isrctn. com/ISRCTN12929657
Deactivation of Glutaminolysis Sensitizes PIK3CA-Mutated Colorectal Cancer Cells to Aspirin-Induced Growth Inhibition

Aspirin is one of the most promising over-the-counter drugs to repurpose for cancer treatment. In particular, aspirin has been reported to be effective against PIK3CA-mutated colorectal cancer (CRC); however, little information is available on how the PIK3CA gene status affects its efficacy. We found that the growth inhibitory effects of aspirin were impaired upon glutamine deprivation in PIK3CA-mutated CRC cells. Notably, glutamine dependency of aspirin-mediated growth inhibition was observed in PIK3CA-mutated cells but not PIK3CA wild type cells. Mechanistically, aspirin induced G1 arrest in PIK3CA-mutated CRC cells and inhibited the mTOR pathway, inducing the same phenotypes as glutamine deprivation. Moreover, our study including bioinformatic approaches revealed that aspirin increased the expression levels of glutaminolysis-related genes with upregulation of activating transcription factor 4 (ATF4) in PIK3CA-mutated CRC cells. Lastly, the agents targeting glutaminolysis demonstrated significant combined effects with aspirin on PIK3CA-mutated CRC cells. Thus, these findings not only suggest the correlation among aspirin efficacy, PIK3CA mutation and glutamine metabolism, but also the rational combinatorial treatments of aspirin with glutaminolysis-targeting agents against PIK3CA-mutated CRC.
Molecular Properties and New Potentials of Plant Nepenthesins

Nepenthesins are aspartic proteases (APs) categorized under the A1B subfamily. Due to nepenthesin-specific sequence features, the A1B subfamily is also named nepenthesin-type aspartic proteases (NEPs). Nepenthesins are mostly known from the pitcher fluid of the carnivorous plant Nepenthes, where they are availed for the hydrolyzation of insect protein required for the assimilation of insect nitrogen resources. However, nepenthesins are widely distributed within the plant kingdom and play significant roles in plant species other than Nepenthes. Although they have received limited attention when compared to other members of the subfamily, current data indicates that they have exceptional molecular and biochemical properties and new potentials as fungal-resistance genes. In the current review, we provide insights into the current knowledge on the molecular and biochemical properties of plant nepenthesins and highlights that future focus on them may have strong potentials for industrial applications and crop trait improvement.
Seasonal changes in the total lipid content of the Opossum shrimp, Mysis relicta (Malacostraca: Mysidacea)

Seasonal changes in the percent total lipid content of Mysis relicta were investigated in four lakes in southern Ontario. Stony and Twelve Mile lakes contain populations of Mysis with a 1-yr life cycle, while Crystal and Boshkung lakes have populations with a 2-yr life cycle. Mature female and male mysids have a lipid content between 15 and 33% and between 14 and 25%, respectively, while juvenile mysids have approximately 10% less total lipids than adults. The relationship between total lipid and lipid-free dry weight is best described by the power curve Y = aXb and is the same (ANCOVA, p < 0.05) in all four mysid populations. Lipid content accumulates steadily with time as the mysid grows, and lipid reserves do not appear to influence mysid time to maturity. For studies on the transfer of energy and lipophilic organic contaminants through the food web, the results imply that seasonal and body size differences of organisms are important considerations.
Perception of the difference between past and present stimulus: A rare orientation illusion may indicate incidental access to prediction error-like signals

