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Abstract Background Tissue differentiation is accompanied by genome-wide changes in the underlying chromatin structure and dynamics, or epigenome. By controlling when, where, and what regulatory factors have access to the underlying genomic DNA, the epigenome influences the cell's transcriptome and ultimately its function. Existing genomic methods for analyzing cell-type-specific changes in chromatin generally involve two elements: (i) a source for purified cells (or nuclei) of distinct types, and (ii) a specific treatment that partitions or degrades chromatin by activity or structural features. For many cell types of great interest, such assays are limited by our inability to isolate the relevant cell populations in an organism or complex tissue containing an intertwined mixture of other cells. This limitation has confined available knowledge of chromatin dynamics to a narrow range of biological systems (cell types that can be sorted/separated/dissected in large numbers and tissue culture models) or to amalgamations of diverse cell types (tissue chunks, whole organisms). Results Transgene-driven expression of DNA/chromatin modifying enzymes provides one opportunity to query chromatin structures in expression-defined cell subsets. In this work we combine in vivo expression of a bacterial DNA adenine methyltransferase (DAM) with high throughput sequencing to sample tissue-specific chromatin accessibility on a genome-wide scale. We have applied the method (DALEC: Direct Asymmetric Ligation End Capture) towards mapping a cell-type-specific view of genome accessibility as a function of differentiated state. Taking advantage of C. elegans strains expressing the DAM enzyme in diverse tissues (body wall muscle, gut, and hypodermis), our efforts yield a genome-wide dataset measuring chromatin accessibility at each of 538,000 DAM target sites in the C. elegans (diploid) genome. Conclusions Validating the DALEC mapping results, we observe a strong association between observed coverage by nucleosomes and low DAM accessibility. Strikingly, we observed no extended regions of inaccessible chromatin for any of the tissues examined. These results are consistent with "local choreography" models in which differential gene expression is driven by intricate local rearrangements of chromatin structure rather than gross impenetrability of large chromosomal regions.

This study tested the effects of deep and subtle mortality cues on state autonomy, in addition to the moderating roles of trait autonomy, psychological flexibility, and curiosity. Australian undergraduate students (N = 442) self-reported on moderator variables before being randomly allocated to receive either deep mortality cues, subtle mortality cues, or a control task, and finally reported their state autonomy for life goals. Trait autonomy did not moderate the effect of mortality cues on state autonomy. However, for individuals high on psychological flexibility, any mortality cues led to increased state autonomy compared to the control. For individuals high on curiosity, there was some evidence that only deep mortality cues led to increased state autonomy. These findings help clarify the nature of growth outcomes (in terms of more authentic, autonomous motivation for life goals), and the personal characteristics that facilitate growth-oriented processing of death awareness. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to compare 3-year overall survival after simultaneous portal (PVE) and hepatic vein (HVE) embolization versus PVE alone in patients undergoing liver resection for primary and secondary cancers of the liver. Methods: In this multicentre retrospective study, all DRAGON 0 centres provided 3-year follow-up data for all patients who had PVE/HVE or PVE, and were included in DRAGON 0 between 2016 and 2019. Kaplan–Meier analysis was undertaken to assess 3-year overall and recurrence/progression-free survival. Factors affecting survival were evaluated using univariable and multivariable Cox regression analyses. Results: In total, 199 patients were included from 7 centres, of whom 39 underwent PVE/HVE and 160 PVE alone. Groups differed in median age (P = 0.008). As reported previously, PVE/HVE resulted in a significantly higher resection rate than PVE alone (92 versus 68%; P = 0.007). Three-year overall survival was significantly higher in the PVE/HVE group (median survival not reached after 36 months versus 20 months after PVE; P = 0.004). Univariable and multivariable analyses identified PVE/HVE as an independent predictor of survival (univariable HR 0.46, 95% c.i. 0.27 to 0.76; P = 0.003). Conclusion: Overall survival after PVE/HVE is substantially longer than that after PVE alone in patients with primary and secondary liver tumours. The multicentre international retrospective DRAGON 0 study showed that simultaneous portal (PVE) and hepatic vein (HVE) embolization in patients with cancer in the liver increases the future liver remnant hypertrophy, kinetic growth rate, and resection rate compared with PVE alone. Mid-term oncological follow-up showed that median 3-year overall survival was significantly increased in the PVE/HVE group. [ABSTRACT FROM AUTHOR]

Use of Instagram has grown rapidly in the last decade, but the effects of Instagram use on well-being are still unclear, with many studies based on younger samples with a female bias. The aim of this study was to examine the associations between Instagram use and levels of anxiety, depression, and loneliness in a nationally representative sample of UK adults by age and gender. An online sample of 498 UK adults were recruited using Prolific (Age: M = 49, SD = 15, range 19-82 years old; 52% female, 47% male). Participants stated whether or not they used Instagram, reported their frequency of Broadcast, Interaction and Browsing Instagram use and completed the Revised UCLA Loneliness Scale, and the Hospital Anxiety and Depression Scale. A genetic matching algorithm was used to match Instagram users (n = 372) and non-Instagram users (n = 100) on age, gender, education and nationality. There were no significant differences between users versus non-users of Instagram in levels of anxiety, depression or loneliness. There were also no significant associations between type of Instagram use (Broadcast, Interaction or Browsing) and levels of anxiety, depression or loneliness. The Bayes Factors for these models moderately to strongly supported the null model of no effect for Depression and Loneliness. This research adds to recent findings that suggests that the overall effect of SNSs on wellbeing may be small to non-existent. Future research should examine how exposure to different types of content on social media are related to well-being. [ABSTRACT FROM AUTHOR]

