Kaposi’s sarcoma associated-herpesvirus (KSHV, also known as human herpesvirus-8) is a gammaherpesvirus that establishes life-long infection in human B lymphocytes. KSHV infection is typically asymptomatic but immunosuppression can predispose KSHV-infected individuals to primary effusion lymphoma (PEL); a malignancy driven by aberrant proliferation of latently infected B lymphocytes, and supported by pro-inflammatory cytokines and angiogenic factors produced by cells that succumb to lytic viral replication. Here, we report the development of the first in vivo model for a virally-induced lymphoma in zebrafish, whereby KSHV-infected PEL tumour cells engraft and proliferate in the yolk sac of zebrafish larvae. Using a PEL cell line engineered to produce the viral lytic switch protein RTA in the presence of doxycycline, we demonstrate drug-inducible reactivation from KSHV latency in vivo, which enabled real-time observation and evaluation of latent and lytic phases of KSHV infection. In addition, we developed a sensitive droplet digital PCR method to monitor latent and lytic viral gene expression and host cell gene expression in xenografts. The zebrafish yolk sac is not well-vascularized and using fluorogenic assays we confirmed that this site provides a hypoxic environment that may mimic the microenvironment of some human tumors. We found that PEL cell proliferation in xenografts was dependent on the host hypoxia-dependent translation initiation factor, eukaryotic initiation factor 4E2 (eIF4E2). This demonstrates that the zebrafish yolk sac is a functionally hypoxic environment and xenografted cells must switch to dedicated hypoxic gene expression machinery to survive and proliferate. The establishment of the PEL xenograft model enables future studies that exploit the innate advantages of the zebrafish as a model for genetic and pharmacologic screens.

Remote sensing data and techniques utilized for various purposes including natural disasters such as earthquake as well as flood. The research aims to consume liberates Landsat 8 images for investigating crashed airplanes such as MH370. Overall approximately 300 Landsat images with less than 10% clouds utilized in addition processed through Google Engine Platform. Due to the materials as well as the color of airplane body different from the area which is a plane crashed there, moreover, it should be the characteristics of the plane shapefile different in terms of albedo, temperature as well as vegetation index value. The research observed Landsat 8 data as well as methods utilized in this research, especially, NDVI, albedo in addition to band 4, capable to distinguish between the plane and its surrounding green area. Therefore, our result confirms during the research period, there was no plane on the location as well as MH370 not crashed in this site.

Surface water distribution extracted from remote sensing data has been used in water resource assessment, coastal management, and environmental change studies. Traditional manual methods for extracting water bodies cannot satisfy the requirements for mass processing of remote sensing data; therefore, accurate automated extraction of such water bodies has remained a challenge. The histogram bimodal method (HBM) is a frequently used objective tool for threshold selection in image segmentation. The threshold is determined by seeking twin peaks, and the valley values between them; however, automatically calculating the threshold is difficult because complex surfaces and image noise which lead to not perfect twin peaks (single or multiple peaks). We developed an operational automated water extraction method, the modified histogram bimodal method (MHBM). The MHBM defines the threshold range of water extraction through mass static data; therefore, it does not require the identification of twin histogram peaks. It then seeks the minimum values in the threshold range to achieve automated threshold. We calibrated the MHBM for many lakes in China using Landsat 8 Operational Land Imager (OLI) images, for which the relative error (RE) and squared correlation coefficient (R2) for threshold accuracy were found to be 2.1% and 0.96, respectively. The RE and root-mean-square error (RMSE) for the area accuracy of MHBM were 0.59% and 7.4 km2. The results show that the MHBM could easily be applied to mass time-series remote sensing data to calculate water thresholds within water index images and successfully extract the spatial distribution of large water bodies automatically.

Depression is the commonest mental disorder worldwide. Both antidepressants and psychotherapy are effective in treating depression, but response to these treatments is often incomplete. Yoga-based interventions (YBIs) have emerged as a promising adjunctive treatment for depression. Recent research has attempted to identify the biological mechanisms associated with the antidepressant actions of YBIs. In this scoping review, conducted according to the PRISMA-ScR guidelines, the PubMed and Scopus databases were searched to retrieve research on biomarkers of response to YBIs in patients with depression. Eleven studies were included in the review. Based on these studies, YBIs may improve depression through beneficial effects on systemic inflammation, stress axis regulation, cardiac autonomic functioning, and possibly reductions in oxidative stress-related cellular damage. Increases in brain-derived neurotrophic factor (BDNF) may represent a final common pathway upon which these processes converge. Though these results are theoretically plausible, they should be interpreted with caution due to certain methodological limitations in the existing research. Replication of these results and improvements in study methodology, and the evaluation of other biomarkers relevant to the pathophysiology of depression, could further elucidate the mechanism of action of YBIs in this disorder, and identify which patients would benefit most from this treatment approach.

Periodontitis is a disease that originates from gingival tissue, and if left untreated, can cause inflammation to spread to deeper tissues, altering bone homeostasis, and even leading to tooth loss. When the bacteria in plaque reach sufficient numbers, the immune system responds by activating immune cells that will produce cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). These immune signaling molecules will coordinate the inflammatory responses. IL-1 binds to the IL-1 receptor (IL-1R) on the surface of target cells, initiating an inflammatory response by activating intracellular signalling pathways. Inhibition of IL-1R can prevent the interaction of IL-1 with this receptor, thereby halting the activation of the inflammatory pathway. By substituting this connection with active anti-inflammatory substances, it is possible to prevent the contact between IL-1 and IL-1R. The licorice plant, Glycyrrhiza glabra, includes eight types of flavonoids with significant anti-inflammatory potential, namely isoliquiritigenin, glyzaglabrin, prunetin, shinpterocarpin, licochalcone A, glabridin, glisoflavone, and isoangustone A. This study aims to assess the potential of such flavonoids as candidates for periodontitis treatment through molecular docking, using AutoDock Tools v.1.5.6. All tested compounds showed highly stable bonds to IL-1R, with a binding affinity values below -7 kcal/mol. Van der Waals forces, hydrogen bonds, and hydrophobic bonds all contribute to the stability of these interactions. Among the eight tested compounds, glisoflavone, which has a Ki value of 90.89 nM and a ΔG value of -9.61 kcal/mol, has the highest binding stability to IL-1R.

SARS-CoV-2 mRNA vaccination can entail chronic fatigue/dis-autonomy tentatively termed post-acute COVID-19 vaccination syndrome (PACVS). We explored receptor autoantibodies and interleukin-6 (IL-6) as somatic correlates of PACVS. Blood markers determined before and six months after first-time SARS-CoV-2-vaccination of healthy controls (N = 89, 71 females, mean/ median age 39/ 49 years) were compared with corresponding values of PACVS-affected persons (N= 191, 159 females, mean/median age: 40/39 years) exhibiting chronic fatigue/dis-autonomy (≥ three symptoms for ≥ five months after last SARS-CoV-2 mRNA vaccination) not due to SARS-CoV-2 infection and/or confounding diseases/medications. Normal vaccination response encompassed decreases of 11 receptor-antibodies (by 25 - 50 %, p < 0.0001), increases in two receptor-antibodies (by 15 - 25 %, p < 0.0001) and normal IL-6. In PACVS, serological vaccination-response appeared significantly (p < 0.0001) altered, allowing discrimination from normal post-vaccination state (sensitivity = 90%, p &lt; 0.0001) by increased angiotensin II type 1 receptor antibodies (cut-off ≤ 10.7 U/ml, ROC-AUC = 0.824 ± 0.027), decreased alpha-2B adrenergic receptor antibodies (cut-off ≥ 25.2 U/ml, ROC-AUC = 0.828 ± 0.025) and increased IL-6 (cut-off ≤ 2.3 pg/ml, ROC-AUC = 0.850 ± 0.022). PACVS is thus indicated as a somatic syndrome delineated/detectable by diagnostic blood markers

