Search Results (16,860)

Skeletal muscle atrophy is a critical health issue affecting the quality of life of elderly individuals and patients with chronic diseases. These conditions induce dysregulation of glucocorticoid (GC) secretion. GCs play a critical role in maintaining homeostasis in the stress response and glucose metabolism. However, prolonged exposure to GC is directly linked to muscle atrophy, which is characterized by a reduction in muscle size and weight, particularly affecting fast-twitch muscle fibers. The GC-activated glucocorticoid receptor (GR) decreases protein synthesis and facilitates protein breakdown. Numerous antagonists have been developed to mitigate GC-induced muscle atrophy, including 11β-HSD1 inhibitors and myostatin and activin receptor blockers. However, the clinical trial results have fallen short of the expected efficacy. Recently, several emerging pathways and targets have been identified. For instance, GC-induced sirtuin 6 isoform (SIRT6) expression suppresses AKT/mTORC1 signaling. Lysine-specific demethylase 1 (LSD1) cooperates with the GR for the transcription of atrogenes. The kynurenine pathway and indoleamine 2,3-dioxygenase 1 (IDO-1) also play crucial roles in protein synthesis and energy production in skeletal muscle. Therefore, a deeper understanding of the complexities of GR transactivation and transrepression will provide new strategies for the discovery of novel drugs to overcome the detrimental effects of GCs on muscle tissues. Full article

Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system (CNS) characterized by inflammation, demyelination, axonal degeneration, and gliosis. Its pathophysiology involves a complex interplay of genetic susceptibility, environmental triggers, and immune dysregulation, ultimately leading to progressive neurodegeneration and functional decline. Although significant advances have been made in disease-modifying therapies (DMTs), many patients continue to experience disease progression and unmet therapeutic needs. Drug repurposing—the identification of new indications for existing drugs—has emerged as a promising strategy in MS research, offering a cost-effective and time-efficient alternative to traditional drug development. Several compounds originally developed for other diseases, including immunomodulatory, anti-inflammatory, and neuroprotective agents, are currently under investigation for their efficacy in MS. Repurposed agents, such as selective sphingosine-1-phosphate (S1P) receptor modulators, kinase inhibitors, and metabolic regulators, have demonstrated potential in promoting neuroprotection, modulating immune responses, and supporting remyelination in both preclinical and clinical settings. Simultaneously, artificial intelligence (AI) is transforming drug discovery and precision medicine in MS. Machine learning and deep learning models are being employed to analyze high-dimensional biomedical data, predict drug–target interactions, streamline drug repurposing workflows, and enhance therapeutic candidate selection. By integrating multiomics and neuroimaging data, AI tools facilitate the identification of novel targets and support patient stratification for individualized treatment. This review highlights recent advances in drug repurposing and discovery for MS, with a particular emphasis on the emerging role of AI in accelerating therapeutic innovation and optimizing treatment strategies. Full article

Dose-dense chemotherapy shortens the interval between chemotherapy cycles and has shown improved outcomes in high-risk breast cancer patients. We retrospectively evaluated the efficacy and safety of dose-dense chemotherapy in 80 breast cancer patients treated at our hospital from 2020 to 2024. The regimen included epirubicin and cyclophosphamide followed by paclitaxel or docetaxel, with pegfilgrastim support. The overall treatment completion rate was 82.5%. Of the 80 patients, 55 underwent neoadjuvant chemotherapy, and the pathological complete response rate was significantly higher in triple-negative breast cancer (59.1%) compared to that in luminal-type cancer (9.1%). Common adverse events included anemia, liver dysfunction, myalgia, and peripheral neuropathy. Febrile neutropenia occurred in 8.8% of patients, with some cases linked to pegfilgrastim body pod use, particularly in individuals with low subcutaneous fat. Notably, two patients developed pneumocystis pneumonia, potentially associated with steroid administration. Despite these toxicities, most were manageable and resolved after treatment. Our findings support the efficacy of dose-dense chemotherapy, particularly in triple-negative breast cancer, while highlighting the importance of individualized supportive care and vigilance regarding hematologic and infectious complications. Full article

