In clinical guidelines, such as National Comprehensive Cancer Network guidelines, it is embodied as first therapeutic option the combination of erlotinib and bevacizumab, based on a small clinical trial which included patients with HLRCC. With this case report we bring out another treatment option, not described before, with extraordinary results based on the combination of a check-point inhibitor and a tyrosine-kinase inhibitor, based on theoretical tumor immunogenic environment.

A recent study from our lab revealed that inhibition of cyclooxygenase-2 exclusively reduces the level of PGE2 amongst the prostanoids and hamper the normal development of several structures, strikingly the cranial vault, in chick embryos. In order to unearth the mechanism behind the deviant development of cranial features, the expression pattern of various factors that are known to influence the cranial neural crest cell (CNCC) migration were checked in chick embryo after inhibiting the COX-2 activity using etoricoxib. The compromised level of cell adhesion molecules and their upstream regulators, namely CDH1, CDH2, MSX1, and TGF-β, observed in the etoricoxib treated embryos indicate that COX-2, through its downstream effector PGE2, regulates the expression of these factors perhaps to aid the migration of CNCC. The histological features and levels of FoxD3 as well as PCNA further consolidates the role of COX-2 in migration and survival of CNCC in developing embryo. The results of the current study indicate that the COX-2 plays a pivotal role in orchestrating the proliferation and migration of CNCC during embryonic development of chick.

The present study is aimed at designing anti-reflective (AR) engraving on the Input-Output surfaces of a rectangular light-guide. We estimate AR efficiency, by the transmittance level in the angular range, determined by the light-guide. Using nano-engraving, we achieve a uniform high transmission over a wide range of wavelengths. In the past, we used smoothed conical pins or indentations on the faces of light-guide crystal as the engraved structure. Here, we widen the class of pins under consideration, following the physical model developed in the previous paper. We analyze the smoothed pyramidal pins with different base shapes. The possible effect of randomization of the pins parameters is also examined. The results obtained demonstrate optimized engraved structure with parameters depending on the required spectral range and facet format. The predicted level of transmittance is close to 99\%, and its flatness (estimated by the standard deviation) in the required wavelength range is 0.2\%. The theoretical analysis and numerical calculations indicate that the obtained results demonstrate the best transmission (reflection) we can expect for a facet with the given shape and size for the required spectral band. The approach is equally useful for any other form and of the facet. We also discuss a simple way of comparing experimental and theoretical results for a light-guide with the designed input and output features. In this study, as well as in our previous work, we restrict ourselves to rectangular facets. We also consider the limitations on maximal transmission produced by the size and shape of the light-guide facets. The theoretical analysis is performed for an infinite structure and serves as an upper bound on the transmittance for smaller-size apertures.

Epithelial-mesenchymal transition (EMT) plays an important role in the acquisition of cancer stem cell (CSC) feature and drug resistance, which are the main hallmarks of cancer malignancy. Although previous findings have shown that several signaling pathways are activated in cancer progression, the precise mechanism of signaling pathways in EMT and CSCs are not fully understood. In this study, we focused on the intestinal and diffuse-type gastric cancer (GC), and analyzed the gene expression of public RNAseq data to understand the molecular pathway regulation in different subtypes of gastric cancer. Network pathway analysis was performed by Ingenuity Pathway Analysis (IPA). Total 2815 probe set IDs were significantly different between intestinal- and diffuse-type GC data in cBioPortal Cancer Genomics. The 10 genes including male-specific lethal 3 homolog (Drosophila) pseudogene 1 (MSL3P1), CDC28 protein kinase regulatory subunit 1B (CKS1B), DEAD-box helicase 27 (DDX27), golgi to ER traffic protein 4 (GET4), chromosome segregation 1 like (CSE1L), translocase of outer mitochondrial membrane 34 (TOMM34), YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), ribonucleic acid export 1 (RAE1), par-6 family cell polarity regulator beta (PARD6B), and MRG domain binding protein (MRGBP) were found to have difference in gene expression in intestinal- and diffuse-type GC. Total 463 direct relationships with 3 molecules (MYC, NTRK1, UBE2M) were found in the biomarker-filtered network generated by network pathway analysis. The networks and features in intestinal- and diffuse-type GC have been investigated and profiled in bioinformatics. Our results revealed the signaling pathways networks in intestinal- and diffuse-type GC, bringing new light for the elucidation of drug resistance mechanisms in CSCs.

Bone innate ability to repair without scaring is surpassed by major bone damage. Current gold-standard strategies do not achieve a full recovery of bone biomechanical properties. To bypass these limitations, tissue engineering techniques based on hybrid materials made up of osteoprogenitor cells, like mesenchymal stem cells (MSCs), and bioactive ceramic scaffolds, like calcium phosphate-based (CaPs), are promising. Biological properties of the MSCs, are influenced by the tissue source. The aim of this study is to define the MSC source and construct (MSC and scaffold combination) most interesting for its clinical application in bone regeneration. iTRAQ generated the hypothesis that anatomical proximity to bone has a direct effect on MSC phenotype. MSCs were isolated from adipose tissue, bone marrow and dental pulp. MSCs were cultured both on plastic surface and on CaPs (hydroxyapatite and β-tricalcium phosphate) to compare their biological features. On plastic, MSCs isolated from dental pulp (DPSCs) were the MSCs with the highest proliferation capacity and the greatest osteogenic potential. On both CaPs, DPSCs are the MSCs with the greatest capacity to colonize bioceramics. Furthermore, results show a trend for DPSCs are the MSCs with the most robust increase in the ALP activity. We propose DPSCs as a suitable MSCs for bone regeneration cell-based strategies.What do you want to do ?New mailCopy

Biologic scaffolds have become an attractive approach for repairing the infarcted myocardium and have been shown to facilitate constructive remodeling in injured tissues. This study aimed to investigate the possible utilization of bacterial cellulose membrane patch containing cocultured cells to limit the myocardium's post-infarction pathology. Myocardial infarction was induced by ligating the left anterior descending coronary artery in 45 Wistar rats, and patches with or without cells were attached to the hearts. After one week, the animals underwent echocardiography for assessing ejection fraction and left ventricular end-diastolic and end-systolic volumes. Following the patch formation, cocultured cells retained viability of >90% over 14 days in culture. The patch was applied to the myocardial surface of the infarcted area after staying 14 days in culture. Interestingly, the bacterial cellulose membrane without cellular treatment showed higher preservation of cardiac dimensions; however, we did not observe improvement in the left ventricular ejection fraction of this group compared to coculture treated membranes. Our results demonstrated an important role for bacterial cellulose in supporting cells known to produce cardioprotective soluble factors and may thus provide effective future therapeutic outcomes for patients suffering from ischemic heart disease.

Necroptosis is a caspases-independent form of programmed cell death exhibiting intermediate features between necrosis and apoptosis. Albeit some physiological roles during embryonic development, tissue homeostasis and innate immune response are documented, necroptosis is mainly considered a pro-inflammatory cell death. Key actors of necroptosis are the receptor-interacting-protein-kinases, RIPK1 and RIPK3, and their target, the mixed-lineage-kinase-domain-like protein, MLKL. The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. Altered necroptosis at the intestinal epithelium leads to uncontrolled microbial translocation and deleterious inflammation. Indeed, necroptosis has been associated to chronic inflammatory diseases and cancer. Drugs that inhibit necroptosis could, therefore, be used therapeutically for the treatment of these diseases, and researches to develop such inhibitors are already underway. In this Review, we outline pathways for necroptosis and its role in chronic inflammation and cancer. We also discuss current and developing therapies that target necroptosis machinery.

Achieving devices to be transparent is the task considered in the last time in many aspects and for different purposes. One issue of these problems is making anti-reflective surfaces in a wide wavelength range and keeping it flat enough. The authors of the previous publication showed that one could enhance a flat facet's transmission efficiency by suitable engraving. They used smoothed conical fingers and holes. Here, we widen the class of anti-reflective metasurfaces under consideration, following the requirements of the model developed in the previous paper. We involve also smoothed pyramidal fingers. The obtained results provide the improved engraved structure, with parameters dependent on the required spectral range, and the facet format. The predicted level of transmittance is close to 99\%, and the flatness(estimated by the standard deviation) as 0.2\%. This improvement is significant enough for high and broadband transmittance. In this work, we show that the randomization of the engraving parameters does not provide any significant effect for small facets. We also discuss a simple way of comparing experimental and theoretical results for a waveguide with the considered input and output features. In this study, as well as in our previous work, we restrict ourselves by rectangular facets. We also discuss the limitations that originated from the size and shape of the waveguide facets.

Many species of the Asteraceae family are used in traditional Mexican medicine for possessing healing properties. Ageratina pichinchensis (Asteraceae) is a plant used for the treatment of gastric ulcers, deep wounds and for its antifungal effects. The aim of this study was to establish a cell suspension culture of A. pichinchensis, quantify the anti-inflammatory constituents 2,3-dihydrobenzofuran and 3-epilupeol, to evaluate the anti-inflammatory potential of its extracts and perform a phytochemical analysis. Cell suspension cultures were established in MS culture medium supplemented with 30 g L-1 sucrose and 1.0 g L-1 α-naphthaleneacetic acid (NAA) plus 0.1 mg L-1 6-furfurylaminopurine (KIN). The ethyl acetate extracts of cell suspension cultures analyzed by GC revealed that the maximum production of compounds The anti-inflammatory activity of these extracts exhibited significant inhibition of NO production. Furthermore, the phytochemical study of EtOAc and MeOH extracts of the biomass on day 20 led to the identification of 17 known compounds. The structures of compounds were assigned by analysis of 1D and 2D NMR data and the remainder by GC-MS. This is the first report of the production of the (-)-Artemesinol, (-)-Artemesinol glucoside, Encecalin and 3,5-diprenyl-acetophenone compounds by a cell suspension cultures of A. pichinchensis.

The consequences of Sickle Cell Disease (SCD), including ongoing hematopoietic stress and hemolysis, vascular damage and chronic therapies , such as blood transfusions and Hydroxyurea on hematopoietic stem and progenitor cell (HSPC) have not been characterized. We have quantified the frequencies of nine HSPC populations by flow cytometry in the peripheral blood of pediatric and adult patients stratified by treatment and controls. We observed broad differences between SCD patients and healthy controls. SCD is associated with 10 to 20-fold increase in CD34dim cells, and two to five-fold more CD34bright cells, a depletion in Megakaryocyte-Erythroid Progenitors and an increase in hematopoietic stem cells, when compared to controls. SCD is also associated with abnormal expression of CD235a and by very high levels of expression of the CD49f antigen. These findings were present to varying degrees in all patients, whether or not they were naïve or on chronic therapy. HU treatment tended to normalizes many of these parameters. Chronic stress erythropoiesis, inflammation caused by SCD and hydroxyurea therapy have long been suspected of causing premature aging of the hematopoietic system, and potentially increasing the risk of hematological malignancies. An important finding of this study was that the observed concentration of CD34bright cells and of all the HSPCs decreased logarithmically with time of treatment with HU. This correlation was independent of age and specific to HU treatment. Although the number of circulating HSPCs is influenced by many parameters, our findings suggest that HU treatment may decrease premature aging and hematologic malignancy risk compared to the other therapeutic modalities in SCD.

Perovskite based solar cells have achieved tremendous progress reaching record efficiency in the past 5 years. Numerous new processes and chemistry have been reported and contribute to the perovskite rapid progress. Continuous efficiency improvements are still necessary for perovskite solar cells, and an exploratory data analysis on devices performance over multiple studies could boost the technology development. Such analysis could identify patterns or provide insights that are not obvious in a single study. Here we present a high quality dataset containing only independently certified Pb-based perovskite solar cells summarizing their efficiency, relevant I-V metrics, manufacturing processes and materials used. Analysis over the dataset provides insights on how aperture size, perovskite deposition methods and materials used in each functional layer affect the final solar cell efficiency and I-V metrics. Future directions are also suggested for efficiency improvements.

Mammary neoplasm affects a population of intact and elderly female dogs and 50% are malignant. In order to study this disease, cell culture is as a promising preclinical model, creating the opportunity to deposit cell lines at a cell bank, allowing a great reproducibility of the assays and making the validation of the results more reliable. Another important aspect is the possibility to establish models for better understanding tumour characteristics, such as vasculogenic mimicry. Due the importance of cancer cell lines in preclinical models, this study aimed to establish and characterize primary cell lines from canine mammary gland tumours according to immunophenotype and tumorigenicity, and with its ability to form vasculogenic mimicry-like structures in vitro and in vivo. Cell cultures were evaluated for morphology, phenotype, vasculogenic mimicry and tumorigenicity abilities. We collected 17 primary mammary carcinoma and 3 metastasis and had a satisfactory result in 10 of them. All cell lines presented spindle shape or polygonal morphology and expressed concomitant pan-cytokeratin and cytokeratin 8/18. Four cell lines had vasculogenic mimicry ability in vitro and two of them showed in vivo tumorigenic potential and forming VM in the xenotransplant tumour. Cell characterization of those lines will help to create a database for more knowledge of mammary carcinomas in dogs, including studies of tumour behaviour and new therapeutic targets.

Hematopoietic stem cells (HSCs) are responsible for the production of blood cells throughout the human life span. Single HSCs can give rise to at least eight distinct blood cell lineages. Together, hematopoiesis, erythropoiesis and angiogenesis coordinate several biological processes, such as cellular interactions in development and proliferation, guided migration, lineage programming and reprogramming by transcription factors. Any dysregulation of these processes may result in hematological disorders and/or malignancies. Several studies of the molecular mechanisms governing HSC maintenance have demonstrated that protein regulation by the ubiquitin proteasomal pathway is crucial for normal HSC function. Recent studies have shown that the reversal of ubiquitination by deubiquitinating enzymes (DUBs) plays an equally important role in hematopoiesis; however, there is only limited additional information regarding the biological function of DUBs. In this review, we focus on recent discoveries that have led to a better understanding of the physiological roles of DUBs in hematopoiesis, erythropoiesis and angiogenesis. In addition, we discuss the DUBs associated with common hematological disorders and malignancies, which may potentially be therapeutic drug targets.

