Cancer is the second leading cause of death worldwide. It is theorized that underlying genetic and epigenetic changes enable cells to proliferate out of control by escaping regulatory mechanisms. Although traditional molecular profiling techniques, i.e., bulk sequencing, can identify common mutations and gene expression patterns in cancer cells, they cannot detect tumour heterogeneity. However, single-cell technology has provided an ample opportunity to overcome this difficulty. Since this technology allows us to detect the heterogeneous properties of all cancer cells, this can further our knowledge of the signaling pathways in cancer cells. Indeed, single-cell transcriptomics technology has paved the road for identifying novel biomarkers and signaling pathways, which can serve as targets. This study aims to review the current knowledge about pathways involved in developing cancer cells and shed light on single-cell studies as promising therapeutic approaches.

The development and optimization of an effective non-viral gene delivery method for genetic manipulation of primary human T cells is a major challenge in clinical immunotherapy researches. According to the low transfection efficiency of conventional methods in human primary T cells, there is an effort in order to increase the transfection rate in these cells. Protamine is an FDA-approved compound with a documented safety profile that enhances DNA condensation for gene delivery. In this study, the effect of protamine on the transfection efficiency of standard transfection reagents, TurboFect, and Lipofectamine 2000 was evaluated in order to transfect primary human T cells. Results demonstrated that protamine condenses DNA and increases the positive charge of DNA/Cargo complex efficiently without any cytotoxic effect on the primary human T cells. The results also revealed that the DNA/Protamine/Cargo complexes effectively transfect human primary T cells.

The objective of this review is to do an overview about the current knowledge of Anti Iglon5 Syndrome, a disease that was first described in 2014. The IgLON proteins are a family of cell adhesion molecules and the presence of antibodies against IgLON5 are crucial for diagnosis of Anti IgLON5 Syndrome. This syndrome has an expanded clinical spectrum that involves prominent sleep disorder, progressive bulbar dysfunction, gait instability with abnormal eye movements reminiscent and cognitive deterioration sometimes associated with chorea. The main neuropathological finding is the neuronal loss with hyperphosphorylated tau (p-Tau) protein accumulation at hypothalamus, brainstem tegmentum, hippocampus, periaqueductal gray matter, medulla oblongata and upper cervical cord. The exact pathogenesis is still unclear and involves a neurodegenerative process and autoimmune response. The early diagnosis is important to avoid unnecessary tests and prevent complications. Important resources for diagnosis are the antibody testing of serum and CSF for IgLON5-IgG. The mortality of anti IgLON5 syndrome is high and new studies published described a good response to immune therapy. However, the response to immune therapy depends of some clinical and analytical characteristic. In addition, future studies are needed to thoroughly study the aspects of pathogenesis and treatment of this important pathological syndrome.

Achieving the best aesthetic result is a key objective of implant-prosthetic therapy. To maximize the aesthetic outcome, ensuring that implant-supported restorations are in harmony with the peri-implant soft tissues and bone is essential. A comparative analysis of zirconia and titanium dental implants revealed that both materials offer high success rates; however, they present distinct advantages and limitations in clinical practice. Titanium implants, with surface modifications but without chemical composition changes, boast remarkable long-term survival. In contrast, zirconia implants, while presenting high aesthetic and biocompatibility qualities, have a relatively high incidence of material-specific failure, ranging from 4% to 2% after 5-10 years. While titanium implants generally show superior long-term performance, zirconia implants benefit from ongoing advancements aimed at improving their osseointegration and longevity. This study emphasizes the need for short-term and long-term studies, complemented by randomized controlled trials (RCTs), which are essential for optimizing implant materials and ensuring patient satisfaction. Continued innovation and research are crucial for advancing dental implant technology and enhancing the quality of life for patients requiring dental restorations. Finally, it is important to understand that all materials have both advantages and disadvantages, so the choice of the optimal material should be based on the specific purpose.

Objectives: In Nigeria, modern contraceptive use remains relatively low despite numerous efforts to increase awareness and accessibility. This study examined the geopolitical factors influencing modern contraceptive use in North-central Nigeria Design: Using data from the 2021 Nigeria Multiple Indicator Cluster Survey, this study quantitatively investigated the factors influencing modern contraceptive use among women of reproductive age. The data were analyzed using R studio. Respondents' characteristics were described using frequency and percentage. A logistic regression model was employed to identify factors associated with modern contraceptive usage in the north-central region of Nigeria. Bivariate logistic regression was carried out between the explanatory and response variables. Settings: This study focused specifically on the north-central zone of Nigeria comprising 6 states, namely, Benue, Kogi, Kwara, Nasarawa, Niger, and Plateau states with the Federal Capital Territory (FCT). Results: Nearly one-third (30.1%) of the respondents are above 35 years of age. 3 out of every 5 (61.2%) respondents are currently married. This study found that the average modern contraceptive usage among women of reproductive age in north Central Nigeria is less than 15%. Age, education, childbirth delivery method, number of children, access to media, and state of residence are key drivers of modern contraceptive adoption and utilization among women of reproductive age in north-central Nigeria. Conclusion: This study finds it plausible to increase the awareness and sensitization of modern contraceptives and contraceptive usage in this region. There is a need for health education on the benefits and relevance of modern contraceptive usage.

Commercial Brazilian wheat flour was subjected to extrusion, oven, and microwave treatments. The solubility, monomeric and polymeric proteins, and glutenin and gliadin profiles of gluten were analyzed. In addition, in vitro digestibility and response against potential celiac disease immune-stimulatory epitopes were investigated. All treatments resulted in low solubility of the polymeric and monomeric proteins. The amounts of insoluble proteins increased from 5.6 % in control flour to approximately 10 % for all treatments, whereas soluble proteins decreased from 6.5 % to less than 0.5 % post treatment. In addition, treatments affected glutenin and gliadin pro-files. The amount of α/β- gliadin extracted decreased after all treatments, while that of γ-gliadin was unaffected. Finally, alteration of the gluten structure and complexity was not sufficient to render a product safe for consumption for individuals with celiac disease; the number of poten-tial celiac disease immune-stimulatory epitopes remained high.

The unravelling of the human genome created new perceptions on the origin and evolution of diseases and for cancer in particular, it established the notion that neoplasia has been a companion of life since its ap-pearance on earth. It is not surprising that neoplasms, in various forms, develop in numerous species of animals and even in plants. Unmistakable accounts of cancer with clinical features as are understood today, begin in the 5th c. B.C. The principles and practice of the Hippocratic and Galenic tradition dominated cancer care virtually into the 20th century. Advanced sequencing technologies at the dawn of the 21st century, generate new ther-apeutic opportunities with immunotherapy, oncolytic virotherapy and gene transfer, the latter especially in cases of hereditary cancer.

The research aimed to identify the effect of high-intensity compound exercises for physical performance skills using the means of hypoxia training in some biochemical variables in the blood of fencing players. The researcher used the experimental approach and determined the community, namely the players of Maysan governorate teams in fencing and for the three weapons (fencing sword, shish, Arab sword) the category of applicants over the age of (20) years, and by (4) players for each weapon, which reached the number of society (12) players, and some procedures were adopted to achieve the objectives of the study. The study came out the results of the study recorded a significant impact on the high level of measurement of blood biochemical variables (EPOs, FERSs, Hb, Hct) and improved by high-intensity compound exercises using the training hypoxic mask among members of the research community.

The cultural transmissions of a society like famous paintings, popular music, good poetry, and enduring religious rituals/doctrines/texts serve as mediums for the embodiment of algorithms that interact with the mind and body in looping, mostly unconscious interactions that are mutually beneficial to the participants of the society and the algorithms themselves. Useful algorithms are also found in the mind and bodies of other people, and individuals in a group can be used to outsource specialized tasks to benefit the society as a whole. Since useful algorithms must be embodied in a medium to work, there are physical limitations to the computations that can be performed in our universe.

Coulomb’s law and Newton’s law of gravitation are formally identical. Is it a mere coincidence? It seems to us that physics has answered yes so far, at least tacitly. We, on the other hand, do not believe in chance. Since the alternative to the fact that the strong similarity is only the result of chance is to believe that it is not, and in this case there must be a reason for this similarity, we have chosen the path of investigating the possibility that the two fields are not distinct, but have a common root that we will try to find. We propose an electrodynamics of electrically neutral bodies based on the hypothesis that the Coulomb constant in the case of attraction between charges of opposite sign is slightly greater than that of the case of repulsion between charges of the same magnitude as the previous ones, but of the same sign. If this difference were to exist, even small to the point of not being directly measurable in the laboratory, it could still produce macroscopic effects detectable in the case of large aggregates of charges, even if globally electrically neutral, as happens in the astronomical field. We deduce the electromagnetism of such a model and show the results obtained applying the theory to some significant cases such the light deflection in a gravitational field, a planet perihelion precession, the power radiated by merging black holes, the behaviour of antimatter in a gravitational field and, when available, we compare the predictions with the experimental data.

Pathogenesis of the connection of HIV-infection and cancer is a nowadays problem for research. More important is also to take into consideration a complexity of abordasions, such as prevention, diagnosis, monitoring, treatment, including control measures. These should be supported by statistical studies that report on restricted or extended geographical areas, to the level of social class and age. In our written text we try to describe from our opinion, strategies in HIV, infection a social and a healthcare problem.

The accurate identification of bacterial infections is critical for effective treatment in intensive care units (ICUs), yet current diagnostic methods face limitations in sensitivity and specificity, along-side cost and accessibility issues. Consequently, there's a pressing need for a marker that is economically feasible, rapid, and reliable. Presepsin (PSP), also known as soluble CD14 subtype (sCD14-ST), has emerged as a promising biomarker for early sepsis diagnosis. PSP, derived from soluble CD14, reflects the activation of monocytes/macrophages in response to bacterial infec-tions. It has shown potential as a marker of cellular immune response activation against patho-gens, with plasma concentrations increasing during bacterial infections and decreasing post-antibiotic treatment. Unlike traditional markers such as procalcitonin (PCT) and C-reactive protein (CRP), PSP specifically indicates monocyte/macrophage activation in bacterial infections. While limited studies in critical illness have explored PSP's role in sepsis, its diagnostic accuracy varies with threshold values, impacting sensitivity and specificity. Recent meta-analyses suggest PSP's diagnostic potential for sepsis, yet its standalone effectiveness in ICU infection management remains uncertain. This review provides a comprehensive overview of PSP's utility in ICU set-tings, including its diagnostic accuracy, prognostic value, therapeutic implications, challenges, and future directions.

Available options to combat bacterial infections are getting scarce. We require innovative and imaginative approaches to enhance the identification and discovery of effective antimicrobials capable of combating bacteria resistant to multiple or all available drugs. These methods should either directly eliminate the resistant bacteria or influence their viability indirectly by inhibiting their virulence or reducing their resistance to antibacterial agents. One interesting approach is to analyze ancient remedies presumably used to treat bacterial infections, try formulating them, and test them against modern microbes. The field was recently named ancientbiotics. This approach allows us to take advantage of centuries of accumulated empirical knowledge, from several traditional medicines of various ancient cultures across the world. The strategy has already resulted in promising formulations to combat the ESKAPE group of nosocomial pathogens. Moreover, molecular de-extinction consists of genome analysis of extinct species in the search for useful antimicrobials, such as peptides. The de-extinction of simple organisms such as bacteriophages may eventually become a resource for novel tools to combat multidrug-resistant bacteria. In this review, we summarize and discuss the reported antimicrobial effects of ancient remedies and de-extinct molecules known to modern science, and discuss possible new strategies to further harness the potential of past remedies and molecules to help us fight the rise of superbugs.

This study delves into innovative approaches and pragmatic remedies to surmount software access barriers in educational contexts. Financial impediments and limited software installation know-how can impede students from fulfilling course requirements.

We present contrast information, a novel application of some specific cases of relative entropy measures, designed to be useful for cognitive modelling of sequential perception of continuous signals. We explain the relevance of entropy in cognitive modelling of music and language. Then, as a first step to demonstrating the utility of constrast information for that purpose, we show empirically that its discrete case correlates well with existing successful cognitive models in the literature. We explain some interesting properties of constrast information. Finally we propose future work towards a cognitive architecture that uses it.

Immune checkpoint inhibitors (ICI) are a promising form of immunotherapy that has significantly changed the therapeutic landscape for many advanced cancers. They have shown unique clinical benefit against a broad range of tumour types and a strong overall impact on survival in studied patient populations. However, there are still many limitations holding back this immunotherapy from reaching its full potential as a possible curative option for advanced cancer patients. A great deal of research is being undertaken in the hope of driving advancements in this area, building a better understanding of the mechanisms behind immune checkpoint inhibition and ultimately developing more effective, safer, and wider-reaching agents. Taking into account the current literature on this topic, this review aims to explore in depth the basis of the use of ICIs in the treatment of advanced cancers, evaluate its efficacy and safety, consider its current limitations, and finally reflect on what the future holds for this very promising form of cancer immunotherapy.

