Homogeneity Analysis Research Articles

Deep Structural Knowledge Exploitation and Synergy for Estimating Node Importance Value on Heterogeneous Information Networks

The classic problem of node importance estimation has been conventionally studied with homogeneous network topology analysis. To deal with practical network heterogeneity, a few recent methods employ graph neural models to automatically learn diverse sources of information. However, the major concern revolves around that their fully adaptive learning process may lead to insufficient information exploration, thereby formulating the problem as the isolated node value prediction with underperformance and less interpretability. In this work, we propose a novel learning framework namely SKES. Different from previous automatic learning designs, SKES exploits heterogeneous structural knowledge to enrich the informativeness of node representations. Then based on a sufficiently uninformative reference, SKES estimates the importance value for any input node, by quantifying its informativeness disparity against the reference. This establishes an interpretable node importance computation paradigm. Furthermore, SKES dives deep into the understanding that "nodes with similar characteristics are prone to have similar importance values" whilst guaranteeing that such informativeness disparity between any different nodes is orderly reflected by the embedding distance of their associated latent features. Extensive experiments on three widely-evaluated benchmarks demonstrate the performance superiority of SKES over several recent competing methods.

Based on the prognosis model of immunogenes, the prognosis model was constructed to predict the invasion of immune genes and immune cells related to primary liver cancer and its experimental validation

BackgroundPrimary liver cancer (PLC) is a prevalent malignancy of the digestive system characterized by insidious symptom onset and a generally poor prognosis. Recent studies have highlighted a significant correlation between the initiation and prognosis of liver cancer and the immune function of PLC patients. PurposeRevealing the expression of PLC-related immune genes and the characteristics of immune cell infiltration provides assistance for the analysis of clinical pathological parameters and prognosis of PLC patients. MethodsPLC-related differentially expressed genes (DEGs) with a median absolute deviation (MAD > 0.5) were identified from TCGA and GEO databases. These DEGs were intersected with immune-related genes (IRGs) from the ImmPort database to obtain PLC-related IRGs. The method of constructing a prognostic model through immune-related gene pairs (IRGPs) is used to obtain IRGPs and conduct the selection of central immune genes. The central immune genes obtained from the selection of IRGPs are validated in PLC. Subsequently, the relative proportions of 22 types of immune cells in different immune risk groups are evaluated, and the differential characteristics of PLC-related immune cells are verified through animal experiments. ResultsThrough database screening and the construction of an IRGP prognosis model, 84 pairs of IRGPs (P < 0.001) were ultimately obtained. Analysis of these 84 IRGPs revealed 11 central immune genes related to PLC, showing differential expression in liver cancer tissues compared to normal liver tissues. Results from the CiberSort platform indicate differential expression of immune cells such as naive B cells, macrophages, and neutrophils in different immune risk groups. Animal experiments demonstrated altered immune cell proportions in H22 tumor-bearing mice, validating findings from peripheral blood and spleen homogenate analyses. ConclusionOur study successfully predicted and validated PLC-related IRGs and immune cells, suggesting their potential as prognostic indicators and therapeutic targets for PLC.

Exacerbation of thromboinflammation by JAK2V617F mutation worsens the prognosis of cerebral venous sinus thrombosis

AbstractCerebral venous sinus thrombosis (CVST) is an uncommon venous thromboembolic event accounting for <1% of strokes resulting in brain parenchymal injuries. JAK2V617F mutation, the most frequent driving mutation of myeloproliferative neoplasms, has been reported to be associated with worse clinical outcomes in patients with CVST. We investigated whether hematopoietic JAK2V617F expression predisposes to specific pathophysiological processes and/or worse prognosis after CVST. Using an in vivo mouse model of CVST, we analyzed clinical, biological, and imaging outcomes in mice with hematopoietic-restricted Jak2V617F expression, compared with wild-type Jak2 mice. In parallel, we studied a human cohort of JAK2V617F-positive or -negative CVST. Early after CVST, mice with hematopoietic Jak2V617F expression had increased adhesion of platelets and neutrophils in cerebral veins located in the vicinity of CVST. On day 1, Jak2V617F mice had a worse outcome characterized by significantly more frequent and severe intracranial hemorrhages (ICHs) and higher mortality rates. Peripheral neutrophil activation was enhanced, as indicated by higher circulating platelet–neutrophil aggregates, upregulated CD11b expression, and higher myeloperoxydase plasma level. Concurrently, immunohistological and brain homogenate analysis showed higher neutrophil infiltration and increased blood-brain barrier disruption. Similarly, patients with JAK2V617F-positive CVST tended to present higher thrombotic burden and had significantly higher systemic immune-inflammation index, a systemic thromboinflammatory marker, than patients who were JAK2V617F-negative. In mice with CVST, our study corroborates that Jak2V617F mutation leads to a specific pattern including increased thrombotic burden, ICH, and mortality. The exacerbated thromboinflammatory response, observed both in mice and patients positive for JAK2V617F, could contribute to hemorrhagic complications.

