Background: As the most invasive breast cancer (BrCa), triple-negative BrCa (TNBC) has the worst survival. The use of dexmedetomidine potentially affected BrCa surgery and dexmedetomidine was reported to have direct effects on TNBC cells. The objective of this study is to explore the mechanisms underlying the effect of dexmedetomidine on TNBC. Methods: Dexmedetomidine targets were predicted using The Cancer Genome Atlas data SwissTargetPrediction. Cell lines MDA-MB-231, MCF7, and MCF10A were used to validate the targets in TNBC with both clinical samples and cell lines. Cancer cell lines and normal breast cell lines were grouped in cancer and normal groups respectively. Both groups were exposed to dexmedetomidine treatment. Cell Counting Kit-8 was used to determine the effect of dexmedetomidine on cells with target silencing. The binding model of the candidate targets was docked and critical amino acids were mutated to validate the binding model. Results: Dexmedetomidine selectively inhibits cancer cells. Catalytic subunit of the DNA-dependent protein kinase (PRKDC), indoleamine 2,3-dioxygenase 1 (IDO1), opioid receptor kappa 1 (OPRK1), glutaminyl-peptide cyclotransferase (QPCT), macrophage migration inhibitory factor (MIF), potassium voltage-gated channel, subfamily H (Eag-related), member 2 (KCNH2), cholinergic receptor, muscarinic 3 (CHRM3), and potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4 (KCNN4) were identified as dexmedetomidine targets in TNBC. The expression levels of PRKDC, IDO1, MIF, KCNH2, CHRM3, and KCNN4 were found to be upregulated in TNBC tissues compared to non-TNBC tissues(p<0.05). Silencing of these genes was found to reduce the sensitivity of TNBC cells to dexmedetomidine(p<0.05). This effect was counteracted when the silenced genes were overexpressed, resulting in an increase in the sensitivity of cells to dexmedetomidine (p<0.05). Furthermore, a direct interaction between dexmedetomidine and IDO1 and CHRM3 was observed, which regulated the sensitivity of cells to dexmedetomidine(p<0.05).Conclusion: IDO1 and CHRM3 are direct targets of dexmedetomidine in TNBC.

Triple negative breast cancer (TNBC) has a negative expression of estrogen receptors (ER), progesterone receptors (PR), or human epidermal growth factor receptors (HER2). The survival rate for TNBC is generally worse than other breast cancer subtypes. TNBC treatment has made significant advances, but certain limitations remain. Treatment for TNBC can be challenging since the disease has various subtypes. Individualized therapy is recommended rather than generalized therapy, given the genetic variations among these TNBC subtypes. A precise and effective treatment for TNBC requires identifying prognostic markers. Depending on the type and stage of TNBC, patients are treated with various therapeutic interventions. A variety of treatment options are available, such as chemotherapy, immunotherapy, radiotherapy, and surgery. Chemotherapy is the most common of these options. TNBC is generally treated with systemic chemotherapy using drugs such as anthracyclines and taxanes in the neoadjuvant or adjuvant settings. Developing resistance to anticancer drugs and off target toxicity are the primary hindrances to chemotherapeutic solutions for cancer. It is imperative that researchers, clinicians, and pharmaceutical companies work together to develop effective treatment options for TNBC. Several studies have suggested nanotechnology as a potential solution to the problem of suboptimal TNBC treatment.

Standard of care for triple negative breast cancer (TNBC) involves the use of microtubule poisons like paclitaxel, which are proposed to work by inducing lethal levels of aneuploidy in tumor cells. While these drugs are initially effective in treating cancer, dose-limiting peripheral neuropathies are common. Unfortunately, patients often relapse with drug resistant tumors. Identifying agents against targets that limit aneuploidy may be a valuable approach for therapeutic development. One potential target is the microtubule depolymerizing kinesin, MCAK, which limits aneuploidy by regulating microtubule dynamics during mitosis. Using publicly available datasets, we found that MCAK is upregulated in triple negative breast cancer and is associated with poorer prognoses. Knockdown of MCAK in tumor-derived cell lines caused a two- to five-fold reduction in the IC50 for paclitaxel, without affecting normal cells. Using FRET and image-based assays, we screened compounds from the ChemBridge 50k library and discovered three putative MCAK inhibitors. These compounds reproduced the aneuploidy-inducing phenotype of MCAK loss, reduced clonogenic survival of TNBC cells regardless of taxane-resistance, and the most potent of the three, C4, sensitized TNBC cells to paclitaxel. Collectively, our work shows promise that MCAK may serve as both a biomarker of prognosis and as a therapeutic target.

The triple-negative breast cancer (TNBC) subtype is one of the most aggressive forms of breast cancer that has poor clinical outcome and still remains as an unmet clinical challenge. Accumulating evidence suggests that intratumoral heterogeneity or the presence of phenotypically heterogeneous cell populations within a tumor plays a crucial role in chemoresistance, tumor progression and metastasis. Increased understanding of the molecular regulators of intratumoral heterogeneity will enable the development of effective therapeutic strategies in TNBC. We have identified a molecular mediator involved in intratumoral heterogeneity in breast cancer using an unbiased approach. We isolated two heterogeneous tumor cell populations from the 4T1 TNBC tumor model and phenotypic characterization revealed that the cells are distinct in terms of their morphology, proliferation and self-renewal ability in vitro; as well as primary tumor formation and metastatic potential in vivo. Further, RNA sequencing on both cell populations was performed to identify the molecular mediators underlying this heterogeneity. Bioinformatic analysis performed on the differentially expressed genes along with the Kaplan-Meier survival analysis in TNBC patients identified Metastasis associated colon cancer 1 (Macc1) as the top candidate gene mediating the aggressive phenotype. The role of Macc1 in regulating the proliferative phenotype was validated using siRNA mediated gene knockdown. The role of Macc1 in the aggressive cancer cell phenotypes and disease progression is being studied further using a small molecule transcriptional inhibitor of Macc1 in cell line and animal models, thus increasing our understanding of the molecular underpinnings of intratumoral heterogeneity in breast cancer that is critical to the improvement in the treatment of women currently living with the highly aggressive TNBC subtype.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the lack of estrogen receptors (ER), progesterone receptors, and HER-2 receptors. Thus, TNBC tumours do not benefit from the current therapies targeting ER or HER-2. Therefore, there is an urgent need to develop novel treatment for this subtype of breast cancer. Marijuana is a common name given to Cannabis plants, a group of plants in the Cannabis genus of the Cannabaceae family. Cannabis plants are among the oldest cultivated crops, traced back at least 12,000 years and are well known for their multi-purpose usage, including medicinal purposes. The main active compounds extracted from Cannabis plants are 21-carbon-containing terpenophenolics, which are referred to as phytocannabinoids. Of these, the tetrahydrocannabinol (THC) group contains highly potent cannabinoids, including delta-9-tetrahydrocannabinol (∆9-THC) and delta-8-tetrahydrocannabinol (∆8-THC), which are the most abundant THCs and are largely responsible for psychological and physiological effects of marijuana. The use of Cannabis plants for medicinal purposes was first recorded in 2337 BC in China, where Cannabis plants were used to treat pains, rheumatism, and gout. Recently, several cannabinoids have been approved for a number of treatments, one of which is the treatment of nausea and vomiting caused by chemotherapy in cancer patients. Furthermore, increasing evidence shows that cannabinoids not only attenuate side effects due to cancer treatment, but might also potentially possess direct antitumor effects in several cancer types, including breast cancer. However, anti-tumour activity of marijuana has been variable in different studies and even promoted tumour growth in some cases. In addition, the mechanisms of cannabinoid action in cancer remain unclear. This review summarizes evidence about the mixed actions of cannabinoids in cancer in general and triple-negative breast cancer in particular.

Triple negative breast cancer (TNBC) is an aggressive subtype of the disease with poor clinical outcomes and limited therapeutic options. Immune checkpoint blockade (CP) has surged to the forefront of cancer therapies with widespread clinical success in a variety of cancer types. However, the percentage of TNBC patients that benefit from CP as a monotherapy is low and clinical trials have shown the need for combined therapeutic modalities. Specifically, there has been interest in combining CP therapy with radiation therapy where clinical studies primarily with external beam have suggested their therapeutic synergy, contributing to the development of anti-tumor immunity. Here, we have developed a therapeutic platform combining radionuclide therapy (RT) and immunotherapy utilizing a radiolabelled biomolecule and CP in an E0771 murine TNBC tumor model. Survival studies show that while neither monotherapy is able to improve therapeutic outcomes, the combination of RT + CP extended overall survival. Histologic analysis showed that RT + CP increased necrotic tissue within the tumor and decreased levels of F4/80+ macrophages. Flow cytometry analysis of the peripheral blood also showed that RT + CP suppressed macrophages and myeloid-derived suppressive cells, both of which actively contribute to immune escape and tumor relapse.

Background: Metastatic triple-negative breast cancer (TNBC) is aggressive with a poor median overall survival (OS), ranging from 8 to 13 months. There exists considerable heterogeneity in the survival at the individual patient level. To better understand the survival heterogeneity and improve risk stratification, our study aims to identify the factors influencing survival utilizing a large patient sample in the National Cancer Database (NCDB). Methods: Women diagnosed with metastatic TNBC from 2010 to 2020 in the NCDB were included. Demographic, clinic-pathological, treatment data, and overall survival (OS) outcomes were collected. Kaplan-Meier curves were used to estimate OS. The log-rank test was used to identify OS differences between groups for each variable in the univariate analysis. For the multivariate analysis, the Cox proportional hazard model with backward elimination was used to identify factors affecting OS. Adjusted hazard ratios and 95% confidence intervals are presented. Results: 2,273 women had a median overall survival of 13.6 months. Factors associated with statistically significantly worse OS included older age, higher comorbidity scores, specific histologies, higher number of metastatic sites, presence of liver or other site metastases in those with only one metastatic site (excluding brain metastases), presence of cranial and extra-cranial metastases, lack of chemotherapy, lack of immunotherapy, lack of surgery to distant sites, lack of radiation to distant sites, and receipt of palliative treatment to alleviate symptoms. In the multivariate analysis, comorbidity score, histology, number of metastatic sites, immunotherapy, and chemotherapy had a statistically significant effect on the OS. Conclusions: Through NCDB analysis, we have identified prognostic factors for metastatic TNBC. These findings will help improve prognostication at diagnosis, optimize treatment strategies, and facilitate patient stratification in future clinical trials.

Triple negative breast cancer (TNBC) has a higher mRNA expression of programmed cell death ligand 1 (PD-L1) which is a ligand to programmed cell death protein 1 (PD-1). The binding of the ligand leads to suppressed activity of T-cell-mediated immune response against cancer cells. The approval of anti-PD-L1 drugs including pembrolizumab and atezolizumab in subgroups of TNBC offer potential improvement to the current treatment regimens available for TNBC. We conducted a meta-analysis to review the efficacy of pembrolizumab and atezolizumab for the treatment of TNBC in both adjuvant and neo-adjuvant settings. A systematic strategy was used as per the PRISMA 2020 statement. All statistical analyses were conducted using Review Manager 5.4. Outcome measures included objective response rate, progression free survival, overall survival in adjuvant therapy groups, and pathological complete response rates in neoadjuvant groups. Six clinical trials were included. For adjuvant therapies, the ORR (OR=1.26, P = 0.04) of Atezolizumab/Pembrolizumab plus chemotherapy was higher in intention to treat (ITT) arms than the placebo groups in TNBC. A positive effect size was found for PFS in the ITT arms (Cohen’s d = 1.55, P<0.001). The Atezolizumab plus chemotherapy group had a positive effect size for OS compared to the control groups (Cohen’s d = 0.52, P<0.001). In the neo-adjuvant setting, patients in ITT arms had higher pCR rates as compared to the control groups (OR= 1.61, P = 0.001). Our findings collate evidence of pembrolizumab and atezolizumab as a viable treatment option among patients with TNBC with PDL1+ subgroups deriving benefits.

Background: Triple negative breast cancer (TNBC) is the most aggressive form of breast cancer with poor outcomes. The molecular basis of TNBC remains poorly understood. The objective of this study was to explore the relationship between obesity and TNBC in premenopausal and postmenopausal Caucasian women using whole genome transcription profiling. Methods: We compared gene expression levels of tumor samples drawn from normal weight, overweight and obese in pre and postmenopausal women diagnosed with TNBC. We performed hierarchical clustering to assess similarity in patterns of gene expression profiles, and conducted network and pathway analysis to identify molecular networks and biological pathways. Results: We discovered gene signatures distinguishing normal weight from obese, normal weight from overweight and overweight from obese individuals in both premenopausal and postmenopausal women. The analysis revealed molecular networks and biological pathways dysregulated in response to obesity. Among the discovered pathways included the unfolded protein response, endoplasmatic reticulum stress, B cell receptor and the autophagy signaling pathways in obese premenopausal women and the integrin, axonal guidance, ERK/MAPK and Glutathione biosynthesis signaling pathways obese postmenopausal women. Conclusions: The results suggest that both overweight and obesity are associated with TNBC, highlighting the need for conformation of these results in independent studies.

Intrinsic subtype of triple-negative breast cancer (TNBC) is based on genomic evaluation. In this study, we report the survival and pathological complete response (pCR) rates of TNBC patients subtyped by IHC and treated with neoadjuvant chemotherapy (NACT). A retrospective cohort of 187 TNBC patients who received NACT between 2008 and 2017 was used, and IHC subtyping was performed on biopsy specimens before chemotherapy. The subtyping revealed predominant basal-like tumors (IHC-BL, 61%), followed by basal-like immune-suppressed (IHC-BLIS, 31%), mesenchymal tumors (12.5%), luminal androgen receptor tumors (IHC-LAR, 12%) and basal-like immune-activated (IHC-BLIA, 10.9%). The pathological complete response (pCR) rate varied among subtypes, with IHC-BLIA showing the highest (30.0%) and IHC-LAR showing the lowest (4.5%). IHC-BLIS led in recurrence sites. Overall and disease-free survival analyses did not show significant differences among subtypes. Although, IHC-BLIA demonstrated a trend toward better survival and IHC-mesenchymal worse. Patients who achieved pCR exhibited significantly better disease-free survival and overall survival than non-responders. This study underscores the potential of IHC-based subtyping in TNBC management, highlighting distinct response patterns to neoadjuvant chemotherapy and potential implications for treatment strategies. Further research is warranted to validate these findings and explore tailored therapeutic approaches for specific TNBC subtypes.