Some global difficulties in the modern period include energy storage conversion. Researchers have looked to renewable energy resources to discover long-term answers to this dilemma. Fuel cells are one example of prospective energy producing technology. Although these technologies appear to be very enticing, they are known to be expensive due to high expenses. Catalyst costs, as well as concerns concerning energy density. Pt based Electrocatalysts have traditionally been used to drive ORR and offer efficient power outputs. However, cost constraints have limited the use of these electrocatalysts, rendering them inefficient. Apart from the high price, Pt-based Electrodes are prone to time-dependent drift and CO deactivation, both of which occur gradually. Electrocatalysts deteriorate over time, reducing the efficiency of fuel cells. This is why alternative electrocatalysts are in high demand for future energy applications. This review covers the comparative study of Platinium and Non-Platinium based electrocatalyst in fuel cells, their shortcomings and recent advancement for efficient and optimized electrocatalyst.

The Diophantine equation for which p is prime 2^n = p^2 + 7 and n is integers with p > 0, is examined in this work. It is demonstrated by examining the characteristics of the equation that the only solutions meeting these requirements are p = 3 with n = 5 and p = 5 with n = 7. In order to analyze the above equation, it is necessary to look at the properties of primes and how they relate to powers of two. These results advance our knowledge of prime numbers and how they behave in certain mathematical problems.

Many studies have addressed sex differences in patients with psoriatic arthritis, although these are aimed more at describing the phenotype than at investigating the causes underlying the differences. Cross-sectional study of 203 patients. The clinical and demographic variables included age, years of education, time since onset, smoking, type of treatment, clinical presentation, number of entheses affected, dactylitis, fatigue, and cutaneous involvement. Disease activity,functioning and disease was measured. The comorbid conditions evaluated included obesity (and leptin as an associated parameter), anxiety and depression, and sleep quality. Mean age was 54.6, and 46.8% of patients were women. Women less frequently presented axial involvement and more frequently presented enthesitis. They also presented greater disease activity, greater disease impact, and poorer functioning, as well as greater fatigue. As for comorbid conditions, women presented a higher leptin/BMI ratio, higher levels of anxiety and depression, and poorer sleep quality. By sex, pain affecting women was associated with the leptin/BMI ratio and sleep quality. The leptin/BMI ratio was not associated with any component of disease activity in men. Sex was associated with several clinical manifestations, disease activity, functioning, and disease impact. Leptin was associated with intensity of pain in women.

This exploration delves into the intricacies of decision-making in business management. It covers decision-making models, influencing factors, real-world case studies, and strategies for effectiveness. Emphasizing the role of data-driven approaches, the exploration highlights the transformative impact of effective decisions on organizational success. Challenges and pitfalls are addressed, providing insights for overcoming obstacles. The importance of mastering decision-making is underlined as a strategic advantage in the competitive landscape of business management. In summary, this exploration offers a nuanced understanding, empowering leaders to make informed choices that shape organizational destinies.

Previous studies have revealed the microbial metabolism of dietary choline in the gut, leading to its conversion into trimethylamine (TMA), a precursor of the cardiovascular inflammatory marker trimethylamine N-oxide (TMAO). Polymethoxyflavones (PMFs), exemplified by tangeretin, demonstrate efficacy in mitigating TMAO-induced cardiovascular inflammation. However, the specific mechanism by which these compounds exert their effects, particularly in modulating the gut microbiota, remains uncertain. This investigation focused on tangeretin, a representative PMFs, exploring its influence on the gut microbiota and the choline-TMA conversion process. Experimental results showed that tangeretin treatment attenuated the population of CutC-active bacteria, specifically Clostridiaceae and Lactobacillus, induced by choline chloride in rat models. This inhibition resulted in reduced efficiency in choline conversion to TMA, thereby ameliorating cardiovascular inflammation resulting from prolonged choline consumption. In conclusion, tangeretin's preventive action against cardiovascular inflammation is intricately linked to its targeted modulation of TMA-producing bacterial activity.

Abstract: this study aimed to evaluate the benefits of applying 5 cmH2O of CPAP using a pediatric helmet during the recovery phase from general anesthesia in brachycephalic dogs. Brachycephalic dogs undergoing various surgical procedures were included in the study, and a total of 64 subjects were randomly assigned to receive either standard oxygen supplementation (NO-CPAP group) or oxygen supplementation combined with CPAP (CPAP group). The study evaluated arterial blood pH, blood gas partial pressures of O2 and CO2, arterial blood O2 saturation, and related parameters during recovery. The dogs were monitored, and helmet tolerance was assessed using predefined criteria. Of the initially assessed 69 dogs, 64 were enrolled, 32 in the CPAP group and 32 in the NO-CPAP group. Fifteen dogs in the NO-CPAP group were excluded based on predetermined criteria. The CPAP group showed significant improvements in PaO2, PaO2/FiO2, P(A-a)O2, F-Shunt, and respiratory rate compared to the NO-CPAP group (p < 0.001). The incidence of reintubation and helmet intolerance was higher in the NO-CPAP group (18% and 15.6%, respectively) than in the CPAP group (0%). This study highlights the potential benefits of incorporating CPAP, delivered through a pediatric helmet, in the perioperative management of brachycephalic dogs. Keywords: Brachycephalic; dog; CPAP; oxygenation; anesthesia

Traditional aquaculture systems appear to be confronted with the high total ammonia nitrogen (TAN) produced during production, which can be harmful to aquatic life. As the demand for global fish production continues to increase, farmers should adopt Recirculating Aquaculture Systems (RAS) to improve production. The biofilter plays a vital role in ammonia removal. However, the drawback of the biofilter operation is needed an automatic and controlled system with a water quality monitoring system to guarantee optimal performance. RAS utilize a monitoring and control system to maintain the water quality and control the biofilm growth in the biofilter to reduce the ammonia. Therefore, this study focuses on developing a water quality monitoring and control system to achieve optimum biofilm performance. From 35 days of the experiment, the water quality was controlled at a level save for the aquatic environment, such as dissolved oxygen, pH, temperature, and TDS. Thus, the highest TAN removal efficiency is 50% when biofilm thickness reaches 119.88 µm.

Accurate estimation of chlorophyll content in wheat leaves can not only reflect its growth and nutritional status, but also provide a scientific basis for field management. In order to evaluate the potential of hyperspectral data to estimate the chlorophyll content of wheat leaves, this study focused on the leaves of wheat at the flag-picking stage, flowering stage, grain filling stage and maturity stage. Based on the framework of five vegetation indexes, the spectral index was con-structed by using the combination of 400-1000nm bands, and the correlation between the con-structed spectral index and the measured chlorophyll value was analyzed, and the optimal spectral index was screened by the correlation coefficient. Based on the optimal spectral index, polynomial regression, random forest, decision tree and artificial neural network were used to establish the estimation model of chlorophyll value, and the optimal model for estimating the chlorophyll value of wheat leaves was selected through model evaluation. The results showed that the five optimal spectral indices at the four growth stages were mainly composed of red band, red edge band and near-infrared band, and the five optimal spectral indices at the grain filling stage had the highest correlation with the chlorophyll value, and the absolute value of the cor-relation coefficient was greater than 0.73, the accuracy of the estimation model established in the four growth stages was different, and the estimation accuracy of the flag stage was the best, with R² and RMSE of 0.79 and 2.63, respectively. The above results show that hyperspectral data is suitable for estimating the chlorophyll value of wheat leaves, and the PR model of flag picking period can be used as the optimal model for estimating the chlorophyll value of wheat leaves.

This paper deals with the design and kinematic analysis of a novel mechanism for the elbow joint of an upper-limb exoskeleton, with the aim of helping operators, in terms of effort and physical resistance, in carrying out heavy operations. In particular, the proposed eight-bar el-bow joint exoskeleton mechanism consists of a motorized Watt I six-bar linkage and a suitable RP dyad, which connects mechanically the external parts of the human arm with the corre-sponding forearm by hook and loop velcro and thus, helping their closing relative motion for lifting objects during repetitive and heavy operations. This relative motion is not a pure rotation and thus, the upper part of the exoskeleton is fastened to the arm, while the lower part is not rigidly connected to the forearm, but through a prismatic pair which allows both rotation and sliding along the forearm axis. Instead, the human arm is sketched by means of a crossed four-bar linkage, which coupler link is considered as attached to the glyph of the prismatic pair, that is fastened to the forearm. Therefore, the kinematic analysis of the whole ten-bar mecha-nism, which is obtained by joining the Watt I six-bar linkage and the RP dyad to the crossed four-bar linkage, is formulated to investigate the main kinematic performance and for design purposes. The proposed algorithm has given several numerical and graphical results. Finally, a double-parallelogram linkage, as particular case of the Watt I six-bar linkage, was considered in combination with the RP dyad and the crossed four-bar linkage, by giving a first mechanical de-sign and a 3D printed prototype.

Machine-learning methods used for classification are challenged by the class imbalance problem, where a certain class is underrepresented. Over/under-sampling the majority/minority class observations or model selection for ensemble methods alone might not be effective if the class imbalance ratio is very high. To address this concern, a novel method is presented for generating synthetic data for minority class observations in conjunction with an optimal tree ensemble classifier (OTEC). This novel synthetic method first generates minority class instances to balance the training data. Then it applies OTEC, where models are selected based on their performance using out-of-bag observations and training subsamples. A total of 20 benchmark problems on binary classification with moderate to extreme class imbalance are used to assess the efficacy of the proposed method against other well-known methods, including optimal tree ensemble, smote random forest, under-sampling random forest, oversampling random forest, k-nearest-neighbor, support vector machine, tree, and artificial neural network, using classification error rate, sensitivity, specificity, precision, recall and F1-score as performance metrics to assess the efficacy of the proposed method. The analyses presented in this study revealed that the proposed method based on data balancing and model selection yielded better results than other methods.

The periodontal ligament (PDL) is a complex connective tissue that connects the tooth root to the dental alveolar bone and plays crucial mechanical roles. PDL also exhibits regenerative roles and regulatory functions to maintain per-iodontium integrity and homeostasis. While PDL exposure to oral microbial pathogens is common, virtually nothing is known regarding viral infections of PDL. In particular, human herpes simplex virus type 1 (HSV-1) persistently infects the oral cavity through infections of the oral epithelium, connective tis-sue and neurons. While the oral spread of HSV-1 is generally asymptomatic, this virus has also been implicated in various oral pathologies. In this study, using a primary cell model derived from PDL (PDL-cells), and whole surgical fragments of PDL, we provide evidence supporting the efficient infection of PDL by HSV-1 and the promotions of cytopathic effects. Infection of PDL by HSV-1 was also associated with an acute innate inflammatory response, as il-lustrated by the production of the antiviral interferons and pro-inflammatory cytokines. Furthermore, this inflammatory response to HSV-1 was exacerbated in the presence of bacterial-derived products, such as peptidoglycans. This work therefore highlights the ability of HSV-1 to infect mesenchymal cells from PDL, suggesting that PDL may serve as a viral reservoir for the perio-dontal spread of HSV-1. Moreover, this raises questions about HSV-1 oral pathogenesis, as HSV-1-associated cytopathic and inflammatory effects may contribute to profound alterations of PDL integrity and functioning.

Barley is rich in phenolic compounds, providing health benefits and making it a valuable addition to a balanced diet. However, most studies focus on these compounds at barley's final maturity, neglecting their synthesis during grain development and its impact on barley quality for food applications. This study investigates phenolic profiles during grain development in four hull-less barley genotypes with different grain colors, specifically bred for food applications. The objectives were to determine the phenolic profile and identify the optimal maturity stage for maximum phenolic content and antioxidant capacity. Using UPLC-MS/MS and in-vitro antioxidant capacity assays, results show that total phenolic compounds decrease as grain matures due to increased synthesis of reserve components. Flavan-3-ols, phenolic acids, and flavone glycosides peaked at immature stages, while anthocyanins peaked at physiological maturity. The harvest stage had the lowest phenolic content, with a gradient from black to yellow, purple, and blue genotypes. Antioxidant capacity fluctuated during maturation, correlating positively with phenolic compounds, especially bound phenolic acids and anthocyanins. These findings suggest that early harvesting of immature grain can help retain bioactive compounds, promoting the use of immature barley grains in foods. To support this market, incentives should offset costs associated with decreased grain weight.

