Search Results (156)

The treatment landscape of metastatic hormone-sensitive prostate cancer (mHSPC) has transformed significantly with the advent of triplet therapy involving androgen deprivation therapy (ADT), docetaxel, and androgen receptor signalling inhibitors (ARSIs). While clinical guidelines increasingly support early intensification, real-world practice remains challenged by patient heterogeneity, evolving evidence, and limited consensus on treatment sequencing. This narrative review integrates evidence from landmark trials, clinical guidelines, and expert insights from oncologists managing mHSPC in India. Findings affirm that triplet therapy, particularly with darolutamide, improves survival in high-volume disease and underscores the need for personalized treatment based on disease burden, comorbidities, and genomic profiles. The review also highlights gaps in real-world data, sequencing strategies, and biomarker-driven therapy, reinforcing the need for precision medicine and locally relevant evidence to guide treatment. Ultimately, optimizing mHSPC management requires harmonizing guideline-based approaches with individualized, real-world decision making to improve patient outcomes. Full article

Background: Prostate cancer (PC) is the second leading cause of cancer-related death in men in the United States. A subset of patients develops non-metastatic, castration-resistant PC (nmCRPC), for which management requires a personalized consideration for appropriate treatment. However, there is no consensus regarding when to switch from androgen deprivation therapy (ADT) to more aggressive treatments like abiraterone or enzalutamide. Methods: We analyzed 5037 nmCRPC patients and employed a Weibull Time to Event Recurrent Neural Network to identify patients who would benefit from switching from ADT to abiraterone/enzalutamide. We evaluated this model using differential treatment benefits measured by the Kaplan–Meier estimation and milestone probabilities. Results: The model achieved an area under the curve of 0.738 (standard deviation (SD): 0.057) for patients treated with abiraterone/enzalutamide and 0.693 (SD: 0.02) for patients exclusively treated with ADT at the 2-year milestone. The model recommended 14% of ADT patients switch to abiraterone/enzalutamide. Analysis showed a statistically significant absolute improvement using model-recommended treatments in progression-free survival (PFS) of 0.24 (95% confidence interval (CI): 0.23–0.24) at the 2-year milestone (PFS rate increasing from 0.50 to 0.74) with a hazard ratio of 0.44 (95% CI: 0.39–0.50). Conclusions: Our model successfully identified nmCRPC patients who would benefit from switching to abiraterone/enzalutamide, demonstrating potential outcome improvements. Full article

Background/Objectives: Androgen deprivation therapy (ADT) is widely used to manage prostate cancer (PC), but the emergence of treatment resistance remains a major clinical challenge. Although the GST family has been implicated in drug resistance, the specific role of GSTM5 remains poorly understood. This study investigates whether GSTM5, alone or in combination with clinical variables, can improve patient stratification based on the risk of early treatment resistance. Methods: In silico analyses were performed to examine GSTM5’s role in protein interactions, molecular pathways, and gene expression. The rs3768490 polymorphism was genotyped in 354 patients with PC, classified by ADT response. Descriptive analysis and logistic regression models were applied to evaluate associations between genotype, clinical variables, and ADT response. GSTM5 expression related to the rs3768490 genotype and ADT response was also analyzed in 129 prostate tissue samples. Results: The T/T genotype of rs3768490 was significantly associated with a lower likelihood of early ADT resistance in both individual (p = 0.0359, Odd Ratios (OR) = 0.18) and recessive models (p = 0.0491, OR = 0.21). High-risk classification according to D’Amico was strongly associated with early progression (p < 0.0004; OR > 5.4). Combining genotype and clinical risk improved predictive performance, highlighting their complementary value in stratifying patients by treatment response. Additionally, GSTM5 expression was slightly higher in T/T carriers, suggesting a potential protective role against ADT resistance. Conclusions: The T/T genotype of rs3768490 may protect against ADT resistance by modulating GSTM5 expression in PC. These preliminary findings highlight the potential of integrating genetic biomarkers into clinical models for personalized treatment strategies, although further studies are needed to validate these observations. Full article

Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy with rising incidence and poor prognosis. TP53, previously identified as the most frequently mutated gene in EAC in our studies, plays a central role in tumor suppression and regulation. However, the metabolic consequences of TP53 mutations in EAC remain largely uncharacterized. We metabolically profiled three TP53-mutant EAC cell models (OE33, OE19, and FLO1) representing progressive stages of tumor differentiation and harboring distinct TP53 alterations. Our analyses revealed different metabolic phenotypes associated with TP53 status. OE33 cells predominantly use glycolytic metabolism but display limited adaptability to environmental changes, possibly due to a higher differentiation state. FLO1 cells exhibit a strong glycolytic dependence, elevated lactate production, and robust proliferation under acidic conditions, consistent with an aggressive and metastatic phenotype. OE19 cells preferentially utilize oxidative phosphorylation, demonstrated by resilience to glucose and glutamine deprivation, and ROS accumulation. These findings highlight the metabolic plasticity of EAC and suggest that TP53 mutation type might influence bioenergetic dependencies. Targeting these metabolic vulnerabilities may offer novel therapeutic avenues for personalized treatment in EAC. Full article

