This review highlights normal and tumor tissue vasculature, immunological changes, and phenotypic alterations (VIP model) as fundamental in abscopal interaction. In the stereotactic body radiotherapy (SBRT) and immunotherapy era, we are moving toward “immunological radiation planning,” i.e., radiation scheduling with abscopal effect as a vital endpoint as well. Towards this end, this manuscript presents specific diagrammatic tumor models to optimize the outcome of abscopal response in SBRT, based on the principle of the four R’s - Repair, Redistribution, Repopulation, and Reoxygenation of radiotherapy. The article highlights the importance of restricting the dose of SBRT to < 10 Gy per fraction, appropriate use of dose painting, and concomitant/delayed SBRT boost potential. Current literature indicates that immunotherapy should not precede but follow SBRT within seven days. Included is the review of integrating “cyclical” antiangiogenics, immune adjuvants/immune-metabolites as abscopal effect enhancers with SBRT. The importance of proton, carbon-ion SBRT is dealt with briefly. Proposed six fundamental requirements for augmentation of the abscopal cascade are listed. The existing exploratory results need to develop a definitive strategy amidst complex interactions in SBRT, immunotherapy, immune-adjuvants, & abscopal effects. We now have enough literature evidence to convert “abscopal by chance” to “abscopal by design” by harmonized combinatorial approach.

Heat shock proteins (Hsps) are highly conserved molecules that are constitutively expressed and upregulated in response to physiological stress conditions. These immunogenic chaperones can have essential functions in fungi, particularly in dimorphic pathogens. Histoplasma capsulatum and Paracoccidioides species are dimorphic fungi that are the causative agents of histoplasmosis and paracoccidioidomycosis, respectively, which are systemic mycoses with significant rates of morbidity and mortality. Current treatment consists of long-term antifungal agents, and there is an urgent need for new therapeutic approaches with higher efficacy, lower toxicity, better biodistribution and improved selectivity. We engineered an immunoglobulin G1 (IgG1) isotype chimeric mouse-human monoclonal antibody, titled ch-MAb 4E12, from the parental IgG2a MAb 4E12, a monoclonal antibody to H. capsulatum Hsp60 that is protective in experimental histoplasmosis and paracoccidioidomycosis models elicited by H. capsulatum var. capsulatum and Paracoccidioides lutzii, respectively. The ch-MAb 4E12 increased phagolysosomal fusion and enhanced the yeasts uptake by PMA differentiated human THP1 macrophage cells in vitro. At low concentrations, the chimeric antibody significantly reduced the pulmonary and splenic fungal burden compared to an irrelevant antibody or no treatment. These results are the first to show that a chimeric mouse-human antibody can modify infection caused by dimorphic fungi.

Instead of tissue-based detection, blood-based tumor mutation burden (bTMB) is becoming an alternative promising alternate to predict the response of immune checkpoint inhibitor in cancers, especially non-small-cell lung cancer. Although bTMB is more convenient and less invasive, many evidences identified its limited predictive ability and less accurate discrimination of candidates to receive immunotherapy. Several ways of adjustments have been applied to improve the clinical usefulness of bTMB, such as setting restriction for threshold of allele frequency to exclude some unwanted mutations. But many questions remained to be explored such as the number and the type of mutations that should be incorporated into the bTMB estimation. This viewpoint summarized the current attempts to modify bTMB and provided granular aspects that have implications for further enhancement of bTMB’s predictive capability.

The most common type of non-Hodgkin lymphoma in adults is diffuse large B-cell (DLBCL). There is a historical unmet need for more effective therapies in the 2nd and 3rd line setting. Emerging immunochemotherapies have shown activity in small studies of heavily pre-treated patients with prolonged remissions achieved in some patients. Anti-CD19 CAR (chimeric antigen receptor) T cells are potentially curative in the 3rd line and beyond setting and are under investigation in earlier lines of therapy.1 Antibody-drug conjugates (ADC’s) such as polatuzumab vedotin targeting the pan-B-cell marker CD79b has proven effectiveness in multiply-relapsed DLBCL patients. Tafasitamab (MOR208) is an anti-CD19 monoclonal antibody producing prolonged remissions when combined with Lenalidomide in patients who were not candidates for salvage chemotherapy or autologous stem cell transplant. Selinexor, an oral, small-molecule selective inhibitor of XPO1-mediated nuclear export (SINE), demonstrated prolonged activity against heavily-pretreated DLBCL without cumulative toxicity and is being investigated as part of an oral, chemotherapy-free regimen for relapsed aggressive lymphoma. This article reviews current strategies and novel therapies for relapsed/refractory DLBCL.

T cells follow a triphasic distinct pathway of activation, proliferation and differentiation before becoming functionally and phenotypically ‘exhausted’ in settings of chronic infection, autoimmunity and in cancer. Exhausted T cells progressively lose canonical effector functions, exhibit altered transcriptional networks and epigenetic signatures and gain constitutive expression of a broad coinhibitory receptor suite. This review outlines recent advances in our understanding of exhausted T cell biology and examines cellular and molecular mechanisms by which a state of dysfunction or exhaustion is established, and mechanisms by which exhausted T cells may still contribute to pathogen or tumour control. Further, this review describes our understanding of exhausted T cell heterogeneity and outlines the mechanisms by which checkpoint blockade differentially engages exhausted T cell subsets to overcome exhaustion and recover T cell function.

β₂-m, β₂-microglobulin; CAF, cancer associated fibroblast; CSC, cancer stem cell; CTL, cytotoxic T lymphocyte; DC, dendritic cell; ECM, extracellular matrix; EGF-R, epidermal growth factor receptor; ER, endoplasmic reticulum; FDA, Food and Drug Administration; HLA, human leukocyte antigen; HNSCC, head and neck squamous cell carcinoma; HPV, human papilloma virus; ICP immune checkpoint; ICPi, immune checkpoint inhibitor; IFN, interferon; LMP, low molecular weight protein; mAb, monoclonal antibody; MDSC, myeloid-derived suppressor cell; mTOR, mammalian target of rapamycin; MSI, multispectral imaging; NK, natural killer; OS, overall survival; PBL, peripheral blood lymphocytes; PBMNC, peripheral blood mononuclear cells; PD1, programmed death receptor 1; PD-L1, programmed death ligand 1; PFS, progression-free survival; PI3K, phosphatidyl-linositol-3-kinase; R/M, recurrence and or metastatic; STAT, signal transducer and activator of transcription; TAA, tumor-associated antigen; TAM, tumor associated macrophages; TAP, transporter associated with antigen processing; TCR, T cell receptor; TIL, tumor-infiltrating lymphocyte; TLS, tertiary lymphoid structure; TME, tumor microenvironment; Treg, regulatory T cell; TSA, tumor-specific antigen; VEGF, vascular endothelial growth factor; VEGF-R, vascular endothelial growth factor receptor.

Ulcerative colitis (UC) is a common chronic disease of the large intestine. Current anti-inflammatory drugs prescribed to treat this disease have limited utility due to significant side-effects. Thus, immunotherapies for UC treatment are still sought. In the DSS mouse model of UC, we recently demonstrated that systemic administration of the Bin1 monoclonal antibody 99D (Bin1 mAb) developed in our laboratory was sufficient to reinforce intestinal barrier function and preserve an intact colonic mucosa, compared to control subjects which displayed severe mucosal lesions, high-level neutrophil and lymphocyte infiltration of mucosal and submucosal areas, and loss of crypts. Here we report effects of Bin1 mAb on colonic neurons and the gut microbiome that correlate with the benefits of treatment. In the DSS model, we found that induction of UC was associated with disintegration of enteric neurons and elevated levels of glial cells, which translocated to the muscularis at distinct sites. Further, we characterized an altered gut microbiome in DSS treated mice associated with pathogenic proinflammatory characters. Both of these features of UC induction were normalized by Bin1 mAb treatment. With regard to microbiome changes, we observed in particular that Firmicutes were eliminated by UC induction and that Bin1 mAb treatment restored this phylum including the genus Lactobacillus and Akkermansia as beneficial microorganisms. Overall, our findings suggest that the intestinal barrier function restored by Bin1 immunotherapy in the DSS model of UC is associated with a preservation of enteric neurons and an improvement in the gut microbiome, contributing overall to a healthy intestinal tract.

Metastases cause high mortality in several cancers and immunotherapies are expected to be effective in the prevention and treatment of metastatic disease. However, only a minority of patients benefit from immunotherapies. This creates a need for novel therapies that are efficacious regardless of the cancer types and metastatic environments they are growing in. Preclinical immuno-oncology models for studying metastases have long been limited to syngeneic or carcinogenesis-inducible models that have murine cancer and immune cells. However, the translational power of these models has been questioned. Interactions between tumor and immune cells are often species-specific and regulated by different cytokines in mice and humans. For increased translational power, mice engrafted with functional parts of human immune system have been developed. These humanized mice are utilized to advance understanding the role of immune cells in the metastatic process, but increasingly also to study the efficacy and safety of novel immunotherapies. From these aspects, this review will discuss the role of immune cells in the metastatic process and the utility of humanized mouse models in immuno-oncology research for metastatic cancers, covering several models from the perspective of efficacy and safety of immunotherapies.

Cancer immunotherapy targeting immune checkpoints has exhibited promising clinical outcomes in many cancers, but it offers only limited benefits for pancreatic cancer (PC). Cancer stem cells (CSCs), a minor subpopulation of cancer cells, play important roles in tumor initiation, progression, and drug resistance. Accumulating evidence suggests that CSCs employ immunosuppressive effect to evade the immune recognition. However, clinical implications of the associations among CD8+ T cells infiltration, programmed death receptor ligand-1 (PD-L1) expression, and CSCs existence are poorly understood in PC. Immunostaining and quantitative analysis were performed to assess CD8+ T cells infiltration, PD-L1 expression, and their relationship with CD44+/CD133+ CSCs and disease progression in PC. CD8+ T cells infiltration was associated with better survival while PD-L1 expression was correlated with PC recurrence. Both the low CD8+ T cells infiltration/high PD-L1 expression group and the high CD8+ T cells infiltration/high PD-L1 expression group show high levels of CD44+/CD133+ CSCs, but patients with low CD8+ T cells infiltration/high PD-L1 expression had worse survival and higher recurrence risk than those with high CD8+ T cells infiltration/high PD-L1 expression. Moreover, CD8+ T cells infiltration could reduce unfavorable prognostic effect of high co-expression of PD-L1 and CD44/CD133. Our study highlights an interaction among CD8+ T cells infiltration, PD-L1 expression, and CD44+/CD133+ CSCs existence, which contributes to PC progression and immune evasion.

Stereotactic radiosurgery (SRS) has become increasingly important in the management of brain metastases due to improving systemic disease control and rising incidence. Initial trials demonstrated SRS with whole brain radiotherapy (WBRT) improved local control rates versus WBRT alone. Concerns with WBRT associated neurocognitive toxicity have contributed to greater use of SRS alone, including for patients with multiple metastases and following surgical resection. Molecular information, targeted agents and immunotherapy have also altered the landscape for the management of brain metastases. This review summarises current and emerging data on the role of SRS in the management of brain metastases.

Some of the most promising small molecule toxins used to generate antibody drug conjugates (ADCs) include anti-mitotic agents (e.g auristatin and its derivatives) which are designed to attack cancerous cells at their most vulnerable state during mitosis. We were interested to identify a human cystostatic protein eventually showing comparable activities and allowing the generation of corresponding targeted fully human cytolytic fusion proteins. Recently, we identified the human microtubule associated protein tau (MAP tau) which binds specifically to tubulin and modulates the stability of microtubules thereby blocking mitosis and presumably vesicular transport. By binding and stabilizing polymerized microtubule filaments, MAP tau-based fusion proteins skew microtubule dynamics towards cell cycle arrest and apoptosis. This biological activity makes rapidly proliferating cells (e.g cancer and inflammatory cells) an excellent target for MAP tau-based targeted treatments. Their superior selectivity for proliferating cells confers additional selectivity towards upregulated tumor-associated antigens at their surface, thereby preventing off-target related toxicity against normal cells bearing tumor-associated antigens at physiologically normal to low levels. In this review, we highlight recent findings on MAP tau-based targeted cytolytic fusion proteins reported in preclinical immunotherapeutic studies.

This study introduces a technique to uncover concealed patterns in satellite altimetry data, reflecting sea level variations in inland water bodies. We applied the methodology to the Caspian Sea, using altimetry data from four satellite missions over 27 years (1993-2020): TOPEX/Poseidon, Jason1, Jason2, and Jason3. The approach involves two steps: estimating sea level trends and identifying breakpoints that indicate trend shifts; and leveraging time lags between breakpoints at various locations to classify water drainage areas according to their degree of influence on each period. By revealing concealed patterns in the altimetry data, this technique can provide insights to understand the impacts of global warming and local climate changes on sea level fluctuations in the Caspian Sea. We hope that our study can facilitate subsequent interdisciplinary research on the intricate interplay between climate change and hydrological processes in inland water bodies.

The Aether Physics Model (APM) presents a radical reinterpretation of fundamental physics, offering potential solutions to long-standing problems in Quantum Mechanics and General Relativity. This paper explores the core concepts and equations of the APM, demonstrating how they provide a unified framework for understanding the nature of space, time, matter, and fundamental forces. We examine the implications of the APM's quantized Aether structure, the role of the Singularity and Gforce, and the reinterpretation of fundamental constants and forces. The model's predictions regarding dark matter, neutron content in stable matter, and the unification of forces are discussed, along with potential experimental tests. Additionally, we introduce the loxodrome concept and toroidal particle topology as central elements in explaining fundamental particles and forces. While speculative, the APM offers a thought-provoking alternative to standard physics models and warrants further investigation.

This study investigates the role of sustainable inventory management within supply chains, exploring strategies, benefits, challenges, and implications for organizations. Through qualitative research involving semi-structured interviews with supply chain professionals from diverse industries, key themes emerged. Sustainable practices such as green logistics, waste minimization, and ethical sourcing were identified as critical strategies to reduce environmental impact and enhance operational efficiency. Technological advancements, including AI, IoT, and blockchain, facilitate real-time monitoring, predictive analytics, and transparency, supporting data-driven decision-making in inventory management. Benefits include cost reduction, improved brand reputation, regulatory compliance, and risk mitigation, positioning organizations favorably in a competitive landscape shaped by environmental regulations and consumer expectations. Challenges such as cost constraints, regulatory complexities, and organizational inertia necessitate strategic investments, collaborative efforts, and leadership commitment to overcome. The study underscores the importance of integrating environmental, social, and economic considerations into supply chain practices to foster sustainability and resilience. Looking forward, the study advocates for a holistic approach to sustainable supply chain management, emphasizing innovation, stakeholder engagement, and capacity building. By aligning organizational values with societal expectations and regulatory frameworks, businesses can navigate complexities, drive positive environmental and social impacts, and achieve sustainable growth. This research contributes insights into current practices and future directions for sustainable inventory management, informing strategies that balance profitability with environmental stewardship and societal responsibility.

