The study focused on Molecular Docking simulations using Autodock Vina in conjunction with the Pyrx program to investigate potential drugs and natural compounds against the Bcr-Abl oncoprotein. From initial virtual screening of 200 compounds, 11 potential candidates were selected for further evaluation. Additional investigations included toxicity prediction using the pKCSM server. Among the compounds, Diosmin and Hesperidin showed high maximum tolerated doses in humans and low toxicity. Conversely, only Eltrombopag among the selected drugs exhibited excellent parameters, albeit with a potential risk of liver damage at high dosages. These findings underscore the need for comprehensive evaluation of efficacy and safety in the development of potential treatments targeting the Bcr-Abl oncoprotein.

For the first time, this study identified seven potential ligands with high binding energies through the docking approach against the Crystal Structure of human Melanoma-associated antigen B1 (MAGEB1). The ligands—Imatinib, Bafatinib, Diosmin, Ginkgetin, Bilobetin, Amentoflavone, and Hypericin—showing strong binding energies around -10 kcal/mol, indicate a potentially robust interaction with the target protein. Moreover, the additional step of predicting toxicity properties using the pKCSM server provides valuable insights into the safety profiles of these ligands. From these results, the parameters for Diosmin: —Max. tolerated dose (human),- Oral Rat Acute Toxicity (LD50), and - Oral Rat Chronic Toxicity (LOAEL)—suggest a favorable safety profile, making it a potential candidate for further consideration against Melanoma. Moving forward, it's advisable to conduct further experimental validations, including in vitro and in vivo studies, to confirm the efficacy and safety of Diosmin and other potential ligands. Consideration of pharmacokinetics, metabolism, and specific mechanisms of action will contribute to a comprehensive understanding of these compounds' potential as therapeutic agents.

Background/Objectives: Although the role of F-18 FDG PET/CT imaging is well established in oncology, its diagnostic value in routine monitoring for recurrent colorectal cancer (CRC) is still controversial. The aim was to evaluate the diagnostic value of FDG PET/CT in detecting recurrent CRC in correlation with CEA, CA 19-9 levels, and conventional imaging modalities (CIM). Methods: Between 2009 and 2023, we retrospectively studied 134 CRC patients referred for FDG PET/CT imaging on the suspicion of recurrence based on elevated CEA and/or CA 19-9, and/or equivocal radiological findings. According to the Institutional Tumor Board CRC protocol, after initial treatment which was dependent on TNM stage (neoadjuvant therapy, primary resection or adjuvant treatment), patients underwent a standard 5-year surveillance including CEA and CA 19-9 measurements, CIM, and colonoscopy every 6 months. The statistics including univariate and multivariable analyses were conducted using the IBM SPSS 20.0 statistical software. P-values <0.05 were considered statistically significant. Results: Recurrent CRC was confirmed in 54/134 (40.3%) patients with elevated tumor markers. FDG PET/CT shows high diagnostic performance in detecting recurrent CRC with sensitivity, specificity, PPV, NPV, and accuracy of 94.4%, 82.5%, 78.5%, 95.7%, and 87.3%, respectively. The CEA shows a high sensitivity of 98.1%, but both low specificity and accuracy of 15% and 48.5%, respectively. The sensitivity, specificity, and accuracy, for CA 19-9 and CIM for the correct diagnosis in CRC patients were: 44.4%, 67.5%, 58.2%, and 51.9%, 98.8%, 79.9%, respectively. The AUC for FDG PET/CT, elevated CEA levels, CIM, and elevated CA 19-9 levels was 0.885 (95% CI: 0.824-0.946; p<0.001), 0.844 (95% CI: 0.772-0.916; p<0.001), 0.753 (95% CI: 0.612-0.844; p<0.001); and 0.547 (95% CI: 0.442-0.652; p=0.358). Univariate analysis shows that both FDG PET/CT- and CIM-positive results were highly associated with CRC recurrence (p<0.001 and p<0.001, respectively), while gender, mucinous tumor type, presence of initial lymph node metastasis (N+), and presence of initial distant metastasis (M+) have no significance (p=0.211, p=0.158, p=0.583, and p=0.201, respectively). Our multivariate analysis shows that independent predictors for CRC recurrence are: positive FDG PET/CT scans (p<0.001), positive CIM results (p=0.001) and elevated CA19-9 levels (p=0.023). Although CA 19-9 was not detected as a statistically significant predictor in the univariate analysis (p=0.358), in a multivariate analysis it was recognized as a significant predicting factor in detecting CRC recurrence (p=0.023). Conclusions: FDG PET/CT shows a high diagnostic efficacy in CRC recurrence detection, in correlation with CEA levels, CA 19-9 levels, and CIM. This imaging modality should be routinely integrated into the postoperative follow-op in patients with elevated tumor markers.

Small RNAs (sRNA) are epigenetic regulators of essential biological processes that have been linked to the onset and progression of leukemia, including acute adult T-cell leukemia-lymphoma (ATLL) caused by the retrovirus Human T-lymphotropic virus type 1. Here, we describe the sRNA profile of a 30-year-old female with ATLL at diagnosis and after maintenance therapy, with the goal of correlating their expression levels with response to therapy.

Liquid biopsies are an integral part of the diagnosis of cancer. Here, we have extended previous validation studies of a new targeted NGS panel to include the detection of copy number amplifications (CNAs), fusions, and exon skipping variants. Detection of these gene classes included specimens from clinical and healthy donors and cell lines (fusions: ROS1, EML4-ALK, NTRK1), (exon skipping: MET exon 14), and (CNAs: HER2, CDK6, EGFR, MYC and MET). The limit of detection (LOD) for fusion/skipping was 42 copies (QC threshold = 3 copies) and was verified using 3 additional fusion/skipping variants. LOD for CNAs was 1.40-fold-change (QC threshold = 1.15-fold change) and was verified with 3 additional CNAs. In precision studies, all fusion/skipping variants were detected in all runs and all days of testing (n=18/18; 100%); average CV for repeatability was 20.5% (range 8.7% - 34.8%), and for reproducibility was 20.8% (range 15.7% - 30.5%). For CNAs, 28/29 (96.6%) copy gains were detected. For CNAs, average CV of 1.85% (range 0% to 5.49%) for repeatability and 6.59% (range 1.65% to 9.22%) for reproducibility. The test panel meets the criteria for being highly sensitive and specific and extends its utility for the detection of clinically relevant variants in cancer.

This study employs molecular docking simulations using Autodock Vina with the Pyrx program to investigate the binding interactions between Human prostate-specific antigen (PSA) and natural compounds, namely Amentoflavone, Ginketin, Rutin, and Hypericin. The evaluation reveals excellent binding energy values, averaging around -10 kcal/mol, suggesting robust and favorable interactions between the selected compounds and PSA. The results provide valuable insights into the potential therapeutic applications of these natural compounds in the context of prostate cancer treatment or management. Further experimental validation is warranted to confirm these findings and explore the viability of these compounds as promising candidates for innovative therapeutic strategies. This research contributes to the growing body of knowledge in the field of molecular docking and its applications in drug discovery and bioinformatics.

(Background) Canine mammary tumors (CMT) have emerged as an important model for understanding pathophysiological aspects of human disease. Liquid biopsy (LB), which relies on blood-borne biomarkers and offers minimal invasiveness, holds promise for reflecting the disease status of patients. Small extracellular vesicles (SEVs) and their protein cargo have recently gained attention as potential tools for disease screening and monitoring. (Objectives) This study aimed to isolate SEVs from canine patients and analyze their proteomic profile to assess their diagnostic and prognostic potential. (Methods) Plasma samples were collected from female dogs grouped into CMT (malignant and benign), healthy controls, relapse, and remission groups. SEVs were isolated and characterized using ultracentrifugation (UC), nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Proteomic analysis of circulating SEVs was conducted using Liquid Chromatography–Mass Spectrometry (LC–MS). (Results) While no significant differences were observed in the concentration and size of exosomes among the studied groups, proteomic profiling revealed important variations. Mass spectrometry identified exclusive proteins that could serve as potential biomarkers for mammary cancer. These included Inter-alpha-trypsin inhibitor heavy chain (ITIH2 and ITI4), phosphopyruvate hydratase or alpha enolase (ENO1), eukaryotic translation elongation factor 2 (eEF2), actin (ACTB), transthyretin (TTR), beta-2-glycoprotein 1 (APOH) and gelsolin (GSN) found in female dogs with malignant tumors. Additionally, Vitamin D-binding protein (VDBP), also known as group-specific component (GC), was identified as a protein present during remission. (Conclusion) The results underscore the potential of proteins found in SEVs as valuable biomarkers in CMT. Despite the lack of differences in vesicle concentration and size between the groups, the analysis of protein content revealed promising markers with potential applications in CMT diagnosis and monitoring. These findings suggest a novel approach in the development of more precise and effective diagnostic tools for this challenging clinical condition.

My innovative entropy measure, Ismail entropy, namely, (IE) is an ultimate generalization to numerous generalized entropies within the literature. The fractal dimension of IE is identified in this paper. On another applicative note, this paper offers some potential applications of fractal dimension to smart cities. The paper ends with closing remarks combined with some challenging open problems and the next phase of research.

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

This paper is a brief review of our own work on the Planck quantized version of general relativity theory. It demonstrates several other straightforward methods to simply rewrite the same equations that we have already presented.

Background: While the clinical factors of the post-COVID-19 condition (PCC) are becoming clearer, the economic implications remain uncertain, posing a challenge to healthcare professionals in terms of understanding and managing this emerging phenomenon. This article aims to investigate the demographic and clinical characteristics of PCC patients and quantify the economic impact of their healthcare resource utilisation. Methods: A retrospective and case-control observational study was conducted, comparing the case group of PCC population before and after diagnosis with a control group. Demographic and clinical variables were analysed with the objective of describing the population. Economic analysis was performed to evaluate the resource costs in procedures and primary, secondary (both outpatient and inpatient) and emergency care. Findings: PCC patients (N=341) exhibited older age and elevated cardiovascular risk factors compared to controls (N=49,078). There were differences in the socio-economic distribution between male and female patients in the PCC patients. Hypertension and diabetes mellitus type 2 were the most common chronic diseases observed among the case patients. Economic analysis revealed that PCC patients were approximately four times as costly as control patients, with increased utilisation of healthcare resources. However, post-diagnosis PCC patients showed a reduction in costs, primarily driven by decreased primary care visits and hospitalisations. Conclusion: Coordinated care management for PCC patients is associated with reduced costs and improved healthcare resource utilisation. Further research is warranted to investigate long-term health outcomes and establish causal relationships between COVID-19 sequelae and healthcare resource utilisation.

Abstract Background: Small Cajal body-specific RNAs (scaRNAs) are a specific subset of small nucleolar RNAs (snoRNAs) that have recently been emerged as pivotal contributors in diverse physiological and pathological processes. However, their defined roles in carcinogenesis remain largely elusive. This study aims to explore the potential function and mechanism of SCARNA12 in bladder cancer (BLCA) and to provide a theoretical basis for further investigations into the biological functionalities of scaRNAs. Materials and Methods: TCGA, GEO and GTEx data sets were used to analyze the expression of SCARNA12 and its clinicopathological significance in BLCA. Quantitative real-time PCR (qPCR) and in situ hybridization were applied to validate the expression of SCARNA12 in both BLCA cell lines and tissues. RNA sequencing (RNA-seq) combined with bioinformatics analyses were conducted to reveal the changes of gene expression patterns and functional pathways in BLCA patients with different expression of SCARNA12 and T24 cell lines upon SCARNA12 knockdown. Single-cell mass cytometry (CyTOF) was then used to evaluate the tumor-related cell cluster affected by SCARNA12. Moreover, SCARNA12 was stably knocked down in T24 and UMUC3 cell lines by lentivirus-mediated CRISPR/Cas9 approach. The biological effects of SCARNA12 on the proliferation, clonogenic, migration, invasion, cell apoptosis, cell cycle and tumor growth were assessed by in vitro MTT, colony formation, wound healing, transwell, flow cytometry assays and in vivo nude mice xenograft models, respectively. Finally, chromatin isolation by RNA purification (ChIRP) experiment were further conducted to delineate the potential mechanisms of SCARNA12 in BLCA. Results: The expression of SCARNA12 was significantly up-regulated in both BLCA tissues and cell lines. RNA-seq data elucidated that SCARAN12 may play a potential role in cell adhesion and extracellular matrix (ECM) related signaling pathways. CyTOF results further showed that an ECM-related cell cluster with vimentin+, CD13+, CD44+, CD47+ was enriched in BLCA patients with high SCARNA12 expression. Additionally, SCARNA12 knockdown significantly inhibited the proliferation, colony formation, migration, and invasion abilities in T24 and UMUC3 cell lines. SCARNA12 knockdown prompted cell arrest in the G0/G1 and G2/M phase, and promoted the apoptosis in T24 and UMUC3 cell lines. Furthermore, SCARNA12 knockdown could suppress the in vivo tumor growth in nude mice. ChIRP experiment further suggested that SCARNA12 may combine transcription factors H2AFZ to modulate transcription program and then affect BLCA progression. Conclusion: Our study is the first to propose aberrant alteration of SCARNA12 and elucidate its potential oncogenic roles in BLCA via the modulation of ECM signaling. The interaction of SCARNA12 with the transcriptional factor H2AFZ emerges as a key contributor to the carcinogenesis and progression of BLCA. These findings suggest SCARNA12 may serve as a diagnostic biomarker and potential therapeutic target for the treatment of BLCA.