In recent years, the utilization of machine learning algorithms and advancements in Unmanned Aerial Vehicle (UAV) technology have marked significant shifts in remote sensing practices. In particular, the integration of machine learning with physical models and their application in UAV-satellite data fusion have emerged as two prominent approaches for estimating vegetation biochemistry. This study evaluates the performance of five machine learning regression algorithms (MLRAs) for mapping crop canopy chlorophyll at the Kellogg Biological Station (KBS) in Michigan, USA, across three scenarios: (1) application to Landsat 7, RapidEye, and PlanetScope satellite images; (2) application to UAV-satellite data fusion; and (3) integration with the PROSAIL radiative transfer model (hybrid methods PROSAIL + MLRAs). The results indicate that the majority of the five MLRAs utilized in UAV-satellite data fusion perform better than the five PROSAIL + MLRAs. The general trend suggests that the integration of satellite data with UAV-derived information, including the normalized difference red-edge index (NDRE), canopy height model, and leaf area index (LAI), significantly enhances the performance of MLRAs. The UAV-RapidEye dataset exhibits the highest coefficient of determination (R2) and the lowest root-mean-square errors (RMSE) when employing kernel ridge regression (KRR) and Gaussian processes regression (GPR) (R2 = 0.89 and 0.89 and RMSE = 8.99 µg/cm2 and 9.65 µg/cm2, respectively). Similar performance is closely observed for the UAV-Landsat and UAV-PlanetScope datasets (R2 = 0.86 and 0.87 for KRR, respectively). For the hybrid models, maximum performance is attained with Landsat data using KRR and GPR (R2 = 0.77 and 0.51 and RMSE = 33.10 µg/cm2 and 42.91 µg/cm2, respectively), followed by R2 = 0.75 and RMSE = 39.78 µg/cm2 for PlanetScope data upon integrating partial least squares regression (PLSR) into the hybrid model. Across all hybrid models, RapidEye data yielded the most stable performance, with R2 ranging from 0.45 to 0.71 and RMSE ranging from 19.16 µg/cm2 to 33.07 µg/cm2. The study highlights the importance of synergizing UAV and satellite data which enables effective monitoring of canopy chlorophyll in small agricultural lands.

Efficient resource allocation is crucial in clusters with frugal Single-Board Computers (SBCs) possessing limited computational resources. These clusters are increasingly being deployed in edge computing environments in resource-constrained settings where energy efficiency and cost-effectiveness are paramount. A major challenge in Hadoop YARN scheduling is load-balancing, as frugal nodes within the cluster can become overwhelmed, resulting in degraded performance and frequent occurrences of out-of-memory errors, ultimately leading to job failures. In this study, we introduce an Adaptive Multi-criteria Selection for Efficient Resource Allocation (AMS-ERA) in Frugal Heterogeneous Hadoop Clusters. Our criterion considers CPU, memory and disk requirements for jobs and aligns the requirements with available resources in the cluster for optimal resource allocation. To validate our approach, we deploy a heterogeneous SBC-based cluster consisting of 11 SBC nodes and conduct several experiments to evaluate the performance using Hadoop wordcount and terasort benchmark for various workload settings. The results are compared to the Hadoop-Fair, FOG and IDaPS scheduling strategies. Our results demonstrate a significant improvement in performance with the proposed AMS-ERA, reducing execution time by 27.2%, 17.4% and 7.6% respectively using terasort and wordcount benchmarks.

Dengue, a perilous fever-type illness transmitted by mosquitoes, remains a significant global health concern. The incidence of dengue outbreaks is primarily influenced by climate factors, contributing to fluctuating dengue cases. Therefore, this study aims to develop predictive models for dengue outbreaks employing Machine Learning (ML) techniques. Four distinct ML models, namely K-Nearest Neighbor (KNN), Random Forest (RF), Gradient Boosting Regressor (GBR), and Support Vector Regressor (SVR), were employed in this study. Prior to model analysis, thorough data preprocessing was conducted. In some instances, certain attributes exhibiting sparse correlations with dengue occurrence were eliminated based on correlation analysis. Upon finalizing the models, performance evaluation was executed through comparison based on Mean Absolute Error (MAE) metrics. The findings of this comparative analysis revealed that the KNN model exhibited significantly superior performance compared to the other three models. This outcome underscores the potential of KNN in enhancing the accuracy of dengue outbreak predictions.

Contrary to previous belief, mutation frequency also depends on how essential a gene is. Mutation frequency is substantially lower in the coding regions of essential genes and higher in less essential genes. Even though the mutation bias based on gene essentiality is incapable of invalidating Darwinism, this bias certainly added a rather unsubtle obstacle to it by contradicting a paradigm that was widely held: that mutations are random in the sense of being independent of their function for the organism. The reason this bias occurs is currently unknown. Here, I present the theoretical solution of why genetic mutations also depend on whether the gene is more or less essential. My theory is that each gene or epigene has its own level of resistance to entropic elevation, something directly proportional to the frequency of its expression. The more a gene is expressed, the higher is its resistance to entropic elevation and vice versa. For genetic information to be conserved instead of suffering mutation, a relevant factor is also the frequency of its expression. The energy expenditure directed to a gene of current utility engenders resistance to entropic elevation of the information encoded in that gene, as energy enables not only the existence of information but also its conservation. My theory—which is based on fundamental physics and contains predictions that can be empirically tested—solves a crucial problem in evolutionary biology and genetics; if I am right, I will have established a biological law. Finally, my aim here is also to provide a substantial advance in knowledge about the relationship between information, genetics, and thermodynamics.

Transition to renewable energy has been recognized as a crucial step to addressing climate change and achieving greenhouse gas reduction targets, but it can also cause energy sprawl if not planned properly. Clean renewable energy communities (CREC) are emerging globally as an approach for decentralized energy systems and an alternative to traditional centralized energy systems. CREC aims to lower the energy carbon footprint, enhance local energy resilience, and improve the quality of life of residents. Through a comprehensive literature review, this study reviews metrics that can assess the impact of energy transition plans and support decision-making to select technologies that create efficient, reliable, and accessible energy systems. It classifies these metrics into a five-dimensional sustainability approach: environmental, technical, social, economic, political and institutional. The paper proposes a conceptual framework to guide decision-makers in recognizing the role of sustainable land development, sustainable energy planning, and resiliency as an integrated approach to energy transition planning. This framework stresses mapping the place-based potential for clean renewable energy at various scales, highlights the importance of resilience in energy planning, and addresses challenges associated with energy source selection, built environment efficiency, and energy trade. While the framework can serve as a starting point for evaluating energy transition plans, further work is needed to address the limitations of existing metrics and identify additional evaluations for energy mixed land use that are critical to managing energy sprawl on ecosystem services and other land uses.

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. The rise in airways epithelial barrier permeability alters the tissue homeostasis and allows the allergen and other external agents penetration. Different factors contribute to barrier impairment, such as eosinophilic infiltrate and allergens proteases action: the eosinophilic cationic proteins and the allergens' proteolytic activity have a central role in contributing to epithelial damage. In the airways, the allergens proteases degrade the epithelial junctional proteins allowing the allergen penetration and the uptake by dendritic cells. The increase in allergen-immune system interactions induce the release of the alarmins and the activation of type 2 inflammatory pathways causing, or worsening, the main symptoms at skin, bowel and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic proteases-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance and progression. We further will explore clinical and radiological potential biomarkers of airways remodeling in allergic asthma patients.

Pancreatic cancer presents formidable challenges due to rapid progression and resistance to conventional treatments. Oncolytic viruses (OVs) selectively infect cancer cells and cause cancer cells to lyse, releasing molecules that can be identified by the host’s immune system. Moreover, OV can carry immune-stimulatory payloads such as interleukin-12 which when delivered locally can enhance immune system-mediated tumor killing. OV’s are very well tolerated by cancer patients due to their ability to selectively target tumors without affecting surrounding normal tissues. OV’s have recently been combined with other therapies including chemotherapy and immunotherapy to improve clinical outcomes. Several OVs including adenovirus, herpes simplex viruses (HSV), vaccinia virus, parvovirus, reovirus, and measles virus have been evaluated in preclinical and clinical settings for the treatment of pancreatic cancer. We evaluated the safety and tolerability of a replication-competent oncolytic adenoviral vector carrying two suicide genes (thymidine kinase, TK; and cytosine deaminase, CD) and human interleukin-12 (hIL12) in metastatic pancreatic cancer patients in a phase 1 trial. This vector was found to be safe and well-tolerated at the highest doses tested without causing any significant adverse events (SAE). Moreover, long-term follow-up studies indicated an increase in the overall survival (OS) in subjects receiving the highest dose of the OV. Our encouraging long-term survival data provide hope for patients with advanced pancreatic cancers, a disease that has not seen a meaningful increase in OS in the last five decades. In this review article, we highlight several preclinical and clinical studies and discuss future directions for optimizing OV therapy in pancreatic cancer. We envision OV-based gene therapy to be a game changer in the near future with the advent of newer generation OVs that have higher specificity and selectivity combined with personalized treatment plans developed under AI guidance.

Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptors, human epidermal growth factor receptor 2, and progesterone receptors (PR). TNBC has the poorest prognosis among breast cancer subtypes and is more likely to respond to immunotherapy due to its higher expression of PD-L1 and a greater percentage of tumor-infiltrating lymphocytes. Immunotherapy has revolutionized TNBC treatment, especially with the FDA's approval of pembrolizumab (Keytruda) combined with chemotherapy for advanced cases, opening new avenues for treating this deadly disease. Although, immunotherapy can significantly improve patient outcomes in a subset of patients, achieving the desired response rate for all remains an unmet clinical goal. Strategies that improve responses to immune checkpoint blockade, including combining immunotherapy with chemotherapy, molecularly targeted therapy, or radiotherapy may improve response rates and clinical outcomes.  In this review, we provide a short background on TNBC and immunotherapy and explore the different types of immunotherapy strategies that are currently being evaluated in TNBC. Additionally, we review why combination strategies may be beneficial, provide an overview of the combination strategies, and discuss the novel immunotherapeutic opportunities that may be approved in the near future for TNBC.

Acute myeloid leukemia (AML) is a malignant disease of the blood and bone marrow that is characterized by uncontrolled clonal proliferation of abnormal myeloid progenitor cells. Nucleophosmin 1 (NPM1) gene mutations are the most common genetic abnormality in AML, detectable in blast cells from about one third of adults with AML. AML NPM1mut is recognized as a separate entity in the World Health Organization (WHO) classification of AML. Clinical and survival data suggest that patients with this form of AML often have a more favorable prognosis, which may be due to the immunogenicity created by the mutations in the NPM1 protein. Consequently, AML with NPM1mut can be considered an immunogenic subtype of AML. However, the underlying mechanisms of this immunogenicity and associated favorable survival outcomes need to be further investigated. Immune checkpoint molecules, such as the programmed cell death-1 (PD-1) protein and its ligand, PD-L1, play important roles in leukemogenesis through their maintenance of an immunosuppressive tumor microenvironment. Preclinical trials have shown that the use of PD-1/PD-L1 (PDx) checkpoint inhibitors in solid tumors and lymphoma work best in novel therapy combinations. Patients with NPM1mut AML may be better suited to immunogenic strategies that are based on the inhibition of the immune checkpoint pathway of PDx than patients without this mutation, suggesting the genetic landscape of patients may also inform best practice for the use of PDx inhibitors.

Results from the phase III Keynote-024 clinical trial have established Pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR and ALK wild-type. However, given the differences between patients treated in routine clinical practice and within a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-up, we designed a retrospective observational study of patients with NSCLC who were treated with Pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were to assess PFS and OS using the Kaplan-Meier method, treatment response and safety. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6-10.0) and 25.5 months (95% CI: 21.8-31.6), respectively. We also found that ECOG PS, PD-L1 expression and smoking habit were prognostic factors for PFS, while age, sex, ECOG PS, smoking habit and histology had an impact on OS. Multivariable analysis confirms prognostic role of PD-L1 for PFS and ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of Pembrolizumab in the first-line setting as well as a safety profile consistent with the results of Keynote-042. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution.

Multiple biological pathways manifest and latent, meant for human survival, become a liability in cancer cure. With an increasing understanding of innumerable complex paths, cancer progression and development of resistance is no surprise. For the three “vasculature-immune-phenotypic” fundamental changes, hypoxia is the maestro orchestrating the whole gamut of changes (through the master manipulator - HIF-1 α), simultaneously transactivating hundreds of pro-angiogenic genes. Such a complex molecular bio-network begs the question, “Is our cancer research caught in such a tangled web that we have lost sight of the Spider?”. Hypoxia is this Spider weaving compensatory webs with every intervention/ obstruction. Anti-angiogenic (AAG) research has been conducted mainly in silos – exploring independent paths. This review conceptualizes a convergence of a multitude of research worldwide to a single theme of normalizing vasculature as a primary baseline for overcoming resistance to AAGs or their combinations.

Glioblastoma (GBM) is the most common primary brain tumor. Due to high resistance to treatment, local invasion, and high risk of recurrence, GBM patient prognoses are often dismal, with median survival around 15 months. The current standard of care is threefold: surgery, radiation therapy and chemotherapy with temozolomide (TMZ). However, patient survival has only marginally improved. Radioimmunotherapy (RIT) is a fourth modality under clinical trials and aims at combining immunotherapeutic agents with radiotherapy. Here, we develop in vitro assays for rapid evaluation of RIT strategies. Using a standard cell irradiator and an Electric Cell Impedance Sensor, we quantify cell migration following the combination of radiotherapy and chemotherapy with TMZ and RIT with durvalumab, a PD-L1 immune checkpoint inhibitor. We measure cell survival using a cloud-based clonogenic assay. Irradiated T98G and U87 GBM cells migrate significantly (p < 0.05) more than untreated cells in the first 20-40 hours post-treatment. Addition of TMZ increased migration rates for T98G at the 20 Gy (p < 0.01). Neither TMZ nor durvalumab significantly changed cell survival in 21 days post-treatment. Interestingly, durvalumab abolished the enhanced migration effect, indicating possible potency against local invasion. These results provide parameters for rapid supplementary evaluation of RIT against brain tumors.