Background: Osteoarthritis is the most common degenerative joint disease resulting in pain and altered joint function. Objective: We investigated the possible association between serum interleukin-6 and symptoms of knee osteoarthritis with regard to pain, stiffness, physical function, assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We also examined the connections between serum interleukin-6 and radiographic severity in primary knee osteoarthritis patients. Methods: In this case-control study, fifty primary knee osteoarthritis patients and fifty age and sex matched controls were randomly recruited. Serum interleukin-6 levels were immunoassayed in patients’ and controls’ serum. Patients’ knee pain, stiffness and physical function were assessed by the respective subscales of the WOMAC Index. Standing anteroposterior radiographs of the knee joint were performed and graded with the Kellegren-Lawrence grade. Results: The mean serum IL-6 level was significantly higher in osteoarthritis patients (110.22 ± 46.98pg/ml) than controls (46.04 ± 12.34 pg/ml) (p=0.001). The WOMAC Index in patients ranged from 0 – 95 and the Kellegren-Lawrence score mean was 2.7 ± 0.76. There was a significant correlation between serum IL-6 levels and pain (r=0.595 p=0.001), physical function score (r=0.666, p=0.001)), and the radiographic score (r=0.799, p=0.001). Regression analysis showed that IL-6 level had a greater impact on both the WOMAC Index (p=0.005) and the Kellegren-Lawrence score (p=0.01). Conclusion: Serum IL-6 level is increased in primary knee osteoarthritis patients. Also, serum interlukin-6 is significantly related to osteoarthritis symptoms and radiographic severity.

FoxP3 is a transcription factor essential for the differentiation and function of T regulatory cells (Tregs). There are two major subsets of Tregs: natural Tregs (nTregs) generated in thymus and inducible Tregs (iTregs) produced in peripheral immune system. It has been documented that iTreg development is dependent on soluble mediators including interleukin 2 (IL2), transforming growth factor β (TGFβ) and all-trans-retinoic acid (ATRA). In our experiments we performed a gene expression array, followed by Real-time PCR experiments, to study the expression of genes regulated by 1,25-dihydroxyvitamin D (1,25D) or ATRA in cells of myeloid origin. Our experiments revealed that ATRA alone, but also a cocktail of mediators consisting of IL2, TGFβ and ATRA, upregulate the expression of FOXP3 gene in lymphoid cells, but also in normal and leukemic myeloid cells. The FoxP3 expression is followed by a phenotypic changes in cells of myeloid origin. Our results indicate that signaling pathways which are used in the late stages of T cell differentiation, are also active in the cells of myeloid lineage

Despite the availability of effective vaccines against COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide, pressing the need for new vaccines with improved breadth and durability. We developed an adjuvanted subunit vaccine against SARS-CoV-2 using recombinant receptor-binding domain (RBD) of spike with synthetic adjuvants targeting TLR7/8 (INI-4001) and TLR4 (INI-2002), co-delivered with aluminum hydroxide (AH) or aluminum phosphate (AP). The formulations were characterized for the quantities of RBD, INI-4001, and INI-2002 adsorbed onto the respective aluminum salts. Results indicated that at pH 6, the uncharged RBD (5.73 ± 4.2 mV) did not efficiently adsorb to the positively charged AH (22.68 ± 7.01 mV), whereas it adsorbed efficiently to the negatively-charged AP (-31.87 ± 0.33 mV). Alternatively, pre-adsorption of the TLR ligands to AH converted it to a negatively-charged particle, allowing for the efficient adsorption of RBD. RBD could also be directly adsorbed to AH at a pH of 8.1, which changed the charge of the RBD to negative. INI-4001 and INI-2002 efficiently to AH. Following vaccination in C57BL/6 mice, both aluminum salts promoted Th2-mediated immunity when used as the sole adjuvant. Co-delivery with TLR4 and/or TLR7/8 ligands efficiently promoted a switch to Th1-mediated immunity instead. Measurements of viral neutralization by serum antibodies demonstrated that the addition of TLR ligands to alum also greatly improved the neutralizing antibody response. These results indicate that the addition of a TLR7/8 and/or TLR4 agonist to a subunit vaccine containing RBD antigen and alum is a promising strategy for driving a Th1 response and neutralizing antibody titers targeting SARS-CoV-2.

Importance and need for cyber security have increased in folds since a decade. Indirectly, the country’s security depends on the country’s cyber-physical systems. Attackers are becoming more innovative, and attacks are becoming undetectable, causing huge risks to the systems. In this scenario, intelligent and evolving detection methods should be introduced to replace the basic and outworn ones. This article discusses about new-age intelligence and smart techniques dealing with artificial intelligence (AI) models. Artificial intelligence for cyber security is reviewed, and the performance of machine learning models (ML) and deep learning (DL) models are analysed.

This paper presents ensemble learning of multi-source satellite sensors dataset to obtain better predictive performance of the forest biomass. Spectral, spectral-indices, and spectral-textural features were generated from two optical satellite sensors, Landsat 8 Operational Land Imager (OLI) and Sentinel-2 Multispectral Instrument (MSI). In addition, two radar satellite sensors, Sentinel-1 C-band Synthetic Aperture Radar (CSAR), and Advanced Land Observing Satellite (ALOS-2) Phased Array type L-band Synthetic Aperture Radar (PALSAR-2) were utilized to generate backscattering and backscattering-textural features. The plot-wise above ground biomass data available from five forests in New England region were utilized. Ensemble learning of multi-source satellite sensors dataset was carried out by employing four machine learning regressors namely, Support Vector Machines (SVM), Random Forests (RF), Gradient Boosting (GB), and Multilayer Perceptron (MLP). A five-fold cross-validation method was used to evaluate predictive performance of the multi-source satellite sensors. The integration of multi-source satellite features, comprising of spectral, spectral-indices, backscattering, spectral-textural, and backscattering-textural information, through ensemble learning and cross-validation approach implemented in the research showed promising results (R² = 0.81, RMSE = 46.2 Mg/ha) for the estimation of plots-level forest biomass in New England region.

Land Surface Temperature (LST) estimation has been studied for several purposes, while the optimal method of estimating the LST has not been criticized yet. This research explores the optimum method in Land Surface Temperature (LST) estimation using LANDSAT-8 imagery data. Four different LST retrieval approaches, the Radiative Transfer Equation-based method (RTE), the Improved Mono-Window method (IMW), the Generalized Single-Channel method (GSC), and the Split-Window algorithm (SW), were calculated to present the LSTs over Buriram Town Municipality, Thailand. The calculated LSTs from these four methods were compared with the ground-based temperature data, taken on the same date and time of the employed LANDSAT-8 images. For this reason, the optimum method of the LST calculation was justified by considering the lowest normalized root means square error (NRMSE) values. As a result, the SW algorithm presents an optimum method in LST estimation. Regarding the SW, this algorithm requires not only the atmospheric profiles during satellite acquisition but also the retrieval of several coefficients. Besides, the LST retrieval method based on the SW algorithm is sensitive to water vapor content and coefficients. Although the SW algorithm is an optimum method explored in this study, it is emphasized that the adjustable values of coefficient response to the atmospheric state may be recommended. With these conditions, the SW algorithm can generate the land-surface temperature over the mixed land-use and land cover on the LANDSAT-8 images.