Obesity is one of the most prevalent chronic diseases and has become a global epidemic. Obesity leads to a greater risk of breast cancer (BC), metastases, recurrence, and decreased survival. For sustained weight loss, bariatric surgery is effective as a long-term solution. Bariatric surgery is associated with improved outcomes of several cancers including BC, although the mechanisms mediating this protection are unknown. We hypothesized that elevated bile acid pools detected after bariatric surgery may be factors that contribute to improved BC outcomes. Indeed, patients with greater expression of the bile acid receptor FXR displayed improved survival in specific BC subtypes. Patients with tumors that are estrogen receptor negative (ER-) displayed significantly elevated survival with higher FXR (NR1H4) expression compared to lower expression. FXR is a nuclear hormone receptor activated by bile acids. Therefore, we posited that activating FXR using an established FDA-approved agonist would display anticancer effects. Indeed, FXR agonism by the bile acid mimetic known commercially as OCALIVA (“OCA”), or Obeticholic acid (INT-747), significantly reduced BC progression and overall tumor burden in a pre-clinical model. In human and murine BC analyses in vitro, agonism of FXR significantly and dose-dependently inhibited proliferation, migration, and viability. In contrast, synthetic agonism of another common bile acid receptor, the G protein-coupled bile acid receptor (GPBAR1, TGR5) which is mainly activated by secondary bile acids, failed to significantly alter cancer cell dynamics. In conclusion, agonism of FXR by primary bile acid memetic OCA yields potent anti-tumor effects potentially through inhibition of proliferation and migration and reduced cell viability. Findings suggest that FXR is a tumor suppressor gene with high potential for personalized therapeutic strategies for individuals with BC.

Triple-negative breast cancer (TNBC), characterized by deficiency in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (HER2), is among the most lethal subtypes of breast cancer (BC). Nevertheless, the molecular determinants that contribute to its malignant phenotype such as tumor heterogeneity and therapy resistance remain elusive. In this study, we sought to identify the stemness-associated genes involved in TNBC progression. Using bioinformatics approach, we found 55-up and 9-down regulated genes in TNBC. Out of the 55 upregulated genes, a 5 gene-signature (CDK1, EZH2, CCNB1, CCNA2, and AURKA) involved in cell regeneration, was positively correlated with status of tumor hypoxia and clustered with stemness-associated genes, as recognized by Parametric Gene Set Enrichment Analysis (PGSEA). Also, enhanced infiltration of immunosuppressive cells was positively correlated with the expression of these 5 genes. Moreover, our experiments showed that depletion of the transcriptional co-factor nucleus accumbens-associated protein 1 (NAC1), which is highly expressed in TNBC, reduced the expressions of these genes. Thus, the five genes signature identified by this study warrants further exploration as a potential new biomarker of TNBC heterogeneity/stemness characterized by high hypoxia, stemness enrichment, and immune-suppressive tumor microenvironment.

The present studies were undertaken to address the role of fetuin-A in the growth and invasion potential in a triple negative breast cancer (TNBC) cell line, MDA-MB-468. Basal like TNBC that express high levels of ectopic fetuin-A have poorer prognosis for the patients compared to those that express low levels of the protein. We overexpressed fetuin-A in MDA-MB-468 and then determined the invasive potential of fetuin-A overexpressing cells vs controls transfected with empty vector. We also determined the adhesion and growth potential of the cells in the presence of only fetuin-A in serum free medium and also in complete medium. Our data suggest that fetuin-A overexpression significantly enhances the invasive potential of the cells and also the expression of Toll like receptor 4 (TLR4) on these cells. More importantly, the cells rely on fetuin-A-TLR4 signaling network for growth and invasion because the specific TLR4 inhibitor CLI-095 (resatorvid) abrogates fetuin-A mediated growth and invasion. Taken together, the data suggest that fetuin-A-TLR4 signaling network plays a significant role in the growth and invasion potential of TNBC.

Triple-negative breast cancer (TNBC) is characterized by an active immune response. We evalu-ated intratumoral interrelation between FOXP3+ tumor-infiltrating lymphocytes and other cy-tokines in TNBC. Network analysis refined cytokines significantly correlate with FOPX3 in TNBC. Treatment response and prognosis imformation of patients and survival data from the TGCA and METABRIC databases were analyzed according to refined cytokines. Interleukin (IL)-33 was sig-nificantly expressed by TNBC cell lines than luminal cell lines (log2 fold change: 5.31, p <0.001) and IL-33 and TGFB2 showed a strong correlation with FOXP3 in the TNBC cell line. Immunohisto-chemistry demonstrated IL-33 high group was a significant predictor of complete response of neoadjuvant chemotherapy (odds ratio (OR) 4.12, p<0.05) and a favorable survival compared to IL-33 low group (OR 6.48, p<0.05) in TNBC. Survival data from TGCA and METABRIC revealed that FOXP3 was a significantly favorable marker in IL-33 high group com-pared to the low IL-33 low group (hazard ratio (HR) 2.1, p=0.02), and IL-33 high/TGFB2 high subgroup showed significant favorable prognosis in the FOXP3 high group compared to the FOPX3 low group in TNBC (HR 3.5, p=0.01). IL-33 and TGFB2 were key cytokines of intratumoral interrelation among FOXP3 in TNBC.

Pseudopterosin, produced by the sea whip of the genus Antillogorgia, possesses a variety of promising biological activities including potent anti-inflammatory effects. However, few studies examined pseudopterosin in the treatment of cancer cells and, to our knowledge, the ability to inhibit triple negative breast cancer (TNBC) proliferation or invasion has not been explored. Thus, we evaluated the as yet unknown mechanism of action of pseudopterosin: Pseudopterosin was able to inhibit proliferation of TNBC. Interestingly, analyzing breast cancer cell proliferation after knocking down glucocorticoid receptor α (GRα) revealed that anti-proliferative effects of pseudopterosin were significantly inhibited when GRα expression was reduced. Furthermore, pseudopterosin inhibited invasion of MDA-MB-231 3D tumor spheroids embedded in an extracellular-like matrix. Remarkably, the knockdown of GRα in 3D tumor spheroids revealed increased ability of cells to invade the surrounding matrix. In a co-culture, encompassing peripheral blood mononuclear cells (PBMC) and MDA-MB-231 cells, production of interleukin 6 (IL-6) and interleukin 8 (IL-8) significantly increased compared to monoculture. Notably, pseudopterosin proved to block cytokine elevation, representing key players in tumor progression, in the co-culture. Thus, our results reveal pseudopterosin treatment as a potential novel approach in TNBC therapy.

Immune checkpoint receptors play a crucial role in steering tumor progression, prompting a focused investigation into the role of TIM3 in breast cancer. Analysis of TCGA BRCA data unveiled diverse correlations between TIM-3 expression and immune cell infiltration across subtypes. In our in-house cohort studied through IHC, significant changes in TIM3 expression with tumor grades were observed. Higher TIM3 expression correlated with increased disease-free survival in pan breast cancer, marking the first revelation of TIM3's positive role in pan BC prognosis. The study indicates that alluring TIM3 response, rather than suppression, may enhance breast cancer prognosis.

Background: Extracellular Vesicles are pivotal mediators in intercellular communication, facilitating the exchange of biological information among healthy, pathological and tumor cells. Between the diverse subtypes of extracellular vesicles, exosomes have unique properties, clinical and therapeutical applications, even towards cancer. Breast cancer ranks as one of the most prevalent malignancies across the globe. Both the tumor core and its surrounding microenvironment engage in a complex, orchestrated interaction that facilitates the cancer’s growth and spread. Methods: The most valuable and significant PubMed Literature about extracellular vesicles and adipose–derived stem cells exosomes was selected and analyzed in order to report their biological properties and potential applications, in particular on the Triple–Negative Breast Cancer. Results: Adipose–derived stem cells exosomes represent a potential tool to target the tumor core of the Triple–Negative Breast Cancer, its microenvironment and surrounding tissues including metastasis. The authors are developing a supportive Triple–Adipose–derived stem cells Exosomes [T.A.E.] Technology against breast cancer in order to perform a selective preconditioning of the cancer before or while the traditional oncological treatments are running. Conclusion: The possibility to exploit the impact of Adipose–derived stem cells exosomes within the T.A.E. Technology against the Triple–Negative breast cancer is real, highlighting a new era for supportive measures against breast cancer.Keywords: Extracellular vesicles; Exosomes; Adipose–derived stem cells, Tumor microenvironment, Triple–Negative Breast Cancer, T.A.E. Technology.

Triple negative breast cancers (TNBCs) are molecularly heterogeneous, and the link between their aggressiveness with African ancestry is not established. We investigated primary TNBCs for gene expression among self-reported race (SRR) groups of African American (AA, n=42) and European American (EA, n=33) women. Using The Cancer Genome Atlas (TCGA) approaches, we analyzed RNA sequencing data to measure changes in genome-wide expression and used logistic regressions to identify ancestry-associated gene expression signatures. To determine global ancestry, GATK best practices were followed for variant calling, and used the 1000 Genomes Project as reference data. We identified >150 African ancestry-associated genes and found that, compared to SRR, quantitative genetic analysis was a more robust method to identify racial/ethnic-specific genes that were differentially expressed. A subset of African ancestry-specific genes that were upregulated in TNBCs of our AA patients were validated in TCGA data. In AA patients, there was a higher incidence of basal-like 2 tumors and altered TP53, NFB1, and AKT pathways. The distinct distribution of TNBC subtypes and altered oncologic pathways show that the ethnic variations in TNBCs are driven by shared genetic ancestry. Thus, to appreciate the molecular diversity of TNBCs, tumors from patients of various ancestral origins should be evaluated.

Breast cancer stands as the prevailing malignancy across all six Gulf Cooperation Council (GCC) nations. In this literature review, we highlighted the incidence and trend of BC in the GCC. Most of the studies reported a consistent increase in BC incidence over the past decades, which was particularly attributed to the adoption of a westernized lifestyle in the region and the implications of emerging risk factors and other environmental and societal factors, the increase in screening uptake, as well as the improvement in data collection and reporting in the GCC. The data about BC risk factors in GCC was limited. In this geographic region, breast cancer frequently manifests with distinctive characteristics, including an early onset, typically occurring before the age of 50, an advanced stage at presentation, and a higher pathological grade. Additionally, it often exhibits more aggressive features such as human epidermal growth factor receptor 2 (HER2) positivity or the presence of triple-negative (TN) attributes, particularly among younger patients. Despite the growing body of literature on breast cancer in the GCC, data pertaining to survival rates are, regrettably, meager. Reports on breast cancer survival rates emanating from the GCC region are largely confined to Saudi Arabia and the United Arab Emirates (UAE). In the UAE, predictive modeling reveals 2-year and 5-year survival rates of 97% and 89%, respectively, for the same period under scrutiny. These rates, when compared to Western counterparts such as Australia (89.5%) and Canada (88.2%), fall within the expected range. Conversely, Saudi Arabia reports a notably lower 5-year survival rate, standing at 72%. This disparity in survival rates underscores the need for further research directed towards elucidating risk factors and barriers that hinder early detection and screening. Additionally, there is a pressing need for expanded data reporting on survival outcomes within the GCC. In sum, a more comprehensive and nuanced understanding of breast cancer dynamics in this region is imperative to inform effective strategies for prevention, early detection, and improved patient outcomes.

Pregnancy associated plasma protein-A (PAPP-A) plays an integral role in breast cancer (BC), especially triple negative breast cancer (TNBC). This subtype accounts for the most aggressive BC, possesses high tumor heterogeneity, is least responsive to standard treatments and has the poorest clinical outcomes. There is a critical need to address the lack of effective targeted therapeutic options available. PAPP-A is a protein that is highly elevated during pregnancy. Frequently, higher PAPP-A expression is detected in tumors than in healthy tissues. The increase in expression coincides with increased rates of aggressive cancers. In BC, PAPP-A has been demonstrated to play a role in tumor initiation, progression, metastasis including epithelial-mesenchymal transition (EMT), as well as acting as a biomarker for predicting patient outcomes. In this review, we present the role of PAPP-A, with specific focus on TNBC. The structure and function of PAPP-A, belonging to the pappalysin subfamily, and its proteolytic activity are assessed. We highlight the link of BC and PAPP-A with respect to the IGFBP/IGF axis, EMT, the window of susceptibility and the impact of pregnancy. Importantly, the relevance of PAPP-A as a TNBC clinical marker is reviewed and its influence on immune-related pathways are explored. The relationship and mechanisms involving PAPP-A reveal the potential for more treatment options that can lead to successful immunotherapeutic targets and the ability to assist with better predicting clinical outcomes in TNBC.

Triple-negative breast cancer (TNBC) is an aggressive and highly metastatic type of tumor. TNBC is often enriched in tumor-infiltrating neutrophils (TINs), which support cancer growth in part by counteracting tumor-infiltrating lymphocytes (TILs). Prior studies identified the enhancer of zeste homolog 2 (EZH2) as a pro-tumor methyltransferase in primary and metastatic TNBC. We hypothesized that EZH2 inhibition in TNBC cells per se would exert anti-tumor activity by altering the tumor immune microenvironment. To test this hypothesis, we used CRISPR to generate EZH2-knockout (KO) and overexpressing lines from parent (wild-type -WT) 4T1 cells, an established murine TNBC model. In vitro, EZH2 KO and OE cells showed little change in replicative capacity and invasiveness, but marked changes in surface marker profile and cytokine/chemokine secretion compared to WT cells. On in vivo injection, EZH2 KO cells showed significantly reduced primary tumor growth and a 10-fold decrease in lung metastasis compared to WT cells, while EZH2 OE cells were unchanged. Compared to WT tumors, TIN:TIL ratios were greatly reduced in EZH2 KO tumors but unchanged in EZH2 OE tumors. Our findings show a tumor-intrinsic role of EZH2 in the 4T1 TNBC model in regulating TIN/TIL poise, primary tumor progression and lung metastasis in vivo.