The first member of the family, visual arrestin-1, was discovered in the late 1970s. Later the other three mammalian subtypes were identified and cloned. The first described function was regulation of GPCR signaling: arrestins bind active phosphorylated GPCRs, blocking their coupling to G proteins. It was later discovered that receptor-bound and free arrestins interact with numerous proteins, regulating GPCR trafficking and various signaling pathways, including those that determine cell fate. Arrestins have no enzymatic activity, they function by organizing multi-protein complexes and localizing their interaction partners to particular cellular compartments. Today we understand the molecular mechanism of arrestin interactions with GPCRs better than the mechanisms underlying other functions. However, even limited knowledge enabled the construction of signaling-biased arrestin mutants and extraction of biologically active monofunctional peptides from these multifunctional proteins. Manipulation of cellular signaling with arrestin-based tools has research and likely therapeutic potential: re-engineered proteins and their parts can produce effects that conventional small molecule drugs cannot.

C-C motif chemokine receptor-8 (CCR8) belongs to class A of G protein-coupled receptors (GPCRs). CCR8 interacts with the specific chemokine ligand CCL1/I-309 in humans, which is produced by various cells, including tumor-associated macrophages and regulatory T cells (Treg). CCR8 is highly expressed on Treg and T-helper 2 (T_H2) cells recruited to the inflammation site and is implicated in allergy, asthma, and cancer progression. The CCR8⁺Treg has been suggested to be an important regulator in the immunosuppressive tumor microenvironment (TME); therefore, it has been desired to develop sensitive monoclonal antibodies (mAbs) for CCR8. This study developed a specific mAb for human CCR8 (hCCR8), which is useful for flow cytometry by employing the Cell-Based Immunization and Screening (CBIS) method. The established anti-hCCR8 mAb, C₈Mab-21, (mouse IgM, kappa) reacted with hCCR8-overexpressed Chinese hamster ovary-K1 (CHO/hCCR8) cells, TALL-1 (acute T lymphoblastic leukemia), CCRF-HSB2 (human T-lymphoblastic leukemia), and natural killer cells, which express endogenous hCCR8 by flow cytometry. Furthermore, C₈Mab-21 demonstrated a moderate binding affinity for CHO/hCCR8 and TALL-1 with a dissociation constant of 6.5×10^-8 M and 2.0×10^-8 M, respectively. C₈Mab-21, which was established by the CBIS method, could be a useful tool for analyzing the hCCR8-related biological response using flow cytometry.

Studies have established the crucial role of sleep among the students which plays a significant role in their mood. This study aimed to examine the mood disorders and sleep quality among undergraduate students at the University of Georgia (UG) and comparison between students’ nationality.This cross-sectional study was a self-reported questionnaire comprised of demographics including age, gender, year of study, current location, lifestyle data (Exercise and smoking), the Depression, Anxiety, and Stress Scale (DAS21) and the Pittsburgh Sleep Quality Index (PSQI). We performed a descriptive analysis, and the Chi-square was statistically significant at p<0.05. The prevalence was at a 95% confidence interval (95% CI) as multivariate analysis examined the multicollinearity. The female students were most of the respondents, below the age of 20 years. The student's mean age was 20.20 (SD± 3.0). DAS report presented 72.7% of students with depressive symptoms, 77.8% with anxiety symptoms, and 62.2% had stress. Georgian students were more at risk of having depressive complaints (95% Cl[1.567-3.788]), anxiety (95% Cl[1.612-4.285]), and stress symptoms (95% Cl[1.743-3.831]). There was a strong relationship between the students who experienced poor sleeping patterns and depressive complaints (aOR 0.10). The students who were smokers (aOR 0.39) were more likely to report anxiety symptoms than the students that do not exercise (aOR 1.68). It was observed that students with depressive symptoms, anxiety, and complaints of stress had a significantly high risk of poor sleep quality. Further studies are recommended to curb psychological symptoms of mood changes in association with sleep disorders among students.

Therapies targeting amyloid, such as monoclonal antibodies like Lecanemab, Aducanumab, and Donanemab, have garnered FDA approval but remain controversial due to limited clinical benefits and significant side effects against Alzheimer. The present theorical work utilized Virtual Screening and Docking techniques to explore potential small natural molecules' interactions with the KIBRA protein, a promising target for drug development. Kibra protein is considered a biomarker for synaptic dysfunction and cognitive decline. Employing Autodock Vina and Pyrx software, on several natural compounds and found Hypericin to exhibit the lowest binding energy of approximately -9 kcal/mol. Previous studies have highlighted Hypericin's strong affinity for Alzheimer's Disease-associated targets like ABAD and BACE1. These findings suggest Hypericin could be as a potential therapeutic agent for Alzheimer's Disease. Further research is warranted to validate its efficacy and safety for clinical use.

Security in the Internet of Things (IoT) is a critical concern due to the growing number of connected devices and the limited resources to implement robust security mechanisms in most of them. Adopting standard assessment frameworks, such as CVSS (Common Vulnerability Score System), allows for systematic vulnerability assessment. At the same time, CVE (Common Vulnerabilities and Exposures) records provide unique identifiers for known security issues, making it easier to share information. However, comparing security solutions is still challenging due to the diverse nature of IoT devices and the ever-evolving threat landscape, requiring continual innovation and collaboration between stakeholders. Furthermore, there still needs to be a simple way to compare technologies and solutions, taking into account the security provided by them. In this sense, in this article, we propose a tool for calculating a security score based on the CVSS index of each existing vulnerability in a given technology. We explain how the tool performs the calculation, discuss some challenges, and propose improvements for future work.

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

(1) Background: Although multiple studies have reported on the therapeutic effects of Atezo+Bev for the treatment of NASH-related liver cancer, few studies have focused on its effect on liver reserve. Here, we aimed to compare the changes in hepatic reserve during the Atezo+Bev treatment of NAFLD/NASH-related HCC and of non-NAFLD/non-NASH-related HCC. (2) Methods: We retrospectively compared the changes in ALBI score in 109 patients with NAFLD/NASH or non-NAFLD/non-NASH during 12 weeks of treatment with Atezo+Bev for advanced HCC between September 2019 and January 2022. PSM was performed, and the OS, PFS, and PPS of the two groups were compared. (3)Results: The ALBI after 12 weeks of Atezo+Bev treatment was significantly worse in the NAFLD/NASH group than in the non-NAFLD/non-NASH group. Analysis of the 24 propensity score-matched pairs of cases with NAFLD/NASH or non-NAFLD non-NASH yielded similar results. The prognoses of the two groups were similar with respect to OS and PFS, but the NAFLD/NASH group had a significantly shorter PPS. The 24 matched pairs had similar OS and PFS, but the PPS of the NAFLD/NASH group was shorter. (4)Conclusion: Atezo+Bev treatment may worsen hepatic reserve, and there-fore life expectancy, in patients with NAFLD/NASH-related liver cancer.

Recently, federated learning (FL) has been receiving great attention as an effective machine learning method to avoid the security issue in raw data collection as well as to distribute the computing load to edge devices. However, even though wireless communications is a essential part for implementing FL in edge networks, there have been a few works that analyze the effect of wireless networks on FL. In this paper, we investigate FL in small-cell networks where multiple base stations (BSs) and users are located according to homogeneous Poisson point process (PPP) with different densities. We comprehensively analyze the effects of geographic node deployment on the model aggregation in FL on the basis of stochastic geometry-based analysis. We derive the closed-form expressions of coverage probability with tractable approximations and discuss the minimum required BS density for achieving a target model aggregation rate in small-cell networks. Our analysis and simulation results provide insightful information for understanding the behaviors of FL in small-cell networks, and it can be exploited as a guideline for designing the network facilitating the wireless FL.

The development of targeted therapeutics for cancer continues to receive intense research attention as laboratories and pharmaceutical companies seek to develop drugs and technologies that improve treatment efficacy and mitigate harmful side effects. In the aftermath of World War I, it was discovered that mustard gas destroys rapidly dividing cells and could be used to treat cancer. Since then, chemotherapy has remained a predominant treatment for cancer; however, the destruction of dividing cells throughout the body yields devastating side effects including off-target damage of the digestive tract, bone marrow, skin, and reproductive tract. Furthermore, the high mutation rate of cancerous cells often renders chemotherapy ineffective long-term. Therapies with improved specificity, localization, and efficacy are redefining cancer treatment. Herein, we define and summarize the principal advancements in targeted cancer treatment and briefly comment on the march towards personalized medicine in the treatment of human cancer.

This study proposes the first extracellular domain (residues 1-34) of the CCR1 protein as the Gc protein-derived Macrophage Activating Factor (GcMAF) receptor. The CCR1 gene, expressed in monocytes and 168 other cell types or tissues, encodes this transmembrane protein. Electrostatic and hydrophobic interactions, along with hydrogen bonds mediate the molecular interactions between the TPT^420-GalNAcELAK (or TPK⁴²⁰ELAK) sequences of GcMAF (or Gc2 protein variant) and the TTEDYDTTT sequence of its receptor.

This study provides a comprehensive comparison of the Peter Chew Sum method and Newton's Sum in Quadratic Root Function Computations. Both methods offer significant advancements by alleviating the need for memorization of multiple formulas. However, when confronted with higher-order quadratic root functions such as the calculation of power 33. Newton's Sum method proves cumbersome due to its requirement of all previous answers for final computation, leading to increased steps and error risks. In contrast, the Peter Chew Sum method simplifies the computational process by requiring only a few previous answers, resulting in a more straightforward series of operations. We contextualize our analysis within the historical progression of mathematical techniques, highlighting the transformative leap represented by the Peter Chew Sum method in quadratic root function computations. Peter Chew Sum addressing the limitations of Newton's Sum , especially concerning higher-order functions such as the calculation of power 256. Furthermore, study demonstrates that the innovative approach of the Peter Chew Sum method not only simplifies complex computations but also fosters enhanced conceptual understanding among students. In conclusion, study findings underscore the profound impact of the Peter Chew Sum method on quadratic root function computations.

BACE1 is involved in the production of beta-amyloid peptides, and inhibiting its activity is a potential therapeutic strategy for managing Alzheimer's disease, as excessive beta-amyloid accumulation is a characteristic feature of the disease.Computational results suggest that hypericin has the potential to act as an inhibitor of BACE1. The Molecular Docking results indicate a high binding affinity between hypericin and BACE1, with a notable binding energy score of -10.3 kcal/mol. Additionally, the formation of various chemical bonds, including hydrogen bonds and hydrophobic bonds, further supports the idea that hypericin may effectively interact with the active site of BACE1. It's important to note that while the in silico Molecular Docking results are promising, further in vitro and in vivo studies would be necessary to validate and better understand the inhibitory potential of hypericin against BACE1. Additionally, the practical application of hypericin as a BACE1 inhibitor in a therapeutic context would require careful consideration of factors such as bioavailability, safety, and efficacy.

Background: Thousands of genetic variants have been associated with hematological traits, though target genes remain unknown at most loci. Also, limited analyses have been conducted in African ancestry and Hispanic/Latino populations; hematological trait associated variants more common in these populations have likely been missed. Methods: To derive gene expression prediction models, we used ancestry-stratified datasets from the Multi-Ethnic Study of Atherosclerosis (MESA, including N=229 African American and N=381 Hispanic/Latino participants, monocytes) and the Depression Genes and Networks study (DGN, N = 922 European ancestry participants, whole blood). We then performed a transcriptome-wide association study (TWAS) for platelet count, hemoglobin, hematocrit, and white blood cell count in African (N = 27,955) and Hispanic/Latino (N = 28,324) ancestry participants. Results: Our results revealed 24 suggestive signals (p < 1×10^(-4)) that were conditionally distinct from known GWAS identified variants and successfully replicated these signals in European ancestry subjects from UK Biobank. We found modestly improved correlation of predicted and measured gene expression in an independent African American cohort (the Genetic Epidemiology Network of Arteriopathy (GENOA) study (N=802), lymphoblastoid cell lines) using the larger DGN reference panel; however, some genes were well predicted using MESA but not DGN. Conclusions: These analyses demonstrate the importance of performing TWAS and other genetic analyses across diverse populations and of balancing sample size and ancestry background matching when selecting a TWAS reference panel.

