Search Results (11,650)

The green ecological property is increasingly recognized as a sustainable option in remanufacturing. In practice, despite the environmental concerns expressed by consumers, the growth of the remanufacturing industry falls short of expectations, largely due to the fact that, although remanufacturing conserves costs and is beneficial to our environment, it may not be a profitable option for OEMs, a major barrier in its appearance to green consumers. Many researchers have proposed that environmental groups and similar entities should provide necessary subsidies to encourage green consumerism and improve the profitability of the remanufacturing industry. In this paper, we intend to address how the subsidy policy on green consumerism impacts an OEM’s incentives in remanufacturing; more specifically, we develop two theoretical models: Model N, in which the OEM does not undertake remanufacturing, and Model R, in which the OEM does undertake remanufacturing under the subsidy policy for encouraging green consumerism. In addition to confirming the traditional wisdom that the subsidy policy encourages the remanufacturing industry, our analysis surprisingly reveals that, if a few consumers characterize green consumerism, the aggressive subsidy policy may potentially result in a cannibalization problem, in which remanufacturing hurts the OEM’s overall profits. Therefore, the government and environmental protection agencies need to fully consider the characteristics of the industry to avoid a “good intention, bad result” situation. Full article

Background: Multiparametric MRI (mpMRI) as a non-invasive imaging tool is important in prostate cancer (PCa) detection and localization. Combined with radiomics analysis, features extracted from mpMRI have been utilized to predict PCa aggressiveness. T2 mapping provides quantitative information in PCa diagnoses but is not routinely available in clinical practice. Previous work from our group developed a deep learning-based method to estimate T2 maps from clinically acquired T1- and T2-weighted images. This study aims to evaluate the added value of the estimated T2 map by combining it with conventional T2-weighted images for detecting clinically significant PCa (csPCa). Methods: An amount of 76 peripheral zone prostate lesions, including clinically significant and insignificant cases, were retrospectively analyzed. Radiomic features were extracted from conventional T2-weighted images and deep learning-estimated T2 maps, followed by feature selection and model development using five-fold cross-validation. Logistic regression and Gaussian Process classifiers were employed to develop the prediction models, with performance evaluated by area under the curve (AUC) and accuracy metrics. Results: The model incorporating features from both T2-weighted images and estimated T2 maps achieved an AUC of 0.803, significantly outperforming the model based solely on T2-weighted image features (AUC of 0.700, p = 0.048). Conclusions: Radiomics features extracted from deep learning-estimated T2 maps provide additional quantitative information that improves the prediction of peripheral zone csPCa aggressiveness, potentially enhancing risk stratification in non-invasive PCa diagnostics. Full article

Breast Cancer (BrCa) exhibits a high phenotypic heterogeneity, leading to the emergence of aggressive clones and the development of drug resistance. Considering the BrCa heterogeneity and that metabolic reprogramming is a cancer hallmark, we selected seven BrCa cell lines with diverse subtypes to provide their comprehensive metabolome characterization: five lines commonly used (SK-Br-3, T-47D, MCF-7, MDA-MB-436, and MDA-MB-231), and two patient-derived xenografts (Hbcx39 and Hbcx9). We characterized their endometabolomes using ¹H-NMR spectroscopy. We found distinct metabolite profiles, with certain metabolites being common but differentially accumulated across the selected BrCa cell lines. High levels of glycine, lactate, glutamate, and formate, metabolites known to promote invasion and metastasis, were detected in all BrCa cells. In our experiment setting were identified unique metabolites to specific cell lines: xanthine and 2-oxoglutarate in SK-Br-3, 2-oxobutyrate in T-47D, cystathionine and glucose-1-phosphate in MCF-7, NAD⁺ in MDA-MB-436, isocitrate in MDA-MB-231, and NADP⁺ in Hbcx9. The unique and enriched metabolites enabled us to identify the metabolic pathways modulated in a cell-line-specific manner, which may represent potential candidate targets for therapeutic intervention. We believe this study may contribute to the functional characterization of BrCa cells and assist in selecting appropriate cell lines for drug-response studies. Full article