Personal relative deprivation (PRD) is closely linked to a range of mental health problems. In the digital era, the association between social media use and PRD has received increasing attention. However, most studies have been conducted in Western contexts, and the underlying mechanisms in China remain unclear. This study examined the relationship between social media use and PRD among 2504 adult urban residents in China. Based on relative deprivation theory, it further explored the mediating role of subjective social status and the moderating role of belief in a just world. Results revealed that social media use was negatively associated with PRD. Subjective social status mediated this relationship: social media use was positively associated with subjective social status, while subjective social status was negatively associated with PRD. Moreover, belief in a just world strengthened the direct negative link between social media use and PRD, as well as the positive link between social media use and subjective social status. These findings suggest that social media are not always a risk factor for mental health. Their impact should be considered within specific cultural contexts and regulatory policies. Full article

Background: Sleep is a fundamental component of health, and deprivation has been linked to numerous adverse outcomes, including reduced academic and occupational performance, greater risk of accidents, and increased susceptibility to chronic diseases and premature mortality. Dietary and lifestyle behaviors are increasingly recognized as key determinants of sleep quality. Women are particularly susceptible to sleep disturbances due to hormonal fluctuations and psychosocial factors. However, women remain underrepresented in sleep research. This study aims to examine the associations between sleep quality, nutrition, and lifestyle in a large cohort of Spanish women. Methods: A cross-sectional study was conducted with 785 women aged 18–64. Participants completed the Pittsburgh Sleep Quality Index (PSQI) and the NutSo-HH questionnaire on dietary and lifestyle behaviors. Descriptive analyses, correlation matrices, Gaussian Graphical Models, and Principal Component Analyses were used to assess relationships between variables. Results: More than half of the participants rated their sleep quality as good or very good, although over 30% experienced frequent nighttime awakenings. Poor sleep quality was significantly associated with higher alcohol consumption, lower vegetable and white fish intake, and lower levels of physical activity. Diets rich in ultra-processed foods correlated moderately with subjective poor sleep and daytime dysfunction. However, no strong associations were found between stimulant consumption, late meals, or dietary patterns (e.g., Mediterranean diet) and sleep. Self-perceived health emerged as a protective factor, while nocturnal lifestyles were linked to longer sleep latency and fragmented sleep. Conclusions: In adult women, better sleep quality is linked to healthy dietary choices, regular physical activity, and a positive perception of general health. In contrast, alcohol use and irregular lifestyles are associated with poor sleep. Individual variability and cultural adaptation may moderate the impact of some traditionally harmful behaviors. Personalized, multidimensional interventions are recommended for promoting sleep health in women. Full article

Background: This study aimed to develop a predictive model for acute gastrointestinal (GI) and genitourinary (GU) toxicity in prostate cancer patients treated with salvage radiotherapy (SRT) post-prostatectomy, using machine learning techniques to identify key prognostic factors. Methods: A multicenter retrospective study analyzed 454 patients treated with SRT from three Italian radiotherapy centers. Acute toxicity was assessed using Radiation Therapy Oncology Group criteria. Predictors of grade ≥ 2 toxicity were identified through Least Absolute Shrinkage and Selection Operator (LASSO) regression and Classification and Regression Tree (CART) modeling. The analyzed variables included surgical technique, clinical target volume (CTV) to planning target volume (PTV) margins, extent of lymphadenectomy, radiotherapy technique, and androgen-deprivation therapy (ADT). Results: No patients experienced grade ≥ 4 toxicity, and grade 3 toxicity was below 1% for both GI and GU events. The primary determinant of acute toxicity was the surgical technique. Open prostatectomy was associated with significantly higher grade ≥ 2 GI (41.8%) and GU (35.9%) toxicity compared to laparoscopic/robotic approaches (18.9% and 12.2%, respectively). A CTV-to-PTV margin ≥ 10 mm further increased toxicity, particularly when combined with extensive lymphadenectomy. SRT technique and ADT were additional predictors in some subgroups. Conclusions: SRT demonstrated excellent tolerability. Surgical technique, CTV-to-PTV margin, and treatment parameters were key predictors of toxicity. These findings emphasize the need for personalized treatment strategies integrating surgical and radiotherapy factors to minimize toxicity and optimize outcomes in prostate cancer patients. Full article