We studied the prognostic impact of tumor immunoglobulin kappa C (IGKC) mRNA expression as a marker of the humoral immune system in the FinHer trial patient population, where 1,010 patients with early breast cancer were randomly allocated to either docetaxel-containing or vinorelbine-containing adjuvant chemotherapy. HER2-positive patients were additionally allocated to either trastuzumab or no trastuzumab. Hormone receptor-positive patients received tamoxifen. IGKC was evaluated in 909 tumors using quantitative real-time polymerase chain reaction, and the influence on distant disease-free survival (DDFS) was examined using univariable and multivariable Cox regression and Kaplan-Meier estimates. Interactions were analyzed using Cox regression. IGKC expression, included as continuous variable, was independently associated with DDFS in a multivariable analysis including also age, molecular subtype, grade, and pT and pN stage (HR 0.930, 95% CI 0.870 – 0.995, P = 0.034). An independent association with DDFS was also found in a subset analysis of triple-negative breast cancers (TNBC) (HR 0.843, 95% CI 0.724 – 0.983, P = 0.029), but not in luminal (HR 0.957, 95% CI 0.867 – 1.056, P = 0.383) or HER2-positive (HR 0.933, 95% CI 0.826 – 1.055, P = 0.271) cancers. No significant interaction between IGKC and chemotherapy or trastuzumab administration was detected (Pinteraction = 0.855 and 0.684, respectively). These results show that humoral immunity beneficially influences the DDFS of patients with early TNBC.

Bromodomain-containing protein 4 (BRD4) is an intracellular protein that regulates expression of various cellular functions. This study investigated whether BRD4 inhibition can alter the immunomodulatory and antitumor effects of radiation therapy (RT). A murine breast cancer cell line was implanted into BALB/c mice. The dual-tumor model was used to evaluate the abscopal effects of RT. A total of 24 Gy was delivered and BRD4 inhibitor was injected intravenously. Tumor size was measured and in vivo imaging was performed to evaluate tumor growth. Flow cytometry and immunohistochemistry were performed to examine immunologic changes upon treatment. The combination of BRD4 inhibitor and RT significantly suppressed tumor growth compared to RT alone. BRD4 inhibitor reduced the size of the unirradiated tumor indicating that it may induce systemic immune responses. Expression of HIF-1α and PD-L1 in tumor was significantly downregulated by the BRD4 inhibitor. Proportion of M1 tumor-associated macrophages (TAMs) increased, and proportion of M2 TAMs decreased upon BRD4 inhibition. BRD4 inhibitor expanded CD4+ and CD8+ T cell populations and reduced the population of monocytic myeloid-derived suppressor cells (M-MDSCs). RT-induced splenic M-MDSCs decreased upon addition of BRD4 inhibitor. Therefore, addition of BRD4 inhibition significantly enhanced the systemic antitumor responses of local RT.

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

Patients with metastatic triple negative breast cancer (TNBC) need new therapies to improve the low survival rates achieved with standard treatments. In this work, we show that the survival of mice with metastatic TNBC can be markedly increased by replacing their normal diet with artificial diets in which the levels of amino acids (AAs) and lipids are strongly manipulated. After observing selective anticancer activity in vitro, we prepared five artificial diets and evaluated their anticancer activity in a challenging model of metastatic TNBC. The model was established by injecting 4T1 murine TNBC cells into the tail vein of immunocompetent BALB/cAnNRj mice. First-line drugs doxorubicin and capecitabine were used as positive controls. AA manipulation led to modest improvements in mice survival when the levels or lipids were normal. Reducing lipid levels to 1% markedly improved the activity of several diets with different AA content. Mice fed the artificial diets as monotherapy lived longer than mice treated with doxorubicin and capecitabine. An artificial diet without 10 non-essential AAs, with reduced levels of essential AAs, and with 1% lipids improved the survival not only of mice with TNBC but also of mice with other types of metastatic cancers.

Breast cancer brain metastasis (BCBM) is a challenging condition with limited treatment options and poor prognosis. Understanding the interactions between tumor cells and the blood-brain barrier (BBB) is critical for developing novel therapeutic strategies. One promising target is estrogen receptor β (ERβ), which promotes the expression of key tight junction proteins, sealing the BBB and reducing its permeability. In this study, we investigated the effects of 17β-estradiol (E2) and the selective ERβ agonist diarylpropionitrile (DPN) on endothelial and cancer cells. Western blot analysis revealed the expression patterns of ERs in these cell lines, and estrogen treatment upregulated claudin-5 expression in brain endothelial cells. Using in vitro models of the BBB, we found that DPN treatment significantly increased BBB tightness about suppressed BBB transmigration activity of representative HER2-positive (BT-474) and triple-negative (MDA-MB-231) breast cancer cell lines. However, the efficacy of DPN treatment decreased when cancer cells were pre-differentiated in the presence of E2. Our results support ERβ as a potential target for the prevention and treatment of BCBM and suggest that targeted vector-based approaches may be effective for future preventive and therapeutic implications.

Patients diagnosed with unresectable locally advanced Triple Negative Breast Cancer (TNBC) usually have poor outcome for its aggressive clinical behaviour. Atezolizumab plus nanoparticle albumin-bound (nab)-Paclitaxel prolonged progression-free survival (PFS) and overall survival (OS) among patients with unresectable locally advanced TNBC but its use is hampered by the lack of reliable predictors of tumor response. Seventy-seven consecutive patients with unresectable locally advanced TNBC treated with Atezolizumab plus nab-Paclitaxel were studied by blood draws at baseline, 28 days and 56 days after initiation of treatment. Exosomal PD-L1 mRNA in plasma was determined using Bio-Rad QX100 digital droplet PCR system and exoRNeasy kit and objective responses were defined following the RECIST criteria v.1.1. The study evaluates whether PD-L1 mRNA copies per ml in plasma-derived exosomes may predict response to anti-PD-L1 antibodies early in the course of therapy. Our data showed patients with unresectable locally advanced TNBC and higher levels of PD-L1 mRNA expression in plasma-derived exosomes at baseline demonstrated greater response to atezolizumab plus nab-paclitaxel. Furthermore, the levels of mRNA decreased with successful treatment while the copy number increased in patients experiencing disease progression following atezolizumab plus nab-paclitaxel. For the first time, our data showed the usefulness of assessment of exosomal PD-L1 as non-invasive real-time biopsy in patients diagnosed with TNBC suggesting exosomal PD-L1 is significantly associated with outcome and response to Atezolizumab plus nab-Paclitaxel.

G protein-coupled receptors (GPCRs, also called seven-transmembrane or heptahelical receptors) are a superfamily of cell surface receptor proteins that bind to many extracellular ligands and transmit signals to an intracellular guanine nucleotide-binding protein (G protein). When a ligand binds, the receptor activates the attached G-protein by causing the exchange of Guanosine-5'-triphosphate (GTP) for guanosine diphosphate (GDP). They play a major role in many physiological functions as well as in the pathology of many diseases including cancer progression and metastasis. Only a few GPCR members have been exploited as targets for developing drugs with therapeutic benefit in cancer. Present review deals with the Prostaglandin E receptor EP4, a member of the EP family of GPCR, as a promising newer therapeutic target for treating breast cancer. We show that aberrant over-expression of cyclooxygenase (COX)-2, an inflammation-associated enzyme, occurring in 40-50% of breast cancer patients leads to tumor progression and metastasis due to multiple cellular events resulting from an increased prostaglandin (PG) E2 production in the tumor milieu. They include inactivation of host anti-tumor immune (NK and T) cells, increased immuno-suppressor function of tumor-associated macrophages, promotion of tumor cell migration, invasiveness and tumor-associated angiogenesis (due to upregulation of VEGF-A), lymphangiogenesis (due to upregulation of VEGF-C/D) and a stimulation of stem-like cell (SLC) phenotype in cancer cells. All these events were primarily mediated by activation of the PGE receptor EP4 on tumor or host cells. We show that selective EP4 antagonists (EP4A) could mitigate all these events tested with cells in vitro as well as in vivo in syngeneic COX-2 expressing mammary cancer bearing mice or immune-deficient mice bearing COX-2 over-expressing human breast cancer xenografts. We suggest that EP4A can avoid thrombo-embolic side effects of long term use of COX-2 inhibitors by sparing cardio-protective roles of PGI2 via IP receptor activation or PGE2 via EP3 receptor activation. Furthermore, we identified two COX-2/EP4 induced oncogenic and SLC-stimulating microRNAs - miR526b and miR655, one of which (miR655) appears to be a potential blood biomarker in breast cancer patients, for monitoring SLC-ablative therapies such as with EP4A. We suggest that EP4A will likely produce the highest benefit in aggressive breast cancers such as COX-2 expressing triple-negative breast cancers, when combined with other newer agents such as PD-1 or PD-L1 inhibitors.

We describe the development and validation of a HPLC-MS/MS method to assess the pharmacokinetics and tumour distribution of ZST316, an arginine analogue with inhibitory activity towards dimethylarginine dimethylaminohydrolase 1 (DDAH1) and vasculogenic mimicry, and its active metabolite L-257 in a xenograft model of triple negative breast cancer (TNBC). The method proved to be reproducible, precise, and highly accurate for the measurement of both compounds in plasma and tumour tissue following acute and chronic (five days) intraperitoneal administration of ZST316 (30mg/Kg daily) in six-week-old SCID mice inoculated with MDA-MB-231 TNBC cells. ZST316 was detected in tumour tissue and plasma after 1 hour (6.47 and 9.01M, respectively) and 24 hours (0.13 and 0.16M, respectively) following acute administration, without accumulation during chronic treatment. Similarly, the metabolite L-257 was found in tumour tissue and plasma after 1 hour (15.06 and 8.72M, respectively) and 24 hours (0.17 and 0.17M, respectively) following acute administration of ZST316, without accumulation during chronic treatment. The half-live after acute and chronic treatment ranged between 4.4-7.1hrs (plasma) and 4.5-5.0hrs (tumour) for ZST316, and 4.2-5.3hrs (plasma) and 3.6-4.9hrs (tumour) for L-257. The results of our study demonstrate the a) capacity to accurately measure ZST316 and L-257 concentrations in plasma and tumour tissue in mice using the newly developed HPLC-MS/MS method, b) rapid conversion of ZST316 into L-257, c) good intra-tumour penetration of both compounds, and d) lack of accumulation of both ZST316 and L-257 in plasma and tumour tissue during chronic administration. The new HPLC-MS/MS method is useful to investigate the in vivo effects of ZST316 and L-257 on vasculogenic mimicry, tumour mass, and metastatic burden in xenograft models of TNBC.

BOLD-100, a ruthenium-based complex, sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (also known as IT-139, NKP1339 or KP1339), is a novel small molecule drug that demonstrated a manageable safety profile at the maximum tolerated dose and modest antitumor activity in a phase I clinical trial. BOLD-100 has been reported to inhibit the upregulation of the endoplasmic reticulum stress sensing protein GRP78. However, response to BOLD-100 varies in different cancer models and the precise mechanism of action in high-response versus low-response cancer cells remains unclear. In vitro studies have indicated that BOLD-100 induces cytostatic rather than cytotoxic effects as a monotherapy. To understand BOLD-100 mediated signaling mechanism in breast cancer cells, we used estrogen receptor positive (ER+) MCF7 breast cancer cells to obtain gene-metabolite integrated models. Particularly, BOLD-100 significantly reduced expression of genes involved in the DNA repair pathway. BOLD-100 also induced reactive oxygen species (ROS) and phosphorylation of histone H2AX, gH2AX (Ser139), suggesting disruption of proper DNA surveillance. In estrogen receptor negative (ER-) breast cancer cells, combination of BOLD-100 with a PARP inhibitor, olaparib, induced significant inhibition of cell growth and xenografts and increased gH2AX. Thus, BOLD-100 is a novel DNA repair pathway targeting agent and can be used with other chemotherapies in ER- breast cancer.

(1) Background: Retroareolar breast tumors are common, but they rarely progress to malignancy. This report presents a case of a 41-years-old woman with a superficial breast tumor, emphasizing the significance of considering a wide range of options when evaluating breast lumps. (2) Methods: The patient presented with a steadily growing, ulcerating superficial tumor in her left breast. To determine the nature of the tumor, a diagnostic assessment was conducted, which included a positron emission tomography (PET) scan and histological analysis. (3) Results: The diagnostic assessment confirmed the presence of a malignant Grade II superficial infiltrating ductal carcinoma. Following the diagnosis, the patient underwent a modified radical mastectomy under general anesthesia. Subsequently, she received four cycles of adjuvant chemotherapy, followed by taxol administrations. (5) Conclusions: This case report underscores the importance of conducting a thorough examination and maintaining a high index of suspicion for breast tumors. By documenting this case, the report contributes to the existing knowledge on various manifestations of breast cancer and highlights the necessity of early identification and aggressive treatment. This knowledge can be applied to identify and manage similar cases in the future, leading to improved patient outcomes.

Breast cancer represents the most common neoplasm worldwide. Viral infections are involved with carcinogenesis, especially those caused by oncogenic Human Papillomavirus (HPV) genotypes. The relationship between HPV and various types of cancer, such as breast and lung, still requires further studies. After infection with HPV, there is a remodeling of the tumor microenvironment, providing a post-infection alteration with immunosuppressive characteristics. This study evaluated the role of HPV in breast adenocarcinoma cell lineage (MDA-MB-231), transfected with the HPV16 E5, E6, and E7 oncogenes and co-cultured with PBMCs. Immunophenotyping was performed. There was an increase in CD4+ T cells number when compared with non-transfected and transfected MDA-MB-231, especially the Treg profile. Moreover, proinflammatory intracellular cytokines, such as IFN-γ, TNF-α, and IL-17 were impaired by transfected cells and a decrease in the cytolytic ac-tivity of the CD8+ and CD56+ lymphocytes was also observed in the presence of HPV oncogenes, mainly with E6 and E7 in NK and TCD8+ cells. In conclusion, MDA-MB-231 breast cell lineage transfected with HPV oncogenes can downregulate the number and function of lymphocytes and monocytes.