Although cancers account for over 16% of all global deaths annually, at present, no reliable therapies exist for most types of the disease. As protein folding facilitators, heat shock proteins (Hsps) play an important role in cancer development. Not surprisingly, Hsps are among leading anticancer drug targets. Generally, Hsp70s are divided into two main subtypes: canonical Hsp70 (E. coli Hsp70/DnaK homologues) and the non-canonical (Hsp110 and Grp170) members. These two main Hsp70 groups are delineated from each other by distinct structural and functional specifications. Non-canonical Hsp70s are considered as holdase chaperones, while canonical Hsp70s are refoldases. This distinct characteristic feature is mirrored by the distinct structural features of these two groups of chaperones. Hsp110/Grp170 members are larger as they possess an extended acidic insertion in their substrate binding domains. While the role of canonical Hsp70s in cancer has received a fair share of attention, the roles of non-canonical Hsp70s in cancer development has received less attention in comparison. In the current review, we discuss the structure-function features of non-canonical Hsp70s members and how these features impact on their role in cancer development. We further mapped out their interactome and discussed the prospects of targeting these proteins in cancer therapy.

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

Nonionizing millimeter-waves (MMW) are reported to interact with cells in a variety of ways. Possible mechanisms of the inhibited cell division effect were investigated using 85-105 GHz MMW irradiation within the ICNIRP (International Commission on Non-Ionizing Radiation Protection) non-thermal 20 mW/cm² safety standards. ~1.0 mW/cm² exposure over 5-6 hours treatment on 50 cells/μl samples of Saccharomyces cerevisiae model organism, resulted in 62% growth rate reduction compared to control (sham). The effect was specific for 85-105 GHz range and energy dose and cell density dependent. Irradiation of wild type and Δrad52 (DNA damage repair gene) deletion cells presented no differences of colony growth profiles indicating non-thermal MMW treatment does not cause genetic alterations. Dose versus response relations studied using a standard horn antenna (~1.0 mW/cm²) and compared to that of a compact waveguide (17.17 mW/cm²) for increased power delivery resulted in complete termination of cell division via non-thermal processes supported by temperature rise measurements. Combinations of MMW mediated Structure Resonant Energy Transfer (SRET), membrane modulations eliciting signaling effects, and energetic resonance with biomolecules were indicated to be responsible for the observations reported. Our results provide novel mechanistic insights enabling innovative applications of nonionizing radiation procedures for eliciting targeted biomedical outcomes.

Pathogens such as bacteria, fungi and viruses are important components of soil and aquatic communities, where they can benefit from decaying and living organic matter, and may opportunistically infect human and animal hosts. One-third of human infectious diseases is constituted by sapronotic disease agents that are natural inhabitants of soil or aquatic ecosystems. They are capable of existing and reproducing in the environment outside of the host for extended periods of time. However, as ecological research on sapronosis is infrequent and epidemiological models are even rarer, very little information is currently available. Their importance is overlooked in medical and veterinary research, as well as the relationships between free environmental forms and those that are pathogenic. Here, using dynamical models in realistic aquatic metacommunity systems, we analyze sapronosis transmission, using the human pathogen Mycobacterium ulcerans that is responsible for Buruli ulcer. Our work constitutes the first set of metacommunity models of sapronotic disease transmission, and is highly flexible for adaptation to other types of sapronosis. The importance of sapronotic agents on animal and human disease burden needs better understanding and new models of sapronosis disease ecology to guide the management and prevention of this important group of pathogens.

Human T-lymphotropic virus type 1 (HTLV-1)–associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a slowly progressive spinal cord disorder with no effective treatment. There is much of interest in developing potential biomarkers for predicting the pathogenesis of HAM/TSP disorder. This study used Illumina massive parallel sequencing (MPS) technology to assess the cellular global noncoding RNAome expression profile in HAM/TSP patients (n = 10), asymptomatic HTLV-1 infected carriers (ASP, n = 8), and a second group of healthy controls (n = 5). Using various bioinformatics tools, the sRNA MPS reads were aligned, annotated, and profiled. There were 251 known and 50 potential novel sRNAs among the 402 detected sRNAs in the HAM and ASP groups versus the HC group. Sixty-eight known sRNAs were found to be significantly different between the ASP and HAM groups. In HAM vs ASP subjects, 88 mature miRNAs were downregulated. Three of these miRs (hsa-miR-185-5p, 32-5p, and 192-5p) have the potential to be used as biomarkers for predicting the pathogenesis of HAM/TSP. The top seven deregulated miRS target genes were linked to a variety of biological processes and molecular functions. Relevant reactome pathways to our findings provide a rich source of data and an opportunity to further understand sRNA regulation and function in HTLV-1 pathophysiology.

In this paper, we introduce a novel controlled quantum communication protocol utilizing a quantum random walk involving one sender, one receiver, and multiple controllers. Inspired by classical random walk theory, quantum random walk serves as the foundation of our proposed protocol. With this protocol, we demonstrate the ability to transfer any n- dimensional quantum state to any party facilitated by any m number of controllers. Furthermore, any of the (m+1) individuals has the freedom to accept the role of the receiver. Rigorous testing of the protocol’s performance is conducted through quantum state tomography. We have run different variations of the circuits in IBMQ QASM simulator. Additionally, we explore the effectiveness of a weak measurement-based protocol designed to mitigate amplitude-damping noise’s detrimental effects on quantum states. By analyzing fidelity versus amplitude damping noise-strength plots for scenarios with and without the weak measurement protocol, we provide valuable insights into its protective capabilities across various levels of noise. These find- ings illuminate the protocol’s potential applications in quantum information processing

The dynamic landscape of AI adoption and its impact on employment in Malaysia demands a multifaceted approach to navigate the challenges and harness the opportunities presented. While the government's commitment to fostering AI adoption through initiatives like the National AI Framework and the Malaysia Digital Economy Blueprint is commendable, it is imperative to address concerns regarding job displacement and ensure inclusive growth. This study identifies the pressing research problem of workforce readiness for the AI-driven future, emphasizing the need to explore strategies for reskilling and upskilling affected workers. By employing critical lenses such as Marxist, feminist, and postcolonial perspectives, scholars highlight the power dynamics and societal implications inherent in AI deployment, guiding the development of policies and interventions that prioritize workers' interests and address social inequalities. Moving forward, a comprehensive approach combining policy interventions, educational reforms, and inclusive strategies is essential to maximize the benefits of AI adoption while mitigating its potential risks. Longitudinal studies, interdisciplinary research, and comparative analyses will further advance our understanding and inform evidence-based policymaking in this evolving field. Ultimately, by prioritizing workforce preparedness, social equity, and sustainable development, Malaysia can position itself as a leader in the AI-driven global economy, fostering a resilient, inclusive, and prosperous society for all.

Scholars and policymakers see sustainability as depending on the interrelationships between the three pillars of the environment, society and the economy. However, it remains less clear how key stakeholders with a responsibility for educating the next generation perceive the concept of sustainability and act accordingly. In order to gain new insights, this research scrutinises participant perceptions on sustainability and climate change in two eco-schools in England for primary children (aged 5-11 years). Our case study involved individual interviews with classroom teachers and headteachers, group interviews with fourth- and fifth-year students (ages 10-12 years), and in-class observations. We also analysed data from student exercise books and photographs of school grounds to understand participants’ self-reported knowledge and perceptions of sustainability and climate change. Within a framework drawing on theories of science communication and transformative learning (a learning approach based on having challenging experiences), the results show that the integration of sustainability into the curriculum was limited and problematic. That is despite the fact that all students and teachers were aware of the environmental dimensions of sustainability, like climate change and the overuse of natural sources. These findings suggest that schools are no different to other institutional settings when it comes to dealing with the challenges of integrating sustainability into daily practice. We conclude that there is a need for in-service teacher education programmes to enable and motivate teachers to provide richer teaching-learning environments so as to enable effective learning in schools about sustainability and climate change.

Background: Atopic dermatitis (AD), a common dermatological condition, is often associated with significant economic and social burdens. Despite extensive studies globally, there is a gap in understanding the comprehensive impact of this condition in Romania. Objectives:This study evaluated the economic burden and quality of life impact of AD in Romania, considering both direct and indirect costs. Materials & Methods: A mixed methods cost of illness study was conducted from April to October 2023. A patient survey, expert reviews, and national health data analysis were used to assess direct medical costs (treatments, medical services), direct non-medical costs (transportation, accommodation), and indirect costs (productivity losses). Quality of life was evaluated using the EuroQol EQ-5D-5L instrument. Results: In 2022, the total cost of atopic dermatitis in Romania was 32.983.498 EUR for adults and 31.573.968 EUR for children. Adult costs included 24.534.603 EUR in direct and 8.429.884 EUR in indirect medical costs, with an average annual cost per patient of 447 EUR. Pediatric costs involved 15.026.781 EUR in direct and 16.516.410 EUR in indirect costs, averaging 290 EUR per patient annually. Conclusion: Care expenditure with AD management in Romania is substantially lower than in other countries, posing a significant economic burden, primarily driven by indirect costs. This study provides a foundation for future policy interventions and highlights the need for targeted management strategies for AD.

Background : Probiotics are composed of microorganisms that have positive effects on health when consumed in prescribed quantities. Lately, studies have attempted to establish this role of probiotics in enhancing health. Aim : The aim of this study was to compare the antifungal activity of 3 different probiotics against Candida albicans.Methodology :This was an in-vitro study. 3 types of commercially available probiotics - Bifilac, Pre pro HS and VSL-3 were cultured separately with Candida albicans and were placed under incubation. The maximum zone of inhibition was recorded for each of the probiotic solutions.Results : In this study, it was found that among the three probiotic products, Bifilac exhibited a maximum zone of inhibition of 13mm at concentration of 100µL against C. albicans, while Pre pro HS and VSL-3 showed zone of inhibition of 11mm at concentrations of 50µL and 100µL, respectively.Conclusion : Within the limits of the present study, This study could prove that probiotics can be considered as an alternative and safe treatment option for treatment of Oral candidiasis infections.

In order to search possible residual minor phases in Y-Ba-Cu-O family, powdered mixtures of Y₂O₃ + BaCO₃ + CuO and, independently, superconducting compound YBa₂Cu₃O_7-x have been treated in evacuated cells and elevated temperatures.YBa₂Cu₃O_7-x was reduced to YBa₂Cu₃O₅ by use of the special home designed Taconis-Knudsen vacuum device. A subsequent doping by oxygen converts produced insulator YBa₂Cu₃O₅ to semiconductor or metal YBa₂Cu₃O_5+x (0<x<0.3). In addition to YBa₂Cu₃O₅, 0.05 volume percent of the minor delafossite phase Y₂Cu₂O₄ was being spotted in the powder mixture 1/2 Y₂O₃ + 2BaCO₃+6Cu₂O, heated up to 818 °C in an inert gas atmosphere. An attempt to prepare the insulating bulk delafossite samples was successful, and subsequent doping by oxygen produces novel metallic phases.

A cell-surface ectonucleotidase CD39 mediates the conversion of extracellular ATP into immunosuppressive adenosine with another ectonucleotidase CD73. The elevated adenosine in the tumor microenvironment (TME) attenuates antitumor immunity, which promotes tumor cell immunologic escape and progression. Anti-CD39 monoclonal antibodies (mAbs), which suppress the enzymatic activity, can be applied to antitumor therapy. Therefore, an understanding of the relationship between the inhibitory activity and epitope of mAbs is important. We previously established an anti-mouse CD39 (mCD39) mAb, C₃₉Mab-1 using the Cell-Based Immunization and Screening (CBIS) method. In this study, we determined the critical epitope of C₃₉Mab-1 using flow cytometry. We performed the PA tag (12 amino acids)-substituted analysis (named PA scanning) and RIEDL tag (5 amino acids)-substituted analysis (named RIEDL scanning) to determine the critical epitope of C₃₉Mab-1 using flow cytometry. By the combination of PA scanning and RIEDL scanning, we identified the conformational epitope, spanning three segments of 275^th to 279^th, 282^nd to 291^st, and 306^th to 323^rd amino acids of mCD39. These analyses would contribute to the identification of the conformational epitope of membrane proteins.

Molecular docking, a computational method predicting how molecules bind to target proteins, is employed in this study to explore Polydatin's interactions with Ras-related protein Rab (Rab) proteins using the Mcule Database. This database validates the docking results and offers insights into the pharmacological properties of Polydatin. Notably, specific Rab proteins like Rab-5A, HRas, and Rab-18 exhibit robust interactions with Polydatin, indicated by favorable binding energies.These findings illuminate the potential roles of Polydatin in therapeutic and biological contexts, emphasizing its interaction with Rab proteins. The Mcule Database enhances the credibility of the study, providing additional perspectives on Polydatin's applications. The observed interactions, particularly with key proteins like HRas, present a promising avenue for modulating cellular signaling pathways. This modulation holds therapeutic potential, potentially addressing conditions associated with pathway overactivity, including specific cancer types.