Survey on the Compliance of the Assumptions of Variance Analysis of Experimental Designs in Undergraduate Theses of Peruvian Universities

The main objective of the research was to verify compliance with the assumptions of the analysis of variance, using some experimental design, in undergraduate theses from Peruvian universities. For this purpose, 200 undergraduate theses from professional degrees in Agricultural Sciences from 13 Peruvian universities were chosen at random. A descriptive textual analysis was carried out with the sentiment analysis classification algorithm and the text mining technique was used to discover patterns and trends. The result showed that, in almost all of the theses, the verification of the two most important assumptions of the analysis of variance, normality and homogeneity of variances, were not taken into consideration. Ignoring the importance of assumptions and the significance they have on the validity of research results, forces us to pay attention to the way in which the statistical methodology of experimental designs is being carried out in undergraduate theses.&#x0D; &#x0D; Received: 20 December 2023 / Accepted: 26 February 2024 / Published: 5 March 2024

Analysis of Electrothermal Homogenization for the Fast and Accurate Modeling of Windings in Power Electronics Magnetic Components

Analysis of Electrothermal Homogenization for the Fast and Accurate Modeling of Windings in Power Electronics Magnetic Components

Multicriteria Machine Learning Model Assessment—Residuum Analysis Review

The use of machine learning (ML) and its applications is one of the leading research areas nowadays. Neural networks have recently gained enormous popularity and many works in various fields use them in the hope of improving previous results. The application of the artificial intelligence (AI) methods and the rationale for this decision is one issue, but the assessment of such a model is a completely different matter. People mostly use mean square error or less often mean absolute error in the absolute or percentage versions. One should remember that an error does not equal an error and a single value does not provide enough knowledge about the causes of some behavior. Proper interpretation of the results is crucial. It leads to further model improvement. It might be challenging, but allows us to obtain better and more robust solutions, which ultimately solve real-life problems. The ML model assessment is the multicriteria task. A single measure delivers only a fraction of the picture. This paper aims at filling that research gap. Commonly used integral measures are compared with alternative measures like factors of the Gaussian and non-Gaussian statistics, robust statistical estimators, tail index and the fractional order. The proposed methodology delivers new single-criteria indexes or the multicriteria approach, which extend the statistical concept of the moment ratio diagram (MRD) into the index ratio diagram (IRD). The proposed approach is validated using real data from the Full Truck Load cost estimation example. It compares 35 different ML regression algorithms applied to that task. The analysis gives an insight into the properties of the selected methods, enables their comparison and homogeneity analysis and ultimately leads towards constructive suggestions for their eventual proper use. The paper proposes new indexes and concludes that correct selection of the residuum analysis methodology makes the assessment and the ML regression credible.

