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Single-cell technologies have enabled the characterization of the tumour microenvironment at unprecedented depth and have revealed vast cellular diversity among tumour cells and their niche. Anti-tumour immunity relies on cell–cell relationships within the tumour microenvironment 1 , 2 , yet many single-cell studies lack spatial context and rely on dissociated tissues 3 . Here we applied imaging mass cytometry to characterize the immunological landscape of 139 high-grade glioma and 46 brain metastasis tumours from patients. Single-cell analysis of more than 1.1 million cells across 389 high-dimensional histopathology images enabled the spatial resolution of immune lineages and activation states, revealing differences in immune landscapes between primary tumours and brain metastases from diverse solid cancers. These analyses revealed cellular neighbourhoods associated with survival in patients with glioblastoma, which we leveraged to identify a unique population of myeloperoxidase (MPO)-positive macrophages associated with long-term survival. Our findings provide insight into the biology of primary and metastatic brain tumours, reinforcing the value of integrating spatial resolution to single-cell datasets to dissect the microenvironmental contexture of cancer. Imaging mass cytometry of human brain tumours provides spatial information that, combined with existing transcriptomic data, reveals the existence of a cellular neighbourhood containing a rare macrophage population associated with prolonged survival.

Purpose: The paper presents empirical evidence of sustainable practices adopted by rural tourism stakeholders. It explores the concept and meaning of sustainable practices and what motivates rural tourism stakeholders to adopt sustainable tourism practices as well as recommendations to enhance sustainable rural tourism practices. Design/methodology/approach: This paper describes an exploratory qualitative research project designed to investigate sustainable tourism practices of the rural tourism stakeholders. An inductive approach was adopted to address the research objectives. Specifically, this paper focuses on individuals' subjectivity and understanding of sustainable tourism practices in terms of meaning, motivations, and areas of improvement. The respondents' opinions were collected through semi-structured interviews. A total of 29 rural tourism operators participated in the data collection from the two rural tourism associations in Sabah, Malaysia. The data collection was held at Kota Marudu and Kuala Penyu from April to May 2022. Findings: The findings revealed that sustainable tourism practices relate to conservation and preservation, economic benefits, collaboration and protection, environmental impact, future growth, awareness, knowledge, and improvement. Interestingly, the meaning of sustainable tourism practices is strongly connected to the term “fairness”, to competitive products and quality attractions, and to meeting tourists' needs. This implies the meaning of sustainable tourism practices is not limited to economic, environmental, and sociocultural impacts; it also relates to quality tourism products and the needs of tourists. Key drivers for sustainability practices include economic, social, environmental, and government support. Relevant approaches for improving sustainable rural tourism practices include greater participation and collaboration among rural tourism operators, conservation and preservation, destination uniqueness, long-term growth, and 3Rs practices (reduce, reuse, and recycle). Research limitations/implications: Findings implicate sustainable rural tourism destination management and the rural tourism stakeholders to adopt and enhance the sustainability of the rural sites and destination. It also extends the scope of existing literature on the meaning, motivation and sustainability practices of rural tourist destinations. Originality/value: This study focuses on the importance of sustainability in rural tourism in Sabah, Malaysia, an area on which limited empirical research has been done. The study provides an in-depth understanding of the meaning and drivers of sustainable practices from the rural tourism operators' perspectives. Additionally, it proposes sound strategies for sustainable rural tourism practices. Such practices and development are attributed to an individual's understanding of the concept of and motives for adopting sustainable development practices, government support, and core infrastructure. Finally, this study offers practical implications for sustainable development of rural tourism.

Extracellular vesicles (EVs) are a unique mode of intercellular communication capable of incredible specificity in transmitting signals involved in cellular function, including germ cell maturation. Spermatogenesis occurs in the testes, behind a protective barrier to ensure safeguarding of germline DNA from environmental insults. Following DNA compaction, further sperm maturation occurs in the epididymis. Here, we report reproductive tract EVs transmit information regarding stress in the paternal environment to sperm, potentially altering fetal development. Using intracytoplasmic sperm injection, we found that sperm incubated with EVs collected from stress-treated epididymal epithelial cells produced offspring with altered neurodevelopment and adult stress reactivity. Proteomic and transcriptomic assessment of these EVs showed dramatic changes in protein and miRNA content long after stress treatment had ended, supporting a lasting programmatic change in response to chronic stress. Thus, EVs as a normal process in sperm maturation, can also perform roles in intergenerational transmission of paternal environmental experience. Evidence for sperm small noncoding RNA-mediated intergenerational transmission implies communication from responsive somatic cells to sperm. Here, authors show that epididymal cells alter extracellular vesicle cargo after stress exposure, to impact offspring neurodevelopment and stress reactivity.