The Wnt signaling pathway is critical in the onset and progression of gastrointestinal (GI) cancers. Anomalies in this pathway, often stemming from mutations in critical components such as adenomatous polyposis coli (APC) or β-catenin, lead to uncontrolled cell proliferation and survival. In the case of colorectal cancer, dysregulation of the Wnt pathway drives tumor initiation and growth. Similarly, aberrant Wnt signaling contributes to tumor development, metastasis, and resistance to therapy in other GI cancers, such as gastric, pancreatic, and hepatocellular carcinomas. Targeting the Wnt pathway or its downstream effectors has emerged as a promising therapeutic strategy for combating these highly aggressive GI malignancies. Here, we review the dysregulation of the Wnt signaling pathway in the pathogenesis of GI cancers and further explore the therapeutic potential of targeting the various components of the Wnt pathway. Furthermore, we summarize and integrate the preclinical evidence supporting the therapeutic efficacy of potent Wnt pathway inhibitors with completed and ongoing clinical trials in GI cancers. Additionally, we discuss the challenges of Wnt pathway-targeted therapies in GI cancers to overcome these concerns for effective clinical translation. Full article

Glioblastoma (GB) is a highly malignant brain tumor with a poor prognosis, with a median survival of only 14.6 months despite aggressive treatments. Resistance to chemotherapy, particularly temozolomide (TMZ), is a significant challenge. The DNA repair enzyme MGMT and glioblastoma stem cells (GSCs) often mediate this resistance. Recent studies highlight the therapeutic potential of natural compounds, particularly delphinidins, found in deep purple berries. Delphinidins are known for their ability to inhibit NF-κB signaling, a critical pathway for GB progression, chemoresistance, and MGMT expression. Our research demonstrates that glycosylated delphinidins have potential adjuvant use in the treatment of GB, offering a promising natural strategy to combat TMZ resistance. Specifically, we observed that delphinidin 3,5 di-glucoside has potent anticancer effects when used alone. Meanwhile, delphinidin 3 glucoside acted in synergy with temozolomide to decrease cell viability, highlighting its potential as an adjuvant. It also exerted a faster and more sustained inhibition of NF-κB, highlighting its potential for long-lasting therapeutic effects. These findings open new avenues for targeted therapies against glioblastoma, particularly to overcome treatment resistance. Full article

Background: Multiple endocrine neoplasia type 2A (MEN 2A) is a rare hereditary cancer syndrome caused by pathogenic variants in the rearranged during transfection (RET) gene and is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), primary hyperparathyroidism (PHPT), cutaneous lichen amyloidosis (CLA), and Hirschsprung’s disease. Phenotypic data on the RET C611Y variant remain sparse. Consequently, we aimed to establish a clinical risk profile. Methods: We conducted a nationwide study of all cases (n = 128) born after 1 January 1930 and recognized as carrying the RET C611Y variant in Denmark before 1 April 2021. Results: The median follow-up after birth was 47 years (range, 3–92). Age-related penetrance at age 70 years for MTC was 98% (CI, 91–100), for PHEO 24% (CI, 16–37), and for PHPT 10% (CI, 5–20). None had CLA or Hirschsprung’s disease. The age-related progression of MTC was significant (p < 0.001). The median age at T0N0M0 was 11 years (2–62), at T1-4N0M0 was 37 years (12–65), at TxN1M0 was 47 years (16–79), and at TxNxM1 was 50 years (28–70). At the last follow-up, 56% of thyroidectomized cases (n = 103) were biochemically cured. Overall survival at 70 years was 74% (CI, 59–84). Conclusions: RET C611Y is associated with a very high penetrance of MTC and a low penetrance of PHEO and PHPT. CLA and Hirschsprung’s disease almost never occur. MTC seems moderately aggressive, but large variability can be seen. Overall survival may be comparable to that of the general population. Full article