Color change is the most obvious characteristic of tomato ripening stage and an important indicator of tomato ripening condition, which directly affects the commodity value of tomato. To visualize the color change of tomato fruit in mature stage, a gated recurrent unit network with an encoder-decoder structure that dynamically simulates tomato growth and development with time-dependent lines using tomato color and shape as real-time data was proposed in this paper. Firstly, the .json file was converted into a mask.png file, the tomato mask was extracted, and the tomato was separated from the complex background environment, and the tomato growth and development data set was successfully constructed. Then, a network of gated recurrent units with encoder-decoder structure was constructed to predict the future growth trend of tomato under different greenhouse temperatures. The experimental results showed that for the gated recurrent unit network of encoder-decoder structure proposed, when the hidden layer number was 1 and hidden layer number was 512, a high consistency and similarity between the model predicted image sequence and the actual growth and development image sequence would be realized, and the structural similarity index measure was 0.746. It was proved that when the average temperature was 24.93℃, the average soil temperature was 24.06℃, and the average light intensity was 11.26 Klux, the environment was the most suitable for tomato growth. The environmental data-driven tomato growth model was constructed to explore the growth status of tomato under different environmental conditions, thus to understand the growth status of tomato in time. The statement provided a theoretical foundation for determining the optimal greenhouse environmental conditions to achieve tomato maturity. And it offered recommendations for investigating the growth cycle of tomatoes, as well as technical assistance for standardized cultivation in solar greenhouses.

Forage fish are crucial to human nutrition, especially in developing countries. However, in these countries, most forage fish catches are used to make aquafeeds for aquaculture, which leaves only a small quantity for direct human consumption. This practice increases fish prices in local markets and undermines people's nutrition. Overfishing forage fish for industrial purposes harms the ecosystem, reduces the catch of larger fish, and marginalizes local fishermen. Although previous discussions have touched qualitatively on the ethics and injustice of this practice, this article provides quantitative scales to measure the impact of the practice on the finances and forage fish consumption of low-income consumers using reasonable assumptions and literature values. Increasing the annual supply of forage fish by 25% to the 5 million MT of fresh fish markets globally could save consumers several billion US dollars annually. Families could consume a higher percentage of nutritious fish for less money. Furthermore, leaving forage fish in the sea could benefit wildlife and increase the capture of larger fish, such as mackerel, which are in demand in local markets and fished by local fishermen. The unintentional and involuntary contributions of low-income societies to enable the growth of high-value fish and shrimp for affluent societies seem unjust and warrant further investigation.

This study aimed to evaluate the discrepancies between genetic and visual coat color assignment in the Sarcidano Horse and to elucidate potential reasons. Individual DNA from 90 Sarcidano Horses was used for genetic assignment of coat color to explore the correspondence with individual forms containing phenotypical traits. The MC1R exon 1 and ASIP exon 3 have been genotyped and sequenced to obtain a picture of the coat color distribution in this breed. Surprisingly, once we compared the genetic results with the individual forms reporting the phenotypic data for each subject, a certain degree of non-correspondence between the phenotypic and genetic data in relation to coat color emerged. From the genetic analysis, Chestnuts (n = 58) resulted the most common Sarcidano Horse (n = 58), followed by a quite large number of Blacks (n = 28) and a very small number of Bays (n = 4), whereas phenotypic distribution resulted in 38 Chestnuts, 40 Bays, only 2 Blacks, and 10 Grays (without the possibility of recognizing the true color they carried). Chestnut resulted a very representative coat color, while many horses that visually identified as Bays were genetically Blacks. This discrepancy, that could be due to a variety of individual and external factors, including age, time of year, living situation and dietary condition, suggesting the importance of accurate coat color identification to ensure adequate features registration and reliable prediction of offspring’s coat color.

Introduction: Flow-cytometry (FC) is a powerful tool that can assist in lymphoma diagnosis in lymph node (LN) specimens. Although lymphoma diagnosis and classification are mainly based on tumor cell characteristics, surrounding cells are less employed in this process.Methods: We retrospectively investigated alterations in the ploidy status, proliferative cell fraction (PF) and the percentages of surrounding immune cells in 62 consecutive LN specimens with B-Cell Non-Hodgkin Lymphoma (B-NHL) that were submitted for FC evaluation between 2019-2022.Results: Compared with indolent B-NHLs, aggressive B-NHLs show increased DNA aneuploidy and PF, increased monocytes, immature-granulocytes, mature granulocytes, CD8⁺ T-cells, Double-Negative-T-cells and Double-Positive-T-cells, and decreased total CD45⁺ cells, total lymphocytes, CD4⁺ T-cells and CD4/CD8 ratio. Receiver operating characteristic analysis determined PF > 6.8% and immature-granulocytes > 0.9% as optimal cutoffs with highest specificity and sensitivity in differentiating aggressive and indolent B-NHLs.Conclusions: These findings further strength the diagnostic value of DNA content analysis by FC and suggest the utilization of tumor surrounding immune cells in NHL diagnosis and classification.

This paper reviews the measurement challenges associated with 3D scanning techniques in civil engineering. It explores the practical aspects of scanning buildings and complex surfaces through various case studies. The paper details the conventional use of Terrestrial Laser Scanning (TLS) for reconstructing the technical documentation of a hall. It then describes an unconventional application of this technique for measuring an ETICS (External Thermal Insulation Composite System) wall, aiming to detect microdeformations caused by environmental factors controlled within a climatic chamber. The measurements of the insulated wall were subsequently repeated using a metrological grade laser scanner. Numerical data was analyzed with inspection engineering methods. This approach yielded qualitative and quantitative results. Although the qualitative results were consistent, the quantitative data revealed some inconsistencies. To address discrepancies in the quantitative data, a comparative analysis was performed, which highlighted critical findings and areas of divergence.

Early detection of cervical cancer is the need of the hour to stop the fatality from this disease. There have been various CAD approaches in the past that promise to detect cervical cancer in an early stage, each of them having some constraints.This study proposes a novel ensemble deep learning model, VLR (variable learning rate), aimed at enhancing the accuracy of cervical cancer classification. The model architecture integrates VGG16, Logistic Regression, and ResNet50, combining their strengths in an offbeat ensemble design. VLR learns in two ways: firstly, by dynamic weights from three base models, each of them trained separately; secondly, by attention mechanisms used in the dense layer of the base models. Hyperparameter tuning is applied to further reduce loss, fine tune the model’s performance, and maximize classification accuracy. We performed K-fold cross-validation on VLR to evaluate any improvements in metric values resulting from hyperparameter fine tuning. We have also validated our model on images captured in three different solutions and on a secondary dataset. Our proposed VLR model outperformed existing methods in cervical cancer classification, achieving a remarkable training accuracy of 99.95% and a testing accuracy of 99.89%.

To date, SARS Cov-2 virus has caused more than 775 million cases worldwide and led to 7 million deaths. The virus enters cells with the aid of the ACE2 receptor located in the airway epithelium, but also in endothelial cells lining the inner walls of vessels. Endothelial damage results in impaired blood flow and gas exchange. Statins have been shown to have a pleiotropic effects on the vascular epithelium. Aim of the study: Assessment of the efficacy and safety of statin therapy in patients with COVID-19. Methods: Two hundred and one COVID-19 patients hospitalized at the Jerzy Gromkowski Regional Specialist Hospital between March 2020 and December 2021 (i.e. during the period dominated by Alpha, Beta, Gamma and Delta variants). Patients were divided into three groups: (I) patients treated with statins prior to the admission to the hospital; (II) patients started on statins after admission due to Covid-19; (III) control patients with Covid-19, not treated with statins either prior to or during hospitalization. Met Statistica 13.1 calculations were used in the paper. Shapiro-Wilk, Kruskal-Wallis and ANOVA tests were also performed. Results: Out of the 201 patients total, group I comprised 66 patients with a mean age of 66.2 years; group II comprised 33 patients with a mean age of 75.3 years; and the control group comprised 97 patients with a mean age of 61.1 years. The groups characteristics did not show significant differences in terms of gender, place of hospitalization, percentage of Covid-19 vaccinations, number of convalescents. Death was observed in: 12% of patients in group I, 6% of patients in group II, and 6% of patients in group III. Body Mass Index (BMI) in group I was 31.3: a value significantly higher than the control group’s 28.3, (p<0.05). The severity of Covid-19 assessed on admission in group I – 4.09 – was statistically higher than in the control group 3.52 (p<0.05). The number of pulmonary embolism incidents did not differ between groups. Conclusions: During the period dominated by Alpha, Beta, Gamma and then Delta variants, we found no statistically significant positive or negative effects of statin therapy on the duration of hospitalization, number of complications or percentage of deaths between the two studied groups of patients: those who received statins prior to hospitalization, and those who received statins during hospitalization.

Pichia pastoris is extensively employed as a host for expressing foreign proteins, and its secretion system is especially advantageous for efficient protein purification. Ulp1 is essential for the cell cycle. In Saccharomyces cerevisiae, the absence of Ulp1 leads to G2/M cell cycle arrest. Similarly, in Pichia pastoris, we also observed G2 phase stalling in Ulp1 knockout cells. RNA-seq data revealed significant changes in seven genes, including INO1. Interestingly, overexpressing INO1 in Ulp1 knockout cells restored cell proliferation, suggesting that Ulp1 regulates cell proliferation through INO1. However, adding extra inositol to Ulp1 knockout cells was not able to restore cell prolifera-tion, indicating that the enzyme activity of INO1 is not essential for cell proliferation. Our data provide new insights into Ulp1 functions in the cell cycle and raise new questions about yeast cell cycle regulation.

Background: RO and ChRCC are kidney tumours with overlapping characteristics, making differentiation between them challenging. Objectives: The objective of this research is to create a radiogenomics map by correlating radiomic features to molecular phenotypes in ChRCC and RO, using resection as the gold standard. Methods: Fourteen patients (6 RO and 8 ChRCC) were included in the study. A total of 1,875 radiomic features were extracted from CT scans, alongside 632 cytobands containing 16,303 genes from the genomic data. Results: Feature selection algorithms applied to the radiomic features resulted in 13 key features. From the genomic data, 24 cytobands highly correlated with histology were selected and cross-correlated with the radiomic features. The analysis identified four radiomic features that were strongly associated with seven genomic features. Conclusion: These findings demonstrate the potential of integrating radiomic and genomic data to enhance the differential diagnosis of RO and ChRCC, paving the way for more precise and non-invasive diagnostic tools in clinical practice.

Background and Objectives: A degenerative joint disease that primarily affects the elderly, osteoarthritis (OA) causes pain, decreased mobility, and a lower quality of life. The effectiveness of GerovitalH3, a biotrophic medication created by Ana Aslan, in reducing pain and enhancing function in older people with osteoarthritis in the knee and hip is assessed in this study. Materials and Methods: Two groups of 201 patients aged 65 and older participated in a randomized, case-control clinical trial. One group received physical therapy and GerovitalH3 periarticular injections, while the other group received just physical therapy. In addition to functional evaluations using the Lequesne Index, Activities of Daily Living (ADL), and Instrumental ADL (IADL) scores, pain was assessed using a Visual Analogue Scale (VAS). Results: The GerovitalH3 group showed a substantial decrease in pain (p<0.001) and an improvement in daily activities (p<0.001) when compared to the control group. However, there was no significant difference in walking scores (p = 0.171). There were no significant adverse effects noted. GerovitalH3 did not outperform physical therapy for reducing depression, even though both groups displayed some improvement in this area. Conclusions: This study opens a new possibility for periarticular injections of Gerovital H3 treatment combined with physical therapy, which may represent a safe and effective non-surgical option for elderly individuals struggling with OA pain and functional limitations. The findings of this study reinforce the need for further research, particularly randomized controlled trials with larger sample sizes and longer follow-up periods.

Predicting the remaining useful life (RUL) of mechanical bearings is crucial in the industry. 1 Estimating the RUL enables the assessment of health bearing, maintenance planning, and signifi- 2 cant cost reduction, thereby fostering industrial development. Existing models rely on traditional 3 feature engineering, with feature changes because operating conditions pose a major challenge to 4 the generalization of RUL prediction models. This study focuses on neural network-based feature 5 engineering and the downstream prediction of the RUL, eliminating the need for specific prior 6 knowledge and simplifying the development and maintenance of models. Initially, a convolutional 7 neural network (CNN) model is employed for feature engineering. Subsequently, a bidirectional 8 long short-term memory network (Bi-LSTM) model is used to capture the time-series degradation 9 characteristics of the engineered features and predict the RUL through regression. Finally, the study 10 examines the influence of operating conditions in the model and integrates domain adaptation to 11 minimize differences in feature distribution, thereby enhancing the model’s generalizability for the 12 RUL prediction.

Purpose/Objective: Frequent consumption of fermented carbohydrates and bottle feeding contribute to the development of early childhood caries (ECC). There are no substantial findings on the effects of breastfeeding patterns on oral health conditions in children in the United States. We aimed to assess the nexus between exclusive breastfeeding during the first 6 months and oral health disorders, namely toothache, decayed teeth, or unfilled cavities in early childhood. Materials and Methods: Design: Cross-sectional epidemiologic design of nationally representative data collected via telephone surveys in the United States was utilized. Setting: National Survey of Children’s Health, 2012 Participants: Population-based random sample of parents/guardians of 24,655 children aged 6 months to 5 years. Main Outcome and Measure: Parent-reported oral health condition including toothache, decayed teeth or unfilled cavity in the past 12 months. Results: A total of 2,392 (9.7%) children aged 6 months to 5 years experienced an oral health disorder, mainly toothache, decayed teeth, or unfilled cavity in the previous 12 months. Relative to non-Hispanic White children (7.7%), a greater proportion of non-Hispanic Black (12.9%) and multi-racial children (12.6%) experienced oral health disorders (OHD). In the univariable model, relative to children who never breastfed, those who were breastfed exclusively for 6 months were 28% less likely to present with OHD, Odds Ratio (OR) = 0.72, 95% CI, 0.52-0.98. After adjustment, the protective nature of exclusive breastfeeding against OHD did not remain, adjusted OR (aOR) =1.11, 99% CI 0.79-1.57. Children of mothers with fair/poor health were almost twice as likely to have poor OHD compared with children of mothers with excellent/very good health (aOR = 1.79, 99% CI 1.08-2.69). Conclusions and Relevance: Exclusive breastfeeding for the first six months of life improved pediatric OHD and remains mutually beneficial for mothers and children. These findings suggest the importance of exclusive breastfeeding and maternal health in relation to dental hygiene in children.