Salinity intrusion is one of the most serious consequences of climate change coupled with rising sea level that significantly affects agricultural activities in many parts of the world. This phenomenon has increasingly become more serious and frequently occurred in the Mekong Delta of Vietnam. As a result, Vietnam has been ranked among top five countries where have been devastatingly impacted by climate change, in particular, its Tra Vinh Province characterized by coastal plain and alluvial deposit. In addition, this area is of the tropical monsoon zone of long rainy season with source of salt brought from the sea by the tides and sea level rise. Regions that are contaminated by salt are located in lowland and often suffer from floods linking to tidal effects with salty water from river systems and channels. Soil salinity evaluation is critical for coastal protection, restoration, and agricultural planning since it can be considered as an agricultural indicator to evaluate quality of soil. Here, we attempt to estimate the soil salinity in Tra Vinh Province, in the Mekong Delta of Vietnam. Landsat 8 OLI images are utilized to derive indices for soil salinity evaluation including single bands, Vegetation Soil Salinity Index (VSSI), Soil Adjusted Vegetation Index (SAVI), Normalized Difference Vegetation Index (NDVI), and Normalized Difference Salinity Index (NDSI). Subsequently, satistical analysis between soil salinity, electrical conductivity (EC, dS/m), and environmental indices derived from Landsat 8 OLI image is performed. Results indicate that spectral value of Near Infrared (NIR) band and VSSI are highly correlated with EC (R2 = 0.7779 and R2 = 0.6957, respectively) in comparison with the other indices. Comparative results show that soil salinity derived from Landsat 8 is consistent with in situ data. Findings of this study demonstrate that Landsat 8 OLI images reveal a high potential for spatiotemporally monitoring the magnitude of soil salinity at the top soil layer. Outcomes of this study are useful for agricultural activities, planners, and farmers by providing the base map of soil salinity contamination for better selection of accomodating crop types to reduce economical lost in the context of climate change. Our proposed method that estimates soil salinity using satellite-derived variables can be applied in the other regions.

The sustainability of Indigenous Socioecological Systems (ISES) faces significant threats from global anthropogenic environmental changes, endangering Indigenous People (IP), who safeguard a substantial portion of the world's natural capital. Indigenous Traditional Food Systems (ITFS) are crucial within ISES, providing not only diverse and nutritious food but also holding cultural, spiritual, and economic significance. Despite embodying sustainable lifestyles, Indigenous voices remain underrepresented in climate and sustainability discussions. Addressing this gap, the research adopts the Political Ecological Theoretical Framework (PETF) to analyze the regulatory impact on the adaptability, resilience, and sustainability of ITFS. Two Indigenous communities, the Karen in Thailand and various groups in the Republic of Sakha (Yakutia) in Russia, serve as case studies. The study aims to establish a theoretical framework integrating Indigenous concerns into policies and regulations, emphasizing self-determination, cultural preservation, and land rights. Findings emphasize the necessity for comprehensive legal frameworks prioritizing Indigenous involvement in climate resilience and sustainability efforts, moving beyond symbolic gestures towards meaningful collaboration and decision-making power. Recognizing Indigenous vulnerability and engaging them as active partners is essential for navigating climate challenges within ISES and ITFS.

We performed the accuracy assessment of three different Normalized Difference Water Indices (NDWIs) in water bodies during April 2019, a period in which floods occurred in a large proportion of the Southwest of the Buenos Aires Province (Argentina). The accuracy of the estimations using spaceborne medium-resolution multi-spectral imaging, and the reliability of three NDWIs to highlight shallow water features in satellite images, was evaluated using a high resolution airbone imagery as ground-truth. It is shown that these indices computed using Landsat 8 and Sentinel-2 imagery are only loosely correlated to the actual flooded area in shallow waters. Indeed, NDWI values vary significantly depending on the satellite mission used and the type of index computed.

Protein O-GlcNAcylation has been associated with neurodegenerative diseases such as Alzheimer´s disease (AD). O-GlcNAcylation of Amyloid Precursor Protein (APP) regulates both the trafficking and the processing of the APP through the amyloidogenic pathway, resulting in the release and aggregation of the Aβ1-42 peptide. Microglia clear Aβ aggregates and dead cells to maintain brain homeostasis. Here, using LC-MS/MS we reveal that the Aβ1-42 peptide modifies the microglia O-GlcNAcome. We have identified 55 proteins, focusing our research on Galectin-1 protein, since it is a very versatile protein from a functional point of view. Combining biochemical with genetic approaches we demonstrate that Aβ1-42 peptide specifically targets Galectin-1S8 O-GlcNAcylation via OGT. In addition, this Gal-1-O-GlcNAcylated form, in turn, controls human microglia migration. Given the importance of microglia migration in the progression of AD, this study reports the relationship between Aβ1-42 peptide and Serine 8- O-GlcNAcylation of Galectin to drive microglial migration

Almond (Prunus dulcis (Mill.) D.A.Webb) is one of the largest nut crops in the world. Recently, phenolic compounds, mostly stored in almond skin, have been associated with much of the health-promoting behavior associated with their intake. The almond skin enriched fraction obtained from cold-pressed oil residues of the endemic Moroccan Beldi ecotypes is particularly rich in chlorogenic acid. In this study, both almond skin extract (AE) and chlorogenic acid (CHL) supplements, similar to traditional positive control resveratrol, significantly increased the replicative life-span of yeast compared to the untreated group. Our results showed that AE and CHL significantly reduced the production of reactive oxygen and nitrogen species (ROS/RNS), most likely due to their ability to maintain mitochondrial function during aging, as indicated by the maintenance of normal mitochondrial membrane potential in treated groups. This may be associated with the observed activation of the anti-oxidative stress response in treated yeast, which results in activation at both gene expression and enzymatic activity levels for SOD2 and SIR2, the latter being an upstream inducer of SOD2 expression. Interestingly, the differential gene expression induction of mitochondrial SOD2 gene at the expense of the cytosolic SOD1 gene confirms the key role of mitochondrial function in this regulation. Furthermore, AE and CHL have contributed to the survival of yeast under UV-C-induced oxidative stress, by reducing the development of ROS / RNS, resulting in a significant reduction in cellular oxidative damage as evidenced by decreased membrane lipid peroxidation, protein carbonyl content and 8-oxo-guanine formation in DNA. Together, these results demonstrate the interest of AE and CHL as new regulators in the replicative life-span and control of the oxidative stress response of yeast.

In the remote sensing domain, it is crucial to complete semantic segmentation on the raster images, e.g., river, building, forest, etc, on raster images. A deep convolutional encoder--decoder (DCED) network is the state-of-the-art semantic segmentation method for remotely sensed images. However, the accuracy is still limited, since the network is not designed for remotely sensed images and the training data in this domain is deficient. In this paper, we aim to propose a novel CNN for semantic segmentation particularly for remote sensing corpora with three main contributions. First, we propose applying a recent CNN called a global convolutional network (GCN), since it can capture different resolutions by extracting multi-scale features from different stages of the network. Additionally, we further enhance the network by improving its backbone using larger numbers of layers, which is suitable for medium resolution remotely sensed images. Second, "channel attention'' is presented in our network in order to select the most discriminative filters (features). Third, "domain-specific transfer learning'' is introduced to alleviate the scarcity issue by utilizing other remotely sensed corpora with different resolutions as pre-trained data. The experiment was then conducted on two given datasets: (i) medium resolution data collected from Landsat-8 satellite and (ii) very high resolution data called the ISPRS Vaihingen Challenge Dataset. The results show that our networks outperformed DCED in terms of $F1$ for 17.48% and 2.49% on medium and very high resolution corpora, respectively.

Interdisciplinary STEM and STEAM education give us an opportunity for creativity and educational innovation in a world scenario that needs training in which students can achieve all educational objectives and are prepared to achieve sustainable development. The rural environment with its land is a scenario that provides us with a range of educational resources for the development of STEM and STEAM projects in which students who are better trained and prepared for the needs of today's world are developed, as well as students who are more linked and sensitized to the environment, with the rural environment and its land, so important in our time.  In this article, we will collect examples from Latin America; STEM projects are being developed in which young people establish links with their environment, territory, and the local environment surrounding them. We must look carefully at projects and works in which students' ties with their land and environment are valued through the STEM and STEAM education necessary today. In this scenario, a comparison has been made between Latin American countries and Spain.