A190 HELICOBACTER PYLORI INDUCES AN AUTO-REACTIVE PHENOTYPE IN PINK1 DEFICIENT MICE THAT CORRELATES WITH MOTOR DYSFUNCTION

Abstract Background Parkinson’s disease (PD) is a chronic neurodegenerative disorder. Several genetic predispositions, including the PTEN-induced kinase 1 (PINK1) mutation, have been implicated in early onset family cases. Besides the loss of dopaminergic neurons in the brain, PD patients have a unique immune phenotype that includes increased inflammation, blood serum, brain levels of proinflammatory cytokines, brain infiltration with cytotoxic CD8 T cells, and loss of regulatory T cells (Treg) and their anti-inflammatory phenotype. The role of the gut microbiota and gastrointestinal infections are increasingly recognized as a cofactor in PD. One of pathogens associated with the risk of PD is Helicobacter pylori. The prevalence of this Gram-negative bacteria in PD patients is higher than in the general population and its eradication in PD patients improves motor function. Loss of the PD-associated PINK1 alters induced Treg function in vitro. We previously have shown that in PINK1 knock-out (KO) mice, gut infection with Gram-negative bacteria, Citrobacter rodentium, induces mitochondrial antigen presentation (MitAP) to the CD8 T cells that later infiltrate the brain. In this model, PINK1 KO mice develop a Parkinson-like L-DOPA-responsive motor phenotype after four C. rodentium infections. Aims Here we aimed to scrutinize potential role of the H. pylori infection in the induction of motor dysfunction and disbalanced immune tolerance in PINK1 KO mice. Methods In addition to standard behavioural testing, at 2- and 6-months post-infection we performed a multiplex cytokine analysis of gastric homogenates and spectral flow cytometry of gastric lamina propria, mesenteric lymph nodes, blood, spleen, and brain infiltrating immunocytes. As well as in vitro immunocytes response and function assays to H.pylori exposure in PINK1 KO and wild-type (WT) littermate controls. Results We show that infection with H. pylori causes a long-lasting inflammation in the stomach; and local and systemic immune phenotype that remains 6 months post-infection. This phenotype, though present in some WT infected mice, is higher in PINK1 KOs and similarly to PD patients includes a decrease in Treg proportion, FoxP3 downregulation in regulatory T cells, Gata3+ CD4 T cell loss, as well as increase of circulating mitochondrial antigen-specific CD8 T cells. Moreover, the immune phenotype in the H. pylori infected PINK1 KO mice correlates with motor dysfunction and CD8 T cell brain infiltration with no such association seen in the WT mice. Conclusions These results provide insight to the gut-immunity-brain axis in the pathogenesis of Parkinson’s disease, and further investigate the role of Gram-negative bacteria in the establishment of immune tolerance-autoreactivity balance. Funding Agencies ASAP

Automated eccentricity measurement from raw eclipsing binary light curves with intrinsic variability

Eclipsing binary systems provide the opportunity to measure the fundamental parameters of their component stars in a stellar-model-independent way. This makes them ideal candidates for testing and calibrating theories of stellar structure and (tidal) evolution. Large photometric (space) surveys provide a wealth of data for both the discovery and the analysis of these systems. Even without spectroscopic follow-up there is often enough information in their photometric time series to warrant analysis, especially if there is an added value present in the form of intrinsic variability, such as pulsations. Our goal is to implement and validate a framework for the homogeneous analysis of large numbers of eclipsing binary light curves, such as the numerous high-duty-cycle observations from space missions like TESS. The aim of this framework is to be quick and simple to run and to limit the user's time investment when obtaining, amongst other parameters, orbital eccentricities. We developed a new and fully automated methodology for the analysis of eclipsing binary light curves with or without additional intrinsic variability. Our method includes a fast iterative pre-whitening procedure that results in a list of extracted sinusoids that is broadly applicable for purposes other than eclipses. After eclipses are identified and measured, orbital and stellar parameters are measured under the assumption of spherical stars of uniform brightness. We tested our methodology in two settings: a set of synthetic light curves with known input and the catalogue of Kepler eclipsing binaries. The synthetic tests show that we can reliably recover the frequencies and amplitudes of the sinusoids included in the signal as well as the input binary parameters, albeit to varying degrees of accuracy. Recovery of the tangential component of eccentricity is the most accurate and precise. Kepler results confirm a robust determination of orbital periods, with 80.5&lt;!PCT!&gt; of periods matching the catalogued ones. We present the eccentricities for this analysis and show that they broadly follow the theoretically expected pattern as a function of the orbital period. Our analysis methodology is shown to be capable of analysing large numbers of eclipsing binary light curves with no user intervention, and in doing so provide a basis for a further in-depth analysis of systems of particular interest as well as for statistical analysis at the sample level. Furthermore, the computational performance of the frequency analysis, extracting hundreds of sinusoids from Kepler light curves in a few hours, demonstrates its value as a tool for a field like asteroseismology.