Hundreds of microRNAs (miRNAs) are expressed in distinct spatial and temporal patterns during embryonic and postnatal mouse development. The loss of all miRNAs through the deletion of critical miRNA biogenesis factors results in early lethality. The function of each miRNA stems from their cumulative negative regulation of multiple mRNA targets expressed in a particular cell type. During development, miRNAs often coordinate the timing and direction of cell fate transitions. In adults, miRNAs frequently contribute to organismal fitness through homeostatic roles in physiology. Here, we review how the recent dissection of miRNA-knockout phenotypes in mice as well as advances related to their targets, dosage, and interactions have collectively informed our understanding of the roles of miRNAs in mammalian development and adaptive responses.MicroRNAs (miRNA) exert essential functions in mammalian development and physiology. The authors review recent insights from the phenotypic analysis of miRNA knockouts in mice that emphasize roles for these non-coding RNAs at different developmental stages and in adults, and illustrate the importance of functional miRNA targets, miRNA dosage, miRNA interactions and cellular context.

Background Glucocorticoids are frequently required for management of cough because of inflammatory airway disease (IAD) and airway collapse (AWC). Objectives/Hypothesis To determine the efficacy and feasibility of inhaled administration of corticosteroids in controlling cough in dogs with noninfectious airway disease. Animals Thirty‐six client‐owned dogs. Methods Dogs were prospectively recruited for this placebo‐controlled cross‐over study. Inflammatory airway disease was diagnosed through bronchoalveolar lavage cytology. Airway collapse was diagnosed through bronchoscopy, or if dogs were unsuitable anesthetic candidates, by crackles on auscultation, radiographic changes in airway diameter, or fluoroscopy. Dogs were randomly assigned to receive placebo or fluticasone propionate for the first 2 weeks of the trial then crossed over to fluticasone. A quality of life (QOL) survey (best score 0, worst score 85) was completed at 0 and 6 weeks. A visual‐analog cough survey was submitted at 0, 2, 4, and 6 weeks to assess cough, feasibility, and adverse effects of treatment. Results For 32 dogs, QOL score at study end (mean 11.3 ± 9.7) was significantly lower (P < .0001) compared to entry (mean 28.1 ± 14.1), with a median change of 69% in QOL score, indicating improved quality of life. Cough frequency, duration, and severity were significantly (P < .0001) decreased at study end. Feasibility of aerosolized delivery improved with continued use (P = .05) with only 1 dog unable to accept inhaled medication. Conclusion and Clinical Importance This study supports the utility of fluticasone propionate by inhalation in management of cough in dogs with IAD and AWC.

Recognizing the importance of local community participation in responsible tourism and its benefits, this case study explores and analyses the local community participation and responsible tourism practices at Lower Kinabatangan, Sabah, a premier ecotourism destination from the stakeholders’ perspectives. It also describes the perception and attitudes towards tourism development including the key issues and challenges faced by the local communities. The case study adopted multiple methods involving focus-group interviews and survey questionnaires with the respective local communities residing in Lower Kinabatangan. Findings reveal that local communities recognized that Lower Kinabatangan has great potential to be developed as a sustainable ecotourism destination and to generate economic benefit. Despite this, there is limited participation of local communities in ecotourism development and responsible tourism practices among the local communities. The socio-economic demographic of the local community shows that only 42.4% of respondents have work related to tourism activities. Lack of capital and knowledge in tourism activities are the key barriers for local participation in ecotourism development. For Lower Kinabatangan to be a sustainable ecotourism destination, the participation and engagement of the local community and the practices of responsible tourism can no longer be ignored.

A comprehensive study of global AIDS activism over the past twenty-five years. Few diseases have provoked as many wild moralistic leaps or stringent attempts to measure, classify, and define risk and treatment standards as AIDS. In Politics in the Corridor of Dying, Jennifer Chan documents the emergence of a diverse range of community-based, nongovernmental, and civil society groups engaged in patient-focused AIDS advocacy worldwide. She also critically evaluates the evolving role of these groups in challenging authoritative global health governance schemes put in place by what she describes as overcontrolling or sanctimonious governments, scientists, religious figures, journalists, educators, and corporations. Drawing on more than 100 interviews conducted across eighteen countries, the book covers a broad spectrum of contemporary sociopolitical issues in AIDS activism, including the criminalization of HIV transmission, the fight against \"big pharma,\" and the politics of the President's Emergency Plan for AIDS Relief. Chan argues that AIDS activism disrupts four contemporary regimes of power—scientific monopoly, market fundamentalism, governance statism, and community control—by elevating alternative knowledge production and human rights. This multidisciplinary book is aimed at students and scholars of public health, sociology, and political science, as well as health practitioners and activists. Politics in the Corridor of Dying makes specific policy recommendations for the future while revealing how AIDS activism around the world has achieved much more than increased funding, better treatment, and more open clinical trial access: by forcing controlling entities to democratize, activists have changed the balance of power for the better and helped advance permanent social change.