Several therapeutic monoclonal antibodies are approved by FDA against the PD-1/PD-L1 (programmed death-1/programmed death ligand-1) immune checkpoint, which has been a great success in cancer treatment. However, existing therapeutics, including small molecules inhibitors against PD-L1 checkpoint have certain drawbacks such as high cost and drug resistance that challenge the current available anti-PD-L1 therapy. Thereof, this study presents the screening of 32552 compounds from Natural Product Atlas database against PD-L1, including three steps of structure-based virtual screening and binding free energy refinement for the selection of potent PD-L1 inhibitors. Subsequently, five natural compounds, i.e., Neoenactin B1, Actinofuranone I, Cosmosporin, Ganocapenoid A, and 3-[3-hydroxy-4-(3-methylbut-2-enyl)phenyl]-5-(4-hydroxybenzyl)-4-methyldihydrofuran-2(3H)-one, were collected based on the ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling and binding free energy (>-70 kcal/mol) for further computational investigation by comparison to co-crystallised ligand, i.e. JQT inhibitor. Based on interaction mapping, explicit 100 ns molecular dynamics simulation, and post binding free energy calculations, all the compounds exhibited intermolecular interactions (hydrogen and hydrophobic) with essential residues and substantial complex stability by comparison to the JQT inhibitor. Collectively, the calculated results advocate the selected natural compounds as the putative potent inhibitors of PD-L1 and, therefore, can be considered for further development of PD-L1 immune checkpoint inhibitor in cancer immunotherapy.

This review of the meaningful data from 2021 on cervical, endometrial, and ovarian cancers aims to provide an update of the most clinically relevant studies presented at important oncologic congresses during the year [the American Society of Clinical Oncology (ASCO) Annual Meeting, the European Society for Medical Oncology (ESMO) Congress and the Society of Gynecologic Oncology (SGO) Annual Meeting]. Despite the underlying existence of the COVID-19 pandemic, the last year has been notable in terms of research, with significant and promising advances in gynecologic malignancies. Several major studies reporting the effects of innovative therapies for patients with cervical, endometrial, and ovarian cancers might change the medical practice in the future.

Background: Ovarian cancer (OC) represents the eighth most common cancer and the fifth leading cause of cancer-related deaths among the female population. In the advanced setting, chemotherapy represents the first-choice treatment, despite a high recurrence rate. In the last ten years, immunotherapy based on immune checkpoint inhibitors (ICIs) has profoundly modified the therapeutic scenario of many solid tumors. We sought to summarize the main findings regarding the clinical use of ICIs in the OC. Methods: We searched the PubMed, Embase, and Cochrane Databases, and conference abstracts from international congresses (such as ASCO, ESMO, SGO) for clinical trials, focusing on ICIs both as monotherapy and as combinations in the advanced OC. Results: 20 studies were selected, of which 16 were phase I or II and 4 phase III trials. ICIs targeting PD1 (nivolumab, pembrolizumab), PD-L1 (avelumab, atezolizumab, durvalumab), and CTLA4 (ipilimumab, tremelimumab) were employed. No significant survival improvement was achieved; conversely, early terminations due to futility or toxicity were recorded. Combinations with chemotherapy, anti-VEGF, and, overall, PARP-inhibitors seem feasible and enhance the response rate and survival, notwithstanding a worse safety profile. Conclusions: The identification of biomarkers with a predictive role for ICIs’ efficacy is mandatory. Moreover, genomic and immune profiling of the OC might lead to an improved treatments selection and design of tailored trials.

The Herpes Virus Entry Mediator (HVEM) delivers a negative signal to T cells mainly through the B and T Lymphocyte Attenuator (BTLA) molecule and thus, could represent a novel immune checkpoint during an anti-tumor immune response. A formal demonstration that HVEM can be targeted for cancer immunotherapy is however still lacking. Here, we first show that HVEM and BTLA were associated to a worse prognosis in patients with prostate adenocarcinomas, indicating a detrimental role for this pair of molecule during prostate cancer progression. We then show that a monoclonal antibody to human HVEM significantly impacted the growth of a prostate cancer cell line in immuno-compromised NOD.SCID.gc-null mice reconstituted with human T cells. Using CRISPR/Cas9, we showed that HVEM expression by the tumor was mandatory to observe the therapeutic effect. Mechanistically, tumor control was dependent on CD8+ T cells and was associated to an increase in the proliferation and number of tumor-infiltrating leukocytes. Accordingly, the expression of genes belonging to various T cell activation pathways were enriched in tumor infiltrating leukocytes, whereas genes associated with immuno-suppressive pathways were decreased, possibly resulting in modifications of leukocyte adhesion and motility. Finally, we developed a simple in vivo assay in humanized mice to directly demonstrate that HVEM was an immune checkpoint for T-cell mediated tumor control. Our results show that targeting HVEM is a promising strategy for prostate cancer immunotherapy.

Different therapeutic strategies have been investigated to target and eliminate HIV-1-infected cells by using armed antibodies specific to viral proteins, with varying degrees of success. Herein, we propose a new strategy by combining photodynamic therapy (PDT) with HIV Env-targeted immunotherapy, and refer to it as HIV photoimmunotherapy (PIT). A human anti-gp41 antibody (7B2) was conjugated to two photosensitizers with different charges through different linking strategies; “Click” conjugation by using an azide-bearing porphyrin attached via a disulfide bridge linker with a drug-to-antibody ratio (DAR) of exactly 4, and “Lysine” conjugation by using phthalocyanine IRDye 700DX dye with average DARs of 2.1, 3.0 and 4.4. These photo-immunoconjugates (PICs) were compared via biochemical and immunological characterizations regarding the dosimetry, solubility, and cell targeting. Photo-induced cytotoxicity of the PICs were compared using assays for apoptosis, reactive oxygen species (ROS), photo-cytotoxicity, and confocal microscopy. Targeted phototoxicity seems to be primarily dependent on the binding of PS-antibody to the HIV antigen on the cell membrane, whilst being independent of the PS type. This is the first report of the application of PIT for HIV immunotherapy by killing HIV Env-expressing cells.

Background: Prostate cancer (PCa) is characterized by significant heterogeneity in its molecular, genomic, and immunologic characteristics. Methods: Whole transcriptome RNAseq data from The Cancer Genome Atlas of prostate adenocarcinomas (n=496) was utilized. The immune microenvironment was characterized using the CIBERSORTX tool to identify immune cell type composition. Unsupervised hierarchical clustering was performed based on immune cell type content. Analyses of progression-free survival (PFS), distant metastases, and overall survival (OS) were performed using Kaplan-Meier estimates and Cox-regression multivariable analyses. Results: Four immune clusters were identified, largely defined by plasma cell, CD4+ Memory Resting T Cells (CD4 MR), M0 and M2 macrophage content (CD4 MRHighPlasma CellHighM0LowM2Low, CD4 MRLowPlasma CellHighM0LowM2Low, CD4 MRHighPlasma CellLowM0HighM2Low, and CD4 MRHighPlasma CellLowM0LowM2High). The two macrophage-enriched/plasma cell non-enriched clusters (3&4) demonstrated worse PFS (HR 2.24, 95% CI 1.46–3.45, p=0.0002) than the clusters 1&2. No metastatic events occurred in the non-macrophage-enriched clusters. Comparing clusters 3 vs 4, in patients treated by surgery alone, cluster 3 had zero progression events (p<0.0001). However, cluster 3 patients had worse outcomes after post-operative radiotherapy (p=0.018). Conclusion: Distinct tumor immune clusters with a macrophage-enriched phenotype and reduced plasma cell enrichment independently characterize an aggressive phenotype in localized prostate cancer that may differentially respond to treatment.

The recent pandemic has greatly stressed supply chains, treatment modalities, and medical resources. Cold atmospheric plasma (CAP) has been used for a wide range of applications in biomedical engineering due to its many components including electrons, charged particles, reactive oxygen species (ROS), reactive nitrogen species (RNS), free radicals, ultraviolet (UV) photons, molecules, electromagnetic fields, physical forces, and electric fields. In this manuscript, we develop CAP devices for COVID-19. Our manuscript indicates the advantages of highlydeployable CAP devices for both sanitation and treatment, without the need for supply chains of special consumables such as hand sanitizers and the like. We hope that this timely research will help engage the broader community of engineers that wish to help the medical community with this pandemic and to prevent and treat future outbreaks.

The analysis of aggregate data has received increasing attention in the statistical discipline over the past 20 years. Much of this attention has been focused on estimating the cells frequencies of a 2×2 contingency table given only the marginal totals; the analyses proposed have been received with missed reviews. More recently, the focus has shifted toward analysing the overall association structure rather than on the estimation of the cell frequencies. This article provides some insight int how informative the aggregate data of a single 2×2 contingency table is for assessing the association. The information contained in the margins of the table is quantified using the squared deviation of the expected cell frequencies over the possible range of values, where the row and column totals are known and fixed. The new measure we discuss to quantify this association is referred to as the aggregate informative index (AII) and is shown to be the standardized area under the squared deviation curve.

Smith-Magenis syndrome is a complex neurobehavioral genetic disorder. The spectrum of SMS phenotype is broad but commonly includes craniofacial, neurobehavioral, and otolaryngologic features. While the etiology of SMS is commonly attributed to one copy interstitial deletion in the 17p11.2 region (90-95% of cases), variants identified by sequence analysis in RAI1 have also been reported in 5-10% of cases. The phenotypic spectrum of patients with RAI1 sequence alterations is not clear. In this study, we report a 9-year-old male with global cognitive and psychomotor developmental delay, musculoskeletal and cardiovascular abnormalities, and dysmorphic craniofacial features. Whole genome quad analysis of the proband, unaffected parent, and unaffected brother identified a novel de novo RAI1:c.2736delC variant. This is the first report of this variant in the literature. This report also highlights the details of the genome analysis and this patient's phenotypic spectrum.

Exploiting the van der Waals model of liquids, it is possible to derive analytical formulas for the thermodynamic functions governing solvation, the transfer of a solute molecule from a fixed position in the ideal gas phase to a fixed position in the liquid phase. The solvation Gibbs free energy change consists of two contributions: (a) the high number density of all liquids and the repulsive interactions due to the basic fact that each molecule has its own body lead to the need of spending free energy to create a cavity suitable to host the solute molecule; (b) the ubiquitous intermolecular attractive interactions lead to a gain in free energy for turning on attractions between the solute molecule and surrounding liquid molecules. Also the solvation entropy change consists of two contributions: (a) there is an entropy loss in all liquids because the cavity presence limits the space accessible to liquid molecules during their continuous translations; (b) there is an entropy gain in all liquids, at room temperature, due to the liquid structural reorganization as a response to the perturbation represented by solute insertion. The latter entropy contribution proves to be balanced by a corresponding enthalpy term. This scenario emerged from the van der Waals model is in qualitative agreement with experimental results.

A significant challenge encountered in mmWave and Sub-terahertz systems used in 5G and 1 the upcoming 6G networks is the rapid fluctuation in signal quality across various beam directions. Extremely high-frequency waves are highly vulnerable to obstruction, making even slight adjustments in device orientation or the presence of blockers capable of causing substantial fluctuations in link quality along a designated path. This issue poses a major obstacle because numerous applications with low-latency requirements necessitate precise forecasting of network quality from many directions and cells. The method that is proposed in this research demonstrates an avant-garde approach for assessing the quality of multi-directional connections in mmWave systems by utilizing the Liquid Time Constant network (LTC) instead of the conventionally used Long Short-Term Memory (LSTM) technique. The method’s validity was tested through an optimistic simulation involving the monitoring of multi-cell connections at 28 GHz in a scenario where humans and various obstructions were moving arbitrarily. The results with LTC are significantly better than those obtained by conventional approaches such as LSTM. The latter resulted in a test Root Mean Squared Error (RMSE) of 3.44 dB, while the former, 0.25 dB, demonstrating a 13-fold improvement. For better interpretability and to illustrate the complexity of prediction, an approximate mathematical expression is also fitted to the simulated signal data using Symbolic Regression.

Optimizing warehouse operations and leveraging data insights are driving forces behind the rise of automation. This research explores the development of the SWIF warehouse management system (WMS) using the Agile methodology, a departure from traditional software development approaches. Agile’s iterative and step-by-step approach facilitated a streamlined development process. It allowed for quick adjustments based on evolving needs and feedback from stakeholders. This resulted in a substantial decrease in development time and a noticeable improvement in the final product’s quality. The study emphasizes the positive effect of Agile on teamwork and customer satisfaction. Developers reported enhanced communication and collaboration, leading to a stronger sense of ownership and engagement. Customers expressed greater satisfaction with the features and functionalities delivered in stages. The successful implementation of Agile in SWIF’s development showcases its effectiveness in managing complex and ever-changing software development projects. The study encourages the adoption of Agile methodology for similar projects to boost responsiveness, quality, and overall project success.