With the rise of novel immunotherapies able to stimulate the antitumor immune response, increasing literature data concerning the immunogenicity of breast cancer have been published in recent years. Numerous clinical studies have been conducted in order to identify novel biomarkers that could reflect the immunogenicity of BC and predict response to immunotherapy. In this regard, TILs have emerged as an important immunological biomarker related to the antitumor immune re-sponse in BC. TILs are more frequently observed in triple-negative breast cancer and HER2+ sub-types where increased TIL levels have been linked to better response to neoadjuvant chemotherapy and with improved survival. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in breast cancer is observed in about 10–30% of cases and is extremely variable based on tumor stage and molecular subtypes . In detail, TNBC shows the highest percentages of PD-L1 positivity, followed by HER2+ tumors. On the other hand, PD-L1 is rarely expressed (0-10% of cases) in hormone-receptor positive BC. The prognostic role of PD-L1 expression in BC is still controversial since different immunohistochemistry (IHC) clones, cut-off points and scoring systems have been utilized across published studies. In the present paper an extensive review on the current knowledge of immune landscape of BC is provided. In detail TILS and PD-L1 expression across different BC subtypes is discussed also providing a guide for their pathological assessment and reporting.

Accurate diagnosis for the 400 million people with rare diseases is critical for healthcare decisions, prognosis, understanding disease mechanisms, and identification of treatments. Despite advances in genome sequencing, barriers such as high interpretation costs, diagnostic expertise, throughput associated delays, and uncertain variant classifications persist, with demand exceeding capacity. Many variant classification methods focus narrowly on specific consequences, leading to the use of complex integrative pipelines that often overlook transcript variability and lack prediction transparency. To overcome these limitations, we introduce DITTO. This transparent, transcript-aware machine-learning method demonstrates superior overall performance in accuracy, recall, and precision when compared to existing tools. DITTO is publicly available at https://github.com/uab-cgds-worthey/DITTO

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that disproportionally accounts for the majority of breast cancer-related deaths due to the lack of specific targets for effective treatments. In this review, we highlight the complexity of the transforming growth factor-beta family (TGF-β) pathway and discuss how the dysregulation of the TGF-β pathway promotes oncogenic attributes in TNBC which negatively affects patient prognosis. Moreover, we discuss recent findings highlighting TGF-β inhibition as a potent method to target mesenchymal (CD44⁺/CD24^-) and epithelial (ALDH^high) cancer stem cell (CSC) populations. CSCs are associated with tumorigenesis, metastasis, relapse, resistance, and diminished patient prognosis; however, due to differential signal pathway enrichment and plasticity, these populations remain difficult to target and persist as a major barrier barring successful therapy. This review highlights the importance of TGF-β as a driver of chemoresistance, radioresistance and reduced patient prognosis in breast cancer and highlights novel treatment strategies which modulate TGF-β, impede cancer progression and reduce the rate of resistance generation via targeting the CSC populations in TNBC and thus reducing tumorigenicity. Potential TGF-β inhibitors targeting based on clinical trials are summarized for further investigation which may lead to the development of novel therapies to improve TNBC patient prognosis.

Background: Autonomic balance measurement (ABM) is a valuable tool in clinical practice for assessing the functioning of the autonomic nervous system (ANS), which controls involuntary bodily functions. Here we summarize the current understanding of the utility of autonomic balance measurement in clinical practice. Methods: A narrative review of relevant literature was conducted, focusing on studies investigating the use of autonomic balance measures in various clinical settings. Results: ABM holds potential benefits in clinical practice, including aiding in diagnosing autonomic dysfunction, monitoring treatment efficacy, and predicting potential health complications. ABM can be crucial for diagnosing various conditions, including cardiovascular diseases (Heart failure, arrhythmias, and hypertension), neurological disorders (Parkinson's disease, Alzheimer's disease, and diabetic neuropathy), in sports medicine athletes can undergo ABM to optimize training regimens, enhance performance, assessing the impact of training stress, preventing overtraining, and promoting overall well-being and probably to assess potential health risks, in metabolic syndromes ABM can aid in the early detection of autonomic neuropathy, a diabetes-related complication, allowing for timely intervention and better management of the disease, and psychiatric disorders (Anxiety, depression, and post-traumatic stress disorder). In addition, ABM can be helpful in monitoring of treatment efficacy, by tracking changes in autonomic balance, clinicians can assess if treatments for conditions impacting the autonomic nervous system are effective. ABM can also be helpful in predicting outcomes by facilitating early recognition of future health complications in certain populations. However, limitations exist, including non-specificity, variability in measurements, and limited evidence for routine use in specific clinical settings. Conclusion: Incorporating autonomic balance measurement into routine clinical assessments provides a more comprehensive understanding of a patient's health. It complements traditional diagnostic methods, offering additional insights into the body's regulatory mechanisms. While autonomic balance measurement offers potential benefits, careful interpretation and consideration of its limitations are crucial for its effective use in clinical practice. ABM remains a valuable and versatile tool in clinical practice for a deeper understanding of the autonomic nervous system, enabling early detection, targeted interventions, and improved management of various medical conditions across different specialties.

Development of targeted therapies for triple-negative breast cancer (TNBC) is an unmet medical need. Cisplatin has demonstrated its promising potential for the treatment of TNBC in clinical trials; however, cisplatin treatment is associated with hypoxia that in turn promotes cancer stem cell (CSC) enrichment and drug resistance. Therapeutic approaches to attenuate this may lead to increased cisplatin efficacy in the clinic for the treatment of TNBC. In this report, we analyzed clinical dataset of TNBC and found that TNBC patients possessed higher levels of EGFR and hypoxia gene expression. A similar expression pattern was also observed in cisplatin-resistant ovarian cancer cells. We thus developed a new therapeutic approach to inhibit EGFR and hypoxia by combination of metformin and gefitinib that sensitized TNBC cells to cisplatin and led to the inhibition of both CD44+/CD24- and ALDH+ CSCs. We demonstrated a similar inhibition efficacy on organotypic cultures of TNBC patient samples ex vivo. Since these drugs have already been used frequently in the clinic, this study illustrates a novel, clinically translatable therapeutic approach to treat patients with TNBC.

Well-exposed fluvio-deltaic Surma Group successions of the northeastern Surma Basin provide a direct analogue to its equivalent subsurface successions—the main hydrocarbon reservoirs in Bangladesh. The various levels of lateral and vertical heterogeneities lead to changes in the subsurface sandbody distributions and their reservoir qualities across fields. The present study aims to identify the heterogeneities in the fluvio-deltaic Surma Group successions by detailed sedimentological analysis of the Mio-Pliocene-aged Surma Group successions. Eleven lithofacies have been identified and based on the recurring pattern of these facies within the Surma Group, five facies associations have been identified. The facies associations indicate that these deposits originated from diverse depositional settings, ranging from the prodelta to the alluvial to delta plain. As a whole, they represent a progressive shallowing upward succession with two transgressive events in the upper and lower parts of the Surma Group. Five levels of heterogeneities such as prodelta mud (HL-I), tidal heterolithic deposits (HL-II & III), interbedded mud units in delta front (HL-IV), and intercalated mud laminae, drapes (HL-V) have been identified in the fluvio-deltaic Surma Group. The study suggests that the various levels of reservoir heterogeneities are controlled by the occurrence and distribution of various facies associations.

This study focuses on examining various approaches for Tensor Decompositions (TDs) and their potential applications in satellite imaging (SI) and deep learning (DL). The research highlights how these decompositions can contribute to the advancement of SI and DL, providing valuable insights for future utilization of TDs in research. It explores how these techniques contribute to the advancement of SI and DL methods, providing insights into their potential applications and suggesting future research directions. The study aims to enhance the use of TDs techniques to further advance research efforts in these fields. More importantly, the current investigation offers a thorough analysis of the potential advantages and reasons for employing TDs techniques in different domains, including satellite imaging and deep learning. The aim is to enhance research outcomes by utilizing TDs. The review also identifies unresolved issues and proposes future directions for further investigation in this field. Fundamentally, these proposed open problems will open new grounds to the research community to articulate, innovate, and provide more real-life applications to improve the current state of the art by delving into a wider vision for a higher-level performance of both satellite imaging (SI) and deep learning (DL). Looking at the bigger scenario, this also suggests that TDs could be potentially employed to revolutionize existing machine learning technologies as well as the current space AI industry.

Actually, the study aimed to manage and to analyse the results of the laboratory methods, using liver samples, preparing and analizing in pathology service. This mentioned, are known as routinally practice for hepatitis C diagnosis, which conduct to hepatic cirrhosis. In this study direction, chronic liver diseases stimulate a degree of hepatocyte injury. So previously mentioned modifications, alters thet affect the liver architecture and finally ends in cirrhosis are well analyse on microscopic preparates. Folowing morphological steps, it is possible to analyse normal and alterate liver structure, on colored preparates.

Sulfur dioxide (SO2) reduction remains an area of global necessity further enhanced by the current international focus on pandemic diseases mitigation, elimination of air pollution, and promotion of renewable green energy. The dynamics of chemical bond-strength breaking and reformation in the transition state (TS) is a fundamental process in the reduction of SO2 by CO. Density Functional Theory (DFT) has been used to determine optimal TS reaction pathway via a novel triple-hybrid catalyst utilizing doubly-charged negative atomic V, Mn, and Au. The triple-hybrid catalyst is furthermore tailored to the subsequent minimization of each individual step of the 3-Step SO2 reduction by CO chemical reaction. Each optimized step 1, 2, and 3 is minimized with doubly-charged V, Mn, and Au, respectively, with TS barrier reductions ranging from 1.18 eV to 0.002 eV. Super-benzene, armchair (6, 6) single wall carbon nanotube, and fullerene TS reaction pathways have also been calculated to compare the nanoscale catalytic effectiveness with that of the atomic scale transition metals.

The global textile sector, pivotal to economic development, significantly contributes to environmental degradation, prompting a shift towards sustainable raw material sources. Embracing circular economy principles, this industry is exploring the valorization of agricultural by-products. This study introduces an innovative approach to repurposing mango waste into valuable textile fibers, a byproduct of the fruit processing industry, predominantly generated during juice and jam production. The focus is on the lignocellulosic constituents of mango waste, specifically the peel, seed, and fibrous material, traditionally considered as refuse. Previous research has predominantly utilized mango peel in pectin extraction for food applications, whereas the potential of seed and fibrous content remains underexplored. This investigation endeavors to transform these fibrous by-products into high-value materials suitable for textile manufacturing. The process involved washing, drying, and comprehensive physicochemical characterization of mango fibers, emphasizing lignin quantification, revealing a composition of 12.2% lignin. An experimental design was employed to elucidate the impact of variables such as liquid-to-solid ratio, reaction duration, and sodium hydroxide concentration on lignin dissolution through alkaline hydrolysis. Optimal conditions—10% NaOH concentration, 30 mL/g liquid-to-solid ratio over six hours—achieved an 83% reduction in lignin content. The resulting fibers exhibited properties akin to conventional natural fibers, including a favorable aspect ratio indicative of their suitability for textile applications. A subsequent softening process using propylene glycol enhanced the fibers' spinability, producing a durable, textured fabric ideal for eco-conscious fashion applications, including bags, footwear, and accessories. This research demonstrates the feasibility of converting mango waste into a textile-worthy material and underscores the importance of waste revalorization in promoting sustainability within the circular economy framework.

This study explored what motivates university counselors. By analyzing various factors like personal values and work environment, they found counselors experience greater career satisfaction when their work aligns with their own values and societal impact, and when they receive recognition and opportunities for growth. Universities can utilize these findings to create a more supportive environment for counselors by highlighting their impact, offering development opportunities, and fostering a positive work culture. This can ultimately lead to a more motivated and effective counseling team, benefiting both the counselors and the students they serve.

This work is concerned with studying the change of some Optical and Electrical Properties of Ba_xFe_(1-x)TiO₄ thin films due to the change of the nano crystal size. Simple theoretical explanation based on the string theory was developed. The empirical results obtained indicated that the absorption coefficient, electrical conductivity, and the magnetic permeability increase upon decreasing the nano crystal size. However, the transmission coefficient, and the refractive index increase upon increasing the nano crystal size. All these changes are explained using a simple string model with the aid of Newton's laws. The capability of the string theory to explain this nano quantum behavior comes from the fact that the string theory recognize both the particle and the wave nature of the nano system. This is similar of course to the quantum approach which is based mainly on the dual wave particle nature of atomic systems and entities.

ABSTRACTIntroduction and Purpose: Nurses are expected to be competent in practice based on the domain of standards and interpersonal soft skills (ISS). Nurses are faced with inadequate physical assessment 28%, formulating diagnoses 56%, plans 34%, implementation 31%, evaluation 37,5%, and communication skills 41%. Aims to develop an ISS learning model based on transformative learning theory and digitalization (TLTD) to improve nurses’ competencies. Method: Used Explanatory cross-sectional involved 190 practitioner nurses. Variables of individual characters (X1), facilities (X2), Social environment support/SES (X3), TLTD (X4), ISS (X5), and nursing competencies (Y) were measured. Data was collected using a checklist questionnaire, conducted on 6 June to 10 August 2022 at Dili, Baucau, and Maliana hospitals. Used descriptive and inferential analysis with SEM-PLS. Result: Five of the 11 hypotheses of statistical p-value < 0,05 and T-Test > 1,96, including X2>X4, X3>X5, X4>X5, and X5>y, to form ISS learning model. The characteristic of respondents were 81,8% young adults, 67,9% women, 57,8% undergraduates, judging the previous training 35% was unsuccessful, and 45,8% did not meet expectations. Learning facilities that are still lacking include policies 23,7%, curriculum 23,4%, guideline 22,7%, modules 27,9%, infrastructure 20,3%, social environment support 24,2% low, organizational support, 30,0% low peer support and 26,3% low family support. The average TLTD is 25,3% to 34,2%, ISS 22,1% to 30,5%, and nurse competence 25,3% to 30,5%.Suggestion: Result of the study become base to improve nurse’s competencies. Conclusion: Learning model was formed by facilities, SES, TLTD, ISS, and nurses’ competencies.