Neuroprotective Effect of Resveratrol against Manganese-Induced Oxidative Stress and Matrix Metalloproteinase-9 in an "In Vivo" Model of Neurotoxicity.

Chronic exposure to manganese (Mn) leads to its accumulation in the central nervous system (CNS) and neurotoxicity with not well-known mechanisms. We investigated the involvement of matrix metalloproteinase (MMP)-2 and -9 in Mn neurotoxicity in an in vivo model of rats treated through an intraperitoneal injection, for 4 weeks, with 50 mg/kg of MnCl2 in the presence or in the absence of 30 mg/kg of resveratrol (RSV). A loss of weight was observed in Mn-treated rats compared with untreated and RSV-treated rats. A progressive recovery of body weight was detected in rats co-treated with Mn and RSV. The analysis of brain homogenates indicated that RSV counteracted the Mn-induced increase in MMP-9 levels and reactive oxygen species production as well as the Mn-induced decrease in superoxide dismutase activity and glutathione content. In conclusion, Mn exposure, resulting in MMP-9 induction with mechanisms related to oxidative stress, represents a risk factor for the development of CNS diseases.

The European biological variation study (EuBIVAS): Biological variation data for testosterone, follicle stimulating hormone, prolactin, luteinizing hormone and dehydroepiandrosterone sulfate in men

BackgroundKnowledge of biological variation (BV) of hormones is essential for interpretation of laboratory tests and for diagnostics of endocrinological and reproductive diseases. There is a lack of robust BV data for many hormones in men. MethodsWe used serum samples collected weekly over 10 weeks from the European Biological Variation Study (EuBIVAS) to determine BV of testosterone, follicle-stimulating hormone (FSH), prolactin, luteinizing hormone (LH) and dehydroepiandrosterone sulfate (DHEA-S) in 38 men. We derived within-subject (CVI) and between-subject (CVG) BV estimates by CV-ANOVA after trend, outlier, and homogeneity analysis and calculated reference change values, index of individuality (II), and analytical performance specifications. ResultsThe CVI estimates were 10 % for testosterone, 8 % for FSH, 13 % for prolactin, 22 % for LH, and 9 % for DHEA-S, respectively. The IIs ranged between 0.14 for FSH to 0.66 for LH, indicating high individuality. ConclusionsIn this study, we have used samples from the highly powered EuBIVAS study to derive BV estimates for testosterone, FSH, prolactin, LH and DHEA-S in men. Our data confirm previously published BV estimates of testosterone, FSH and LH. For prolactin and DHEA-S BV data for men are reported for the first time.

Biological variation in the estimated glomerular filtration rate of healthy individuals within 24h calculated using 2021CKD-EPI equations.

Use the MDRD (Modification of Diet in Renal Disease) and 2021 CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation void of race coefficients (CKD-EPICrea, CKD-EPICys-C, and CKD-EPICrea+Cys-C) to estimate the BV (Biological variation) of eGFR (estimated glomerular filtration rate) within 24h in a healthy population to help explain future studies using eGFR in the context of a known BV. Blood samples were collected from 30 healthy subjects at six time points within 24h. Serum creatinine (S-Crea) and serum cystatin C (S-Cys-C) were measured, and the BV of eGFR was calculated. Outlier and variance homogeneity analyses were performed, followed by CV-ANOVA on trend-corrected data. The eGFR CVI for the four equations (MDRD, CKD-EPICrea, CKD-EPICys-C, and CKD-EPICrea+Cys-C) were 8.39% (7.50-9.51%), 3.90% (3.49-4.42%), 6.58% (5.88-7.46%), and 5.03% (4.50-5.71%), respectively. The corresponding II and RCVpos/neg values were 0.69, 0.48, 0.51, and 0.31, and (29.30%, - 22.66%), (12.69%, - 11.2 6%), (20.97%, - 17.33%), and (15.88%, - 13.70%), respectively; RCVpos /neg of eGFR was highest in the MDRD equation and lowest in the CKD-EPI Crea equation. Additionally, the RCVpos/neg values of the individual was highest in the MDRD equation and lowest in the CKD-EPICrea+Cys-C equation; they are (56.51%, - 36.11%) and (5.01%, - 4.77%), respectively. We present data on the 24h BV eGFR of the 2021 CKD-EPI equations. The presence of BV has impact on the interpretation of GFR results, affecting CKD disease grading. The RCVpos/neg differences were large among the individuals. When using eGFRs based on the MDRD and CKD-EPI equations, it is necessary to combine RCVpos/neg values before interpreting the results.