White adipose tissue (WAT) is distributed in several depots that have distinct metabolic and inflammatory functions. In our body there are subcutaneous (sWAT), visceral (vWAT) and bone marrow fat depots (BFAT). Obesity affects size, function and inflammatory state of WATs. This process can alter the stem cell niches present in these tissues and affect the functions of stem cells residing within. In particular, obesity may affect the activity of mesenchymal stromal cells (MSCs) present in WAT. MSCs are an heterogenous population containing stromal cells, progenitor cells, fibroblasts and stem cells that are able to differentiate in adipocytes, chondrocytes, osteocytes and other mesodermal derivatives. We performed a comparison of the effects of obesity on MSCs obtained from sWAT, vWAT and BFAT. Our study evidenced that obesity affected mainly the biological functions of MSCs obtained from bone marrow and vWAT with a decrease in proliferation rate, reduced percentage of cells in S phase and trigger of senescence. The onset of senescence was confirmed by expression of genes belonging to RB and P53 pathways. Our study evidenced that negative consequences of obesity on body physiology may be related also to impairment in the functions of stromal compartment present in the several adipose tissues. This finding provides new insights on the targets that should be considered for an effective treatment of obesity-related diseases.

Background: The central channel of the nuclear pore complex (NPC) plays an important role in the selective transport of proteins between the nucleus and cytoplasm. Previous studies have demonstrated that depletion of the Nup62 complex, constructing the nuclear pore channel in premeiotic Drosophila cells, resulted in absence of meiotic cells. We attempted understanding the mechanism underlying the cell cycle arrest before meiosis. Methods: We induced dsRNAs against the nucleoporin mRNAs using the Gal4/UAS system in Drosophila. Results: The cell cycle of the Nup62-depleted cells was arrested before meiosis without CDK1 activation. Ectopic over-expression of CycB, but not constitutively active CDK1, resulted in partial rescue from the arrest. CycB accumulated precociously in the nuclei of Nup62-depleted cells and cells depleted of exportin (encoded by emb). Protein complexes containing CycB, Emb, and Nup62 complex components were observed in premeiotic spermatocytes. CycB, which had precociously migrated into the nucleus, was associated with Emb, and the complex was transported back to the cytoplasm through the central channel, interacting with the Nup62 complex. Conclusion: We proposed that CycB is exported with Emb through the channel interacting with the Nup62 complex before initiation of meiosis. The nuclear export ensures production of active CycB-CDK1 in the cytoplasm.

Poor survival of human pluripotent stem cells (hPSCs) following freezing, thawing, or passaging hinders maintenance and differentiation in stem cell research. Rho-associated kinases (ROCKs) play a crucial role in hPSC survival. To date, a typical ROCK inhibitor, Y-27632, has been the primary agent used in hPSC research. Here, we report that another ROCK inhibitor, fasudil, can be used as an alternative. Fasudil increased hPSC growth due to survival rather than proliferation following thawing and passaging, similar to Y-27632. It did not affect pluripotency and genetic integrity including mitochondrial genome (mtDNA). Notably, the genes related to metabolism, mTORC1, and TP53 have mainly displayed a faster recovery pattern with ROCK inhibitors than control. Furthermore, fasudil was confirmed as useful for the single dissociation of hPSCs and for aggregation. It also increased retinal pigment epithelium (RPE) differentiation and the survival of neural crest cells during differentiation. These findings suggest that fasudil can replace Y-27632 for use in stem cell research.

Accurate channel estimation is of utmost importance for massive MIMO systems that allow providing significant improvements in spectral and energy efficiency. In this work, we investigate the spectral efficiency performance and present a channel estimator for multi-cell massive MIMO systems subjected to pilot-contamination. The proposed channel estimator performs well under moderate to aggressive pilot contamination scenarios without prior knowledge of the inter-cell large-scale channel coefficients and noise power. The estimator approximates the performance of a linear Minimum Mean Square Error (MMSE) as the number of antennas increases. Following, we derive a lower bound closed-form spectral efficiency of the Maximum Ratio Combining (MRC) detector in the proposed channel estimator. The simulation results highlight that the proposed estimator performance approaches the linear minimum mean square error (LMMSE) channel estimator asymptotically.

Accurate channel estimation is of utmost importance for massive MIMO systems to provide significant improvements in spectral and energy efficiency. In this work, we present a study on the distribution of a simple but yet effective and practical channel estimator for multi-cell massive MIMO systems suffering from pilot-contamination. The proposed channel estimator performs well under moderate to aggressive pilot contamination scenarios without previous knowledge of the inter-cell large-scale channel coefficients and noise power, asymptotically approximating the performance of the linear MMSE estimator as the number of antennas increases. We prove that the distribution of the proposed channel estimator can be accurately approximated by the circularly-symmetric complex normal distribution, when the number of antennas, M, deployed at the base station is greater than 10.

Carbon-based nanomaterials, such as carbon nanomaterials, play an important role in many promising nanomaterials in the field of biomedicine. Among them, carbon nanomaterials are a new kind of porous carbon nanomaterials with great application potential. Therefore, based on carbon nanomaterials, the interaction between biomaterials and cells and surface modification were analyzed. Studies have shown that the interaction between the surface of biological materials and cells is mainly the mutual molecular recognition between the surface receptors of cell membranes and the ligands on the surface of biomaterials. Therefore, biomimetic modification of the surface of biomaterials is used to enhance cell affinity and specific recognition. The carbon nanomaterial has a large specific surface area and pore volume, can provide high drug-loading capacity, has an adjustable pore structure and pores, can control the release of the drug molecules, and has a good application prospect in the field of drug delivery systems.

Brain cancer is the tenth leading cause of death in the U.S. Glioblastoma multiforme (GBM) is the most lethal primary malignant central nervous system tumor in adults. The present study employed samples from 1985-2014 to discover the difference in prognosis among glioblastoma subtypes after the evolution of treatment modalities over the past few years. The current study aims to find the differences between Glioblastoma multiforme (GBM) and giant cell glioblastoma (GCG) in terms of prognosis among adults and elderly patients in the U.S. This study is a historical cohort type of study and is conducted on adults and elderly individuals with GBM or GCG from the years 1985-2014 in the U.S. Data were collected from the Surveillance, Epidemiology, and End Results Program (SEER) database. The study exposure was GBM or GCG and the outcome was mortality. The potential confounders were age, sex, race, ethnicity, year of diagnosis, primary site, and surgery. A chi-square test was used for categorical data. A univariate analysis was used for variables having a p-value < 0.05. Potential confounders were selected and evaluated using multivariate logistic regression models to calculate the odds ratio with stepwise selection. The study sample was 25,117. The incidences of GBM and GCG were not similar in relation to age group. Also, Spanish-Hispanic ethnicity was independently protective of GBM and GCG as compared to Non-Spanish-Hispanic ethnicity patients with GBM have a higher mortality rate than do GCG patients. The mortality rate was higher among patients diagnosed before 2010. In conclusion, GCG was not statistically significant in association to reduced mortality. Non-Spanish-Hispanics with GBM or GCG had a higher mortality rate than did Spanish-Hispanics. Factors such as being female, being age >59, and having a year of diagnosis before 2010 were independently associated with increased mortality.

The advent of the genome editing era brings forth the promise of adoptive cell transfer using engineered chimeric antigen receptor (CAR) T-cells for targeted cancer therapy. CAR T-cell immunotherapy is probably one of the most encouraging developments for the treatment of hematological malignancies. In 2017, two CAR T-cell therapies were approved by the U. S Food and Drug Administration; one for the treatment of pediatric Acute Lymphoblastic Leukemia (ALL), the other for adult patients with advanced lymphomas. However, despite significant progress in the area, CAR T-cell therapy is still in its early days and faces significant challenges, including the complexity and costs associated with the technology. B-cell lymphoma is the most common hematopoietic cancer in dogs, with an incidence approaching 0.1% and a total of 20-100 cases per 100,000 individuals. It is a widely accepted naturally occurring model for human non-Hodgkin’s lymphoma. Current treatment is with combination chemotherapy protocols, which prolong life for less than a year in canines and are associated with severe dose-limiting side effects, such as gastrointestinal and bone marrow toxicity. To date, one canine study generated CAR T-cells by transfection of mRNA for CAR domain expression. While this was shown to provide a transient anti-tumor activity, results were modest, indicating that stable, genomic integration of CAR modules is required in order to achieve lasting therapeutic benefit. This Commentary summarizes the current state of knowledge on CAR T-cell immunotherapy in human medicine and its potential applications in animal health, while discussing the potential of the canine model as a translational system for immuno-oncology research.

The present study examined differences in operant responses in adult male and female rats during distinct phases of addiction. Males and females demonstrated escalation in methamphetamine (0.05 mg/kg, i.v.) intake with females showing enhanced latency to escalate, and bingeing. Following protracted abstinence, females show reduced responses during extinction, and have greater latency to extinguish compared with males, indicating reduced craving. Females demonstrated lower context-driven reinstatement compared to males, indicating that females have less motivational significance to the context associated with methamphetamine. Whole-cell patch-clamp recordings on dentate gyrus (DG) granule cell neurons (GCNs) were performed in acute brain slices from controls and methamphetamine experienced male and female rats and neuronal excitability were evaluated from GCNs. Reinstatement of methamphetamine seeking reduced spiking in males, and increased spiking in females compared to controls, demonstrating distinct neuroadaptations in intrinsic excitability of GCNs in males and females. Reduced excitability of GCNs in males were associated with enhanced levels of neural progenitor cells, expression of plasticity-related proteins including CaMKII and choline acetyltransferase in the DG. Enhanced excitability in females were associated with increased GluN2A/2B ratio, indicating changes in postsynaptic GluN subunit composition in the DG. Altered intrinsic excitability of GCNs were associated with reduced mossy fiber terminals in the hilus and pyramidal projections, demonstrating compromised neuroplasticity in the DG in both sexes. The alterations in excitability, plasticity-related proteins and mossy fiber density were correlated with enhanced activation of microglial cells in the hilus, indicating neuroimmune responses in both sexes. Together, the present results indicate sexually dimorphic adaptive biochemical changes in excitatory neurotransmitter systems in the DG and highlight the importance of including sex as a biological variable in exploring neuroplasticity and neuroimmune changes that predict enhanced relapse to methamphetamine-seeking behaviors.

Stem cells are undifferentiated cells which can give rise to any types of cells in our body. Hence, they have been utilized for various applications such as drug testing and disease modeling. However, for the successful of those applications, the survival and differentiation of stem cells into specialized lineages should be well controlled. Growth factors and chemical agents are the most common signals to promote the proliferation and differentiation of stem cells. However, those approaches holds several drawbacks such as the negative side effects, degradation or denaturation, and expensive. To address such limitations, nanomaterials have been recently used as a better approach for controlling stem cells behaviors. Graphene oxide is the derivative of graphene, the first 2D materials in the world. Recently, due to its extraordinary properties and great biological effects on stem cells, many scientists around the world have utilized graphene oxide to enhance the differentiation potential of stem cells. In this mini review, we highlight the key advances about the effects of graphene oxide on controlling stem cell growth and various types of stem cell differentiation. We also discuss the possible molecular mechanisms of graphene oxide in controlling stem cell growth and differentiation.

Aflatoxins, which have been classified as a group-1 carcinogen are the well-known mycotoxins produced by Aspergillus flavus. Aflatoxins have been linked to liver diseases, acute hepatic necrosis, resulting in cirrhosis or hepatocellular carcinomas due to which it incurs a loss of value in international trade for peanuts contaminated with it. The four main aflatoxins are B1, B2, G1, and G2 of which B1 is predominant. In plants, the cell wall is the primary barrier against pathogen invasion. Cell wall fortifications such as deposition of callose, cellulose, lignin, phenolic compounds and structural proteins help to prevent the pathogen infection. Further, the host cell’s ability to rapidly repair and reinforce its cell walls will result in a reduction of the penetration efficiency of the pathogen. Peanut seed coat acts as a physical and biochemical cell wall barrier against both pre and post-harvest pathogen infection. The structure of seed coat and the presence of polyphenol compounds have been reported to inhibit the growth of A. flavus, however, not successfully employed to develop A. flavus resistance in peanut. A comprehensive understanding of peanut seed coat development and biochemistry will provide information to design efficient strategies for the seed coat mediated A. flavus resistance and Aflatoxin contamination.

PEM fuel cell is a technology successfully used in the production of energy from hydrogen, allowing the use of hydrogen as an energy vector. It is scalable for stationary and mobile applications. However, the technology demands more research. An important research topic is fault diagnosis and condition monitoring to improve the life and the efficiency and to reduce the operation costs of PEMFC devices. Consequently, there is a need of physical models that let deep analysis. These models must be accurate enough to represent the PEMFC behavior and to allow the identification of different internal signals of a PEM fuel cell. This work presents a PEM fuel cell model that uses the output temperature in a closed loop, so it can represent the thermal and the electrical behavior. The model is used to represent a NEXA Ballard 1.2 kW; therefore it is necessary to fit the coefficients to represent the real behavior. Five optimization algorithms were tested to fit the model, three of them were taken from literature and two were proposed. Finally, the model with the parameters identified was validated with real.

Photodynamic inactivation (PDI) combines the nontoxic photosensitizer (PS) and visible light to generate reactive oxygen species (ROS), which can cause oxidative damages in (on) microbial organisms. Previously, we have shown that chitosan can augment the bactericidal efficacy mediated by PDI against bacteria and Candida. In this study, we showed that the antimicrobial action of chitosan to augment PDI relates to the enlargement of cell surface destruction. The microbial cell surfaces exhibit severe irregular shapes after PDI in the presence of chitosan. Furthermore, increase in the concentrations or incubation time of chitosan significantly reduce the amounts of photosensitizers TBO required, indicating that chitosan could be a synergistic agent with PDI against human pathogens. A prolonged lag phase was found in PDI surviving microbial cells, in which chitosan can act to synergistically eradicate the cells. Once the impaired cells rebuild their cellular functions from PDI-induced damage, the increased cytotoxic effect of chitosan disappeared. Together, our results suggest that chitosan with an augmented bactericidal activity after PDI is to inhibit the rehabilitation of PDI surviving cells, leading to microbial death.

