Search Results (478)

This study estimates the prevalence of co-use of alcohol and cannabis, assesses the sociodemographic risk factors of co-use, and examines the associations between mental health and heavy episodic drinking (HED) and alcohol–cannabis co-use in Canada during the early years of the COVID-19 pandemic. Nine successive cross-sectional surveys, held from May 2020 to January 2022, of adults (aged ≥18 years) living in Canada were pooled for 9011 participants. The prevalence of co-use was calculated across sociodemographic groups. Logistic regressions were used to assess associations. Alcohol–cannabis co-use was associated with a greater likelihood of engaging in HED and experiencing symptoms of anxiety, depression, and loneliness. The prevalence of co-use of alcohol was different across sociodemographic groups. The highest prevalence was among TGD people (35.5%), followed by individuals aged 18–39 years (14.5%). Additionally, being TGD (aOR = 3.61, 95% CI 2.09–6.25), separated/divorced/widowed (aOR = 1.60, 95% CI 1.23–2.07), living in an urban area (aOR = 1.26, 95% CI 1.07–1.56), and having a high household income (aOR = 1.41, 95% CI 1.09–1.82) increased the likelihood of reporting alcohol–cannabis co-use. These findings underscore the fact that developing public health and clinical interventions for preventing and treating excessive alcohol or cannabis use must consider both alcohol and cannabis use patterns and should be tailored to the highest-risk TGD and young adults. Full article

T-cell-engaging antibodies are a promising new type of treatment for patients with refractory or relapsed (R/R) diffuse large B-cell lymphoma, which has changed the prognosis and evolution of these patients in clinical trials. Bispecific antibodies (BsAbs) bind to two different targets (B and T lymphocytes) at the same time and in this way mimic the action of CAR (chimeric antigen receptor) T-cells. They are the T-cell-engaging antibodies most used in practice and are a solution for patients who do not respond to second- or later-line therapies, including chemoimmunotherapy, followed by salvage chemotherapy and hematopoietic stem cell transplantation. They are a therapeutic option for patients who are ineligible for CAR T-cell therapy and are also active in those with prior exposure to CAR T-cell treatment. A remarkable advantage of BsAbs is their rapid availability, even if the disease progresses rapidly, unlike CAR T-cell treatment, and they avoid the practical and financial challenges raised by autologous CAR T-cell therapies. CAR-T has been proven to have better efficacy compared to BsAbs, but cytokine release syndrome and neurotoxicity have appeared significantly more frequently in patients treated with CAR T-cells. The possibility of combining BsAbs with chemotherapy and their administration for relapses or as a frontline therapy is being studied to increase their efficacy. BsAbs are a life-saving therapy for many patients with diffuse large B-cell malignant non-Hodgkin’s lymphoma (NHL) who have a poor prognosis with classical therapies, but are not without adverse effects and require careful monitoring. Full article

This study investigates how young Chinese consumers across generational lines engage with wine, addressing three key research questions: What motivates their wine purchases? What sensory preferences do they exhibit? And through which channels do they prefer to buy wine? Based on a qualitative design combining focus groups and semi-structured interviews, the study identifies significant generational differences between millennials and post-millennials. Millennials treat wine as a social tool for networking and status, while post-millennials view wine as a medium of personal identity shaped by digital culture. Similarly, millennials prefer a balance of traditional and digital retail, whereas post-millennials favour online platforms. Experiential consumption follows the same pattern, from formal tourism to virtual tastings. By linking these findings to institutional and cultural theories of consumer behaviour, the study contributes to a nuanced understanding of wine consumption in an emerging market. It provides practical implications for wine marketers aiming to localize their strategies for younger Chinese segments. Full article