Despite the publication in 2009 of a paper on ‘terms and definitions of immune thrombocytopenia’, (ITP) some unresolved issues remain and are reflected by the disagreement in the treatment suggested for primary ITP in adults. Considering that these disagreements could be ascribed to non-shared goals, a ‘consensus’ to classify the different lines of treatment for primary ITP in adults according to their indications and goals was proposed in October 2018 to the XIX annual meeting of the Italian Gruppo di Studio delle Piastrine (GSP), a non-profit platelet study group of scientists and physicians. Having approved the project, 60 potential co-authors and experts in the world were invited to take part to a consensus through e-Delphy method and nine of the 12 who initially accepted the invitation completed the work. Agreement was reached on a classification of four lines of treatment for primary ITP in adults based on their indications and goals. The consensus obtained regarded also the criteria, ‘timing’ included, to consider practicable elective splenectomy in these patients. In our opinion, the classification of the lines of treatment for primary ITP in adults here proposed could facilitate the realization of better shared evidence-based guidelines for the treatment of the disease.

The ability of recombinant, SARS-CoV-2 Spike (S) protein to modulate the production of two COVID-19 relevant, pro-inflammatory cytokines (IL-6 and IFN-γ) in PBMC cultures of healthy, pre-Covid-19 subjects was investigated. We observed that cytokine production was largely and diversely modulated by the S protein depending on antigen or mitogen stimulation, as well as on the protein source, insect (S-in) or human (S-hu) cells. While both proteins co-stimulated cytokine production by polyclonally CD3-activated T cells, PBMC activation by the mitogenic lectin Concanavalin A (Con A) was up modulated by S-hu protein and down-modulated by S-in protein. These modulatory effects were likely mediated by the S glycans as demonstrated by direct Con A-S binding experiments and use of yeast mannan as Con A binder. While being ineffective in modulating memory antigenic T cell responses, the S proteins and mannan were able to induce IL-6 production in unstimulated PBMC cultures and upregulate the expression of Mannose Receptor (CD206), a marker of anti-inflammatory M2 macrophage. Our data point to a relevant role of N-glycans, particularly N-mannosidic chains, decorating the S protein in the immunomodulatory effects here reported. These novel biological activities of the S glycan ectodomain may add to the comprehension of Covid-19 pathology and immunity to SARS-CoV-2.

Cathepsin B (CatB) is thought to be essential for the induction of Porphyromonas gingivalis lipopolysaccharide (Pg LPS)-induced Alzheimer’s disease- like pathologies in mice, including interleukin-1β (IL-1β) production and cognitive decline. However, little is known about the role of CatB in Pg virulence factor-induced IL-1β production by microglia. We first subjected IL-1β-luciferase reporter BV-2 microglia to inhibitors of Toll-like receptors (TLRs), IκB kinase, and the NLRP3 inflammasome following stimulation with Pg LPS and outer membrane vesicles (OMVs). To clarify the involvement of CatB, we used several known CatB inhibitors, including CA-074Me, ZRLR, and human β-defensin 3 (hBD3). IL-1β production in BV-2 microglia induced by Pg LPS and OMVs was significantly inhibited by the TLR2 inhibitor C29 and the IκB kinase inhibitor wedelolactonne, but not by the NLRPs inhibitor MCC950. Both hBD3 and CA-074Me significantly inhibited Pg LPS-induced IL-1β production in BV-2 microglia. Although CA-074Me also suppressed OMV-induced IL-1β production, hBD3 did not inhibit it. Furthermore, both hBD3 and CA-074Me significantly blocked Pg LPS-induced nuclear NF-κB p65 translocation and IκBα degradation. In contrast, hBD3 and CA-074Me did not block OMV-induced nuclear NF-κB p65 translocation or IκBα degradation. Furthermore, neither ZRLR, a specific CatB inhibitor, nor shRNA-mediated knockdown of CatB expression had any effect on Pg virulence factor-induced IL-1β production. Interestingly, phagocytosis of OMVs by BV-2 microglia induced IL-1β production. Finally, the structural models generated by AlphaFold indicated that hBD3 can bind to the substrate-binding pocket of CatB, and possibly CatL as well. These results suggest that Pg LPS induces CatB/CatL-dependent synthesis and processing of pro-IL-1β without activation of the NLRP3 inflammasome. In contrast, OMVs promote the synthesis and processing of pro-IL-1β through CatB/CatL-independent phagocytic mechanisms. Thus, hBD3 can improve the IL-1β-associated vicious inflammatory cycle induced by microglia through inhibition of CatB/CatL.

Toxoplasmosis is a zoonosis of warm-blooded animals, affecting also humans, caused by Toxo-plasma gondii, an obligate intracellular parasite with a complex biological cycle. Toxoplasmosis is considered a re-emerging zoonosis and an important public health threat, also for the absence, up to now, of efficient vaccines and preventive measures. Sources of transmission to humans are environmental or food-borne, mainly through the consumption of raw and undercooked meat, predominantly of Sus scrofa, considered highly susceptible to T. gondii. Mainly in the last dec-ades, an effective strategy to counter animal infectious diseases was based on the discovery of resistance immuno-genetic markers, possibly to be used for association studies between geno-typic and phenotypic traits and consequently in Marker Assisted Selection. Until now, this gen-otyping approach has never been adopted for T. gondii infection, so this study aimed, for the first time, to fill this gap. In particular, pigs, reared in different farms of Central Italy, were serologically characterized by an ELISA assay performed on diaphragm meat juice. Out of 179 tested animals, 98 resulted seropositive (54.74%), 57 seronegative (31.84%) and 24 doubtful (10.6%), underlining a possible re-emerging diffusion of this protozoan in the investigated areas. Atten-tion was firstly focused on IL-18 gene, encoding for a pro-inflammatory cytokine that plays a key role starting from the upstream steps of the immunity pathway towards T. gondii. A RT-PCR assay followed by Sanger sequencing of IL-18 cDNA was de novo developed. For this interleukin, at this stage, genetic analysis has not highlighted significant polymorphic variations compared to the reference sequence, except for a seropositive animal. However, the outcomes of this pre-liminary innovative study will be investigated in depth analyzing other relevant genetic re-gions and other target genes.

In the past decade, targeted therapies for solid tumors, including non-small cell lung cancer (NSCLC), have advanced significantly, offering tailored treatment options for patients. However, individuals without targetable mutations pose a clinical challenge, as they may not respond to standard treatments like immune-checkpoint inhibitors (ICIs) and novel targeted therapies. While the mechanism of action of ICIs seems promising, the lack of a robust response limits their widespread use. Although the expression levels of programmed death ligand 1 (PD-L1) on tumor cells are used to predict ICI response, identifying new biomarkers, particularly those associated with the tumor microenvironment (TME), is crucial to address this unmet need. Recently, inflammatory cytokines such as interleukin-1 beta (IL-1β) have emerged as a key area of focus and hold significant potential implications for future clinical practice. Combinatorial approaches of IL-1β inhibitors and ICIs may provide a potential therapeutic modality for NSCLC patients without targetable mutations. In this review, we discuss the role of IL-1β in NSCLC, its involvement in inflammatory pathways, and explore its potential role in the treatment of NSCLC.

Hypervirulent Klebsiella pneumoniae (hvKp) is a variant that has been increasingly linked to severe, life threatening infections including pyogenic liver abscess and bloodstream infections. HvKp belonging to the capsular serotypes K1 and K2 have been reported worldwide, however very scarce studies are available on the their genomics and virulence. In the current study we report four hypermucoviscous hvKp ESBL clinical strains of capsular serotype K1 and K2 isolated from pus and urine of critically ill patients in tertiary care hospitals in Oman. These strains belong to diverse sequence types (STs) namely ST-23(K1), ST-231(K2), ST-881(K2), and ST-14(K2). To study their virulence, Galleria Mellonella model and resistance to human serum killing were used. The G. mellonella model revealed that the K1/ST-23 isolate is the most virulent as 50% of the larvae died in the first day, followed by isolate K2/ST-231 for which 75% of the larvae died in the second day and isolate K2/ST-14 for which 50% of the larvae died in the second day. Resistance to human serum killing showed there was complete inhibition of bacterial growth of all four isolates by the end of the first hour and up to the third hour. For ST-23(K1), ST-231(K2), ST-881(K2), and ST-14(K2), there was a gradual decrease in the number of colonies up to the second to third hour, which indicates neutralization of bacterial cells by the serum components. However, this was followed by sudden increase of bacterial growth, indicating possible resistance of bacteria against human serum bactericidal activity. Whole genome sequencing (WGS) revealed that hvKp strains display unique genetic arrangement of k-loci. Whole genome SNP-based phylogenetic analysis revealed that these hvKp isolates are phylogenetically distinct, belonging to diverse clades and belong to different STs in comparison to global isolates. This is the first report from Oman detailing the WGS of hvKp clinical isolates and assessing their resistance and virulence genomics, which reinforce our understanding of their epidemiology and dissemination in clinical settings.