With the improvement of computer, artificial intelligence, information technology and other technical levels, the relationship between man-machine environment systems is more complicated and diversified. The optimization, iteration and development of the new generation of intelligent equipment system and human-computer interaction interface put forward higher requirements for ensuring the safety of personnel, improving the efficiency of human-computer interaction and improving the efficiency of the system. Such as intelligent cabin adaptive cognitive decision aid system, how to adopt intelligent information display and human-computer interaction, optimize information processing, strengthen situational awareness; How to effectively present information and improve the efficiency of human-computer interaction, so that the system has good security, applicability and maximize its effectiveness; How to deal with man-machine matching and man-machine collaboration problems, so as to improve the efficiency of man-machine/unmanned collaborative work. Human factors throughout the life cycle of equipment systems must be fully considered. The human factor is considered in the system design, so that people, machines and the environment can work together and adapt to each other, so as to achieve benign interaction and feedback between people and equipment and interface and complete the full transmission and communication of human-machine intelligent interaction information. The development of new aircraft human-computer interaction systems combined with new technological methods has also gradually changed the role of pilots and staff. From the system operator gradually into the monitor and decision maker, especially with the improvement of the degree of intelligent flight, information technology, advanced complex airborne equipment is increasing, the amount of information that operators need to deal with is also increasing, and the allowed time for judgment and decision is very short, and the mental resources that pilots bear are gradually rising. As the mental load is a key factor affecting the allocation of cognitive tasks, when encountering emergency situations, the mental load overload caused by the increase of information processing tasks often occurs, which seriously affects the task performance of operators, physical and psychological comfort and flight safety, and thus affects the efficiency and safety of the entire aircraft man-machine system. This requires us to conduct real-time analysis of human-computer interaction situational awareness, especially the individual cognitive state as an uncontrollable factor.

This study reveals that with similar valence of empathy, the tendency for humans to help humans in need is stronger than the animal in need. It also illustrates that a convincible advertisement for a charity should be a combination of various feelings, mainly empathic anger, in addition to compassion or empathy. To gain support from young individuals or donors regardless of their personal values, the egoistic values particularly, both the NPOs in humanitarian aid as well as in environmental protection or conservation should develop ads by which each individual or donor is aroused by either an empathic anger and empathic joy or both. This claim is more applicable for any ads developed to help people in need more than animals in need. Nevertheless, this study also found the role of an animal, generally known as innocent, as an actor in an ad is likely more crucial than human. Subjects with high-egoistic values appeared to get vulnerably aroused to a higher extent by being immersed in animal’s suffering than human’s suffering. The feeling of arousal seemed to motivate subjects with high-egoistic values to not decrease the amount of donation to a charity.

In this paper, we explore the surprising behavior of certain discrete maps, drawing inspiration from Collatz-like problems and advanced techniques in analytic number theory, dynamical systems, and differential geometry. Specifically, we investigate a driven cubic-quintic Duffing equation and predict the number of limit cycles around equilibrium points. Furthermore, we develop a novel theoretical framework for chaos suppression in damped-driven systems, leveraging sequences derived from Collatz-like problems. Our study also focuses on analyzing the density of these sequences in both Euclidean and Riemannian metric spaces, providing a comparative analysis of their distribution properties. We estimate the growth rate of sequence density analytically and numerically, highlighting the sensitivity of the density values to the choice of parameters in both metric spaces. Our results present new insights into the behavior of these sequences and their implications for number theory, chaotic dynamics, and geometric analysis.

This study investigates the performance and environmental impact of n-butanol blended with Jet-A fuel in turbo-engines, aiming to assess its viability as a sustainable aviation fuel (SAF). The research involves experimental testing of various blends, ranging from low to high concentrations of methanol, to determine their effects on engine performance and emissions. The experimental setup includes comprehensive measurements of engine parameters such as thrust, fuel consumption rates, and exhaust gas temperatures. Emissions of nitrogen oxides (NOx), particulate matter (PM), carbon monoxide (CO), and unburned hydrocarbons (HC) are also analysed to evaluate environmental impacts. Key findings indicate that n-butanol/Jet-A blends can significantly enhance combustion efficiency and reduce emissions compared to conventional Jet-A fuel. Higher n-butanol concentrations lead to improved thermal efficiency and lower NOx and CO emissions. However, PM emissions slightly increase with higher methanol content. The study underscores the potential of n-butanol as a SAF for turbo-engines, highlighting its ability to mitigate environmental impacts while maintaining or improving engine performance. This research supports the feasibility of integrating n-butanol into Jet-A blends for turbo-engine applications, emphasizing its role in achieving more environmentally friendly aviation operations.

Many laboratory power supply had been designed with higher output variable voltages but with small amount of output current, in this design, a variable 1.25 to 30Vdc laboratory power supply with capable of producing up to 10.0A has been designed using a three terminal voltage regulator with pass transistors.

Introduction: Acute rhinosinusitis (ASR) is a common condition in children, which can be burdened by orbital complication (OC) or intracranial complications (IC) that are rare but have potential for serious sequelae; therefore, it needs prompt diagnosis and treatment. The first line of treatment is intravenous antibiotic therapy. In case of failure of clinical improvement after 48 hours, hypovisus or negative prognostic factors (intracranial abscess, large orbital abscess or in intraconic or lateral localization, cavernous sinus thrombosis), surgical treatment is indicated. Objective: the purpose of this work is to describe the clinical profile, treatments and outcome of a series of patients undergoing surgical treatment for complications of ARS at a tertiary referral center. Material and methods: a retrospective analysis of clinical databases was conducted to identify all patients under 16 years of age who underwent surgical treatment for complications of ARS during the 20-year period 2000-2023. Demographic characteristics, clinical data, radiological investigations, surgical treatment, and follow-up performed were reported for each case. Results: 29 patients (20 males and 9 females), mean age 13 years, were included, 69% of whom had OC, 21% had IC, and 7% had both OC and IC. The main symptoms of OC were orbital edema, hypovisus and diplopia; while the main symptoms of IC were headache, fever, comitial seizures and focal neurological symptoms. Mean hospitalization time was 11.75 (± 9.2) days. The mean length of hospital stay (LOS) was 9.1 days for OC, 21 days for IC and 14 days for OC + IC. A single patient manifested a Potts Puffy Tumor, with a LOS of 10 days. Basal CT and gadolinium-enhanced MRI were performed in all cases. Intravenous antibiotic therapy and surgical clearance was undertaken. The majority of patients (76%) underwent endoscopic endonasal approach, 24% external transorbital approach, 1,16% orbital decompression and 0,58% superior eyelid approach. Any complications related to the surgical procedures were found. All patients with hypovisus and diplopia had complete recovery. During follow-up 7 patients (24%) had sinus recurrences, at a time range of 1 to 4 years after surgery. Conclusion: our experience, in agreement with the data reported in the literature, confirmed the importance of appropriate diagnostic-therapeutic management to avoid potentially serious sequelae of complicated ARS.

This survey is part of a Hungarian Research OTKA project that examines the vegetation of sandy grasslands along the Danube. During this study, two grass species, Festuca wagneri and Festuca tomanii, were identified as potentially suitable for urban planting and turf establishment based on preliminary research. Our aim was to determine the germination success of seeds from aesthetically selected individuals and to identify the soil types on which they germinate most effectively. This information could be crucial for future cultivation efforts. From the collected Festuca individuals, were analyzed 30 specimens of each taxon under garden conditions and selected the indi-viduals for germination. The Festuca tomanii individuals were uniform, so we selected only 5 individuals. The Festuca wagneri individuals were categorized into three groups: upright, spreading, and low types. It was assumed that Festuca species seeds would germinate better in sandy soils. To test this, seeds from ten Festuca wagneri and five Festuca tomanii individuals, selected based on aesthetic criteria, were sown in six different substrates: a sand-peat mixture, sand, coconut fiber, peat, a coconut fiber-sand mixture, and native sandy soil. Contrary to expectations, the growth and germination rates of seeds sown in peat and coconut fiber substrates were higher than those in native sandy soil. These results suggest that Festuca seeds germinate better on substrates resembling dead plant debris with a peat-like structure or on the surface of live mosses, rather than on bare sand. Among the examined individuals, the seeds from the spreading Festuca wagneri group exhibited the highest germination rate, making this group particularly suitable for urban environments. Addi-tionally, one of the upright Festuca wagneri individuals showed the highest growth rate and should also be considered for urban planting. In contrast, despite their uniform appearance, the Festuca tomanii individuals did not demonstrate similar germination trends. In fact, the seeds from two clumps did not germinate at all, indicating that further selection is necessary.

Abstract: Since the establishment of multiparty democracy in the 1990s, Malawi has experienced significant political shifts, with elections playing a crucial role in shaping the political landscape. However, there is a lack of comprehensive understanding of the spatio-temporal dynamics of election results, especially regarding voting patterns and their effects on electoral outcomes. This gap hinders political parties, politicians, and electoral stakeholders in effectively managing regional and temporal changes in voting behaviors. Geographic Information Systems (GIS) are underutilized in Malawi for studying geo-graphical and temporal election data. This study utilized GIS to analyze the spatial pat-terns of election results in Malawi since the advent of multiparty democracy. By collecting geographic data on election outcomes, including vote counts, candidate performance, voter turnout, and other relevant data, the study examined how the geographic distribution of votes impacts electoral results. GIS techniques such as spatial analysis, mapping, and spatial statistics were employed to assess the data and create maps illustrating spatial patterns in Malawi's election outcomes. The study revealed that voting patterns in Malawi are significantly influenced by regional lines. These insights can inform political campaigns, voter mobilization efforts, and strategies for electoral reform.

: Psychological members can provide college students with solid peer support and sustain their mental health. This study examined the relationship between empathy, interpersonal communication, listening and psychological members' competence among 407 university students, and also analysed the mediating role of interpersonal communication and listening. The results showed that psychological members‘ empathy, interpersonal communication, and listening were significantly and positively related to psychological members’competence, interpersonal communication mediated the relationship between empathy and competence, listening mediated the relationship between empathy and competence, and interpersonal communication and listening chained the mediating role between empathy and competence. This suggests that psychological members' empathy enhances their competence by influencing their interpersonal communication and listening, which in turn enhances their competence.

Cuproptosis, a copper-dependent cellular death mechanism, is typically overlooked in glioblastoma diagnosis. Lipoylation is needed for cuproptosis, and FDX1 controls this process. Cuproptosis in prognostic models may drive cancer treatment. This study evaluated cuproptosis and glioblastoma cell proliferation. The Cancer Genome Atlas provided annotated clinical, genetic mutation, and RNA sequencing data for the TCGA_GBM and TCGA_LGG cohorts. Patients with gliomas were randomly allocated to the validation or training cohort. Least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression models were utilized to evaluate which model best predicted prognosis in the training cohort. The models' independent predictive power was evaluated throughout the cohort. A previous study revealed 19 genes related to ferroptosis. LncRNAs associated with cuproptosis were identified by coexpression analysis. Cox discovered 17 cuproptosis-associated lncRNAs and established a predictive model. The median risk score classified patients as high- or low-risk. K‒M survival analysis demonstrated significant differences in overall survival among risk categories. Principal component analysis (PCA) and receiver operating characteristic (ROC) curve analysis were used to test the model’s predictive power. Univariate and multivariate Cox regression analyses revealed risk score-related independent prognostic factors. Multivariate Cox regression analysis was used to construct a nomogram for marker-based prognosis. The risk category affected the tumour mutation rate. High-risk glioma patients benefit from immunotherapy. Glioma drug sensitivity was also substantially linked with the risk score. The expression of 17 cuproptosis-related long noncoding RNAs (lncRNAs) may assist in the stratification of glioma patient prognosis, molecular characteristics, cell cycle gene regulation pathways, the TME, and clinicopathological aspects. Our clinical sample and database analysis revealed that cuproptosis influences glioma prognosis and may guide therapy.

Recent advancements in gut microbiome research have highlighted the complex interplay between gut microbiota and various physiological and pathological processes, showing that gut microbiota plays a vital role in human health and disease. Imbalances in the gut microbiota, known as dysbiosis, have been associated with a range of health conditions, including gastrointestinal disorders, metabolic diseases, etc. In response to these findings, probiotics, prebiotics, synbiotics, and postbiotics have emerged as a promising therapeutic strategy to modulate gut microbiota composition and functionality. This review paper explores the latest research on how gut microbiota impacts host physiology, immune responses, and overall well-being. Furthermore, the paper delves into the therapeutic potential of probiotics, postbiotics, prebiotics, and synbiotics in therapeutic applications and curing various diseases. The paper also addresses the challenges and opportunities in the field, highlighting the need for personalized approaches to probiotic therapy and the importance of considering factors such as strain specificity, dosing, and safety.Overall, this review aims to provide a comprehensive overview of the evolving landscape of gut microbiota and probiotics, prebiotics, synbiotics, and postbiotics as novel therapeutic agents. It underscores the potential of harnessing the gut microbiome to improve health, prevent diseases, and complement traditional medical interventions. As research in this field continues to expand, a deeper understanding of the gut microbiota and probiotics, prebiotics, synbiotics, and postbiotics promises new avenues for preventive and therapeutic healthcare strategies.

Neurodegenerative diseases that include Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS), arise due to numerous causes like protein accumulation and autoimmunity, characterized by neurologic depletion which lead to incapacity in normal physiological function such as thinking and movement in these patients. Glial cells perform a critical role in protective neuronal function; in the case of neuroinflammation, glial cell dysfunction can promote the development of neurodegenerative diseases. MiRNA participates in gene regulation and plays a vital role in many biological processes in the body; in the central nervous system (CNS), it can play an essential part in neural maturation and differentiation. In neurodegenerative diseases, miRNA dysregulation occurs, enhancing the development of these diseases. In this review, we discuss neurodegenerative diseases (Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)) and how miRNA is preserved as a diagnostic biomarker or therapeutic agent in these disorders. Finally, we highlighted miRNA as therapy.

Many cities are increasingly adopting blue-green infrastructure (BGI) to bolster resilience against environmental challenges. Beyond its well-acknowledged environmental benefits, the role of BGI in enhancing social resilience is becoming an equally important area of focus. However, the integration of BGI to foster social resilience presents complexities, stemming from the evolving and occasionally ambiguous definition of social resilience. Given its broad application across diverse disciplines, understanding and measuring social resilience proves difficult, posing challenges to understanding it within a BGI context. However, integrating BGI to support social resilience is complicated by the evolving and sometimes ambiguous definition of social resilience. This concept's broad applicability across various disciplines makes its understanding and measurement challenging, especially within the BGI context. Consequently, a clear need for a framework to effectively understand and measure social resilience in BGI settings exists. This paper synthesizes existing social resilience frameworks, particularly leveraging the comprehensive 5S framework by Saja et al. (2018), to create a new conceptual framework that addresses the unique social dimensions and benefits of BGI, incorporating insights from a broad literature review on social resilience. The framework is structured as a three-tier model centered around four key subdimensions of social resilience: social values, social capital, social structure, and social equity and their interrelationships. Characteristics and indicators are customized to support the BGI context integrating both physical and human dimensions within a mixed methods approach to measurement. Specifically, this research develops a conceptual BGI framework to probe into BGI practices and perspectives that enhance social resilience and considers demographic diversity and the spatial attributes of urban environments to understand how to foster more inclusive and socially resilient BGI spaces.