Despite growing academic interest in platform work and the gig economy, most existing research focuses on Western Europe, often neglecting the unique institutional and socioeconomic contexts of Central and Eastern Europe. This study addresses that gap by exploring the working conditions of platform workers in Poland, with particular emphasis on both material and psychosocial dimensions from the workers’ own perspectives. Data were collected from a nationally representative sample of 450 platform workers engaged in both online and location-based tasks, using the computer-assisted web interviewing (CAWI) method. The findings show a high level of perceived autonomy, with 74% of respondents feeling that they are independent in their work. However, autonomy is often limited by external factors, in particular, the availability of work. Workers who treat platform work as a side job are significantly more likely to report a sense of autonomy. In terms of health and safety, only 27% expressed concerns about negative health impacts, and 24% reported poor working conditions. Those who received health and safety information from the platform were more likely to acknowledge potential risks. Interestingly, workers relying on platform work as their primary source of income were more likely to perceive their work as safe, compared to those treating it as supplementary employment. Full article

Current structural barriers experienced by First Nations in Canada shape access and engagement for testing and treatment of hepatitis C virus (HCV) infections. This non-systematic informative review considers transdisciplinary perspectives, regional data, and published literature connecting context to the disproportionate HCV burden experienced by First Nations populations in the prairie provinces of Canada, and offers examples of participatory and community-led initiatives working toward the elimination of HCV as a public health threat. First Nations in Canada are disproportionately impacted by chronic HCV infection, with a reported rate of newly diagnosed HCV cases in First Nations communities five times the respective rate in the general Canadian population in 2022. This review explores the reasons underlying the disproportionate burden of HCV infection. Significant over-representation of First Nations in the Canadian Prairies is seen in the major risk categories for HCV acquisition, and the impact of these risk factors is aggravated by barriers to accessing healthcare services and medication coverage. These barriers stem from the legacy of colonialism, discrimination, disenfranchisement, and are exacerbated by stigmatization, victimization, and racism in the justice and healthcare systems. Other contributory factors that impede access to care include inadequate healthcare clinic staffing and infrastructure in First Nations communities, and significant geographical distances between First Nations reserves and laboratories, pharmacies, and treating/prescribing healthcare providers. Recent recognition of historical harms and early steps towards nation-to-nation reconciliation, along with support for culturally connected, holistic, and First Nations-led wellness programs, instill hope that elimination strategies to eradicate HCV infection in First Nations populations will be successful in Canada. Full article

Background/Objectives: In contemporary nursing education, clinical competence and psychological resilience are both essential; however, they are often treated as separate outcomes. Clinical placements are a central component of nursing education, and often expose students to high levels of stress, emotional challenges, and complex clinical demands. Building both clinical competence and psychological resilience during this phase is crucial to preparing students for the realities of professional practice. This narrative review, grounded in Bandura’s social cognitive theory (SCT), explores how educator behaviors, teaching strategies, and learning environments interact to influence both domains in undergraduate nursing students. Methods: A comprehensive search was conducted in PubMed, CINAHL, and PsycINFO for peer-reviewed articles published between 1 January 2000 and 2 May 2025. Relevant studies were thematically analyzed and were guided by Bandura’s SCT constructs, including observational learning, self-efficacy, and reciprocal determinism. No formal study appraisal was conducted due to the narrative nature of the review. Findings: Nineteen studies were included in the review. The findings highlight that reflective practices, structured feedback, peer learning, and strategies to build self-efficacy are central to building resilience and competence. Supportive educator behaviors such as mentoring, emotional support, and professional role modeling, were strongly associated with increased student confidence, emotional regulation, and adaptability. Psychologically safe clinical learning environments further enhanced self-efficacy and active engagement. In contrast, unsupportive or inconsistent environments were linked to student stress, disengagement, and reduced performance. Conclusions: This review highlights the need to move beyond traditional competency-based models toward an integrated approach that equally values psychological preparedness and resilience. Findings suggest a shift toward emotionally and socially integrated clinical education. Full article