We previously designed and synthesized dehydroxyepoxyquinomicin (DHMEQ) as an inhibitor of NF-κB based on the structure of microbial secondary metabolite epoxyquinomicin C. DHMEQ showed anti-inflammatory and anticancer activity in various in vivo disease models without toxicity. Cell detachment from the primary tumor and subsequent invasion are considered to be early phase of metastasis, while tumor cell attachment to the tissue and secondary tumor formation the late phase. The assay system for late phase was set up with intra-portal-vein injection of pancreatic cancer cells. Administration of DHMEQ was found to inhibit the liver metastasis possibly by decreasing the expression of MMP-9 and IL-8. Also when the pancreatic cancer cells treated with DHMEQ was inoculated into the peritoneal cavity of mice, the metastatic foci formation was inhibited. These results indicate that DHMEQ is likely to inhibit the late phase of metastasis. Meanwhile, we have recently employed three-dimensional (3D) culture of breast cancer cells for the model of early phase metastasis. DHMEQ inhibited the 3D invasion of breast cancer cells without toxicity. In this way, DHMEQ was shown to inhibit the late and early phases of metastasis. Thus, DHMEQ is likely to be useful for the suppression of cancer metastasis.

The focus of this research is to improve the performance of dye-sensitized solar cells (DSSC) through the adoption of high-quality FTO thin films and incorporation of graphene with DSSC photoanode to enhance its electrical transport. In this research, nanostructured FTO films were first grown with homemade Streaming Process for Electroless and Electrochemical Deposition technology (SPEED) using Tin (II) chloride dihydrate and ammonium fluoride and other chemical formulations. The FTO structural property was measured by X-ray diffraction (XRD); the films’ optical property was determined with transmittance spectra to curve over the wavelength range of 200-1000 nm measured with a spectrophotometer while scanning electron microscope (SEM) was used to determine the morphological properties of the samples. The electrical transport was evaluated by Hall Effect measurements at room temperature with a four-point probe. The FTO samples with the best structural, optical and electrical properties were employed as electrodes and counter electrodes of DSSC along with titanium dioxide. Thus, effect of graphene on the efficiency of DSSC was investigated. It was shown that a graphene-based DSSC showed an efficiency of 7.98% which is slightly higher than that of DSSC prototype without graphene (6.02%). The higher efficiency obtained with graphene can be credited to the ultrahigh surface area and thermal conductivity of graphene which tend to enhance the charge mobility and photovoltaic performance of DSSC. More research is however required to determine the exact amount of graphene that could achieve optimal DSSC performance. Further studies will also offer an adequate clarification for starting point of the better incorporation of graphene in DSSCs.

Synthesis of new series of 1-phenyl-3-(4-(pyridin-3-yl) phenyl) urea derivatives and its in vitro antiproliferative activities against NCI-60 human cancer cell lines of nine different cancer types are described. Fourteen compounds 5a-n have been synthesized with three different hydrogen bondable moieties (4-hydroxylmethylpiperidinyl and trimethoxyphenyloxy and 4-hydroxyethylpiperazine) attached to the core structure 1-phenyl-3-(4-(pyridin-3-yl) phenyl) urea. Different substituents with different π and σ values were added on the terminal phenyl group. Compounds with 4-hydroxymethylpiperidine moiety showed higher mean percentage inhibition values over the 60-cell line panel at 10-µM concentration. They showed broad-spectrum antiproliferative activity over many cell lines of different cancer types. For instance, compound 5a elicited some lethal rather than inhibition effects on SK-MEL-5 melanoma cell line, 786-0, A498, RXF 393 renal cancer cell lines, and MDA-MB-468 breast cancer cell line by 146.1, 108.7, 136.2, 134.8, 116.6 % at 10 µM, respectively. Compounds 5a-e exhibited superior antiproliferative activity than Paclitaxel and Gefitinib against the most sensitive cell lines. Two compounds, 5a and 5d showed promising mean growth inhibitions and thus were further tested at five-dose testing mode to determine their IC₅₀ values. The data revealed that 5a and 5d urea compounds are the most active derivatives with significant efficacies and superior potencies than Paclitaxel in 21 different cancer cell lines, belonging particularly to renal cancer and melanoma cell lines. Moreover, 5a and 5d had superior potencies than Gefitinib in 38 and 34 cancer cell lines, respectively; belonging particularly to colon cancer, breast cancer and melanoma cell lines.

This paper proposes a novel model for a PV cell with parameters variance dependency on temperature and irradiance included. The model relies on commercial available data, calculates the cell parameters for standard conditions and then extrapolates them for the whole operating range. An up-to-date review of the PV modeling is also included with series and parallel parasitic resistance values and dependencies discussed. The parameters variance is analyzed and included in the proposed PV model, where the self-heating phenomenon is also considered. Each parameter variance is compared to the results from different authors. The model includes only standard components and can be run on any SPICE-based simulator. Unlike other approaches that consider the internal temperature as a parameter, our proposal relies on air temperature as an input and computes the actual internal temperature accordingly. Finally, the model is validated via experiments and comparisons to similar approaches are provided.

Autophagy is a highly conserved catabolic mechanism that mediates the degradation of damaged cellular components by inducing their fusion with lysosomes. This process provides cells with an alternative source of energy for the synthesis of new proteins and the maintenance of metabolic homeostasis in stressful environments. Numerous studies have demonstrated beneficial roles for the induction as well as the suppression of autophagy in cancer cells. Autophagy may induce either survival or death depending on the cell/tissue type. Radiation therapy is widely used therapeutic option to treat cancer, and it induces autophagy in human cancer cell line. Also, melatonin seems to affect cancer cell death via regulation of programmed cell death. In this review, we summarize the current understanding of autophagy and its regulation in cancer.

Esophageal cancer is an extremely deadly tumor that accounts for 5% of all cancer deaths. The two main subtypes of the disease are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). To date, few studies analyse EAC for transcriptional signatures associated with diagnosis and/or prognosis, while most focus on the analysis of transcriptional profiles of ESCC. In this study, we used single-cell RNA sequencing (scRNA-seq) analysis of CD45+ cells enriched from Tumors and matched Non Tumor tissues from therapy naїve patients to identify all types of immune cells present in tumor immune infiltrate and its transcriptional profile. In addi-tion, we analysed the entire transcriptome in a cohort of 23 patients whose tissue biopsies were taken from Tumors and matched with Non Tumor tissue. The transcriptional signatures we obtained were then used to stratify a large cohort of TCGA EAC patients, demonstrating a strong association with their prognosis, as well as the ability to predict a patient's clinical outcome and better define the prognosis of EAC after surgery. In addition, these features may lead patients to effective therapies including immunotherapy approaches.

The observation that certain therapeutic strategies for targeting inflammation benefit patients with distinct immune-mediated inflammatory diseases (IMIDs) is exemplified by the success of TNF blockade in conditions including rheumatoid arthritis, ulcerative colitis and skin psoriasis, albeit only for subsets of individuals with each condition. This suggests intersecting "nodes" in inflammatory networks at a molecular and cellular level may drive and/or maintain IMIDs, being “shared” between traditionally distinct diagnoses without mapping neatly to a single clinical phenotype. In line with this proposition, integrative tumour tissue analyses in oncology have highlighted novel cell states acting across diverse cancers, with important implications for precision medicine. Drawing upon advances in the oncology field, this narrative review will first summarise learnings from the Human Cell Atlas in health as a platform for interrogating IMID tissues. It will then review cross-disease studies to date that inform this endeavour, before considering future directions in the field.

Aurora Kinase A being overexpressed in majority of cancers, appear to be an attractive therapeutic target. However, a Phase III clinical trial of Alisertib, a selective AURKA inhibitor, resulted in no better response compared to the comparator arm of chemotherapeutic regimen raising question regarding ability of the same to target the undetectable stem cell functions. In silico analysis indicated regulation of AURKA by the stemness factors Oct4 and Sox2. TCGA data indicated positive correlation of each of the factors with AURKA which were eventually validated in cell lines, patient tissues and blood by flow cytometry along with Oct4 binding on AURKA promoter being detected by ChIP assay. However, indirect immunofluorescence and cell cycle analyses indicated proliferation-independent AURKA functions during asymmetric cell division, a characteristic feature of stem cells. Thorough screening of the AURKA positive cells in patient samples denoted epithelial to mesenchymal transition and significant upregulation of Vimentin, a mesenchymal marker and ABCG2, a drug resistance marker under Oct4 or Sox2 influence. Overall, our study demonstrated combinatorial selection Oct4, Sox2, AURKA, Vimentin and ABCG2 for diagnostics and intervention of circulating breast cancer stem cells as a blood-based, cost-effective and simple approach which will be beneficial in reducing relapse.

Malignant neoplasms arising from the gastrointestinal (GI) tract are among the most common cancer types with a high mortality rate. Despite advances in treatment in a small subgroup harboring targetable mutations, the outcome remains poor, accounting for one in three cancer-related deaths observed globally. As a promising therapeutic option in various tumor types, immunotherapy with immune checkpoint inhibitors has also been evaluated in GI cancer, albeit with limited efficacy except for a small subgroup expressing microsatellite instability. In the quest for more effective treatment options, energetic efforts have been placed to evaluate the role of several immunotherapy approaches comprising of cancer vaccines, adoptive cell therapies and immune checkpoint inhibitors. In this review, we report our experience with personalized dendritic cell cancer vaccine and cytokine-induced killer cell therapy in three patients with GI cancers and summarize current clinical data on combined immunotherapy strategies.

Inflammatory bowel disease (IBD), including Crohn’s Disease (CD) and Ulcerative Colitis (UC) are chronic multifactorial disorders which affect the gastrointestinal tract with variable extent. Despite extensive research, their etiology and exact pathogenesis are still unknown. Cell-free DNAs (cfDNAs) are defined as any DNA fragments which are free from origin cell and able to circulate into bloodstream with or without microvescicles. CfDNAs are now being increasingly studied in different human diseases, like cancer or inflammatory diseases. However, to date it is unclear how IBD etiology is linked to cfDNAs in plasma. Extrachromosomal circular DNA (eccDNA) are non-plasmidic, nuclear, circular and closed DNA molecules found in all eukaryotes tested. CfDNAs appear to play an important role in autoimmune diseases, inflammatory processes, and cancer; recently, interest has also grown in IBD, and their role in the pathogenesis of IBD has been suggested. We now suggest that eccDNAs also plays a role in IBD. In this review we have comprehensively collected available knowledge in literature regarding cfDNA, eccDNA, and structures involving them such as neutrophil extracellular traps and exosomes, and their role in IBD. Finally, we focused on old and novel potential molecular therapies and drug delivery systems, such as nanoparticles, for IBD treatment.

Pure titanium is limited to be used in biomedical applications due to its lower mechanical strength compared to its alloy counterpart. To enhance its properties and improve medical implants feasibility, advancements in titanium processing technologies are necessary. One such technique is equal channel angular pressing (ECAP) for its severe plastic deformation (SPD). This study aimed to surface modify commercially pure titanium using micro arc oxidation (MAO) technology and mineral solutions containing Ca and P. The composition and shape of the changed surface were characterized using X-ray diffraction (XRD) and scanning electron microscope (SEM), respectively. The weight % of Ca and P in the coating was determined using Energy Dispersive Spectroscopy (EDS), and the corrosion resistance was evaluated through potentiodynamic measurement. The behavior of human dental pulp cell and periodontal cell behavior was also studied through a biomedical experiment over a period of 1-, 3-, and 7-days using trypsin as the culture medium and ELISA as the observation method. This study showed that the mechanical grain refinement method and surface modification significantly improved the biomechanical properties of commercially pure (CP) Titanium. Although the results showed variations in the absorbance values of cells cultured on different surfaces, this study provides valuable insights into pulp cell behavior and advances the field of biomedical research.

Proprotein convertases activate various envelope glycoproteins and participate in cellular entry of many viruses. We recently showed that the convertase furin is critical for the infectivity of SARS-CoV-2. This study investigated the implication of the two cholesterol-regulating convertases SKI-1 and PCSK9 in SARS-CoV-2 entry. We used cell-to-cell fusion assays in HeLa cells and pseudoparticle entry into Calu-3 cells. SKI-1 increases cell-to-cell fusion by enhancing the activation of SREBP-2, whereas PCSK9 reduces cell-to-cell fusion by promoting the cellular degradation of ACE2. Metalloprotease activation is sensitive to enhanced cholesterol levels resulting from SKI-1-activated SREBP-2 that leads to enhanced S2’ formation. However, high metalloprotease activity results in S2’ shedding into a new C-terminal fragment (S2”), leading to reduced cell-to-cell fusion. Indeed, S-mutants that increase S2’’ formation, abolish S2’ and cell-to-cell fusion, as well as pseudoparticles entry, indicating that the formation of S2’’ prevents SARS-CoV-2 cell-to-cell fusion and entry. We next demonstrated that PCSK9 enhanced the cellular degradation of ACE2, thereby reducing cell-to-cell fusion. However, different from the LDLR, a canonical target of PCSK9, the C-terminal CHRD domain of PCSK9 is dispensable for the PCSK9-induced degradation of ACE2. Molecular modeling suggested binding of ACE2 to the Pro/Catalytic domains of mature PCSK9. Thus, both cholesterol-regulating convertases SKI-1 and PCSK9 can modulate SARS-CoV-2 entry via two independent mechanisms.

Tumor cells exhibit a resistance-associated secretory phenotype involving extracellular vesicles (EVs) and heat shock proteins (HSPs). This response occurs in response to cell stress and cancer therapeutics. HSPs are stress-responsive molecular chaperones promoting proper protein folding, while also being released from cells with EVs as well as in free form as alarmins. We have here investigated the secretory phenotype of castration-resistant prostate cancer (CRPC) cells using proteome analysis. We have also examined the roles of the key co-chaperone CDC37 in stressome release, epithelial-to-mesenchymal transition (EMT), and tumor progression. A number of HSP family members and their common receptor CD91/LRP1 were enriched at high levels in CRPC cell-derived EVs among over 700 other protein species. The small EVs (30 to 200 nm in size, potentially exosomes) were released even in a non-heated condition from the prostate cancer cells, whereas EMT-coupled release of EVs (200 to 500 nm, likely ectosomes) with associated HSP90α was increased after heat shock stress (HSS). Lactate dehydrogenase, a marker of membrane leakage/damage of cells, was also released upon HSS from the prostate cancer cells. During this stress response, intracellular CDC37 was also transcriptionally inducible by heat shock factor 1, and knockdown of CDC37 decreased EMT-coupled release of EVs. Triple knockdown of CDC37, HSP90α, and HSP90β was required for efficient reduction of the chaperone trio and to reduce tumorigenicity of the CRPC cells in vivo. Taken together, the data indicated that CDC37 and HSP90 are essential for stressome release and for tumorigenesis in resistant cancer.