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

Thyroid hormones are essential for regulating the metabolic rate, growth, development, and maintenance of many physiological processes in vertebrates. They are synthesized by the thyroid gland, which is an ancient organ that evolved early in vertebrate evolution. This study aims to characterize the evolutionary path of polymorphic variants associated with the hypothalamus-pituitary-thyroid (HPT) axis by comparing ancient DNA (aDNA) sequences of Late Pleistocene-Holocene hominin populations with those of modern humans. We evaluated the genetic sequences of several populations, including Neanderthals, Denisovans, Palaeolithic hunter-gatherers from European Russia and Sunghir, and Neolithic hunter-gatherers/farmers from Anatolia focusing on genes involved in the development of the thyroid gland and thyroid hormone (TH) biosynthesis, secretion, and transport. Results showed interesting variants in the DIO2 (rs225014), TPO (rs4927611), and TG (rs2069556 and rs1133076) genes. All SNPs seemed to confirm that Neanderthals, and in part Denisovas, were physiologically hypothyroidic. Probably they had lower T3 levels due to defective production or peripheral conversion. From the moment that the most favourable alleles in terms of T3 production appear during the Paleolithic, we are inclined to assume that their selection was linked to environmental pressure.Our study supports insight into the evolutionary history of the endocrine system and can help in providing understanding into the evolution of physiological systems and their adaptation to changing environments. Understanding the evolution of thyroid hormones can also shed light on the mechanisms underlying thyroid disorders in humans.

We review the basics of nuclear binding energy scheme assumed to be associated with the existence of a new strong elementary charge associated with square root of reciprocal of the strong coupling constant.

The theory of Ismail's non-extensive maximum entropy solution (NME) is described in detail. It is used as an inductive inference technique for heavy-tailed queues with a non-robust mean queue length and a non-extensive "long-range" interaction. In our novel method, we substitute the non-robust mean queue length for the conventional Pollaczeck-Khinchin mean queue length. In other words, the new non-extensivity parameter q will be included in the resulting state probability function. Numerical portraits are provided to capture the influential effect of the derived formalism, , on the stable M//1 queue with heavy tails. More potentially, some applications of Hurst Exponent to social computing and connected health are provided. Conclusion with some challenging open problems and possible future research pathways are given.

Improving the level of farmers' participation in collective action is an important way to promote rural revitalization and improve the sustainable livelihood level of farmers in underdeveloped areas. Based on 312 questionnaires of farmers in Shanxi Province, this paper investigates the status of farmers' participation in collective action, their sustainable livelihood level and the sustainable livelihood effect of collective action participation. The results show that: farmers' willingness to participate in collective action is strong, and the participation effect is obvious, but the participation frequency is low, and the participation time is less; The farmers' sustainable livelihood level is relatively low, Empirical research shows that the level of collective action participation will have a significant positive impact on Farmers' livelihood risk prevention, livelihood capital accumulation, livelihood mode selection and livelihood income improvement, and the frequency, time and value perception of participation in collective action will have varying degrees of impact on Farmers' sustainable livelihoods. In order to promote farmers' active participation in collective action, it is proposed to strengthen the construction of collective organizations Provide incentives and improve the quality and skills of farmers to enhance the collective concept and other policy recommendations.

Azobenzene photoswitches are fundamental components in contemporary approaches aimed at light-driven control of intelligent materials. Significant endeavors are directed towards enhancing the light-triggered reactivity of azobenzenes for such applications and obtaining water-soluble molecules able to act as crosslinkers in a hydrogel. Here, we report the rational design and the synthesis of azobenzene/alginate photoresponsive hydrogels endowed with fast reversible sol-gel transition. We started with the synthesis of three cationic azobenzenes (AZO A, B, and C) and then incorporated them in sodium alginate (SA) to obtain photoresponsive supramolecular hydrogels (SMHGs). The photoresponsive properties of the azobenzenes were investigated by UV-Vis and ¹H NMR spectroscopy. Upon irradiation with 365 nm UV light, the azobenzenes demonstrated efficient trans-to-cis isomerization, with complete isomerization occurring within seconds. The return to the trans form took several hours, with AZO C exhibiting the fastest return, possibly due to higher trans isomer stability. In the photoresponsive SMHGs, the minimum gelation concentration (MGC) of azobenzenes was determined for different compositions, indicating that small amounts of azobenzenes could induce gel formation, particularly in 5 wt% SA. Upon exposure to 365 nm UV light, the SMHGs exhibited reversible gel-sol transitions, underscoring their photoresponsive nature. This research offers valuable insights into the synthesis and photoresponsive properties of cationic, water-soluble azobenzenes, as well as their potential application in the development of photoresponsive hydrogels.

A rare genetic disorder caused by col18.a1 mutations, inherited mostly in autosomal recessive and rarely in autosomal dominant pattern, giving rise to ocular abnormalities and other associated disorders, the condition is referred to as Knobloch syndrome. This paper overviews the anterior and posterior ocular symptoms in Knobloch patients, thus demonstrating the major findings in Knobloch cases including the mutational analysis which discusses the proteins involved and exon number on which mutations are detected. Animal modeling done by knocking out col18.a1 has also been discussed to determine the functions of this gene which have been identified based on anomalies found in knock-out mice.

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.

Uchino first initiated the study of generalized Reynolds operators on associative algebras. Recently, related research has become a hot topic. In this paper, we first introduce the notion of generalized Reynolds operators on Hom-Lie triple systems associated to a representation and a 3-cocycle. Then, we develop cohomology of generalized Reynolds operators on Hom-Lie triple systems with coefficients in a suitable representation. As applications, we use the first cohomology group to classify linear deformations and we study the obstruction class of an extendable order $n$ deformation. Finally, we introduce and investigate Hom-NS-Lie triple system as the underlying structure of generalized Reynolds operators on Hom-Lie triple systems.

Antibiotic prescription is the first line of treating bacterial diseases. But it affects the composition and function of non-targeted intestinal microbiota. Antimicrobial resistance will be the cause for the death of millions of people worldwide. By considering collateral damage of antibiotics, searching an alternative antimicrobial agent will be a solution to minimize the problems. Probiotics, prebiotics and synbiotics are an alternative to antibiotics. Thanks to GIT microbes as they are responsible for metabolism, energy production, protection from pathogens and immunomodulation. So, it is appreciable if the gut microbiota modulated through consumption of probiotics, prebiotics and synbiotics. Probiotic effects are genus and species specific. To get good health benefit of probiotics, safety of probiotics should be assessed before using them. This is mandatory for prebiotics and synbiotic selection. So this review paper gives information about side effects of antibiotics on gut microbiota, description of probiotics, prebiotics and synbiotics as alternative to antibiotics in modulating GIT microbiota, techniques of assessing safety of probiotics and health benefits of probiotics, prebiotics and synbiotics with scientific evidence in clinical trial and some disagreement and challenges of using probiotics, prebiotics and synbiotics.

Abstract—Hydraulic switching actuators are high efficiency, fast response, and low cost solutions for hydraulic control systems. One of the challenging problems is throttling losses during valve transitions. Previously the authors proposed a zero-flowrate switching method to reduce throttling energy loss of the switching valve, where a hydraulic resonator is applied to make the flowrates through the lines approaching zero before the valves are switched off. The major challenge of this approach is fast switching valves whose transition times are less than 2 ms. In this paper, an improved zero-flowrate switching method is presented. It utilizes the capacity with independent inlet/outlet ports to regulate flowrates through the lines. Models of capacity applied in a simple line with different pressure signals are developed to explore characteristics of the capacity, based on which a complete actuation system is developed. In the complete model, resistance and inductance are optimized to achieve desired flowrate response. The improved zero-flowrate switching method reduces throttling energy losses by 99.945% compared to a hard switching system. The simulation results demonstrated that the improved zero-flowrate switching method performs as expected in the design condition. A capacity with proper volume is able to regulate flowrates through all the lines to zero, with the help of appropriate resistance and inductance. Compared to previous zero-flowrate switching method, the novel strategy allows slower switching valves applied in hydraulic actuation systems and achieves better efficiency performance. This research paves a new avenue for reducing throttling energy losses and improves system efficiency in hydraulic switching actuators, as well as most of the hydraulic switch-mode circuits.

In the process of oil and gas development and production, when the flow rate in the wellbore is large, the materials underground will be eroded, causing the operation to be unable to proceed smoothly and reducing the efficiency of oil and gas production. Therefore, optimizing the anti-erosion coating under high-speed flow conditions in wellbore is a very interesting thing. It can greatly improve operational efficiency. In this paper, laser cladding was used to prepare the new coating used in the PDC drill bit. Then, the effects of tungsten carbide and multi-layer graphene on the microstructure and properties of the tungsten carbide coating were studied. The research results indicate that, for new coatings, 60% tungsten carbide and 0.3% graphene are the optimal ratios. After adding WC, the hardness has significantly improved. However, when the WC content further increases more than 30%, the increase in hardness is relatively small. In addition, when the content of graphene is more than 0.3%, the branched structure became thicker, and not only the segregation of Cr, Si and W became very obvious again, but also the segregation of Fe occurred at the Ni enrichment site. The research results contribute to improving oil and gas production and operational efficiency under high-speed fluid flow conditions in the wellbore.

The escalating demand for multifunctional and advanced materials for growing industries has turned scientific exploration to graphene-based hybrid filler polymer composites. The introduction of graphene with other fillers into polymer matrices results in astonishing properties and thus has gained significant attention in recent years. This study addresses the significance of graphene-based hybrid filler polymer composites in progressive materials science and engineering. The paper encloses some traditional and current preparation techniques employed in the fabrication of composites and a comprehensive review of successfully prepared graphene hybrid polymer composites with enhanced mechanical, thermal, and electrical properties reported in published research. The role of different factors, e.g., filler type, aspect ratios, filler-matrix compatibility, dispersion effects, homogeneity, filler orientation through polymer matrices, and curing conditions, are summarized. Finally, the applications in heavy industries, e.g., aerospace, electronics, energy storage, and automotive sectors were also analyzed. We hope this study will serve as a practical resource for new researchers and practitioners to understand and harness the full potential of these composites in various scientific and industrial fields.

Background –The brinjal is of much importance in the warm areas of Far East, being grown extensively in India, Bangladesh, Pakistan, China and the Philippines. It is also popular in Egypt, France, Italy and United States. Preserving soil fertility throughout time by preserving organic matter and soil biological diversity, mechanical intervention, as well as exercise is highly needed in upcoming future. Effect of six different fertilizer, five organic and one synthetic fertilizers listing vermicompost, poultry manure, mustard cake, neem cake, bonemeal and N:P:K study were main concern of this investigation to find out the most suitable fertilizer for the brinjal.Result - the final growth and development through N:P:K @ 1.5%(19:19:19) outperformed all the organic fertilizers but when considering only organic fertilizer performance vermicompost@5 ton/ha was outperforming all the other organic fertilizers. Coming close to it, mustard cake@1.5ton/ha has shown its inheritance in providing nutrients. Use of other organic fertilizers are also effective use of poultry manure can provide nitrogen in higher amount in short time. Higher temperature above 25 degree Celsius cause slow growth, temperature range between 21 to 14 degrees Celsius was found better in terms of growth of flower and fruit formation.Conclusion – our experiment demonstrate specific organic fertilizer use over other fertilizers in terms of brinjal different developemental parameters and there is even comparision between synthetic fertilizer with organic fertilizer readily available in market. Vermicompost showed promising result followed by mustard cake for this specific brinjal genotype in northern plain of Indian subcontinent.

Permafrost covers about 23% ~ 25% of the land in the northern hemisphere, mainly in Russia, Canada, Alaska, Northeast and Qinghai Tibet Plateau (QTP) in China. Many engineering especially the transportation has been in the permafrost regions above. Under the action of highways construction and global warming, permafrost under infrastructures is degraded and causes serious damage. Two phases closed thermosyphon (TPCT) is a widely accepted green countermeasure against the problem in permafrost regions. Although it has been applied to prevent permafrost degradation, their application presents significant challenges on account of the stronger endothermic action of asphalt pavement. This paper focused on the thermosyphon technology and application in the permafrost. Moreover, the article highlighted the excellent working performance of the TPCT that improving the stability of the infrastructures and prevent it degrading due its excellent efficiency of heat transfer. The industrial applications of the TPCT were also summarized, along with their limitations. Finally, the results reported in this paper can provide a valuable guidance for the design of the TPCT and construction of the permafrost regions in the future.

The bioindicator potential of seagrass ecosystems in coastal trace metal monitoring is low for tropical island ecosystems. This study evaluated the bioindicator potential of six seagrass species exposed to anthropogenic trace metal pollution in the Andaman and Nicobar Islands (ANI) of India. Sediment and seagrass biomass, samples were analyzed for trace metals (Co, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Zn) from four locations of ANI exposed to anthropogenic contamination. Geo accumulation Index values indicated moderate trace metal contamination in seagrass sediment. Seagrass trace metal accumulation from sediment was both species-specific and location- specific for ANI. Small seagrass species such as H. ovalis, H. beccarii and H. uninervis accumulated the maximum concentration of six trace metals (Cr, Cu, Fe, Ni, Pb, Zn) in their tissues compared to big seagrass species like T. hemprichii and E. acoroides of ANI. This study indicates leaves of small seagrass and roots of big seagrass species can serve as short- and long-term bioindicators respectively, of coastal trace metal contamination in tropical islands of ANI.