Magnetic resonance imaging assessment of substantia nigral iron deposition in Parkinson's disease: a meta-analysis.

The pathogenesis of Parkinson's disease (PD) is associated with abnormal iron accumulation. Magnetic resonance imaging (MRI) studies have shown that patients with Parkinson's disease have an increased amount of iron in their substantia nigra (SN). We have undertaken a meta-analysis of studies using MRI in PD, to explore the potential role of MRI in diagnosing PD using abnormal iron deposition in SN as a candidate biomarker. Searches of PubMed, Embase, and Medline databases revealed 16 studies that compared PD patients and healthy controls (HC). A sensitivity analysis and subgroup analysis were performed to evaluate the reliability of our results. Estimates were pooled by the fixed-effects model. As an expression of I2, we computed the proportion of variation due to heterogeneity. We included 16 studies with sample sizes of 435 PD and 355 HC in our meta-analysis. Results showed that SN iron deposition was significantly elevated (p<0.00001) in patients with PD compared to HC ones (SMD=0.72, 95% confidence interval 0.57 to 0.87, p<0.00001). Our findings, based on a homogeneous group-level analysis, suggest that MRI-based SN iron deposition could be used to distinguish PD from HC. For a more rigorous investigation of SN iron deposition in PD, larger cohort studies are needed.

Measuring Tracers of Planet Formation in the Atmosphere of WASP-77A b: Substellar O/H and C/H Ratios, with a Stellar C/O Ratio and a Potentially Superstellar Ti/H Ratio

We present a comprehensive atmospheric retrieval study of the hot Jupiter WASP-77A b using eclipse observations from the Hubble Space Telescope (HST) and JWST. Using atmospheric retrievals, the spectral features of H2O, CO, and TiO are identified, with volume mixing ratios estimated at log10(VMR) = −4.40 −0.11+0.14 , −4.44 −0.28+0.34 , and −6.40 −0.23+0.22 , respectively. We derive the atmospheric C-to-O ratio—a key planetary formation tracer—to be C/O = 0.54 ± 0.12, which is consistent with both the stellar host value and previous studies of the planet’s atmosphere, suggesting a relatively close-in formation. Computing other elemental ratios (i.e., C/H, O/H, and Ti/H), we conclude that the general enrichment of the atmosphere (i.e., metallicity) is substellar, depleted in C and O, but that Ti appears slightly superstellar. A low C and O content could be obtained, in combination with a stellar C/O ratio if the planet formed outside of the CO2 snow line before migrating inwards. Meanwhile, a superstellar Ti/H could be obtained by late contamination from refractory rich planetesimals. While broadly in agreement with previous works, we do find some differences and discuss these while also highlighting the need for homogeneous analyses when comparative exoplanetology is conducted.

Self-consciousness mediated the role of the insula in self-disclosure: Evidence from rs-fMRI data