The integration of artificial intelligence (AI) in education offers novel opportunities to enhance critical thinking while also posing challenges to independent cognitive development. In particular, Human-Centered Artificial Intelligence (HCAI) in education aims to enhance human experience by providing a supportive and collaborative learning environment. Rather than replacing the educator, HCAI serves as a tool that empowers both students and teachers, fostering critical thinking and autonomy in learning. This study investigates the potential for AI to become a collaborative partner that assists learning and enriches academic engagement. The research was conducted during the 2024–2025 winter semester within the Pedagogical and Teaching Sufficiency Program offered by the Audio and Visual Arts Department, Ionian University, Corfu, Greece. The research employs a hybrid ethnographic methodology that blends digital interactions—where students use AI tools to create artistic representations—with physical classroom engagement. Data was collected through student projects, reflective journals, and questionnaires, revealing that structured dialog with AI not only facilitates deeper critical inquiry and analytical reasoning but also induces a state of flow, characterized by intense focus and heightened creativity. The findings highlight a dialectic between individual agency and collaborative co-agency, demonstrating that while automated AI responses may diminish active cognitive engagement, meaningful interactions can transform AI into an intellectual partner that enriches the learning experience. These insights suggest promising directions for future pedagogical strategies that balance digital innovation with traditional teaching methods, ultimately enhancing the overall quality of education. Furthermore, the study underscores the importance of integrating reflective practices and adaptive frameworks to support evolving student needs, ensuring a sustainable model. 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

Approximately 185,000 people in the United states experience limb loss each year. There is a need for an intuitive neural interface that can offer high-fidelity control signals to optimize the advanced functionality of prosthetic devices. Regenerative peripheral nerve interface (RPNI) is a pioneering advancement in neuroengineering that combines surgical techniques with biocompatible materials to create an interface for individuals with limb loss. RPNIs are surgically constructed from autologous muscle grafts that are neurotized by the residual peripheral nerves of an individual with limb loss. RPNIs amplify neural signals and demonstrate long term stability. In this narrative review, the terms “Regenerative Peripheral Nerve Interface (RPNI)” and “RPNI surgery” are used interchangeably to refer to the same surgical and biological construct. This narrative review specifically focuses on RPNIs as a targeted approach to enhance prosthetic control through surgically created nerve–muscle interfaces. This area of research offers a promising solution to overcome the limitations of existing prosthetic control systems and could help improve the quality of life for people suffering from limb loss. It allows for multi-channel control and bidirectional communication, while enhancing the functionality of prosthetics through improved sensory feedback. RPNI surgery holds significant promise for improving the quality of life for individuals with limb loss by providing a more intuitive and responsive prosthetic experience. Full article

Background: Papillary thyroid microcarcinoma (PTMC) is associated with certain features that carry an increased risk of local recurrence, underscoring the importance of preoperative risk assessment. This study investigated the clinicopathological factors associated with high-risk lymph node metastasis (HRLNM) and patient outcomes. HRLNM is defined as ≥5 metastatic lymph nodes and/or lateral neck metastasis. Methods: We conducted a retrospective review of 985 patients with PTMC who underwent thyroidectomy at the Kaohsiung Chang Gung Memorial Hospital from 2013 to 2022. Results: Among the 985 patients, 100 (10.2%) had lymph node metastasis (LNM), and 27% of these were classified as having HRLNM. Male sex (OR 3.61, p = 0.04) and extranodal extension (OR 3.76, p = 0.043) were independent predictors of HRLNM. Patients with LNM exhibited lower rates of excellent treatment response (75% vs. 87%, p = 0.001), higher recurrence rates (9.0% vs. 0.6%, p = 0.001), and an increased risk of distant metastasis (2.0% vs. 0%). Recurrence-free survival (RFS) was significantly shorter in patients with LNM (120.9 vs. 198.6 months, p < 0.001). Although HRLNM showed a trend toward reduced RFS (113.5 vs. 124.6 months, p = 0.177), its impact on long-term survival remains uncertain. Conclusions: Male sex and extranodal extension were significant risk factors for HRLNM in patients with PTMC. These findings highlight the need for individualized risk stratification to guide treatment strategies and improve patient outcomes. Full article