Serine/threonine kinase (AKT) signaling regulates diverse cellular processes and is one of the most important aberrant cell survival mechanisms associated with tumorigenesis, metastasis, and chemoresistance. Targeting AKT has become an effective therapeutic strategy for the treatment of many cancers. AKT3 (PKBγ), the least studied isoform of the AKT family, has emerged as a major contributor to malignancy. AKT3 is frequently overexpressed in human cancers, and many regulatory oncogenic or tumor suppressor small non-coding RNAs (ncRNAs), including microRNAs (miRNAs), have recently been identified to be involved in regulating AKT3 expression. Therefore, a better understanding of regulatory miRNA/AKT3 networks may reveal novel biomarkers for diagnosis of patients with cancer and provide invaluable information for developing more effective therapeutic strategies. The aim of this review is to summarize current research progress in the isoform-specific functions of AKT3 in human cancers and the roles of dysregulated miRNA/AKT3 in specific types of human cancers.

The large production of non-degradable petrol-based plastics has become a major global issue due to its environmental pollution. Biopolymers produced by microorganisms such as polyhydroxyalkanoates (PHAs) are gaining potential as a sustainable alternative, but the high cost associated to their industrial production has been a limiting factor. Post-transcriptional regulation is a key step to control gene expression in changing environments and has been reported to play a major role in numerous cellular processes. However, limited reports are available concerning the regulation of PHA accumulation in bacteria, and many essential regulatory factors still need to be identified. Here, we review studies where the synthesis of PHA has been reported to be regulated at the post-transcriptional level, and we analyze the RNA-mediated networks involved. Finally, we discuss the forthcoming research on riboregulation, synthetic and metabolic engineering which could lead to improved strategies for PHAs synthesis in industrial production, thereby reducing the costs currently associated with this procedure.

A sufficient amount of tissue sample is required to perform next-generation sequencing (NGS) with a high success rate, but the majority of patients with advanced non-small-cell lung cancer (NSCLC) are diagnosed with small biopsy specimens. Biopsy samples were collected from 184 patients with bronchoscopically diagnosed NSCLC. The tissue surface area, tumor cell count, and tumor content rate of each biopsy sample were evaluated. The impact of the cut-off criteria for the tissue surface area (≥ 1 mm2) and tumor content rate (≥ 30%) on the success rate of Oncomine Dx Target Test (ODxTT) was evaluated. The mean tissue surface area of the transbronchial biopsies was 1.23 ± 0.85 mm2 when small endobronchial ultrasonography with a guide sheath (EBUS-GS) was used, 2.16 ± 1.49 mm2 with large EBUS-GS, and 1.81 ± 0.75 mm2 with endobronchial biopsy (EBB). The proportion of samples with a tissue surface area of ≥ 1 mm2 was 48.8% for small EBUS-GS, 79.2% for large EBUS-GS, and 78.6% for EBB. Sixty-nine patients underwent ODxTT. The success rate of DNA sequencing was 84.1% and that of RNA sequencing was 92.7% over all patients. The success rate of DNA (RNA) sequencing was 57.1% (71.4%) for small EBUS-GS (n = 14), 93.4% (96.9%) for large EBUS-GS (n = 32), 62.5% (100%) for EBB (n = 8), and 100% (100%) for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) (n = 15). Regardless of the device used, a tissue surface area of ≥ 1 mm2 is adequate for samples to be tested with NGS.

Background and objectives: The initiation of apoptotic death in cancer cells is the aim of many chemotherapeutic strategies. As many anticancer agents have been discovered in natural plant sources, the search for novel phytochemicals displaying anticancer activities continues at a tremendous rate. This study was conducted to evaluate the effect of extractable polyphenols (EPP); non-extractable polyphenols (NEPP); nobiletin (NOB); tectorigenin (TEC) and persicogenin (PERS) from Barhi date palm kernels (BDPK) extracts on the induction of apoptosis in human lung cancer A549 and colon cancer HT29 cell lines. Materials and Methods: The anticancer activities were determined using MTT and trypan blue exclusion assays. Flow cytometry analysis was performed to study the cell viability, cell cycle arrest and apoptosis. The underlying mechanism of apoptosis induced by crude extracts and the purified compounds was investigated using caspase-3, -8 and -9 assays and the mitochondrial membrane potential assay. Results: The findings indicate that both BDPK extracts and the purified compounds do exert induced cell death on A549 and HT29 cells. The results observed from MTT- assay and trypan blue exclusion indicate that the cytotoxic effects of both plant extracts and the three isolated flavonoids are dose-dependent with higher cell death after 72 hours treatment. Treatment of human lung and colon cancer cells with EPP, NEPP, NOB, TEC and PERSI induced late stages of apoptosis as there was evidence of the DNA degradation and high percentage of the cells population was situated at sub-G1 phase, indicating a high population of apoptotic cells. Conclusions: Study of the apoptotic mechanism demonstrated that EPP and NEPP exhibited dependent mitochondrial signalling pathway as seen with caspase-9 and induced receptor-mediated (extrinsic) apoptotic pathway as seen with caspase-8. Therefore, our results suggest that BDPK extracts and the three isolated flavonoids could be a good candidate for developing anticancer agents.

The bivalve mollusc Pinna nobilis, endemic to the Mediterranean Sea, since 2016 is vanishing from the whole basin because of an infection by multiple pathogens that caused mass mortality events. In the Eastern Mediterranean some little populations seem to be resistant to the infection. These individuals could represent the only possibility for the species to recolonize now desert habitats. Thus, according to the recommendations of IUCN, the looking for living specimens of P. nobilis is a priority. As a result of a monitoring activity carried out in 2022-2024, along the Ionian cost of Apulia, in Southern Italy, the species has completely disappeared leaving only empty shells. Concurrent to the vanishing of P. nobilis, its congeneric P. rudis, resistant to the infection, seems to be taking advantage, becoming more common and colonizing habitats once exclusive of P. nobilis. In fact, from different areas of the Mediterranean, the sightings of P. rudis are increasing, together with the discovering of individuals exhibiting morphological traits that are a mixing between the two species. In some cases, these morphological features are not easy to detect, anyway the presence of these hybrids, resistant to the infection, is important for the conservation of the species.

: Molecular targeting strategies have been used for years to control cancer progression and are often based on targeting various enzymes involved in metabolic pathways. Keeping that in mind, it is essential to know the role of each enzyme in a particular metabolic pathway. In this review, we are providing in-depth knowledge of various enzymes such as ceramidase, sphingosine kinase, sphingomyelin synthase, dihydroceramide desaturase, and ceramide synthase, which are associated with multiple types of cancer that depend on ceramide metabolism. Focus has also been given to discussing physicochemical properties of well-studied inhibitors of natural products origin and their related structures for these enzymes. Targeting ceramide metabolism exhibited promise in mono and combination therapies at preclinical stages to prevent cancer progression and paved the way for the significance of sphingolipid metabolism in cancer treatments. Targeting ceramide metabolizing enzymes will help the medicinal chemist to design potent and selective small molecules for treating cancer progression at various levels.

We used light, electron microscope and teased fiber autoradiography to show that myelinating Schwann cells synthesize phospholipids and proteins in perinuclear cytoplasm and superficial cytoplasmic channels or Cajal bands (SCC/CB). Neither phospholipid nor protein syntheses occur in paranodal loops, Schmidt-Lanterman incisures or adaxonal cytoplasm. Autoradiographic studies also show that in support of local protein synthesis, RNAs move from the nucleus into perinuclear cytoplasm and out along SCC/CB. Unlike other phospholipids, phosphatidylinositol synthesis occurs extensively in axons. This finding indicates differences in the distributions of phospholipid synthesizing enzymes in smooth endoplasmic reticulum of Schwann cell processes and axoplasm.Autoradiographs of nerves at longer survival times show that tritiated phosphatidylcholine and fucose-labeled glycoproteins move from synthetic sites to outermost myelin lamellae. From there, phosphatidylcholine spreads inward reaching innermost lamellae of thicker sheaths in days. Coupled with retention of fucose glycoproteins in outer myelin lamellae is the presence of fucose glycoprotein synthesized during early myelination in inner lamellae of thicker sheaths, a result consistent with growth of myelin sheaths from inner lamellae out. In this review, we revisit these studies because they provide temporal and spatial perspectives needed in understanding dynamic aspects of myelinogenesis and how myelinating cells respond to injury and from altered gene expression.

We demonstrate how a rigorous mathematical approach can be used to extract a current CMB temperature of 2.7276 ±0.0723 K from the 580 type Ia supernova data points in the Union2 database. Using redshift formula: z = Sqrt(Rh/R_t) − 1, incorporated into our new CMB redshift prediction redshift formula, we find that the above current CMB temperature value is a remarkably good match for this particular data set. In addition, we can alternatively start out with the measured current CMB temperature and extract the Hubble constant from all 580 supernovae. We then get an estimated Hubble constant of H0 = 66.8711+0.0019 km/s/Mpc when using the CMB temperature from the recent Dhal et al study [1] in combination with redshifts from all 580 supernovae. Furthermore, we get an estimated Hubble constant value of H_0 = 66.8943+0.0287 km/s/Mpc when using the CMB temperature measured by Fixsen [2]. In summary, our simple model essentially perfectly matches all 580 type Ia supernova redshifts while extracting H_0 or T_0 values. The Hubble constant we extract by this method fits very well with the Hubble constant extracted from the CMB by other studies. We believe that our new approach likely solves the Hubble tension problem, at least inside R_h = ct cosmology.

The Jakarta LARP community, established in March 2020 and primarily active in Gelora Bung Karno, fosters inclusivity, diversity, and physical role-playing activities. It adheres to a policy of excluding ultra-nationalist ideologies and integrates new members despite language barriers. Bruhn (2011) defines this kind of community sharing the same goals, values, and lifestyles, while McMillan & Chavis (1986) outline four aspects of the sense of community.The research discovered that communities endure by utilizing solidarity built on the basis of their peculiarities. This study employed ethnographic methods alongside grounded research to identify the community's culture and their efforts to sustain and utilize it as community solidarity.

The C-C motif chemokine receptor 8 (CCR8) is highly and selectively expressed in regulatory T (Treg) cells and is associated with tumor progression. The massive accumulation of Treg cells into tumors suppresses the effector function of CD8⁺ cells against tumor cells. Therefore, selective depletion of Treg cells using anti-CCR8 monoclonal antibodies (mAbs) reinvigorates antitumor immune responses and improves responses to cancer immunotherapy. Previously, we developed an anti-mouse CCR8 (mCCR8) mAb, C₈Mab-2, using the Cell-Based Immunization and Screening (CBIS) method. In this study, the binding epitope of C₈Mab-2 was investigated using flow cytometry. The mCCR8 extracellular domain-substituted mutant analysis showed that C₈Mab-2 recognizes the N-terminal region (1–33 amino acids) of mCCR8. Next, 1×alanine (or glycine) scanning and 2×alanine (or glycine) scanning were conducted in the N-terminal region. The results revealed that the _17-DFFTAP_-22 sequence is important for the recognition by C₈Mab-2, and Thr20 is a central amino acid of the epitope. These results revealed the involvement of the N-terminus of mCCR8 in the recognition by C₈Mab-2.

AbstractBackground: Empowering Communities, Combating HIV/AIDS: The Indispensable Role of Community-Based Strategies in Awareness and PreventionObjective: Highlight the significance of community-based approaches in addressing the ongoing HIV/AIDS pandemic through enhanced awareness, reduced stigma, and effective prevention measures.Method: This article provides a theoretical analysis of community-based HIV/AIDS interventions, drawing upon key strategies and successful examples from diverse settings.Results: Community-based initiatives emerge as critical factors in empowering individuals and communities to take ownership of their health. Through culturally-sensitive education, accessible testing, and comprehensive support services, these initiatives effectively diminish the social stigma surrounding HIV/AIDS and promote preventative behaviors. Examples of successful programs illustrate the potential of community-driven approaches to achieve measurable reductions in transmission rates and improved health outcomes.Conclusion: The fight against HIV/AIDS necessitates robust community engagement. Community-based interventions, grounded in local knowledge and addressing specific needs, offer a promising pathway towards fostering health equity, reducing stigma, and ultimately curtailing the spread of the virus. Further research and investment in these initiatives are crucial to ensuring their scalability and sustained impact on global HIV/AIDS prevention efforts.

In the wake of increasing digital fraud, this paper introduces an innovative application of Artificial Intelligence (AI) in detecting fraudulent activities across finance, healthcare, and e-commerce sectors. It presents a detailed analysis of machine learning methodologies, specifically focusing on the advantages of supervised, unsupervised, and deep learning techniques. The paper addresses the challenges such as data imbalance, model interpretability, and ethical implications in AI-based fraud detection. It also discusses the necessity of high-quality datasets and advocates for the integration of traditional and advanced machine learning methods to enhance accuracy and adaptability in fraud identification. However, it acknowledges the limitations including computational demands and overfitting risks. The study underscores the importance of collaborative efforts between AI experts and industry professionals to develop ethical, efficient, and reliable AI solutions for fraud detection.