IntroductionSelf-disclosure is integral to forming intimate connections within interpersonal exchanges. While its advantages are widely acknowledged, the cerebral basis of self-disclosure is not thoroughly understood. Insight into its neural underpinnings is crucial for refining therapeutic approaches, especially for challenges associated with self-disclosure. MethodsOur study probed the association between spontaneous neural activity, gauged via resting-state fMRI, and self-disclosure tendencies among 258 healthy university students, employing Regional Homogeneity (ReHo) and behavioral correlation analysis. We also explored the mediating effect of self-consciousness on this relationship. ResultsThe ReHo-behavior correlation analysis uncovered that higher ReHo values in the insula are predictive of greater self-disclosure in social settings. Additionally, the mediation analysis identified self-consciousness as a partial intermediary between spontaneous neural activity in the insula and self-disclosure behaviors. ConclusionThe findings imply that decreased similarity in the insula during rest-state may amplify self-conscious emotions such as embarrassment, thus illuminating the cognitive processes that underlie disclosure behaviors. Critically, these insights have practical ramifications for enhancing therapeutic methods and communication skills by aiding individuals in navigating self-consciousness obstacles, thereby promoting more transparent and efficacious self-disclosure.

Can radial temperature profiles be inferred using NH3 (1, 1) and (2, 2) observations?

ABSTRACT A number of works infer radial temperature profiles of envelopes surrounding young stellar objects using several rotational transitions in a pixel-by-pixel or azimuthally averaged basis. However, in many cases the assumption that the rotational temperature is constant along the line of sight is made, while this is not the case when a partially resolved envelope, assumed to be spherically symmetric, is used to obtain values of temperature for different projected radii. This kind of analysis (homogeneous analysis) is intrinsically inconsistent. By using a spherical envelope model to interpret NH3 (1,1) and (2,2) observations, we tested how robust it is to infer radial temperature profiles of an envelope. The temperature and density of the model envelope are power laws of radius, but the density can be flat for an inner central part. The homogeneous analysis was applied to obtain radial temperature profiles, and resulted that for small projected radii, where the optical depth of the lines is high, the homogeneous temperature can be much higher than the actual envelope temperature. In general, for larger projected radii, both the temperature and the temperature power-law index can be underestimated by as much as 40 per cent, and 0.15, respectively. We applied this study to the infrared dark cloud G14.225–0.506 for which the radial temperature profile was previously derived from the dust emission at submillimetre wavelengths and the spectral energy distribution. As expected, the homogeneous analysis underestimated both the temperature and the temperature power-law index.

Functional profile of perilesional gray matter in focal cortical dysplasia: an fMRI study.

We aim to investigate the functional profiles of perilesional gray matter (GM) in epileptic patients with focal cortical dysplasia (FCD) and to correlate these profiles with FCD II subtypes, surgical outcomes, and different antiseizure medications (ASMs) treatment response patterns. Nine patients with drug-responsive epilepsy and 30 patients with drug-resistant epilepsy (11 were histologically confirmed FCD type IIa, 19 were FCD type IIb) were included. Individual-specific perilesional GM and contralateral homotopic GM layer masks were generated. These masks underwent a two-voxel (2 mm) dilation from the FCD lesion and contralateral homotopic region, resulting in 10 GM layers (20 mm). Layer 1, the innermost, progressed to Layer 10, the outermost. Amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) analyses were conducted to assess the functional characteristics of ipsilateral perilesional GM and contralateral homotopic GM. Compared to the contralateral homotopic GM, a significant reduction of ALFF was detected at ipsilateral perilesional GM layer 1 to 6 in FCD type IIa (after Bonferroni correction p < 0.005, paired t-test), whereas a significant decrease was observed at ipsilateral perilesional GM layer 1 to 2 in FCD type IIb (after Bonferroni correction p < 0.005, paired t-test). Additionally, a significant decrease of the ReHo was detected at ipsilateral perilesional GM layer 1 compared to the CHRs in FCD type IIb. Notably, complete resection of functional perilesional GM alterations did not correlate with surgical outcomes. Compared to the contralateral homotopic GM, a decreased ALFF in the ipsilateral perilesional GM layer was detected in drug-responsive patients, whereas decreased ALFF in the ipsilateral perilesional GM layer 1-6 and decreased ReHo at ipsilateral perilesional GM layer 1 were observed in drug-resistant patients (after Bonferroni correction p < 0.005, paired t-test). Our findings indicate distinct functional profiles of perilesional GM based on FCD histological subtypes and ASMs' response patterns. Importantly, our study illustrates that the identified functional alterations in perilesional GM may not provide sufficient evidence to determine the epileptogenic boundary required for surgical resection.