This document is a journal article that discusses the potential benefits of connecting local archive data, specifically the Archives of the National Debt Redemption Movement, to Wikidata. The article highlights the importance of enhancing accessibility and utilization of cultural heritage records and explains how integrating with Wikidata can provide rich resources, improve data quality, and offer new services. It also discusses the use cases of Wikidata in linking cultural heritage resources and the current status of the National Debt Redemption Movement Digital Archive. Additionally, the document provides information on various properties related to Wikimedia, such as copyright status and catalog codes. [Extracted from the article]

The timing and complexity of the 2014 Farm Bill required quick dissemination of technical information to allow participants to make decisions affecting risk management strategies for their farms. Using existing organizational structures and incorporating a team approach allowed Ohio State University Extension educators to successfully meet the educational needs of Ohio's farmers and landowners. Program success followed due to Extension's commitments to providing proper training, support, and reward to educators and to working cooperatively with external agencies to achieve the identified outcomes.

Introduction: Research driven by real‐world clinical data is increasingly vital to enabling learning health systems, but integrating such data from across disparate health systems is challenging. As part of the NCATS National COVID Cohort Collaborative (N3C), the N3C Data Enclave was established as a centralized repository of deidentified and harmonized COVID‐19 patient data from institutions across the US. However, making this data most useful for research requires linking it with information such as mortality data, images, and viral variants. The objective of this project was to establish privacy‐preserving record linkage (PPRL) methods to ensure that patient‐level EHR data remains secure and private when governance‐approved linkages with other datasets occur. Methods: Separate agreements and approval processes govern N3C data contribution and data access. The Linkage Honest Broker (LHB), an independent neutral party (the Regenstrief Institute), ensures data linkages are robust and secure by adding an extra layer of separation between protected health information and clinical data. The LHB's PPRL methods (including algorithms, processes, and governance) match patient records using "deidentified tokens," which are hashed combinations of identifier fields that define a match across data repositories without using patients' clear‐text identifiers. Results: These methods enable three linkage functions: Deduplication, Linking Multiple Datasets, and Cohort Discovery. To date, two external repositories have been cross‐linked. As of March 1, 2023, 43 sites have signed the LHB Agreement; 35 sites have sent tokens generated for 9 528 998 patients. In this initial cohort, the LHB identified 135 037 matches and 68 596 duplicates. Conclusion: This large‐scale linkage study using deidentified datasets of varying characteristics established secure methods for protecting the privacy of N3C patient data when linked for research purposes. This technology has potential for use with registries for other diseases and conditions. [ABSTRACT FROM AUTHOR]

Research over the past several decades suggests that meaningful psychedelic experiences can engender long-term effects on subjective wellbeing. However, less research has investigated the psychological mechanisms through which these effects may emerge. In the present study, participants (N = 201) completed an online survey that retrospectively measured the acute effects of a meaningful psychedelic experience, as well as changes in subjective well-being and death anxiety. Reductions in death anxiety significantly mediated the effects of mystical experience on satisfaction with life, positive affect, and negative affect. Reductions in death anxiety did not mediate any of the effects of psychological insight. Although correlational, the findings are consistent with the hypothesis that some of the benefits of psychedelic-induced mystical experiences on subjective well-being may emerge due to reductions in death anxiety. Nevertheless, further research is needed to establish a causal effect of reduced death anxiety on well-being in the context of psychedelic experiences. [ABSTRACT FROM AUTHOR]

Abstract Digitalisation and the Internet of Things (IoT) help city councils improve services, increase productivity and reduce costs. City‐scale monitoring of traffic and pollution enables the development of insights into low‐air quality areas and the introduction of improvements. IoT provides a platform for the intelligent interconnection of everyday objects and has become an integral part of a citizen's life. Anyone can monitor from their fitness to the air quality of their immediate environment using everyday technologies. With caveats around privacy and accuracy, such data could even complement those collected by authorities at city‐scale, for validating or improving policies. The authors explore the hierarchies of urban sensing from citizen‐to city‐scale, how sensing at different levels may be interlinked, and the challenges of managing the urban IoT. The authors provide examples from the UK, map the data generation processes across levels of urban hierarchies and discuss the role of emerging sociotechnical urban sensing infrastructures, that is, independent, open, and transparent capabilities that facilitate stakeholder engagement and collection and curation of grassroots data. The authors discuss how such capabilities can become a conduit for the alignment of community‐ and city‐level action via an example of tracking the use of shared electric bicycles in Bristol, UK.

Abstract Growth differentiation factor 15, GDF15, and glucagon-like peptide-1 (GLP-1) analogues act through brainstem neurons that co-localise their receptors, GDNF-family receptor α-like (GFRAL) and GLP1R, to reduce food intake and body weight. However, their use as clinical treatments is partially hampered since both can also induce sickness-like behaviours, including aversion, that are mediated through a well-characterised pathway via the exterolateral parabrachial nucleus. Here, in mice, we describe a separate pathway downstream of GFRAL/GLP1R neurons that involves a distinct population of brain-derived neurotrophic factor (BDNF) cells in the medial nucleus of the tractus solitarius. Thus, BDNFmNTS neurons are required for the weight-reducing actions of both GDF15 and the GLP1RA, Exendin-4. Moreover, acute activation of BDNFmNTS neurons is sufficient to reduce food intake and drive fatty acid oxidation and might provide a route for longer-term weight loss.