A popular model for sensory processing, known as predictive coding, proposes that incoming signals are iteratively compared with top-down predictions along a hierarchical processing scheme. At each step, error signals arising from differences between actual input and prediction are forwarded and recurrently minimized by updating internal models to finally be “explained away”. However, the neuronal mechanisms underlying such computations and their limitations in processing speed are largely unknown. Further, it remains unclear at which step of cortical processing prediction errors are explained away, if at all. In the present study, human subjects briefly viewed the superposition of two orthogonally oriented gratings followed by abrupt removal of one orientation after either 33 or 200 milliseconds. Instead of strictly seeing the remaining orientation, observers report rarely but highly significantly an illusory percept of the arithmetic difference between previous and actual orientations. Previous findings in cats using the identical paradigm suggest that such difference signals are inherited from first steps of visual cortical processing. In light of early modeling accounts of predictive coding, in which visual neurons were interpreted as residual error detectors signaling the difference between actual input and its temporal prediction based on past input, our data may indicate continued access to residual errors. Such strategy permits time-critical perceptual decision making across a spectrum of competing internal signals up to the highest levels of processing. Thus, the occasional appearance of a prediction error-like illusory percept may uncover maintained flexibility at perceptual decision stages when subjects cope with highly dynamic and ambiguous visual stimuli.
The Use of Ensemble Models for Multiple Class and Binary Class Classification for Improving Intrusion Detection Systems

The pursuit to spot abnormal behaviors in and out of a network system is what led to a system known as intrusion detection systems for soft computing besides many researchers have applied machine learning around this area. Obviously, a single classifier alone in the classifications seems impossible to control network intruders. This limitation is what led us to perform dimensionality reduction by means of correlation-based feature selection approach (CFS approach) in addition to a refined ensemble model. The paper aims to improve the Intrusion Detection System (IDS) by proposing a CFS + Ensemble Classifiers (Bagging and Adaboost) which has high accuracy, high packet detection rate, and low false alarm rate. Machine Learning Ensemble Models with base classifiers (J48, Random Forest, and Reptree) were built. Binary classification, as well as Multiclass classification for KDD99 and NSLKDD datasets, was done while all the attacks were named as an anomaly and normal traffic. Class labels consisted of five major attacks, namely Denial of Service (DoS), Probe, User-to-Root (U2R), Root to Local attacks (R2L), and Normal class attacks. Results from the experiment showed that our proposed model produces 0 false alarm rate (FAR) and 99.90% detection rate (DR) for the KDD99 dataset, and 0.5% FAR and 98.60% DR for NSLKDD dataset when working with 6 and 13 selected features.
Group IIA Secretory Phospholipase A2 Predicts Graft Failure and Mortality in Renal Transplant Recipients by Mediating Decreased Kidney Function