In order to supply adequate iron during pregnancy, the levels of the iron regulatory hormone hepcidin in the maternal circulation are suppressed, thereby increasing dietary iron absorption and storage iron release. Whether this decrease in maternal hepcidin is caused by changes in factors known to regulate hepcidin expression, or by other unidentified pregnancy factors, is not known. To investigate this, we examined iron parameters during pregnancy in mice. We observed that hepatic iron stores and transferrin saturation, both established regulators of hepcidin production, were decreased in mid and late pregnancy in normal and iron loaded dams, indicating an increase in iron utilization. This can be explained by a significant increase in maternal erythropoiesis, a known suppressor of hepcidin production, by mid-pregnancy, as indicated by an elevation in circulating erythropoietin and an increase in spleen size and splenic iron uptake. Iron utilization increased further in late pregnancy due to elevated fetal iron demand. By increasing maternal iron levels in late gestation, we were able to stimulate the expression of the gene encoding hepcidin, suggesting that the iron status of the mother is the predominant factor influencing hepcidin levels during pregnancy. Our data indicate that pregnancy-induced hepcidin suppression likely occurs because of reductions in maternal iron reserves due to increased iron requirements, which predominantly reflect stimulated erythropoiesis in mid-gestation and increased fetal iron requirements in late gestation, and that there is no need to invoke other factors, including novel pregnancy factor(s), to explain these changes.

Purpose: This study explores the COVID-19 pandemic on the tourism sector and tourist destinations by expanding the Tourism Area Life Cycle (TALC) model, thus providing a more comprehensive understanding of the pandemic's influence on destination and insights for developing effective revitalization strategies for tourism destinations. Design/methodology/approach: Employing a qualitative research approach, the study utilizes the TALC model to conduct qualitative interviews with tour operators and hoteliers, aiming to gather nuanced insights into the im-pacts of the pandemic on tourism destinations. Nine tour operators and four hoteliers participated in the online interviews. Data analysis was driven by the interview responses, and thematic analysis was guided by concepts of the COVID-19 pandemic impacts and the six stages of Butler's TALC model. Findings: Severe impact of the pandemic on tourism businesses, encompassing a decline in tourist arrivals, business closures, and substantial job and income loss. Tourist destination impacts can be classified into four distinct stages― stagnation, exploration, involvement, development, and consolidation providing a structured framework for inter―preting the evolving dynamics of tourism destinations. Contextual issues and diverse approaches are suggested to revitalize tourist destinations in order remain attractive, competitive, and sustainable. Research limitations/implications: The restriction of the sample size to only two tourism sectors and generalizing findings due to the exploratory and qualitative nature of the research. Originality/value: It provides insightful of pandemic impacts on tourist destination and relevant strategies, drawing upon Butler's theory. The practical implications for destination management and stakeholder engagement are in-strumental in shaping the development of effective destination management strategies.

Study of the origin and development of cerebellar tumours has been hampered by the complexity and heterogeneity of cerebellar cells that change over the course of development. Here we use single-cell transcriptomics to study more than 60,000 cells from the developing mouse cerebellum and show that different molecular subgroups of childhood cerebellar tumours mirror the transcription of cells from distinct, temporally restricted cerebellar lineages. The Sonic Hedgehog medulloblastoma subgroup transcriptionally mirrors the granule cell hierarchy as expected, while group 3 medulloblastoma resembles Nestin + stem cells, group 4 medulloblastoma resembles unipolar brush cells, and PFA/PFB ependymoma and cerebellar pilocytic astrocytoma resemble the prenatal gliogenic progenitor cells. Furthermore, single-cell transcriptomics of human childhood cerebellar tumours demonstrates that many bulk tumours contain a mixed population of cells with divergent differentiation. Our data highlight cerebellar tumours as a disorder of early brain development and provide a proximate explanation for the peak incidence of cerebellar tumours in early childhood. Sequencing data from the developing cerebellum are compared with bulk sequencing data from paediatric tumours, providing insights into their potential origins and suggesting that many cerebellar tumours have their origins early in utero.