Search Results (6,844)

Background/Objectives: Mild Cognitive Impairment (MCI), a condition between normal aging and dementia, is characterized by cognitive changes that do not significantly affect instrumental activities of daily living. The Memory Support System (MSS), an evidence-based behavioral intervention developed by the Mayo Clinic, has been shown to aid those living with MCI and their support partners in coping with cognitive challenges. However, the MSS has not been offered clinically within the Canadian context. Therefore, we conducted a study assessing the feasibility of the MSS from the perspectives of individuals living with MCI and their support partners. Methods: Participants from an institutional registry of research participants, patients, and support partners at a memory clinic, as well as members of a local Dementia Society, were approached to complete an online or paper version of a survey assessing feasibility dimensions. Responses were compared between and within groups for differences in mean scores and associations between linked binary choice response questions. Results: A total of 77 responses were received; 39 surveys were completed by participants with MCI, and 38 by support partners. Respondents found the MSS to be acceptable and practical. On average, participants thought it would be more difficult to train in using the MSS than support partners. Both groups expressed interest in the intervention. On average, participants with MCI and support partners preferred virtual MSS training to in-person and indicated more interest in participating in training over six weeks as compared to two weeks. Conclusions: Flexibility in duration and format when offering the MSS are important considerations when offering the intervention as part of a clinical program. Future research should evaluate cost-effectiveness (e.g., financial, staff resources, etc.) of the MSS approach if it were to be institutionalized in the Ontario healthcare system. Full article

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive malignancy characterized by complex interactions within the tumor microenvironment (TME) that facilitate immune evasion and tumor progression. The TME consists of diverse cellular components, including cancer-associated fibroblasts, immune and endothelial cells, and extracellular matrix elements, that collectively modulate tumor growth, metastasis, and resistance to therapy. Immune evasion in HNSCC is orchestrated through multiple mechanisms, including the suppression of cytotoxic T lymphocytes, recruitment of immunosuppressive cells, such as regulatory T and myeloid-derived suppressor cells, and upregulation of immune checkpoint molecules (e.g., PD-1/PD-L1 and CTLA-4). Natural killer (NK) cells, which play a crucial role in anti-tumor immunity, are often dysfunctional within the HNSCC TME due to inhibitory signaling and metabolic constraints. Additionally, endothelial cells contribute to tumor angiogenesis and immune suppression, further exacerbating disease progression. Recent advancements in immunotherapy, particularly immune checkpoint inhibitors and NK cell-based strategies, have shown promise in restoring anti-tumor immunity. Moreover, TP53 mutations, frequently observed in HNSCC, influence tumor behavior and therapeutic responses, highlighting the need for personalized treatment approaches. This review provides a comprehensive analysis of the molecular and cellular mechanisms governing immune evasion in HNSCC with a focus on novel therapeutic strategies aimed at improving patient outcomes. Full article

The advancement of artificial intelligence (AI), deep learning, and radiomics has introduced novel methodologies for the detection, classification, prognosis, and treatment evaluation of pancreatic ductal adenocarcinoma (PDAC). As the integration of AI into medical imaging continues to evolve, its potential to enhance early detection, refine diagnostic precision, and optimize treatment strategies becomes increasingly evident. However, despite significant progress, various challenges remain, particularly in terms of clinical applicability, generalizability, interpretability, and integration into routine practice. Understanding the current state of research is crucial for identifying gaps in the literature and exploring opportunities for future advancements. This literature review aims to provide a comprehensive overview of the existing studies on AI applications in PDAC, with a focus on disease detection, classification, survival prediction, treatment response assessment, and radiogenomics. By analyzing the methodologies, findings, and limitations of these studies, we aim to highlight the strengths of AI-driven approaches while addressing critical gaps that hinder their clinical translation. Furthermore, this review aims to discuss future directions in the field, emphasizing the need for multi-institutional collaborations, explainable AI models, and the integration of multi-modal data to advance the role of AI in personalized medicine for PDAC. Full article