The widespread adoption of mobile work, driven by advancements in information and communication technology, has increasingly blurred the boundaries between work and personal life. This phenomenon can increase job stress, potentially leading to sleep deprivation, which affects not only employees’ health and well-being but also organizational performance. Grounded in Conservation of Resources theory, this study examines the pathway through which mWork contributes to sleep deprivation, focusing on the mediating role of job stress, and investigates the moderating effects of gender and number of children on this relationship. Data were collected using a stratified random sampling method across three waves with 4-week intervals, involving 325 employees in South Korea engaged in diverse occupations, including the administrative, technical, service, and sales sectors. The findings reveal that mWork increases sleep deprivation through the mediation of job stress. Furthermore, the relationship between mWork and job stress was found to vary depending on gender and number of children, with stronger moderating effects observed among women and employees with children. This study underscores the need for organizations to develop tailored management strategies that address the unique challenges posed by mWork, taking particular note of employees’ gender and family responsibilities. By mitigating the negative effects of mWork on job stress and sleep deprivation, organizations can enhance employee well-being and promote sustainable long-term performance. Full article

The article seeks to read the contribution of religious practices in prison education within the broader framework of spirituality as a search for meaning in life. It argues that religious engagement can foster cognitive and emotional development, providing inmates with a sense of purpose, community, and resilience that supports their reintegration into society. In light of an exceptional and extremely significant experience with APAC in Brazil’s police-free prison model, the authors aim to highlight the nexus between spirituality and re-education in contexts of deprivation and restriction of personal liberty. Indeed, the APAC (Association for the Protection and Assistance of the Convicted) model, central to this study, emphasizes nonviolent coexistence, responsibility, and spiritual care as part of its rehabilitative framework, with a significant reduction in recidivism rates and costs compared to traditional prisons. The model’s approach, grounded in a collective sense of responsibility and spirituality, aligns with Viktor Frankl’s and Paulo Freire’s theories on meaning and liberation, illustrating how spirituality can transform prison environments and promote social justice. The study concludes that spirituality in prisons not only aids individual redemption but also calls for structural changes to support reintegration, marking a shift towards a more human-centered penitentiary system. Full article

This narrative review examines the issue of sleep deprivation among children and adolescents in Japan, exploring its cultural origins and evaluating the current state of sleep education and interventions. It emphasizes the profound influence of the Bushidō spirit, with its focus on self-sacrifice and asceticism, as a core factor in the undervaluation of sleep in Japanese society. While educational initiatives and interventions highlighting the importance of sleep exist, significant limitations remain in improving sleep habits. Sleep deprivation continues to affect children and adolescents, despite its considerable impact on mental health and academic performance. This review presents a method for personalized sleep duration estimation and assesses its potential impact on improving sleep health by using optimal sleep duration calculations. The review also proposes practical steps to improve sleep duration through individualized strategies, integrating cultural context to mitigate the serious health risks associated with insufficient sleep. Ultimately, it underscores the need for targeted strategies to improve sleep among children and adolescents—particularly through personalized optimal sleep duration estimation—while advocating for a shift in cultural perspective beyond self-sacrifice and asceticism. The review highlights the importance of cultural transformation and suggests future research directions and practical applications. Full article

Metastatic hormone-sensitive prostate cancer (mHSPCa) presents de novo or represents significant disease progression and requires systemic treatment. However, progression to castration resistance is inevitable. The treatment landscape has evolved with the introduction of intensified systemic therapy, including androgen deprivation therapy (ADT) combined with either androgen receptor signaling inhibitors (ARSIs) or cytotoxic chemotherapy (doublet therapy) or combined therapy with both agents (triplet therapy). Landmark trials such as CHAARTED, STAMPEDE, LATITUDE, ENZAMET, and TITAN have established combination therapies as the standard of care, demonstrating significant overall survival benefits. More recently, triplet therapy—integrating ADT, docetaxel, and an ARSI—has emerged as an effective approach, particularly in high-volume metastatic disease, as supported by ARASENS and PEACE-1. Advances in imaging, such as PSMA PET-CT, have improved disease detection, allowing earlier detection of metastasis and appropriate therapy. Similarly, genomic profiling has enabled biomarker-driven, personalized treatment strategies. The role of treatment of the primary tumor, by either radiation therapy or cytoreductive prostatectomy, in low-volume disease continues to be explored. As novel therapies, targeted agents, and immunotherapies undergo investigation, optimizing treatment selection based on disease burden, molecular characteristics, and patient factors will be essential. The future of mHSPCa management lies in multidisciplinary, precision-based approaches to improve patient outcomes while balancing treatment efficacy and tolerability. Full article