Periprostatic adipose tissue (PPAT) contributes to the pathogenesis of prostate cancer. The purpose of this study was to review and summarize the literature on the role of PPAT in prostate cancer pathogenesis. Moreover, we evaluated the clinical implication of PPAT in patients with prostate cancer. We performed a scoping literature review of PubMed from January 2002 to November 2024. Search terms included “periprostatic adipose tissue”, “adipokines”, and “prostate cancer”. Secondary search involved reference lists of eligible articles. The key criterion was to identify studies that included PPAT, adipokines, and their role in prostate cancer biology and clinical features. In total 225 publications were selected for inclusion in this review. The studies contained in publications allowed us to summarize the data on the pathogenesis of PPAT as a contributor to prostate cancer biology and its aggressiveness. The review also presents new research directions for PPAT as a new target for the treatment of prostate cancer. Based on the current review, it can be stated that PPAT plays an important role in prostate cancer pathogenesis. Moreover, PPAT seems to be a promising target point when it comes to finding new therapies in patients with more aggressive and/or advanced stages of prostate cancer. Full article

Epithelial-to-mesenchymal transition (EMT) is a critical process in malignant ovarian cancer metastasis. EMT involves the conversion of epithelial cells to mesenchymal cells, conferring enhanced migratory and invasive capabilities. Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor and exhibits an aggressive invasive phenotype that mimics some steps of EMT but does not undergo true metastasis, i.e., the invasion of other organ systems. This study conducts a comparative genomic analysis of EMT in ovarian cancer and invasion in GBM—two malignancies characterized by poor prognosis and limited therapies. Investigating the molecular biology in ovarian cancer and GBM demonstrates shared mechanisms of tumor progression, such as similar genetic and molecular pathways influencing cell plasticity, invasion, and resistance to therapy. The comparative analysis reveals commonalities and differences in the regulatory networks and gene expression profiles associated with EMT and invasion in these cancers. Key findings include the identification of core EMT regulators, such as TWIST1, SNAIL, and ZEB1, which are upregulated in both ovarian cancer and GBM, promoting mesenchymal phenotypes and metastasis. Additionally, the analysis uncovers EMT-related pathways, such as the PI3K/AKT and TGF-β signaling, which are critical in both cancers but exhibit distinct regulatory dynamics. Understanding the intricacies of EMT in ovarian cancer and invasion in GBM provides valuable insights into their aggressive behavior and identifies potential common therapeutic targets. The findings stress the importance of targeting EMT/invasion transitions to develop effective treatments to halt progression and improve patient outcomes in these malignancies. Full article

It has been shown that the pathogenic variants (PVs) of the DNA Damage Response (DDR) genes, whether of a germinal or somatic nature, represent a predictive biomarker of high sensitivity to treatment with inhibitors of the enzyme poly-ADP-ribose polymerase (PARP) in patients with hormone-resistant metastatic prostate cancer (HRPCa). Moreover, the detection of PVs of the Homologous Recombination Repair (HRR) genes in PCa patients can help to define the patient’s prognosis and the choice of the therapeutic procedure. Among men with metastatic PCa, the frequency of PVs in HRR genes ranges from 11% to 33%, which is a significantly higher rate compared to non-metastatic PCa, where the incidence is between 5% and 10%. Next-Generation Sequencing (NGS) results were more commonly obtained from newly acquired somatic samples compared to archived samples (prostate biopsy or prostatectomy). We developed an experimental multidisciplinary prospective study in patients with a new diagnosis of high-risk PCa at biopsy. The aim was to evaluate the presence of PVs of different HRR genes in patients with the first diagnosis of PCa in relation to a metastatic or non-metastatic stage, tumor aggressiveness, and early risk of progression. Among 43 initial tumor samples from 22 patients, 25 samples from 12 patients were selected for library preparation based on their DNA concentration and quality. After the NGS, 14 different DNA variants were prioritized. Oncogenetic and likely oncogenetic variants were found in the ATM, BRCA1, PTEN, KMT2D, and CDH1 genes. Moreover, variants of uncertain significance were found in ATM, DDR2, FANCA, FOXA1, PLCB4, PTCH1, and RB1. Full article