Background: Waterborne diseases pose a significant global public health threat, compelling enhanced comprehensive surveillance. This study investigates the current infectious disease and antimicrobial resistance (AMR) surveillance systems, including wastewater and environmental surveillance (WES), in three sub-Saharan African countries: Tanzania, Burkina Faso, and the Democratic Republic of the Congo (DRC). The three countries have their specificities regarding wastewater networks and logistic systems. So, emphasizing the need to strengthen existing disease surveillance, the paper advocates for incorporating WES systems specifically designed for countries' context to monitor waterborne and re-emerging pathogens, as well as AMR.Methods: National workshops were conducted to assess the current clinical and environmental surveillance systems and identify priority pathogens for new environmental monitoring. Data were collected through surveys from experts in academia, research, policy, and healthcare. Results: Prioritized pathogens for WES include waterborne (poliovirus, Salmonella Typhi, Vibrio cholerae), respiratory (influenza A&B, SARS-CoV-2), other (Measles and Rubella, Mycobacterium tuberculosis). Recommended AMR pathogens include drug-resistant Mycobacterium tuberculosis, Salmonella spp., methicillin-resistant Staphylococcus aureus, and extended-spectrum beta-lactamase and carbapenemase-producing E. coli. Tanzania, Burkina Faso, and the DRC employ DHSI2-based centralized electronic systems for clinical data collection, complemented by Excel and paper-based registries. The WES approach is commonly employed for monitoring poliovirus and rarely for AMR and other pathogens. Discussion and conclusions: WES is a valuable tool for early detection of locally circulating human-derived pathogens, aiding in outbreak detection, data-driven epidemic response, and prevention. The availability of WES results underscores the importance of effective sanitation for safeguarding human, animal, and environmental health. WES is a pivotal tool for integrated risk management, preventing waterborne outbreaks, protecting drinking water sources, and ultimately gaining various UN Sustainable Development Goals. The study highlights the importance of customized WES systems in line with each country's context, emphasizing localized approaches for effective monitoring of waterborne pathogens and AMR.

Microplastics and nanoplastics (MP/NPs) have been found everywhere they have been searched. On the top of Everest, in the Mariana Trench, on the clouds e recently, microplastics have been discovered in the human placenta, meconium and babies’ feces. In this review we explain what the consequences of the presence of these pollutants in fetuses and newborns are, with particular attention to human breastfeeding. Finally, we outline the possible political and social solutions to the problem of plastic overproduction that characterizes the modern world.

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.

Enhancing traffic safety is one of the fundamental objectives of Intelligent Transport Systems (ITS), and it aligns closely with the principles of sustainable transport. Due to specific differences in infrastructure, vehicles, and users’ behaviour, places where different modes of traffic intersect are recognized as critical points of the traffic system, making them crucial aspects of Sustainable Urban Mobility Plans (SUMPs) implementation. The SUMPs aim to create urban mobility that is not only environmentally friendly and efficient but also safe for all users. The continuous development and widespread adoption of innovative ITS technologies have paved the way for a system that could provide drivers with real-time information about both immediate and potential dangers at these critical points. This paper provides an overview of previous research in the field, investigating the impact of information systems on drivers’ behaviour, various detection and communication solutions that can be effectively integrated into such a system, as well as a brief overview of models and solutions that have been developed to warn drivers in a similar context. The reviewed literature offered valuable insights on which a novel driver information system architecture framework is proposed. This framework can contribute to the ongoing safety improvement in multimodal transport networks within the context of sustainable transport.

Quantum correlations, especially time correlations, are crucial in ghost imaging in order to significantly reduce the background noise on the one hand while increasing the imaging resolution. Moreover, the time correlations serve as a critical reference, distinguishing between signal and noise, which in turn enable clear visualization of biological samples. Quantum imaging also addresses the challenge involved in imaging delicate biological structures with minimal photon exposure and sample damage. Here we explore the recent progress in quantum correlation-based imaging, notably its impact on secure imaging and remote sensing protocols as well as on biological imaging. We also exploit the quantum characteristics of heralded single-photon sources (HSPS) combined with decoy-state methods for secure imaging. This method uses Quantum Key Distribution (QKD) principles to reduce measurement uncertainties and protect data integrity. It is highly effective in low-photon-number regimes for producing high-quality, noise-reduced images. The versatility of decoy-state methods with WCSs (WCS) is also discussed, highlighting their suitability for scenarios requiring higher photon numbers. We emphasize the dual advantages of these techniques: improving image quality through noise reduction and enhancing data security with quantum encryption, suggesting significant potential for quantum imaging in various applications, from delicate biological imaging to secure quantum communication.

The normative and safeguarding role of ethics and law in the development of biomedical science and technology, as well as their importance in promoting the progress of the industry, analyzed the key role of ethics and law in the field of biomedical science and technology, by restricting scientific research behavior, protecting the rights and safety of subjects, providing a solid guarantee for scientific research activities, and promoting the healthy development of biomedical science and technology. At the same time, the positive role of ethics and law in promoting international cooperation and exchange of biomedical science and technology is also discussed, which will inject strong impetus into the global development of biomedical science and technology. In addition, through case analysis, the paper demonstrates the key role of ethical review in the field of biomedical science and technology, as well as the importance of law in maintaining market order, protecting subjects' rights and interests, and fairness and justice. The successful practice of ethics and law in the development of biomedical science and technology is emphasized, which proves that following ethical principles and legal framework is the key factor to promote the progress of biomedical science and technology. This paper explores the important role of ethics and law in the development of biomedical science and technology, and provides valuable reference and guidance for practitioners in the industry. By following ethical principles and legal norms, we will jointly promote the prosperity and development of biomedical science and technology, and contribute to the common progress of human health.

Understanding mechanisms of ageing remains a complex challenge for biogerontologists, but recent adaptations of evolutionary ageing theories offer a compelling lens in which to view both age-related molecular and physiological deterioration. Ageing is commonly associated with a progressive loss of biochemical processes and degeneration of molecular material, however, the mechanisms of diminishing function are not simply a result of aberrant expression of these pathways. Natural selection pressures are at their highest in youthful periods to select genes advantageous to maximising reproductive capacity. After sexual maturation, selective pressure diminishes, subjecting individuals to maladaptive pleiotropic gene function once beneficial for developmental growth, but pathogenic later in life. Due to this selective ‘shadowing’ in ageing, mechanisms to counter hyperfunctional genes are unlikely to evolve within a given species. These genetic ‘run-on’ programmes are not dysfunctional per se and, in fact, remain highly robust. Thus, interventions capable of optimising gene function during the ageing process represent as attractive therapeutic modalities. Caenorhabditis elegans offers a unique model to explore high-throughput screening of interventions to combat hyperfunctional pathways involved in ageing. However, the majority of research to date employ whole-life vs late-life pathway manipulation of developmental/growth-related systems to claim ageing attenuation, despite significant impairments in early-life fitness and discordance with healthspan. Here, we discuss data supporting hyperfunctional changes at a global molecular and functional level in C. elegans, and how classical lifespan-extension mutants alter these dynamics. We later discuss the relevance of such mutant models for exploring mechanisms of ageing, highlighting that post-reproductive gene manipulation represents a far more translatable approach for C. elegans research not routed within pleiotropic constraints. More so, lifespan has become a routine readout for quantifying ‘ageing’, however, we make the argument that a compression of gerospan vs lifespan extension is a more meaningful goal for anti-ageing regimes with current knowledge. Similarly, mechanisms governing lifespan are distinct from those regulating health, and slowing senescent pathology accumulation appears more applicable for the abstraction to human ageing.

Abstract Introduction: Poor structural quality of health facilities for tuberculosis (TB) diagnosis and treatment contributes to unfavorable health outcomes among TB patients. Improving the quality of healthcare services helps to avert TB-related morbidity. Despite these facts, the level of structural quality of health facilitieSs to deliver TB services is not in line with what the national TB and leprosy program (NTLP) recommends. Hence, the present study was conducted to assess the structural quality of health facilities to deliver quality TB services to TB patients among public health facilities in the Sidama region.Objectives: To determine the quality of the structural domain of TB services at public health facilities in the Sidama region of southern Ethiopia.Methods: An institution-based cross-sectional study was conducted from June to July 2023 among randomly selected public health facilities in the Sidama region. We included 40 randomly selected public health facilities that delivered TB services in the study area. Data was collected by experienced data collectors using facility audits, clinical observation checklists, structured questionnaires, and in-depth interviews. An Open Kit Mobile (ODK) application was used to collect data and exported to SPSS version 26. All statistical analysis was done using SPSS version 26.Results: The overall mean quality score for the structural dimension was 50.25 among the 40 health facilities audited in the study area.Conclusion: The quality of TB services regarding structural dimensions was poor in the study area. Therefore, any strategies must give careful attention to increasing the comprehensive structural dimension of quality TB services.

This review explores the transformative impact of sensor technologies in early disease detection. It highlights recent advancements in nanotechnology-based sensors, particularly focusing on their applications in identifying disease biomarkers at early stages. The integration of these sensors with artificial intelligence for predictive analytics in healthcare is also discussed. Applications in cancer, infectious diseases, and chronic disease management underscore their diverse utility. Challenges in sensor technology adoption and future directions, including multiplexed sensors and wearable devices, are examined. This review underscores sensors' potential in enhancing disease management and patient outcomes.

Computed tomography (CT) is a widely employed imaging modality with diverse clinical applications in pediatric and adult populations, offering numerous advantages. Despite several alternatives to imaging modalities with ionising radiation, CT scans have demonstrated persistent global popularity, contributing to a substantial amount of effective radiation doses for patients. This exposure results in hazards, including stochastic effects that amplify the radiation-induced cancer risk proportionally to the radiation dose received. CT-related radiation comprises a substantial portion of cumulative effective doses within diagnostic radiology, specifically impacting younger patient cohorts undergoing repeated investigations for chronic diseases over time. Scientific literature over recent decades has explored various methods to mitigate radiation doses during medical imaging. One notable strategy involves implementing low-dose and ultralow-dose CT protocols, maintaining diagnostic efficacy in acute and non-acute medical and surgical conditions. Utilising innovative image reconstruction algorithms, such as iterative reconstruction and emerging deep-learning algorithms based on artificial intelligence, plays a pivotal role in achieving an approximately 80% reduction in patient radiation compared to standard doses. This review article discusses the significance of low-dose protocols across a spectrum of acute and chronic medical conditions affecting different body systems.

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.

The assessment of Histone deacetylases in conjunction with Curcumin, conducted through the Mcule Database employing the Autodock Vina algorithm, involves an examination of molecular interactions. This analysis includes the calculation of binding energies, revealing the strength and stability of the interactions between Curcumin and various Histone deacetylase targets. The comparison encompasses diverse aspects such as binding energies, specific binding sites, interactions across different targets, structural details, and potential implications for biological activity. The results imply that Curcumin shows heightened affinity for Histone deacetylase 4 in comparison to other investigated histone deacetylases.

This article explores the cutting-edge advancement of gypsum and cement building boards infused with shape-stabilized n-octadecane, an organic phase change material (PCM). The primary focus is on improving energy efficiency and providing electromagnetic interference (EMI) shielding capabilities for contemporary buildings. The research investigates the integration of these materials into construction materials, using red-mud Carbon Foam as a stabilizer for n-octadecane (OD@CCF). Various analyses, including microstructural examination, porosity assessment, and additive dispersion, were conducted using X-ray microtomography and density measurements. Thermal conductivity measurements demonstrated the enhancement of composite boards as the OD@CCF content increased, while mechanical tests indicated an optimal additive content of up to 20%. The thermal-regulated capabilities of these advanced panels were evaluated in a custom-designed room model equipped with a homemade environmental chamber, illustrating a consistent temperature environment during heating and cooling cycles. The incorporation of OD@CCF into cement boards exhibited improved thermal energy storage properties. Moreover, the examined composite boards displayed efficient electromagnetic shielding performance within the frequency range of 3.2–7.0 GHz, achieving EMI values of approximately 18 and 19.5 dB for gypsum and cement boards, respectively, meeting the entry-level value required for commercial applications.

Colonization of distant organs by tumor cells is a critical step of cancer progression. The initial avascular stage of this process (micrometastasis) remains almost inaccessible to study due to the lack of relevant experimental approaches. Here, we introduce an in vitro/in vivo model of organ-specific micrometastases of triple-negative breast cancer (TNBC) that is fully implemented in a cost-efficient chick embryo (CE) experimental platform. The model is built as three-dimensional (3D) tissue engineering constructs (TECs) combining human MDA-MB-231 cells and decellular-ized CE organ-specific scaffolds. TNBC cells colonized CE organ-specific scaffolds in 2-3 weeks, forming tissue-like structures. The feasibility of this methodology for basic cancer research, drug development and nanomedicine was demonstrated on a model of hepatic micrometastasis of TNBC. We revealed that MDA-MB-231 differentially colonize parenchymal and stromal com-partments of the liver-specific extracellular matrix (LS-ECM) and become more resistant to the treatment with molecular Doxorubicin (Dox) and Dox-loaded mesoporous silica nanoparticles than in monolayer cultures. When grafted on CE chorioallantoic membrane, LS-ECM-based TECs induced angiogenic switch. These findings may have important implications for the diag-nosis and treatment of TNBC. The methodology established here is scalable and adaptable for pharmacological testing and cancer biology research of various metastatic and primary tumors.

Green economy has emerged as a significant pillar of sustainable development in the current global context, and the unpredictability of economic policy has progressively garnered the interest of businesses and government officials as one of the obstacles they must confront. This paper examines how uncertainty in the green economy impacts the green economy's efficacy. The research concentrates on how changes in a particular region can result in geospatial diffusion (spatial spillover), which is a form of spatial spillover wherein the uncertainty of the green economy can impact its efficacy. This paper examines the policy formulation and current state of the green economy across various regions, as well as the diffusion of economic policy uncertainty across geographical areas and the subsequent impact on the green economy's status quo. There is a negative correlation between economic policy uncertainty and green economy efficacy, according to research. There is a spatial spillover effect between economic policy uncertainty and the efficacy of the green economy. Regional variations exist in the impact of economic policy uncertainty on the efficacy of the green economy. The findings indicate that the implementation of AI has a more substantial beneficial effect on carbon emissions. An increase in carbon dioxide emissions poses a growing challenge for the industrial sector in its pursuit of carbon neutrality.