Trends and impacts of temperature and fire regimes in South Africa’s coastal national parks: implications for tourism

Climate change poses significant risks on coastal national park-based tourism through its effect on accessibility, comfort levels, and spatiotemporal changes of attractions. Wildfires and extreme temperatures have become issues of concern. Due to the widespread occurrence of fires in national parks along coastal areas and the noticeable changes in temperature regimes, more needs to be done to deepen understanding of their trends and impacts and devise appropriate management regimes. This study analyses the trends and impacts of fires and temperature-related variables in six coastal South African national parks, namely Agulhas, Garden Route, West Coast, Table Mountain, Namaqua, and Addo Elephant National Park. The triangulation and convergence model of the mixed-methods research design was adopted as the inquiry strategy. Data on statistical weather variables from the South African Weather Services and the National Aeronautics and Space Administration were used to calculate temperature trends using Mann–Kendall trend tests and homogeneity analysis. Data collection included questionnaire surveys, key informant interviews, field observations, and document analysis. The study observed statistically significant (p < 0.05) changes in temperature-related variables in all coastal national parks. There is also an increase in the intensity and spatial spread of fires, resulting in increased fire damage over time. Despite the current efforts of the coastal parks to manage wildfires and the changing climatic patterns, the fire and temperature regimes are threatening the biophysical environment with resultant effects on tourism and the economic viability of the national parks. The need to reengineer the fire suppression mechanisms and temperature-resilient tourism facilities has been observed.

Exploration of the effects of Yang's pricking-cupping therapy on eczema-induced pruritus based on rs-fMRI.

To explore the clinical effect of Yang's pricking-cupping therapy and its central mechanism in treatment of eczema-induced pruritus using resting-state functional magnetic resonance imaging (rs-fMRI). Fifty patients with eczema-induced pruritus were enrolled in the observation group, and 50 healthy subjects were enrolled in the control group. No any intervention was delivered in the control group. Yang's pricking-cupping therapy was operated at Dazhui (GV 14) and bilateral Quchi (LI 11), Xuehai (SP 10) and Sanyinjiao (SP 6), once a week, lasting 6 weeks in the observation group. The scores of the 12-item pruritus severity scale (12-PSS), the eczema area and severity index (EASI), the dermatology life quality index (DLQI), the Pittsburgh sleep quality index (PSQI), and the self-rating anxiety scale (SAS) were compared before and after treatment in the observation group. The rs-fMRI scanning was conducted and the regional homogeneity (ReHo) analysis performed in all of the participants before and after treatment in the observation group, as well as at the time of subject enrollment in the control group. The correlation was analyzed between ReHo values in the different areas of the brain and the scores of the above scales. Compared with those before treatment, the scores of 12-PSS, EASI, DLQI, PSQI, and SAS were reduced after treatment in the observation group (P<0.01, P<0.05). ReHo values were increased in the right caudate nucleus, the right middle temporal gyrus, the right orbitofrontal gyrus, the right thalamus and the left angular gyrus before treatment in the observation group when compared with those in the control group (P<0.001); and ReHo values in the above areas of the brain were decreased after treatment when compared with those before treatment in the observation group (P<0.001). In comparison with the control group, ReHo values were reduced in the left middle temporal gyrus, the left superior parietal lobule and the left supplementary motor area in the observation group before treatment (P<0.001); while when compared with those before treatment, ReHo values in the above areas of the brain were elevated after treatment in the observation group (P<0.001). Before treatment, ReHo value in the left supplementary motor area was positively correlated with 12-PSS score (r=0.432, P=0.004), and the value in the right orbitofrontal gyrus was negatively correlated with PSQI score (r=-0.318, P=0.04) in the observation group. After treatment, ReHo value in the left superior parietal lobule was positively correlated with 12-PSS score (r=0.384, P=0.012) in the observation group. The abnormal cerebral functional activities are exhibited in multiple areas of the brain involved in stimulus response, emotional regulation, behavior control and attention in the patients with eczema-induced pruritus. Yang's pricking-cupping therapy can effectively relieve the pruritus symptoms and skin lesions of the patients, which may be related to reversing the abnormal cerebral functional activities induced by pruritus.