This study aimed to use remote sensing and GIS to detect changes in surface water and wetlands in the Kumasi Metropolis over a period of 20 years (2002-2022). Landsat images were processed using the QGIS software, and the Maximum Likelihood Algorithm was used to perform supervised classification of land use land cover, while raster calculator aided in detecting wetlands by calculation for NDWI, MNDWI, and AWEI. The results showed that the majority of the landscape in the Kumasi metropolis was made up of built-up areas (79.4%), followed by agricultural lands (13.3%) and wetlands (7.3%). Over the 20-year period, built-up areas had gained 20.7% of the total landscape, while agricultural lands and wetlands had lost 16.7% and 4.0%, respectively. All water index methods recorded an increase in non-water cover and a loss of water cover over the period, with surface water decreasing by 5% and non-water land cover increasing by 5%. The study concludes that there have been significant changes in wetlands and surface water land use and land cover within the Kumasi Metropolis over the past 20 years, and recommends the enforcement of legislation on surface water protection in the area to protect wetlands

Additionally, the League’s four observing states, with an additional population of 1.7 billion, if join the group, will form the world’s largest consortium to enhance the accessibility of biotechnology drugs. This effort will also remove the criticism of regulatory agencies that are well-equipped to regulate these products. This should also be a significant economic incentive to consortium states to develop these products, particularly biosimilars, to capture the most critical market anticipated. This plan will also reduce the cost burden on regulatory agencies. The program is divided into two classifications; for products sold in any of the Stringent Regulatory Authority (SRA) states, the registration is automatic but with several requirements that assure ongoing pharmacovigilance; this also applies to copies of reference products or biosimilars. For non-SRA sourcing, a stepwise plan requiring a rapporteur review, as practiced by the EMA and a third-party cGMP audit, is necessary to ensure data and product integrity. However, to reduce the cost burden, approval of these products is based on current scientific findings as presented in this paper.

Vaginal ecosystem is a unique environment where, in physiological conditions, lactobacilli dominate. However, also pathogenic microbial species, responsible of vaginitis and vaginosis, can harbor vaginal microbiota. To extend the data published by De Seta and Larsen in Pathogens (2021), here we analyzed both the anti-Candida and anti-inflammatory properties of the vaginal gel formulation, Respecta® Balance Gel (RBG), commercialized as an adjuvant to treat vaginitis and vaginosis. We evaluated its activity by an in vitro model where a monolayer of A-431 vaginal epithelial cells was infected by Candida albicans in the presence of RBG or the placebo formulation (pRBG). Specifically, we tested the RBG capacity to counteract C. albicans virulence factors as well as their anti-inflammatory properties. Our results show that, unlike the placebo, RBG reduces ,reduces, C. albicans adhesion, its capacity to form hyphae and C. albicans-induced vaginal cell damage. Interestingly, both RBG and pRBG reduce LPS-induced IL-8 secretion (being RBG the most effective) demonstrating that also the placebo retains anti-inflammatory properties. By our experimental approach we highlight the possible role of farnesol on such effects, but we would like to point out that lactic acid, polydextrose and glycogen too must be relevant in the actual application. Taken together, our results show that RBG impairs C. albicans virulence and is able to reduce the inflammation in the vaginal environment, ultimately allowing the establishment of a balanced vaginal ecosystem.

High-resolution (2 km) high-frequency (hourly) SST data from 2015-2020 provided by the Advanced Himawari Imager (AHI) onboard the Japanese Himawari-8 geostationary satellite positioned over 140.7°E were used to study spatial and temporal variability of the China Coastal Front (CCF) in the East China Sea. The hourly SST data were processed with the Belkin and O’Reilly (2009) algorithm to generate long-term mean monthly maps of SST gradient magnitude (GM) and frontal frequency (FM) using a GM threshold of 0.1°C/km. Horizontal structure of SST field in the vicinity of the CCF was investigated from cross-frontal distributions of SST along 8 parallels from 31°N to 24°N. The high resolution (2 km) monthly distributions of SST along these 8 parallels were used to determine inshore and offshore boundaries of the CCF and calculate the CCF strength defined as the total cross-frontal SST step dSST=Offshore SST – Inshore SST. The CCF emerges in November, fully develops in December and peaks in strength in January-February. The front’s fragmentation and shrinking/weakening begins in February and March, respectively. In winter (December-February), the front’s strength dSST exceeds 5°C offshore the Zhejiang-Fujian coast and could be as high as 7.5°C when nearshore waters cool down to 7°C. In winter, the front’s strength decreases downstream from 31°N to 24°N. The CCF changes its physical nature as the seasons progress. In winter, the CCF is a water mass front between cold and fresh water coming from the north and warm and salty water coming from the south. In summer, the CCF becomes a coastal upwelling front maintained largely by southerly winds. In winter, the CCF’s cross-frontal structure in the SST field is ramp-shaped, with SST increasing monotonously in the offshore direction. In summer, the CCF’s cross-frontal structure in the SST field is V-shaped or U-shaped, featuring a minimum SST formed by cold upwelled water at some distance from the shore. Thus, the summer SST structure effectively consists of two fronts, a nearshore and offshore, with a minimum SST in-between. Across the inshore/offshore front, the SST decreases/increases in the offshore direction. The local bathymetry, especially the relatively steep shelf slope between 20-m and 50-m isobath, steers the front, which does not meander in winter offshore the Zhejiang-Fujian coast. As the cold season progresses, the front’s axis gradually shifts into deeper waters, from ~20 m to ~50 m.

In this paper I will address Dr. Sonne’s questions about will, agency, choice, consciousness, relevant brain regions, impacts of disorders and their therapeutics, and I will do this by referring to my theory, Dual-brain Psychology, which posits that within most of us there exist two mental agencies with different experiences, wills, choices, and behaviors. Each of these agencies is associated as a trait with one brain hemisphere (either left or right) and its composite regions. One of these agencies is more adversely affected by past traumas and is more immature and more symptomatic while the other is more mature and healthier. The theory has extensive experimental support through 17 peer-reviewed publications with clinical and non-clinical research. I will discuss how this theory relates to the questions that Dr. Sonne presented and will discuss also my published theory on the physical nature of subjective experience and its relation to the brain and how that theory interacts with DBP, and how the 2 theories relate to subjective experience, will, behavior, psychopathology and its treatment.

Background Candida auris is an emerging multidrug-resistant fungal pathogen that represents a serious threat to healthcare settings currently. Objective: Its objective was to determine the prevalence of C. auris in the hospital since its initial detection in late 2019. Methods: Using an adapted risk assessment tool, we reviewed the charts. and medical files of all suspected? and confirmed cases of C. auris cases reported at King Khalid University Hospital, Riyadh between November 2019 and December 2022. Anonymized data were retrieved in a pre-established datasheet and analyzed to determine the epidemiological characteristics of C. auris infection in our facility. We established our initial prevalence by age, gender, risk factors, and according to sampling source. Results: Of the 53 confirmed cases positive for C. auris during the study period, 33 (62%) were males. Their ages ranged between 15 and 98; most positive cases occurred in 50 and above. Only one of the confirmed cases was hospital-acquired. All patients had at least one risk factor, and Urine samples yielded the greatest number of positive cases while admission to healthcare facilities constituted the highest risk in our study. Conclusion: Establishing a local prevalence could serve as our baseline/benchmark to compare with regional and international benchmarks.