Climate change will pose a challenge for the winemaking sector worldwide, bringing progressively drier and warmer conditions and increasing the frequency and intensity of weather extremes. The short-term adaptation strategy of applying biostimulants through foliar application serves as a crucial measure in mitigating the detrimental effects of environmental stresses on grapevine yield and berry quality. The aim of this study was to evaluate the effect of foliar application of a seaweed based biostimulant (A. nodosum – ANE) and glycine betaine (GB) on berry quality, bioactive compounds, antioxidant activity, and elucidated their action on the secondary metabolism. A trial was installed in a commercial vineyard (cv. ‘Touriga Franca’) in the Cima Corgo (Upper Corgo) sub-region of the Douro Demarcated Region. A total of four foliar sprayings were performed during the growing season: at flowering, pea size, bunch closer, and veraison. There was a positive effect of GB in the berry quality traits. Both ANE and GB increased the synthesis of anthocyanins and other phenolics in berries and influenced the expression of genes related to the synthesis and transport of anthocyanins (CHS, F3H, UFGT, MATE1 and GST). So, they have the potential to act as elicitors of secondary metabolism, leading to improved grape quality, but also sets the foundation for sustainable agricultural practices in the long run.

With reference to our 4G model of final unification, strong coupling constant and strong interaction charge of magnitude $e_s\cong 2.95e$, it is possible to understand the nuclear stability range with a simple power law of the form, $A_s\cong \left(Z+2.95\right)^{1.2\pm0.015}$

This paper explores the views of a group of young men aged 16–18, studying towards a Level 1 diploma in music in the North East area of England. It uses the conceptualization of “social haunting” to focus our discussions about how Level 1 learners articulated their experiences in the context of their learning journeys and perceived marginalization. The research took place at a large Further Education (FE) college and included a series of five “research encounters” with the group of Level 1 learners. These encounters included a range of activities, resulting in a variety of data being collected, including several activity worksheets, structured and unstructured focus group interviews, and questionnaires. This paper focusses on the outcomes of a single research activity that focused on exploring the topic of marginalization. We present a discussion on social haunting as one of the emerging findings from this research encounter, outlining how the reality of the social and cultural legacy of the UK’s industrial past can shape today’s youth and their futures. We will talk about the young men’s views of marginalization, their school-to-work transitions, the formation of masculinity in post-industrial communities and the role of Further Education in it. The paper concludes by discussing some insights for practice and future research.

Proteins are considered to be the main carriers of antigenic properties of Mycobacterium tuberculosis and Mycobacterium bovis, the causative agents of tuberculosis, the most serious infectious disease. Neutrophils, following resident macrophages, are among the first to attack the mycobacteria in defense of the organism. Neutrophils themselves are also the target of mycobacterial products; and their effect on neutrophil functions has been less studied. We have obtained about 70 protein fractions from M. bovis lysate; among them four protein fractions (10, 22, 24, and 40 kDa) had high serological activity against the serum of a rabbit immunized with M. bovis cells. We studied the effect of the serologically active proteins isolated from M. bovis on the generation of reactive oxygen species by bone marrow granulocytes of the Balb/c mouse, evaluated by luminol-dependent chemiluminescence. For comparison, two synthetic peptides (both 3 kDa) carrying immunogenic epitopes of MPB 70 protein (M. bovis) were taken. Proteins of 10, 22, and 24 kDa at concentrations of 83, 80, and 59 ng/mL, respectively, were found to activate ROS generation by mouse granulocytes. The 10- and 40-kDa antigens inhibited the receptor-mediated respiratory responses to opsonized zymosan (OZ) and N-formyl-MLF peptide (fMLF) but significantly enhanced the response to the phorbol ester PMA, which directly activates protein kinase C. Antigens with molecular weights of 22 and 24 kDa enhanced the fMLF-induced response and had no effect on the response activated by PMA. The response to OZ was suppressed in the presence of the 22 kDa protein. Synthetic peptides over a wide range of concentrations showed no activity in any case. All M. bovis proteins examined did not affect both proliferation and cell viability of the A549 and THP-1 cells; therefore, they have no cytotoxic or proliferative effects. Thus, serologically active proteins with molecular weights of 10, 22, 24, and 40 kDa isolated from M. bovis modulated the respiratory responses of mouse granulocytes induced by the formyl peptide, while proteins of 10, 22, and 40 kDa inhibited the responses induced by OZ.

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.

The effects of the coolant pulsation and the film cooling with the plasma aerodynamic actuation (PAA) could be herein explored via large eddy simulations. The electrohydrodynamic force derived from the PAA was solved through the phenomenological plasma model. The Strouhal number of the sinusoidal coolant pulsation and the averaged pulsation blowing ratio were 0.25 and 1.0, respectively. Comprehensive analyses were carried out on the time-averaged flow fields, and the results revealed that the pulsed cooling jet might cause a deeper penetration into the crossflow, and this phenomenon could be remarkably mitigated by the downward force of the PAA. Furthermore, because of the coolant pulsation, the counter rotating vortex pair (CRVP) expanded to lifted off the wall less well, and the PAA lessened the negative lift-off impact and entrapment from the CRVP. Then, the spatial-temporal development of the coherent structures was figured out by the alterations of the centerline temperature, reflecting formation of the intermittent coherent structures rather than hairpin vortices due to the coolant pulsation, and their size and upcast behaviors were reduced by the PAA. Consequently, there was a basic suppression of the turbulent mixing of the cooling fluid with the crossflow. Finally, the three-dimensional streamlines confirmed that the coherent structure dynamic behaviors were significantly regulated by the PAA for alleviating the adverse influences of the coolant pulsation. In summary, through controlling how the dominating coherent structures evolve throughout time and space, the PAA can effectively increase the pulsed film cooling efficiency.

In this paper, some characterizations of fuzzifying strong compactness are given, including characterizations in terms of nets and pre -subbases. Several characterizations of locally strong compactness in the framework of fuzzifying topology are introduced and the mapping theorems are obtained.

The strong coupling between individual quantum emitters and resonant optical micro/nanocavities is beneficial to understand light and matter interactions. Here we propose a plasmonic nanoantenna placed on a metal film to achieve an ultra-high electric field enhancement in the nanogap and ultra-small optical mode volume. The strong coupling between a single quantum dot and the designed structure is investigated in detail by both numerical simulations and theoretical calculations. When a single QD is inserted into the nanogap of the silver nanoantenna, scattering spectra show remarkably large spectral splitting and typical anti-crossing behavior of the vacuum Rabi splitting, which can be realized in the scattering spectra by varying the nanoantenna thickness. Our work shows a possible way to enhance light-matter interaction at a single quantum emitter limit, which can be useful for future quantum and nanophotonic applications.

New setting is introduced to study chromatic number. Neutrosophic chromatic number and chromatic number are proposed in this way, some results are obtained. Classes of neutrosophic graphs are used to obtains these numbers and the representatives of the colors. Using colors to assigns to the vertices of neutrosophic graphs is applied. Some questions and problems are posed concerning ways to do further studies on this topic. Using strong edge to define the relation amid vertices which implies having different colors amid them and as consequences, choosing one vertex as a representative of each color to use them in a set of representatives and finally, using neutrosophic cardinality of this set to compute neutrosophic chromatic number. This specific relation amid edges is necessary to compute both chromatic number concerning the number of representative in the set of representatives and neutrosophic chromatic number concerning neutrosophic cardinality of set of representatives. If two vertices have no strong edge, then they can be assigned to same color even they’ve common edge. Basic familiarities with neutrosophic graph theory and graph theory are proposed for this article.

The purpose of this paper is to bring to light a method through which the global in time existence for arbitrary large in H¹ initial data of a strong solution to 3D periodic Navier-Stokes equations follows. The method consists of subdividing the time interval of existence into smaller sub-intervals carefully chosen. These sub-intervals are chosen based on the hypothesis that for any wavenumber m, one can find an interval of time on which the energy quantized in low-frequency components (up to m) of the solution u is lesser than the energy quantized in high-frequency components (down to m) or otherwise the opposite. We associate then a suitable number m to each one of the intervals and we prove that the norm ||u(t)||_H1 is bounded in both mentioned cases. The process can be continued until reaching the maximal time of existence T_max which yields the global in time existence of strong solution.

The importance of conflict analysis and safety considerations during work zone intervals at signalized intersections cannot be overstated, as these periods pose unique challenges and safety risks for both motorists and pedestrians. Work zones introduce temporary changes to traffic patterns, lane configurations, and signal timings, which can disrupt the flow of traffic and increase the likelihood of conflicts between vehicles and pedestrians. By conducting comprehensive conflict analysis, it is possible to identify potential conflict points, such as merging areas, pedestrian crossings, and lane transitions, and implement targeted safety measures to mitigate risks. Additionally, considering safety considerations during work zone intervals is paramount to safeguarding the well-being of road users and minimizing the occurrence of conflicts or collisions. Measures such as enhanced signage, temporary traffic control devices, and increased enforcement efforts can help promote compliance with traffic regulations and ensure the safe passage of vehicles and pedestrians through work zones. This study investigates the dynamics of traffic behavior and safety implications within work zones at signalized intersections, aiming to address key challenges and enhance intersection management strategies. Through comprehensive analysis, varying frequencies of Vehicle-to-Vehicle (V2V) conflicts were observed across different movement directions, with significant occurrences identified in specific phases of the traffic signal cycle. Specifically, 69 V2V conflicts in phase #1, 181 in phase #2, 31 in phase #3, 207 in phase #4, 1 in phase #5, 274 in phase #6, 93 in phase #7, and 186 in phase #8 were recorded. Furthermore, the examination of Vehicle-to-Pedestrian (V2P) conflicts underscored the importance of prioritizing pedestrian safety, with notable occurrences observed in phases associated with pedestrian crossing movements. Meanwhile, despite the closure of left-turn movements, instances of red light running persisted, with 69 red light running events in phase #1, 181 in phase #2, 31 in phase #3, 207 in phase #4, 1 in phase #5, 274 in phase #6, 93 in phase #7, and 186 in phase #8.To mitigate these safety concerns during work zone intervals, proactive measures are essential. Strategies include improving communication through clear signage and advanced warning systems, enhancing enforcement efforts with red light cameras and increased police presence, and investing in infrastructure improvements such as temporary pedestrian facilities. Integration of real-time data from sensors, particularly LiDAR technology, offers significant advantages in detecting conflicts and red light runners during work zone intervals. LiDAR's precise, real-time data on vehicle and pedestrian movements, combined with its 360-degree coverage and high spatial resolution, facilitates accurate detection and tracking of potential conflict scenarios, contributing to enhanced intersection safety and traffic management efficiency. This study endeavored to conduct a traffic safety analysis during work zone intervals at a signalized intersection in Baltimore City, known for its high rate of traffic crashes, utilizing LiDAR sensor technology.

In the decarbonization of the steel, cement, and chemical industry in Germany, green hydrogen is expected to play a crucial role. The utilization of green hydrogen in the production processes of said industries requires organizations to modify their business model, requiring sustainable business model innovation (SBMI). Numerous tools and frameworks that support organizations in the process of SBMI have been proposed in the literature in recent years. However, the applicability of these tools and frameworks for steel, cement, and chemical companies that intend to utilize green hydrogen to produce their goods remains unexplored. By conducting a systematic literature review on tools and frameworks for SBMI, a literature and practice review to identify and analyze existing green hydrogen projects of steel, cement, and chemical companies, and an evaluation of the identified tools and frameworks in an evaluation matrix, this paper aims to assess the suitability of SBMI tools and frameworks for steel, cement, and chemical companies that plan to use green hydrogen to produce their goods. Based on the evaluation, the Cambridge Business Model Innovation Process (CBMIP) was identified as the most suitable SBMI framework.

Sorghum grain processing can improve the nutritional content by promoting dietary properties that contribute to food security and economic development. The quality, nutritional content, and processing properties of sorghum bicolor grain can greatly affected by the inbred line races and variance in pericarp colour.The current study assessed the influence of the Husking Fraction Time Units (HFTU) process, which employed set time units per second (S), on the variation in the nutritional profile of fifty-one inbred line sorghum varieties based on distinct pericarp colours. When the assessment of the nutritional profile was involved: dry matter, total protein besides, namely mineral (P, K, S, Ca, Mg, Na, Fe, Zn, and Mn). The variety groups showed a significance value of (P < 0.05), indicating the study hypothesis's truth.The results demonstrated substantial impacts implied by the Husking Fraction Time Unit (HFTU) technique. This occurrence was noted when the dry matter percentage was increased in the husked products, specifically the endosperm (grits) and bran. The protein percentage redistributed by 19.2% compared to the whole grain and bran content. In comparison, the ratio of N/S was 14:1 in the S. bicolor and 12:1 in the kafirin in the bran part. Moreover, a strong correlation was observed among the examined minerals of S.bicolor and kafirin, such as the correlation between Ca: P, K: Na, and Fe: Zn attributed 80 (S) time unit, with correlation coefficients of R = 0.784 and R = 0.586, R= 517, R= 0.884, R= 0.745, and R = 0.893, respectively. At the same time, the 80 (S) time unit showed a significant effect on the colour property profile.The study results could benefit breeders and nutrition specialists in developing genotypes and processing sorghum grains, promoting research, and aiding several industrial sectors owing to the grain's adaptability and nutritional properties.

In this preliminary investigation, a concise molecular docking study using the Pyrx program screened thousands of compounds against the active site of HIV-1 reverse transcriptase. The Virtual Screening library was employed to assess binding energetics scores, focusing on identifying candidates with high Vina Scores. Eight compounds, including Tetrophan, Imatinib, Amentoflavone, Alprazolam, Bilobetin, Bafetinib, Nilotinib, and Ginketin, emerged as promising candidates with significant binding energies.Recognizing compounds that strongly bind to HIV-1 reverse transcriptase holds potential for antiretroviral drug development in the fight against HIV infection. Subsequently, the study evaluated the toxicity properties of these candidates using pKCSM. Amentoflavone, a natural biflavonoid found in Ginkgo biloba and Nilotinib, a tyrosine kinase inhibitor, demonstrated lower overall toxicity profiles compared to other candidates. Further toxicity analysis using Pro-Tox-II revealed Amentoflavone's higher predictive LD50, lower toxicity class, and reduced probabilities of hepatotoxicity, carcinogenicity, mutagenicity, and moderate immunotoxicity compared to Nilotinib. While Nilotinib, a pharmaceutical drug, exhibited higher probabilities of adverse effects in these categories. In summary, Amentoflavone and Nilotinib present as promising candidates with lower toxicity concerns. Amentoflavone, as a natural substance, showcases a more favorable toxicity profile than Nilotinib, offering valuable insights for potential therapeutic applications.