This study examines the association between problematic internet use, or internet addiction, and adolescent mental health, focusing on key psychological variables, assessing the strength of these associations, and identifying potential moderating factors. Methods: A search of the Web of Science databases over the past five years identified 830 articles. Of these, 33 met the inclusion criteria, involving 303,243 participants (average age 14.57; 49.44% female). The selection process was verified by two researchers. Results: Nine psychological variables were analyzed: depression, anxiety, stress, suicidal behaviour, psychological well-being, self-esteem, externalizing problems, aggressiveness, and impulsiveness. Internet addiction showed positive correlations with aggressiveness (r+ = 0.391), depression (r+ = 0.318), anxiety (r+ = 0.252), and suicidal behaviour (r+ = 0.264). Negative correlations were observed with psychological well-being (r+ = −0.312) and self-esteem (r+ = −0.306). No significant associations were found for externalizing problems, impulsiveness, or stress. None of the moderators showed a significant correlation with internet addiction and depression. Conclusions: Although limited by small sample sizes for some variables and the cross-sectional design of most studies, the findings confirm that there is a negative relationship between internet addiction and adolescent mental health. It is related to poorer self-perceived health, greater psychological distress, and greater aggression. Full article

Background and objectives: We aimed to assess the significance of sex and age compared to other clinical-pathological parameters in colorectal cancer (CRC). Materials and methods: Our study included a retrospective approach to CRC patients who underwent surgery at the ‘Pius Brinzeu’ County Clinical Emergency Hospital in Timisoara (PBECCHT), Romania. The analyzed parameters were: patient age and sex, tumor location, histological type, differentiation grade (G), extent of tumor (pT), lymph-node status (pN), distant metastasis status (pM), and lymphovascular invasion (LVI). The population was divided into three groups based on age, with those under 49 years old, 50 to 69 years old, and elderly (>70). Results: The study’s inclusion criteria were met by 1885 patients, with a male-to-female ratio of 1.39:1. There were significant differences between the sexes in the anatomical location of tumors (p < 0.0001). Younger patients were more likely to have deeply invasive tumors (p = 0.0096), LVI (p = 0.0332), lymph-node metastases (p = 0.0158), and metastatic disease (p = 0.0017). Conclusions: Over the ten-year period reviewed, the frequency of CRC cases has progressively increased, with males being diagnosed more often. In terms of patient age, the young population exhibits clinical features of aggressive evolution. Patient sex did not influence the analyzed parameters, except for tumor location, where right colon tumors are slightly more common in females. Full article

Radiomics and deep learning computer vision algorithms can extract clinically relevant information from medical images, providing valuable insights for accurate diagnosis of cancerous lesions, tumor differentiation and molecular subtyping, prediction of treatment response, and prognostication of long-term outcomes. In head and neck squamous cell carcinoma (HNSCC), growing evidence supports the potential role of radiomics and deep learning models in predicting treatment response, long-term outcomes, and treatment complications following radiation therapy. This is especially important given the pivotal role of radiotherapy in early-stage and locally advanced HNSCC, as well as in post-operative and concomitant chemoradiotherapy. In this article, we summarize recent studies highlighting the role of radiomics in predicting early post-radiotherapy response, locoregional recurrence, survival outcomes, and treatment-related complications. Radiomics-guided tools have the potential to personalize HNSCC radiation treatment by identifying low-risk patients who may benefit from de-intensified therapy and high-risk individuals who require more aggressive treatment strategies. Full article