The Metaverse of Things (MoT) is an advanced technology that has the potential to revolutionise urban living in the present era. This article explores the advantages, uses, and transformative outcomes of MoT in smart cities. The covered subjects encompass sustainability, urban planning, citizen participation, infrastructure management, and various more. MoT integrates the Internet of Things (IoT) with metaverse technologies. The ultimate objective is to develop virtual environments that are highly interactive, interconnected, and immersive while maintaining a high level of fidelity to reality. The IoT utilises virtual reality (VR), augmented reality (AR), and other digital technologies to gather data, facilitate communication, and automate certain processes, thereby enhancing several elements of urban living. It is all a component of the metaverse. The IoT will bring about a profound transformation in the way cities gather and utilise data to enhance services and optimise efficiency. Cities that can efficiently distribute this data can enhance public safety, optimise energy usage, regulate traffic, and manage waste properly. MoT apps that utilise immersive technologies and the IoT can be used to generate more intelligent and captivating cityscapes. The implementation of MoT can greatly enhance the quality of life for residents of smart cities through improvements in transportation, healthcare, education, and community engagement. The study's author examined how smart cities utilise the IoT to enhance the daily experiences of their inhabitants. This study examines the technical structure, possible advantages, and difficulties of implementing MoT in urban settings, aiming to enhance the resilience, responsiveness, and adaptability of cities. The findings emphasise the importance of robust legislative frameworks, stringent security requirements, and well-developed infrastructure to facilitate the extensive use of MoT technology. These factors are crucial for establishing a highly interconnected and efficient urban environment.

The Double Diaphragm Forming (DDF) process uses vacuum pressure and heat to pre-shape composite reinforcements between flexible diaphragms. Accurate modelling of heat transfer within DDF requires knowledge of the thermophysical properties of the constituent materials. This study investigates the specific heat and thermal conductivity of silicone diaphragms, carbon fibers (chopped and powdered), thermoplastic veils, and their combinations. Experiments measured the specific heat of each material using differential scanning calorimetry and the thermal conductivity of silicone and carbon fabric preforms using the transient plane source method and modified transient plane source method respectively. The influence of reheating cycles on specific heat of carbon fiber-veil samples and the effect of compaction on thermal conductivity of silicone and carbon fabrics were explored. While silicone exhibited linear specific heat behavior, the thermoplastic veil showed non-linearity due to phase change. The combined carbon fiber-veil samples demonstrated slight non-linear specific heat variations depending on reheating cycles. Thermal conductivity of the fabric preforms decreased with the addition of thermoplastic veil and under vacuum-compaction conditions. The established temperature-dependent property relationships provide valuable data for optimizing DDF preforming parameters and enhancing energy efficiency in composite manufacturing.

The growth rate in academic and scientific publications increased very fast. Researchers must choose a good representative and significant literature in publications, which has become challenging worldwide. Usually, the paper citation number indicates this paper's potential influence and importance. However, this standard metric of citation numbers cannot be used as a measurement to judge the popularity and significance of the recently published papers. To address this challenge, this paper presents an effective prediction method called FutureCite to predict the future citation level of research articles. FutureCite combines machine learning with text and graph mining techniques, leveraging their abilities in classification, datasets in-depth analysis, and feature extraction. FutureCite aims to predict future citation levels of research articles applying a multilabel classification approach. FutureCite can extract significant semantic features and capture the interconnection relationships found in scientific articles during feature extraction using textual content, citation networks, and metadata as feature resources. Our goal is to contribute to the advancement of substantial effective approaches impacting the citation counts in scientific publications by enhancing the precision of future citations. We conducted several experiments using a comprehensive publication dataset to evaluate our method and determine the impact of using a variety of machine learning algorithms. FutureCite demonstrated its robustness and efficiency and showed promising results based on different evaluation metrics. Using the FutureCite model has significant implications in improving the researchers' ability to determine targeted literature for their research and better understand the potential impact of research publications.

A recent study revealed a persistent presence of the PP-Spike recombinant protein in 50% of individuals who received ModRNA injections, contrasting with unvaccinated controls, whether SARSCoV-2 infected or not, up to 187 days post-injection. The implications of these findings are discussed in the context of PP-Spike recombinant protein-induced hyperimmune/inflammatory reactions and thrombotic vasculitis as mechanisms to elucidate the serious side effects, long-term organ complications, and excess deaths observed after administering Covid ModRNA products. These results underscore the urgent need for a comprehensive reassessment of the risk-benefit profile of ModRNA injections, including an immediate halt in their use for any person, and a renewed emphasis on understanding and addressing their long-term effects on human health

Automation is transforming ship design by enhancing flexibility, efficiency, and accuracy in Computer-Aided Ship Design (CASD). This review highlights advancements in automation and parametric techniques that streamline the design process. Variable geometry and task automation improve performance optimization, enabling designers to concentrate on complex elements. The review will talk about advanced tools and methodologies, their effects on design optimization, production workflows, and some of the challenges associated with software interoperability and increased design complexity. It will also look at how AI and machine learning can be leveraged for better automation. The review identifies several future opportunities in automated ship design but frames such technologies as revolutionary in the shipbuilding sector and highlights their potential to bring significant transformation to shipping.

The structural integrity of the gastrointestinal tract is important because it dictates the functionality of this system. Regarding this, GALT (gut-associated lymphoid tissues) have a significant role in immunity. Most cancer research focuses on organized lymphoid structures and less on diffuse structures such as the lamina propria (LP). Therefore, this paper aims to investigate the link between LP and cancer in humans. The interstitial matrix and loose connective tissue layer located directly under the epithelium is known as the LP. In this area, there are a lot of IgA+ plasma cells (PCs), T and B lymphocytes, macrophages, dendritic cells (DCs), and stromal cells (SCs). Antigens from the lumen are picked up by LP DCs and presented directly to B cells, which may cause IgA class switching and differentiation in the presence of T cells. In humans, the GALT of the mucosa has been proposed as the source of a unique malignancy known as "GALT carcinoma," which is thought to represent the "third pathway of colorectal carcinogenesis." However, present colorectal cancer classifications do not define GALT carcinoma as a separate histologic category.

This paper explores the intersection of geometry and music, investigat- ing how mathematical structures shape musical theory, composition, and perception. It begins by examining the geometric foundations of pitch organization, including the circular representation of pitch classes and the tonal space. We then explore rhythmic structures through symmetry, analysing how patterns in time are geometrically conceived. Finally, the study examines more recent developments in computational music theory, such as the use of topological data analysis to model musical transformations and voice leading.

A simple model of a measurement in a laboratory isolated from the environment is analyzed in detail, demonstrating the features of the collapse effect. Such an experiment can readily be implemented today under the idealization of an observer's memory as a simple quantum system. The central role of loss of information is emphasized.

Background and Objectives: Proteomics encompasses the exploration of protein composition, regulation, function, and pathways. Its influence spans diverse clinical fields and holds promise in addressing various women’s health conditions, including cancers, osteoporosis, and cardiovascular disorders. However, no comprehensive summary of proteomics and menopausal health exists. Our objective was to summarize proteomic profiles associated with diseases and disorders in peri and postmenopausal women. Materials and Methods: We conducted a comprehensive search of databases including PubMed, Google Scholar, Cochrane database, Elsevier, and ScienceDirect until 2022. A total of 253 studies were identified, 41 studies met the inclusion criteria to identify data of interest. These included study design, disease, and proteomics/proteins of significance as described by the authors. Results: The 41 studies, covered diverse areas including bone disorders (10 studies), cardiovascular diseases (5 studies), oncological malignancies (10 studies), and conditions such as obesity, nonalcoholic liver disease, the effects of hormone replacement therapy, and neurological diseases (16 studies). Results of our study indicate that proteomic profiles correlate with heart disease in peri- and postmenopausal women, with distinct sex differences. Furthermore, proteomic profiles significantly differed between women with and without osteoporosis. Additionally, patients with breast, ovarian, and endometrial cancer exhibited notable variations in proteomic profiles compared to those without these conditions. Conclusions: Proteomics has the potential to enhance risk assessment and disease monitoring in peri- and postmenopausal women. By analyzing unique protein profiles, clinicians can identify individuals with heightened susceptibility to specific diseases or those already affected by established conditions. This review suggests that there is sufficient preliminary data for proteomics in peri- and postmenopausal women for early identification of cardiovascular disease, osteoporosis, and cancers, in disease monitoring, and in tailoring individualized therapies. Rigorous validation studies involving large populations are essential before drawing definitive conclusions regarding the clinical applicability of proteomic findings.

Treatment of HIV-associated lymphoma (HIV-Ly) with autologous stem cell transplantation (ASCT) has shown a surprisingly low relapse rate in several series. The aim of this study was to compare the clinical outcomes of HIV-Ly and lymphomas of the general population receiving ASCT. We compared two series of consecutive HIV-positive and HIV-negative patients, based on a 1:1 propensity score analysis, matching for age, sex, histology, disease status and prior therapies. We identified 44 patients in both groups. All HIV-positive patients received combination antiretroviral therapy (cART). With a median follow-up of 51 months, PFS was significantly higher in HIV-positive patients (4-years PFS 81% and 51%, in HIV-positive and HIV-negative patients, respectively, p=0.027). Four-year OS was 81% for HIV-positive and 67% in HIV-negative patients (p=0.15). The relapse rate was significantly higher in HIV-negative patients (36% vs 23%) (p=0.04). Our results clearly show that ASCT is an effective curative option for HIV-Ly, with better PFS and lower relapse rate compared to uninfected patients. A favourable effect of ASCT on HIV infection and immune system recovery, potential off-target effects of cART or other yet unknown factors may account for this observation.

The concept of intelligence has many applications, such as coatings and cyber security. Smart coatings have the ability to sense and/or response to external stimuli and generally interact with their environment. Self-healing coatings represent a significant advance in improving material durability and performance using microcapsules and nanocontainers loaded with self-healing agents, catalysts, corrosion inhibitors, and water-repellents. These smart coatings can repair damage on their own and restore mechanical properties without external intervention and are inspired by biological systems. Properties that are affected by either momentary or continuous external stimuli in smart coatings can be related to corrosion, fouling, fungal, self-healing, pie-zoelectric, microbiological, etc. These coating properties can be obtained via combinations of either organic or inorganic polymer phases, additives and pigments. In this article, a review on the advancements of micro/nanocapsules for self-healing coatings is reported from the aspect of ex-trinsic self-healing ability. The concept of extrinsic self-healing coatings is based on the use of capsules or multichannel vascular systems loaded with healing agents/inhibitors. The outcome is that self-healing coatings exhibit improved properties compared to traditional coatings. It is mentioned that self-healing anticorrosive coating not only has enhanced passive barrier function, but also realizes active defense. As a result, there is a significant improvement of the service life and overall performance of the coating. Future research should be devoted to refining self-healing mechanisms and developing cost-effective solutions for a wide range of industrial applications.

Game-based learning assessments lean on educational data mining approaches such as stealth assessments and quasi mixed-methods that help gather student learning proficiency. Rarely do we see approaches where student proficiency in learning is woven into the game's design. Educational Burst Games (EBGs) is a new approach to improving learning proficiency by designing fast-paced, short, repetitive, and skill-based games. They have the potential to be effective learning interventions both during instruction in the classroom and during after-school activities such as assignments and homework. Over five years we have developed two EBGs aimed at improving linear algebra concepts of undergraduate students. In this study, we provide results of an in-depth evaluation of the two EBGs developed with 45 participants that represent our target population. We discuss the role of EBGs and their design constructs such as pace and repetition, the effect of the format (2D vs. 3D), the complexity of the levels and the influence of prior knowledge on the learning outcomes.

Orificed Hollow Cathodes are electric devices necessary for the functioning of common plasma thrusters for space applications. From their reliability mainly depends the success of a spacecraft’s mission equipped by electric propulsion. The development of plasma models is crucial in the evaluation of plasma properties within the cathodes that are difficult to measure due to the small dimensions. Many models, based on non-linear system of plasma equations, have been proposed in the open literature. These are solved commonly by means of iterative procedures. This paper investigates the possibility to solve them by means of Particle Swarm Optimization method. The results of the validation tests confirm the expected trends for all the unknowns; the confidence bound of the discharge current as function of mass flow rate is very narrow (2÷5V), moreover the results match very well the experimental data except at the lowest mass flow rate (0.08mg/s) and discharge current (1A), where the computations underpredict the discharge current to the utmost by 40%; the highest data dispersion regards the plasma density in the emitter region (± 20 % of the average value) and the wall temperatures (± 50K respect to the average values) of orifice and insert; those of the others variables are very tiny.

