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During tumor progression, cancer cells come into contact with various non-tumor cell types, but it is unclear how tumors adapt to these new environments. Here, we integrate spatially resolved transcriptomics, single-cell RNA-seq, and single-nucleus RNA-seq to characterize tumor-microenvironment interactions at the tumor boundary. Using a zebrafish model of melanoma, we identify a distinct “interface” cell state where the tumor contacts neighboring tissues. This interface is composed of specialized tumor and microenvironment cells that upregulate a common set of cilia genes, and cilia proteins are enriched only where the tumor contacts the microenvironment. Cilia gene expression is regulated by ETS-family transcription factors, which normally act to suppress cilia genes outside of the interface. A cilia-enriched interface is conserved in human patient samples, suggesting it is a conserved feature of human melanoma. Our results demonstrate the power of spatially resolved transcriptomics in uncovering mechanisms that allow tumors to adapt to new environments., During tumor progression, cancer cells contact different neighboring cell types, but it is unclear how these interactions affect cancer cell behavior. Here, the authors use spatially resolved transcriptomics and single-cell RNA-seq to study the role of cilia at the tumormicroenvironment interface.

Innovative solutions to help older adults increase physical activity are critically important. In this qualitative study, we explored older adults’ acceptance, capability, and experiences of using three different types of electronic wearable devices over a period of 4–24 weeks for self-monitoring and promoting physical activity. We conducted 23 semistructured interviews with older adults who participated in three physical activity intervention studies. Two researchers analyzed the data using NVivo version 12, applying a directed content analysis that was partially guided by the Unified Theory of Acceptance and Use of Technology 2 (UTAUT2). Six themes emerged: (1) device learning, (2) hedonic motivation, (3) habit and adherence, (4) facilitating conditions, (5) effort expectancy, and (6) performance expectancy. Although most older adults (95.8%) from this study were first-time users, they reflected positive experiences and generally enjoyed using electronic wearable devices. Participants reported issues related to electronic wearable device functionalities that can be improved to better enhance user experience and motivate increased physical activity. Future research should explore the role of electronic wearable devices in older adults’ physical activity with an emphasis on behavioral change over time.

This study aims to comprehensively review and update the literature concerning the correlates of sleep disturbance among caregivers of persons living with Alzheimer's disease and related dementias to identify gaps in the literature and antecedent targets for interventions.We searched PubMed, CINAHL, PsycINFO, and Embase using terms related to "sleep," "caregiver," and "dementia."Thirty-six articles were included in this review. Based on the antecedents within the 3P model of insomnia, predisposing factors associated with caregiver sleep included caregiver demographics, and physiological factors like genotype and biomarkers. Precipitating factors related to caregiver sleep included caregiving status and responsibilities, and person living with dementia factors.Sleep disturbance is a significant issue for caregivers of persons living with dementia. However, this review has identified multiple precipitating factors that are modifiable targets for interventions to improve or enhance caregiver sleep.Numerous predisposing and precipitating factors contribute to caregivers of persons living with dementia being susceptible to sleep disturbance. Healthcare providers should ask patients about their caregiving status during annual visits. Healthcare providers should also evaluate caregivers' sleep patterns, and the predisposing and precipitating factors of sleep disturbance, with a focus on the modifiable factors, to enable timely intervention.

Background: Due to overnight caregiving demands; exacerbation of high rates of anxiety, depression, and distress; and inadequate support, millions of family caregivers of patients receiving in-home hospice are at risk of poor sleep and negative health effects. Aim: To describe sleep experiences of family caregivers of in-home hospice patients and perceptions of these experiences on caregivers’ wellbeing in the context of caregiver health and live-in status. Design: Developed using the Symptom Management Model, this mixed methods study featured a concurrent nested design prioritizing qualitative reflexive thematic analysis. Setting/participants: About 47 family caregivers of in-home hospice patients from two randomized clinical trials (NCT03712410, NCT02929108) were interviewed (United States, 2021). Anxiety (GAD-7), depression (PHQ-9), quality-of-life (QOL) (CQLI-R), and self-rated health and energy were reported prior to interviews. Results: Qualitative analysis revealed three themes: compromised sleep quality, factors influencing sleep, effects of sleep. 72.5% of hospice family caregivers described “fair” or “poor” sleep quality, with “ interrupted” sleep and frequent night-waking due to “ on-call” “ vigilance” and anxiety. Negative effects included exhaustion, mental and physical health decline, and reduced caregiver function. Live-in caregivers reported higher mean depression scores (8.4 vs 4.3, p = 0.08), higher mean anxiety scores (7.7 vs 3.3, p = 0.06), and lower mean QOL scores (24.8 vs 33.6, p Conclusion: End-of-life family caregivers experience disrupted sleep with negative effects and inadequate support. Clinicians must assess sleep, offer sleep interventions, and provide more supports to hospice family caregivers.

Sleep disruption is common among older adults. Non-pharmacological interventions involving music has emerged as a promising approach to address sleep disruption. The purpose of this systematic review was to examine the effects of music interventions on sleep outcomes among older adults (age ≥ 50). We searched five databases through May 2020 and found 16 eligible studies focused on two types of music interventions: music listening (n = 11) and multi-component (n = 5). We found mixed evidence in the efficacy of music interventions to improve sleep outcomes in older adults, which included sleep quality, objective and subjective sleep characteristics. Music listening interventions contained relaxing music with research teams personalizing music choice based on participants’ preferences. Multi-component interventions included listening to music in addition to one other approach, such as massage, tai chi, and nature scenes. Future higher-quality studies should provide a detailed description of music interventions and tailor music selections to older adults’ preferences.