Background: Understanding interactions between cytokine antagonists and drugs is essential for effective medication management in inflammatory conditions. Recent regulatory authority guidelines emphasise a systematic, risk-based approach to evaluating these interactions, underscoring the need for mechanistic insight. Proinflammatory cytokines, such as interleukin-6 (IL-6), modulate cytochrome P450 (CYP) enzymes, reducing the metabolism of CYP substrates. Cytokine antagonists (such as IL-6 receptor antagonists) can counteract this effect, restoring CYP activity and increasing drug clearance. However, quantitative prediction of cytokine-mediated drug interactions remains challenging, as existing models often lack the mechanistic detail needed to capture the dynamic relationship between cytokine signalling, receptor engagement, and downstream modulation of drug metabolism. Methods: A physiologically based pharmacokinetic (PBPK) framework incorporating cytokine–receptor binding, subsequent downregulation of CYP expression, and blockade of the cytokine signalling by a therapeutic protein antagonist was developed to simulate and investigate cytokine antagonist-drug interactions. Tocilizumab, a humanised IL-6 receptor antagonist used to treat several inflammatory conditions associated with elevated IL-6 levels, was selected as a model drug to demonstrate the utility of the framework. Results: The developed PBPK model accurately predicted the pharmacokinetics profiles of tocilizumab and captured clinically observed dynamic changes in simvastatin exposure before and after tocilizumab treatment in rheumatoid arthritis (RA) patients. Simulated IL-6 dynamics aligned with observed clinical profiles, showing transient elevation following receptor blockade and associated restoration of CYP3A4 activity. Prospective simulations with commonly co-administered CYP substrates (celecoxib, chloroquine, cyclosporine, ibuprofen, prednisone, simvastatin, and theophylline) in RA patients revealed dose regimen- and drug-dependent differences in interaction magnitude. Conclusions: This study demonstrated the utility of PBPK models in providing a mechanistic understanding of cytokine antagonist-drug interactions, supporting enhanced therapeutic decision-making and optimising patient care in inflammatory conditions. Full article

Proton pump inhibitors (PPIs) are widely prescribed medications primarily used to treat gastroesophageal reflux disease, peptic ulcer disease, and upper gastrointestinal bleeding. Despite clear therapeutic benefits in appropriate contexts, widespread overprescribing and extended use without clear indications have prompted significant concerns about associated risks. Accumulating evidence, predominantly from observational studies, suggests that long-term PPI use may lead to complications such as vitamin and mineral deficiencies, increased risks of infections, dysbiosis, renal dysfunction, bone fractures, cardiovascular disease, and certain malignancies. This narrative review not only synthesizes the current evidence surrounding PPI-related harms and existing deprescribing guidelines but also offers a novel perspective on how stewardship principles can be applied to promote responsible PPI prescribing. In particular, we propose a stewardship-oriented deprescribing framework rooted in implementation science, focusing on provider behavior, patient engagement, and health system-level integration. Recognizing these potential harms, evidence-based deprescribing strategies such as tapering, intermittent dosing, and transitions to alternative therapies are critical to mitigate unnecessary patient exposure. Effective implementation of deprescribing requires addressing patient, provider, and institutional barriers through educational initiatives, policy support, and structured monitoring. By promoting judicious PPI prescribing and proactive stewardship practices, clinicians can significantly reduce medication-related harm and improve patient safety. Full article

Background/Objectives: University students are particularly susceptible to mental health issues, exhibiting a higher prevalence of insomnia and depressive symptoms compared to the general population. These mental problems adversely affect their academic performance and overall well-being. Understanding this issue is essential for developing effective prevention and intervention strategies for the academic community. The present study investigates the complex role of problematic TikTok use and insomnia in relation to depression among university students. Methods: An online cross-sectional survey was conducted between November 2024 and January 2025, involving a sample of 173 university students in Poland. The participants had a mean age of 23 years (M = 23.09, SD = 3.92), with 73.4% being women, and 49% were enrolled in medical and healthcare faculties. The questionnaire comprised a demographic survey, the Patient Health Questionnaire (PHQ-9) for assessing symptoms of depression, the Athens Insomnia Scale (AIS-8) for measuring symptoms of insomnia, and the modified Bergen Facebook Addiction Scale (BFAS) for evaluating problematic TikTok use (PTTU). The hypotheses were verified using Student’s t-test, Pearson’s correlation, and general linear model (GLM) mediation analysis. Results: The study found no significant gender (women vs. men) and faculty (medical vs. non-medical) differences in the level of symptoms of depression, insomnia, or problematic TikTok use. Insomnia, depression, and PTTU were positively inter-related. Insomnia completely mediates the relationship between PTTU and depression in university students. However, these results must be treated with caution due to the uneven gender distribution and cross-sectional nature of these studies, which limits causal relationships. Conclusions: Excessive engagement with TikTok has been associated with an increase in insomnia symptoms, which subsequently exacerbates depression symptoms among university students. Prevention and intervention strategies should prioritize reducing TikTok usage while simultaneously enhancing sleep hygiene and mental health within the academic population, irrespective of gender and university faculty affiliation. Full article