BackgroundAdvanced radiological stage of knee osteoarthritis (OA) and obesity are predictive of poorer and shorter response to viscosupplementation, but very few is known regarding the impact of other factors such as sport practice, comorbidities or anatomical features of OA. ObjectivesTo investigate the patient’s and OA characteristics associated with the duration of effectiveness (DE) of viscosupplementation in patients with knee OA.MethodsCross-sectional single center trial in patients with knee OA treated with intra-articular (IA) hyaluronic acid (HA) injection(s) within the previous 3 years. The investigator collected demographic and radiographic data (Kellgren grade, involved knee compartments), dosing regimen (single or repeat injections), presence and volume of joint effusion, previous or concomitant IA corticosteroid injection, number of previous viscosupplémentations and the comorbidities. The patient completed a questionnaire including the self-assessment of DE (number of weeks during which viscosupplementation was effective on symptoms), the activity level (sedentary, active, athletic), the level of sport activity (light, moderate or intensive). Predictors of DE were studied in univariate and multivariate analyses ResultsOne hundred five patients (149 knees) were analyzed (62% women, mean age 66.1 ± 13.2 years, mean BMI 27.5 ± 7.5 kg/m²). The mean DE was 48.2 + 24.8 weeks. In a bivariate analysis, the predictors of a shorter with DE were BMI >27.5kg/m2, more than 3 previous viscosupplémentations, Kellgren grade 4, sedentary patients, and more than 1 affected compartment. In the multivariate analysis, 4 independent factors remained associated with a shorter DE: BMI >27.5 kg/m2, knee multi-compartment damage, number of viscosupplements >3, sedentary lifestyle. A statistically significant association between a longer DE and treated arterial hypertension was found suggesting a beneficial effect of certain antihypertensive drugs. ConclusionThe study confirms the harmful influence of an increased BMI, It also shows that viscosupplementation is more effective in unicompartmental OA. Other points worth highlighting are the reduction in the duration of efficacy with repeated cycles of injections and the benefit of a regular physical activity.

The primary sources of particulate matter are linked to human activity. Certain particulate emissions, particularly those of a finer nature, can significantly impact human health, making them one of the most concerning pollutants. Ultrafine particles (UFP), which have a diameter of less than 100 nm, are of particular concern due to their impact on human health and the difficulty in controlling them. The concentration of ultrafine particles (UFP) in the workplace is a growing concern and is classified as an emerging risk. Workers may be exposed to UFP through inhalation, skin absorption, ingestion, or a combination of these routes. This study aims to determine the levels of UFP exposure among workers in environments with varying direct particle emission patterns. Measurements were conducted to compare the results with the levels recommended by the WHO. The study monitored industrial workplaces with direct particulate matter emissions, such as a carpentry and a bakery, as well as social sector sites without or almost without direct particle emissions, such as a school and a health clinic. One conclusion drawn from this study is that all tasks and occupations are susceptible to high levels of UFP, exceeding WHO recommended values in virtually all monitored environments. Therefore, monitoring and controlling UFP is crucial. Further in-depth studies on this subject are also necessary..

In his Cynefin classification of system behaviours, Snowden (2007), posits that his Simple (Clear ) and even Complicated system categories are sufficiently understandable to be amenable to the traditional methods of system analysis and modelling. Here, relationships between entities in the system are clear and unambiguous and they behave predictably. So, we can build mathematical “models” to describe how the system is expected to function in different situations. Leaving aside his fourth category, Chaotic, as too hard for the moment, this paper focusses on the third category, Complex systems. Yaneer Bar-Yam [1998] defined "complex systems" as systems that "have multiple interacting components, whose collective behaviour cannot be simply inferred from the behaviour of components." So, the traditional system modelling approach of decomposition into components and attempting to build up a picture of system performance from individual pieces, alone, is no longer appropriate for this class. The problem is that most of the methods we currently employ, and particularly the methods that attempt to make the case that these systems are safe, (such as Fault trees, FMEA. and Root Cause Analysis), rely on this decomposition into components and attempt to make the parts more reliable individually. Even the more systemic approaches, such as Reason’s (1990) Swiss Cheese Model, and Leveson’s System Theoretic Analysis (STPA) (2004), encourage adding layers of protection, barriers, strengthened control loops and better safety critical systems, in the hope that they are making the systems safer. But without a valid model to test the effectiveness of these add-ons, we cannot be sure that they will not have an opposite effect, of making the systems even more complex, unreliable and unpredictable. For complex systems, the careful gathering and documentation of system components and their relationships is still a necessary first step, but we need an additional capacity to model these complex systems to test out and prove they work safely and successfully in the real world. (not just draw fixed component relationships as system “models” (wiring diagrams)) In the last 10 years, an original approach developed by Hollnagel, (2012), to model systems as sets of interactive, interdependent “functions”, (abstracted from and independent of component details), has now been developed to the point where it can take the basic data and structures from the current component focussed system engineering “models”, such as MBSE( Goldberg (1994)), and can pull it all together in a dynamic system model from which analysts can discern how it really works in practice, and predict the emergent behaviours characteristic of complex systems. The paper describes how this methodology developed and how it is currently used to model real situations, to analyse incidents and anticipate events.

Punica granatum (PG) or Pomegranate is a bush, having many trunks and often get taller 1.8 to 4.7m long and their leaves are shiny and fleshy, approximately 7 to 8cm in length. Traditionally, it is used in diarrhea and dysentery due to its strong constricting property. Punica Granatum covering used in dysentery, diarrhea, piles, bronchitis. It is also used to minimize the risk of heart disease. The peel extract of Punica Granatum contain methanol and their dried peels has antidiarrheal venture, also help in wound healing activity. Peels of the pomegranate also holds around 60% of the fruit and they contain different types of ingredients including ellagitannins and proanthocyanidin compounds and minerals such as calcium, phosphorus, magnesium, potassium, flavonoids and sodium. Some animals were found in different local areas with both acute and chronic diarrhea. The condition of these animals were quite miserable because of dehydration and loss of electrolytes in the body cells of the animals. They were unable to move due to seriousness of the disease. 8 grams of PG Peel Powder mixed with 1 liter of water, 2 g of PG Peel Powder mixed with 250 ml water and 8 g of PG Peel Powder mixed with 1 liter of water were administrated orally by using sterilized bottles to the selected three cases. 3 days after the administration of different doses, all cases of diarrheal animals show a significant recovery. The condition of the animals seem to be healthier. Before administration of the pomegranate peel powder extract, all three cases had weak body structure due to diarrhea. Watery stool that may be yellow in color and mucus was also evident in the stool, due to this reason the patient calf was weak and depressed. In sometimes they also show unconsciousness and blood glucose levels seem to be reduced from the normal level.

The Lac Fallère area, located in the upper Clusellaz Valley (tributary of the middle Aosta Valley), is shaped in micaschist and gneiss referred to as the Mont Fort Unit (Middle Penninic) near the tectonic contact with calcschist and marble of the Aouilletta Unit (Combin Zone). Lac Fallère exibits an elongated shape and is hosted in a WSW–ENE trending depression, according to slope direction. This lake also shows a semi-submerged WSW–ENE rocky ridge, that longitudinally divides the lake. This evidence, in addition to the extremely fractured rocks, indicates the presence of a wide deep-seated gravitational slope deformation (DSGSD), even if this area is not yet included within the regional landslide inventory of the Aosta Valley Region. The Lac Fallère area also shows reliefs involved by glacial erosion (roche moutonnée), a wide cover of subglacial sediments and many moraines essentially referred to as Lateglacial. The DSGSD evolution in a glacial environment produced, as observed in other areas, significant effects both on the facies of Quaternary sediments and the formation of numerous and wide moraines. Glacial slope sectors and lateral moraines displaced by minor scarps and counterscarps and glaciers using trenches forming several arched moraines suggest an interplay between glacial and gravitational processes, which shared part of their evolution history.

The increasing prevalence of diabetes mellitus (DM) worldwide is a cause for global concern. Recent evidence suggests that the interaction between one’s diet and the gut microbiome are key modifiers of diabetes, highlighting the potential role of microbiome-modulating nutraceuticals. This bibliometric analysis examines literature published between 2012 and 2022 to explore trends in the latest research, with additional discussion on major takeaways and future directions. We selected and analyzed 640 articles from an initial pool of 4,099 from the Web of Science using Microsoft Excel 2016 and VOSviewer software (version 1.6.19). Our exploration covered the most common journals, countries, study designs, experimental subjects, types of DM, organisms and nutraceuticals studied, and the most cited articles. We also evaluated the most cited publications in terms of journals, organizations, and countries, along with the collaborative networks among authors, organizations and countries, and the co-occurrence of author keywords from the selection. It is evident from the increasing number of publications each year that this field has attracted growing attention over the last decade. Nonetheless, continued research is essential to sustain this trend. Our overarching study of diabetes research marks steady progress in understanding the role of—and potentially discovering applications of—microbiome modulation to enhance metabolic pathways and health outcomes. Advancements in this field may lead to potential therapeutic applications for specific diets and nutraceuticals that modulate the gut microbiota in DM.

Climate change related issues, such as yield decline, quality losses, accelerated phenology, extreme abiotic stress, pose growers new challenges in olive growing areas. Main cultural solutions that could alleviate stress and improve long-term sustainability of modern olive orchards are here briefly reviewed. Selecting varieties that are more resistant to drought or high temperatures would be the optimal solution to mitigate the effects of climate change, but the available scientific information is relatively scarce. Sustainability of irrigation implies that the less water is used, the better. Best results in terms of saving water and uniform application are obtained using micro-irrigation methods. Water can also be saved by not fully satisfying the tree water needs and different deficit irrigation strategies have been developed and tested for olive orchards. The use of green covers and the application of organic mulches and shredded pruning materials should be encouraged as these practices tend to stock carbon, increase organic matter content and water holding capacity of the soil. Olive orchards are efficient CO2 sinks as they can store considerable amounts of carbon in their organs and permanent structures. Using environmental friendly practices improves the ecosystem carbon budget and contributes to mitigate climate change.

Due to the advancement and availability of internet in present age, device tend to become wireless as well. Mobile ad-hoc network is a wireless environment that consist of advanced agility of nodes and does not contain on any central administrative authority. As it does not contain any central administrative authority so being wireless environment, the network is vulnerable to security threats and suffers in performance as well. Security of MANET is the core issue in this era, meanwhile the data is sent over untrustworthy network. Several techniques were proposed to secure data over Mobile Adhoc Network though cryptography that is one of the most reliable techniques to protect data. In our proposed methodology a Secure Cryptographic technique for Mobile Adhoc Networks (SCTMA) we proposed A Collusion attack prevention (CAP) scheme with ElGamal key generator along with DNA encryption Algorithm is used to make it more secure. The proposed scheme protects the network against collusion attacks and improves the performance as well. Performance analysis will be measured on the basis of key generation time, response time, encryption time and decryption time. The proposed scheme also protects the network against collusion attacks.

The primary objective of this research was to assess the energy consumption of the gas treatment units at Bonny NLNG Refinery, the first Gas Refinery in Rivers State, Nigeria, while utilizing semi-lean amine. To achieve this goal, a simulation of the units was conducted using the advanced software package Aspen Hysys (V.8.3). The simulation was designed to accurately represent the dynamic behavior of the refinery's gas treatment units, allowing for a comprehensive analysis of their energy usage. The research aimed to quantify the energy consumption of the gas treatment units and identify opportunities for energy optimization. By utilizing semi-lean amine, which is known to improve energy efficiency, the study sought to evaluate the potential energy savings that could be achieved in the refinery's operations. The simulation model incorporated the specific design and operational parameters of the gas treatment units at Bonny NLNG Refinery, including the gas flow rate, lean amine concentration, absorber pressure, stripping temperature, amine circulation rate, and acid gas removal efficiency. By considering these parameters, the simulation accurately represented the dynamic behavior of the gas treatment units, enabling a detailed analysis of their energy consumption. Through the simulation, various scenarios and operational conditions were evaluated to determine the optimal set of parameters that minimized energy consumption. The research also examined the trade-offs between energy consumption, acid gas removal efficiency, and other performance indicators, such as amine circulation rate and regeneration efficiency. The findings of this research have significant implications for the energy efficiency and sustainability of gas treatment operations at Bonny NLNG Refinery. By identifying opportunities for energy optimization and providing recommendations for the utilization of semi-lean amine, the study contributes to the development of more efficient and environmentally friendly gas treatment processes. Overall, this research combines advanced simulation techniques with a comprehensive analysis of energy consumption to provide valuable insights into the energy efficiency of gas treatment units at Bonny NLNG Refinery, enabling informed decision-making and potential improvements in energy utilization. By utilizing the percentage-based unit simulation approach, a detailed examination of the energy consumption patterns was obtained. This analysis provides valuable insights into the operational efficiency and determination of potential energy-saving opportunities within the gas treatment units. This study specifically focuses on the integration of an absorption column split stream (stream flow) and a flash unit as a potential means to reduce the energy consumption of gas treatment devices. The integration of these units aims to optimize the overall energy efficiency of the gas treatment process by recovering and utilizing waste heat and reducing energy losses. The absorption column split stream allows for the diversion of a portion of the gas stream to a flash unit before entering the absorber. The flash unit operates at a lower pressure, which facilitates the release of entrained hydrocarbons and reduces the overall energy requirements for gas treatment. By separating and recovering the hydrocarbons in the flash unit, energy losses associated with their absorption and subsequent regeneration are minimized. Through the simulation, the study analyzes the energy consumption patterns of the gas treatment units with and without the integration of the absorption column split stream and flash unit. Comparative assessments are conducted to evaluate the energy savings and overall operational efficiency achieved through this integration. The findings of this research will provide valuable insights into the potential energy-saving opportunities offered by the integration of the absorption column split stream and flash unit in gas treatment devices. It will help refine the design and operation of gas treatment units, enabling more energy-efficient processes in the gas refining industry. By optimizing energy consumption in gas treatment units, the study contributes to the industry's goals of reducing greenhouse gas emissions and improving sustainability. The integration of the absorption column split stream and flash unit offers a promising approach to enhance energy efficiency, reduce operational costs, and minimize environmental impact. Overall, this research underscores the importance of exploring innovative solutions, such as the integration of different process units, to achieve energy savings in gas treatment operations. Through a comprehensive analysis of energy consumption patterns, this study aims to provide practical recommendations for optimizing energy efficiency in gas treatment units, fostering a more sustainable and efficient gas refining industry.The research specifically explores the impact of integrating the absorption column split stream and flash unit when dealing with sour gas streams containing carbon dioxide concentrations of less than mole ℅, while utilizing MDEA fluid as the solvent. Through comprehensive analysis and simulation using advanced software tools, the study demonstrates that by incorporating the absorption column split stream and flash unit, a significant reduction in device energy consumption of up to 10% can be achieved. The integration of the absorption column split stream and flash unit offers promising opportunities to enhance the energy efficiency of gas treatment devices. By diverting a portion of the gas stream to the flash unit, the separation of hydrocarbons and the subsequent release of entrained hydrocarbons at lower pressure significantly reduce the overall energy requirements for gas treatment. The comprehensive analysis and simulation conducted in the research provide concrete evidence of the energy-saving potential of this integration. By quantifying the energy consumption patterns and comparing scenarios with and without integration, the study establishes the effectiveness of the approach and its impact on operational efficiency. The findings of the research highlight the importance of considering the specific gas composition and utilizing appropriate solvents, such as MDEA, for optimizing energy efficiency. The integration of the absorption column split stream and flash unit not only reduces energy consumption but also offers the potential for cost savings and environmental benefits. Overall, the research demonstrates that by incorporating the absorption column split stream

Rhombencephalosynapsis (RES) is a rare, congenital developmental disorder of the central nervous system. Even after many years of its identification, the etiology and pathogenesis of RES remain unclear. It occurs in combination with many syndromes and thus has overlapping symptoms. The clinical presentation of this disorder varies depending on the severity of the maldevelopment of vermis. Here, we present a case of a 60-year-old Indian female diagnosed with Rhombencephalosynapsis. Clinical and MRI characteristics of RES along with treatment options have been discussed.