Deuterium is a heavy nonradioactive isotope of hydrogen, having a neutron as well as a proton, making it twice as heavy. It is a natural element, present at 156 parts per million in seawater. The ATPase pumps in the mitochondria utilize proton motive force to drive ATP synthesis, and deuterons damage the pumps, producing a stutter that can cause reactive oxygen release and inefficiencies in ATP synthesis. Cellular metabolism incorporates several novel mechanisms to assure low deuterium content in the mitochondria and other organelles. Nicotinamide adenine dinucleotide (NAD) is a major carrier of deuterium depleted (deupleted) protons to supply the mitochondria. Many enzymes, especially flavoproteins, are able to use proton tunneling to fractionate out deuterium. In this paper, we argue that the amino acid proline is able to trap and sequester deuterium, and that peptidyl prolyl isomerases (PPIases) play a central role in facilitating deuterium trapping in proline-rich proteins, most notably collagen. The endothelial glycocalyx also sequesters deuterium in gelled water lining the blood vessels, creating a battery and promoting low deuterium in the circulation. Excess deuterium promotes cancer growth, and cancer cells release large quantities of lactate via aerobic glycolysis to help reverse deuterium overload, systemically.

The generation at the helm faces an unprecedented responsibility in the near future of artificial intelligence. The implications of setting up the founding rules that will regulate the operation of AI are heavy since after they’re set they last forever. Once this first AI is commenced, it can be such that no other subsequent AIs could emerge thereby assuming dominion over its own creation stand. As a result, retaining control becomes necessary. Lest humanity surrender agency to its own creation. At this juncture of big talks, critical issue are raised concerning AI administration owners. Is it appropriate for only a few people to have unrestricted control on AI commands while leaving out all precautionary measure? Therefore, we have to always consider between control and constraint when dealing with AI issues which involves authority plays off against morality. The direction Artificial Intelligence takes in the future depends on the decisions made by today’s generation. We will determine how we are viewed historically in terms of technology based on how well we take on such an important duty. There’s a major turning point ahead of us where we who are the stewards of tomorrow must make a choice that protects humanity’s right to self-determination and also exploits the power of AI for change.

In this article, we discuss the concept of infinity (∞), infinitesimals □ , and a new mathematical operation that expands calculations into the realm of the infinite. This breakthrough allows for the computation of infinite numbers, leading to new possibilities for mathematical research and practical applications. By introducing infinite numbers, numerous advantages arise, such as accurately representing limits, divergences in integrals and infinite series, and extending calculations to infinity. This mathematical advancement opens doors to exploring uncharted territories, offering valuable insights and breakthroughs

Vaccination, particularly against pneumoccus and influenza, is a low-cost primary prevention, useful to avoid hard complications, particularly among frail older people. In this study, we aimed to assess the effect of a strategy for influenza and pneumococcal vaccination for outpatients, never practiced before, evaluating what could stimulate or demotivate vaccination among older people. This study was conducted during the 2023-2024 influenza season at the outpatient clinics of the Geriatrics section, University Hospital of Palermo (Italy). A total of 101 vaccinations were carried out. Half of the patients could be considered as pre-frail and about 20% frail, according to a comprehensive geriatric evaluation. Among participants, 46.3% received only vaccination against Pneumococcus and 26.8% only anti-influenza or the combination of anti-pneumococcus and anti-influenza. Compared with the previous seasons, a 19.5% increase of influenza and 90.2 % of pneumococcal vaccine uptake was observed. Side effects of vaccination were the main reason of the previous rejections, namely 74.8% for influenza and 29.5% for anti-pneumococcal vaccination. In conclusion, our study indicates how a new vaccination strategy in different settings is possible. Proposing influenza and pneumococcal vaccination for outpatients could be an effective instrument to improve immunization coverage that is still low among older people.

The KOSovan Acute Coronary Syndrome (KOS-ACS) Registry is established as a prospective, continuous, nationwide, web-based registry that is operated online. The KOS-ACS registry is designed with the following objectives: 1) to obtain data on the demographic, clinical, and laboratory characteristics of ACS patients treated in Kosovo; 2) to create a national database with information on health care in ACS patients treated in Kosovo; 3) to identify the national features of associations between ACS characteristics and clinical outcomes, including mortality, complications, length of hospital stay, and quality of clinical care; and 4) to propose a practical guide for improving the quality and efficiency of ACS treatment in Kosovo. The Kosovo Society of Cardiology and University of Prishtina will be responsible for the development of the KOS-ACS registry and centralized data analysis at the national level. The KOS-ACS Registry will enroll all patients admitted, at any of the registered clinical centers, with the diagnosis of ACS and who will be clinically managed at any of the Kosovo hospitals. Data on patient demographics, clinical characteristics, previous and hospital drug treatment, and reperfusion therapy will be collected. The type of ACS (Unstable angina, NSTEMI or STEMI) will also be clearly defined. The time from first medical contact to balloon inflation (FMC-to-balloon) and door-to-ballon time will be registered. In-hospital death and complications will be registered. Data on post-hospital primary outcome (MACE: cardiac death, all-cause mortality, hospitalization, stroke, need for coronary revascularization) of patients, at 30 days and 1 year, will be included in the Registry.

Domestic crime, conflict, and instability pose a significant threat to many contemporary governments. These challenges have proven to be particularly acute within modern-day Mexico. While there have been significant developments in predicting intrastate armed and electoral conflict in various contemporary settings, such efforts have thus far been limited in their use of spatial as well as temporal correlations, as well as in the features they have consid- ered. Machine learning, especially deep learning, has been proven to be highly effective in predicting future conflicts using word embeddings in Convolutional Neural Networks (CNN) but lacks the spatial structure and, due to the black box nature, cannot explain the importance of predictors. We develop a novel methodology using machine learning that can accurately classify future anti-government violence in Mexico. We further demonstrate that our approach can identify important leading predictors of such violence. This can help policymakers make informed decisions and can also help governments and NGOs better allocate security and humanitarian resources, which could prove beneficial in tackling this problem. Using a variety of political event aggregations from the ICEWS database alongside other textual and demographic features, we trained various classical machine learning algorithms, including but not limited to Logistic Regression, Random Forest, XGBoost, and a Voting classifier. We considered a mix of CNN + Long Short Term Memory (LSTM) networks to decode the spatial and temporal relationship in the data. The performance of all the black box deep learning models was not at par with the classical machine learning models. We also evaluated the temporal relationships in the data to identify important predictors that fuel anti-government violence along with their directions using Shapley additive values. The voting classifier, utilizing a subset of features derived from LASSO across 100 simulations, consistently surpasses alternative models in performance and demonstrates efficacy in accu- rately classifying future anti-government conflicts. Notably, Random Forest feature importance indicates that some features, including but not limited to homicides, accidents, material conflicts, and positive worded citizen information sentiments emerge as pivotal predictors in the classification of anti-government conflicts. Finally, we conclude the research by analysing the spatial structure of the data using Moran’s I index extended version for spatiotemporal data to identify the global spatial dependency and local clusters followed by modelling the data spatially and evaluating the same using Gaussian Process Boost(GPBoost). The global spatial autocorrelation is minimal, characterized by local- ized conflicts cluster within the region. Furthermore, in Phase 3, the Voting Classifier method demonstrates superior performance over GPBoost, leading to the inference that no substantial spatial dependency exists among the various locations.

The study aimed to evaluate the impact of community policing on maintaining community safety and security by measuring the rate of crime prevention. Specifically, it sought to find out how the city administration of Addis Ababa demonstrated and promoted understanding of the community policing effort, information sharing, and community members' opinions regarding community policing in relation to local security procedures. Law enforcement initiatives to improve quality of life and reduce crime are also included. In order to be successful, community policing requires concrete actions and projects, and given the pervasive mistrust in today's public, both police departments and individual officers must take the lead. The findings demonstrated the influence of community policing, information sharing, and their results on local security practices as well as community policing among community members. According to one suggestion, the police should make sure that they interact positively with the community and that people are aware of their involvement in community policing. This way, people will be happy to provide the police with information that could help prevent crime. The public should be encouraged to maintain good connections with the police, as they can enhance community policing. Because it were obvious that doing so will improve society's peace and security, this study showed the need for additional efforts to further cement relationships of collaboration between the police and the community.

The purpose of the study is to analyse and to identify specific structural characteristics of melanocytic nevi. So, for better conclusions, using the optical microscope, could be possible a proper describtion related melanocytic nevi, reffering to youth pacients. In this research direction, good to mention that in a human individual life, play a significant role, different factors. That include in line, genetic, epigenetic, microbiomic, and proteomic factors. Future directions refers to preventive and prophylactic methods.

This analyses the impact of competition on liquidity creation in the banking industry of the United States. For the purposes of this paper panel data of US banks for the period of 1976-2000 is chosen as a sample. The plausible endogeneity issue is addressed by employing instrumental variables and then implementing two stages least squares method. Besides this, crisis period of 1990-1992 is also analyzed to compare effect with in “normal times”. The results show that decrease in the level of competition negatively affects the liquidity creation ability of banks in the US and this impact is even more negative during the crisis period.

In this paper, we consider particles together with the surrounding space as an indivisible system, and then investigate the maximum symmetry of the system at the quantum level. We introduce a new quantity to describe the evolution of this system before and after measurement. The effective mass of gravity is estimated. We also show that a free quantum particle as the source of energy and momentum do not produce gravity.

Let $\mathcal{X}$ be a Banach space. Let $\{\tau_j\}_{j=1}^n, \{\omega_k\}_{k=1}^m\subseteq \mathcal{X}$ and $\{f_j\}_{j=1}^n$, $\{g_k\}_{k=1}^m\subseteq \mathcal{X}^*$ satisfy $ |f_j(\tau_j)|\geq 1$ for all $ 1\leq j \leq n$, $|g_k(\omega_k)|\geq 1 $ for all $1\leq k \leq m$. If $x \in \mathcal{X}\setminus \{0\}$ is such that $x=\theta_\tau\theta_f x=\theta_\omega\theta_g x$, then we show that \begin{align}\label{FKDB} \|\theta_fx\|_0\|\theta_gx\|_0\geq \frac{\bigg[1-(\|\theta_fx\|_0-1)\max\limits_{1\leq j,r \leq n,j\neq r}|f_j(\tau_r)|\bigg]^+\bigg[1-(\|\theta_g x\|_0-1)\max\limits_{1\leq k,s \leq m,k\neq s}|g_k(\omega_s)|\bigg]^+}{\left(\displaystyle\max_{1\leq j \leq n, 1\leq k \leq m}|f_j(\omega_k)|\right)\left(\displaystyle\max_{1\leq j \leq n, 1\leq k \leq m}|g_k(\tau_j)|\right)}. \end{align} We call Inequality (\ref{FKDB}) as \textbf{Functional Kuppinger-Durisi-B\"{o}lcskei Uncertainty Principle}. Inequality (\ref{FKDB}) improves the uncertainty principle obtained by Kuppinger, Durisi and B\"{o}lcskei \textit{[IEEE Trans. Inform. Theory (2012)]} (which improved the Donoho-Stark-Elad-Bruckstein uncertainty principle \textit{[SIAM J. Appl. Math. (1989), IEEE Trans. Inform. Theory (2002)]}). We also derive functional form of the uncertainity principle obtained by Studer, Kuppinger, Pope and B\"{o}lcskei \textit{[EEE Trans. Inform. Theory, (2012)]}.

Computational Fluid Dynamics (CFD) is revolutionizing the oil and gas industry by offering powerful insights and innovative solutions. This paper explores the cutting-edge applications of CFD in enhancing and innovating within the sector. CFD simulations provide engineers with invaluable insights into fluid behavior, enabling optimized designs and informed decision-making. The software facilitates foresight by predicting system performance, optimizing drilling techniques, and maximizing reservoir management strategies. Moreover, CFD optimizes equipment design, increases operational efficiency, and reduces costs through virtual testing, eliminating the need for costly physical prototypes. The application of CFD aligns with the United Nations Sustainable Development Goals (SDGs), promoting energy efficiency, climate action, responsible production, and sustainable consumption. It addresses flow assurance challenges, enhances safety protocols, and mitigates environmental impacts. CFD is a powerful tool driving innovation, resilience, and sustainability within the oil and gas industry, ensuring a more efficient, safe, and environmentally conscious future. As advancements in CFD methodologies continue, the potential for further enhancements and breakthroughs within the sector becomes even more promising, driving the industry towards a sustainable and prosperous future.

Proximal tubular epithelial cells (PTEC) are constantly exposed to potentially toxic metabolites and xenobiotics. The regenerative potential of the kidney enables the replacement of damaged cells either via the differentiation of stem cells or the regain of proliferative properties of the PTEC. Nevertheless, it is known that renal function declines, suggesting that the deteriorated cells are not replaced by fully functional cells. To understand the possible causes of this loss of kidney cell function, it would be beneficial to understand the role of toxins during the regeneration process. Therefore, we investigated the sensitivity and function of human induced pluripotent stem cells (hiPSC), hiPSC differentiating, and hiPSC differentiated into proximal tubular epithelial-like cells (PTELC) to known nephrotoxins. hiPSC were differentiated into PTELC, exhibiting a similar morphology to PTEC, expressing prototypical PTEC markers and performing albumin endocytosis. When treated with two nephrotoxins, hiPSC and differentiating hiPSC were more sensitive to cisplatin than differentiated PTELC, whereas all stages were equally sensitive to cyclosporin A. Both toxins also had an inhibitory effect on albumin uptake. Our results suggest a high sensitivity of differentiating cells towards toxins, which could have an unfavorable effect on regenerative processes. To study this, our model of hiPSC differentiating into PTELC appears suitable.

