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This scoping review explored the effect of different strength training (ST) programs on Phase Angle (PhA), a marker of cellular health, in healthy young adults. A systematic search was conducted in PubMed, SciELO, Web of Science, and Scopus until April 2025, following the PRISMA framework (PICOS) for longitudinal controlled trials with healthy adults (18-35 years) undergoing ST (dynamic/isometric) for at least 4 weeks. Of 8722 records, four studies were included, revealing variable immediate effects of ST on PhA (increases, decreases, and no significant changes). The synthesised evidence suggests, however, that ST protocols with higher training volumes and intensities may be associated with more favourable long-term changes in PhA. It is concluded that, although ST with higher volume and intensity may be beneficial, the immediate effects on PhA are variable. Modalities such as low-load blood flow restriction training or low-frequency isometric training may not improve, or may even decrease, PhA in the short term. Given the scarcity and heterogeneity of studies, this review is exploratory, and further research is needed to optimise PhA through ST in young adults. Esta revisão de escopo explorou o efeito de diferentes programas de treino de força (TF) no Ângulo de Fase (PhA), marcador de saúde celular, em adultos jovens saudáveis. Realizou-se uma pesquisa sistemática (PubMed, SciELO, Web of Science, Scopus; até abril de 2025; PRISMA; PICOS) por ensaios controlados longitudinais com adultos saudáveis (18-35 anos) submetidos a TF (dinâmico/isométrico) por ≥4 semanas. Dos 8722 registos, quatro estudos foram incluídos, revelando efeitos imediatos variáveis do TF no PhA (aumentos, diminuições, sem alterações significativas). A evidência sintetizada sugere, contudo, que protocolos de TF com maiores volumes e intensidades podem associar-se a alterações mais favoráveis no PhA a longo prazo. Conclui-se que, embora TF com maior volume e intensidade possa ser benéfico, os efeitos imediatos no PhA são variáveis. Modalidades como treino com restrição de fluxo sanguíneo de baixa carga ou isométrico de baixa frequência podem não melhorar, ou até diminuir, o PhA a curto prazo. Dada a escassez e heterogeneidade dos estudos, esta revisão é exploratória, sendo necessária mais investigação para otimizar o PhA através do TF em adultos jovens.

Tissues are dynamically shaped by bidirectional communication between resident cells and the extracellular matrix (ECM) through cell-matrix interactions and ECM remodelling. Tumours leverage ECM remodelling to create a microenvironment that promotes tumourigenesis and metastasis. In this review, we focus on how tumour and tumour-associated stromal cells deposit, biochemically and biophysically modify, and degrade tumour-associated ECM. These tumour-driven changes support tumour growth, increase migration of tumour cells, and remodel the ECM in distant organs to allow for metastatic progression. A better understanding of the underlying mechanisms of tumourigenic ECM remodelling is crucial for developing therapeutic treatments for patients. Tumors are more than cancer cells — the extracellular matrix is a protein structure that organizes all tissues and is altered in cancer. Here, the authors review recent progress in understanding how the cancer cells and tumor-associated stroma cells remodel the extracellular matrix to drive tumor growth and metastasis.

A recent increase in the literature regarding the evidence base for clozapine has made it increasingly difficult for clinicians to judge “best evidence” for clozapine use. As such, we aimed at elucidating the state-of-the-art for clozapine with regard to efficacy, effectiveness, tolerability, and management of clozapine and clozapine-related adverse events in neuropsychiatric disorders. We conducted a systematic PRISMA-conforming quantitative meta-review of available meta-analytic evidence regarding clozapine use. Primary outcome effect sizes were extracted and transformed into relative risk ratios (RR) and standardized mean differences (SMD). The methodological quality of meta-analyses was assessed using the AMSTAR-2 checklist. Of the 112 meta-analyses included in our review, 61 (54.5%) had an overall high methodological quality according to AMSTAR-2. Clozapine appears to have superior effects on positive, negative, and overall symptoms and relapse rates in schizophrenia (treatment-resistant and non-treatment-resistant subpopulations) compared to first-generation antipsychotics (FGAs) and to pooled FGAs/second-generation antipsychotics (SGAs) in treatment-resistant schizophrenia (TRS). Despite an unfavorable metabolic and hematological adverse-event profile compared to other antipsychotics, hospitalization, mortality and all-cause discontinuation (ACD) rates of clozapine surprisingly show a pattern of superiority. Our meta-review outlines the superior overall efficacy of clozapine compared to FGAs and most other SGAs in schizophrenia and suggests beneficial efficacy outcomes in bipolar disorder and Parkinson’s disease psychosis (PDP). More clinical studies and subsequent meta-analyses are needed beyond the application of clozapine in schizophrenia-spectrum disorders and future studies should be directed into multidimensional clozapine side-effect management to foster evidence and to inform future guidelines.

Cellular senescence is a state of stable, terminal cell cycle arrest associated with various macromolecular changes and a hypersecretory, pro-inflammatory phenotype. Entry of cells into senescence can act as a barrier to tumorigenesis and, thus, could in principle constitute a desired outcome for any anticancer therapy. Paradoxically, studies published in the past decade have demonstrated that, in certain conditions and contexts, malignant and non-malignant cells with lastingly persistent senescence can acquire pro-tumorigenic properties. In this Review, we first discuss the major mechanisms involved in the antitumorigenic functions of senescent cells and then consider the cell-intrinsic and cell-extrinsic factors that participate in their switch towards a tumour-promoting role, providing an overview of major translational and emerging clinical findings. Finally, we comprehensively describe various senolytic and senomorphic therapies and their potential to benefit patients with cancer.The entry of cells into senescence can act as a barrier to tumorigenesis; however, in certain contexts senescent malignant and non-malignant cells can acquire pro-tumorigenic properties. The authors of this Review discuss the cell-intrinsic and cell-extrinsic mechanisms involved in both the antitumorigenic and tumour-promoting roles of senescent cells, and describe the potential of various senolytic and senomorphic therapeutic approaches in oncology.