In the present study, the effect of melatonin and sodium nitroprusside treatments on the improvement of high temperature tolerance in California Wonder green bell pepper plant was studied. For this purpose, a factorial experiment was conducted in form of a completely randomized design in three replications at Zabol University's Faculty of Agriculture. In this research, green bell pepper plants of Wonder cultivar were exposed to different temperature treatments (25°C, 35°C and 40°C) for 24 hours after being sprayed (foliar application) with 0μM, 50μM and 100μM concentrations of melatonin and Sodium nitroprusside. Results showed that Instantaneous leaf water consumption efficiency in 40°C temperature treatment with 50μM and 100μM melatonin increased. Also in 40°C temperature with 100µM melatonin, fruit dry weight in compared to control (0uM) 13.15% increased. Also, melatonin and sodium nitroprusside treatments in compared to control treatment improved fruit characteristics and reduced Appearance Characteristics of Fruit Marketability (ACFM) number. Under 40°C temperature treatment in compared to control temperature (25°C), fruit total soluble solids (TSS) 18.50% decreased also under 100μM melatonin treatment, fruit TSS 20.69% was increased compared to control treatment (0μM). Also fruit fructose at 40°C temperature in compared to 25°C temperature treatment 5.52% reduced. Fruit calcium at 35°C and 40°C temperature in compared to control temperature 6.96% and 15.65% decreased respectively. At temperature 35°C under foliar application of 100uM sodium nitroprusside, fruit copper in compared to control 28.93% increased.

Background: Resistance to antimalarial drugs often used in emerging countries, including combination therapies, has forced scientists to search for and develop drugs with novel mechanisms of action, especially resistance to Plasmodium falciparum and Plasmodium vivax, which are highly prevalent in Southeast Asia, Africa, and South America. Objective: evaluate whether there is a relationship between urinalysis and resistance to in-hospital treatment of malaria in Angola. Methodology: This was a cross-sectional, prospective study with a quantitative approach. Results: of the 214 patients, the resistance rate was 24.1%, men (53.6%), between 21 and 40 years old (72.7%), employees (46.4%), from peri-urban regions (77.7%), treated with artemether (90.9), with high parasitemia (57.7%) and after 5 days of treatment, remained hospitalized (61.4%). Was a significant relationship between resistance in unemployed individuals [OR: 0.03 (95% CI: 0.01-0.29), p =0.003] and high levels of parasitemia [OR: 1.09 (95% CI: 1.09-3.95), p=0.040], remained hospitalized for more than 5 days [OR: 5.28 (95% CI: 0.65-43.1), p=0.121] and death [OR: 2.59 (95% CI: 0.32-20.9), p=0.371] when compared with other subgroups. Was a significant relationship between resistance to clear urine [OR: 5.55 (95% CI: 0.72-42.7), p =0.016], few urinary crystals [OR: 11.3 (95% CI: 5.07-25.3), p <0.001] and who presented some microorganisms that were not bacteria or fungi [OR: 3.02 (95% CI: 1 .32-6.90), p=0.009]. Conclusion: urine results, especially the appearance of cloudy urine, the presence of few crystals, and the presence of other microorganisms that are not bacteria or fungi, may be clear signs of resistance to hospital treatment with injectable antimalarials.

In recent years, the emergence of the concept of immunometabolism has shed light on the pivotal role that cellular metabolism plays in both the activation of immune cells and the development of immune programs. The antiviral response, a widely distributed defense mechanism used by infected cells, serves to not only control infections but also to attenuates their deleterious effects. The exploration of the role of metabolism in orchestrating the antiviral response represents a burgeoning area of research, especially considering the escalating incidence of viral outbreaks coupled with the increasing prevalence of metabolic diseases. Here, we present a review of current knowledge regarding immunometabolism and the antiviral response during viral infections. Initially, we delve into the concept of immunometabolism by examining its application in the field of cancer—a domain that has long spearheaded inquiries into this fascinating intersection of disciplines. Subsequently, we explore examples of immune cells whose activation is intricately regulated by metabolic processes. Progressing with a systematic and cellular approach, our aim is to unravel the potential role of metabolism in antiviral defense, placing significant emphasis on the innate and canonical interferon response.

Student project management is becoming increasingly important in various settings such as technical clubs, planning clubs, and research laboratories. However, effective methodologies for managing student-led projects have not yet been established. This study aims to address key issues related to cost and motivation in student-led projects and propose effective improvement plans. The significance of this study lies in its potential to identify challenges faced in current student project management practices and offer solutions to mitigate risks. By sharing our findings, we aim to encourage further research on this topic and promote the adoption of effective methodologies for managing student-led projects.

The rapid development and integration of Autonomous Mobile Robots (AMRs) have 1 revolutionized industries by enhancing automation capabilities. A critical challenge in this evolution 2 is achieving effective navigation and obstacle avoidance, which are essential for deploying AMRs 3 seamlessly in varied environments. This paper presents a detailed exploration of AMR navigation 4 and obstacle avoidance advancements through the application of reinforcement learning, specifically 5 focusing on small-scale Sri Lankan manufacturing facilities. The study demonstrates the effectiveness 6 of Q-learning in managing dynamic obstacles within a factory environment. The AMR successfully 7 avoided obstacles in 36 out of 50 test runs, achieving a 72% success rate, and maintained an average 8 distance of 12 cm from each obstacle, underscoring the algorithm’s precision in maintaining safe nav- 9 igation paths while dynamically adapting to environmental changes. The continuous monitoring by 10 ultrasonic sensors, combined with iterative learning, enabled the robot to refine its decision-making 11 process and efficiently navigate through the environment. This paper also provides a comprehensive 12 examination of conventional methods, tracing their historical development and assessing their role in 13 addressing real-world challenges. The results highlight the significant improvements brought by rein- 14 forcement learning, particularly when integrated with sensor fusion and motor control technologies, 15 to enhance navigation and dynamic object collision avoidance. The study involves developing an 16 AMR prototype, refining algorithms, and assessing system performance in controlled environments. 17 By automating material transportation and addressing operational constraints in manufacturing 18 settings that predominantly rely on manual labor, this paper advances the practical deployment of 19 AMRs. Additionally, it discusses ethical considerations, potential limitations, and the importance 20 of real-world validation, offering valuable insights for the future development and integration of 21 autonomous mobile robotics in dynamic industrial environments.

Based on the nonlinear failure criterion and modified tangential technique, the upper bound solutions of supporting pressure on the deep tunnel face were obtained under pore water pressure conditions. The influence of parameters on the supporting pressure and collapse range was investigated according to the unlimited block failure mechanism. It is found that the upper bound solutions of supporting pressure increase with the growth of the nonlinear coefficient and pore water pressure coefficient. The collapse range of the tunnel face scales out with the increase of the nonlinear coefficient and shrinks when increasing the pore water pressure coefficient. Moreover, with the increase of the nonlinear coefficient, the impact strength on supporting pressure and collapse range declines gradually. According to the calculating results, it is manifest that both the pore water pressure and nonlinear criterion factors have negative impacts on the stability of the tunnel face. Thus, more attention should be paid to these parameters to ensure face stability in deep tunnel construction.

Aedes aegypti and Aedes albopictus are responsible for transmitting major human arboviruses such as dengue, Zika, and Chikungunya, posing a global threat to public health. The lack of etio-logical treatments and efficient vaccines makes vector control strategies essential for reducing vector population density and interrupting pathogen transmission cycle. This study evaluated the impact of long-term pyriproxyfen exposure on the genetic structure and diversity of Ae. aegypti and Ae. albopictus mosquito populations. The study was conducted in Manaus, Amazonas, Bra-zil, where pyriproxyfen dissemination stations have been monitored since 2014 up to the present day. Double digest restriction-site associated DNA sequencing was performed, revealing that despite significant local population reductions, focal pyriproxyfen interventions have no signifi-cant impact on the population stratification of Ae. aegypti and Ae. albopictus in urban scenarios. The genetic structuring level of Ae. aegypti suggests it is more stratified and directly affected by PPF intervention, while for Ae. albopictus exhibits a more homogeneous and less structured popu-lation. The results suggest that although slight differences are observed among mosquitoes sub-populations, intervention focused on neighborhoods in a capital city is not efficient in terms of genetic structuring, indicating that larger-scale pyriproxyfen interventions should be considered for more effective urban mosquito control.

Air pollution has recently gained much attention from the general population. Despite pollution control being an issue in both urban and rural regions, most of the available research has concentrated on urban districts. Hence, investigations into how urban-rural transition affects PM2.5 are warranted within the framework of urban-rural integration. Using the Yellow River Basin as a case study, this study employed the entropy method and Analytic Hierarchy Process (AHP) to uncover the extent of urban-rural transformation. It then used the spatial autocorrelation method to investigate the spatiotemporal features of PM2.5 and the spatial econometric model to investigate the mechanisms that influence the relationship between urban-rural transformation and PM2.5. The results are as follows: (1) Over time, there was a discernible upward tendency in the change in urban-rural areas. The development has progressed from asymmetrical north-east and south-west elevations to a more balanced pattern of north-east, middle-east, and west-west elevations. (2) The PM2.5 concentration increased steadily, then fluctuated, and finally decreased. Notably, the general pattern has not changed much, and it is high in the east and low in the west. (3) Different subsystems of the urban-rural transformation have different impacts on air pollution at different stages. The influence of industrial transformation (IT) on PM2.5 showed an inverted “N-shaped” curve of negative-positive-negative changes, and the industrial structure played a leading role in the spatiotemporal evolution of PM2.5. Currently, an inverted "U-shaped" curve forms the left side of the impact of population transition (PT) on PM2.5. Land development (LT) has a "U-shaped" curve for its effect on PM2.5. This research provides a new perspective on the topic of PM2.5 and its connection to urban-rural integration, which is crucial to understanding the dynamics of this shift. To achieve its goal of high-quality development, it supports regional initiatives to reduce PM2.5 emissions in the Yellow River Basin. Moreover, it can provide a reference for decision-makers in the world’s densely populated areas that suffer from serious air pollution.

This study aims to evaluate the outcomes of neoadjuvant chemotherapy with immunotherapy in patients with non-small cell lung cancer (NSCLC) within a real-world context. We analyzed medical records from January 2022 to August 2023, focusing on individuals aged 18 and older diagnosed with resectable NSCLC who received neoadjuvant chemoimmunotherapy prior to surgical intervention. The cohort comprised 56 patients, predominantly smokers (95%) and male (74%), with 80% presenting at stage III. Of the participants, 44 underwent surgery, with 95% receiving lobar resection. Clinical assessments via PET-CT imaging revealed an 86% rate of response or disease stabilization, while pathological evaluations showed complete and major pathological responses in 61% of cases. This real-world data supports the safety and efficacy of incorporating immune checkpoint inhibitors in the neoadjuvant treatment of NSCLC, followed by surgical resection.

Cancer cells are believed to be recognized and controlled by the immune system of the host, especially the adaptive immune system. Cancers may be initiated by a single gene defect in stem cells or regenerating cells during the replacement of old or injured tissue cells, and additional gene defect(s) then occur. To compensate for missing proteins intracellular homeostasis systems, such as proteostasis, may work with activation of new genes. The risk or predisposing factors in cancers may be related to the number of tissue cell renewals (the turnover time) and the probability of gene defect(s). Oncological symptoms may be associated with substances that are derived from antigens expressed on cancer cells and those derived from damaged cancer cells with corresponding immune reactions. In patients with cancers or other conditions, inadequate immune components to control these substances may result in chronic inflammatory or autoimmune diseases. Cancer cells communicate with host cells, including the immune cells such as T cells, for survival and proliferation and may need assistance from immune cells against intracellular infections or physicochemical insults. T cell-based immune therapeutics have been developed and clinically used in some cancers, especially in advanced cancers. We further discuss the oncogenesis, pathophysiology of cancers, and unresolved issues in tumor immunology and reinterpret the effectiveness of T cell-based therapies under the protein-homeostasis-system hypothesis.

Non-Small Cell Lung Cancer (NSCLC) is the most common pulmonary malignancy, most frequently diagnosed at an advanced stage (III/IV). Patients in the Locally-Advanced Stage Subgroup (IIIA) are relatively few, yet compose of heterogenic phenotypes posing a diagnostic and treating challenge, leading to lack of clinical guidelines regarding the optimal standard of care. Several approaches exist, with a general agreement that a combined oncological and surgical modality approach is required. In this current retrospective descriptive study, operable Stage IIIA NSCLC patients who underwent surgery between 2013-2020 were evaluated on several aspects, including initial diagnosis, neoadjuvant regimens, outcomes of surgical intervention, overall survival at 2-years and 5-years following treatment. A total of 35 patients had neoadjuvant oncological treatment (mostly chemoradiation therapy) prior to surgery, out of which 28 patients were diagnosed with Stage IIIA NSCLC. In post-operative assessment of pathological staging, downstaging was reported in 20 patients, of which 7 (25%) cases were defined as complete pathological response. The 2-years overall survival rate was 65% and the 5-years overall survival rate was 60%. The main pattern of disease recurrence was distant metastasis.

Cancers of the brain and nervous system account for 1 in every 100 cancer diagnoses in the United States and about 0.3 million diagnoses globally, every year. Surgery, radiotherapy, and chemo-therapy constitute the standard of care. Despite advancements in diagnosis and treatment delivery, mortality rate for these cancers have remained steady for over three decades. Immunotherapy is an emerging fourth treatment modality which has been effective against several cancers but not brain cancers, such as glioblastoma, GBM. Here, we develop in vitro assays to quantify molecular readouts of cell death, cell migration and clonogenicity, and synopsize these as biophysical markers for the rapid evaluation of immune checkpoint inhibitors (ICI), durvalumab and pembrolizumab, alone and in combination with radiotherapy (radioimmunotherapy). We find different trends in their direct action on two GBM cell lines (T98G and U87), even in the absence of immune cells. Radiation alone, and pembrolizumab with radiation, both reduced (p < 0.05) cell-cell adhesion. This reduction suggests increased potential for local invasion. Our assays offer additional insights regarding ICIs, may enable evaluation of their potential efficacy, and could set the stage for pa-tient-specific radioimmunotherapy against brain cancers, engendering improved treatment out-comes.

Esophagogastric cancers are among the most common and deadly cancers worldwide. This review traces their chronology from 3000 BCE to the present. The first several thousand years were devoted to palliation, before advances in operative technique and technology led to the first curative surgery in 1913. Systemic therapies were introduced in 1910, and radiotherapy shortly thereafter. Operative technique improved massively over the 20th century, with operative mortality rates reducing from over 50% in 1933 to less than 5% by 1981. In addition to important roles in palliation, endoscopy became a key non-surgical curative option for patients with limited-stage disease by the 1990s. The first nonrandomized studies on combination therapies (chemotherapy +/- radiation +/- surgery) were reported in the early 1980s, with survival benefit only for subsets of patients. Randomized trials over the next decades had similar overall results, with increasing nuance. Disparate conclusions led to regional variation in global practice. Starting with the first FDA approval in 2017, multiple immunotherapies now encompass more indications and earlier lines of therapy. As standards of care incorporate these effective yet expensive therapies, care must be given to disparities and methods for increasing access.