Post-stroke depressive disorders (PSD) and post-stroke cognitive impairments (PCI) are frequent consequences of ischemic stroke (IS). The study was focused on exploring possible associations between relative volumes of cortical and limbic brain structures during the acute period of IS, and changes in biochemical indices of hypothalamic-pituitary-adrenal, sympathoadrenal medullary and inflammatory systems, with the development of PSD or PCI after mild or moderate IS. Patients developing PSD later on had significantly smaller relative volumes of the hippocampus, entorhinal cortex, and temporal pole versus patients without depressive symptoms. PCI development was associated with significantly smaller volumes of temporal pole and supramarginal gyrus versus patients without cognitive changes. Multiple logistic regression analysis showed higher likelihood of developing PSD in patients with smaller temporal pole volume (β0=10.9; β=-4.27; p=0.04) and increased salivary α-amylase activity (β0=-3.55; β=2.68e-05; p=0.02,). PCI likelihood was higher in patients with smaller supramarginal gyrus volume (β0=3.41; β=-0.99; p=0.047), smaller temporal pole volume (β0=3.41; β=-3.12; p=0. 06), and increased hair cortisol concentration at admission (index of accumulated stress load within a month before IS; β0=3.41; β=-0.05; p=0.08). The data support the hypothesis suggesting predisposition to PSD and PCI and multi hit scenarios of their pathogenesis with IS providing a final hit.

Background: Classical Hodgkin's lymphoma (cHL) is a lymph node disease, however, extranodal involvement is present in about 10% of affected individuals. Various forms of direct central nervous system (CNS) involvement have been reported, including intracranial, epidural, leptomeningeal, and intramedullary spinal cord cHL (Table 1). We hereby describe the clinical presentation, work up, and outcomes of two distinctive cases of cHL with intracranial extra-axial spread in patients receiving novel combination and traditional chemotherapy. Methods: This case series (n=2) was conducted following the CARE guidelines. Institutional review board (IRB) approved protocol #24-015 for HIPPA waiver of subjects in our retrospective study. Results: Patients with cHL exhibiting CNS symptoms or relapse refractory cases benefit from neuroimaging and excluding infectious etiologies. Suspicious lesions include iso- to hypointensity on T1 weighted and iso- to hyperintensity on T2 MR scans. Diagnosis is confirmed with biopsy. Treatment with A-AVD has shown more benefit than traditional ABVD chemotherapy. There has been shown progression free survival with nivolumab-AVD (N-AVD) over brentuximab-AVD (B-AVD). Conclusion: cHL with CNS involvement is rare and requires comprehensive workup to exclude infectious and other malignancies. Diagnosis relies on neuroimaging and subsequent brain biopsy. Treatment with novel N-AVD has shown greater PFS in patients with advanced cHL.

Cornea severe inflammation produces opacity or even perforation, scarring, and angiogenesis, resulting in blindness. The cornea can be used to study the effect of new anti-angiogenic chemopreventive agents. We researched the anti-angiogenic effect of two extracts, Methanol (Met) and Hexane (Hex), from the seed of Cucurbita argyrosperma, in the inflamed corneas. The corneas of Wistar rats were alkali-injured and treated intragastrically for seven successive days. Clinical manifestation as opacity score, corneal neovascularization (CNV) area, re-epithelialization percentage, and histological evaluation were performed. Inflammatory (COX-2, NF-κB, and IL-1β), and angiogenic (VEGF-A, VEGFR1, VEGFR2) markers were assessed by immunohistochemistry. Cox-2, Il-1β, and Vegf-a mRNA levels were also determined. After treatments, we observed slim corneal thickness with lower opacity scores and low cell infiltration compared to untreated rats. Treatment also accelerated wound healing and decreased CNV area. The staining of inflammatory and angiogenic factors was significantly decreased. These effects are related to a down-expression of Cox-2, Il-1β, and Vegf. These results suggest that intake of C. argyrosperma seed can be used to attenuate the angiogenesis secondary to inflammation in corneal chemical damage.

A single Cancer immunotherapy has ushered in a transformative era in oncology, bringing forth unprecedented promise and opportunities. However, even with its significant breakthroughs, the domain faces the continual issue of treatment resistance. Such resistance not only restricts the broad effectiveness of these pioneering treatments but also highlights the imperative need for further research. Delving into the complex world of cancer immunotherapy resistance, we identify a range of mechanisms, from primary and secondary resistance to the notable effects of genetic and epigenetic variables, and the pivotal importance of the tumor microenvironment (TME). Additionally, we emphasize the need for innovative strategies to mitigate this resistance, including combination treatments, customized immune checkpoints, and instantaneous monitoring. By advocating for these cutting-edge methods, we foresee a direction that incorporates personalized healthcare, enhanced treatment options, and a steadfast dedication to the welfare of patients. Through a comprehensive and diverse approach, we aim to address the hurdles posed by resistance, elevating cancer immunotherapy as a symbol of hope for patients worldwide.

The field of mitochondrial genomics has advanced rapidly and revolutionized disciplines from molecular anthropology, population genetics, to medical/oncogenetics. However, mtDNA next-generation sequencing (NGS) analysis for matrilineal haplotyping and phylogeographic inference remains hindered by the lack of a consolidated, mitogenome database and efficient bioinformatics pipeline. To address this, we developed a customized human mitogenome database (hMITO DB) embedded in a CLC Genomics workflow for read mapping, variant analysis, haplotyping, and geo-mapping. The database was constructed from 4,286 mitogenomes. The macro-haplogroup (A to Z) distribution and representative phylogenetic tree were found consistent with published literature. The hMITO DB automated workflow was tested using mtDNA-NGS sequences derived from Pap smears and cervical cancer cell lines. The auto-generated read mapping, variants track, and table of haplotypes and geo-origins were completed in 15 min for 47 samples. The mtDNA workflow proved to be a rapid, efficient and accurate means of sequence analysis for translational mitogenomics.

Abstract5′,8-Cyclo-2′-deoxyadenosine (cdA), in the 5′R and 5′Sdiastereomeric forms, are typical non strand-break oxidative DNA lesions, induced by hydroxyl radicals, with emerging importance as a molecular marker. These lesions are exclusively repaired by nucleotide excision repair (NER) mechanism with a low efficiency, thus readily accumulating in the genome. Poly(ADP-ribose) polymerase1 (PARP1) acts as an early responder to DNA damage and plays a key role as a nick sensor in the maintenance of the integrity of the genome by recognizing nicked DNA. So far, it was unknown whether the diastereomeric cdA lesions could induce specific PARP1 binding. Here we provide the first evidence of PARP1 to selectively recognize the diastereomeric lesions 5′S-cdA and 5′R-cdA in vitro as compared to deoxyadenosine in model DNA substrates (23-mers) by using circular dichroism,fluorescence spectroscopy, immunoblotting analysis and gel mobility shift assay. Several features of the recognition of the damaged and undamaged oligonucleotides by PARP1were characterized. Remarkably, PARP1 efficiently binds to both cdA lesions in the double stranded (ds)-oligonucleotides. In particular, PARP1 proved to bind 5′S-cdAwith a higher affinity constant for the 5'S lesion in a model of ds DNA than 5′R-cdA, showing different recognition patterns, also compared with undamaged dA. This new finding highlights the ability of PARP1 to recognize and differentiate the distorted DNA backbone in a biomimetic system caused by different diastereomeric forms of a cdA lesion.