Spatial variation in cellular phenotypes underlies heterogeneity in immune recognition and response to therapy in cancer and many other diseases. Spatial transcriptomics (ST) holds the potential to quantify such variation, but existing analysis methods address only a small part of the analysis challenge, such as spot deconvolution or spatial differential expression. We present BayesTME, an end-to-end Bayesian method for analyzing spatial transcriptomics data. BayesTME unifies several previously distinct analysis goals under a single, holistic generative model. This unified approach enables BayesTME to (i) be entirely reference-free without any need for paired scRNA-seq, (ii) outperform a large suite of methods in quantitative benchmarks, and (iii) uncover a new type of ST signal: spatial differential expression within individual cell types. To achieve the latter, BayesTME models each phenotype as spatially adaptive and discovers statistically significant spatial patterns amongst coordinated subsets of genes within phenotypes, which we term spatial transcriptional programs. On human and zebrafish melanoma tissues, BayesTME identifies spatial transcriptional programs that capture fundamental biological phenomena like bilateral symmetry, differential expression between interior and surface tumor cells, and tumor-associated fibroblast and macrophage reprogramming. Our results demonstrate BayesTME’s power in unlocking a new level of insight from spatial transcriptomics data and fostering a deeper understanding of the spatial architecture of the tumor microenvironment. BayesTME is open source and publicly available (https://github.com/tansey-lab/bayestme).

This study aimed to describe frailty and fear of falling and examine the cross-sectional association between frailty and fear of falling in community-dwelling older adults in China. We recruited 165 older adults from five selected communities in the five districts of Changchun, Jilin Province. Participants were asked to complete a demographic questionnaire, the Short Falls Efficacy Scale-International, and the Tilburg Frailty Indicator. We found that 60% of our participants were frail and that 81% reported a fear of falling. Using binary logistic regression, we found that the participants with fear of falling were 7.2 times more likely to be frail. These findings suggest that fear of falling should be regularly screened in clinical practice to help identify older adults with greater risks of frailty. Future longitudinal studies of larger sample size are needed to confirm the association. Moreover, frailty prevention programs that include strategies to reduce the fear of falling should be tested among community-dwelling older adults.

Recruitment for dementia research is challenging and costly. Using Ajzen’s Theory of Planned Behavior we explored attitudes, perceived norms, and perceived behavioral control of persons living with dementia (PLWD) and their caregivers who participated in one clinical trial to better understand factors that influence dyads’ decisions to enroll. We conducted semi-structured telephone interviews with 12 PLWD and 9 caregivers and utilized directed content analysis. Categories connected with positive attitudes about study enrollment were personal desires of wanting to learn and in-person meetings with knowledgeable staff. Additionally, participants said the money always helps in terms of the financial incentive. Participants reported enrolling to support another person (perceived norm). Study requirements were thought to be easy (perceived behavioral control). Participants highlighted the importance of flexible scheduling and study tasks being completed at their home. Findings can inform future recruitment efforts and should be investigated as effective recruitment methods in other clinical trials.

Background Daytime napping may improve cognitive function in older adults. However, the association can be complicated by specific features of napping and the older adult’s health. This systematic review aims to synthesize the current literature on napping and cognition in older adults and provide recommendations for future research and daytime sleep practice in older adults. Methods Systematic searches for relative research published between January 1995 and October 2022 were conducted at PubMed, MEDLINE, PsycINFO, and Google Scholar using keywords individually and in multiple combinations. Manual searches were performed to identify additional studies. All included studies were critically appraised by 2 authors. Results Thirty-five studies, including 23 observational and 12 intervention studies, were reviewed. Findings from observational studies suggest a possible inverted U-shaped association between napping duration and cognitive function: short and moderate duration of naps benefited cognitive health in older adults compared with both non-napping and long or extended napping. Findings from intervention studies suggest one session of afternoon napping might improve psychomotor function and working memory, although with some inconsistency. The effect of multiple nap sessions on cognition was inconclusive due to a limited number of studies. Conclusion More rigorous research studies are needed to investigate what causes different patterns of daytime napping, the associations between these distinct patterns and cognitive function, and to determine whether interventions targeting napping patterns can improve cognition in older adults. In addition, future research needs to comprehensively assess daytime napping using a combination of measures such as sleep diary and actigraphy.

Oncogenic alterations to DNA are not transforming in all cellular contexts1,2. This may be due to pre-existing transcriptional programmes in the cell of origin. Here we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet or under the nails3. We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma and enrichment for CRKL amplifications in acral melanoma. We modelled these changes in transgenic zebrafish models and found that CRKL-driven tumours formed predominantly in the fins of the fish. The fins are the evolutionary precursors to tetrapod limbs, indicating that melanocytes in these acral locations may be uniquely susceptible to CRKL. RNA profiling of these fin and limb melanocytes, when compared with body melanocytes, revealed a positional identity gene programme typified by posterior HOX13 genes. This positional gene programme synergized with CRKL to amplify insulin-like growth factor (IGF) signalling and drive tumours at acral sites. Abrogation of this CRKL-driven programme eliminated the anatomic specificity of acral melanoma. These data suggest that the anatomic position of the cell of origin endows it with a unique transcriptional state that makes it susceptible to only certain oncogenic insults.