Joint attention, the capacity of two or more individuals to focus on a common event simultaneously, is fundamental to human–human interaction, enabling effective communication. When considering the field of social robotics, emulating this capability might be necessary for promoting natural interactions and thus improving user engagement. Responding to joint attention (RJA), defined as the ability to react to external attentional cues by aligning focus with another individual, plays a critical role in promoting mutual understanding. This study examines how RJA impacts user engagement during human–robot interaction. The participants play a turn-taking game against a social robot under two conditions: with our RJA system active and with the system inactive. Auditory and visual stimuli are introduced to simulate real-world dynamics, testing the robot’s ability to detect and follow the user’s focus of attention. We use a twofold approach to evaluate the system’s impact on the user’s experience during the interaction. On the one hand, we use head pose telemetry to quantify attentional aspects of engagement, including measures of distraction and focus during the interaction. On the other hand, we use a post-experimental questionnaire incorporating the User Engagement Scale Short Form to assess engagement. The results regarding telemetry data reveal reduced distraction and improved attentional consistency, highlighting the system’s ability to maintain attention on the current task effectively. Furthermore, the questionnaire responses show that RJA significantly enhances self-reported engagement when the system is active. We believe these findings confirm the value of attentional mechanisms in promoting engaging human–robot interactions. Full article

The large number of underutilized tree residues in Japan is a matter of concern, and their appropriate application needs to be promoted. Trees are very diverse, and there are differences in the volatile essential oil compounds and biological activities among different tree species. However, the effects of these tree species’ characteristics on human sensitivity and mental and physical functionality remain underexplored. This study investigated the effects of essential oils from multiple tree species on subjective and physiological responses. The essential oils from nine tree species were tested, subjective scent assessments were conducted, and their effect on autonomic nervous activity was measured. The volatile profiles of the oils were analyzed using gas chromatography–mass spectrometry. Our findings revealed clear differences in the composition of volatile essential oils among species, which influenced the scent evaluation and individual preferences. We suggest that scent preferences have the potential to influence physiological responses. The findings indicate that volatile essential oils could play a potential role in making use of tree resources effectively, and they may also be beneficial for maintaining human health. Full article

Objectives: Topical lubricants are the fundamental treatment for dry eye disease (DED). However, the molecular mechanisms underlying their efficacy remain unknown. Here, the protective effects of Thealoz^® Duo with 3% trehalose and 0.15% hyaluronic acid are investigated in DED patients by a longitudinal clinical study and subsequent elucidation of the tear proteome and cell signaling changes. Methods: Participants were classified as moderate to severe DED (DRY, n = 35) and healthy (CTRL, n = 23) groups. Specific DED subgroups comprising evaporative (DRYlip) and aqueous-deficient with DRYlip (DRYaqlip) were also classified. Only DED patients received Thealoz^® Duo. All participants were clinically examined before (day 0, T1) and after the application of Thealoz^® Duo at day 28 (T2) and day 56 (T3). Next, 174 individual tear samples from all groups at three time-points were subjected to proteomics analysis. Results: Clinically, Thealoz^® Duo significantly improved the ocular surface disease index at T2 vs. T1 (DRY, p = 1.4 × 10⁻²; DRYlip, p = 9.2 × 10⁻³) and T3 vs. T1 (DRY, p = 2.1 × 10⁻⁵; DRYlip, p = 1.2 × 10⁻⁴), and the tear break-up time at T3 vs. T1 (DRY, p = 3.8 × 10⁻²; DRYlip, p = 1.4 × 10⁻²). Thealoz^® Duo significantly ameliorated expression of inflammatory response proteins (p < 0.05) at T3, which was observed at T1 (DRY, p = 3.4 × 10⁻⁴; DRYlip, p = 7.1 × 10⁻³; DRYaqlip, p = 2.7 × 10⁻⁸). Protein S100-A8 (S100A8), Alpha-1-antitrypsin (SERPINA1), Annexin A1 (ANXA1), and Apolipoprotein A-I (APOA1) were found to be significantly reduced in all the DED subgroups. The application of Thealoz^® Duo showed the therapeutic characteristic of the anti-inflammatory mechanism by promoting the expression of (Metalloproteinase inhibitor 1) TIMP1 in all the DED subgroups. Conclusions: Thealoz^® Duo substantially improved the DED symptoms and restored the functionality of the tear lipid layer to near normal in DRYlip and DRY patients by ameliorating inflammation. Notably, this study unravels the novel mechanistic alterations underpinning the healing effects of Thealoz^® Duo in DED subgroups in a time-dependent manner, which supports the improvement in corresponding clinical attributes. 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