In interepidemic periods, a sapronoses typically employs a variety of mechanisms for maintaining viability of its causative agent in terrestrial parasitic systems, associated with different adaptive strategies utilized by its populations to survive. Unlike spore-forming bacteria, causative agents of sapronoses use resistant cell forms, which is a viable but nonculturable (VBNC) state, and persistence. Implementation of these strategies is conditioned by effects of various stress factors of the habitat and is characterized by decreased metabolism, alteration of the morphology and physiology of bacterial cell, and cessation of its replication. It is important that the resistant forms of cells retain virulence and, as favorable conditions come, turn back into the active vegetative form again. The discovery of the genetic modules of bacterial toxin–antitoxin systems in recent years has made it possible to identify a number of complicated regulatory molecular mechanisms responsible for maintaining the pathogenic potential of resistant forms of causative agents of natural-focus sapronoses in interepidemic periods.

Cancer is a complex and devastating disease that has engaged scientists and researchers for decades. Despite tremendous efforts, previous hypotheses about cancer development have not achieved significant breakthroughs. Evolutionary Cancer Cell Biology (ECCB) is a novel and emerging branch of oncological science that provides an evolutionary perspective on the origin of cancer. It reveals that the cancer genome evolved hundreds of millions of years ago, long before multicellular organisms such as metazoans and humans emerged. ECCB aims to unify all evolutionary insights, hypotheses, and theories into a cohesive framework. It investigates the intricate relationship between cancer genomics and ancient pre-metazoan genes that emerge when normal cells transform into cancer cells. It challenges the conventional wisdom of cancer research by suggesting that cancer could arise through intrinsic cellular mechanisms without genetic alterations and mutations. Furthermore, it postulates that somatic mutations are only secondary, downstream events in the process of oncogenesis.

Fractional cointegration in time series data has been explored by several authors, but panel data applications have been largely neglected. A previous study of ours discovered that the Chen and Hurvich fractional cointegration test for time series was fairly robust to a moderate degree of heterogeneity across sections, out of the six tests considered. Therefore, this paper advances a customized version of the Chen and Hurvich methodology to detect cointegrating connections in panels with unobserved fixed effects. Specifically, we develop a test statistic that accommodates variation in the long-term cointegrating vectors and fractional cointegration parameters across observational units. The behaviour of our proposed test is examined through extensive Monte Carlo experiments under various data generating processes and circumstances. The findings reveal that our modified test performs quite well comparatively and can successfully identify fractional cointegrating relationships in panels even in the presence of idiosyncratic disturbances unique to each cross-sectional unit. Furthermore, the proposed modified test procedure established the presence of long-run equilibrium between the exchange rate and labour wage of 36 countries agricultural markets.

Graphene-based materials (GBMs) are a prospective material of choice for rechargeable battery electrodes because of their unique set of qualities, which include tunable interlayer channels, high specific surface area, and strong electrical conductivity characteristics. The market for commercial rechargeable batteries is now dominated by lithium-ion batteries (LIBs), however issues with organic electrolyte safety, high lithium pricing, and limited lithium resources have hindered LIB development. Zinc-based rechargeable batteries have emerged as a viable substitute for rechargeable batteries due to their affordability, safety, and improved performance. This review article explores recent developments in the synthesis and advancement of GBMs for rechargeable zinc‐air batteries (ZABs), and common graphene-based electrocatalyst types. An outlook on the difficulties and probable future paths of this extremely promising field of study is provided at the end.

Session-based recommendations which aim to predict subsequent user-item interaction based on historical user behavior during anonymous sessions can be challenging tasks. Two main challenges need to be addressed and improved: (1) How to analyze these sessions to accurately and completely capture users’ preferences, and (2) how to identify and eliminate any interference caused by noisy behavior. Existing methods have not adequately addressed these issues since they either neglected the valuable insight that can be gained from analyzing consecutive groups of items or failed to take these noisy data in sessions seriously and handled them properly, which can jointly impede recommendation systems from capturing users’ real intentions. To address these two problems, we designed a multi-order semantic denoising (MSD) model for session-based recommendations. Specifically, we grouped items of different lengths as varying multi-order semantic units to mine the user’s primary intention from multiple dimensions. Meanwhile, a novel denoising network was designed to alleviate the interference of noisy behavior and provide a more precise session representation. The result of extensive experiments on three real-world datasets demonstrated that the proposed MSD model exhibited improved performance compared with existing state-of-the-art methods in session-based recommendation.

Cardiovascular diseases, which are the leading cause of death in Croatia, are linked to the high prevalence of hypertension. Both are associated with high salt intake which was determined almost two decades ago when Croatian Action on Salt and Health (CRASH) was launched. The main objective of the present study was to evaluate salt, potassium, and iodine intake using 24-hour urine samples in a random sample of adult Croatian population, and to analyse trends in salt consumption after the CRASH has intensively started. Methods: In this national population-based EH-UH 2 study performed in 2018-2021 (participation rate 72 %) in which we analysed a single 24-hour urine sample, 1067 adult participants (mean age 57.12 (SD 13.9), men 35%) were included. Results: Mean salt and potassium intakes were 8.6 g/day (IQR 6.2-11.2) and 2.8 g/day (IQR 2.1-3.5), respectively, with sodium-to-potassium ratio of 2.6 (IQR 1.8-3.3). We detected a decrease of 17.6% (2 g/day less) in salt consumption compared to our previous salt-mapping study. However, only 13.7%, and 8.9 % met the WHO salt and potassium recommended target of 5 g/day, and 3.5 g/day, respectively. Salt intake was higher, and potassium ingestion was lower in rural vs. urban regions, and in continental vs. Mediterranean parts of Croatia. Moderate to severe iodine insufficiency was determined in only 3% adult participants. Conclusion: In the last fifteen years, salt consumption has been significantly reduced in Croatian adult population because of intensive and broad CRASH program led by the Croatian Society of Hypertension and the Croatian Hypertension League. However, salt intake is still too high, and potassium ingestion is too low. With expected more active engagement and help of the government, obtained results could be significantly improved. Salt reduction programs are most cost-effective methods of cardiovascular disease prevention and should be considered more seriously by the government and health policy makers.

The majority of local IPv6 networks continue to remain insecure and vulnerable to neighbor spoofing attacks. The Secure Neighbor Discovery (SEND) standard and its concomitant Cryptographically Generated Addressing (CGA) scheme were accepted by large standards bodies to codify practical mitigations. SEND and CGA have never seen widespread adoption due to their complexities, obscurity, costs, compatibility issues, and continued lack of mature implementations. In light of their poor adoption, research since their standardization has continued to find new perspectives and proffer new ideas. The orthodox solutions for securing Neighbor Discovery have historically struggled to successfully harmonize three core ideals: simplicity, flexibility, and privacy preservation. This research introduces Voucher-Based Addressing, a low-configuration, low-cost, and high-impact alternative to IPv6 address generation methods. It secures the Neighbor Discovery address resolution process while remaining simple, highly adaptable, indistinguishable, and privacy-focused. Applying a unique concoction of cryptographic key derivation functions, link-layer address binding, and neighbor consensus on the parameters of address generation, resolved address bindings are verifiable without the need for complex techniques that have hindered the adoption of canonical specifications.

In this work, zinc oxide (ZnO)/ granular activated carbon (GAC) composites at different ZnO concentration (0.25M-ZnO@GAC, 0.5M-ZnO@GAC, and 0.75M-ZnO@GAC) were prepared by an in-situ hydrothermal method and demonstrated synergistic photocatalytic degradation and ad-sorption of Rhodamine B (RhB). The thermal stability, morphological structure, elemental com-position, crystallographic structure, and textural properties of developed catalysts were charac-terized by thermal gravimetric analysis (TGA/DTG), scanning electron microscopy equipped with energy dispersive-x-ray (SEM-EDS), x-ray diffraction (XRD), and Brunauer–Emmett–Teller (BET) analysis. Successful loading of ZnO onto GAC was confirmed by SEM-EDS and XRD analysis. The BET surface areas of GAC, 0.25M-ZnO@GAC, 0.5M-ZnO@GAC, and 0.75M-ZnO@GAC were 474 m2/g, 450 m2/g, 453 m2/g, and 421 m2/g, respectively. The decrease in GAC could be attributed to the successful loading of ZnO on the GAC surface. Notably, 0.5M-ZnO@GAC exhibited the best photocatalytic degradation efficiency of 82% and 97% under UV-A and UV-C light over 120 min, attributed to improved crystallinity and visible light absorption. The photocatalytic degradation parameters revealed that lowering the RhB concentration, raising the catalyst dosage and pH be-yond the point of zero charge (PZC) would favor the RhB degradation. Photocatalytic reusability was demonstrated over 5 cycles. Scavenger tests revealed that the hydroxyl radicals (•OH), su-peroxide radicals (O2−•), and photoinduced hole (h+) radicals play a major role during the RhB degradation process. Based on the TOC results, the RhB mineralization efficiency of 79.1% was achieved by 0.5M-ZnO@GAC. Additionally, GAC exhibited a strong adsorptive performance towards RhB with adsorption capacity and RhB removal of 487.1 mg/g and 99.5% achieved within 90 min equilibrium time. The adsorption characteristics were best described by pseu-do-second-order kinetics, suggesting chemical adsorption. This research offers a new strategy for the development of effective photocatalyst materials with potential for wider wastewater treat-ment applications.

Demand for environmentally friendly types of energy is growing all over the world, which naturally increases the intensity of work on the production of hydrogen-containing fuel mixtures. Steam reforming of methanol is one of the most effective areas of research, as it is a process with low energy consumption. The results of steam reforming of methanol on the catalysts prepared by solution combustion synthesis (SCS) and impregnation by moisture capacity are presented. Investigation of the activity of Cu-Ce-Al catalysts of different composition was carried out for production of hydrogen and comparison of SCS with traditional impregnation method. Methanol conversion reaches 99%, while the selectivity of H2 was 88%, at 500 °C. It was found that CuAl2O4 spinel formation is due to substitution of Al3+ with Cu2+ Ce3+ cations. A consequence CuAl2O4 and CeAlO3 lattice parameters increase because of difference in ionic radius of Al3+ (0.53 Å) and Cu2+ (0.73 Å), Ce3+ (1.07 Å). Advantages of SCS catalysts in steam reforming of methanol were shown. The aim of this research is to develop a new catalyst for conversion of methanol into hydrogen containing fuel mixtures, which will further promote the organization of a new era of environmentally friendly energy-saving production methods.

This study investigates the application of frequency augmentation techniques to improve condition-based maintenance (CBM+) systems for airborne weapon systems, focusing on the predictive accuracy of velocity and acceleration parameters. Utilizing MIL-STD-1553B MUX data from 138 sorties of fixed-wing aircraft, we explored six augmentation methods, including traditional interpolations (linear, quadratic, cubic spline) and advanced machine learning models (K-Nearest Neighbor, LSTM, and Bi-LSTM). Our findings indicate that while traditional methods like linear interpolation are more effective for velocity parameters, advanced ML techniques, particularly Bi-LSTM, provide better results for acceleration parameters, which exhibit more complex and rapid variability. The study underscores the necessity of tailoring augmentation approaches to specific parameter characteristics and highlights the potential of ML models in capturing intricate patterns within time-series data. These insights are critical for advancing CBM+ systems in military avionics, enhancing reliability and operational efficiency through improved data processing strategies. Future work should explore more performant augmentation techniques, such as by integrating multi-dimensional datasets, and explore ways to develop automated tools for a more powerful predictive maintenance framework.

Lysine plays a crucial role in promoting development, enhancing immune function, and improving the function of central nervous system tissues. The two configurational isomers of amino acids have significantly different effects. Currently, methods for chiral recognition of lysine all have drawbacks such as expensive equipment and complicated detection processes, whereas fluorescence analysis boasts high sensitivity, strong selectivity, and simple operation. In this study, we synthesized four novel Binaphthyl-Amine (BINAM)-based fluorescent probes capable of specifically identifying the L-configuration of lysine among the twenty amino acids constituting human proteins. The enantiomeric fluorescence enhancement ratio (ef or ΔIL/ΔID) reached up to 15.29, demonstrating high enantioselectivity. We also evaluated the probe's recognition ability under different pH, reaction times, and metal ion conditions, as well as the Limit of Detection of the probe. Our findings indicate that this probe is a highly stable tool for detecting chiral lysine.

In Pakistan, 2018 National Nutrition Survey reported 40% of under five children were stunted. This study assesses the effectiveness of nutritional supplementation in reducing stunting among under-five children in two rural districts in Sindh, Pakistan. This was a mixed-method quasi-experimental study with intervention and control population. 3397 and 3277 under-five children participated in the baseline and end-line surveys. Both study areas were matched for demographic and economic circumstances. The participants received nutrient supplements underpinned by nutrition behaviour change communication for appropriate complementary feeding practices and hand hygiene targeted at primary caregivers during the first 1000 days of an infant's life. The impact was assessed using the difference in difference analysis with kernel propensity score matching to adjust the differences among control and intervention populations.