Background: Dietary advice for Paralympic athletes (PAs) with a spinal cord injury (PAs-SCI) requires particular attention and has been widely studied. However, currently, no particular attention has been addressed to nutritional guidelines for athletes with an amputation (PAs-AMP). This study aimed at filling up this gap, at least partially, and compared veteran PAs-SCI with PAs-AMP. Methods: A sample of 25 male PAs (12 with SCI and 13 with AMP), recruited during two training camps, was submitted to the following questionnaires: allergy questionnaire for athletes (AQUA), Nordic Musculoskeletal Questionnaire (NMQ), Starvation Symptom Inventory (SSI), neurogenic bowel dysfunction (NBD), orthorexia (ORTO-15/ORTO-7), alcohol use disorders identification test (AUDIT), and Mediterranean diet adherence (MDS). The PAs were also submitted to the following measurements: dietary Oxygen Radical Absorbance Capacity (ORAC) and intakes, body composition, handgrip strength (HGS), basal energy expenditure (BEE), peak oxygen uptake (VO_2peak), peak power, peak heart rate (HR), post-exercise ketosis, and antioxidant response after a cardiopulmonary exercise test (CPET) to voluntary fatigue. Results: Compared to PAs-AMP, PAs-SCI had higher NBD and lower VO_2peak (p < 0.05), peak power, peak HR, peak lactate, phase angle (PhA) of the dominant leg (p < 0.05), and ORTO15 (p < 0.05). The latter was related to NBD (r = −0.453), MDS (r = −0.638), and ORAC (r = −0.529), whereas ORTO7 correlated with PhA of the dominant leg (r = 0.485). Significant differences between PAs-AMP and PAs-SCI were not found in the antioxidant response, glucose, and ketone levels after CPET, nor in dietary intake, AUDIT, AQUA, NMQ, SSI, BEE, HGS, and FM%. Conclusions: The present study showed that PAs-SCI and PAs-AMP display similar characteristics in relation to lifestyle, energy intake, basal energy expenditure, and metabolic response to CPET. Based on both the similarities with PAs-SCI and the consequences of the limb deficiency impairment, PAs-AMP and PAs-SCI require personalized nutritional advice. Full article

Background/Objectives: The COVID-19 pandemic caused pronounced disorder in healthcare delivery globally, including ophthalmology. Our study explores how ophthalmologists in Puerto Rico (PR) altered their practices during the pandemic, confronting obstacles such as resource shortages, evolving public health mandates, and unique socio-economic and geographic constraints. The study aims to enhance preparedness for future public health crises. Methods: We conducted descriptive analyses on four online surveys distributed at crucial time points of the pandemic (March 2020, May 2020, August 2020, August 2021) to all practicing ophthalmologists in PR (N ≈ 200), capturing data on closures, patient volume, personal protective equipment (PPE) access, telemedicine use, and financial relief. Results: Survey responses ranged from 41% (n = 81) to 56% (n = 111). By March 2020, 22% (24/111) of respondents closed their offices. By May 2020, 20% (19/93) of respondents maintained a closed office, while 89% (64/72) of open offices reported seeing less than 25% of their usual patient volume. Access to PPE was a challenge, with 59% (65/111) reporting difficulty obtaining N95 masks in March 2020. Telemedicine usage increased initially, peaking in May 2020 and declining in July 2020. By August 2021, all respondents were fully vaccinated and most practices returned to pre-pandemic levels. Overall, 86% (70/81) of respondents found the surveys to be useful for navigating practice changes during the pandemic. Conclusions: PR ophthalmologists showed adaptability during the COVID-19 pandemic to maintain care given limited resources. Guidelines from professional organizations and real time surveys play an important role in future crisis preparedness. Full article