The acute phase protein group IIA secretory phospholipase A2 (sPLA2-IIA) has intrinsic proatherosclerotic properties. The present prospective cohort study investigated whether plasma sPLA2-IIA associates with graft failure, cardiovascular, and all-cause mortality in renal transplant recipients (RTRs), patients with accelerated atherosclerosis formation both systemically and within the graft. In 511 RTRs from a single academic center with stable graft function >1 year, baseline plasma sPLA2-IIA was determined by ELISA. Primary end points were death-censored graft failure and mortality (median follow-up, 7.0 years). Baseline sPLA2-IIA was higher in RTRs than in healthy controls (median 384 ng/dL (range 86–6951) vs. 185 ng/dL (range 104–271), p < 0.001). Kaplan–Meier analysis demonstrated increased risk for graft failure (p = 0.002), as well as cardiovascular (p < 0.001) and all-cause mortality (p < 0.001), with increasing sPLA2-IIA quartiles. Cox regression showed strong associations of sPLA2-IIA with increased risks of graft failure (hazard ratio (HR) = 1.42 (1.11–1.83), p = 0.006), as well as cardiovascular (HR = 1.48 (1.18−1.85), p = 0.001) and all-cause mortality (HR = 1.39 (1.17−1.64), p < 0.001), dependent on parameters of kidney function. Renal function during follow-up declined faster in RTRs with higher baseline sPLA2-IIA levels. In RTRs, sPLA2-IIA is a significant predictive biomarker for chronic graft failure, as well as overall and cardiovascular disease mortality dependent on kidney function. This dependency is conceivably explained by sPLA2-IIA impacting negatively on kidney function.
A Model for Estimating Dose-Rate Effects on Cell-Killing of Human Melanoma after Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) is a type of radiation therapy for eradicating tumor cells through a 10B(n,α)7Li reaction in the presence of 10B in cancer cells. When delivering a high absorbed dose to cancer cells using BNCT, both the timeline of 10B concentrations and the relative long dose-delivery time compared to photon therapy must be considered. Changes in radiosensitivity during such a long dose-delivery time can reduce the probability of tumor control; however, such changes have not yet been evaluated. Here, we propose an improved integrated microdosimetric-kinetic model that accounts for changes in microdosimetric quantities and dose rates depending on the 10B concentration and investigate the cell recovery (dose-rate effects) of melanoma during BNCT irradiation. The integrated microdosimetric–kinetic model used in this study considers both sub-lethal damage repair and changes in microdosimetric quantities during irradiation. The model, coupled with the Monte Carlo track structure simulation code of the Particle and Heavy Ion Transport code System, shows good agreement with in vitro experimental data for acute exposure to 60Co γ-rays, thermal neutrons, and BNCT with 10B concentrations of 10 ppm. This indicates that microdosimetric quantities are important parameters for predicting dose-response curves for cell survival under BNCT irradiations. Furthermore, the model estimation at the endpoint of the mean activation dose exhibits a reduced impact of cell recovery during BNCT irradiations with high linear energy transfer (LET) compared to 60Co γ-rays irradiation with low LET. Throughout this study, we discuss the advantages of BNCT for enhancing the killing of cancer cells with a reduced dose-rate dependency. If the neutron spectrum and the timelines for drug and dose delivery are provided, the present model will make it possible to predict radiosensitivity for more realistic dose-delivery schemes in BNCT irradiations.
Interspecific competition in ground-beetle assemblages (Carabidae): what have we learned?

Studies of interspecific competition and resource partitioning among ground-beetles (Coleoptera, Carabidae) are reviewed. Half of the 32 papers reported that interspecific competition was operating in extant carabid assemblages or was responsible for apparent resource partitioning. However, severe effects, such as competitive exclusion, were not demonstrated. Although action of competition in the past was often invoked to explain apparent resource partitioning, in general evidence is weak. Overall, many authors emphasized the role of competition in their systems but could not dismiss alternative explanations for community patterns
Evolutionary optimization of an anatomical suction cup: Lip collagen content and its correlation with flow and substrate in Neotropical suckermouth catfishes (Loricarioidei)

In riverine ecosystems, downstream drag caused by fast‐flowing water poses a significant challenge to rheophilic organisms. In neotropical rivers, many members of a diverse radiation of suckermouth catfishes (Loricarioidei) resist drag in part by using modified lips that form an oral suction cup composed of thick flesh. Histological composition and morphology of this cup are interspecifically highly variable. Through an examination of 23 loricarioid species, we determined that the tissue most responsible for lip fleshiness is collagen. We hypothesized that lip collagen content is interspecifically correlated with substrate and flow so that fishes living on rocky substrates in high‐flow environments have the largest, most collagenous lips. By mapping the amount and distribution of lip collagen onto a phylogeny and conducting ANOVA tests, we found support for this hypothesis. Moreover, these traits evolved multiple times in correlation with substrate and flow, suggesting they are an effective means for improving suction‐based attachment. We hypothesize that collagen functions to reinforce oral suction cups, reducing the likelihood of slipping, buckling, and failure under high‐flow, high‐drag conditions. Macroevolutionary patterns among loricarioid catfishes suggest that for maximum performance, biomimetic suction cups should vary in material density according to drag and substrate requirements.
Anti-Obesity Effects of Petasites japonicus (Meowi) Ethanol Extract on RAW 264.7 Macrophages and 3T3-L1 Adipocytes and Its Characterization of Polyphenolic Compounds