Macro-autophagy (autophagy hereafter) is an evolutionarily conserved cellular process that has long been recognized as an intracellular mechanism for maintaining cellular homeostasis. It involves the formation of a membraned structure called the autophagosome, which carries cargo that includes toxic protein aggregates and dysfunctional organelles to the lysosome for degradation and recycling. Autophagy is primarily considered and studied as a cell-autonomous mechanism. However, recent studies have illuminated an underappreciated facet of autophagy, i.e., non-autonomously regulated autophagy. Non- autonomously regulated autophagy involves the degradation of autophagic components, including organelles, cargo, and signaling molecules, and is induced in neighboring cells by signals from primary adjacent or distant cells/tissues/organs. This review provides insight into the complex molecular mechanisms governing non-autonomously regulated autophagy, highlighting the dynamic interplay between cells within tissue/organ or distinct cell types in different tissues/organs. Emphasis is placed on modes of intercellular communication that include secreted molecules, including microRNAs, and their regulatory roles in orchestrating this phenomenon. Furthermore, we explore the multidimensional roles of non-autonomously regulated autophagy in various physiological contexts, spanning tissue development and aging, as well as its importance in diverse pathological conditions, including cancer and neurodegeneration. By studying the complexities of non-autonomously regulated autophagy, we hope to gain insights into the sophisticated intercellular dynamics within multicellular organisms, including mammals. These studies will uncover novel avenues for therapeutic intervention to modulate intercellular autophagic pathways in altered human physiology.

Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. Generally, it originates from serosal surface of abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1-WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within 3 years. The dismal survival makes DSRCT an orphan disease with urgent need of new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors have been evaluated in small studies. Recent works using comprehensive molecular profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the current studies conducted to better understand DSRCT biology and to explore the new therapeutic strategies under investigation in preclinical models and in early phase clinical trials.

The purpose of this paper is to explore the implementation of Retrieval-Augmented Gen- 14 eration (RAG) technology with open-source Large Language Models (LLMs). For this purpose, a 15 web-based application named PaSSER that integrates RAG with three models - Mistral:7b, 16 Llama2:7b: Orca2:7b, is developed. In its development various technologies are used, including 17 Blockchain for managing and storing assessment results of built-in testing modules. PaSSER em- 18 ploys a set of evaluation metrics for LLMs’ performance - METEOR, ROUGE, BLEU, Perplexity, 19 Cosine similarity, Pearson correlation, and F1 score. The specialized knowledge base is in the smart 20 agriculture domain. As an illustration, the paper presents results and analysis of two tests. First one 21 is assessing the performance of LLMs across different hardware configurations, the other is deter- 22 mining the model that delivers most accurate and contextually relevant responses within the RAG. 23 The paper also discusses the integration of blockchain technology with LLMs to manage and store 24 assessment results within a blockchain environment. The tests revealed that Mistral:7b demon- 25 strates the best results across most of the evaluated metrics. The discussion section comments on 26 technical and hardware considerations that affect the performance of LLMs. Future development 27 will focus in leveraging new larger pre-trained open-source LLMs, exploring different finetuning 28 approaches, and further integration with Blockchain and IPFS.

Background. Azithromycin (AZM) is widely used in cystic fibrosis (CF) treatment following clinical trials demonstrating improved lung function and fewer pulmonary exacerbations. While the precise mechanisms remain elusive, immunomodulatory actions are thought to be involved. We previously reported impaired phagocytosis and defective anti-inflammatory M2 macrophage polarization in CF macrophages. This study systematically analyzed the effect of AZM on the functions of unpolarized and M1/M2 polarized macrophages in CF. Methods: Monocytes, isolated from the venous blood of patients with CF (pwCF) and healthy controls (HCs) were differentiated into monocyte-derived macrophages (MDMs) and infected with P. aeruginosa. P. aeruginosa uptake and killing by MDMs in the presence or absence of AZM was studied. M1 and M2 macrophage polarizations were induced and their functions and cytokine release were analyzed. Results: Following AZM treatment, both HC and CF MDMs exhibited a significant increase in P. aeruginosa uptake and killing, however, lysosomal acidification remained unchanged. AZM treatment led to higher activation of ERK1/2 in both HC and CF MDMs. Pharmacological inhibition of ERK1/2 using U0126 significantly reduced P. aeruginosa uptake in HC MDMs. M1 macrophage polarization remained unaffected, however, AZM treatment led to increased IL-6 and IL-10 release in both HC and CF M1 macrophages. AZM also significantly increased the phagocytic index for both pHrodo E. coli and S. aureus in CF M1 macrophages. In CF, AZM treatment promoted anti-inflammatory M2 macrophage polarization, with an increased percentage of CD209+ M2 macrophages, induction of the M2 gene CCL18, along with its secretion in the culture supernatant. However, AZM did not restore endocytosis in CF, another essential feature of M2 macrophages. Conclusions: This study highlights the cellular functions and molecular targets of AZM which may involve improved uptake of both gram-positive and gram-negative bacteria, restored anti-inflammatory macrophage polarization in CF. This may in turn shape the reduced lung inflammation observed in clinical trials. In addition, we confirmed the role of ERK1/2 activation for bacterial uptake.

This study centered on examining 60 different antibiotics by assessing their primary toxicity parameters through the pkCSM database. The parameters included Max. Tolerated Dose (Human) (log mg/kg/day), Oral Rat Acute Toxicity (LD50) (mol/kg), Oral Rat Chronic Toxicity (LOAEL) (log mg/kg_bw/day), and Minnow Toxicity (LC50) (log mM). The results highlight four potential antibiotics—cefotaxime, ceftriaxone, imipenem, and meropenem—that exhibited lower toxicity effects compared to other compounds. These findings imply a relatively favorable safety profile for these antibiotics concerning the specified toxicity parameters. However, it is crucial to interpret these outcomes within the context of the specific clinical application and to consider additional factors for a comprehensive safety assessment. It's essential to acknowledge that evaluating toxicity is intricate, and the determination of what is considered "less toxic" can rely on specific criteria and the context of use. Furthermore, individual responses to antibiotics may vary, and the selection of an antibiotic should be based on diverse factors, including the specific infection being treated, the patient's health, and potential side effects.

This study demonstrates a global, non-parametric, non-iterative optimization of time-mean value of a kind of index vibrated by time-varying forcing. It is based on the fact that the (steady) forced vibration of non-autonomous ordinary differential equation systems is well approximated by an analytical solution when the amplitude of forcing is sufficiently small and its base state without forcing is linearly stable and steady. It is applied to optimize a time-averaged heat-transfer rate on a two-dimensional thermal convection field in a square cavity with horizontal temperature difference, and the globally optimal way of vibrational forcing, i.e. the globally optimal, spatial distribution of vibrational heat and vorticity sources, is first obtained. The maximized vibrational thermal convection corresponds well to the state of internal gravity wave resonance. In contrast, the minimized thermal convection is weak, keeping the boundary layers on both sidewalls thick.

We will demonstrate that the photon energy density parameter Ωγ of the universe can be derived exactly in Rh = ct cosmology. We find that it must be Ωγ = 1/5760π ≈ 5.52621330180192× 10^(−5). This indicates that there is no uncertainty in the radiation density within at least somesub-classes of Rh = ct cosmology.

IMPORTANCE: On December 10, 2021, the FDA published a Determination Letter, along with a Statistical Review and Evaluation Report, and concluded that under the non-informative prior, the local Bayesian optimal interval design (BOIN) design, in its revised form, can be designated fit-for-purpose for identifying the maximum tolerated dose of a new drug, assuming that dose-toxicity relationship is monotonically increasing. Although setting the BOIN design parameter p.tox = 1.4 * target.DLT.rate is recommended in almost all BOIN methodology articles and is the default value in the R package BOIN, it's unclear if the choice of p.tox should only depend on the target DLT rate and if certain range of p.tox could produce the same BOIN boundary table. DESIGN: In this simulation study, following parameters were varied one at a time, using R package BOIN, to explore their effects on the equivalence intervals of p.saf and p.tox: 1) target DLT rate, 2) n.earlystop, 3) cutoff.eli, 4) cohortsize, and 5) ncohort. And a simple 3+3 design was used as an example to explore equivalent sets of BOIN design parameters that can generate the same boundary table. RESULTS: When the early stopping parameter n.earlystop is relatively small or the cohortsize value is not optimized via simulation, it might be better to use p.tox < 1.4 * target.DLT.rate, or try out different cohort sizes, or increase n.earlystop, whichever is both feasible and provides better operating characteristics. This is because if the cohortsize was not optimized via simulation, even when n.earlystop = 12 and cohortsize > 3, the BOIN escalation/de-escalation rules generated using p.tox = 1.4 * target.DLT.rate could be exactly the same as those calculated using p.tox > 3 * target.DLT.rate, which might not be acceptable for some pediatric trials targeting 10% DLT rate. The traditional 3+3 design stops the dose finding process when 3 patients have been treated at the current dose level, 0 DLT has been observed, and the next higher dose has already been eliminated. If additional 3 patients were required to be treated at the current dose in the situation described above, the decision rules of this commonly used 3+3 design could be generated using BOIN design with target DLT rates ranging from 18% to 29%, p.saf ranging from 8% to 26%, and different p.tox values ranging from 39% to 99%. These BOIN parameters also need to satisfy a set of conditions. Meaning: This study demonstrates the importance of interpreting BOIN design parameter p.tox as an interval of toxicity rates that are considered too toxic, rather than one prespecified value that corresponds to the lowest toxicity probability that is deemed overly toxic. When designing a dose-finding trial using BOIN, it is important to perform simulation studies to identify equivalent sets of BOIN design parameters that can generate the same boundary table so that we can better compare the safety properties of different boundary tables.

We will apply Pascal’s hydrostatic pressure law to black holes and also to the Hubble sphere. Haug has recently demonstrated how hydrostatic pressure in water can be utilized to determine the Planck length. One can conceptualize the energy in the Hubble sphere as a type of superfluid, and if this is correct, then Blaise Pascal’s hydrostatic pressure formula may also be applicable to such a superfluid, even within the Hubble sphere. By employing the same method on the Hubble sphere and considering it as a Schwarzschild black hole with the critical Friedmann mass, we can estimate the Planck length based on its hypothetical hydrostatic pressure.

The presence of the mite, Varroa destructor, requires the use of acaricide treatments in most honeybee colonies. Amitraz is one of the most common acaricide substances used by beekeepers. Some Varroa mite populations have developed resistance to amitraz leading to a loss of efficacy of amitraz-based treatments. Two products, Apivar and Supatraz were applied in the same apiary. Both treatments are amitraz-based but have a different galenics. Thanks to field data, a dynamic model was used to simulate the action of Apivar and Supatraz on the mite population. We consider two parameters to compare the products: daily mortality rate and treatment duration. In the field, the percentage of efficacy between the two products was not significantly different but Supatraz kills mite faster and decreases 90% of the mite infestation in 28.4 days compared to 50.9 days for Apivar. Thanks to modelling, we showed the daily impact of the two different products on mite population. Supatraz has a higher daily mortality rate during the first two weeks than Apivar. Supatraz requires a lower efficacy to stabilize the varroa mite population due to its faster release of active ingredient than Apivar, needing a shorter period to achieve the same result. Depending on the model, Supatraz conserve a good efficacy for low resistant mites but not for high resistant mites. These results show that the comparison of the efficacy of two products with different characteristics (duration of treatment and daily mortality rate) should be analyzed with caution.

In the field of delta-sigma modulators, reducing system power consumption without sacrificing accuracy has become a challenge. The summing circuit, as the main part of the cascade-of-integrator-in-feedforward delta-sigma modulator, consumes a significant amount of power in active summing. On the other hand, passive summing circuits have low power consumption but can cause attenuation in the summing results. This article proposes a low-power multi-bit delta-sigma modulator based on passive and attenuationless summation scheme. The summation circuit achieves multiplication of the voltage signal carried on the summation capacitor through bidirectional sampling technique, compensating for the inherent attenuation caused by passive summation, thus eliminating the need for active OTA to achieve perfect summation. A 2-order delta-sigma modulator based on 4-bit 1-order passive noise-shaping (NS) SAR quantizer is designed to verify the scheme. By combining a passive NS SAR as the 4-bit quantizer and the third-stage integrator of the system, and incorporating an energy-efficient cascode floating inverter amplifier (FIA) structure as the core active OTA, these elements have significantly enhanced the energy-efficiency of the modulator. Simulation results show that at a supply voltage of 1.2 V and a bandwidth of 20 kHz, the SNDR reaches 102.62 dB, power consumption is only 148.32 μW, and Schreier figure-of-merit (FoM) of SNDR is 183.92 dB.