Liquid biopsy has emerged as a valuable tool for the detection and monitoring of colorectal cancer (CRC), providing minimally invasive insights into tumor biology through circulating biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Additional biomarkers, including tumor-educated platelets (TEPs) and exosomal RNAs, offer further potential for early detection and prognostic role, although ongoing clinical validation is still needed. This review summarizes the current evidence on the diagnostic, prognostic, and predictive capabilities of liquid biopsy in both metastatic and non-metastatic CRC. In the non-metastatic setting, liquid biopsy is gaining traction in early detection through screening and in identifying minimal residual disease (MRD), potentially guiding adjuvant treatment and reducing overtreatment. In contrast, liquid biopsy is more established in metastatic CRC for monitoring treatment responses, clonal evolution, and mechanisms of resistance. The integration of ctDNA-guided treatment algorithms into clinical practice could optimize therapeutic strategies and minimize unnecessary interventions. Despite promising advances, challenges remain in assay standardization, early-stage sensitivity, and the integration of multi-omic data for comprehensive tumor profiling. Future efforts should focus on enhancing the sensitivity of liquid biopsy platforms, validating emerging biomarkers, and expanding multi-omic approaches to support more targeted and personalized treatment strategies across CRC stages. Full article

The relationship between metabolic dysfunction and mental health disorders is complex and has received increasing attention. This review integrates current research to explore how stress-related growth differentiation factor 15 (GDF15) signaling, ceramides derived from gut microbiota, and mitochondrial dysfunction in the brain interact to influence both metabolic and psychiatric conditions. Evidence suggests that these pathways converge to regulate brain energy homeostasis through feedback mechanisms involving the autonomic nervous system and the hypothalamic–pituitary–adrenal axis. GDF15 emerges as a key stress-responsive biomarker that links peripheral metabolism with brainstem GDNF family receptor alpha-like (GFRAL)-mediated anxiety circuits. Meanwhile, ceramides impair hippocampal mitochondrial function via membrane incorporation and disruption of the respiratory chain. These disruptions may contribute to sustained pathological states such as depression, anxiety, and cognitive dysfunction. Although direct mechanistic data are limited, integrating these pathways provides a conceptual framework for understanding metabolic–psychiatric comorbidities. Furthermore, differences in age, sex, and genetics may influence these systems, highlighting the need for personalized interventions. Targeting mitochondrial function, GDF15-GFRAL signaling, and gut microbiota composition may offer new therapeutic strategies. This integrative perspective helps conceptualize how metabolic and psychiatric mechanisms interact for understanding the pathophysiology of metabolic and psychiatric comorbidities and highlights therapeutic targets for precision medicine. Full article

In an increasingly complex global context, higher education faces the challenge of preparing professionals who are innovative, committed, and socially responsible. Entrepreneurial competence is particularly prominent among the key skills required to meet this goal, given its significant personal and social impact. This study examines how final-year undergraduate students at the University of Deusto (Spain) perceive the importance of entrepreneurial competence—defined as a set of transversal skills, knowledge, and attitudes enabling initiative and opportunity recognition across various contexts—rather than entrepreneurial competence strictly understood as business creation. The sample included 267 students from different faculties. Descriptive, comparative, and ordinal logistic regression analyses (SPSS) were used. The results show that, while entrepreneurial competence was given significant importance, it was ranked comparatively low relative to other competencies. Significant differences by gender were observed, with women rating entrepreneurial competence more highly than men. The faculty variable showed slight disparities, and there were no relevant differences between campuses. These findings highlight the need to reinforce the integration of entrepreneurial competence into educational curricula on a transversal basis, adapting the teaching of this competence to the sociocultural context of students, as well as the need to increase students’ awareness of the importance of entrepreneurial competence. It is proposed that further research should focus on the relationships between intrapreneurship, gender, and academic disciplines, in order to enrich entrepreneurial competence education and its impact on the employability and social commitment of students. Full article