Development of multi-targetable chalcone derivatives bearing N-aryl piperazine moiety for the treatment of Alzheimer's disease

The multi-target directed ligand (MTDL) discovery has been gaining immense attention in the development of therapeutics for Alzheimer’s disease (AD). The strategy has been evolved as an auspicious approach suitable to combat the heterogeneity and the multifactorial nature of AD. Therefore, multi-targetable chalcone derivatives bearing N-aryl piperazine moiety were designed, synthesized, and evaluated for the treatment of AD. All the synthesized compounds were screened for thein vitro activityagainst acetylcholinesterase (AChE), butylcholinesterase (BuChE), β-secretase-1 (BACE-1), and inhibition of amyloid β (Aβ) aggregation. Amongst all the tested derivatives, compound 41bearing unsubstituted benzylpiperazine fragment and para-bromo substitution at the chalcone scaffold exhibited balanced inhibitory profile against the selected targets. Compound 41 elicited favourable permeation across the blood–brain barrier in the PAMPA assay. The molecular docking and dynamics simulation studies revealed the binding mode analysis and protein–ligand stability ofthe compound with AChE and BACE-1. Furthermore,itameliorated cognitive dysfunctions and signified memory improvement in thein-vivobehavioural studies (scopolamine-induced amnesia model). Theex vivobiochemical analysis of mice brain homogenates established the reduced AChE and increased ACh levels. The antioxidant activity of compound 41 was accessed with the determination of catalase (CAT) and malondialdehyde (MDA) levels. The findings suggested thatcompound 41, containing a privileged chalcone scaffold, can act as a lead molecule for developing AD therapeutics.

ANTIHYPERTROPHIC EFFECT OF PGE2 ON CHONDROCYTES SUGGESTS ADJUSTMENTS OF OA ANALGESIA

The signaling molecule prostaglandin E2 (PGE2), synthesized by cyclooxygenase-2 (COX-2), is immunoregulatory and reported to be essential for skeletal stem cell function. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in osteoarthritis (OA) analgesia, but cohort studies suggested that long-term use may accelerate pathology. Interestingly, OA chondrocytes secrete high amounts of PGE2. Mesenchymal stromal cell (MSC) chondrogenesis is an in vitro OA model that phenocopies PGE2 secretion along with a hypertrophic OA-like cell morphology. Our aim was to investigate cause and effects of PGE2 secretion in MSC-based cartilage neogenesis and hypertrophy and identify molecular mechanisms responsible for adverse effects in OA analgesia.Human bone marrow-derived MSCs were cultured in chondrogenic medium with TGFβ (10ng/mL) and treated with PGE2 (1µM), celecoxib (COX-2 inhibitor; 0.5µM), AH23848/AH6809 (PGE2 receptor antagonists; 10µM), or DMSO as a control (n=3–4). Assessment criteria were proteoglycan deposition (histology), chondrocyte/hypertrophy marker expression (qPCR), and ALP activity. PGE2 secretion was measured (ELISA) after TGFβ withdrawal (from day 21, n=2) or WNT inhibition (2µM IWP-2 from day 14; n=3).Strong decrease in PGE2 secretion upon TGFβ deprivation or WNT inhibition identified both pathways as PGE2 drivers. Homogeneous proteoglycan deposition and COL2A1 expression analysis showed that MSC chondrogenesis was not compromised by any treatment. Importantly, hypertrophy markers (COL10A1, ALPL, SPP1, IBSP) were significantly reduced by PGE2 treatment, but increased by all inhibitors. Additionally, PGE2 significantly decreased ALP activity (2.9-fold), whereas the inhibitors caused a significant increase (1.3-fold, 1.7-fold, 1.8-fold). This identified PGE2 as an important inhibitor of chondrocyte hypertrophy.Although TGFβ and WNT are known pro-arthritic signaling pathways, they appear to induce a PGE2-mediated antihypertrophic effect that can counteract pathological cell changes in chondrocytes. Hampering this rescue mechanism via COX inhibition using NSAIDs thus risks acceleration of OA progression, indicating the need of OA analgesia adjustment.