Аnalysis of small RNA sequencing data across a range of biofluids is a significant research area, given the diversity of RNA types that holds potential diagnostic, prognostic, and predictive value. The intricate task of segregating the complex mixture of small RNAs from both human and other species, including bacteria, fungi, and viruses, poses one of the most formidable challenges in the analysis of small RNA sequencing data, currently lacking satisfactory solutions. This study introduces sRNAflow, a user-friendly bioinformatic tool with a web interface designed for the analysis of small RNAs obtained from biological fluids. Tailored to the unique requirements of such samples, the proposed pipeline addresses various challenges, including filtering potential RNAs from reagents and environment, classifying small RNA types, managing small RNA annotation overlap, conducting differential expression assays, analysing isomiRs, and presenting an approach to identify the sources of small RNAs within samples. sRNAflow also encompasses an alternative alignment-free analysis of RNA-seq data, featuring clustering and initial RNA source identification using BLAST. This comprehensive approach facilitates meaningful comparisons of results between different analytical methods. The source code can be accessed at https://github.com/zajakin/sRNAflow under the GPL3 licence.

From the formalism of the thermodynamics of irreversible processes and the theory of complex systems, characterization of longevity and aging and its relationship with the emergence and evolution of cancer was carried out. It was found that: 1. The rate of entropy production can be used as an index of robustness, plasticity, the aggressiveness of cancer, and as a measure of biological age; 2. The aging process, as well as the evolution of cancer, goes through what we have called “biological phase transition”; 3. The process of metastasis, which occurs through epithelial-mesenchymal transition (EMT), appears as a phase transition far from thermodynamic equilibrium and exhibits Shilnikov chaos-like dynamic behavior. This dynamic guarantees the robustness of the process and, in turn, its unpredictability; 4. It was shown that as the ferroptosis process is strengthened, the complexity of the dynamics associated with the emergence and evolution of cancer decreases. The theoretical framework developed contributes to a better understanding of the biophysical-chemical phenomena of longevity and aging and their relationship with cancer.

In this review, we will cover a general overview of the current panorama on lncRNAs with an actual or potential role as biological markers in cancer. We will discuss examples of multi-omics approaches that integrates information on somatic aberrations, gene expression and epigenomics, with the scope of providing a more comprehensive view of the functional impact of lncRNA profiles and how these paradigm can be exploited for the discovery and selection of lncRNAs with a functional role and their use as variables informing on progression and prognostic and help guiding the selection of therapeutic strategies for cancers. Finally, we propose a perspective for future evolution of the study of lncRNAs and the discovery of their functional and harnessing their potential to assist in clinical management of malignancies.

Extracellular vesicles (EVs), including exosomes, microvesicles, and other lipid vesicles derived from cells, play a pivotal role in intercellular communication by transferring information between cells. EVs secreted by progenitor and stem cells have been associated with the therapeutic effects observed in cell-based therapies, and they also contribute to tissue regeneration following injury, such as in orthopedic surgery cases. This review briefly explores the involvement of EVs in tissue repair and nerve regeneration, their potential as drug carriers, and their significance in stem cell research and cell-based therapies. It underscores the importance for bioengineers to comprehend and manipulate EV activity to optimize the efficacy of tissue engineering and regenerative therapies.

Corneal ulcers are a common and potentially vision-threatening condition in horses that can be challenging to treat with conventional therapies alone. This case report describes the successful treatment of a non-healing corneal ulcer in a 28-year-old Hispano-Bretón mare using the secretome derived from adipose tissue-derived mesenchymal stem cells (ASCs). Despite initial treatment with antibiotics, anti-inflammatory drugs, and surgical debridement, the corneal ulcer failed to heal properly, exhibiting persistent epithelial defects and stromal complications. As an alternative regenerative approach, the ASC secretome, a rich source of trophic factors, cytokines, and extracellular vesicles, was topically administered to the affected eye. Remarkably, within one week of secretome treatment, the clinical signs of blepharospasm and epiphora resolved, and the corneal ulcer exhibited complete re-epithelialization, regained transparency, and reduced neovascularization. No recurrence was observed during the 1.5-year follow-up period. This case highlights the potential therapeutic benefits of ASCs secretome in promoting corneal wound healing and suggests its promise as a novel cell-free therapy for treating refractory corneal ulcers in horses.

Thyroid cancer is the most prevalent malignancy of the endocrine system and the ninth most common cancer globally. Despite the advances in the management of thyroid cancer, there are critical issues with the diagnosis and treatment of thyroid cancer that result in the poor overall survival of undifferentiated and metastatic thyroid cancer patients. Recent studies have revealed the role of different non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) that are dysregulated during thyroid cancer development or the acquisition of resistance to therapeutics, and may play key roles in treatment failure and poor prognosis of the thyroid cancer patients. Here, we systematically review the emerging roles and molecular mechanisms of ncRNAs that regulate thyroid tumorigenesis and drug response. We then propose the potential clinical implications of ncRNAs as novel diagnostic and prognostic biomarkers for thyroid cancer.

The purpose of this project is to develop and build an extensible fixture. This fixture is ideal to milling, drilling, and shaping operations. Jigs and fittings are often the most cost-effective methods of mass fabricating a component. As a result, jigs and fittings are used and play a vital part in the mass production system. These are specialist work holding and tool-guiding devices. The quality of jigs and fixtures used in a process has a substantial impact on its performance. A fixture is distinctive because it is meant to fit a given area or shape. The basic purpose of a fixture is to find and, in certain instances, hold a workpiece throughout an operation. A jig differs from a fixture in that it leads the tool to the right position or movement during an operation, in addition to locating and supporting the workpiece. When a key is reproduced, the original key serves as a base for the path reader, which regulates the tool's movement to construct the duplicate key. In this situation, a CWC machine's route reader works as a jig, with the original being referred to as the template. Sometimes the template and jig refer to the same part of a production system.

During the development of new medicines mutually exclusive specificity appears to be required but hitherto is most often included at the late clinical trial stage. Here, I describe the use of Hedgehog signalling in Drosophila as a model to represent a mutually exclusive relationship within the context and report the identification of CG43658, a putative Rho guanine nucleotide exchange factor and orthologue of the Charcot-Marie-Tooth disease associated gene ARHGEF10. Furthermore, a Computer that is able to consider the whole and describe the sum of everything in it absolutely in unambiguous terms is a useful tool. Here I describe such a computer with a suggestion for an application to examine any component in the context where a medicine is sought. Taken, together I would like to propose this method as a fundamental necessity and improvement upon current existing methods related not only to Hedgehog signalling but plausibly to life science research and the search for medicines in general.

This work addresses the intricate task of predicting the prices of diverse financial assets, including stocks, indices, and cryptocurrencies, each exhibiting distinct characteristics and behaviors under varied market conditions. To tackle the challenge effectively, a novel hybridized architecture, AE-GRU, integrating the encoder-decoder principle with GRU is designed. The experimentation involves multiple activation functions and hyperparameter tuning. With extensive experimentation and enhancements applied to AE-LSTM, the proposed AE-GRU architecture still demonstrates significant superiority in forecasting the annual prices of volatile financial assets from multiple sectors mentioned above. Thus, the novel AE-GRU architecture emerges as a superior choice for price prediction across diverse sectors and fluctuating market scenarios by extracting important non-linear features of financial data and retaining the long-term context from past observations.

Corrugated board is a composite material characterized by strong orthotropy in both the elastic and plastic phases. Additionally, due to its layered structure, which consists of alternately arranged flat and wavy layers of paper, its mechanics becomes complicated. Therefore, a precisely selected set of laboratory tests is needed to correctly identify all the necessary material parameters of cardboard. The work attempts to define a full set of laboratory tests in order to determine material parameters describing the linear-elastic, orthotropic behavior of cardboard and the basic parameters defining popular plasticity criteria, such as the asymmetric orthotropic Hoffman criterion. For this purpose, sensitivity analysis and numerical models of several selected basic laboratory tests were used. Since the aim of the work is to choose appropriate laboratory tests necessary to correctly determine the material parameters of corrugated board (not its individual layers), the numerical models do not contain detailed cardboard geometry, but only its homogenized representation in the form of the flat shell models. All numerical models are based on the nonlinear finite element method and constitutive modelling in the form of UMAT subroutines implemented in the ABAQUS software. Based on the analyses, appropriate measurements and laboratory tests were indicated that are most sensitive to the material parameters sought.

Precision farming is transforming how antibiotics get used on farms. It fights the overuse that creates superbugs and harms nature. Farmers now have high-tech tools to use antibiotics ultra-precisely. Drones, AI, and advanced watering equipment help them pinpoint only sick plants and animals needing treatment. This shields crops while avoiding environmental damage. More careful antibiotic use makes livestock healthier and boosts harvests too. And it prevents resistant germs, where antibiotics stop working altogether. The approach helps farms in multiple ways, using fewer resources for even better results. There are some growing pains, like high costs for small farms. And questions around data privacy also cause concern. But overcoming these hurdles could help precision farming spread far and wide. This technology promises safer, greener, and more productive agriculture. Targeted use of antibiotics protects both crops and people from drug-proof germs. And nature benefits when less medicine spreads into soil and water. The future looks bright for farming with precision.

Artifact metrics is a technology for authenticating artifacts based on their unique characteristics. The artifact-metric system offers "clone resistance," i.e., it makes it highly improbable to create another object exhibiting the same measured values as a genuine artifact. However, determined adversaries may still attempt to create imitations or clones with close physical characteristics to those of registered products, even if they cannot perfectly replicate the genuine product. Such clones serve to deceive users into believing they are genuine rather than counterfeits. Thus, in this study, we consider a scenario in which we measure raster-scanning-generated clones via a non-raster scanning method. Further, we employ image processing techniques to generate image data representing the clones and theoretically assess the filtering effects on these images. Our findings reveal that applying filters to specific frequency components in the spatial frequency domain can effectively highlight differences between raster-scanning-created clones and the corresponding genuine artifacts. Thus, we demonstrate directional emphasis filtering in artifact metrics as an effective approach for rejecting raster-scanning-created clones.

We discuss three key points: defining mathematically the notions of phase, symmetry breaking, topological defects and their stability in a formal language of homotopy theory and fiber bundle formalism; postulating and proving two theorems for successive symmetry breaking scenarios in condensed matter physics and cosmology, and demonstrating application of theorems to superfluid Helium 3 and Kibble-Lazarides-Shafi (KLS) walls, supporting and mathematically justifying the results of [Volovik, 2020].

Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Since the 70s, many countries have adopted different CRC screening programs which has resulted in a decrease in mortality. However, current screening test options still present downsides. The commercialized stool-based tests present high false-positive rates and low sensitivity, which negatively affects the detection of early stage carcinogenesis. The gold standard colonoscopy has low uptake due to its invasiveness and the perception of discomfort and embarrassment that the procedure may bring.In this review, we collected and described the latest data about alternative CRC screening techniques that can overcome these disadvantages. Web of Science and PubMed were employed as search engines for studies reporting on CRC screening tests and future perspectives. The searches generated 555 articles, of which 93 titles were selected. Finally, a total of 50 studies, describing 14 different CRC alternative tests, were included. Among the investigated techniques the main feature that could have an impact on CRC screening perception and uptake was the ease of sample collection. Urine, exhaled breath and blood-based tests promise to achieve good diagnostic performance (sensitivity of 63-100%, 90-95%, 47-97%, respectively) while minimizing stress and discomfort for the patient.

The genome sequencing technologies reveal the molecular mechanisms of differentiated thyroid cancer (DTC). Unlike somatic mutation analysis from thyroidectomy samples, germline mutations showing genetic susceptibility to DTC are less understood. The study aimed to assess the prevalence of germline mutations predisposing to DTC in a cohort of Polish individuals based on their whole genome sequencing (WGS) data. We analyzed sequencing data from 1076 unrelated individuals, released openly for academic and clinical research as The Thousand Polish Genomes database (https://1000polishgenomes.com). The list of genes chosen for further analysis was based on the review of previous studies. The cohort contained 104 variants located within the coding and noncoding DNA sequences of 90 genes selected by ClinVar classification as pathogenic and potentially pathogenic. The frequency of variants in the Polish cohort (our study) was compared to the frequency estimated for the non-Finnish European population, obtained from the gnomAD database (gnomad.broadinstitute.org). Statistically significant variants included 23 genes. Even though the Polish population is genetically similar to other European populations, there are significant differences in variant frequencies contributing to the disease development and progression, such as RET, CHECK2, BRCA1, SLC26A4 or TERT. Further studies are needed to identify genomic variants associated directly with DTC.

According to Young Minds [1] ‘everyone gets angry sometimes’. Their website offers a number of de-escalating strategies, including staying calm, managing responses and setting limits to help young people who most deem resistive. Yet, Young Minds are not alone because such logical advice is ubiquitous in the literature about challenging behaviour despite the fact that in our experience when faced with high states of arousal, most young people tend to act first and deal with the consequences later. It’s not that they are stupid or non-caring, but they are human capable of great feats as well as stupidity. The same is true for any claims that solution focused (SF) conversations can put right the several decades of psychological theory suggesting resistance requires logic and better cognition. By giving the correct thinking skills, young people will walk away from risk, avoid physical confrontation, handle challenging situations like logical thinkers, and generally discount that the process of growing up is part of the challenge. It is with this in mind that over recent years in our current SF practice (with staff group supervision) we have examined the concept of ‘resistance’ and how it can be put to use as a process of collaboration. To do this, we have revisited SF theory that preoccupied many of its pioneers during the 1980’s and 1990’s and attempted to make it useful for the early 2020’s for professionals having conversations with young people, who, in traditional models, are labelled challenging. We want to introduce key differences of solution focused practice and how Anita started to formulate a 6D-SF model (details, dynamics, dimensions, dispositions, dislocations, descriptions) for contemplating how groups of professionals relate to each other and are triggered by challenging behaviour. We do not claim to have proof, logic or exactness on our side, but we’re happy to suggest how our resistance mirrors what many of the staff teams feel and describe when working through their work.