The sustainable development of resource-based cities has long been a focal point for both governmental policies and academic research. A wealth of academic literature identifies the 'resource curse' as a critical barrier to sustainable development in these urban areas. Despite extensive studies, a consensus on effective strategies to circumvent or resolve this challenge remains elusive. Recent empirical data reveals a noticeable pattern of economic growth differentiation in China's resource-based cities. Why do some resource-based cities experience economic decline while others achieve sustainable economic growth? Therefore, this paper analyzes the reasons for the divergence of economic growth in resource cities from the perspective of heterogeneity. The results of the study show that the phenomenon of the resource curse is conditional, and the heterogeneity of demo-graphic changes, geographic location and institutional environment has a significant impact on the economic growth of resource cities. These factors are investigated to elucidate the observed diversification and heterogeneity in the economic growth of resource-based cities. Building upon this analysis, the paper proposes a framework for differentiated sustainable development pathways tailored to the unique contexts of these cities. This approach not only contributes to the current understanding of the 'resource curse' but also offers novel insights for future research aiming to adopt a more nuanced and context-specific perspective in examining sustainable urban development.

Among the different steps in software development software testing is one of the inevitable steps. Manual testing is considered to be more expensive and time-consuming, and this led to the formation of automated testing tools. Automated software testing tools offer a comprehensive system testing solution that minimizes the risk of any errors that could result in financial losses. One such tool is selenium. Selenium testing is an advantageous method employed by developers and testers to assess their code. Selenium is compatible with numerous widelyused programming languages like C#, Java, Python, and more. This paper focuses on understanding the in and outs of software testing using selenium

Recently, interest in STEM education has grown among researchers and educators, also considering the skills required to address the challenges of the 21st century. Supporting learning in STEM subjects is an open challenge, especially during secondary education, which is reflected in the implementation of innovative pedagogical practices, including approaches focused on Game-Based Learning (GBL). This study analyzed the main issues addressed by research on game-based educational approaches applied to STEM teaching and learning in secondary school and their evolving trends. A text analysis of abstracts published in the past decade was conducted using T-lab software. The “Word Analysis” function was used for preliminary visual mapping; then the “Specificity Analysis” and “Thematic Analysis of Elementary Contexts” functions were applied to explore changes in research directions and to map the themes covered by the most recent studies. The results showed that the implementation of games in STEM disciplines is a promising area of inquiry. A shift in research directions also emerged, currently more focused on studying how GBL can foster engagement and the emotional component of learning. Adapting to rapidly changing technology and integrating essential skills such as coding and computational thinking are additional challenges that the research community is facing.

This review highlights the potential and limitations of mRNA vaccines with a particular focus on mucosal delivery as an alternative to parenteral administration. The strengths of mRNA vaccines are: a) Versatility: they can be adapted to target a wide range of pathogens; b) Faster development: designed and produced more quickly than traditional vaccines; c) High efficacy: effective in preventing severe disease, as demonstrated during the COVID-19 pandemic. Current challenges: a) Delivery: current methods (mainly intramuscular injection) may not be optimal for inducing mucosal immunity; b) Stability: mRNA is fragile and needs to be protected from degradation; c) Safety: potential side effects, including myocarditis, blood clotting, allergic reactions need further investigation. Mucosal delivery could be more effective in preventing the transmission of pathogens and is generally better accepted by the population. Pros: offers the potential to induce local immunity at the site of pathogen entry, potentially providing broader protection; Cons: developing effective delivery systems and adjuvants for mucosal delivery is difficult. Extracellular vesicles as a mucosal delivery system are promising and offer a potentially safe, scalable, and needle-free approach. Future directions: a) Optimizing mRNA constructs: strategies like codon optimization and self-amplifying RNA can improve stability and translation efficiency; b) Rigorous pre-clinical studies are essential before human trials.

Most recent university campuses follow the North American model, built on city limits or countryside, with large separate buildings in open green spaces. Studies suggest that prevalence and severity of mental health issues among university students are increasing over the past decade in most countries. University services were created to face this growing problem, however individual based interventions have limited effects on mental health and well-being of a large population. Our aim was to verify if and how the natural environment in Campuses is focused on programs to cope with the issue of mental health and well-being among students. Systematic review of literature was undertaken with search in Scopus and LILACS with the keywords “green areas” AND “well-being” AND “Campus”, following PRISMA guidelines. As a result, 32 articles were selected. Research on the topic is recent, mostly in the USA, Bulgaria, and China. Most studies used objective information on campuses’ greenness and/or university students’ perception. Mental health was usually measured by validated scores. Findings of all the studies indicated positive association between campus greenery and well-being of students. We conclude that there is a large potential for use of university campuses in programs and sites for students´ restoration and stress relief.

OBJECTIVE: Cervical cancer is a major cause of cancer-related mortality, necessitating effective screening and diagnostic methods. This study aimed to assess the performance of cervicovaginal smear (CVS) and Human papilloma virus (HPV)-DNA cotest. STUDY DESIGN: The pathology results of 225 female patients who underwent HPV-DNA testing with CVS between 2014 and 2022 and were subsequently diagnosed by colposcopic cervical biopsy or second CVS were retrospectively analyzed. RESULTS: CVS samples showed Atypical Squamous Cells of Undetermined Significance (ASCUS), Low-grade squamous intraepithelial lesion (LSIL), High-grade squamous intraepithelial lesion (HSIL) and cervical cancer. Concordance between the first and second diagnoses demonstrated moderate agreement for LSIL. ASCUS cases exhibited a significant correlation with HPV-DNA positivity and higher-grade cervical lesions. In biopsy, sensitivity and specificity for CIN 2 were 67.8% and 67.9%, respectively, while for CIN 3, they were 81.8% and 58.5%. HPV testing showed significant correlation with histopathologic results. In women over 40 years, more intraepithelial lesions were diagnosed compared to younger women (p<0.005). The conventional smear technique proved reliable in detecting high-grade lesions. CONCLUSION: Despite the limitations of our study, our results emphasize the value of HPV-DNA testing to avoid unnecessary interventions and to establish appropriate follow-up strategies.

Flooding during the rainy season poses a significant threat to the city of Hargeisa, impacting the well-being of both its residents and the local ecosystems. This research focuses on urban flood control, with a specific emphasis on finding sustainable solutions for managing large stream in Hargeisa. The study identifies five key dimensions, including infrastructure, transportation, environmental soil, life, and property, as critical factors in addressing the issue. By employing a comparative method and collecting data through closed-ended questions, the research aims to analyze and weigh eleven potential solutions, seeking to identify the most effective approaches. The findings of the study indicate that constructing a dam emerges as a promising and sustainable solution, with a weightage of 70 percent. This highlights the potential of a dam in mitigating the impact of floods in the region. Additionally, considering the government's economic capacity, the implementation of check dams is identified as another viable option, with a weightage of 95 percent for reducing the flood power of the stream. These solutions offer practical and effective measures to address the recurring problem of flooding in Hargeisa. To support future decision-making and planning, the research underscores the need for establishing a comprehensive rainfall data database. This database would store relevant information on rainfall patterns, enabling better understanding and prediction of flood events. The study emphasizes the importance of collaboration between local government authorities, environmental organizations, and stakeholders to develop and implement effective flood control strategies. This research provides a systematic approach that can inform and benefit regional and global researchers, policymakers, and municipal governments in their efforts to address urban flood control challenges, not only in Hargeisa but also in similar contexts worldwide.

Carbon offsetting is currently a major tool in managing carbon emissions and the drive to Net-Zero. This study aims to identify the offsetting potential of existing conservation schemes, and whether carbon offsetting credits could potentially finance the continued management of the conservation activities. The results from Dorset, in the UK indicate that many existing conservation schemes in woodland, heathland and grasslands can not only enhance biodiversity but also capture significant amounts of carbon. We show that the cost per additional tonne of carbon sequestered as a result of conservation activities varies considerably between different conservation projects. On average, the cost of this offsetting is £80 per tonne CO2e sequestered and ranging between £120 and £0 depending on the project and whether existing biodiversity grants would be available. However, this figure was based on adapting and refining existing conservation projects, and did not involve expensive factors such as purchase of land, which make the prices potentially unrealistic. While the costs identified are higher than many offsetting schemes at present, it could present a useful option for those wishing to localise their offsetting, and could be combined with biodiversity credits or other credit schemes to make the higher costs more attractive.

Hepatic carboxylesterase 1(CES1) metabolizes many prodrugs into active ingredients or direct-acting drugs into inactive metabolites. We aim to develop a semi-physiologically based pharmacokinetic model(Semi-PBPK model) to simultaneously predict pharmacokinetics of CES1 substrates and their active metabolites in liver cirrhosis(LC) patients. Six prodrugs(enalapril, benazepril, cilazapril, temocapril, perindopril and oseltamivir) and three direct-acting drugs (flumazenil, pethidine and remimazolam) were selected. The parameters including organ blood flows, plasma binding protein concentrations, functional liver volume, hepatic enzymatic activity, glomerular filtration rate(GFR) and gastrointestinal transit rate were introduced into the simulation. Pharmacokinetic profiles of these drugs and their active metabolites were simulated in 100 virtual subjects. The developed semi-PBPK model, following validation in healthy subjects, was extrapolated to LC patients. Most of the observations are within the 5% and 95% quantile of simulations from 100 virtual patients. The estimated AUC and Cmax are within 0.5-2-fold of observation. The sensitivity analysis showed that the decreased plasma exposure of active metabolite due to the decreased CES1 was partly attenuated by the decreased GFR. Conclusion: The developed PBPK model has successfully predicted pharmacokinetics of CES1 substrates and their metabolites in healthy subjects and LC patients, which assists in tailoring dosages of CES1 substrates in LC patients.

The role of land surface temperature (LST) is of utmost importance in multiple academic disciplines such as climatology, hydrology, ecology, and meteorology. Until to now, many methods have been proposed to estimate LST from satellite thermal infrared data. The Thermal Infrared Sensor (IRS) on the Chinese ZY1-02E satellite is a pivotal instrument employed for gathering thermal infrared (TIR) data of land surfaces. The objective of this research is to evaluate the feasibility of a single-channel approach based on water vapor scaling (WVS) for deriving LST from ZY1-02E IRS data because of its wide spectrum range, i.e., 7~12μm, affected strongly by both atmospheric water vapor and ozone. Three study areas, namely Baotou, Heihe River Basin, and Yantai-sea sites, were selected as validation sites to evaluate the LST inversion accuracy. This evaluation was also conducted by cross-comparison between the retrieved LST and MODIS LST product. The results revealed that the WVS-based method exhibited an average bias of 0.63K and an RMSE of 1.62K compared to the in-situ LSTs. The WVS-based method demonstrated reasonable accuracy through cross-validation with the MODIS LST product, with an average bias of 0.77K and RMSE of 2.0K. These findings provide that the WVS-based method is effective to estimate LST from ZY1-02E IRS data.

This study measured secondary students’ digital literacy using a digital game-based assessment system that was designed and developed based on the Evidence-Centered Game Design (ECGD) approach. A total of 188 secondary students constituted the valid samples in this study. Fine-grained behavioral data generated from students’ gameplay processes were collected and recorded with the assessment system. The Delphi method was used to extract feature variables related to digital literacy from the process data, and the Analytic Hierarchy Process (AHP) method was used to construct the measurement model. The assessment results of the ECGD-based assessment had a high correlation with standardized test scores, which have been shown to be reliable and valid in prior large-scale assessment studies.

This article focuses on the variation of how the U.S. Circuit Court of Appeals uses the language of trauma in gender-based asylum claims. Gender-based asylum claims include female genital mu-tilation (FGM), domestic violence, forced marriage, coercive population control (CPC) in the form of forced abortions and forced sterilizations, and rape. The Circuit Courts have reviewed appeals from petitioners with asylum claims since 1946, yet the language of trauma did not appear in the Court’s decisions until 1983. From 1983-2023 only 385, 3.85% or less, of the over 10,000 asylum cases before the Circuit Courts used the language of trauma in its legal interpretation of persecution. I have identified 101 gender-based asylum cases that were reviewed by one of the eleven U.S. Circuit Court of Appeals that apply the language of trauma in its legal interpretation of persecution for this analysis. This study found that U.S. Circuit Courts use the language of trauma in four ways: precedent cases, psychological trauma, physical trauma, and policies and reports when reviewing gender-based asylum claims.

Modelling and presenting mathematical relationships for human behaviour is one of the most complex issues that researchers have always dealt with. In this article, a bottom-up framework for calculating agricultural needs is presented using the socioeconomic characteristics of farmers (such as education level, age, and dependence on income on agriculture) and how their lands are located concerning each other (interactions between neighbours). The objective function of this framework is to maximize the profit of individual farmers based on the amount of water received. Two scenarios, ABM1 (not considering neighbourhood effects) and ABM2 (all cases of farmers' placement and feeling neighbourhood effects), were investigated. In the first scenario (ABM1), there was a noteworthy reduction in water deficit volumes by approximately 35%, accompanied by a 20% increment in farmers' profits. Interestingly, higher risk-taking tendencies correlated with reduced profit margins. The second scenario (ABM2) underscored the significant role of neighborhood dynamics in cultivating diverse behavioral patterns among farmers, subsequently affecting their profitability. A granular examination revealed that farmers with a higher propensity for risk-taking generally accrued lower profits. Additionally, the study facilitated the calculation of total annual profits and average water consumption for each farmer, offering valuable insights for optimizing water resource management and allocation strategies. These findings are instrumental for planners and water resource managers aiming to promote sustainable agricultural practices and efficient water use.

Fuzzy Rule Interpolation (FRI) offers an innovative methodology for inferring outcomes from data points that match no established rules in a sparse fuzzy rule base. Generally, a traditional fuzzy rule-based system suffers from the inability to perform inference while facing an unmatched observation, given a sparse fuzzy rule base that is derived from insufficient data or inadequate human experience and that fails to cover parts of a specific problem domain. Fortunately, starting with a sparse rule base, Fuzzy Rule Interpolation (FRI) can help to formulate interpolated rules specifically in instances where observations fail to activate any existing rule. An interpolated rule gives a result called consequent, which is related to the unmatched observation so that the inference system will not fail to generate an outcome corresponding to the observation as the output. Conventionally, these interpolated rules will be discarded after obtaining outcomes. However, valuable information may be potentially embedded within those discarded rules addressing the limitation regarding the coverage of the original sparse knowledge space. Moreover, without exploiting the potential value of the interpolated rules, the fuzzy inference system based on a sparse rule base will never improve its efficiency and robustness in the long run. Therefore, this underscores the necessity for Dynamic Fuzzy Rule Interpolation (D-FRI), which aims to collate interpolated rules that cover particular knowledge spaces absent in the sparse rule base. Intuitively, those frequently appeared interpolated rules are considered valuable because future observations are more likely to hit the respective problem areas. Promoting selected interpolated rules to the sparse rule base can enhance the overall coverage of the knowledge space and increase the inference efficiency over time. This paper introduces a framework for Dynamic Fuzzy Rule Interpolation that integrates the widely used Transformation-based Fuzzy Rule Interpolation (T-FRI) with an effective form of clustering of interpolated results. Experimental findings validate the effectiveness of this approach.