Economic inequality has been linked to changes in individual risk-taking behavior, yet the underlying mechanisms remain underexplored. In this study, I examine whether feelings of relative deprivation from upward social comparisons influence risk preferences. In the randomized experiments, participants were exposed to false information feedback designed to evoke feelings of relative deprivation, and their risk aversion was assessed through hypothetical and incentivized gambles. The results indicate that exposure to relative deprivation reduced risk aversion among men in incentivized lottery experiments, while it had no significant association with risk aversion for either gender in hypothetical gambles. Additionally, relative deprivation lowered perceived social standing and increased anxiety and concerns about personal deservingness—emotional outcomes commonly associated with experiences of relative deprivation. This study provides suggestive evidence that social comparison may influence risk preferences among men through emotional changes and offers insights into how societal inequality affects individual preferences. These findings have important implications for policy interventions aimed at addressing economic disparities and their behavioral consequences. Full article

Background/Objectives: Prostate cancer is one of the most prevalent cancers among men, with a significant proportion progressing to metastatic disease. Traditional treatments for metastatic prostate cancer have primarily been palliative, focusing on symptom relief. However, recent advances in radiotherapy have shown promise in improving outcomes for these patients. Methods: This study presents a modern treatment plan for extensive metastatic prostate cancer. Pre-treatment imaging revealed extensive lymph node metastases and high metabolic activity in the prostate. The treatment regimen included bicalutamide, androgen deprivation therapy with leuprorelin, and six cycles of docetaxel chemotherapy, followed by a targeted radiotherapy regimen aimed at both the primary tumor and metastatic lymph nodes. Results: Following the comprehensive radiotherapy regimen, the patient’s PSA level dropped below the edge of detection, indicating complete biochemical remission. Follow-up imaging and clinical assessments confirmed the absence of active metastatic sites. Conclusions: The findings support the integration of radiotherapy into comprehensive treatment plans for metastatic prostate cancer, demonstrating that radiotherapy can achieve complete remission even in patients with extensive metastatic disease. This suggests a need for re-evaluating traditional approaches and exploring more personalized, multimodal treatment strategies. Enhanced imaging techniques, such as PET/PSMA scans, play a crucial role in accurately targeting metastatic sites, enabling more effective and individualized treatment. Full article

The rise in international terrorism has led to a rise in citizenship deprivation. Depriving a person of citizenship represents a harsh national security measure. Although both Australia and the UK have citizenship deprivation legislation, the judicial response has differed. In Australia, two laws providing for deprivation of citizenship have been found unconstitutional. In the UK, significant challenges to citizenship deprivation decisions have failed, including those relating to Shamima Begum, deprived of UK citizenship in 2019, whose request for permission to appeal in respect of the decision was rejected by the UK Supreme Court in August 2024. In this context, it is striking that despite the lesser degree of human rights protection under the Australian Constitution and federal statutes compared with the UK, the Australian courts may have arrived at a significantly rights protective approach to citizenship deprivation, leading to an important procedural safeguard by requiring courts to make decisions on citizenship deprivation. This underlines interesting features of the Australian system, in which the development of doctrines under a written constitution that limits legislative power, such as through the separation of powers, can sometimes lead to significant (if uneven) rights protective outcomes. Short of a shift in UK constitutional law doctrine around the separation of powers (which is unlikely), the Australian decisions cannot be mirrored in the UK. However, they may point towards the possibility of stronger procedural safeguards in the context of citizenship deprivation, as well as some potential human rights law implications. Full article

Background: Salivary gland cancers (SGCs) are a rare and heterogeneous group of malignancies, accounting for approximately 5% of head and neck cancers. Despite their rarity, advances in molecular profiling have revealed a variety of genetic and molecular pathways, many of which are potentially actionable with targeted therapies. Methods: We reviewed the current literature involving the molecular landscape of SGCs, encompassing the diagnostic and prognostic value of tissue and liquid biomarkers and the potential therapeutic targets across various histological subtypes. Results: Our review highlights key molecular diagnostic findings such as the CRTC1-MAML2 fusion in mucoepidermoid carcinoma and MYB-NFIB rearrangements in adenoid cystic carcinoma, but also targetable alterations such as HER2 and AR positivity in salivary duct carcinoma and ETV6-NTRK3 fusion in secretory carcinoma. Liquid biopsy (both blood- or salivary-based), including circulating tumor DNA, circulating tumor cells, and miRNAs, offers novel, noninvasive approaches for disease monitoring and personalized treatment. Emerging therapies such as HER2 inhibitors, androgen deprivation therapy, and TRK inhibitors underscore the shift towards precision oncology in managing these malignancies. Conclusions: Despite promising advances, challenges remain due to the rarity and phenotypic heterogeneity of SGCs, emphasizing the need for molecularly stratified clinical trials. This review presents an overview of tissue and liquid biomarkers, focusing on molecular targets and therapeutic innovations that lay the foundation for improved diagnostic and treatment strategies for SGCs. Full article