Background: Critical states present scale-free dynamics, optimizing neuronal complexity. We explored electroencephalogram (EEG) criticality in amnesic Mild Cognitive Impairment (aMCI) patients with clinical improvement in working memory, verbal memory, verbal fluency and overall executive functions after the completion of a 6-month prospective memory training. (2) Methods: We compared “before” and “after” stationary resting-state EEG records of right-handed MCI patients (n = 17; 11 females), using the method of critical fluctuations and Haar wavelet analysis. (3) Results: Significant criticality enhancement was present in frontotemporal electrodes [mean dif: 0.10; Z = 7, p = .019] and isolated electrodes T6 [mean dif: 0.204; t (10) = - 2.3, p = .044] and F4 [mean dif: 0.0194; t (10) = - 2.82; p = .018]. (4) Conclusions: EEG criticality agreed with clinical improvement, consisting a possible monitoring biomarker in MCI and Alzheimer’s disease. Further evaluation is needed in patients under cognitive training or even drug-modifying therapies.

This study investigates the potential of natural compounds against HIV-1 protease, a critical enzyme in the replication cycle of human immunodeficiency virus type 1 (HIV-1). HIV-1 protease is essential for cleaving large precursor proteins into smaller functional proteins necessary for viral maturation and infectivity. Protease inhibitors, specifically targeting HIV-1 protease, effectively suppress viral replication, aiding in the management of HIV infection. Using the SWISS DOCK Server, several natural compounds were investigated for their potential as inhibitors of HIV-1 protease. Docking results revealed that Amentoflavone showed excellent binding affinity with high Estimated ΔG values, suggesting its potential as an inhibitor of HIV-1 protease. Additionally, Amentoflavone exhibited similar promising results when tested against Roussarcoma virus protease. These findings indicate the potential of Amentoflavone as a natural compound against HIV and warrant further investigation into its therapeutic applications.

Urbanization influences food culture, particularly in low- and middle-income countries, where there is an increasing consumption of processed and pre-packaged foods. This shift is contributing to a rise in non-communicable diseases. Food labeling standards are crucial for regulating manufacturing practices and aiding consumers in making healthy food choices. We aimed to assess the compliance of local and imported pre-packaged snacks with Tanzanian and international labeling standards in Dar es Salaam, Tanzania. A cross-sectional study was conducted on 180 snack products. A checklist based on Tanzanian and Codex labeling standards was used to evaluate adherence. We also examined factors influencing adherence, such as product origin, price, category, purchase location, and package size. The majority of the snacks demonstrated partial adherence to labeling standards. Imported products showed significantly better full adherence to both Tanzanian and International standards. Notably, over half of the products used English for labeling, and infrequently used the recommended World Health Organization Front-of-Pack nutrition Labeling. Product category, origin, and package size were significantly associated with higher levels of International standard adherence (p<0.05). The inadequate adherence to mandatory labeling standards, scarce use of Swahili and FoPL highlight the need to strengthen labeling practices and potential challenges faced by consumers in understanding nutritional information. Thus, strengthening and emphasizing good labeling practices is of urgency as we seek to address diet-related Non-communicable diseases.

Intelligent ship technology is currently an international research hotspot, and model predictive control is widely used in the path-tracking control of intelligent vehicles. To construct an intelligent ship anti-disturbance path-tracking control method, firstly, an environmental disturbance model was constructed with the actual meteorological data of the target sea area. Secondly, the Fossen ship equation of motion is linearized and discretized as the ship motion model. Thirdly, the expression of the prediction equation is derived from the ship motion model. Fourthly, the cost function is constructed by using the polar diameter and polar angle values of the ship. Fifth, the power function in the cost function is replaced with an exponential function to obtain an improved cost function. Sixthly, according to the Lyapunov theory and the MPC terminal constraint theory, the stability of the improved cost function is verified. Seventh, different test paths are set up, the environmental disturbance model is taken as the external disturbance, the ship motion model, the prediction equation, and the improved cost function are used to design the anti-disturbance path-tracking control algorithm according to the model prediction control idea for simulation experiments. Finally, different MATLAB simulation results show that the improved cost function can resist disturbance of the external wave, current, and wind, and effectively track the target path. Therefore, this study provides a reference for improving the navigation safety of ship path-tracking.

This paper presents data supporting the IC Regimen for potentiating the effectiveness of lorlatinib in treating ALK positive cancers, and specifically non-small cell lung cancer. Lorlatinib is an effective treatment for ALK driven non-small cell lung cancer and other ALK driven cancers. Lorlatinib inhibits ALK kinase and achieves good brain tissue levels, a common site for metastases in lung cancers. However, resistance to lorlatinib usually supervenes and the cancer awakens and starts growing again, resistant to lorlatinib. This paper analyses data indicating that adding two common generic drugs, itraconazole and cilostazol, to lorlatinib treatment may delay resistance development. Itraconazole is marketed worldwide as a generic antifungal drug that also inhibits Hedgehog signaling, CYP3A4, and the p-gp efflux pump. Cilostazol is a generic anti-thrombosis, phosphodiesterase 3 inhibiting drug that carries minimal bleeding risk. Cilostazol may enhance lorlatinib by deprivation of trophic growth factors supplied by platelets. Itraconazole may enhance lorlatinib effectiveness by reducing or stopping a Hedgehog centered amplifying feedback loop with ALK kinase. The combination of metastatic non-small cell lung cancer being a low-survival disease and the general safety itraconazole plus cilostazol augmentation, make a clinical trial of this trio worthwhile.

In this work,the wave behaviour propagation of single-walled fluid conveying carbon nanotubes (SWCNT) under longitudinal magnetic fields and elastic foundations is studied, based on the nonlocal strain gradients theory(NSGT). With considertion of surface effect, the governing differential equation are obtained utilising Timoshenko beam theory and Hamilton's variational principle. The influence of small-scale parameters, fluid density, magnetic flux, surrounding elastic medium and surface effects on wave behaviour characteristics of carbon nanotubes are discussed in detail. The numerical results illustrated that with the magnetic flux increase，the phase velocities of the carbon nanotube will increase. When the fluid effects inside the carbon nanotube, the wave frequencies of the system reduces with increase in the non-local coefficient, while promotes with increase in the strain gradient coefficient. In addition, fluid density, surrounding elastic medium and surface effects have meaningful influence on the phase velocity of the system.

Abstract: This review addresses the complexities of type 1 diabetes (T1D)and its associated complications, with a par-ticular focus on diabetic retinopathy (DR). This review outlines the progression from non-proliferative to proliferative diabetic retinopathy and diabetic macular edema, highlighting the role of dysglycemia in the pathogenesis of these conditions. A significant portion of the review is devoted to technological advances in diabetes management, particu-larly the use of Hybrid Closed Loop systems (HCLS) and to the potential of open-source HCLS systems, which could be easily adapted to different patiens’needs using big data analytics and machine learning. Personalized HCLS algorithms that integrate factors such as patient lifestyle, dietary habits, and hormonal variations are highlighted as critical to reducing the incidence of diabetes-related complications and improving patient outcomes.

We experimentally demonstrate waveguide and microring resonator (MRR) polarizers by integrating 2D graphene oxide (GO) films onto silicon (Si) photonic devices. The 2D GO films with highly anisotropic light absorption are on-chip integrated with precise control over their thicknesses and sizes. Detailed measurements are performed for the fabricated devices with different GO film thicknesses, coating lengths, and Si waveguide widths. The results show that a maximum polarization-dependent loss (PDL) of ~17 dB is achieved for the hybrid waveguides, and the hybrid MRRs achieved a maximum polarization extinction ratio (PER) of ~10 dB. We also characterize the wavelength- and power-dependent response for these polarizers. The former demonstrates a broad operation bandwidth of over ~100 nm, and the latter verifies performance improvement enabled by photo-thermal changes in GO films. By fitting the experimental results with theoretical simulations, we find that the anisotropy in the loss of GO films dominates the polarization selectivity of these devices. These results highlight the strong potential of 2D GO films for realizing high-performance polarization selective devices in Si photonic platform.

Background: Research articles are essential for describing new ideas, techniques, and procedures and consolidating concepts. It creates an opportunity to expose studies and publicly assimilate published knowledge. Therefore, one of them is the most used and accepted index to verify the author’s scientific impact is the H-index or Hirsch index. It provides a robust single metric that combines quality and quantity. Therefore, it presents disadvantages, (1) researchers with shorter scientific carriers may have fewer articles and citations than those with longer scientific life; (2) it allows scientists to receive citations even if no new papers are published; (3) it is only useful for comparing the better scientists in a field; (4) this indicator can never decrease; (5) it is only weakly sensitive to the number of citations received; (6) the major and minor (or no) contributor in the research gained equal h-index. Then, the H-index ignores the total of citations and the time of a researcher's experience (“scientific age” [sa]). Objective: Thus, the goal of this study was to present a new index system (GFsa index ©) based on the two variables completely forgotten (total of citations and “scientific age”), introducing a new terminology “scientific age”, to evaluate the best-ranked researchers in Dentistry. Methods: The AD Scientific Index was used, and all researchers included in this study were cited in the AD Scientific Index (2024) in the Dentistry field and had the Google Scholar page accessible for a consultation to manually obtain the total of citations and calculate the “scientific age”. The information was retrieved by two authors (G.V.O.F. and J.C.H.F.), who assessed the data twice to avoid errors or mistakes. For inclusion: a minimum H-index value of 30; for exclusion: (i) the author did not have a Google Scholar page; (ii) duplicated author; or (iii) presented any suspicious activities about manipulation of articles. Then, a dataset of all researchers who were reported in Dentistry was prepared (name, H-index, i10 index, and publications). The formula developed and applied was GFsa=(total number of citations)/(“scientific age)². The Pearson correlation statistically evaluated the data obtained; the confidence interval was 95%. Results: A total of 9,093 researchers in Dentistry were recorded, of whom 1,020 were included. Then, we collected all 1,020 researchers' Google Scholar data (publications, citations, and indexes), and each researcher's total citations and “scientific age” were registered and calculated. The mean “scientific age” registered was 34.18 ± 13.34 (standard error of mean = 0.4181). With this information and data collected, GFsa index © was calculated, presenting a minimum value of 0.2186 and a maximum of 154.8 (mean = 10.33 ± 11.82; standard error of mean = 0.3706). Then, the data was organized and sorted following the ranking obtained in the GFsa index ©. The Pearson correlation showed that the H-index had a weakly positive association with the researcher’s “scientific age”; this fact means that the H-index will increase according to the “scientific age” increase. Otherwise, a moderately negative correlation between GFsa and “scientific age” was demonstrated, whereby a higher GFsa © had a lower “Scientific age”. This assessment shows that the variables introduced were fairly used. Moreover, a positive correlation was observed between both indexes (H-index and GFsa). Conclusion: It is possible to conclude that the new variable reported (“Scientific age”) and using the total citations brought a fairer and more feasible evaluation among the researchers. Thus, we are launching the new GFsa index © and the new information named “Scientific age” for the first time in the literature. The future perspective of the GFsa © application will be (1) the evaluation of the 9,093 researchers in Dentistry (total initially registered), including more authors/researchers in the Dentistry field, (2) expanding the exposition of this new index for other areas of the knowledge, and (3) provide free access of all data through the website (http://gfindex.us.to).

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

This study investigated the relationship between aluminum adjuvant vaccines and the prevalence of 4 childhood diseases (Autism, Allergies, Asthma, ADD/ADHD) using data from the 2020-2021 National Survey of Children's Health (NSCH) [1] and the Centers for Disease Control National Immunization Survey (CDC NIS) [2]. The study found an association with aluminum adjuvant dosage and the prevalence of each disease studied (Autism, Allergies, Asthma, ADD/ADHD) through a weighted regression analysis of disease prevalence against the summed likelihood of aluminum adjuvant vaccine uptake.

This paper presents the perspective that universe is relative. The universe, which changes according to the traveler’s proper time, is dynamic. While the universe generally expands, it could also contract if traveler accelerates sufficiently. The Hubble parameter merely represents that change. If the Hubble parameter is dependent on the proper time, the measurement can only be uncertain. Identifying the factors that influence the proper time could potentially lead to a more accurate measurement of the universe’s age, and it could also offer insights into the state of the early universe and the causes of the accelerated expansion observed in the current epoch.