The swift evolution of information technology and growing connectivity in critical applications have elevated cybersecurity, protecting and certifying software and designs against rising cyber threats. For example, software and hardware have become highly susceptible to various threats, like reverse engineering, cloning, tampering, and IP piracy. While various techniques exist to enhance software and hardware security, including encryption, native code, and secure server-side execution, obfuscation emerges as a preeminent and cost-efficient solution to address these challenges. Obfuscation purposely converts software and hardware to improve complexity for probable adversaries, targeting obscure realization operations while preserving safety and functionality. Former research has commonly engaged features of obfuscation, deobfuscation, and obfuscation detection approaches. A novel departure from conventional research methodologies, this revolutionary comprehensive article reviews these approaches in depth. It explicates the correlations and dynamics among them. Furthermore, it conducts a meticulous comparative analysis, evaluating obfuscation techniques across parameters such as the methodology, testing procedures, efficacy, associated drawbacks, market applicability, and prospects for future enhancement. This review aims to assist organizations in wisely electing obfuscation techniques for firm protection against threats and enhances the strategic choice of deobfuscation and obfuscation detection techniques to recognize vulnerabilities in software and hardware products. This empowerment permits organizations to proficiently treat security risks, guaranteeing secure software and hardware solutions, and improving user satisfaction for maximized profitability. Full article

Background: Headache disorders, particularly migraine, are a leading cause of disability among active-duty military personnel, significantly affecting operational readiness and fitness for duty. Despite their high prevalence, limited data exist on how headache disorders are managed within military primary care systems. This study aimed to evaluate diagnostic confidence, treatment strategies, and structural challenges in the management of headache disorders from the perspective of military primary care physicians. Methods: A prospective, nationwide cross-sectional survey was conducted between May and July 2023 among all active-duty military physicians in primary care roles. An anonymous 15-item questionnaire assessed diagnostic practices, therapeutic approaches, referral pathways, perceived knowledge gaps, and suggestions for system improvements. The survey was distributed across military medical centers and outpatient clinics in Germany. Results: Ninety military physicians participated. Migraine and tension-type headache were commonly encountered, with 70% having treated at least one headache patient in the week prior to the survey. Diagnostic confidence was high for migraine (83.4%) and tension-type headache (77.8%) but lower for medication-overuse headache (65.5%) and cluster headache (47.8%). Acute treatment was widely implemented, but only 27.8% of respondents regularly initiated preventive therapies. Awareness of clinical guidelines was limited: only 23.3% were familiar with the ICHD-3, and just 58.9% with national headache treatment guidelines. Respondents expressed strong demand for targeted education, practical diagnostic tools, and improved interdisciplinary coordination. Conclusions: Headache disorders are a prevalent and clinically significant issue in military primary care. While military physicians show high engagement, important gaps exist in preventive treatment, guideline familiarity, and access to specialist care. Structured training, standardized treatment protocols, and system-level improvements are essential to optimize headache care and maintain operational readiness. Full article

Since the advent of recombinant DNA technologies and leading up to the clinical approval of T cell engager blinatumomab, the modular design of therapeutic antibodies has enabled the fusion of antibody fragments with proteins of various functionalities. This has resulted in an expansive array of possible mechanisms of action and has given birth to fragment-based antibodies (fbAbs) with immune cell engager modalities. In searchable databases, the preclinical development of these antibodies has shown promise; however, clinical outcomes and restructuring efforts involving these agents have produced mixed results and uncertainties. Amid budgetary cuts in both academia and industry, critical planning and evaluation of drug R&D would be more essential than ever before. While many reviews have provided outstanding summaries of preclinical phase fbAbs and cataloged relevant clinical trials, to date, very few of the articles in searchable databases have comprehensively reviewed the details of clinical outcomes along with the underlying reasons or potential explanations for the success and failures of these fbAb drug products. To fill the gap, in this review, we seek to provide the readers with clinically driven insights, accompanied by translational and mechanistic studies, on the current landscape of fragment-based immune cell engager antibodies in treating cancer, infectious, and autoimmune diseases. Full article