Background: Increase of collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. We hypothesized that COL I/COL III ratio is increased in the brain arteriovenous malformations (bAVMs), which is associated with bAVM hemorrhage. Method: Surgically resected human bAVM samples and mouse bAVMs induced in three transgenic mouse lines with activin receptor-like kinase 1 or endoglin deletion in the endothelial cells or in the brain focally. Colony-stimulating factor receptor inhibitor was used to transiently deplete microglia. COL I and COL III levels, hemorrhage, and gene expression in bAVMs were analyzed. Results: The COL I and COL III levels and the COL I/COL III ratio were higher on human and mouse bAVMs than controls, which was associated with bAVM hemorrhage. Col I and Col III mRNAs were also increased in mouse bAVMs. The degree of microhemorrhage in mouse bAVMs was positively correlated with Col I/Col III ratios. Transient depletion of microglia reduced Col I/Col III ratio and microhemorrhage in mouse bAVMs. Conclusion: COL I/COL III ratio are increased in bAVM vessels, which is associated with bAVM hemorrhage. Depletion of microglia reduces Col I/Col III ratio and hemorrhage in mice bAVMs.

An explanation of aerodynamic lift still is under controversial discussion as can be seen, for example, in a recent published article in Scientific American [1]. In contrast to an approach via integral conservation laws we here review an approach via the classical Kutta-Condition and its relation to boundary layer theory. Thereby we summarize known results for viscous correction to the lift coefficient for thin aerodynamic profiles and try to remember the work on triple-deck or higher order Boundary Layer theory, its connection to interactive boundary layer theory, viscous/inviscid coupling as implemented to well-known engineering code Xfoil. Finally we compare its findings to simple 2D numerical solution of full Navier Stokes equations (CFD)models. As a conclusion, a clearer definition of terms like understanding and explanation applied to the phenomenon of aerodynamic lift will be given.

This work aimed to characterize a DBD plasma equipment through optical and electrical measurements, seeking to obtain a greater knowledge of the plasma production process and how it behaves through the adopted parameters, such as frequency and voltage applied between electrodes, at a fixed distance of 1.7 mm. In order to measure them, three different characterization techniques were applied. The first method was the Lissajous figures, a technique quite effective for a complete electrical characterization of DBD equipment. The second technique used was the Optical Emission Spectroscopy, a tool used for the diagnosis of plasma, being it possible to identify the excited species produced in filamentary and diffuse discharge in the plasma. And finally, the triple Langmuir probe technique was used to obtain the electron temperature and electron density. Based on this study, it was possible to identify the equipment efficiency in different regimes. The electron temperature measurement for both systems analyzed were 27.96 eV and 20.69 eV to the filamentary and diffuse regimes, respectively. The density of electrons number to these regimes were 1.09 × 10²¹ m⁻³ and 1.56 × 10²¹ m⁻³.

Different from national systems of innovation, a knowledge-based economy is grounded in the volatility of discursive knowledge enabling us to specify expectations. Expectations can be improved by testing against observations. Furthermore, expectations can differently be codified; for example, in terms of market perspectives and technological opportunities. The Triple Helix of university-industry-government relations provides first a (neo-)institutional model. However, three functions are recombined at the systems level in each instantiation: wealth generation (by industry), novelty production (academia), and legislation and regulation (government). The Triple-Helix synergy indicator enables us to use the institutional arrangements as instantiations of the knowledge-dynamics and thus to assess the generation of options and reduction of uncertainty in information-theoretical terms. The Fourth Industrial Revolution entails the transition to the reflexive entertaining of expectations in terms of models as increasingly the sources of innovations.

To understand the mystery of final unification, in our earlier publications, we proposed that, 1) There exist three atomic gravitational constants associated with electroweak, strong and electromagnetic interactions; and 2) There exists a strong interaction elementary charge (e_s) in such a way that, it's squared ratio with normal elementary charge is close to inverse of the strong coupling constant. In this context, starting from lepton rest masses to stellar masses, we have developed many interesting and workable relations. We noticed that, electroweak field seems to be operated by a primordial massive fermion of rest energy 585 GeV. It can be considered as the zygote of all elementary particles and galactic dark matter. Proceeding further, with a characteristic fermion-boson mass ratio of 2.27, quarks can be classified into quark fermions and quark bosons. Considering strong charge conservation and electromagnetic charge conservation, fractional charge quark fermions and quark bosons can be understood. Quark fermions that generate observable massive baryons can be called as Fluons. Quark bosons that generate observable mesons can be called as Bluons. By considering a new hadronic fermion of rest energy 103.4 GeV, rest masses of fluons and bluons can be estimated and there by baryon masses and meson masses can be estimated.

The organic solar cells (OSCs) have drawn attention in the past decade due to its cynosure in industrial manufacturing because of its promising properties such as low weight, highly flexible and low cost production. However, low η restricts the utilization of OSCs for potential application such as low cost energy harvesting devices. In this paper, OSCs structure based on triple junction tandem scheme is reported with three different absorber materials with the objective to enhance the absorption of photons which in turn improves the η, as well as its correlating performance parameters. The investigated structure gives the higher value of η = 14.33% with Jsc=16.87 (mA/m2), Voc=1.0 (V), and FF=84.97% by utilizing a stack of three different absorber layers with different band energies. The proposed structure is tested under 1.5 (AM) with 1 sun (W/m2). The impact of top, middle and bottom sub cells thickness on η is analyzed with a terse to find the optimum thickness for three sub cells to extract high η. The optimized structure is then tested with different electrode combination and the highest η is recorded with FTO/Ag. Moreover, the influence of upsurge temperature is also demonstrated on the proposed structure and observed that the upsurge temperature has greatly affected the electrical parameters of the device and η decreases from 14.33% to 11.40% when the temperature of the device rises from 300-400 K.

Shipbreaking research has not been in the forefront until the last decade in which environmental and occupational hazards have been highlighted while economic sustainability and contextual conditions were not equally considered. The adoption of a triple bottom line approach across core business issues (environmental impacts, workplace safety ) as well as peripheral stakeholders expectation (environmental sustainability focus) has been retarded due to the less attention on the latter. Based on the findings of the 128 review papers, the study suggests that organizational learning and economic sustainability needs to prioritize through the formation of strange alliance among the stakeholders. The study argues that the dialogue and discussion on the peripheral stakeholders (NGOs, yard managers, national and international policy organizations) would lead to a more sustainable shipbreaking industry in the south Asian regions.

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

Background: Thyroid nodules are common, affecting nearly 65% of the general population. While they are widespread, it's crucial to recognize that the majority of these nodules are not cancerous and can be effectively managed through careful monitoring. Thyroid ultrasound is commonly used to evaluate thyroid nodules owing to its low cost, wide availability and technical ease of application. In sonography, it's crucial to assess characteristics and vascular flow. Yet, conventional color and power Doppler ultrasound may not always effectively capture small vessels and low velocities due to their limitations. Superior Microvascular Imaging can display the blood flow of small vessels and low-velocity blood flow, which is difficult to visualize with conventional Doppler ultrasound. Meanwhile other thyroid scans, that utilize either [99mTc] pertechnetate or (18)F-fluorodeoxyglucose, can categorize nodules as hyperactive ('hot'), exhibiting normal activity ('warm'), or having reduced/no activity ('cold'). Thus, the main goal of screening and tracking thyroid nodules is to improve the management of potentially worrisome thyroid malignancies. Methodology: The study was conducted within the structural framework of a network meta-analysis, with the index tests being - SMI, Radionuclide Scanning and Color Doppler, and the general link between them being the reference gold standard. The data collection involved searching for all pertinent literature using PubMed, Google Scholar, and the Cochrane Library databases. The essential data was extracted following the application of specific inclusion and exclusion criteria.This meta-analysis included 7 RCTs with 1,152 patients for Radionuclide Scanning, 10 RCTs with 1,847 patients for SMI and 8 RCTs with 4,480 patients for Color Doppler. They were analyzed using the QualSyst tool and the risk of bias was evaluated by using QUADAS-2 analysis.The statistical software packages MetaDiSc 1.4, RevMan (Review Manager, version 5.3), SPSS (Statistical Package for the Social Sciences, version 20) and Excel in Stata 14 were used to perform the statistical analyses. Result: According to the findings, the sensitivity for Radionuclide Scanning is calculated as 0.79 (range: 0.76 to 0.81) and specificity as 0.55 (range: 0.50 to 0.60) with a 95% confidence interval. The overall diagnostic odds ratio (DOR) for Radionuclide Scanning Is 10.54.Additionally, with a 95% confidence interval, SMI exhibits a sensitivity of 0.82 (with a range of 0.79 to 0.84) and a specificity of 0.86 (with a range of 0.84 to 0.88), while the overall DOR is approximately 25.73. Color Doppler demonstrates a calculated sensitivity of 0.71 (ranging from 0.69 to 0.74) and specificity of 0.81 (ranging from 0.79 to 0.83) with a 95% confidence interval, while its DOR is 13.48.Conclusion: As evidenced by this meta-analysis, blood flow dependent imaging techniques are superior in their abilities to be used as diagnostic tests, especially in conjunction with their use in detecting thyroid nodules. This study offers a starting point for delving deeper into the utilization of Radionuclide Imaging, Superior Microvascular Imaging and Color Doppler in diagnosing thyroid nodules in a clinical setting. Key Words: - Thyroid Nodule, Radionuclide Scanning, Superior Microvascular Imaging, Color Doppler Diagnosis, Sensitivity, Specificity, Diagnostic imaging

Harnessing the Remarkable Bio-Remediation Potential of Vernonia spp. for the Sustainable Restoration of Hydrocarbon-Polluted Clay Soil in Ogoni Land, Nigeria This study explores the potential of utilizing Vernonia spp. for eco-friendly bio-remediation of hydrocarbon-polluted clay soil in Ogoni Land, Nigeria. The aim is to find a sustainable and effective solution that promotes the restoration of the polluted soil while minimizing the use of external additives. The process of bio-remediation can occur naturally, through natural attenuation or intrinsic bio-remediation. However, it has been observed that in certain cases, the addition of fertilizers, oxygen, or organic matter is required to enhance the effectiveness of bio-remediation. In this research, we focus on the bio-remediation potential of Vernonia spp., a native plant species known for its strong phytoremediation abilities. By harnessing the remarkable bio-remediation properties of Vernonia spp., we seek to restore the hydrocarbon-polluted clay soil in Ogoni Land in an environmentally friendly and sustainable manner. Our methodology involves conducting greenhouse experiments to assess the bio-remediation efficiency of Vernonia spp. in different soil conditions. We will analyze the soil's physical and chemical properties, as well as the degradation of hydrocarbons over time. The experimental results will provide valuable insights into the effectiveness of Vernonia spp. in removing hydrocarbon pollutants from clay soil. Through this study, we aim to develop a cost-effective and sustainable approach to restore hydrocarbon-polluted clay soil in Ogoni Land. By leveraging the natural bio-remediation potential of Vernonia spp., we can potentially reduce the reliance on external additives, thus minimizing the environmental impact associated with traditional remediation methods. The research article explores methods to promote the growth of pollution-eating microbes in order to enhance bio-remediation. Bio-remediation refers to the use of naturally occurring organisms to break down harmful substances into less toxic or non-toxic forms. In situ bio-remediation involves treating the contaminated material directly at the site, while ex-situ bio-remediation involves removing the contaminated material for treatment elsewhere. This study specifically investigates ex-situ bio-remediation techniques for hydrocarbon-contaminated clay soil. The researchers found that the application of room dry and wet blended bitter leaf showed promising results in the bio-remediation of hydrocarbons in the clay soil. Using Vernonia galamensis, a concentration as high as 0.55 ug/ml was achieved, while Vernonia amygdalina yielded a concentration as high as 0.67 ug/ml when applied at 35g and 40g respectively, based on the wet blended approach. These findings highlight the effectiveness of wet blended Vernonia species in the bio-remediation process.During the remediation process of the clay soil, the pH levels showed a trend of increasing from acidic to normal to alkaline. This can be attributed to the remediation of excessive metals present in the soil. After 40 days, the pH of the clay soil reached 6.97 when treated with 40 grams of Vernonia galamensis, and 7.00 when treated with 40 grams of Vernonia amygdalina. Interestingly, while the remediation efficiency of HC (hydrocarbon) decreased with increasing mass of Vernonia galamensis, the remediation efficiency of HC increased when using Vernonia amygdalina. These observations highlight the varying effects of different Vernonia species on hydrocarbon remediation.The highest remediation values were observed when using Vernonia galamensis at 35g and Vernonia amygdalina at 40g. These particular amounts of these Vernonia species demonstrated effective remediation of the targeted pollutants. However, in comparison to other metals, the remediation effects were relatively lower for zinc (Zn), with only approximately 0.25 ug/ml being remediated. This suggests that the remediation potential of the Vernonia species may vary depending on the specific contaminant.The higher remediation effects observed for Zn metal in the soil can be attributed to the wet blended preparation method of the Vernonia species. In contrast, the room dried Vernonia species exhibited the lowest performance in remediating the soil, with approximately 0.17 ug/ml and 0.10 ug/ml remediation for galamensis and amygdalina, respectively. Both Vernonia leaf extracts achieved a remediation of 0.5 ug/ml for chromium. The sun dried and room dried methods also showed considerable remediation potential, with values above 0.4 ug/ml. The level of significance for the model was attained at 0.05, and the r2 value was appreciable. These findings indicate the effectiveness of different preparation methods and Vernonia species in soil remediation