Background: Cognitive behavioral therapy (CBT) has shown consistent efficacy in individuals with psychosis, as supported by many trials. One classical distinction is that between affective and non-affective psychosis. Few studies have specifically examined the possible moderating role of substantial affective elements. In this systematic review and meta-regression analysis, we assess how CBT response differs across the affective spectrum in psychosis. Methods: We included studies assessing various CBT modalities, including third-wave therapies, administered in people with psychosis. The study protocol is published in the Open Science Framework. Meta-regression was conducted to assess whether the proportion of participants with affective psychosis (AP), as proxied by a documented diagnosis of schizoaffective (SZA) disorder, moderated CBT efficacy across positive, negative, and depressive symptom domains. Results: The literature search identified 4457 records, of which 39 studies were included. The median proportion of SZA disorder participants was 17%, with a total of 422 AP participants represented. Meta-regression showed a trend toward lower CBT efficacy for positive symptoms with a higher SZA disorder proportion (β = +0.10 SMD per 10% increase in AP; p = 0.12), though it was not statistically significant. No significant associations were found for negative (β = +0.05; p = 0.73) or depressive symptoms (β = −0.02; p = 0.78). Heterogeneity was substantial across all models (I² ranging from 54% to 80%), and funnel plot asymmetry was observed in negative and depressive symptoms, indicating possible publication bias. Risk of bias assessment showed the anticipated inherent difficulty of psychotherapies in blinding and possibly dropout rates affecting some studies. Conclusions: Affective symptoms may reduce the effectiveness of CBT for positive symptoms in psychotic disorders, although the findings did not reach statistical significance. Other patient-level characteristics in psychosis could indicate which patients can benefit most from CBT modalities. Full article

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. Although the aetiology of IBD remains largely unknown, several studies suggest that an individual’s genetic susceptibility, external environmental factors, intestinal microbial flora, and immune responses are all factors involved in and functionally linked to the pathogenesis of IBD. Beyond the gastrointestinal manifestations, IBD patients frequently suffer from psychiatric comorbidities, particularly depression and anxiety. It remains unclear whether these disorders arise solely from reduced quality of life or whether they share overlapping biological mechanisms with IBD. This review aims to explore the bidirectional relationship between IBD and depressive disorders (DDs), with a focus on four key shared mechanisms: immune dysregulation, genetic susceptibility, alterations in gut microbiota composition, and dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis. By examining recent literature, we highlight how these interconnected systems may contribute to both intestinal inflammation and mood disturbances. Furthermore, we discuss the reciprocal pharmacologic interactions between IBD and DDs: treatments for IBD, such as TNF-alpha and integrin inhibitors, have demonstrated effects on mood and anxiety symptoms, while certain antidepressants appear to exert independent anti-inflammatory properties, potentially reducing the risk or severity of IBD. Overall, this review underscores the need for a multidisciplinary approach to the care of IBD patients, integrating psychological and gastroenterological assessment. A better understanding of the shared pathophysiology may help refine therapeutic strategies and support the development of personalized, gut–brain-targeted interventions. Full article

Background: Quality care of individuals with sickle cell disease (SCD) is dependent upon education of the providers on their care team. Previous studies demonstrate lack of resident and provider comfort regarding care of patients with SCD, yet none have assessed these in medical students. Objective: This study aims to evaluate the adequacy of the research instrument for measuring medical students’ knowledge, confidence, and comfort regarding SCD and related complications prior to wider distribution. Methods: A self-assessment survey was distributed to medical students at two universities to evaluate their knowledge, confidence, and comfort in general SCD topics, in all clinical settings, and regarding common complications. Results: Of the 98 responses, knowledge (p < 0.001) and confidence (p = 0.02) were significantly different between topics, including epidemiology and genetics, pathophysiology, and treatment options. For “treatment options”, there were significant differences in knowledge (p = 0.02) and confidence (p = 0.02) between medical students at different levels of training. Students felt least knowledgeable and least comfortable with care of pregnant women and most knowledgeable and most comfortable with acute pain management. Caring for patients with specific SCD-related conditions increased knowledge and comfort across all domains. Conclusions: This instrument was adequate for measuring knowledge, confidence, and comfort in caring for those with SCD across all clinical settings. We identified a lack of knowledge, confidence, and comfort regarding treatment for those with SCD starting early in medical careers, which improves after caring for patients with various complications. Thus, educating and providing SCD patient experiences is crucial for medical student management confidence related to SCD. Full article