In recent years, sedentary behaviour and physical inactivity have seen an evident increase. Many individuals who embark on an exercise regimen end up leaving it within the first three to six months, often citing barriers such as a lack of time or motivation. Research shows that the pleasure and enjoyment derived from exercise play a crucial role in preventing people from giving up. This suggests that theories related to the emotional aspects of exercise, including an individual’s exercise intensity preference and tolerance, should be integrated into broader motivation theories such as Self-Determination Theory (SDT). This chapter aims to provide a theoretical framework for these theories, emphasised by empirical evidence and proposes potential avenues for future research.

- This review aims to summarise the studies’ insightful exploration of the relationship between adapted sport, social support, resilience, and well-being among Portuguese athletes with disabilities. The research emphasises the crucial role of social support in access to sport, but interestingly, it may not always be directly correlated with resilience or subjective well-being. Athletes with disabilities show high resilience and positive affect while scoring lower regarding negative affect. Technical support is vital for federated athletes with disabilities, and friendships are universally significant. Resilience emerges as a central factor, with strong associations with subjective well-being, indicating its importance in the sporting context. In addition, resilience appears to buffer negative emotions, emphasising its crucial role. In conclusion, these results challenge existing assumptions and emphasise the multifaceted nature of the relationship between social support, resilience and well-being among athletes with disabilities. This knowledge has practical implications for stakeholders, including parents, coaches, therapists, psychologists, and society. They underline the importance of fostering inclusive sports programmes and promoting awareness and partnerships to improve the well-being, resilience and social support of individuals with disabilities, ultimately contributing to their personal development, quality of life and social integration. Policymakers and organisations should consider these conclusions when formulating education and sports policies.

Obesity is a chronic disease associated with increased risk of obesity-related complications and mortality. Our better understanding of the weight regulation mechanisms and the role of gut-brain axis on appetite has led to the development of safe and effective entero-pancreatic hormone-based treatments for obesity such as glucagon-like peptide-1 (GLP-1) receptor agonists (RA). Semaglutide 2.4 mg once weekly, a subcutaneously administered GLP-1 RA approved for obesity treatment in 2021, results in 15–17% mean weight loss (WL) with evidence of cardioprotection. Oral GLP-1 RA are also under development and early data shows similar WL efficacy to semaglutide 2.4 mg. Looking to the next generation of obesity treatments, combinations of GLP-1 with other entero-pancreatic hormones with complementary actions and/or synergistic potential (such as glucose-dependent insulinotropic polypeptide (GIP), glucagon, and amylin) are under investigation to enhance the WL and cardiometabolic benefits of GLP-1 RA. Tirzepatide, a dual GLP-1/GIP receptor agonist has been approved for glycaemic control in type 2 diabetes as well as for obesity management leading in up to 22.5% WL in phase 3 obesity trials. Other combinations of entero-pancreatic hormones including cagrisema (GLP-1/amylin RA) and the triple agonist retatrutide (GLP-1/GIP/glucagon RA) have also progressed to phase 3 trials as obesity treatments and early data suggests that may lead to even greater WL than tirzepatide. Additionally, agents with different mechanisms of action to entero-pancreatic hormones (e.g. bimagrumab) may improve the body composition during WL and are in early phase clinical trials. We are in a new era for obesity pharmacotherapy where combinations of entero-pancreatic hormones approach the WL achieved with bariatric surgery. In this review, we present the efficacy and safety data for the pipeline of obesity pharmacotherapies with a focus on entero-pancreatic hormone-based treatments and we consider the clinical implications and challenges that the new era in obesity management may bring.

This article reviews the rapidly growing domain of global value chain (GVC) research by analyzing several highly cited conceptual frameworks and then appraising GVC studies published in such disciplines as international business, general management, supply chain management, operations management, economic geography, regional and development studies, and international political economy. Building on GVC conceptual frameworks, we conducted the review based on a comparative institutional perspective that encompasses critical governance issues at the micro-, GVC, and macro-levels. Our results indicate that some of these issues have garnered significantly more scholarly attention than others. We suggest several future research topics such as microfoundations of GVC governance, GVC mapping, learning, impact of lead firm ownership and strategy, dynamics of GVC arrangements, value creation and distribution, financialization, digitization, the impact of renewed protectionism, the impact of GVCs on their macro-environment, and chainlevel performance management.

Large language models (LLMs) can respond to free-text queries without being specifically trained in the task in question, causing excitement and concern about their use in healthcare settings. ChatGPT is a generative artificial intelligence (AI) chatbot produced through sophisticated fine-tuning of an LLM, and other tools are emerging through similar developmental processes. Here we outline how LLM applications such as ChatGPT are developed, and we discuss how they are being leveraged in clinical settings. We consider the strengths and limitations of LLMs and their potential to improve the efficiency and effectiveness of clinical, educational and research work in medicine. LLM chatbots have already been deployed in a range of biomedical contexts, with impressive but mixed results. This review acts as a primer for interested clinicians, who will determine if and how LLM technology is used in healthcare for the benefit of patients and practitioners. This review explains how large language models (LLMs), such as ChatGPT, are developed and discusses their strengths and limitations in the context of potential clinical applications.

Recent advancements in computational inverse-design approaches — algorithmic techniques for discovering optical structures based on desired functional characteristics — have begun to reshape the landscape of structures available to nanophotonics. Here, we outline a cross-section of key developments in this emerging field of photonic optimization: moving from a recap of foundational results to motivation of applications in nonlinear, topological, near-field and on-chip optics.