Koreans have been consuming Petasites Japonicus (PJ) as food. Although the therapeutic effect of PJ on allergic or inflammatory reactions associated with asthma has been proven, its effect on obesity is unclear. Therefore, the present study was aimed to assess the obesity related anti-inflammatory and anti-adipogenic effects of ethanol extract PJ (EPJ) on the inflammatory response in RAW 264.7 macrophages and on differentiation in 3T3-L1 adipocytes. In addition, the polyphenolic compound was quantitatively characterized from the EPJ using ultra performance liquid chromatography coupled with diode array detector, quadrupole time-of-flight-mass spectrometry (UPLC-DAD-QToF-MS). In RAW 264.7 or 3T3-L1, reduction of nitric oxide (in macrophages) production as well as monocyte chemoattractant protein-1 and tumor necrosis factor-α were observed. Treatment of EPJ in adipocyte differentiation showed an improvement in adiponectin and lipid accumulation and a significant reduction of PPARγ and FABP-4 mRNA expression levels. On the other hand, mRNA expression of UCP-1, PPARα, and ACO increased in the EPJ treated group. In addition, a total of 26 polyphenolic compounds were detected and of which 12 are reported for the first time from PJ. The higher content of diverse polyphenolic compounds presented in EPJ might be responsible for the observed anti-inflammatory and anti-adipogenic effect. These results suggest that PJ is valuable in improving obesity-related inflammatory responses.
The Gut Microbiota of the Egyptian Mongoose as an Early Warning Indicator of Ecosystem Health in Portugal

The Egyptian mongoose is a carnivore mammal species that in the last decades experienced a tremendous expansion in Iberia, particularly in Portugal, mainly due to its remarkable ecological plasticity in response to land-use changes. However, this species may have a disruptive role on native communities in areas where it has recently arrived due to predation and the potential introduction of novel pathogens. We report reference information on the cultivable gut microbial landscape of widely distributed Egyptian mongoose populations (Herpestes ichneumon, n = 53) and related antimicrobial tolerance across environmental gradients. The panel of isolated species is consistent with the typical protein-based diet of a carnivore: Firmicutes predominate (89% of individuals), while Clostridiales, Enterobacteriales, and Lactobacillales are the major classes. Forty-one individuals (77.4%) harbour Clostridium spp. A spatial influence on mongooses’ microbiota is confirmed by nonmetric multidimensional scaling analysis, with a significant contribution of municipality to their microbiota composition. Antimicrobial susceptibility testing of mongoose commensal bacteria to 28 compounds evidences xenobiotic tolerance of Escherichia coli (E. coli), enterococci, Salmonella Spartel and Mbandaka serotypes and Pseudomonas bacteria, among others. The common isolation of antimicrobial tolerant microbiota from the mongoose’s gut suggests this species is exposed to anthropogenic influence and is affected by forestry and agricultural-related practices, reflecting its easy adaptation to ecological gradients across agroecosystems. We thus propose regular microbial and phenotypic resistance profiling of widely distributed mongooses as a sentinel tool for xenobiotics’ lifecycle and ecosystem health in Portugal.
Independent roles of beta-adrenergic and glucocorticoid receptors in systemic and pulmonary effects of ozone