Skin cancer is a condition characterized by the abnormal growth of skin cells, primarily caused by exposure to ultraviolet (UV) radiation from the sun or artificial sources like tanning beds. Different types of skin cancer include melanoma, basal cell carcinoma, and squamous cell carcinoma. Despite the advancements in targeted therapies, there is still a need for a safer, highly efficient approach to preventing and treating cutaneous malignancies. Spices have a rich history dating back thousands of years and are renowned for their ability to enhance the flavor, taste, and color of food. Derived from various plant parts like seeds, fruits, bark, roots, or flowers, spices are important culinary ingredients. However, their value extends beyond the culinary realm. Some spices contain bioactive compounds, including phenolic compounds, which are known for their significant biological effects. These compounds have attracted attention in scientific research due to their potential health benefits, including their possible role in disease prevention and treatment, such as cancer. This review focuses on examining the potential of spice-derived phenolic compounds as preventive or therapeutic agents for managing skin cancers. By compiling and analyzing the available knowledge, this review aims to provide insights that can guide future research in identifying new anticancer phytochemicals and uncovering additional mechanisms for combating skin cancer.

Immune-cell reprogramming driven by mitochondria-derived reactive electrophilic immunometabolites (mt-REMs—e.g., fumarate, itaconate) is an emerging phenomenon of major biomedical importance. Despite their localized production, mt-REMs elicit significantly-large local and global footprints within and across cells, through mechanisms involving electrophile signaling. Burgeoning efforts are being put into profiling mt-REMs’ potential protein-targets and phenotypic mapping of their multifaceted inflammatory behaviors. Yet, precision indexing of mt-REMs’ first-responders with spatiotemporal intelligence and locale-specific function assignments remains elusive. Highlighting the latest advances and overarching challenges, this perspective aims to stimulate thoughts and spur interdisciplinary innovations to address these unmet chemical-biotechnological needs at therapeutic immuno-signaling frontiers.

Background: Chronic Myeloid Leukemia (CML) is initiated in the bone marrow due to the chromosomal translocation t(9;22), resulting in the fusion oncogene BCR-ABL. Tyrosine kinase inhibitors (TKIs) targeting BCR-ABL have transformed fatal CML into an almost curable disease. However, TKIs lose efficacy during disease progression, and the mechanism of CML progression remains to be fully understood. Additionally, common molecular biomarkers for CML progression are lacking. Our studies previously detected ANKRD36 (c.1183_1184 delGC and c.1187_1188 dupTT) associated exclusively with advanced phase CML. However, clinical validation of this finding was pending. Therefore, this study aimed to clinically validate mutated ANKRD36 as a novel biomarker of CML progression. Materials and Methods: The study enrolled 124 patients in all phases of CML, recruited from Mayo Hospital and Hameed Latif Hospital in Lahore, Punjab, between January 2020 and September 2023. All response criteria were adopted from the European LeukemiaNet guideline 2020. Informed consent was obtained from all study subjects. The study was approved byscientific and ethical review committees of all participating centers. Sanger sequencing was employed to detect ANKRD36mutations in CML patients in accelerated phase (AP) (n=11) and blast crisis (BC) (n=10), with chronic-phase CML (CP-CML) patients as controls (n=103). Samples were processed using Big Dye Terminator Cycle Sequencing Ready Reaction kits and sequenced using ABI Prism 3730 Genetic Analyzer, and sequencing using forward and reverse primers for ANKRD36.Results: During our study, 17% of CML patients progressed to advanced phases AP-CML n= 11 (8.9%) and BC-CML n=10(8.1%). The chronic- and advanced-phase patients showed significant difference with respect to male-to-female ratio, hemoglobin level, WBC count, and platelet count. Sanger sequencing detected ANKRD36 mutations c.1183_1184 delGC and c.1187_1185 dupTT exclusively in all AP- and BC-CML patients but in none of the CP-CML patients. Nevertheless, mutations status was not associated with male-to-female ratio, hemoglobin level, WBC count, and platelet count, which makes ANKRD32 as an independent predictor of early and terminal disease progression in CML. Conclusions: The study confirms ANKRD36 as a novelgenomic biomarker for early and late CML progression. Further prospective studies should be carried out in this regard. ANKRD36, although fully uncharacterized in humans, shows the highest expression in bone marrow, particularly myeloid cells. Functional integrated genomic studies are recommended to further explore the role of ANKRD36 in the biology and pathogenesis of CML.

The automotive industry is continuously developing to meet the needs of users in terms of efficiency and convenience. The Thailand government has set a policy for Thailand to be a hub for the production of electric vehicles and key components in the region, with a target to produce electric and zero-emission vehicles by 2030. This article is an example of communication in an electric vehicle system. The CAN Bus system is a communication system in electric vehicles that can receive and send communication data via CAN-Hight/Low lines designed for vehicles. CAN Bus is a standard communication system supported by global organizations and used in modern automotive systems. The design of the communication system in electric vehicles uses MRS Developers Studio software to help write programs to receive and send data and prioritize the importance of the received data. The system consists of communication examples studied, such as pressing the start button, turning on/off the headlights, turning on/off the turn signal, turning on/off the brake light, turning on/off the emergency light, sending the horn signal, sending the signal to shift forward/backward, and tuning the motor gear system. From the communication examples mentioned, the communication will be a prototype transport set for small electric vehicles under the scope of the lithium battery energy storage system, NMC type, size 72 V 25 Ah, to test the use, efficiency, and stability in CAN Bus communication up to 1000 times.

At present, the applications and efficacy of non-ionizing radiations (NIR) in oncotherapy are limited. In terms of potential combinations, the use of biocompatible magnetic nanoparticles as heat mediators has been extensively investigated. Nevertheless, the development of more efficient heat nanomediators that may exhibit high specific absorption rates still is an unsolved problem. Our aim was to investigate if externally applied magnetic fields and a heat-inducing NIR affect tumor cell viability. To this end, under in vitro conditions, different human cancer cells (A2058 melanoma, AsPC1 pancreas carcinoma, MDA-MB-231 breast carcinoma) were treated with the combination of electromagnetic fields (EMFs, using solenoids) and hyperthermia (HT, using a thermostated bath). The effect of NIR was also studied in combination with standard chemotherapy and targeted therapy. An experimental device combining EMFs and high intensity focused ultrasounds (HIFU)-induced HT was tested in vivo. EMFs (25 T, 4h) or HT (52C, 40 min) showed a limited effect on cancer cell viability in vitro. However, their combination decreased viability to approx. 16%, 50%, and 21% of controls values in A2058, AsPC1, and MDA-MB-231 cells, respectively. Increased lysosomal permeability, release of cathepsins into the cytosol and mitochondria-dependent activation of cell death are the underlying mechanisms. Cancer cells could be completely eliminated combining EMFs, HT and standard chemotherapy or EMFs, HT and anti-Hsp70-targeted therapy. As a proof of concept, in vivo experiments performed in AsPC1 xenografts showed that combination of EMFs, HIFU-induced HT, standard chemotherapy and a lysosomal permeabilizer induces a complete cancer regression.

Despite identical genetic constitution, a cancer cell population can exhibit phenotypic variations termed as non-genetic/non-mutational heterogeneity. Such heterogeneity – a ubiquitous nature of biological systems – has been implicated in metastasis, therapy resistance and tumour relapse. Here, we review the evidence for existence, sources and implications of non-genetic heterogeneity in multiple cancer types. Stochasticity/ noise in transcription, protein conformation and/or external microenvironment can underlie such heterogeneity. Moreover, the existence of multiple possible cell states (phenotypes) as a consequence of the emergent dynamics of gene regulatory networks may enable reversible cell-state transitions (phenotypic plasticity) that can facilitate adaptive drug resistance and higher metastatic fitness. Finally, we highlight how computational and mathematical models can drive a better understanding of non-genetic heterogeneity and how a systems-level approach integrating mathematical modelling and in vitro/in vivo experiments can map the diverse phenotypic repertoire, and identify therapeutic vulnerabilities of an otherwise clonal cell population.

Natural and synthetic small molecules from the NCI Developmental Therapeutics Program (DTP) were employed in molecular dynamics-based docking with DNA repair proteins whose RNA-Seq based expression was associated with overall cancer survival (OS) after adjustment for the PCNA metagene. The compounds employed were required to elicit a sensitive response (vs. resistance) in more than half of the cell lines tested for each cancer. Methodological approaches included peptide sequence alignments and homology modeling for 3D protein structure determination, ligand preparation, docking, toxicity and ADME prediction. Docking was performed for unique lists of DNA repair proteins which predict OS for AML, cancers of the breast, lung, colon, and ovaries, GBM, melanoma, and renal papillary cancer. Results indicate hundreds of drug-like and lead-like ligands with best-pose binding energies less than -6 kcal/mol. Ligand solubility for the top 20 drug-like hits approached lower bounds, while lipophilicity was acceptable. Most ligands were also blood-brain barrier permeable with high intestinal absorption rates. While the majority of ligands lacked positive prediction for Herg channel blockage and Ames carcinogenicity, there was considerable variation for predicted fathead minnow, honey bee, and Tetrahymena pyriformis toxicity. The computational results suggest the potential for new targets and mechanisms of repair inhibition and can be directly employed for in vitro and in vivo confirmatory laboratory experiments to identify new targets of therapy for cancer survival.

A novel concept of ion separation Anisotropic Diffusion Mobility Analyser (ADMA) with Individual Ion Counter (IIC) was shown by numerical modelling to be able to separate ions with high resolution and ultra-high sensitivity. An ADMA-IIC device has been developed and tested at sheath flow rates below 40 l/min with a number of chemicals relevant to airport security and military applications. The resolving power of the ADMA was observed to be in the range of 40 to 80. These data were close to the resolution obtained in numerical modelling predictions. It is greater than or comparable with the RP of currently available on-the-market devices for airport security and other applications. It was also confirmed that the ADMA technology enables very fast detection of analytes, at least 100 times faster than ion mobility spectrometers. It was shown that Brownian diffusion can be controlled and even overpowered by generating highly anisotropic diffusion in the ADMA device. The ultimate sensitivity of single-ion detection below the ppq range has been demonstrated.

The fractal dimension of is identified in this paper. More importantly, the undertaken research has shown how affects the Koch snowflake . The study has demonstrated the existence of negative values of (Koch snowflake), which connects to a considerable number of extremely intriguing mathematical and physical research areas. The information-theoretic impact on the Sierpiniski Gasket dimension , which corresponds to , was treated in a more fundamental way. Notably, the credibility of this current study adds to the existing kThe fractal dimension of is identified in this paper. More importantly, the undertaken research has shown how affects the Koch snowflake . The study has demonstrated the existence of negative values of (Koch snowflake), which connects to a considerable number of extremely intriguing mathematical and physical research areas. The information-theoretic impact on the Sierpiniski Gasket dimension , which corresponds to , was treated in a more fundamental way. Notably, the credibility of this current study adds to the existing knowledge for the information- theoretic fractal dimensions. On another applicative note, this paper offers some potential applications of fractal dimension to smart cities. The investigation of the threshold theorems for and in terms of the triad is part of the next study phase. Additionally, investigating the newly obtained 's corresponding arbitrary Sierpinski Gasket for the first time.applicative note, this paper offers some potential applications of fractal dimension to smart cities. The investigation of the threshold theorems for and in terms of the triad is part of the next study phase. Additionally, investigating the newly obtained 's corresponding arbitrary Sierpinski Gasket for the first time.

Amidst the challenges posed by the COVID-19 crisis, marked variations in individuals' resilience and vulnerability have emerged. This eight-month longitudinal study engaged 535 community adults (58% female, M_age = 43.97) to explore the nuanced aspects of coping and personal growth during the challenging period. Grounded in Self-Determination Theory, the research examines the influence of autonomy support from close others—manifested through active listening and providing choices—on psychological need satisfaction (i.e., autonomy, competence, and relatedness), integrative regulation of emotions; posttraumatic growth; and subjective well-being (positive affect and life satisfaction). Structural equation modeling revealed that, over time, the experience of psychological need satisfaction was intricately related to integrative regulation, posttraumatic growth, positive affect, and life satisfaction. Notably, the impact was partially mediated by autonomy support. These findings shed light on the pivotal role that autonomy supported relationships play in fostering personal growth and meaning making during life's difficult junctures. The study underscores the practical significance of purposeful support from close others and paves the way for future research endeavors.

Analysis of complex DNA mixtures is limited by the selected genetic markers characterized and assay technology. Small panels of short tandem repeats (STRs) are the current standards in most countries. Extension of STRs with hundreds of single nucleotide polymorphisms (SNPs) is now commercially available. The current set of extension SNPs focus on phenotypic and biogeographic ancestry informative SNPs. Larger panels with thousands of SNPs have been developed that can identify up to 10 contributors to forensic DNA samples. Herein, multiple sets of SNPs were selected with the focus of increasing the upper limit of detectable contributors. Larger SNP panel sets with lower minor allele frequency (MAF) alleles can detect large numbers of contributors to in silico mixtures of randomly selected profiles from the 1,000 Genomes project. These results provide a path to enable characterization of complex DNA mixtures that are currently impossible to analyse.