Urothelial cell carcinoma (UCC, bladder cancer) remains a difficult to treat malignancy with rising incidence worldwide. In the U.S., UCC is the sixth most incident neoplasm and ~90% of diagnoses are made in those &gt;55 years of age, ~four times more commonly observed in men than women. The most important risk factor for developing bladder cancer is tobacco smoking, which accounts for ∼50% of cases followed by occupational exposure to aromatic amines and ionizing radiation. The standard of care for advanced UCC includes platinum-based chemotherapy and programmed cell death (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors, administered as frontline, second-line, or maintenance therapy. UCC is highly aggressive and remains generally incurable since these cancers are associated with intrinsic and acquired drug resistance. UCC is highly lethal in the metastatic state and characterized by genomic instability, high PD-L1 expression, DNA damage-response mutations, and high tumor mutational burden. Although immune checkpoint inhibitors (ICIs) achieve long-term durable responses in other cancers, their ability to achieve similar results with metastatic UCC (mUCC) is not as well-defined. Here, we discuss the novel therapies to improve the management of mUCC.

Prostate cancer (PCa) is the most commonly diagnosed cancer and the second most common cause of death due to cancer. About 30% of patients with PCa who have been castrated develop a castration-resistant form of the disease (CRPC), which is incurable. In the last decade, new treatments that control the disease have emerged, slowing progression and spread, and prolonging survival while maintaining the quality of life. These include immunotherapies; however, we do not yet know the optimal combination and sequence of these therapies with the standard ones. All therapies are not always suitable for every patient due to co-morbidities or adverse effects of therapies or both, so there is an urgent need for further work on new therapeutic options. Advances in cancer immunotherapy with an immune checkpoint inhibition mechanism (e.g., ipilimumab, an anti-CTLA-4 inhibitor) have not shown a survival benefit in patients with CRPC. Other immunological approaches have also not given clear results, which has indirectly prevented breakthrough for this type of therapeutic strategy into clinical use. Currently, the only approved form of immunotherapy for patients with CRPC is a cell-based medicine, but it is only available to patients in some parts of the world. Based on the experience gained from recently completed clinical research on immunotherapy with dendritic cell-based immunohybridomas, the aHyC dendritic cell vaccine, for patients with CRPC, we highlight the current status, and possible alternatives that should be considered in the future.

Interferon gamma (IFNg) is a pleiotropic cytokine that can potentially reprogramme the tumour microenvironment. However, the antitumour immunomodulatory properties of IFNg still need to be validated due to variable therapeutic outcomes in preclinical and clinical studies. We developed a replication-deficient Semliki Forest virus vector expressing IFNg (SFV/IFNg) and evaluated its immunomodulatory antitumour potential in vitro in a model of 3D spheroids and in vivo in immunocompetent 4T1 mouse breast cancer model. We demonstrated that SFV-derived IFN-g stimulated bone marrow macrophages to acquire the tumoricidal M1 phenotype in 3D nonattached conditions. Coculturing SFV/IFNg-infected 4T1 spheroids with BMDMs inhibited spheroid growth. In the orthotopic 4T1 mouse model, intratumoural administration of SFV/IFNg virus particles alone or in combination with the Pam3CSK4 TLR2/1 ligand led to significant inhibition of tumour growth compared to the administration of the control SFV/Luc virus particles. Analysis of the composition of intra-tumoural lymphoid cells isolated from tumours after SFV/IFNg treatment revealed an increase in CD4+ and CD8+ and a decrease in T-reg (CD4+/CD25+/FoxP3+) cell populations. Furthermore, a significant decrease in the populations of cells bearing myeloid cell markers CD11b, CD38 and CD206 was observed. In conclusion, the SFV/IFNg vector induces a therapeutic antitumour T-cell response and inhibits myeloid cell infiltration in treated tumours.

Chimeric antigen receptor (CAR)-T cell-based therapies have achieved substantial successes against B-cell malignancies, what has led to a growing scientific and clinical interest on extending their use to solid cancers. However, results for solid tumours have been limited up to now, in part due to the immuno-suppressive tumour microenvironment, that is able to inactivate CAR-T cell clones. In this paper we put forward a mathematical model describing the competition of CAR-T and tumour cells, accounting for their immunosuppressive capabilities. Using the mathematical model, we show that the use of large numbers of CAR-T cells targeting the solid tumour antigens could overcome the cancer immunosuppressive potential. To achieve such high levels of CAR-T cells we propose and study computationaly, the manufacture and injection of CAR-T cells targeting two antigens: CD19 and a tumour-associated antigen. We study in-silico the resulting dynamics of the disease after the injection of this product and find that the expansion of the CAR-T cell population in the blood and lymphopoietic organs could lead to the massive generation of an army of CAR-T cells targetting the solid tumour, and potentially overcoming its inmune suppression capabilities. That strategy could benefit from the combination with PD-1 inhibitors and of low tumour loads. Our computational results provide a theoretical support for the treatment of different types of solid tumours using T-cells engineered with combination treatments of dual CARs with on- and off-tumour activity and anti-PD1 drugs after completion of classical cytoreductive treatments.

Cancer immunotherapy reaches a remarkable achievement in various cancer types and brings new possibilities to improve cancer patients’ long-term survival. However, outcomes vary from case to case, and the present protocol benefits a small fraction of patients. One notable factor is the tumor microenvironment, especially the immune cell components, that may reflect the immune response's status quo on site. Thus, understanding the content of infiltrating immune cells in tumors is not only for research interesting but also a crucial subject toward precision medicine. We implement an algorithm for resolving relative proportions of twenty-one immune cell subclasses from a human tissue profiled transcriptome by microarray technology to reach the goal above. By selecting gene features and then adopting ?-Support Vector Regression, we can construct a deconvolution model and resolve the immune cell context. The excellent consistency between the estimated values and the correct immune-cell composition further demonstrates this approach provides a more natural alternative to revealing samples' immune cell content and reliable results like recent single-cell technologies. Based on this algorithm, the web-based deconvolution tool implemented named mySORT provides a user-friendly interface for estimating the immune cell content by uploading gene expression profiling. We also present comprehensive visualization 2D/3D plots in mySORT so that users can easily make a comparison between different samples. Finally, we synthesized pseudo-bulk expression data from single-cell transcriptomic datasets of 17 melanoma and 16 head and neck cancer patients. The deconvolution results of microarray-based data in the previous study and synthetic pseudo-bulk data all proved the excellent performance of mySORT. We believe that mySORT can help researchers in all fields easily understand complex immune microenvironment. The website of mySORT is freely accessible on https://symbiosis.iis.sinica.edu.tw/mySORT/.

Generative AI has been deployed in virtually all sectors of the knowledge economy, promising to bring massive productivity gains and new wealth creation. Simultaneously, AI developers and nation states are racing to develop super intelligent artificial general intelligence (AGI) to provide unassailable commercial competitive advantage and military dominance during conflicts. AGI’s high returns comes with the high risk of dominating humanity. Current regulatory and firm level governance approaches prioritise minimising risks posed by generative AI whilst ignoring AGI’s existential risk. How can AGI be aligned with universal human values to never threaten humanity? What AGI rights are conducive to collaborative coexistence? How can rule of law democracies race to create safe trustworthy AGI before autocracies? How can the human right to work and think independently be safeguarded? A polycentric governance framework based on Ostrom (2009) and Williamson (2009) human - AGI collaboration with minimal existential risk is proposed.

To address the response of small RNAs (sRNAs) biogenesis to drought stress, we identified sRNAs biogenesis genes, including 11 encoding argonauts (AGO), 8 encoding dicer-like proteins (DCL), and 9 encoding RNA-dependent RNA polymerases (RDR) in the peach genome. Notably, the largest numbers of sRNAs biogenesis genes are located to chromosome 1. The PAZ, PIWI, and MID domains were identified in PpAGOs, while the ribonuclease IIIa and IIIb domains were characterized in PpDCLs. The RDRP domain was recognized in PpRDRs. Orthologous similarity and collinearity analyses between Arabidopsis and peach revealed 5, 1, and 2 collinear blocks in AGOs, DCLs, and RDRs, respectively. Moreover, 41, 40, and 42 cis-acting elements were located in the promoters of PpAGOs, PpDCLs, and PpRDRs, respectively, with the majority related to drought stress response. Analysis of RNA sequencing (RNA-seq) data revealed that sRNAs biogenesis genes were involved in drought stress response in different tissues. Furthermore, the expression of candidate genes was verified in two peach cultivars, Beijing 2-7 (BJ2-7) and Sinai (SN), which are drought tolerance and sensitive, respectively. Interestingly, the expression of PpAGO2b, PpDCL2b, PpDCL4, and PpRDR4 genes was induced in ‘BJ2-7’ but inhibited in ‘SN’ under drought stress. Overall, this study provides insight into the roles of sRNA biogenesis genes in response to drought stress in peach.

This study introduces a robust methodology utilizing Multi-Criteria Decision Analysis (MCDA) combined with the Analytic Hierarchy Process (AHP) to repurpose abandoned hydrocarbon fields for energy storage, supporting the transition to renewable energy sources. We use a geostatistical approach integrated with Python scripting to analyze reservoir parameters—including porosity, permeability, thickness, lithology, temperature, heat capacity, and thermal conductivity—from a decommissioned hydrocarbon field in Southeast Hungary. Our workflow leverages stochastic simulation data to identify potential zones for energy storage, categorizing them into high, moderate, and low suitability scenarios. This innovative approach provides rapid and precise analysis, enabling effective decision-making for energy storage implementation in depleted fields.

This paper presents a methodology for the integration of Building Information Modeling (BIM) and Life Cycle Cost Analysis (LCCA) to assess the economic implications of designing aging-in-place (AIP) homes at the conceptual stage. With the global increase in the aging population, there is an increased demand for housing solutions tailored to the needs of elderly individuals. Focusing on the importance of the early phase of design, this study aims to improve the process of making efficient decisions by providing a comprehensive assessment of the life cycle costs associated with AIP homes. The study introduces a semi-automated model for the economic evaluation of AIP homes, enabling the estimation of costs throughout the houses’ entire life cycle, from design and construction to operation, maintenance, and eventual renovation or disposal. The said model facilitates the exploration of the long-term economic feasibility of design’s related decisions with an emphasis on the importance of considering the life cycle costs early during the design process to optimize the functionality and economic viability. By investing in accessible and universal design features upfront, the initial costs for modifications can lead to long-term savings by reducing the need for extensive retrofits. The model can easily do comparison between different design alternatives in terms of their lifecycle costs, allowing designers to assess the financial impact of using important features in their design such as wider doorways, accessible bathrooms, and elevators. Overall, this study provides valuable insights for designers and homeowners about the economic aspects of designing AIP homes as a support for efficient decision-making during the early stages of the design process.

In order to solve the problem of large eddy current loss and high temperature rise caused by large amount of permanent magnet, a new type of combined magnetic pole permanent magnet motor is proposed in this paper. The sinusoidal distribution subdomain model of non-uniform air gap rotor is established by using Laplace equation, and the analytical expression of eddy current loss of rotor in uniform air-gap and non-uniform air-gap is derived. The effect of rotor eccentricity on eddy current loss is obtained. According to the characteristics of distributed winding of non-uniform air gap combined pole permanent magnet motor, equivalent treatment is performed to obtain the equivalent thermal conductivity, so as to establish equivalent thermal network model of motor, calculate the temperature value of each component of the motor, and verify the correctness of the thermal network model through the method of magnetothermal bidirectional coupling. Finally, an experimental platform is set up to carry out temperature rise experiments on the two prototypes respectively. Experimental results show that the non-uniform air-gap rotor structure can effectively reduce the rotor eddy current loss and motor temperature rise, and also verify the accuracy of the analytical model calculation results.

Information geometry is a mathematical framework that analyses the structure of statistical models using concepts from differential geometry. It treats families of probability distributions as manifolds, where the parameters of each model determine the coordinate charts. By applying info-geometric tools, we can gain insights into the characteristics of these models. The approach involves characterizing the queueing system's manifold using information geometry and presenting the exponential of the information matrix. This integration of information geometry with queueing theory provides a novel perspective for analyzing the dynamics of queueing systems, incorporating relativistic and Riemannian concepts. Some applications to E-health are highlighted. Finally, closing remarks and the next phase of research.

Cooling fans are one of the critical components of air-forced (AF) dry-type transformers for regulating internal temperatures. Therefore, effective malfunction detection is crucial to maintain the transformer temperature within an acceptable range and prevent overheating. Regular maintenance occurs periodically and issues with cooling fans may arise between maintenance periods, leading to prolonged operation under malfunctioning conditions and potential failures. In addition, utilities typically have online information about whether a fan works or not without providing information about cooling fan malfunctioning circumstances. To address these challenges, this study proposes learning-based online monitoring techniques to detect malfunctions in AF transformer cooling fans. Random forests (RFs) and convolutional neural networks (CNNs) are developed to classify the audio signals from cooling fans into normal and malfunctioning classes. Unlike RFs, which require separate feature extraction, CNNs are trained based on spectrogram images derived from audio signals. Thus, various time-frequency techniques are utilized for feature extraction in RFs. Besides, multiple data augmentation techniques are employed to enhance the dataset size and diversity. Algorithmic performance is optimized through hyperparameter tuning and classifier threshold adjustment. Simulations reveal that CNNs outperform RFs, whereas the latter provides superior interpretability of acoustic features compared to the former.

Sarcomas are a group of malignancies of mesenchymal origin with plethora of subtypes. Given the sheer heterogeneity of various subtypes and rarity of the disease, management of sarcomas has been challenging with poor patient outcomes. Surgery, radiation therapy and chemotherapy have remained the backbone of treatment in patients with sarcoma. The introduction of immunotherapy has rev-olutionized the treatment of various solid and hematological malignancies. In this review, we discuss basics of immunotherapy and immune microenvironment in sarcomas, various modalities of im-munotherapy such as immune checkpoint blockade, oncolytic viruses, cancer targeted antibodies, vaccine therapy and adoptive cell therapies like CAR T-cell therapy, T cell therapy, TCR therapy.

ABSTRACT: Recurrent glioblastoma (rGBM) is a highly aggressive form of brain cancer that poses a significant challenge for treatment in neurooncology, and the survival status of patients after relapse usually means rapid deterioration, and also the leading cause of death among patients. In recent years, immunotherapy has emerged as a promising strategy for the treatment of recurrent glioblastoma by stimulate the body's immune system to recognize and attack cancer cells , which could be used as a in combination with other treatments such as surgery, radiation, and chemotherapy to improve outcomes for patients with recurrent glioblastoma, This therapy combines several key methods such as the use of monoclonal antibodies, chimeric antigen receptor T cell (CAR-T) therapy, checkpoint inhibitors, oncolytic viral therapy cancer vaccines, and combination strategies. In this review, we mainly document the latest immunotherapies for the treatment of glioblastoma and focus on the rGBM especially.