Objective: Intrauterine resuscitation (IR) may be employed during labor to reduce emergency deliveries with concerns for fetal wellbeing emanating mostly from increased uterine contraction frequency and/or intensity. However, there is no standard definition of what constitutes IR, and how its impact is assessed. Here, we have created two measures of relative IR effectiveness, determined over a two-hour time frame after Pitocin was first initiated, and asked how fetal risk severity at the time of its initiation impacted IR effectiveness and the clinical decisions made. Methods: We analyzed 118 patients receiving Pitocin who underwent IR at least once during labor. Retrospectively, we assessed risk levels using our Fetal Reserve Index version 2 (FRI v2) scores that were calculated in 20 min timeframes. FRIv2 scores include various maternal, obstetric, and fetal risk factors, uterine contraction frequency, and FHR baseline rate, variability, accelerations, and decelerations. We define 3 IR scenarios to assess relative IR effectiveness. (1) No reduction in PIT infusion rates (PITSAME), (2) decreased PIT infusion rates (DPIT), or (3) PIT turned off (PIT OFF). Maternal repositioning and oxygen administration are nearly universal across all types and, therefore, are not considered in groupings. We then created two measures of IR effectiveness by classifying changes in FRI v2 scores over six 20 min windows coincident with and following IR use as (1) “Improvement” (improvement relative to the FRIv2 score at IR initiation) and (2) “Stabilization” (no further decrease in FRI score relative to the FRIv2 score in the sixth 20 min epoch after IR initiation). We evaluated the relative effectiveness of the three PIT options, and to test whether the level of fetal risk at the time of IR initiation affected its short-term effectiveness, FRI v2 risk scores were assigned to one of three groups (Green [1.00–0.625]; Yellow [0.50–0.25]; Red 0.25–0.0]). Higher scores indicate lower risk. Statistical analysis was performed with ANOVA and t- tests. Results: Overall, the first and/or the only initiation of IR resulted in improvement in 71% of cases and stabilization in 78% of cases. The remaining 22% were failures, meaning that the FRIv2 score in the 6th 20 min period was lower than the score at the time of initiation. There were modest, but not statistically significant, differences in effectiveness (improvement or stabilization) by type of IR. There was a trend toward lower IR effectiveness of PIT OFF during IR initiation when compared to PIT continuation or decreased groups. Conclusions: IR initiation or type did not vary significantly by retrospectively calculated levels of fetal risk, showing that wide variation in clinician practices, not necessarily correlated with what we believe actual risk was, determine how IR was used. The FRI provides contextualization of FHR elements by adding maternal, fetal, and obstetric risk factors, and increased uterine activity enables a more rigorous and reproducible approach to analysis of emerging fetal compromise and IR effectiveness. As practice has shifted from the over-aggressiveness of PIT use to now premature discontinuations with any tracing variation, we need better metrics. FRIv2 further improves its physiologic underpinnings. Thus, we propose a new approach to the overall assessment of IR practice. Full article

Background: Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies and has a poor prognosis. Ataxia telangiectasia mutated and Rad3 related (ATR) is a key regulator for the DNA damage response and a potential target to treat cancer. Methods: We assessed the efficacy of BAY 1895344, an ATR inhibitor, in three ATC cell lines. Results: BAY 1895344 caused dose–response cytotoxicity in three ATC cell lines. BAY 1895344 induced S-phase and G2-phase arrest, activated caspase-3 activity and induced apoptosis in ATC cells. BAY 1895344 meaningfully retarded the tumor growth of an ATC xenograft model. BAY 1895344 therapy, combined with dabrafenib and trametinib, had synergism in vitro and revealed robust tumor growth suppression in vivo in two xenograft models of ATC harboring mutant BRAF^V600E. Furthermore, the combination of BAY 1895344 with lenvatinib was more effective than either agent alone in a xenograft model of ATC. Conclusions: These results reveal that BAY 1895344 has potential in treating ATC. Full article

Background: Atrial fibrillation (AF) and ischemic stroke (IS) are intricately linked to chronic obstructive pulmonary disease (COPD). Patients who suffer from both COPD and AF demonstrate a 2.85-fold greater risk of IS. However, the long-term risk remains insufficiently explored. Methods: This study utilized data from the Taiwanese National Health Insurance dataset spanning 2000 to 2015. Patients who were newly diagnosed with COPD, identified using the International Classification of Disease, Ninth Revision, Clinical Modification [ICD-9-CM] codes of 491, 492, and 496 and diagnosed with AF (ICD-9-CM code 427.3), were included in the study. The measured events included ISs (ICD-9-CM codes 433–437). Multivariate Cox proportional hazard models were employed to evaluate IS risk factors in this longitudinal analysis. Results: The combined presence of COPD and AF increased the risk of IS, with an adjusted hazard ratio of 5.722 (95% CI: 2.737–8.856, p < 0.001), AF without COPD with an adjusted HR of 3.506 (95% CI: 1.459–5.977, p < 0.001), and COPD with AF with an adjusted HR of 2.215 (95% CI: 1.099–3.538, p < 0.001) compared with patients without COPD and AF. Elderly patients exhibited a greater burden of cardiovascular comorbidities, including obstructive sleep apnea, thus further compounding the risk of IS. Conclusions: The coexistence of COPD and AF was associated with a markedly elevated risk of IS. The result highlights the additive and synergistic contributions of COPD and AF to the risk for IS. Aggressive treatment may mitigate the risk of IS. Full article