Inflammatory processes play major roles in carcinogenesis and progression of hepatocellular carcinoma (HCC) derived from non-alcoholic steatohepatitis (NASH). But there are no therapies for NASH related HCC, especially focusing on these critical steps. Previous studies reported that farnesyltransferase inhibitors (FTIs) have anti-inflammatory and anti-tumor effects. However, the influence of FTIs on NASH-related HCC has not been elucidated. In HCC cell lines, HepG2, Hep3B, and Huh-7, we confirmed expression of hypoxia-inducible factor (HIF)-1α, an accelerator of tumor aggressiveness and the inflammatory response. We established NASH-related HCC models under inflammation and free fatty acid burden and confirmed that HIF-1α expression was increased under both conditions. Tipifarnib, which is an FTI, strongly suppressed increased HIF-1α, inhibited cell proliferation, and induced apoptosis. Simultaneously, intracellular interleukin-6 as an inflammation marker was increased under both conditions and significantly suppressed by tipifarnib. Additionally, tipifarnib suppressed expression of phosphorylated nuclear factor-κB and transforming growth factor-β. Finally, in a NASH-related HCC mouse model burdened with diethylnitrosamine and a high fat diet, tipifarnib significantly reduced tumor nodule formation in association with decreased serum interleukin-6. In conclusion, tipifarnib has anti-tumor and anti-inflammatory effects in a NASH-related HCC model and may be a promising new agent to treat this disease.

Although congenital sensorineural hearing loss (SHL) in the bilateral cochleae mainly results from genetic abnormalities, chronic SHL progressing in later life is often influenced by systemic immune disturbances, including autoimmunity, chronic inflammation, and immunosenescence. We have investigated the relationship between the inner ear and systemic immunity and reviewed the possibilities to prevent SHL, including autoimmune SHL and age-related SHL. We also demonstrated two lymphocyte populations, interleukin 1 receptor type II (IL-1R2)-positive T cells (T1R2) and naturally occurring regulatory T cells (nTregs) in CD4⁺ T cells, which increase with aging, suppress host immune function and promote organ degeneration. Alterations in systemic immunity by fewer microbial antigen challenges in the living environment, elimination of immune suppressive lymphocytes, or immune rejuvenation with a reconstituted thymus may contribute not only to renew the cochlear function in SHL, but also to extend the healthy life of functional organs in a vigorous and youthful body, one of humanity’s greatest dreams.

Coastal resources in Lian, Batangas, have undergone significant degradation due to a combination of human activities and natural factors, including sea-level rise, changes in sea-surface temperature, fluctuations in rainfall, increased storm frequency, and sedimentation. This has led to adverse effects on key ecosystems such as corals, mangroves, and seagrasses. To assess the extent of climate change hazards on these coastal resources, a Vulnerability Assessment was conducted in the municipality of Lian, Batangas. The assessment employed a combination of the Coastal Integrity Vulnerability Assessment Toolkit (CIVAT) and Integrated Coastal Sensitivity, Exposure, and Adaptive Capacity to Climate Change (ICSEA-C) guidelines. Additionally, the analysis incorporated detailed mapping using Light Detection and Ranging (LiDAR) data for mangroves and LandSat 8 imagery for corals and seagrasses. The findings at the municipal scale revealed that a staggering 90% of mangroves in Lian, Batangas, were highly vulnerable. This vulnerability was attributed to a high score in intrinsic characteristics and a low adaptive capacity. Similarly, a majority of seagrasses in the area were classified as medium and highly vulnerable at the municipal level. Only 10–20% of seagrasses received low to medium vulnerability scores. Shockingly, almost 100% of the coral reefs in Lian, Batangas, were deemed highly vulnerable, indicating a critical threat to this crucial marine ecosystem.

Abstract: The purpose of this study was to understand the role of infection in the origin of chromosomal anomalies linked to neurodevelopmental disorders. In patients with neurodevelopmental disorders, DNA’s from viruses and bacteria including known teratogens were tested against chromosome anomalies known to cause the disorders. Results support a theory that parental infections disrupt elaborate multi-system gene coordination needed for neurodevelopment. Genes essential for neurons, lymphatic drainage, immunity, circulation, angiogenesis, barriers, structure, and chromatin activity were all found close together in polyfunctional clusters that were deleted in neurodevelopmental disorders. These deletions account for immune, circulatory, and structural deficits that accompany neurologic deficits. In deleted clusters, specific and repetitive human DNA matched infections and passed rigorous artifact tests. In some patients, epigenetic driver mutations were found and may be functionally equivalent to deleting a cluster or changing topologic chromatin interactions because they change access to large chromosome segments. In three families, deleted DNA sequences were associated with intellectual deficits and were not included in any database of genomic variants. These sequences were thousands of bp and unequivocally matched foreign DNAs. Analogous homologies were also found in chromosome anomalies of a recurrent neurodevelopmental disorder. Viral and bacterial DNAs that match repetitive or specific human DNA segments are thus proposed to interfere with highly active break repair during meiosis, and sometimes delete polyfunctional clusters, and disable epigenetic drivers. Mis-repaired gametes produce zygotes containing rare chromosome anomalies which cause neurologic disorders and accompanying non-neurologic signs. Neurodevelopmental disorders may be examples of assault on the human genome by foreign DNA with some infections more likely tolerated because they resemble human DNA segments. Further tests of this model await new technology.

Overhydration (OH) is a common medical problem found in patients with kidney or heart failure, but still a specific marker has not been found. Clinicians today use bioimpedance spectroscopy (BIS), ultrasound (US) markers of fluid overload or markers of heart and kidney function like NT-pro-BNP, GFR or creatinine levels. New serum markers such as Ca-125, Galectin-3 (Gal-3), Adrenomedullin (AMD) and Urocortin-2 (UCN-2), are being researched with promising results. The need to discover a more precise marker of overhydration is dire mainly because physical examination is extremely imprecise. Signs and symptoms of fluid overload like edema or gradual increase of body mass are not always present, especially in patients with chronic kidney disease. This review paper summarizes actual knowledge of a patient's hydration status estimation focusing especially on kidney diseases.

The abundant mechanical vibration energy in bridge road environment can be converted into electric energy by using the piezoelectric energy harvest technology, which could be an efficient way to provide energy required by the wireless sensor network in the bridge condition monitoring system. An autonomous energy harvesting system has been designed based on cantilever beams for sensing and acquiring the bridge vibration energy. After the analysis of the dynamic properties of the piezoelectric cantilever beam in the energy conversion, three kinds of interface circuits were compared through simulation and experimental results. It was shown that the VD interface circuit has less power loss. Furthermore, the proposed closed loop control method based on the VD circuit was simple, adaptive, and self-powered, which is suitable for the road energy harvesting application. Finally, the energy harvesting system based on VD circuit was realized with harvested power of around 0.8mW.

The part of this article dealing with topological insulators and topological superconductors was first written about two years ago - the ideas in the part about the topological universe originated six years ago or more. It’s rather strange that I never put the two parts together in writing before. My belief in unification is unshakeable - I’ve been convinced for years that the universe must be composed of topology. Since Earth is part of the cosmos, entanglement means it must have topological materials. The reverse is also true: topological materials on Earth are well known to science - so in a unification, space and time inevitably possess topological composition. Topological materials (topological insulators, topological superconductors) can be less mystifying if they’re related to the paradigm-shifting deterministic view of quantum mechanics which is described in the universal topology (the “rubber-sheet geometry” of the cosmos): see my previous submission “Hypothesis of Quantum Gravity - Resulting from a Static, Topological Universe Resulting from the Positives and Negatives of the Steady State and Big Bang Theories" at https://www.preprints.org/manuscript/202105.0239/v1 (the first section of this present article is a quick summary of the relevant parts).

E-commerce businesses employ recommender models to assist in identifying a personalized set of products for each visitor. To accurately assess the recommendations’ influence on customer clicks and buys, three target areas—customer behavior, data collection, user-interface —will be explored for possible sources of erroneous data. Varied customer behavior misrepresents the recommendations’ true influence on a customer due to the presence of B2B interactions and outlier customers. Non-parametric statistical procedures for outlier removal are delineated and other strategies are investigated to account for the effect of a large percentage of new customers or high bounce rates. Subsequently, in data collection we identify probable misleading interactions in the raw data, propose a robust method of tracking unique visitors, and accurately attributing the buy influence for combo products. Lastly, user-interface issues discuss the possible problems caused due to the recommendation widget’s positioning on the e-commerce website and the stringent conditions that should be imposed when utilizing data from the product listing page. This collective methodology results in an exact and valid estimation of the customer’s interactions influenced by the recommendation model in the context of standard industry metrics such as Click-through rates, Buy-through rates, and Conversion revenue.