Colorectal cancer (CRC) constitutes a major global health concern, ranking as the third most common cancer and the second leading cause of cancer-related mortality. The current review explores sex-based differences in CRC epidemiology, risk factors, tumor biology, and clinical outcomes. Males exhibit a higher incidence and mortality rate, with left-sided (distal) CRC predominating, while females are more frequently diagnosed with right-sided (proximal) tumors, which tend to be more aggressive and less responsive to conventional chemotherapy. Genetic disparities, including microsatellite instability and X-chromosome tumor suppressor genes, contribute to sex-specific differences in tumor progression and treatment response. Immune variations also influence disease outcomes, with females exhibiting stronger immune surveillance but higher exhaustion markers. Lifestyle factors such as body mass index (BMI), smoking, and hormonal influences further modulate CRC risk. While males are more vulnerable to obesity-related CRC, central obesity (waist-to-hip ratio) emerges as a stronger predictor in females. Additionally, smoking increases CRC risk differentially by tumor location. These findings underscore the importance of sex-specific approaches in CRC prevention, screening, and treatment, advocating for personalized medicine strategies tailored to gender-based biological and clinical distinctions. Full article

Despite the extensive evidence supporting the effectiveness of cognitive stimulation, differences in results may be due to the influence of cognitive and non-cognitive aspects in people with dementia. The aim of this systematic review is to identify the most reliable variables in forecasting the effectiveness of cognitive stimulation in people with mild to moderate dementia. According to PRISMA guidelines, the research was conducted using five databases (PubMed, Scopus, Cochrane, Web of Science, APA PsycInfo), considering randomized controlled trials. A total of six studies were included. Different aspects moderating the gain resulting from cognitive intervention were collected and assessed in terms of demographic, cognitive, emotional, social, and quality of life parameters. People with dementia benefit more from cognitive intervention if they are female, if they have a low formal education level, a low baseline level of cognitive function, and lower depressive symptoms, and if caregivers actively participate in sessions. Quality of life, if low at baseline, also seems to improve following CST intervention. A deeper understanding of the cognitive and non-cognitive aspects ensuring improvement after cognitive stimulation may guide future research to develop more personalized interventions. Full article

Despite significant advances in prostate cancer treatment over the past two decades, metastatic castration-resistant prostate cancer (mCRPC) remains incurable. We present the case of a patient with aggressive prostate cancer diagnosed 20 years ago, underscoring the value of longitudinal genomic profiling and advanced imaging to guide clinical decisions. After multiple treatment failures, genomic analyses of tissue and liquid biopsies revealed dynamic changes in tumor biology and the emergence of resistance mechanisms, particularly AR amplification, identified with a liquid biopsy test and validated by [¹⁸F]-FDHT PET scan. This finding guided treatment with bipolar androgen therapy (BAT), which achieved a dramatic clinical response, reduced AR expression, improved symptoms, and restored sensitivity to enzalutamide. This case exemplifies the utility of serial liquid biopsies in uncovering mechanisms of tumor evolution and resistance, and the crucial role of cutting-edge diagnostics in personalized cancer treatment. Full article

Current learning and development approaches often struggle to capture dynamic individual capabilities, particularly the skills they acquire informally every day on the job. This dynamic creates a significant gap between what traditional models think people know and their actual performance, leading to an incomplete and often outdated understanding of how ready the workforce truly is, which can hinder organizational adaptability in rapidly evolving environments. This paper proposes a novel dynamic learner-state ecosystem—an AI-driven solution designed to bridge this gap. Our approach leverages specialized AI agents, orchestrated via the Model Context Protocol (MCP), to continuously track and evolve an individual’s multi-dimensional state (e.g., mastery, confidence, context, and decay). The seamless integration of in-workflow performance data will transform daily work activities into granular and actionable data points through AI-powered dynamic xAPI generation into Learning Record Stores (LRSs). This system enables continuous, authentic performance-based assessment, precise skill gap identification, and highly personalized interventions. The significance of this ecosystem lies in its ability to provide a real-time understanding of everyone’s capabilities, enabling more accurate workforce planning for the future and cultivating a workforce that is continuously learning and adapting. It ultimately helps to transform learning from a disconnected, occasional event into an integrated and responsive part of everyday work. Full article