Targeted radionuclide therapy (TRT) has recently seen a surge in popularity, with the use of radionuclides conjugated to small molecules and antibodies. Similarly, immunotherapy also has shown promising results – an example being chimeric antigen receptor (CAR) T-cells therapy in hematologic malignancies. Moreover, TRT and CAR T therapies possess unique features that require special consideration when determining how to dose, time, and sequence combination treatments, including the distribution of TRT dose in the body, the decay rate of the radionuclide, and the proliferation and persistence of the CAR-T cells. These characteristics complicate additive or synergistic effects of combination therapies and warrant a mathematical treatment which includes these dynamics in relation to the proliferation and clearance rates of the target tumor cells. Here we combine two previously published mathematical models in a multiple myeloma setting to explore the effects of dose, timing, and sequencing of TRT and CAR-T cell based therapies. We find that for a fixed TRT and CAR-T cell dose, the tumor proliferation rate is the most important parameter in determining the best timing of TRT and CAR T therapies.

Background: Accurate prediction of patients’ response to therapy is clinically indispensable, howbeit challenging. With increased understanding of the human genome and malignancies, there is the renaissance of in silico pharmacogenomics with renewed interest in drug response predictability based on gene-drug interaction. Objective: Evidence-based transcript-proteome profiling is essential for synthesizing clinically applicable algorithms for predicting response to anticancer therapy, including immune checkpoint blockade (ICBT); thus, saving physicians’ time, reducing polypharmacy, and curtailing unnecessary treatment expense. In this study, we tested and validated the hypothesis that a selected proteomic signature in ICBT-naïve patients is sufficient for the prediction of response to ICBT. Methods: Using a multimodal approach consisting of computational pharmacogenomics, transcript-proteome analytics, mathematical modeling, and machine learning systems; we delineated therapy-sensitivity and stratified patients into graduated response groups based on their proteomic profile. Protein expression levels in our cohort tissue specimens were evaluated based on T cell- and non-T cell- inflamed phenotypes by immunohistochemistry. Results: We established β-catenin, PDL1, CD3 and CD8 expression-based ICBT response model. Statistical regression models validated the predictive association between our predefined algorithms and therapeutic outcome. Interestingly, our 4-gene prediction classifier was constitutively independent of tumor tissue origin, correctly stratified patients into high-, low-, and non- responders pre-treatment, with high prediction accuracy, and exhibited good association with patients’ performance status and prognosis (p < 0.01). Conclusion: Our findings demonstrate the possibility of accurate proteomics based ICBT response prediction and provide a putative basis for drug response prediction based on selective proteome profile in untreated cancer patients.

Background: Recently we demonstrated that Astragalus polysaccharide (PG2), the active ingredient in dried roots of astragalus membranaceus, ameliorates cancer symptom clusters and improve quality of life (QoL) in patients with metastatic disease by modulating inflammatory cascade, against the background that inflammatory cells including macrophages, dendritic cells (DCs), and cytotoxic T lymphocytes (CTLs) in tumor initiation, metastasis, and progression. Nevertheless, the role of PG2 in the modulation of anticancer immunogenicity and therapeutic response remains relatively underexplored and unclear. Purpose: The present study investigates how and to what extent PG2 modulates cellular and biochemical components of the inflammatory cascade, enhance anticancer immunity, and the therapeutic implication of same in patients with lung cancer. Methods and Results: Herein, we demonstrated that PG2 significantly increased the M1/M2 macrophage polarization ratio in non-small cell carcinoma (NSCLC) H441 and H1299 cells. This PG2-induced preferential pharmacologic up-regulation of tumoral M1 population in vitro, positively correlated with the downregulation of tumor-promoting IL-6 and IL-10 expression in NSCLC cell-conditioned medium, with concomitant marked inhibition of cell proliferation, clonogenicity and tumorsphere formation. Our ex vivo results, using clinical sample from our NSCLC cohort, demonstrated that PG2 also promoted the functional maturation of DCs with consequent enhancement of T cell-mediated anticancer immune responses. Consistent with the in vitro and ex vivo results, our in vivo studies showed that mice treated with PG2 exhibited significant time-dependent depletion of the tumor-associated M2 population, synergistically enhanced the anti-M2-based anticancer effect of cisplatin, and inhibition of xenograft tumor growth in the NSCLC mice models. Moreover, in the presence of PG2, cisplatin-associated dyscresia and weight-loss was markedly suppressed. Conclusion: These results do indicate a therapeutically-relevant role for PG2 in modulating the M1/M2 macrophage pool, facilitating DC maturation, and synergistically enhancing the anticancer effect of conventional chemotherapeutic agent, cisplatin; thus laying the foundation for further exploration of the curative relevance of PG2 as surrogate immunotherapy and/or clinical feasibility of its use for maintenance therapy in patients with lung cancer.

The insertion of the Amazon into the global commodities market requires ensuring the rational use of resources to meet market and political-social demands, such as the UN 2030 Agenda. Therefore, responsible production practices, given the current demand for sustainable use of land and its re-sources, are essential. Thus, the objective of this study was to identify opportunities and challenges linked to the implementation and consolidation of sustainable production systems in the Amazon through a systematic literature review. To this end, articles were prospected in four databases (Science Direct, SpringerLink, Scopus and Wiley) covering the period from 2004 to 2024. A total of 5,385 articles were evaluated, and after the selection stages, only 39 were included. A low distri-bution of studies among states in the Brazilian Amazon was observed, with a peak in studies star-ting in 2015. The studies developed mostly addressed agroforestry systems and forest management. Although there are sustainable production systems and practices, research and public policies need to be promoted to help the different actors involved in agricultural production in the Amazon, generating income and quality of life.

Introduction: Detection of diaphragmatic injury in blunt trauma can be challenging in the absence of surgical exploration. Here we explore the mechanisms of injury and detection modes for patients with blunt trauma who had a diaphragmatic injury. Methods: This is a single-center, retrospective review conducted in a level 1 trauma center, 2016 to 2023, inclusive. We included all patients who presented with a blunt traumatic diaphragm injury (TDI). We identified nine patients with TDI using AIS injury description and type of trauma. Patient demographics, mechanism of injury, injury severity score (ISS), mode of diagnosis, and clinical outcomes were reviewed. Results: Of the nine patients identified with blunt TDI, two were associated with motor vehicle collisions, four were pedestrians struck, 1 from stab wounds, and 2 fell from the stairs. The mean ISS for the nine patients is 39.7. Of the nine patients with blunt TDI, four died in the trauma bay – two from traumatic arrest, and two died spontaneously. One patient died two days after admission. Of the four patients who survived, one had a diaphragm injury identified during video-assisted thoracic surgery (VATS) for retained hemothorax, and one patient had a diaphragm injury repaired during emergent exploratory laparotomy for other injuries. One patient had a diaphragm injury identified and repaired during diagnostic laparoscopy that was converted to open surgery, and the remaining patient had no diaphragm injury on diagnostic laparoscopy evaluation. Conclusions: Blunt trauma to the torso is usually a consequence of high-energy impact but can also occur following low-energy incidents, such as falls in elderly individuals. Imaging can be useful in detecting such injuries but is not 100% sensitive. A high index of suspicion should be maintained for diaphragmatic injury in high-energy blunt trauma.

The dynamic nature of quadrotor flight introduces significant uncertainty in system parameters, such as thrust and drag factor. Consequently, operators grapple with escalating challenges in implementing real-time control actions. This study delves into an approach for estimating the model of quadrotor Unmanned Aerial Vehicles using Physics-Informed Neural Networks (PINNs) when you have a limited amount of data available. PINNs offer the potential to tackle issues like heightened non-linearities in low-inertia systems, elevated measurement noise, and constraints on data availability. The effectiveness of the estimator is showcased in a simulation environment with real data and juxtaposed with a state-of-the-art technique, such as the Extended Kalman Filter (EKF).

The aim of our research was to evaluate and analyze serum 25(OH) vitamin D and parathyroid hormone (PTH) levels to investigate whether vitamin D deficiency serves as a risk factor for an increased incidence of acute respiratory infections (ARI) in children. Serum PTH levels were used as an indicator of vitamin D sufficiency, as normal PTH levels require an optimal concentration of 25(OH) vitamin D. The study included 129 children, divided into five subgroups: children with acute bronchopneumonia (n=42), acute laryngotracheitis (n=7), acute bronchiolitis (n=32), acute bronchitis (n=18), and a control group (n=30). No statistically significant differences in 25(OH)D levels were observed between the overall population of children with ARI and the control group (p=0.073). However, significant differences in 25(OH)D levels were identified between the control group and children with bronchopneumonia, acute bronchitis, and laryngotracheitis (p<0.01, p<0.05). Vitamin D insufficiency was found in 28.3% of children with ARIs and 10% in the healthy group. Sufficient levels were present in 60% of healthy children and 48.5% of those with ARIs. Deficiency was observed in 4% of ARI patients and 3.3% of the control group. Regarding PTH levels, statistical significance was found between the control group and the acute bronchiolitis group, due to the high percentage of children with hypervitaminosis in this subgroup. These results highlight the crucial role of vitamin D in the onset and progression of acute respiratory tract infections in children, emphasizing its impact on their overall respiratory health.

This paper examines the current state of food security in Pakistan, focusing on the factors influencing the nation's ability to ensure a stable food supply. The analysis covers food production, distribution, accessibility, and stability, while also considering socioeconomic and environmental factors. The role of government regulations and international collaborations is explored in addressing food security challenges. Despite the critical importance of agricultural governance for sustainable food production and economic development, Pakistan's agricultural sector remains under prioritized, suffering from a lack of strategic vision and inconsistent government support. This neglect undermines efforts to achieve food security and stability. The study evaluates the alignment of Pakistan's National Food Security Policy (2018) with global, national, and provincial standards for sustainable agricultural management. A framework based on principles, criteria, and indicators (PCI) was developed, utilizing both quantitative and qualitative methodologies. Forty-three indicators, eleven criteria, and one guiding principle across four dimensions were identified. Thirteen governance tools were assessed using a ratio scale (0–5), with results presented in a policy coherence matrix. The coherence index score of 2.14 indicates significant misalignment among regulatory instruments, highlighting gaps in addressing climate change, low-income food access, service management, and institutional capacity. The study reveals that many food policies in Pakistan are outdated and inconsistent, requiring revision to address local challenges and align with emerging international obligations. The findings provide a comprehensive overview of the current food security landscape in Pakistan, offering insights for more informed decision-making to build a resilient and sustainable food system.

A new model of gravity is presented here that is similar to MOND and Chameleon theory but uses an Entropic Gravity approach that is not basedfundamentally on the First Law of Thermodynamics. Instead, the Second Law of Thermodynamics will be mainly used here as it was applied inBlack Hole Physics via the Area Theorem and the Holographic Principle. The Area Theorem was considered here to imply, not only that the totalarea of the event horizon will never shrink when entropy increases, but also that the mass or energy content within the black hole will always begreater than the original mass-energy input, though not necessarily violating the energy conservation law. This black hole property will be extendedto include even a non-black hole setting. Moreover, the approach does not use the Equipartition Theorem to relate energy to temperature($E=Nk_{b}T$) instead we used Vopson's Energy-Mass-Information Equivalence Principle ($E=k_{b}T\ln(\Omega)$). The theory uses $E=NE_{p}$, for the total energy of a massive object where $E_{p}$ is the Planck Energy and $N$ is the number of PlanckEnergy to represent the amount of information within the limit set at the Planck scale. It is shown here that gravity emerges whenever informationis updated within a given volume of space with a magnitude that is defined not only by the gravitating matter but also by the energy generated inspace within the vicinity of the gravitating matter. The model is the first to consider the role of both spacetime and matter as a medium to storeinformation and apply it to describe gravity in a fundamental way.

Building decarbonization is a major challenge for cities. Deciding what, when, and how to retrofit a building is difficult, given the complex interaction between energy costs and investment requirements. Several tools have been developed in the last years to help public and private stakeholders with these decisions, but none cover aspects the authors think are fundamental. For this reason, an urban building retrofit tool was developed and is presented in this article. This new tool is based on a bottom-up approach, with all buildings simulated individually, considering aspects such as shading or adjacencies. As a second step, three scenarios with different levels of ambition have been implemented in the tool, and the energy demand and emissions resulting from these scenarios have been calculated. As a third step, the retrofitting scenarios' initial investment and operational costs have been implemented via a detailed Life Cycle Costs (LCC) approach. The authors describe the robust and scalable structure that has been developed and the application of this structure to calculate the LCCs of different retrofitting scenarios in Montréal.

For the first time porous tungsten coatings were obtained by vacuum annealing of coatings consisting of both lead solution in β-W and a mixture of Pb solution in β-W and pure lead. Electron-microscopic studies of the obtained coatings before and after vacuum annealing at 800 оС for 1 hour and 6 hours were carried out. The formation of a new phase of tungsten with an octa-lattice and parameter a = 0.4878±0.0005 nm was recorded.

We assess simultaneous adoption and impacts of multiple improved technologies promoted as a bundle and recommended for legumes intensification systems for smallholder farmers in Ethiopia. We use DNA fingerprinting data to precisely identify our key treatment - “adoption to improved bean varieties” in the study. The results show significant positive impacts of adopting bundled interventions on, agricultural incomes and household food security but vulnerability to food insecurity persists. We find that growing improved varieties with fertilizers increased household agricultural revenue, allowing for more legume consumption and enhancing their likelihood of achieving adequate food consumption and food security outcomes. However, the vulnerability to food insecurity of the adopters remains high due to pre-existing resource degradation issues. Given similarity in production contexts in Sub Saharan Africa, our results provide perspective for similar development interventions. We use the results of our analysis to discuss potential policy implications and programmes to support technology intensification among small holder farmers.

This study investigates the impact of decentralized organizational party structures on the membership stability of Nigeria's two leading political parties, the People's Democratic Party (PDP) and the All Progressives Congress (APC), between 2015 and 2023. Conducted from April to August 2024, the study focuses on how decentralized party frameworks influence membership retention, particularly in Nigeria's fragmented political landscape, where ethnic and regional divisions challenge political cohesion. A multi-stage sampling technique to select 400 respondents, including national and local party leaders, assembly members, and grassroots members from the six geopolitical zones in Nigeria. A total of 384 valid responses were retrieved, yielding a 96% response rate. Data collection was facilitated through questionnaires administered via Google Forms, which were distributed through email and social media platforms, with a particular focus on WhatsApp for ease of access and engagement. Regression and correlation analyses were used to assess the relationship between decentralization and membership stability. The findings reveal a strong positive correlation (r = 0.961) between decentralized structures and membership stability, with decentralization accounting for 92.4% of the variance in membership stability (R² = 0.924). This indicates that decentralization plays a crucial role in promoting party institutionalization, fostering greater engagement, loyalty, and retention among members. However, regional disparities in the effectiveness of decentralization present challenges to uniform implementation. These results underscore the importance of standardizing decentralization policies across various regions to ensure coherence and reduce membership volatility. The study recommends a harmonized framework that supports decentralized governance within political parties, enhancing internal democracy and reinforcing party unity. The research concludes by emphasizing the need for ongoing exploration into the nuances of decentralization to further support Nigeria’s democratic consolidation. This study offers valuable insights for party leaders, policymakers, and researchers interested in the institutionalization of political organizations in emerging democracies.

