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All light has structure, but only recently has it been possible to control it in all its degrees of freedom and dimensions, fuelling fundamental advances and applications alike. Here we review the recent advances in ‘pushing the limits’ with structured light, from traditional two-dimensional transverse fields towards four-dimensional spatiotemporal structured light and multidimensional quantum states, beyond orbital angular momentum towards control of all degrees of freedom, and beyond a linear toolkit to include nonlinear interactions, particularly for high-harmonic structured light. Using a simple interference argument, centuries old, we weave a story that highlights the common nature of seemingly diverse structures, presenting a modern viewpoint on the classes of structured light, and outline the possible future trends and open challenges.Recent effort in controlling the structure of light in all its degrees of freedom and dimensions has pushed the limits of structured light and broadened its potential beyond orbital angular momentum, two-dimensional fields, qubits and biphotons, and linear optical manipulation.

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.

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.

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.

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.

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.

The objective of this research is to point out studies that describe variables that are associated with the impact of contingency measures resulting from the pandemic on the mental health of university students. A systematic review was carried out, following the PRISMA-P guidelines and PECO approach, and the review protocol was registered in INPLASTY. The search was conducted in five databases from December 2019 to December 2022. A selection process was carried out by title, abstract and full text, according to the inclusion and exclusion criteria. Initially, 27,458 articles were identified, and after eliminating duplicates, applying the inclusion criteria and critical analysis, 11 original articles were selected for qualitative analysis. The sample size was 47,552 participants, the majority of whom were women (68.07%) with an average age of 21.07 years. It was concluded that contingency measures (social isolation, quarantine, distancing) as a measure to prevent the spread of the pandemic had a negative impact on the psychological well-being of university students. Adequate support and research into which interventions can mitigate these risks are essential. We suggest the implementation of psychological interventions, which should be promoted proactively, to minimise negative impacts. O objetivo desta investigação é sugerir estudos que descrevam variações que estavam relacionadas ao impacto das medidas de contingência decorrentes da pandemia na saúde mental dos estudantes universitários. Foi realizada uma revisão sistemática, seguindo as diretrizes PRISMA-P e abordagem PECO, o protocolo de revisão foi registrado no INPLASTY. A busca foi realizada em cinco bases de dados, no período de dezembro de 2019 a dezembro de 2022. Foi realizado um processo de seleção por título, resumo e texto completo, de acordo com os critérios de inclusão e exclusão. Inicialmente, foram identificados 27.458 artigos, e após a eliminação de duplicatas, aplicação dos critérios de inclusão e análise crítica, foram selecionados 11 artigos originais para análise qualitativa. O tamanho da amostra foi de 47.552 participantes, sendo a maioria do sexo feminino (68,07%) com idade média de 21,07 anos. Conclui-se que as medidas de contingência (isolamento social, quarentena, distanciamento) como medida de prevenção da propagação da pandemia tiveram um impacto negativo no bem-estar psicológico dos estudantes universitários. É essencial um apoio adequado à investigação sobre as disciplinas que podem atenuar estes riscos. Sugerimos a implementação de práticas psicológicas, que devem ser promovidas de forma proativa, para minimizar os impactos negativos.

Recent developments in chip-based nonlinear photonics offer the tantalizing prospect of realizing many applications that can use optical frequency comb devices that have form factors smaller than 1 cm3 and that require less than 1 W of power. A key feature that enables such technology is the tight confinement of light due to the high refractive index contrast between the core and the cladding. This simultaneously produces high optical nonlinearities and allows for dispersion engineering to realize and phase match parametric nonlinear processes with laser-pointer powers across large spectral bandwidths. In this Review, we summarize the developments, applications and underlying physics of optical frequency comb generation in photonic-chip waveguides via supercontinuum generation and in microresonators via Kerr-comb generation that enable comb technology from the near-ultraviolet to the mid-infrared regime.This Review discusses the developments and applications of on-chip optical frequency comb generation based on two concepts—supercontinuum generation in photonic-chip waveguides and Kerr-comb generation in microresonators.