Abstract Background: The release of catecholamines is preceded by glucocorticoids during a stress response. We have shown that ozone-induced pulmonary responses are mediated through the activation of stress hormone receptors. Objective: To examine the interdependence of beta-adrenergic (βAR) and glucocorticoid receptors (GRs), we inhibited βAR while inducing GR or inhibited GR while inducing βAR and examined ozone-induced stress response. Methods: Twelve-week-old male Wistar-Kyoto rats were pretreated daily with saline or propranolol (PROP; βAR-antagonist; 10 mg/kg-i.p.; starting 7-d prior to exposure) followed-by saline or dexamethasone (DEX) sulfate (GR-agonist; 0.02 mg/kg-i.p.; starting 1-d prior to exposure) and exposed to air or 0.8 ppm ozone (4 h/d × 2-d). In a second experiment, rats were similarly pretreated with corn-oil or mifepristone (MIFE; GR-antagonist, 30 mg/kg-s.c.) followed by saline or clenbuterol (CLEN; β2AR-agonist; 0.02 mg/kg-i.p.) and exposed. Results: DEX and PROP + DEX decreased adrenal, spleen and thymus weights in all rats. DEX and MIFE decreased and increased corticosterone, respectively. Ozone-induced pulmonary protein leakage, inflammation and IL-6 increases were inhibited by PROP or PROP + DEX and exacerbated by CLEN or CLEN + MIFE. DEX and ozone-induced while MIFE reversed lymphopenia (MIFE > CLEN + MIFE). DEX exacerbated while PROP, MIFE, or CLEN + MIFE inhibited ozone-induced hyperglycemia and glucose intolerance. Ozone inhibited glucose-mediated insulin release. Conclusions: In summary, 1) activating βAR, even with GR inhibition, exacerbated and inhibiting βAR, even with GR activation, attenuated ozone-induced pulmonary effects; and 2) activating GR exacerbated ozone systemic effects, but with βAR inhibition, this exacerbation was less remarkable. These data suggest the independent roles of βAR in pulmonary and dependent roles of βAR and GR in systemic effects of ozone.
Comparison of the efficacy of kinesiotaping and extracorporeal shock wave therapy in patients with newly diagnosed lateral epicondylitis: A prospective randomized trial

Objective: This study aimed to evaluate the efficacy of kinesiotaping (KT) and Extracorporeal Shock Wave therapy (ESWT) for patients with acute/subacute (complaints exist <3 months) lateral epicondylitis(LE) in terms of pain control, hand grip strength, and functionality. Methods: In total, 40 patients with newly diagnosed LE (27 females and 13 males with a mean age of 42.6 ± 8.4 years) were randomly allocated to receive a 3-week treatment of either KT for 5 days a week (n = 20) or ESWT once a week (n = 20). Patients were evaluated by the visual analog scale (VAS), hand grip strength (HGS), Roles and Maudsley scale (RMS), and quick DASHat baseline, after 4 weeks, and after 8 weeks of the treatment. Results: Both KT and ESWT could achieve significant improvements in VAS, HGS, RMS, and Q-Dash after 4 and 8 weeks of treatment. However, these improvements were more prominent in the KT group compared with ESWT after 4 and 8 weeks. KT group achieved lower VAS scores, higher HGS, lower RMS compared with ESWT (all P < 0.05). Conclusion: Both KT and ESWT could significantly improve pain, hand strength, and functionality in patients with newly diagnosed LE. However, these improvements were more prominent in the KT group. Considering the feasibility and the low cost of KT compared with ESWT, we recommend that KT should be considered for treating patients with newly diagnosed LE.
Glioblastoma Factors Increase the Migration of Human Brain Endothelial Cells In Vitro by Increasing MMP-9/CXCR4 Levels

Background/Aim: Glioblastoma (GB) is the most aggressive type of tumor in the central nervous system and is characterized by resistance to therapy and abundant vasculature. Tumor vessels contribute to the growth of GB, and the tumor microenvironment is thought to influence tumor vessels. We evaluated the molecular communication between human GB cells and human brain microvascular endothelial cells (HBMEC) in vitro. Materials and Methods: We investigated whether GB-conditioned media (GB-CM) influenced HBMEC proliferation and migration, as well as the levels of MMP-9, CXCL12, CXCR4, CXCR7, VEGFs, VEGFR-2, and WNT5a in HBMEC. Results: Although HBMEC proliferation was not modified, increased HBMEC migration was detected after GB-CM treatment. Furthermore, treatment of HBMEC with GB-CM resulted in increased levels of MMP-9 and CXCR4. The levels of WNT5a, VEGFs and VEGFR-2 were not affected. Conclusion: GB-secreted factors lead to increased endothelial cell migration and to increased levels of MMP-9 and CXCR4.