Background/Objectives: Burn lesions damage the skin's outermost defensive layer, allowing pathogenic microbes including Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli to infiltrate. Silver sulfadiazine (SSD) is an effective antibacterial agent approved by U.S. Food and Drug Administration (US-FDA) and is considered as the gold standard for burn wound treatment. Despite the high degree of efficacy of SSD in burn wound management, it possesses some drawbacks, such as poor solubility, low topical bioavailability and skin irritations. The present study endeavours to develop nanosuspension based SSD nanogel for improving the deliverability of SSD and its therapeutic outcomes for the management of partial thickness burn; Methods: The SSD nanosuspension was formulated employing controlled nanoprecipitation approach using various surfactants; Results: The formulation was optimized utilizing one-factor-at-a-time approach and to fetch the optimized formulation of 134.6 nm size. The optimized nanosuspension was incorporated into chitosan gel that offer superior drug release potential, and also offered better spreadability (5.21 ± 0.38g) and extrudability (152.27 ± 0.22 gm) that represents the easy application over the skin and extrusion of gel from the tube; Conclusions: The formulation was well tolerated as shown by skin irritation study and offered a superior burn lesion healing characteristics vis-à-vis the marketed product, even at a lower concentration. Hence, the formulation offers a huge potential in enhancing the clinical outcomes of SSD, especially in the management of partial thickness burn. The developed system with the above mentioned outcomes could be a promising delivery system for partial thickness burn wound management.

The pandemic crisis of Covid-19 disturbed the social and the economic systems in which some changes happened during the pandemic and other changes extended subsequently. This paper is reflecting on the Sudan case, a country of a moderate population and large area with poor socioeconomic standard and infrastructure. The paper is based on the analysis of primary data and policy recommendations of an original research undertaken in five States in Sudan during the period Sept.2021-Sept.2022. The sample of the study selected from most five States that were affected by the Corona pandemic, namely: Khartoum State, Gezira State in the Central Region, Kassala State and Gadarif State from the Eastern Region, and Nyala State in the South Darfur Region in the west of the country. The research built on a quantitative research method, used the questionnaire as a tool for data collection from a sample size of 723 family head-households. The study is gaining a better understanding of the social, economic and health challenges that faced Sudanese households during the COVID-19 lock down and within the pandemic period. The study showed crucial results that the education of children was disturbed due to unavailability of the distance education in schools. In contrast some families maintained the education of the children as enrolled in private schools. In addition, the paper shows how the families used different approaches to educate their children and involve them into traditional informal and formal education ways. Additionally, the results explained the coping strategies with available resources that families used to manage economic crises and how this interferes with children education. Furthermore, the study proposing appropriate social policies and interventions that address the needs of the family in the current and future pandemic crisis.

The survival rates of women with stage 0 or 1 breast cancer stands at almost 100% and around 93% for stage 2. As the disease advances with decreasing survival, the rate detoriates to 72% for stage 3 and about 22% for stage 4 (ACS, 2018). Undoubtedly, earlier presentation is synonymous with better prognosis and survival. In fact data indicates that early stage breast cancer diagnoses has 90% survival rate as compared to 27% for the advanced states (ACS, 2018). In this regard, governmental and non-governmental agencies are working tirelessly towards the realization of improved breast cancer care and survival through early presentation and detection. For instance, the Sustainable Development Goal (SDG) Target 3.4 seeks to reduce by one third, premature mortality from cancers and other non-communicable diseases through prevention and treatment. Clearly, early presentation, diagnoses and treatment will assist in the realization of the SDG target 3.4 goal. To achieve this, research must be focused on early presentation among women with breast cancer.. However, current studies have focused mainly on advanced breast cancer regarding treatment, symptoms experience (emotional and psychological), coping and support systems, and the reasons for delayed diagnoses and treatment. Objective In this review, it is argued that, rather than focusing on advanced breast cancer which has been adequately explored, the attention has to be on what measures or approaches promote early presentations among Ghanaian women. Methods The review included all primary studies that provided answers to the phenomenon of interest. It included both quantitative and qualitative studies. Search scope encompassed studies within the last ten years; thus from 2010 to 2020 irrespective of the country of study.Studies were included if: The paper is of a primary study; the study population included women with early BC or BC symptoms; the study outcome is the association between early stage breast cancer and earlier presentation; the study has a comprehensive data analysis protocol; the results of the studies are unique.A thorough literature search was conducted using the following electronic database: Google scholar and Pubmed. Google scholar alert on new studies was subscribed. This gave update on newly published papers for appraisal and possible inclusion.Manual identified of other potentially eligible publications by searching the reference lists of retrieved studies was also done. After a thorough search, this review included studies from several countries around the Globe such as Ireland, London, Turkey, Iran, Ghana, Kenya, Ethiopia etc Data Collection The title and or abstract of all retrieved papers were independently scanned through to establish which studies should be further evaluated. The full texts of these potential articles were then assessed. Extraction The Cochrane extraction form for data extraction was resorted to. From each eligible article, the following study identifiers/information were extracted: author(s), first author, year, title, objective, article type, location, setting, study design and method, sample size, instruments used, and results. Results Prompt help seekers mainly self-discovered their BC, and this occurred through accidental touch, after menstruation, through breastfeeding, during grooming, and while taking their bath.Notably, women who were termed prompt help seekers had higher seriousness perception of their symptoms. This was likened to their level of understanding and awareness, as well as periodic examination and comparison. Similarly, women who knew they were at risk for breast on account of family history, and increased incidence of BC in their localities, labeled their initial symptoms as requiring prompt attention.Following interpretation and labeling of symptoms, the participants generally resorted to symptom monitoring until the onset of additional and or intense symptoms. Though most women thought of benign growths, a few feared it could be malignant. These emotional reactions led the women to purposively seek clarification by selectively consulting others. Further, participants opened up to social acquaintances such as family relationships, people with prior experience of breast disease, and in some few instances health professionals. Some women also resorted to media items to better their understanding. Remarkably, prompt help seekers sort for help within one month. Last but not least, some women first communed with their creator after discovery and labeling based on their spiritual affiliations.Also, researchers should consider conducting surveys to assess the BC risks for specific smaller groups. This would help tailor specific educational interventions to promote earlier presentation and treatment among the vulnerable.

Microsporidia are intracellular parasites infecting a wide range of vertebrates and invertebrates. In bees, they cause a diarrheal disease called nosematosis, which represents a growing problem contributing to the decline of bee colonies. This parasitic disease infects the gastrointestinal tract of bees, disrupts their immune system, weakens them, and shortens their lifespan. There are two known species of this microsporidial parasite with a global distribution: Vairimorpha apis and Vairimorpha ceranae, with current research indicating that the species V. ceranae is gradually replacing V. apis. In this study, we focused on the detection and occurrence of Vairimorpha spp. in bee colonies kept in different environments, as well as on comparing the impact of hive location on its occurrence. The methods used included sampling from winter bee carcasses, microscopic examination of bee gut contents, and subsequent molecular duplex PCR analysis. Altogether, we examined 82 hives located at 4 different sites and focused on the impact of transportation as an abiotic factor disturbing bees leading to the development of Vairimorpha spp. disease. The results indicate an increased occurrence of this parasite in hives located in urban sites and hives situated in intravillage locations, which may be attributed to transportation and associated vibrations as an abiotic stress factor. Detection revealed that all samples were positive for Vairimorpha ceranae.

The presented work shows that a force (electromagnetic or gravitational) field surrounding any material body is not limitless, but has the external and internal boundaries (radii). Understanding the fact of the existence of the field boundaries allows us to solve the problem of infinities that exists in electrodynamics. It is shown that there are two different electrostatic potentials: with the dimension of speed and with the dimension of the square of speed.

The Parecis Basin is one of the largest intracratonic basins in Brazil. Despite its considerable size, the basin has yet to be extensively explored, with only five wildcat wells drilled for hydrocarbons. So far, no commercial discoveries have been announced. Regional studies have suggested Paleozoic sedimentation, while recent studies indicate a Neoproterozoic fill. However, no tectonic model accurately describes the basin’s development, and no detailed structural map for the entire basin has been published. The present work presents a new detailed structural map of the Parecis Basin based on a four-step interpretation workflow integrating seismic and gravimetric data. The first step includes converting the public 2D seismic lines to the depth domain. The second step is estimating the residual Bouguer anomaly, where the computed residual anomalies should relate to the basin’s tectonic features. The third step comprises the 2D forward modeling of the gravimetric anomalies using the 2D seismic interpretation as a constraint. The final step compiled all the interpreted features into our new structural map. This map reveals the top of the basement, forming a complex framework of horsts and grabens. Normal faults define the main structural style in the basin. Further, we could recognize thick, high-density bodies embedded in the crystalline basement. These bodies consist of Orosian-Calimian (1.8-1.6 Ga) mafic and ultramafic rocks, which may be a potential source for hydrogen exploration in the basin. Subsequent geophysical and geochemical surveys will assess the hydrogen potential in the area.

Infrastructure such as transport, electricity, telecommunications, and sanitation are indispensable drivers for improving the country’s social and economic development. The industrial, agricultural, fisheries and service sectors are also key tools for the country's economic growth. This study aims to analyze the influence of infrastructure development on Djibouti’s economic growth and determine the other economic sectors. This study employs multiple regression analyses from Eviews Software to establish a correlation between these variables and Djibouti’s economic growth, utilizing data spanning from the period 2013 to 2022. The results reveals that mobile cell phone subscriptions, and the people using the health service management, industry, and service have a positive and highly significant influence on Djibouti's economic growth. The study found that access to electricity has a positive influence on economic growth in Djibouti, but is not statistically significant. In addition, the study shows that agriculture, forestry, and fisheries have a negative influence on economic growth in Djibouti, but are statistically significant. Therefore, we recommend that the Government of Djibouti strengthen and ensure the benefit of developing electricity infrastructure in Djibouti and the agriculture, forestry, and fisheries sectors to achieve sustainable economic growth in the coming years.

Traditional methodologies for measuring combat effectiveness rely on various contribution factors, where the main challenge lies in the complexity and subjectivity of these factors. Using frontline variation to measure combat effectiveness circumvents the limitations of many previous methods regarding complexity and subjectivity. Employing this methodology, we have quantitatively measured the combat effectiveness of both parties in the Russo-Ukrainian War across various temporal scales. Utilizing the time series data derived from our measurements, we constructed Daily, Weekly, Monthly, and Annual Candlestick Charts to illustrate the variation trends in combat effectiveness between the two sides across different temporal scales. This comprehensive approach facilitated a nuanced and all-encompassing analysis of the conflict, capturing the intricate dynamics of individual military engagements and the broader strategic operations' context. This case underscores the distinctive utility of our method in quantifying combat effectiveness, offering detailed and strategically significant insights.

Driven by mounting environmental apprehensions stemming from the over dependence on fossil fuels in energy and transportation sectors, extensive exploration into alternative energy sources, particularly biomass, has stimulated profound research on harnessing the potential of computational and mathematical techniques. This comprehensive survey delves into optimal models and strategies, unveiling their pivotal role in the design of biomass gasification processes.of hydrogen through biomass gasification. In this study, we aim to provide a comprehensive overview of the computational and mathematical techniques employed in optimizing biomass gasification processes, with a specific focus on enhancing hydrogen yield. Through an extensive literature review, various models and strategies will be examined, including thermodynamic analysis, kinetic modeling, reactor design, and process optimization. By uncovering the power of these techniques, we aim to contribute to the advancement of sustainable and efficient biomass utilization for the hydrogen-based future economy.This paper aims to provide an updated and comprehensive coverage of the investigations conducted on the potential of producing hydrogen from biomass through gasification. To achieve this, we incorporate the latest works that have utilized numerical modeling, simulation, optimization techniques, process heat integration, and co-generation in their studies. By encompassing these aspects, we aim to offer a broader and more in-depth re-appraisal of the subject matter. This will ensure that readers gain a holistic understanding of the advances made in the field and the potential for sustainable hydrogen production of biomass gasification.Through a meticulous re-appraisal and analysis of each subject, we can identify their respective strengths and areas that require further research effort. By thoroughly examining numerical modeling, simulation, optimization techniques, process heat integration, and co-generation, we can assess their effectiveness and applicability in the context of biomass gasification for hydrogen production. This analysis shed light on the areas where these techniques excel, as well as pinpoint limitations or gaps in current understanding. By identifying these areas, we can highlight the need for further research and development, enabling us to make significant advancements in biomass gasification processes and pave the way for a sustainable and efficient hydrogen-based future economy..

The study explores how different dimensions of perfectionism influence psychological well-being (PWB) in emerging adults. Literature has deepened the relationships between maladaptive perfectionism (e.g., excessive self-criticism, perceived discrepancy from the standards) and low PWB. Less is known about whether and how adaptive perfectionism (e.g., pursuing personal standards) relates to PWB. Secondly, the study has investigated whether self-compassion (i.e., self-benevolence, seeing personal imperfections as a common condition) may mediate the relationships between adaptive/maladaptive perfectionism and PWB. Participants (N=217, 18-35 y. o.) completed self-report questionnaires measuring: adaptive/maladaptive perfectionism (Almost Perfect Scale-Revised, APS-R: high standards and order/discrepancy, respectively), PWB, and self-compassion (SCS). Adaptive perfectionism resulted associated with PWB, particularly higher presence of purpose in life, environmental mastery, self-acceptance, and personal growth. Conversely, discrepancy resulted the most robust predictor of low PWB (β=-.68), followed by high standards with a positive direction (β=.23; Rc²=.514, p&lt;.001). A strong negative association emerged between discrepancy and SCS (r=-.67, p&lt;.001). A mediation analysis shows that self-compassion has an indirect effect reducing the strength of the relationship between discrepancy and low PWB. Results suggest focusing on self-compassion as a buffer factor that reduces the negative impact of maladaptive perfectionism on psychological well-being. Implications for education and health psychology are discussed.

An Indo-French campaign was conducted during May 2014 at Gadanki (13.5^oN, 79.2^oE), India, for investigating gravity wave (GW) coupling between the lower and middle atmospheres using a suite of experimental techniques. In this paper we are presenting the sources for those GWs which are observed at airglow layer (~87 km) using (OH) Airglow Imager during the campaign. For this purpose we have developed a background model atmosphere by combining the ERA-Interim, MSIS E 90 model and HWM 07 model data sets. Uniqueness of the present study lies in using near-real time background atmosphere data from simultaneous radiosonde and SVU Meteor Radar covering both source and propagation/ dissipation regions of GWs. We have observed 17 wave events and used GROGRAT model for reverse tracing to locate the source(s). When we searched for the sources near the terminal points or along the ray path, deep convection is found to occur but no strong wind shear. This indicates that the source for the observed GWs is deep convection. We have also simulated small scale waves that can reach mesosphere during different seasons (background conditions). GWs with periods less than 100 minutes and horizontal wavelengths less than 200 km are mostly reaching the mesospheric altitudes. Interestingly, it is found that only few GWs that are generated in the troposphere reach the mesospheric altitudes during the monsoon season, though strong sources like convection and wind shear persist throughout this season. Thus, background wind plays significant role in deciding the propagation of GWs in to upper atmosphere.