The endophytic fungus Aspergillus sp. SPH2 was isolated from the stems of the endemic plant Bethencourtia palmensis and its extracts were found to have strong fungicidal effects against Botrytis cinerea and ixodicidal effects against Hyalomma lusitanicum at different fermentation times. In this study, the fungus was grown using three different culture media and two methodologies, Microparticulate Enhancement Cultivation (MPEC) and Semi-Solid Fermentation (SSF), to increase the production of secondary metabolites in submerged fermentation. The addition of an inert support to the culture medium (SSF) resulted in a significant increase in extract production. However, when talcum powder was added to different culture media, unexpected results were observed, with a decrease in the production of the biocompounds of interest. Metabolomic analyses showed that the production of aspergillic, neoaspergillic, and neohydroxyaspergillic acids peaked in the first few days of fermentation, with notable differences observed among the methodologies and culture media. Mellein production was particularly affected by the addition of an inert support to the culture medium. These results highlight the importance of surface properties and morphology of spores and mycelia during fermentation by this fungal species.

The ZX Spectrum was a popular 8-bit home computer by Sinclair Research in the 80s. Even though some of these computers may still work, the audio tapes, the TV with an analog tuner and the micro-switch joystick, used with the original ZX Spectrum, nowadays are outdated and hard to find in good working order or replicate. Since many other old closed systems are also very difficult to update to support modern peripherals, there is a necessity to provide a methodology to adapt such systems to support new peripherals while being compatible with existing software. The work proposed in this paper is focused on recreating a ZX Spectrum+/48k computer and interface it with modern peripherals on an FPGA. This is accomplished by adding a co-processor to assist with the control of the new peripherals which would either require to complex architectural changes to the original system and in the end it would perform poorly due to the low performance of the Z80 CPU. This work distances from previous ones on emulating a ZX Spectrum since it focuses on the use of different upgraded peripherals and the use of a NIOS II soft-processor as a co-processor to manage the SD Card accesses. A demonstration of the proposed modernized architecture was made by successfully running a diagnostics ROM and playing original ZX Spectrum games from an SD card for game with a PS/2 keyboard and a pair of joysticks.

Passive dynamics is an aspect of locomotion which is entirely dependent on the mechanical configuration and linkages of adjacent body segments. Tension distribution along mechanical linkages enables execution of movement patterns with reduced need for complex neurological pathways and may play a role in reestablishing postural stability following external disturbances. Here we demonstrate a uni-directional mechanical relationship between the equine forelimb and head, which may have implications for balance and forelimb loading in the horse. These observations suggest that forelimb and head movement coordination (observed in the horse during unrestrained locomotion) is largely controlled by the mechanical linkages between body segments, rather than being entirely dependent on neurological input as previously thought. This highlights the potential significance of research directed at investigating passively induced movements in understanding common locomotory patterns. Additionally, it suggests a mode of postural control which may provide instantaneous adjustments to postural disturbances, thus promoting rapid and efficient locomotion.

The central reason behind emergence of clinically-detectable tumors is evasion from immune surveillance due to lack of cancer cells surface membrane expression of tumor-specific peptides in association with MHC class I molecules, concealment of natural killer cells-activating molecules, and absence of inflammation resulting from inefficient stimulation of innate immunity receptors and co-stimulatory molecules. The tumor microenvironment (TME) also contributes to tumor initiation, progression and resistance to therapeutic interventions because of its dense, fibrogenic, barrier-like composition, aberrant vasculature, and production of cytokines and chemokines responsible for recruitment of immune suppressive cells, notably myeloid-derived suppressor cells, M2 macrophages, regulatory T cells, extracellular trap-forming neutrophils, and cancer-associated fibroblasts. We herein show that the relentless efforts and strategies to overcome the TME elusive tumor-promoting impact produced contrasting, opposed, controversial effects, characterized by limited efficacy and proven adversity, and most importantly deterred from attempts to discover and counteract the fundamental inherent mechanisms initiating, and not consequent to, carcinogenesis.

Analysis of the construction of tall buildings is important because of the changes in the microclimate in its vicinity. Ensuring wind comfort and pedestrian safety are critical requirements in urban environments. This paper reports on the wind flow field at the main campus of the Dhaka University of Engineering & Technology (DUET), Gazipur, using computational fluid dynamics (CFD) to investigate pedestrian wind comfort and safety. The simulations were conducted in ANSYS Fluent employing the Reynolds-averaged Navier-Stokes (RANS) equation. The vertical profile of the streamwise wind speed was validated using the existing observations. The results revealed that the wind speed at the building corners was higher than the air inlet velocity, whereas the wind speeds in the walkways among the buildings were found to vary. The velocity vectors surrounding the building were densely packed, with a recirculation vortex formed in the upstream flow. Furthermore, walkways can display a lower mean wind velocity coupled with high turbulence kinetic energy (TKE). The turbulent kinetic energy is seen to be as high as 1.52 m2 s-2 which exceeds the threshold limit, while wind velocity is 1.81 m/s at the same point. These findings highlight potential pedestrian safety risks and underscore the need for urban design enhancements.

Introduction: Laeverin is an extravillous trophoblast marker playing a significant role in the trophoblast migration. The purpose of this study was to evaluate the association between the amniotic and serum laeverin concentrations at 16-22 weeks of gestation and the fetal and placental ultrasound measurements in healthy, unaffected pregnancies. Materials and methods: This was a prospective cross-sectional study. Pregnant women with singleton pregnancies undergoing amniocentesis were recruited consecutively. Fetal structural malformations and/or aneuploidy were exclusion criteria. Fetal biometric parameters and placental growth/perfusion were measured in 44 high-risk pregnancies who had no pregnancy complication and any other chronic disease. Maternal serum and amniotic levels of laeverin were essayed with sandwich enzyme-linked immunosorbent assay. Results: Serum laeverin levels are decreasing slightly with the maternal age in mid-gestation. Serum laeverin level correlated negatively slightly with head size of the fetus with the gestational length at delivery (β=-0.38, 95% confidence interval (CI) -0.03-0.01), while the amniotic laeverin level correlated strongly with the abdominal circumference of the fetus (β=-0.64, 95% CI: -0.03-0.01). Furthermore, laeverin level in the amnion correlated moderately and positively with the placental volume (β=0.46, 95% CI: 0.01-0.08). Conclusions: Laeverin levels detected in the serum and in the amniotic fluid denotes the fetoplacental growth in uncomplicated high-risk pregnancies.

Digital recruitment systems have revolutionized the hiring paradigm, imparting exceptional efficiencies and extending the reach for both employers and job seekers. This investigation scrutinizes the efficacy of classical machine learning methodologies alongside advanced large language models (LLMs) in aligning resumes with job categories. Traditional matching techniques, such as Logistic Regression, Decision Trees, Naïve Bayes, and Support Vector Machines, are constrained by the necessity of manual feature extraction, limited feature representation, and performance degradation, particularly as dataset size escalates, rendering them less suitable for large-scale applications. Conversely, LLMs like GPT-4, GPT-3, and LLAMA, adeptly process unstructured textual content, capturing nuanced language and context with greater precision. We evaluate these methodologies utilizing two datasets comprising resumes and job descriptions to ascertain accuracy, efficiency, and scalability. Our results reveal that while conventional models excel with structured data, LLMs significantly enhance the interpretation and matching of intricate textual information. This study highlights the transformative potential of LLMs in recruitment, offering insights into their application and future research avenues.

Pollution, urbanization and technological advancements have posed stress on the ecosystem and its matrices. Globally, pollutants are observed in all compartments of ecological communities which affect the integrity of the atmosphere, hydrosphere, lithosphere and biosphere. Xenobiotics bioaccumulate and biomagnify across trophic levels or webs. Heavy metals have been implicated in impacts towards biodiversity and environmental declination. In Nigeria, wastes issues are a cause of concern and landfilling or are waste disposal approaches that cause deleterious effects such as depauperation of diversity and species decline, prompting the non-invasive ecotoxicological hazard assessments. Feathers were used to assess concentration levels of 13 metals (Fe, Mn, Zn, Cu, Co, Cr, Cd, Pb, Ni, Al, B, Se and Hg) using fast atomic absorption spectrophotometer (FAAS), one-way ANOVA was used in comparing variations in mean concentrations across trophic levels, diversity indices and point count methods were used to estimate diversity and abundance. Four avian species were assessed Hirundo aethiopica (insectivore), Streptoptelia senegalensis (granivore), Turdus pelios (omnivore), and Anthus leucophrys. (insectivore). Observed concentrations of important metals like iron were high with the insectivores having the highest concentrations of iron (2.6985 ± 0.1975 ppm) and granivores having the lowest (2.0100 ± 0.3172 ppm). The insectivores had the highest concentrations for cadmium, cobalt and chromium (0.0005 ± 0.0005ppm), nickel (at 00.0012 ± 0.0017 ppm) and least was observed in the granivores (0.0003 ± 0.0006 ppm). Selenium concentrations were quite high in insectivores (0.0775 ± 0.0035 ppm) and lowest in granivores (0.0433 ± 0.0015 ppm) likewise mercury for insectivores (0.0280 ± 0.0010 ppm) and granivores (0.0213 ± 0.0015 ppm). From the study, it is apparent that landfills are sources of pollution and poor management of wastes can affect biota (causing effects such as asymmetry and bioaccumulation) and ecosystem balance. The observation of heavy metals in the feathers serve as good sentinels due to their trophic levels and could be signs for what could be yet to occur. The heavy metal concentrations were significantly different at p < 0.05.

The work presents the results of studying dilute aqueous solutions of commercial Ln(NO3)3 · xH2O salts with Ln=Ce-Lu using X-ray diffraction (XRD), IR spectroscopy, X-ray absorption spectroscopy (XAS: EXAFS/XANES) and pH measurements. As a reference point, XRD and XAS measurements for characterized Ln(NO3)3 · xH2O microcrystalline powder samples were performed. The local structure of Ln-nitrate complexes in 20 mM Ln(NO3)3 · xH2O aqueous solution was studied under total external reflection conditions and EXAFS geometry was applied to obtain high-quality EXAFS data for solutions with low concentrations of Ln3+ ions. Results obtained by EXAFS spectroscopy showed significant contraction of the first coordination sphere during the dissolution process for metal ions located in the middle of the lanthanide series. It was established that in Ln(NO3)3 · xH2O solutions with Ln=Ce, Sm, Gd, Yb (c=134, 100, 50 and 20 mM) there are coordinated and, to a greater extent, non-coordinated nitrate groups with bidentate and predominantly monodentate bonds with Ln ions, the number of which increases upon transition from cerium to ytterbium. Cross-relationships between the concentration of solutions, pH value and antimicrobial activity with the type of Ln = Ce, Sm, Gd, Yb were established, as well as the absence of biocidal properties of solutions with a concentration of 20 mM, except for Ln = Yb. The important role of experimental conditions in obtaining and interpreting the results was noted.

South Africa’s internationally celebrated water legislation placed the responsibility for investing in water services at the door of the government. In recent years South Africa has struggled to invest adequately to keep up with growing demand for these services. The result is a suite of social, economic and environmental risks that are destabilising to the fiscus and the financial sector. This paper explored both operating and capital costs, and applied the ‘Beyond the Gap’ analysis to show that an additional 55% investment (R91 billion annually) is necessary to ensure South Africa meets its water policy goals. The analysis explores the factors that influence the investment amount and shows that a combination of policy choices and exogenous factors such as climate change could render the investment gap anywhere between 30% and 90% of the estimated current allocation to the water sector. The most significant savings are attributed to reducing the extent of “non-revenue water”, an energy transition away from coal, sharing of some water taps between (up to) five houses, reduced water allocations to agriculture, investments in invasive alien plant (IAP) clearing in water catchments above dams, and water demand management, capacity building and more efficient integration of different bulk water schemes. The study revealed important dependencies between capital and operating costs; where operating costs are ignored, the decay of water infrastructure is accelerated. Showing the contingency of investment needs on policy choices, places responsibility for attaining water policy goals and SDG 6 in the hands of a diverse set of actors. Quantifying the investment need also raises the critical question of how to raise the required investment. Recognising the need to balance risks to financiers with the widespread risks to households, companies and government when investment in water services is inadequate, South Africa is exploring a Monetary Architecture approach of inter-balance sheet relationships in an attempt to mobilise investment from new sources.

Cellular senescence has recently been recognized as a hallmark of cancer, reflecting its association with aging and inflammation, its role as a response to deregulated proliferation and oncogenic stress, and its induction by cancer therapies such as radiation, chemotherapy, and targeted agents. While such therapy-induced senescence (TIS) has been linked to resistance, recurrence, metastasis and normal tissue toxicity, TIS has the potential to enhance therapy response and stimulate anti-tumor immunity. In this review, we examine the Jekyll and Hyde nature of senescent cells (SnCs), with a particular focus on how their persistence while expressing the senescence-associated secretory phenotype (SASP) modulates the tumor microenvironment through autocrine and paracrine mechanisms. Via the SASP, the formation of SnCs may alternately mediate resistance or response to conventional therapy. Further, toward fulfilling the unmet potential of cancer immunotherapy, we consider how SnCs may influence tumor inflammation and serve as a source of antigen to potentiate anti-tumor immunity. This new view suggests treatment strategies based on inducing TIS to enhance immune checkpoint blockade. Finally, we describe strategies for mitigating the detrimental effects of senescence, such as modulating the SASP or targeting SnC persistence, toward enhancing the benefits of cancer treatment.