User churn in online games refers to players becoming inactive for an extended period. Even a small increase in churn can lead to significant revenue loss, making churn prediction crucial for sustaining long-term player engagement. Although user churn prediction has been extensively studied, most existing approaches either ignore non-login periods or treat all inactivity uniformly, overlooking key behavioral differences. This study addresses this gap by categorizing non-login periods into three types, as follows: inactivity due to new or dormant users, genuine loss of interest, and temporary inaccessibility caused by external factors. These periods are treated as either non-existent or missing data and imputed using techniques such as mean or mode substitution, linear interpolation, and multiple imputation by chained equations (MICE). MICE was selected due to its ability to impute missing values more robustly by considering multivariate relationships. A random forest (RF) classifier, chosen for its interpretability and robustness to incomplete data, serves as the primary prediction model. Additionally, classifier chains are used to capture label dependencies, and principal component analysis (PCA) is applied to reduce dimensionality and mitigate overfitting. Experiments on real-world MMORPG data show that our approach improves predictive accuracy, achieving a micro-averaged AUC of above 0.92 and a weighted F1 score exceeding 0.70. These findings suggest that our approach improves churn prediction and offers actionable insights for supporting personalized player retention strategies. Full article

Urbanisation in the context of climate change and rapid population growth presents an urgent need for innovative and sustainable urban planning. This study introduces the Green Blueprint, an original, spatially grounded, and evidence-informed conceptual framework designed to systematically embed ecosystem services into the planning, governance, and design of resilient and equitable cities in the United Kingdom. Unlike existing research that typically treats Urban Green Infrastructure (UGI) as a discrete intervention or evaluates its benefits in isolation, the Green Blueprint integrates cross-sectoral governance, multifunctional land use, and participatory planning into a coherent, scalable model for urban resilience. Developed through a qualitative, interpretivist methodology and critical documentary analysis of secondary data including policy documents, academic literature, and case studies from London, Manchester, and Sheffield, this framework highlights how embedding ecosystem services such as carbon sequestration, stormwater management, biodiversity enhancement, and public health into the urban fabric can support long-term climate adaptation and social equity. Rather than serving as a review, this paper advances a novel theoretical contribution through empirical synthesis and thematic cross-case comparison. It further identifies enabling governance structures and implementation pathways to support policy innovation and practical application. This study contributes a transferable planning template for cities aiming to achieve systemic UGI integration, offering clear value for scholars, practitioners, and policymakers engaged in sustainable urban development in the Anthropocene. Full article

Spinal Muscular Atrophy (SMA) is a genetic disorder characterized by the progressive loss of motor neurons and consequent muscle atrophy. Although SMN-targeted therapies have significantly improved survival and motor outcomes, residual muscle weakness remains a major clinical challenge, particularly in patients treated later in the disease course. Myostatin, a potent negative regulator of skeletal muscle mass, has emerged as a promising therapeutic target to address this gap. This review summarizes the preclinical and clinical evidence supporting the modulation of the myostatin pathway in SMA. Preclinical studies have demonstrated that inhibiting myostatin, especially when combined with SMN-enhancing agents, can increase muscle mass, improve motor function, and enhance neuromuscular connectivity in SMA mouse models. These findings provide a strong rationale for translating myostatin inhibition into clinical practice as an adjunctive strategy. Early clinical trials investigating myostatin inhibitors have shown favorable safety profiles and preliminary signs of target engagement. However, large-scale trials have yet to demonstrate widespread, robust efficacy across diverse patient populations. Despite this, myostatin pathway inhibition remains a compelling approach, particularly when integrated into broader treatment paradigms aimed at enhancing motor unit stability and function in individuals with SMA. Further clinical research is essential to validate efficacy, determine optimal timing, and define the patient subgroups most likely to benefit from myostatin-targeted therapies. Full article