The combined efect of shape and electrostatic complementarities (Sc, EC) at the interface of the interacting protein partners (PPI) serves as the physical basis for such associations and is a strong detterminant of their binding energetics. EnCPdock (https://www.scinetmol.in/EnCPdock/) presents a comprehensive web-platform for the direct conjoint comparative analyses of complementarity and binding energetics in PPIs. It elegantly interlinks the dual nature of local (Sc) and non-local complementarity (EC) in PPIs using the Complementarity Plot. It further derives an AI-based ∆G_binding with a prediction accuracy comparable to the state-of-the-art. This book-chapter presents a practical manual to conceptualize and implement EnCPdock with its various features and functionalities, collectively having the potential to serve as a valuable protein engineering tool in the design of novel protein interfaces.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

In recent years the study of the teacher-student relationship in the teaching-learning processes in physical education has had great emphasis. Previous studies have shown that the use of the Spectrum of teaching Styles can enhance intrinsic motivation, enjoyment, adherence to physical activity and physical activity levels in children and adolescents. The present study aims to assess if a physical education (PE) intervention based on the variations in teaching styles, with reference to production ones, can also have positive effects on physical fitness. The sample involved 4 primary school classes (n = 124 children, mean age = 8-10 years) recruited from the SBAM (Health, Wellness, Food Education and Movement at School) Project in Apulia, Southern Italy. Classes were randomly assigned to Experimental Group (EG) and Control Group (CG). EG followed a 5months experimental intervention based on the variation of teaching styles, while CG performed regular PE lessons. Physical fitness test was assessed with Standing Long Jump (SLJ), Medicine Ball Throw 1kg (MBT), and 20m sprint (20m), while two validated questionnaires were used to evaluate physical self-perception (PSP) and enjoyment. A 2x2 (intervention group x time) ANOVA was carried out to assess significant difference and interaction effect pre (t0) and post (t1) intervention protocol. Data analysis showed a significant improvement of physical fitness in both EG and CG, while PSP and enjoyment increased only in EG. Moreover, significant interaction (p&lt;. 05) effects were found for 20m sprint, PSP and Enjoyment with low effect size (η2 ~. 20). The results of the present study highlight the effectiveness of a PE intervention based on the variation of teaching styles in improving physical fitness, self-perception, and enjoyment. Moreover, the use of production teaching styles significantly impacts self-perception and enjoyment, that are important mediating factors for guarantee better adherence to physical activity.

Recently, e-commerce companies have been adopting and continuously enhancing personalized product recommendation systems, and there is active research in this field within academia. However, personalized product recommendations in offline retail stores have not yielded significant outcomes thus far. Especially for small-format offline retail businesses like convenience stores, where customer information might be limited, providing personalized product recommendations poses even greater challenges. To address this issue, this study aimed to find a solution by shifting the perspective on recommendation methods and altering the target of recommendations in existing personalized recommendation models. In this study, recommending products that customers need in an offline store was defined as suggesting products that should be introduced and displayed within the store. In other words, the recommendation focus shifted from individuals to the stores themselves. This recommendation system proposes products that individual stores have not yet introduced but are anticipated to be purchased by customers among the products managed by the headquarters. Building upon this, we devised a store-based product recommendation system. The widely used user-based collaborative filtering model, a common technique in existing recommendation systems, was adapted into a store-based collaborative filtering model. Furthermore, various rules and logic pertinent to store operations and business considerations for convenience stores were integrated to implement this store product recommendation system. The accuracy and effectiveness of the system were demonstrated through its application in actual convenience stores. Results from the pilot implementation of the system showed that 88% of the newly recommended products in individual stores were sold based on one week of sales data, and the sales revenue was 1.75 times higher than the average sales revenue of those products across the entire company. Survey results on business owners' satisfaction yielded a score of 4.2 out of 5, indicating a high level of contentment. Additional observed effects included the expansion of product range and reduction in order lead times. However, 12% of the total recommended SKUs did not sell within one week, and 34% of the SKUs did not meet the overall average sales quantity. This research holds significance in extending the scope of personalized recommendation studies from primarily online platforms to offline retail businesses like convenience stores. It provides tangible methodologies and outcomes that can be implemented in real-world settings through the construction and validation of an actual system. The study also suggests avenues for future research to address some of the identified limitations.

Diabetes mellitus, a metabolic disorder that is persistent in nature, is identified by an elevated concentration of glucose in the bloodstream. The disease has become a major public health problem, affecting millions of people globally, and is associated with significant morbidity and mortality. The increasing prevalence of diabetes and the lack of effective therapeutic interventions have led to the exploration of alternative and complementary forms of therapy, including ethnomedicine. Ethnomedicine is the study of traditional medical systems and the medicinal plants used by Indigenous communities. In other words, Ethnomedicine refers to the traditional medical practices and beliefs of a particular cultural or ethnic group. The most popular example of traditional medicine is the use of Aloe vera for the treatment of various diseases such as sunburn, cuts, burns, hypertension, diabetes, and jaundice for thousands of years [1]. In recent years, there has been increasing interest in the potential role of ethnomedicine in the management of diabetes, given its widespread use in many communities and its potential to offer cost-effective and culturally acceptable treatment options. It encompasses a range of traditional healing practices, including herbalism, acupuncture, and massage therapy. Despite the inconsistencies, there is growing evidence to suggest that certain ethnomedical practices may be effective in the management of diabetes [2,3]. For example, several studies have shown that certain herbal remedies, such as cinnamon, ginseng, and bitter melon, may have potential benefits in terms of improving glucose control and reducing the risk of complications associated with diabetes. Evidence-based ethnomedicine is an approach that applies scientific principles and methods to evaluate the efficacy and safety of traditional medical practices. This approach is crucial in the development of effective and safe ways to treat diabetes. To date, there have been numerous studies conducted to examine the efficacy and safety of various ethnomedical interventions for diabetes, including herbal remedies, dietary changes, and physical activity [4]. However, it is important to note that not all ethnomedical interventions for diabetes have been thoroughly evaluated, and many remain unproven. Furthermore, some interventions may be associated with significant risks, particularly in terms of drug interactions and adverse effects. As such, it is crucial that any ethnomedical interventions for diabetes be carefully evaluated using rigorous scientific methods and that patients be advised to consult with their healthcare provider before using any such interventions. It is important to note that the results of these studies have been mixed, with some showing promising results, while others have failed to demonstrate significant benefits. In this chapter, the evidence-based current state of ethnomedicine for diabetes was reviewed. We first provide an overview of diabetes and its pathophysiology, followed by a discussion of traditional medicinal practices used to treat the disease. We then present a systematic review of the scientific literature on the use of ethnomedicine for diabetes, focusing on herbal remedies and dietary interventions. Our review found that several medicinal plants offered promising results to treat all types of diabetes. For example, Gymnema sylvestre, a traditional Indian herb, has been shown to reduce blood glucose levels and improve insulin sensitivity [5]. Additionally, the use of bitter melon (Momordica charantia) has been shown to reduce fasting blood glucose levels and improve glucose tolerance in individuals with type 2 diabetes [6]. Another important aspect of ethnomedicine for diabetes is the use of dietary interventions [7]. Traditional diets, such as the Mediterranean diet, have been shown to have beneficial particularly in terms of improving glycaemic control, reducing the risk of cardiovascular disease, and insulin sensitivity [8]. Additionally, the use of low-carbohydrate diets, such as the ketogenic diet, has been shown to improve glycaemic control in individuals with type 2 diabetes [9]. Traditional medicine has a long history of treating the symptoms and managing the condition. However, the efficacy and safety of these traditional practices have not always been scientifically tested, and there is a lack of standardization and regulation in the production and use of traditional remedies for diabetes. This creates a challenge for healthcare providers and patients, who need to ensure that the treatments they use are safe and effective. Additionally, there is a need for further research to understand the mechanisms by which traditional remedies may be effective in managing diabetes and to determine the optimal dosage and administration methods [9]. Finally, it is also important to understand that the use of traditional remedies may interact with conventional medications, leading to adverse effects; for example, the use of Chinese traditional medicine, known as “herb ginseng,” for the treatment of various health conditions, including diabetes sometimes cause the side effect such as dizziness, confusion, and fainting while interacting with the anti-diabetic medications [10]. Therefore, it is important to approach the use of ethnomedicine for diabetes with caution and under the guidance of a qualified healthcare professional. In conclusion, evidence-based ethnomedicine offers a promising approach to the treatment of diabetes. While further research is needed to fully understand the mechanisms and safety of these interventions, the results to date suggest that traditional remedies and dietary interventions have the potential to be effective in the management of this disease. However, it is important to approach the use of ethnomedicine for diabetes with caution and under the guidance of a qualified healthcare professional and to continue to conduct rigorous scientific research to fully understand the benefits and risks associated with these interventions.

Domestic abuse and stalking in higher education (HE) have been overlooked in research in comparison to sexual harassment and sexual violence. This article reports on survey data from 725 students at a UK university using measures of ‘dating violence’ – physical and psychological violence from an intimate partner – and stalking from a US survey instrument (the Administrator Researcher Campus Climate Collaborative (ARC3) survey). According to this measure, 26% of respondents had been subjected to ‘dating violence’ and 16% to stalking behaviours. However, these findings need to be contextualised within a critical discussion of the use of the ARC3 survey tool in the UK context. The ARC3 questions on ‘dating violence’ focus on physical and ‘psychological violence’; the questions therefore omit further types of domestic abuse under UK definitions. In relation to stalking, US definitions – as captured in the ARC3 survey instrument – define specific behaviours. By contrast, in the UK stalking involves behaviours that engender fear or distress in a pattern of behaviour over time. These differences mean that the ARC3 modules on stalking and ‘dating violence’ would need to be significantly adapted to be suitable for use in the UK context.

In order to provide a new direction for the diagnosis and treatment of gastric cancer, the differentially expressed blood-based miRNAs in gastric carcinoma were obtained and analyzed from the datasets GSE113486, GSE112264 and GSE113740 by the SangerBox, the miRNA - target genes prediction, GO and KEGG functional enrichment analyses with DAVID 6.8, and the STRING database with Cytoscape, respectively. The correlation between the key miRNAs expression and the prognosis and diagnostic value of gastric cancer patients were detected by survival prognosis and ROC curve. QRT-PCR was used to detect the possible key miRNAs expression in human blood species. The dataset GSE108307 which shows the miRNAs affected by H. pylori infection was analyzed by GEO2R. The expression level of CagA and the clinically used gastric cancer markers were detected in human blood species for contrast. Five key blood-based miRNAs were determined, including hsa-miR-124-3p, hsa-miR-125a-3p, hsa-miR-29b-3p, hsa-miR-4276, and hsa-miR-575.The detection in human blood species as well as the cross analysis with H. pylori infection and clinically used markers expression suggested the importance and efficacy of the specific miRNAs in the early diagnosis and monitoring of gastric carcinoma. The study identified potential novel blood miRNA biomarkers of gastric cancer by bioinformatics and human blood species detection, which may give a new possibility of the important biomarkers for the diagnosis and prognosis of gastric cancer.

As a radiant light source within the dynamic range of most spacecraft payloads, the moon pro-vides an excellent reference for on-orbit radiometric calibration. This research hinges on the pre-cise simulation of lunar spectral irradiances and the Earth-based Moon observation geometry. The paper leverages the Hapke model to simulate the temporal changes in lunar spectral irradi-ances, utilizing datasets obtained from Lunar Reconnaissance Orbiter Camera (LROC). The re-search also details the transformation process from the lunar geographic coordinate system to the instantaneous projection coordinate system, thereby delineating the necessary observational geometry. The insights offered by this study have the potential to enhance future in-orbit space-craft calibration procedures, thereby boosting the fidelity of data gathered from satellite obser-vations.

Prediction markets are heralded as powerful forecasting tools, but models to describe them often fail to capture the full complexity of the underlying mechanisms that drive price dynamics. To address this issue, we propose a model in which agents belong in a social network, have an opinion about the probability of a particular event to occur, and bet on the prediction market accordingly. Agents update their opinions about the event by interacting with their neighbours in the network, following the Deffuant model of opinion dynamics. Our results suggest that a simple market model that takes into account opinion formation dynamics is capable to replicate the empirical properties of historical prediction market time series, including volatility clustering and fat-tailed distribution of returns. Interestingly, the best results are obtained when there is the right level of variance in the opinions of the agents. Moreover, this paper provides a new way to indirectly validate opinion dynamics models against real data by using historical data obtained from PredictIt, an exchange platform whose data has never been used before to validate models of opinion diffusion.

Drilling operation is the major cost factor for the industry. Appropriately designed operations are essential for successful drilling. Optimized drilling operations also allow enhanced drilling performance and reduce the drilling cost. This is achieved by increasing the bit life (minimizing premature bit wear), drilling faster that allows reducing drilling time, and also reducing tripping operations. The paper presents two parts. The first part compares the parametric physic-based swab and surge simulation results obtained from Bingham Plastic, Power Law, and Robertson and Stiff models. The aim is to show how the model predictions deviate from each other. Two 80-20 Oil Water ratios (OWR) and two 90-10 OWR oil-based drilling fluids with 1.96 sg and 2.0 sg were considered in vertical- and deviated wells. Simulation results analysis revealed that the deviations depend on the drilling fluid’s physical and rheological parameters as well as the well trajectory. Moreover, the model’s predictions were inconsistent. Data-driven machine learning (ML) modeling makes up the second section. Data-driven modeling was done using both software-generated datasets and field datasets. Results show that the Random Forest Regressor (RF), Artificial Neural Network (ANN), Long Short-Term Memory (LSTM), LightGBM, XGboost, and Multivariate regression models predict the training and test datasets with higher R-squared and minimum root means square values. Deploying the ML model in real-time applications and the planning phase would have the potential application of artificial intelligence for well planning and optimization processes.