Abstract: In the Western of Mekong Delta belong to Vietnam a amount of alluvium sediments flows from upstream China to Vietnam, they are going from the river branches to in the Mekong Delta, then get out the Western Sea of Vietnam. This sediments accumulated gradually elevation the new land. The increase elevation of the land creates a fertile coastal plain where mangrove forests with a rich ecosystem of plants and animals. Over time, these forests change, with different plant species succeeding each other. This aims of this study to finding plant species in the forest, classification of forest types based on ecological regions, assessement the biodiversity of tree species, and compare the abundance communities, measuring the growth of the forest in these regions. In 2023, a comprehensive survey was conducted by using a systematic approach. The number of survey plots have done depend on the density of the forest, Base on the width of the forest range, the number of survey plots from 500m to 1,000m set up 1-2 plots, sub region set up from 10 to 15 plots. In total, 68 plots have done established in the erea, the area of plot is 100 square meters (10m x 10m). Using the statistical software in forestry to survey and analysis data. The result provided a complete picture of the tree species composition, distribution, and community structure characteristics in each ecological sub-region. The result of survey showed in the sub-region 1 have seven species as Sonneracia ovate, Rhzophora apiculata, Excoecaria agallochha, Avicennia officinalis, Avicennia alba, Agricerasvcoculatum, Bruguiera gymnorhiza. In the sub region 2 have eleven species as Sonneracia caseolaris, Annona reticulata, Lumnitzera littorea, Lumnizera racemosa, Rhizophora apiculata, Excoecaria agallocha, Avicennia officinalis, Avicennia alba, Hibiscus tillacerus, Bruguiera gymorhiza, Aericeras comiculatum. In the sub region 3 have eight as Sonratia caseolaris, Rhizophora mucronata, Rhizophora apiculata, Excoecaria agallocha, Avicennia marine, Avicennia alba, Bruguiera gymorhiza. In the region 4 have ten species as Sonneracia caseolaris, Sonneracia ovate, Lumnizera racemosa, Rhizophoa apiculata, Excoecaria agallocha, Avicennia marina, Avicennia officinalis, Aviecnnia alba, Bruguiera gymorhiza, Bruguiera cylindrica The total species of the mangrove forest in the Western Mekong Delta have 16 species from 11 plant families have been identified. Among these species have 6 dominant species include Avicennia oficinali),Avicennia alba, Rhizophora apiculata, Excoecaria agallocha, Someratia caseolaris, and Bruguiera yipamoriza. Two species easy grow on the new land are Avicennia officinalis Avicennia alba this findings show they can develope on the original new land for the shore of the Western Mekong Delta. The surveyed results also calculated the average of the height, diameter (D1.3), canopy, health of the nature mangrove tree for each sub region and total region. From these results showed the division of foresty structure, the structure of height, diameter (D1.3), canopy, vitality of the sub region and total region in the Western Mekong Delta.

Stroke is a global leading cause of death and disability. Knowledge of related guidelines is crucial for Emergency Department (ED) staff, influencing early diagnosis and timely treatment. We investigated Greek-Cypriot ED healthcare professionals' (nurses and physicians) knowledge in recognizing and managing stroke. A descriptive cross-sectional study spanned November 2019 to April 2020, encompassing four private and seven public EDs in the Republic of Cyprus. The data were collected through a self-reported questionnaire developed by the research team, consisting of 37 questions. Eight questions focused on sociodemographic and employment characteristics, 28 assessed knowledge in stroke recognition and management (each item was equally weighted without deliberate prioritization), and one question addressed self-assessment of knowledge in stroke care. 255 nurses [Response Rate (RR): 74.1%] and 26 physicians (RR: 47.3%) completed the questionnaire. The average correct response rate was 12.9 out of 28 statements (SD: 4.2), with nurses and physicians scoring 12.6 (SD: 4.1) and 15.7 (SD: 4), respectively. Work experience significantly influenced stroke knowledge, with all groups demonstrating superiority over those with less than one year of experience. Participants with previous training scored an average of 1.45 additional correct answers while educational attainment did not significantly influence stroke knowledge. Investigating stroke knowledge among Emergency Department nurses and physicians in the Republic of Cyprus revealed significant deficits. The study stresses targeted interventions, including, education, yearly examinations, workshops with hands-on training, and repeated training, to address these gaps and enhance the overall stroke care capabilities of the healthcare professionals.

In this work, several random Boolean networks (RBN) are generated and analyzed from two characteristics: their time evolution diagram and their transition diagram. To do this, its randomness is estimated using three metrics, of which algorithmic complexity is the only one capable of revealing both transitions towards the chaotic regime and the algorithmic contribution of certain states to the transition diagram and their relationship with the order they occupy in the temporal evolution of the respective RBN.

The incidence of melanoma, the most lethal form of skin cancer, has increased due to ultraviolet exposure. The molecular characterization of melanomas has shown a high mutational burden led to the identification of some recurrent genetic alterations. BRAF gene is mutated in 40-50% of melanomas and its role in melanoma development is paramount. BRAF mutations confer constitutive activation of MAPK signalling. The large majority (abou 90%) of BRAF mutations occur at amino acid 600; the majority are BRAFV600E mutations and less frequently BRAFv600K, V600D and V600M. The introduction of drugs that directly target BRAF-mutant protein (BRAF inhibitors) and of agents that stimulate immune response through targeting of immune check inhibitor consistently improved the survival of melanoma BRAFV600-mutant patients with unresectable/metastatic disease. In parallel, studies in melanoma stage II-III patients with resectable disease have shown that adjuvant therapy with ICIs and/or targeted therapy improves PFS and RFS, but not OS compared to placebo; however, neoadjuvant therapy plus adjuvant therapy improved therapeutic response compared to adjuvant therapy alone.

Introduction: Urinary tract infections (UTIs) are a significant global health issue, especially among women, with growing concerns related to antibiotic resistance and adverse effects. The Uromune® vaccine, a sublingual bacterial lysate, represents a promising therapeutic alternative by enhancing immune responses against uropathogens. Methods: This retrospective study, conducted at Hospital Universitari de Sant Joan de Reus from January 2017 to August 2022, evaluated the effectiveness of Uromune® in treating recurrent UTIs (rUTIs). Patients received personalized autovaccines administered as two sublingual puffs daily for three months. Clinical, microbiological, and demographic data were analyzed to assess treatment outcomes and identify recurrence-associated factors. Results: Forty-nine patients (mean age, 61 years, and 59.2% women) were included in the study. Uromune® treatment decreased UTI episodes, from 3.73 ± 0.97 the year before to 0.98 ± 1.36 (P &lt; 0.001) the year after its administration. The number of patients who suffered three or more episodes per year dropped from 43 (87.7%) before the intervention to 7 (14.3%) afterward. The maximum effectiveness of the autovaccine was observed three months post-administration, with 44 patients not experiencing any UTI episodes. Regression analysis identified having had a urostomy, chronic kidney disease, and being immunosuppressed as predictors of recurrence. Conclusion: The Uromune® autovaccine effectively reduced the frequency of rUTIs and associated hospitalizations, offering substantial relief to patients. These findings support the integration of Uromune® into routine clinical practice as a viable alternative to conventional antibiotic treatments.

Despite the recent availability of immune checkpoint inhibitors, not all patients affected by Non-Small Cell Lung Cancer (NSCLC) benefit from immunotherapy. The reason for this variability relies to a variety of factors which may allow the identification of novel biomarkers. Presently, a variety of biomarkers are under investigation, including the PD1/PDL1 axis, the tumor mutational burden, and the Microbiota. This latter is made by all bacteria and other microorganisms hosted in our body. The gut microbiota is the most represented and has been involved in different physiological and pathological events, including cancer. In this light, it appears that all conditions modifying gut microbiota can influence cancer, its treatment, and its treatment-related toxicities. The aim of this review is to analyze all conditions influencing the gut microbiota and, therefore, affecting response to immunotherapy, iRAEs and their management in NSCLC patients. The investigation of the landscape of these biological events can allow novel insights for optimal management of NSCLC immunotherapy.

Lung neuroendocrine tumors (LNETs) and gastroenteropancreatic neuroendocrine tumors (GEPNETs) are two distinct types of neuroendocrine tumors (NETs) that have traditionally been treated as a single entity despite originating from different sources. Although they share certain phenotypic characteristics and the expression of neuroendocrine markers, they exhibit differences in their microenvironment, molecular mutations, and responses to various therapeutic regimens. Recent research has explored the genetic alterations in these tumors, revealing dissimilarities in the frequently mutated genes, role of EGFR in carcinogenesis, presence of transcription factors, and immunogenicity of the tumor and its microenvironment. Spread Through Air Spaces (STAS), a phenomenon unique to lung carcinomas, appears to play a crucial role in LNET prognosis. These distinctions are also evident in the cascade response of lung and GI tract neuroendocrine tumors to somatostatin analogs, Peptide Receptor Radionuclide Therapy (PRRT), chemotherapy, and immunotherapy. Identifying similarities and differences between the two groups may im-prove our understanding of the underlying mechanisms and facilitate the development of more effective treatment strategies.

Lymphoma is the most prevalent type of cancer in cats, and the search for alternative treatments is of utmost importance given the significant number of animals that exhibit tumor recurrence or are unresponsive to conventional chemotherapy treatment. Oncolytic viruses possess a unique ability to target and eliminate cancer cells while simultaneously stimulating an immune response against these malignant cells. The present study aimed to explore the oncolytic potential of Newcastle Disease Virus expressing green fluorescent protein (NDV-GFP) in a feline leukemia virus (FeLV)-positive lymphoma cell line. Our research suggests that NDV-GFP has a propensity to selectively target, infiltrate, and replicate with-in feline lymphoma cells, resulting in the induction of apoptosis in these cells, as opposed to non-tumor cells. Therefore, our research provides evidence supporting the development of novel oncolytic therapies based on NDV for the treatment of feline lymphomas.

Although the first cancer immunotherapy was given in the clinic more than a century ago, this line of treatment has remained more of a distant goal than a practical therapy due to limited understanding of the tumor microenvironment and the mechanisms at play within it, which lead to failures of numerous clinical trials. However, in the last two decades, the immune checkpoint inhibitors and chimeric antigen receptor-T cell therapies have revolutionized the treatment of cancer and provided proof-of-concept that immunotherapies are a viable option. So far, immunotherapies have majoritarily focused on utilizing T cells, however T cells are not autonomous but rather function as part of, and therefore are influenced by, a vast cast of other immune cells, including innate lymphoid cells (ILCs). Here, we summarize the role of ILCs, especially helper ILCs, in tumor development, progression and metastasis, as well as their potential to be used as immunotherapy for cancer. By reviewing the studies that used helper ILCs as adoptive cell therapy, we highlight the rationale behind considering these cells as novel adoptive cell therapy for cancer as well as identify open questions and areas for future research.

Nowadays molecular and immunological research is essential for the better understanding of tumor cells pathophysiology. The increasing number of neoplasms is taken under ‘the molecular magnifying glass’ therefore it is possible to discover complex relationships between cytophysiology and immune system action. An example could be renal cell carcinoma (RCC) which has deep interactions with immune mediators such as Interleukin 17 (IL-17) - an inflammatory cytokine reacting to tissue damage and external pathogens. RCC is one of the most fatal urological cancer because of its often late diagnosis and poor susceptibility to therapies. IL-17 and its relation with tumors is extremely complex and constitute a recent topic for numerous research. What is worth highlighting is IL-17 dual character in cancer development - it could be pro- as well as antitumorigenic. The aim of this review is to summarize the newest data considering multiple connections between IL-17 and RCC.

Up to 25% of early human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) patients will relapse despite the improvement achieved by the introduction of HER2-targeted therapy. Beyond trastuzumab, other agents approved for early HER2+ BC include the monoclonal antibody pertuzumab, the antibody-drug conjugate (ADC) trastuzumab-emtansine (T-DM1) and the reversible HER2 inhibitor lapatinib. New agents, such as trastuzumab-deruxtecan or tucatinib in combination with capecitabine and trastuzumab, have also shown an improvement in the metastatic setting. Other therapeutic strategies to overcome treatment resistance have been explored in HER2+ BC, mainly in HER2+ that also overexpress estrogen receptors (ER+). One strategy has been to target the cyclin-dependent kinases 4/6 (CDK4/6) as they are downstream of HER2 and many of the cellular pathways associated with resistance to HER2-targeted therapies play a key role in cell cycle and proliferation. Different trials have explored these strategies with encouraging results, but definitive results are needed. In addition, HER2+ BC is known to be more immunogenic than other BC subgroups, with high variability between tumors. Different immunotherapeutic agents have been investigated in this setting, with promising but controversial results obtained to date.