Colorectal cancer (CRC) remains one of the most lethal malignancies worldwide, with high recurrence rates and limited curative options in metastatic settings. Cancer vaccines represent an emerging immunotherapeutic approach that aims to stimulate robust, tumor-specific immune responses. This review summarizes the current state of CRC vaccine development, including tumor cell-based, dendritic cell-based, peptide-based, nucleic acid-based (DNA and mRNA), and virus-based platforms. We highlight findings from key clinical trials that demonstrate immunogenicity, safety, and preliminary efficacy, with particular attention to combinations with chemotherapy and immune checkpoint inhibitors. Furthermore, we explore critical challenges such as tumor heterogeneity, immunosuppressive tumor microenvironments, and the logistical complexity; in this context, we particularly focus on the current development of personalized cancer vaccines, exploring the newly identified encouraging epitopes and their safety and efficacy in recent trials. The integration of cancer vaccines with in silico modeling, advanced delivery systems such as nanoparticles or AI-guided designs, and microbiome modulation represents a promising avenue for enhancing their clinical utility. Overall, therapeutic and prophylactic cancer vaccines may soon contribute meaningfully to the comprehensive management of CRC, especially in settings of minimal residual disease or early recurrence. Full article

The management of acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, critically relies on thiopurine therapy, such as 6-mercaptopurine (6-MP), during the maintenance phase. However, significant inter-individual response variety and high risk of myelosuppression often disrupt therapy efficacy. Pharmacogenetics offer crucial strategies to personalized therapy. While thiopurine methyltransferase (TPMT) was initially the primary focus, the discovery of nudix hydrolase 15 (NUDT15) appears as a more comprehensive determinant of thiopurine intolerance. This review aims to consolidate and critically evaluate the advancement achieved in unraveling the biological mechanism and clinical significance of NUDT15 pharmacogenetics in thiopurine therapy. Foundational studies showed the vital role of NUDT15 in the detoxification of active thiopurines, with common genetic variants (for instance, p. Arg139Cys) significantly disrupting its activity, leading to the accumulation of toxic metabolites. Observational studies consistently associated NUDT15 variants with severe myelosuppression, notably in Asian populations. Recent randomized controlled trials (RCTs) confirmed that NUDT15 genotype-guided dosing effectively reduces thiopurine-induced toxicity without interfering with the therapeutic outcome. Despite these advancements, challenges remain present, including the incomplete characterization of rare variants, limited data in the diverse Asian populations, and the need for standardized integration with metabolite monitoring. In conclusion, NUDT15 pharmacogenetics is essential for improving patient safety and thiopurine dosage optimization in the treatment of ALL. For thiopurine tailored medicine to be widely and fairly implemented, future research should focus on increasing genetic data across different populations, improving the dose adjustment algorithm, and harmonizing therapeutic guidelines. Full article

(1) Background: People living with spinal cord injury (SCI) face numerous challenges in their lives in terms of health conditions, everyday activity, and participation in society, which are not fully recognized. To address such issues, a community survey with 125 questions for people living with SCI was conducted and the response rates, population characteristics, health and functioning problems are reported. (2) Methods: The survey questionnaire comprised 125 questions on SCI characteristics, health conditions, activities, participation, and environmental and personal factors. The survey response rates were calculated, and demographics and health and functioning characteristics were analyzed. (3) Results: A total of 890 individuals responded to the survey. The median age of the participants was 48 years (interquartile range (IQR), 39–56), and 76% of the population were males. Paraplegia (60%) and complete injury (58%) were the most common injury type, and the cause was mostly traumatic (92%). More health problems and lower quality of life were more frequent with older age and in patients without paid work. (4) Conclusions: The Ko-InSCI study provides valuable information in terms of health needs and service gaps for people with SCI in the community. Full article