Alberta Cancer Exercise (ACE) is an exercise oncology program that transitioned from in-person to online delivery during COVID-19. The purpose of this work was to understand participants’ experiences in both delivery modes. Specifically, survivors' exercise facilitators and barriers, delivery mode preference, and experience with program elements targeting behaviour change were gathered. A retrospective cohort design using explanatory sequential mixed methods was used. 57 participants completed a survey, and 19 subsequent, optional interviews were conducted. Most participants indicated preferring in-person programs (58%), followed by online (32%), and no preference (10%). There were significantly fewer barriers (i.e., commute time) (p<0.01), but also fewer facilitators (i.e., social support) (p<0.01), to exercising online. Four themes were generated from the qualitative data surrounding participant experiences in both delivery modes. Key differences in barriers and facilitators highlighted a more convenient experience online relative to a more socially supportive environment in-person. For future work that includes solely online, focusing on building social support and a sense of community will be critical to optimizing program benefits. Beyond the COVID-19 pandemic, results of this research will remain relevant as we aim to increase the reach of online exercise oncology programming to more underserved populations of individuals living with cancer.

Task-Based Instruction (TBI) is a dynamic approach in tertiary language education that emphasizes the integration of authentic and meaningful tasks to enhance language learning outcomes. This study aims to explore the implementation of TBI in the Philippines, investigate its cognitive benefits and transformative nature, identify pedagogical considerations, and provide recommendations for optimization. The study employed a qualitative research design, with data collected from five private schools in Iligan City. A purposive sampling procedure was used to select 20 participants who engaged in interviews, focus group discussions, and thematic analysis. The results revealed that TBI positively influenced language proficiency, cognitive development, learner autonomy, intercultural competence, and pedagogical considerations. Participants reported enhanced language skills and increased confidence in real-life language use. They also highlighted the development of critical thinking, problem-solving, and decision-making skills through engaging in challenging tasks. TBI was found to empower learners by promoting autonomy, ownership, and self-directed learning. Additionally, it cultivated intercultural communicative competence and fostered appreciation for diverse perspectives. Pedagogical considerations included task design, clear instructions, scaffolding, and feedback, while recommendations focused on optimizing TBI, integrating technology-enhanced learning, and supporting professional development for educators. This research contributes to the growing body of literature on TBI in tertiary language education and underscores its potential for creating transformative learning experiences. The findings provide valuable insights for educators, curriculum designers, and policymakers in enhancing language education practices in the Philippines and beyond.

Circular RNAs (circRNAs) are single-stranded RNA molecules often circularized by backsplicing. Growing evidence implicates circRNAs in the underlying mechanisms of various diseases, such as Alzheimer's and Parkinson's disease (PD) - the first and second most prevalent neurodegenerative disorders. Several circRNAs are associated with brain damage, including circSNCA, circHIPK2, circHIPK3, and circSLC8A1. Gain-of-function and loss-of-function studies on circRNAs have shed light on their roles in the pathobiology of various diseases. Gain-of-function approaches typically employ viral or non-viral vectors that hyperexpress RNA sequences capable of circularizing to form the specific circRNA under investigation. In contrast, loss-of-function studies utilize CRISPR/Cas systems, antisense oligonucleotides (ASOs), or RNAi techniques to knockdown the target circRNA. Given that aberrantly expressed circRNAs have been associated with brain pathologies, a critical question arises: could circRNAs serve as viable targets for neuroprotective treatments? Translating any oligonucleotide-based therapy, including those targeting circRNAs, involves developing adequate brain delivery systems, minimizing off-target effects, and addressing the high costs of treatment. Nonetheless, RNAi-based FDA-approved drugs have entered the market, and circRNAs have attracted significant attention and investment from major pharmaceutical companies. Spanning from bench to bedside, circRNAs present a vast opportunity in biotechnology for oligonucleotide-based therapies designed to slow or even halt the progression of neurodegenerative diseases.

Background: There is poor evidence about sensitivity to chemotherapy according to microsatellite instability (MSI)/mismatch repair (MMR) status in endometrial cancer (EC). Methodology: The RAME study is a retrospective analysis aiming to assess response to chemotherapy in MSI-high (h) /deficient (d) MMR and MSI- low (l)/proficient (p)MMR EC patients. Primary endpoints were recurrence-free survival (RFS) for patients with localized disease and progression-free survival (PFS) and overall survival (OS) in patients with advanced/recurrent disease. Results: 312 patients treated between 2010-2022 in 4 high volume Multicenter Italian Trial in Ovarian cancer and gynecological malignancies (MITO) centers were selected. 239 patients had endometrioid EC (76.6%), 151 had FIGO stage I at diagnosis (48.9%) and 71 were MSI-h/dMMR (22.8%). Median age was 65 (range 31–91) years. Among patients with localized disease, median RFS was 100.0 months (95%CI 59.4–140.7) for MSI-l/pMMR and 120.9 months (60.0-181.8) for MSI-h/dMMR (p=0.39). Seventy-seven patients received first-line chemotherapy for advanced/recurrent disease. Patients with MSI-h/dMMR ECs had a significantly worse OS (p=0.039). In patients receiving platinum-based chemotherapy, no statistically significant difference in PFS (p=0.21) and OS (p=0.057) were detected, although PFS and OS were numerically longer in the MSI-l/pMMR population. Conclusion: Patients with metastatic MSI-h/dMMR EC receiving first-line chemotherapy had a significantly worse OS.

This study critically analyses the realities and experiences of gender-based harassment in cyberspace, and aims to unveil the shadows that shroud this phenomenon. It discloses the online spaces that disseminate detrimental attitudes towards women, despite their physical absence. Cyber violence has become a global issue and it causes significant economic and societal consequences. Recognizing and dealing with the adverse effects caused by demeaning cyber gender harassment is essential. The study raises questions to explore the kind of cyberbullying offences that are brought on by misogynistic inclinations in online environments and the experiences of the women who have gone through cyberbullying. This study uses semi-structured interviews and the IPA technique of the analysis of data to thoroughly examine the unique experiences of cyber harassment victims by applying a qualitative research approach. The study looks into various misogynistic cyber harassment offences and analyses women's accounts. Due to obstacles to justice, cyber violence and harassment replicate physical problems like spousal abuse and sexual harassment. A constant assault of intimidation and harassment results from the traditionally male-dominated character of cyberspace, which affects women's social, economic, and psychological well-being. Participants related horrifying tales of families' indifference and law enforcement officials' trivialization. Mental health problems increase isolation and prevent involvement in academic and professional activities. Women's well-being is exacerbated by societal blaming and secondary victimization. This brief analysis clarifies the intricacies of gender-based harassment in cyberspace and emphasizes the urgent need for efficient solutions to address this widespread issue.

To understand forest dynamics under today’s changing environmental conditions, it is important to analyze the state of forests at large scales. Forest inventories are not available for all regions, so it is important to use other additional sources of information, e.g. remote sensing observations. Increasingly, remotely sensed data based on optical instruments and airborne LIDAR are becoming widely available for forests. There is great potential in analyzing these measurements and gaining an understanding of forests state. In this work, we combine the new generation radiative transfer model mScope with the individual-based forest model FORMIND to generate reflectance spectra for forests. Combining the two models allows us to account for species diversity at different height layers in the forest. We compare the generated reflectances for forest stands in Finland, in the region of North Karelia, with Sentinel-2 measurements. We investigate which level of forest representation gives the best results. For the majority of the forest stands, we generated good reflectances with all levels forest representation compared to the measured reflectance. Good correlations were also found for the vegetation indices (especially NDVI with R²=0.62). This work provides a forward modelling tool for relating forest reflectance to forest characteristics. With this tool it is possible to generate a large set of forest stands with corresponding reflectances. This opens the possibility to understand how reflectance is related to succession and different forest conditions.

Chenodeoxycholic acid (CA) is a naturally occurring bile acid that is produced in the liver from cholesterol. Three CA complexes using Zn(II), Mg(II), and Ca(II) ions were synthesized to examine the chelation tendencies of CA towards these metal ions. The complexation reaction of CA with the metal ions under investigation was conducted with a 1:1 molar ratio (CA to metal) at 60-70°C in natural media (pH 7-8), which consisted of a binary solvent of MeOH and H2O (1:1). The resulting CA complexes were characterized using analytical data (metal, H, C, and Cl, analysis) and spectral data (UV-visible, FT-IR, and 1H NMR) to elucidate the complexes’ structures. The results suggested that CA in anion form utilized oxygen atoms of the carboxylate group (-COO−) to capture Zn(II), Mg(II), and Ca(II) ions. This produced complexes with the general compositions of [Zn(CA)(H2O)Cl], [Mg(CA)(H2O)Cl]H2O, and [Ca(CA)(H2O)Cl]2H2O, respectively. The Kirby-Bauer disc diffusion assay was then used to explore the bioactivity of the CA complexes toward three fungal species, three Gram-positive bacteria, and two Gram-negative bacteria. The Ca(II) and Mg(II) complexes exhibited marked inhibitory effects on the cell growth of the fungal species Aspergillus niger with potency equal to 127% and 116% of the activity of the positive control, respectively. The Zn(II) and Ca(II) complexes strongly inhibited the growth of Penicillium sp., while the Zn(II) and Mg(II) complexes showed strong growth inhibition towards the Gram-negative species Pseudomonas aeruginosa.

The chemical reaction between the quinolone antibiotic oxolinic acid (OA) and Fe(III), Zn(II), Ca(II), and Mg(II) ions results in the formation of metal-based complexes with the following formulas: [Fe(OA)(H2O)2Cl2]2H2O, [Zn(OA)(H2O)Cl]2H2O, [Ca(OA)(H2O)Cl], and [Mg(OA)(H2O)Cl]. We used analytical (C, N, H, Cl, metal analysis) and spectral (FT-IR, 1H NMR, UV-visible) data to structurally characterize the synthesized metal-based complexes of the OA molecule. We found that the OA molecule utilizes the two oxygen atoms of the carboxylate group and the pyridone C=O group to bind the investigated metal ions. The morphological properties of the synthesized OA complexes were assessed using X-ray powder diffractometry (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The biological properties, specifically antibacterial and antifungal activity, of the synthesized complexes were evaluated in vitro using the Kirby-Bauer disc diffusion protocol with five bacterial and three fungal strains. The complex containing Ca(II) ions exhibited remarkable antibacterial and antifungal activity against all tested microbial strains, surpassing or equaling the potency of the standard drugs (streptomycin for antibacterial assays and ketoconazole for antifungal assays).

Innovation is rapidly growing and affecting various industries, including hydrocarbon processing. This study aims to conduct a comprehensive and organized review of the literature on innovation ecosystems and their performance. It will examine existing definitions of innovation ecosystems and related concepts and identify metrics and indicators for measuring innovation and entrepreneurial ecosystems. The term "innovation ecosystem" has gained considerable attention from scholars and practitioners over the past fifteen years. Despite the proliferation of research in this area, there are concerns about its fragmented knowledge base. While previous reviews have highlighted the theoretical connections between innovation ecosystems and related concepts, there is still a need for a more comprehensive understanding of the current state of innovation ecosystem research. The study used a systematic literature review approach that combines bibliographic coupling and content analysis methods, drawing on over 100 studies to identify five streams of current innovation ecosystem research: technology innovation, platform innovation ecosystems, regional development, innovation ecosystem conceptualization and theorization, and entrepreneurship and innovation. The study's contribution lies in decoding the intellectual structure of current innovation ecosystem research and providing targeted recommendations for future research.

To develop a lower-cost, excellent performance, and environmentally friendly phe-nol-formaldehyde (PF) resin, soybean meal was used to modify PF resin, and soybean meal-phenol-formaldehyde (SMPF) resins were prepared. Their physicochemical properties and curing performance were investigated, showing that SMPF resins have higher curing tempera-tures than PF resin. The Fourier transform infrared spectroscopy (FTIR) results indicated that the cross-linking reaction occurred between the amino groups of soybean protein and the hy-droxymethyl phenol. Moreover, with the addition of soybean meal, the viscosity of SMPF in-creased while the gel time decreased. It is worth mentioning that SMPF-2 resin has favorable viscosity, short gel time, low curing temperature (135.78 °C), and high water resistance and bonding strength (1.01 MPa). Finally, all the plywoods bonded with SMPF resins have good water resistance and bonding strength, which could meet the Standard (GB/T 17657-2013, type I) for plywood. The optimized SMPF resins showed the potential application to replace part of PF resin in the wood industry.

Hemorrhage is a detrimental event present in traumatic injury, surgery, and disorders of bleeding, that can become life-threatening if not properly managed. Moreover, uncontrolled bleeding can complicate surgical interventions, altering the outcome of surgical procedures. Therefore, to reduce the risk of complications and decrease the risk of morbidity and mortality associated with hemorrhage, it is necessary to use an effective hemostatic agent that ensures immediate control of bleeding. In recent years, there have been increasingly rapid advances in developing novel generation of biomaterials with hemostatic properties. Nowadays, a wide array of topical hemostatic agents is available, including chitosan-based biomaterials that have shown outstanding properties such as: antibacterial, antifungal, hemostatic, analgesic activity, in addition to their biocompatibility, biodegradability, and wound-healing effects. This review provides an analysis of chitosan-based hemostatic and discusses the progress made in their performance, mechanism of action, efficacy, cost, and safety in recent years.

In network analysis, links depict the connections between each pair of network nodes. However, such pairwise connections fail to consider the interactions among more agents, which may be indirectly connected. Such non-pairwise or higher-order connections can be signified by involving simplicial complexes. The higher-order connections become even more noteworthy when it comes to neuronal network synchronization, an emerging phenomenon responsible for the many biological processes in real-world phenomena. However, involving higher-order interactions may considerably increase the computational costs. To confound this issue, map-based models are more suitable since they are faster, simpler, more flexible, and computationally more optimal. Therefore, this paper addresses the impact of pairwise and non-pairwise neuronal interactions on the synchronization state of 10 coupled memristive Hindmarsh-Rose neuron maps. To this aim, electrical, inner linking, and chemical synaptic functions are considered as 2- and 3-body interactions in three homogenous and two non-homogenous cases. The results show that through chemical pairwise and non-pairwise synapses, the neurons achieve synchrony with the weakest coupling strengths.