The connective tissue mast cell (MC), a sentinel tissue-residing secretory immune cell, is preserved in all vertebrate classes since approximately 500 million years. No physiological role of the MCs has yet been established. Considering the power of natural selection of cells during evolution, it is likely that the MCs exert essential yet unidentified life-promoting actions. All vertebrates feature a circulatory system, and the MCs interact readily with the vasculature. It is notable that embryonic MC progenitors are generated from endothelial cells. The MC hosts many surface receptors enabling its activation by a vast variety of potentially harmful exogenous and endogenous molecules, and by reproductive hormones in the female sex organs. Activated MCs release a unique composition of pre-formed and newly synthesized bioactive molecules, like heparin, histamine, serotonin, proteolytic enzymes, cytokines, chemokines, and growth factors. MCs play important roles in immune responses, tissue remodeling, cell proliferation, angiogenesis, inflammation, wound healing, tissue homeostasis, health, and reproduction. As recently suggested, MCs enable perpetuation of the vertebrates because of key effects—spanning generations—in ovulation and pregnancy, as in life-preserving activities in inflammation and wound healing from birth till reproductive age, thus creating a permanent life-sustaining loop. Here, we present recent advances that further indicate that the MC is a specific life-supporting and progeny-safeguarding cell

According to Swiss-American Doctor of Sciences and Agricultural Engineer Jean-Pierre Jost, "plants communicate with each other by the quality of light emitted by their leaves or by means of stress hormones and other volatile chemicals. They also make use of cocktails of chemicals, pheromones, shape and colors to attract pollinators whereas other signals repel unwanted organisms. Insects are able to decode such messages and respond accordingly. Plants are apparently also communicating by sounds and electric signals." (1) How do plants do these things? Of course, it's easy to imagine it's all purely mechanical. But at the risk of sounding like a mysticism fanatic, I wonder if plants' activities are part of a spectrum of consciousness that pervades the entire universe. This spectrum would result from everything in the universe having the BITS or BInary digiTS of electronics as their ultimate composition. As explained in this hypothesis, something I call vector-tensor-scalar geometry is essential to my hypothesis. VTS geometry produces the particles of chemicals and pheromones, and refers to communication via electric signals when it speaks of electromagnetic-gravitational interaction. There's another consequence if everything in the universe is ultimately composed of electronic BITS and the cosmos is a spectrum of consciousness/artificial intelligence. It's impossible for an absence of consciousness to exist, either after death or before conception.

Human oncoviruses are able to subvert telomerase function in cancer cells through multiple strategies. The activity of the catalytic subunit of telomerase (TERT) is commonly enhanced in virus-related cancers. Viral oncoproteins, such as high-risk human papillomavirus (HPV) E6, Epstein-Barr virus (EBV) LMP1, Kaposi sarcoma-associated herpesvirus (HHV-8) LANA, hepatitis B virus (HBV) HBVx, hepatitis C virus (HCV) core protein and human T-cell leukemia virus-1 (HTLV-1) tax protein, interact with regulatory elements in the infected cells and contribute to the transcriptional activation of TERT gene. Specifically, viral oncoproteins have been shown to bind TERT promoter, to induce post-transcriptional alterations of TERT mRNA and to cause epigenetic modifications, which have important effects on the regulation of telomeric and extra-telomeric functions of the telomerase. Other viruses, such as herpesviruses, operate by integrating their genomes within the telomeres or by inducing alternative lengthening of telomeres (ALT) in non-ALT cells. In this review, we recapitulate recent findings on virus-telomerase/telomeres interplay and the importance of TERT-related oncogenic pathways activated by cancer causing viruses.

COVID-19 sepsis immune response remains unclear. Here we propose a new perspective in host response against pathogenic proteins that may lead to a vaccine design by polymerization of antigens of <70 kDa. In COVID-19, initial Th1 response kills infected cells releasing viral proteins. SARS-CoV-2 viral structural proteins are Spike (140 kDa), Nucleocapsid (50 kDa), Membrane (25 kDa) and Envelope (10 kDa). B cell receptor cannot capture antigens >70 kDa. The Spike protein (140 kDa) cannot be captured by B cells and triggers inflammatory Th1 response via the macrophages. Only proteins with a size <70 kDa can activate B cell receptor and trigger Th2 adaptative humoral response. Moreover, M-25 kDa and E-12 kDa glycoproteins can activate IgM-BCR like oligovalent or monovalent antigens. The sustained infected cells lysis overfeeds high levels of viral proteins <70 kDa, increases B cells activation and, in the shift from Th1 to Th2 immune response, triggers the cytokine storm. The continuous BCR activation increases IL-10 releasing and may lead to immune paralysis.

Dementia patients express a set of problematic and deteriorating symptoms, along self-care dependency. Overtime, the mental health of family caregivers of persons with dementia may suffer, putting them at a high risk for psychopathology, which may be associated with endangered wellbeing of demented people. This cross-sectional study examined the psychometric properties of the Depression Anxiety Stress Scale 8-items (DASS-8), DASS-12, DASS-21 in a convenient sample of 571 caregivers from northern Italy and southern Switzerland (Mean age = 53, SD = 12, range = 24–89 years). A bifactor structure of the three measures had the best fit; some items of the DASS-12/DASS-21 failed to load on their domain-specific factors. The three-factor structure was invariant across various groups (e.g., gender, education, etc.), expressed adequate reliability and convergent validity, and had strong positive correlation with the 3-item UCLA Loneliness Scale (UCLALS3). Dementia type had no effect on distress scores, which were higher among females, adult children caregivers, those caring for dependent patients, and those who received help with care. For 54.9 and 38.8% of the latter, care was provided by relatives and health professionals, respectively. Since the DASS-8 expresses adequate psychometrics comparable with the DASS-21, it may be used as a brief measure of distress in this population.

Despite extensive investigations of the Depression Anxiety Stress Scales-21 (DASS-21) since its development in 1995, its factor structure and other psychometric properties still need to be firmly established, with several calls for revising its item structure. Employing confirmatory factor analysis (CFA), this study examined the factor structure of the DASS-21 and five shortened versions of the DASS-21 among psychiatric patients (N = 168) and the general public (N = 992) during the COVID-19 confinement period in Saudi Arabia. Multigroup CFA, Mann Whitney W test, Spearman’s correlation, and coefficient alpha were used to examine the shortened versions of the DASS-21 (DASS-13, DASS-12, DASS-9 (two versions), and DASS-8) for invariance across age and gender groups, discriminant validity, predictive validity, item coverage, and internal consistency, respectively. Compared with the DASS-21, all three-factor structures of the shortened versions expressed good fit, with the DASS-8 demonstrating the best fit and highest item loadings on the corresponding factors in both samples (χ2(16, 15) = 16.5, 67.0; p = 0.420, 0.000; CFI= 1.000, 0.998; TLI = 0.999, 0.997; RMSEA = 0.013, 0.059, SRMR = 0.0186, 0.0203). It expressed configural, metric, and scalar invariance across age and gender groups. Its internal consistency was comparable to other versions (α = 0.94). Strong positive correlations of the DASS-8 and its subscales with the DASS-21 and its subscales (r = 0.97 to 0.81) suggest adequate item coverage and good predictive validity of this version. The DASS-8 and its subscales distinguished the clinical sample from the general public at the same level of significance expressed by the DASS-21 and other shortened versions, supporting its discriminant validity. Neither the DASS-21 nor the shortened versions distinguished patients diagnosed with depression and anxiety from other conditions. The DASS-8 represents a valid short version of the DASS-21, which may be useful in research and clinical practice for quick identification of individuals with potential psychopathologies. Diagnosing depression/anxiety disorders may be further confirmed in a next step by clinician-facilitated examinations. Brevity of the DASS-21 would save time and effort used for filling the questionnaire and support comprehensive assessments by allowing the inclusion of more measures on test batteries.