Acute lymphoblastic leukemia (ALL) is a blood cancer that primarily affects children but also adults. It is due to the malignant proliferation of lymphoid precursor cells that invade the bone marrow and can spread to extramedullary sites. ALL is divided into B cell (85%) and T cell lineages (10 to 15%); rare cases are associated with the natural killer (NK) cell lineage (<1%). To date, the survival rate in children with ALL is excellent while in adults continues to be poor. Despite the therapeutic progress, there are subsets of patients that still have high relapse rates after chemotherapy or hematopoietic stem cell transplantation (HSCT) and an unsatisfactory cure rate. Hence, the identification of more effective and safer therapy choices represents a primary issue. In this review, we will discuss novel therapeutic options including bispecific antibodies, antibody-drug conjugates,chimeric antigen receptor (CAR)-based therapies, and other promising treatments for both pediatric and adult patients.

Cost-effective community engagement is needed to address causes of mental illness related to social issues (i.e. isolation, stigma and lack of purpose) that are typically outside the scope of healthcare. This pilot study evaluated the relationship between clinical healthcare resources and a community-based social engagement organization in a medium-sized community in the midwestern US. Analyses were based on a retrospective longitudinal comparison of clinical visit frequency from two cohorts that joined the Momentum Center for Social Engagement (MC) and either frequently participated (Engaged; n = 9) or had extenuating circumstances limiting participation (Non-engaged; n = 3). The frequency of >1800 visits to the member’s primary mental healthcare provider were compared during the period from November 2016 - May 2021. Engaged MC members reduced frequency of regular visits to their primary mental healthcare provider by 50%, while Non-engaged MC members maintained clinical visit frequency. The financial value of reduced healthcare visits and associated wellbeing improvements was estimated to be $1.0 million, 95% CI: [$0.6-1.4 million], or roughly four times the budget received by the MC from the healthcare provider. Thus, the MC appears to be a valuable approach to improving mental health in conjunction with existing community healthcare services. Clinical implications include considering the unique MC-style community-based support as a component of practice.

Even after debridement and chemical root canal preparation, multispecies bacterial biofilms can still be found in root canals and dentinal tubules. This demonstrates the necessity of using suitable antibacterial endodontic sealers. Due to their well-known biological qualities, calcium silicate based root canal sealers or “bioceramic’ sealers have recently been launched and can be successful in endodontic procedures. This study's objective was to compare the impact of CerasealR, Total Fill BC SealerR, Bio-C SealerR, AH Plus BioceramicR, K-biocerR and SealiteR on the elimination of a multispecies’ endodontic biofilm at 3, 7 and 14 days. Enterococcus faecalis, Pseudomonas Aeruginosa, Candida Albicans and Proteus Mirabilis were cultured on specific agars and later grown in Brain Heart Infusion broth on hydroxyapatite discs pretreated with collagen type 1 and incubated for 18 days. The resulting biofilm was then placed on a 10mm round shaped blotting paper set on a metallic net in a 6cm petri dish with an orthodontic bend filled with the calcium silicate based root canal sealer in direct contact with the biofilm. In all tested groups, the total bacterial count has significantly decreased between day 3 and day 14 (P<0.05) with no statistically significant differences among the different sealers’ groups at all time points. Sealite group was capable of decreasing the Candida Albicans count significantly between day 3 and day 14 (P<0.05) in comparison with the bioceramic groups. All sealers had antibacterial activity against the multispecies biofilm between day 3 and day 14.

Background: Community-based medical education (CBME) is an essential component of medical education, where primary healthcare physicians (PHPs) play a crucial role. This study explores PHPs' awareness and engagement in CBME and investigates the factors influencing their participation. Methods: This mixed study was conducted in two phases. In the first phase, a qual-itative study was conducted using semi-structured interviews with PHPs, and thematic analysis related to their awareness and engagement in CBME. In the second phase, a quantitative survey was conducted among 72 PHPs pre- and post-training programs. Results: Primary healthcare physicians had a positive attitude toward community-based medical education. The participants have an acceptable level of awareness and engagement, which increased substantially (p-value = 0.03) and (p-value = 0.003), respectively. Logistic analysis indicated that non-Saudi physicians were likelier to participate in the CBME (p-value=0.001). Professions and academic experiences influence their willingness and engagement to participate in CBME (OR= 7.5, p-value=0.001) and (OR=0.21, p-value=0.001), respectively. Conclusion: The study findings highlighted the importance of increased awareness and the factors that enhance PHPs' engagement in CBME. This positive perspective of the PHPs helps build effective partnerships and facilitates the extension of the curriculum to apply CBME.

The high penetration of intermittence resources in the energy market accelerates significantly the decarbonization process but, on the other hand, the electrical system has to face the problem of unbalances. Renewable Energies Sources (RES) are hard to precisely forecast, and power plants are not able to predict the amount of energy that they can provide far from the real time delivery. In this frame, the intraday market gets a fundamental role allowing agents to adjust their position close to the delivery time. In this work we suggest an agent-based model of intraday market combined with genetics algorithms to understand what the best strategy could be adopted by players in order to optimize the market efficiency in terms of welfare and unsold quantity. In the first part we show the effect on the market prices of different scenarios in which players aim at maximizing their revenues and selling/buying all their volumes. In the second part we show the effect of a particular genetic algorithm on the model, focusing on how agents can adapt their strategy to enhance the market efficiency. Comparative analyses are also performed to investigate how the welfare of the system increases as well as the unsold quantity decrease when genetic algorithm is introduced

This study aimed at assessing the extent to which the Saudi general population has embraced digital health medical applications to meet their health-related needs so that the Saudi Ministry of Health and government can appropriately be guided on scaling up of digital health across the country. As such, this study was guided by the question of to what extent do the Saudi people use digital health mobile-based applications?. This was a cross-sectional study utilizing snowballing sampling approach. Frequencies, Chi-square, and Spearman rank correlation statistics were used to offer descriptive and inferential analysis of the variables. The majority of the participants were economically able to afford smart devices that have medical apps, had at least an app on such devices, and highly regarded the benefits of the apps. Unfortunately, their understanding of how to use such apps was limited and this posed a barrier to embracing digital health alongside difficulty downloading apps, and medical ethical concerns. Although there is a willingness, extra effort is needed from the Saudi Ministry of Health and government to promote the uptake of digital health in Saudi Arabia.

Cancer is one of the leading causes of death, and latest predictions indicate that cancer- related deaths will increase over the next few decades. Despite significant advances in conventional therapies, treatments remain far from ideal due to limitations such as lack of selectivity, non-specific distribution, and multidrug resistance. Current research is focusing on the development of several strategies to improve the efficiency of chemotherapeutic agents and, as a result, overcome the conventional therapies challenges. In this regard, combined therapy with natural compounds and other therapeutic agents, such as chemotherapeutics or nucleic acids, has recently emerged as a new strategy for tackling the drawbacks of conventional therapies. Taking this strategy into consideration, the co-delivery of the above-mentioned agents in lipid-based nanocarriers provide some advantages by improving the potential of the therapeutic agents carried. This review encompassed different strategies associated with combined therapy, at the same time highlighting the most recent advances and outstanding advantages of lipid-based nanocarriers for achieving a promising combination therapy that may overcome cancer treatment challenges.

Lactobacillus plantarum has been observed to play a crucial role in shaping the sensory properties of chili sauce. However, the specific taste-active metabolites responsible for the desirable flavor profile of chili sauce remain inadequately characterized. This study employed a combination of metabolomics and web-based computational tools analysis to investigate the dynamic changes in taste-active metabolites during chili sauce fermentation. Initially, metabolites were rapidly annotated using a feature-based molecular network, leading to the tentative annotation of 206 metabolites, of which a significant proportion had not been previously reported. Subsequently, the VirtualTaste tool identified dihydrosphingosine, lactic acid, isoleucine, phytosphingosine, and gluconic acid as potential taste markers for quality control. Finally, pathway enrichment analysis revealed that these components were primarily associated with amino acid tRNA, phenylalanine, tyrosine, and tryptophan biosynthesis, as well as sphingolipid metabolism. This study provides valuable insights into the mechanisms underlying the formation of the distinctive flavor of chili sauce.

Due to its built-up chemoresistance after prolonged usage, the demand for replacing platinum in metal-based drugs (MBD) is rising. The first MBD approved by the FDA for cancer therapy was cisplatin in 1978. Even after nearly four and a half decades of trials, there has been no significant improvement in osteosarcoma (OS) therapy. In fact, many MBD have been developed, but the chemoresistance problem raised by platinum remains unresolved. This motivates us to elucidate the possibilities of the copper and zinc (CuZn) combination to replace platinum in MBD. Thus, the anti-chemoresistance properties of CuZn and their physiological functions for OS therapy are highlighted. Herein, we summarise their chelators, main organic solvents, and ligand functions in their structures that are involved in anti-chemoresistance properties. Through this review, it is rational to discuss their ligands’ roles as biosensors in drug delivery systems. Hereafter, an in-depth understanding of their redox and photoactive function relationships is provided. The disadvantage is that the other functions of biosensors cannot be elaborated on here. As a result, this review is being developed, which is expected to intensify OS drugs with higher cure rates. Nonetheless, this advancement intends to solve the major chemoresistance obstacle towards clinical efficacy.

Low-dimensional carbon-based (LDC) materials have attracted extensive research attentions in electrocatalysis because of their unique advantages such as structural diversity, low cost, and chemical tolerance. They have been widely used in a broad range of electrochemical reactions to relief environmental pollution and energy crisis. Typical examples include hydrogen evolution reaction (HER), oxygen evolution reaction (OER), oxygen reduction reaction (ORR), carbon dioxide reduction reaction (CO₂RR), and nitrogen reduction reaction (NRR). Traditional “trial and error” strategies seriously slowed down the rational design of electrocatalysts for these important applications. Recent studies show that the combination of density functional theory (DFT) calculations and experimental research is capable of accurately predicting the structures of electrocatalysts, thus could reveal the catalytic mechanisms. Herein, current well-recognized collaboration methods of theory and practice are reviewed. The history of modern DFT, commonly used calculation methods, and basic functionals are briefly summarized. Special attention is paid to descriptors that are widely accepted as a bridge links the structure and activity, and the breakthroughs for high-volume accurate prediction of electrocatalysts. Importantly, correlating multiple descriptors are used to systematically describe the complicated interfacial electrocatalytic processes of LDC catalysts. In addition, machine learning and high-throughput simulations are crucial in assisting the discovery of new multiple descriptors and reaction mechanisms. This review will guide the further development of LDC electrocatalysts for extended applications from the aspect of DFT computations.

Read-Across Structure-Activity Relationship (RASAR) is an emerging cheminformatic approach that combines the usefulness of a QSAR model and similarity-based Read-Across predictions. In this work, we have generated a simple, interpretable, and transferable quantitative-RASAR (q-RASAR) model which can efficiently predict the cytotoxicity of TiO2-based multi-component nanomaterials. The data set involves 29 TiO2-based nanomaterials which contain specific amounts of noble metal precursors in the form of Ag, Au, Pd, and Pt. The data set was rationally divided into training and test sets and the Read-Across-based predictions for the test set were generated using the tool Read-Across-v4.1 available from https://sites.google.com/jadavpuruniversity.in/dtc-lab-software/home. The hyperparameters were optimized based on the training set data and using this optimized setting, the Read-Across-based predictions for the test set were obtained. The optimized hyperparameters and the similarity approach, which yields the best predictions, were used to calculate the similarity and error-based RASAR descriptors using the tool RASAR-Desc-Calc-v2.0 available from https://sites.google.com/jadavpuruniversity.in/dtc-lab-software/home. These RASAR descriptors were then clubbed with the physicochemical descriptors and were subjected to features selection using the tool Best Subset Selection v2.1 available from https://dtclab.webs.com/software-tools. The final set of selected descriptors was used to develop multiple linear regression based q-RASAR models, which were validated using stringent criteria as per the OECD guidelines. Finally, a random forest model was also developed with the selected descriptors. The final machine learning model can efficiently predict the cytotoxicity of TiO2-based multi-component nanomaterials superseding previously reported models in the prediction quality.

The discovery of first ATP-binding cassette (ABC) transporter, whose overexpression in cancer cells is responsible for exporting anticancer drugs out of tumor cells, initiated enormous efforts to overcome tumor cell multidrug resistance (MDR) by inhibition of ABC-transporter. Because of its many physiological functions, diverse studies have been conducted on the mechanism, function and regulation of this important group of transmembrane transport proteins. In this review, we will focus on the structural aspects of this transporter superfamily. Since the resolution revolution of electron microscope, experimentally solved structures increased rapidly. A summary of the structures available and an overview of recent structure-based studies are provided. More specifically, the artificial intelligence (AI)-based predictions from AlphaFold 2 will be discussed.

Tropical cyclones devastate large areas, take numerous lives and damage extensive property in Bangladesh. Research on landfalling tropical cyclones affecting Bangladesh has primarily focused on events occurring since AD1960 with limited work examining earlier historical records. We rectify this gap by developing a new tornado catalogue that include present and past records of tornados across Bangladesh maximizing use of available sources. Within this new tornado database, 119 records were captured starting from 1838 till 2020 causing 8,735 deaths and 97,868 injuries leaving more than 1,02,776 people affected in total. Moreover, using this new tornado data, we developed an end-to-end system that allows a user to explore and analyze the full range of tornado data on multiple scenarios. The user of this new system can select a date range or search a particular location, and then, all the tornado information along with Artificial Intelligence (AI) based insights within that selected scope would be dynamically presented in a range of devices including iOS, Android, and Windows. Using a set of interactive maps, charts, graphs, and visualizations the user would have a comprehensive understanding of the historical records of Tornados, Cyclones and associated landfalls with detailed data distributions and statistics.