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Epigenetic mechanisms govern the transcriptional activity of lineage-specifying enhancers; but recent work challenges the dogma that joint chromatin accessibility and DNA demethylation are prerequisites for transcription. To understand this paradox, we established a highly-resolved timeline of DNA demethylation, chromatin accessibility, and transcription factor occupancy during neural progenitor cell differentiation. We show thousands of enhancers undergo rapid, transient accessibility changes associated with distinct periods of transcription factor expression. However, most DNA methylation changes are unidirectional and delayed relative to chromatin dynamics, creating transiently discordant epigenetic states. Genome-wide detection of 5-hydroxymethylcytosine further revealed active demethylation begins ahead of chromatin and transcription factor activity, while enhancer hypomethylation persists long after these activities have dissipated. We demonstrate that these timepoint specific methylation states predict past, present and future chromatin accessibility using machine learning models. Thus, chromatin and DNA methylation collaborate on different timescales to mediate short and long-term enhancer regulation during cell fate specification.

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Polyunsaturated fatty acids (PUFAs), especially arachidonic acid (ARA) and docosahexaenoic acid (DHA), are extremely important fatty acids for brain development in the fetus and early childhood. Premature infants face challenges obtaining these two fatty acids from their mothers. It has been reported that supplementation with triacylglycerols (TAGs) with an ARA:DHA (w/w) ratio of 2:1 may be optimal for preterm infants, as presented in commercial formulas such as Formulaid™. This study explored methods to produce TAGs with a 2:1 ratio (ARA:DHA), particularly at the more bioavailable sn-2 position of the glycerol backbone. Blending and enzymatic acidolysis of microalgae oil (rich in DHA) and ARA-rich oil yielded products with the desired ARA:DHA ratio, enhancing sn-2 composition compared to Formulaid™ (1.6 for blending and 2.3 for acidolysis versus 0.9 in Formulaid™). Optimal acidolysis conditions were 45 °C, a 1:3 substrate molar ratio, 10% Candida antarctica lipase, and 4 h. The process was reproducible, and scalable, and the lipase could be reused. In vitro digestion showed that 75.5% of the final product mixture was bio-accessible, comprising 19.1% monoacylglycerols, ~50% free fatty acids, 14.6% TAGs, and 10.1% diacylglycerols, indicating better bio-accessibility than precursor oils.

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Dendritic cells (DCs) play a crucial role in orchestrating immune responses, particularly in promoting IFNγ-producing-CD8 cytotoxic T lymphocytes (CTLs) and IFNγ-producing-CD4 T helper 1 (Th1) cells, which are essential for defending against viral infections. Additionally, the nuclear envelope protein lamin A/C has been implicated in T cell immunity. Nevertheless, the intricate interplay between innate and adaptive immunity in response to viral infections, particularly the role of lamin A/C in DC functions within this context, remains poorly understood. In this study, we demonstrate that mice lacking lamin A/C in myeloid LysM promoter-expressing cells exhibit a reduced capacity to induce Th1 and CD8 CTL responses, leading to impaired clearance of acute primary Vaccinia virus (VACV) infection. Remarkably, in vitro-generated granulocyte macrophage colony-stimulating factor bone marrow-derived DCs (GM-CSF BMDCs) show high levels of lamin A/C. Lamin A/C absence on GM-CSF BMDCs does not affect the expression of costimulatory molecules on the cell membrane but it reduces the cellular ability to form immunological synapses with naïve CD4 T cells. Lamin A/C deletion induces alterations in NFκB nuclear localization, thereby influencing NF-κB-dependent transcription. Furthermore, lamin A/C ablation modifies the gene accessibility of BMDCs, predisposing these cells to mount a less effective antiviral response upon TLR stimulation. This study highlights the critical role of DCs in interacting with CD4 T cells during antiviral responses and proposes some mechanisms through which lamin A/C may modulate DC function via gene accessibility and transcriptional regulation.

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Most EU member states fail to provide essential sexual and reproductive health services to undocumented migrants, a vulnerable population facing limited access, utilization, and worse health-related outcomes. This study systematically reviewed the literature on access to and use of these services, as well as related health, economic, and migratory outcomes for undocumented migrants in the EU-EFTA region. The systematic review is reported based on the PRISMA 2020 checklist and includes 37 studies published between 2017 and 2024. Included studies were based upon original quantitative, qualitative, or mixed-methods data; conducted in one or more European countries; and published in one or more of the following languages: English, Spanish, French, Portuguese, or Romanian. A quality assessment was conducted using the CASP checklist for qualitative studies and the NHLBI Study Quality Assessment Tools for quantitative studies. The findings revealed numerous access barriers, including refusal of care, lack of knowledge about national healthcare schemes, bureaucratic hurdles, and affordability issues. Even when care was available, stigma, fear of deportation, socio-economic precarity, and abuse further hindered utilization. These barriers contributed to generally worse reproductive health outcomes for undocumented migrants in Europe, though the findings may not generalize to all EU-EFTA countries.

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Plastic pollution is a critical environmental issue due to the widespread use of plastic materials and their long degradation time. Hydrocracking (HDC) offers a promising solution to manage plastic waste by converting it into valuable products, namely chemicals or fuels. This work aims to investigates the effect of catalyst accessibility and acidity on the HDC reaction of high density polyethylene (HDPE). Therefore, a variety of materials with significant differences in both textural and acidic properties were tested as catalysts. These include H-USY and H-ZSM.5 zeolites with various Si/Al molar ratios (H-USY: Si/Al = 2.9, 15, 30 and 40; H-ZSM-5: Si/Al = 11.5, 40, 500) and mesostructured MCM-41 materials modified with Ga and Al, also with different Si/metal ratios (Si/Al = 16 and 30; Si/Ga = 63 and 82). Thermogravimetric analysis under hydrogen atmosphere was used as a preliminary screening tool to evaluate the potential of the various catalysts for this application in terms of energy requirements. In addition, batch autoclave reactor experiments (T = 300 °C, PH2 = 20 bar, t = 60 min) were conducted to obtain further information on conversion, product yields and product distribution for the most promising systems. The results show that the catalytic performance in HDPE hydrocracking is determined by a balance between the acidity of the catalyst and its structural accessibility. Accordingly, for catalyst series where the structural and textural properties do not vary with the Si/Al ratio, there is a clear correlation of the HDPE degradation temperature and of the HDPE conversion with the Si/metal ratio (which relates to the acidic properties). In contrast, for catalyst series where the structural and textural properties vary with the Si/Al ratio, no consistent trend is observed and the catalytic performance is determined by a balance between the acidic and textural properties. The product distribution was also found to be influenced by the physical and chemical properties of the catalyst. Catalysts with strong acidity and smaller pores were observed to favor the formation of lighter hydrocarbons. In addition to the textural and acidic properties of the catalyst, the role of coke formation should not be neglected to ensure a comprehensive analysis of the catalytic performance.

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Most balance assessment studies using inertial measurement units (IMUs) in smartphones use a body strap and assume the alignment of the smartphone with the anatomical axes. To replace the need for a body strap, we have used an anatomical alignment method that employs a calibration maneuver and Principal Component Analysis (PCA) so that the smartphone can be held by the user in a comfortable position. The objectives of this study were to determine if correlations existed between angular velocity scores derived from a handheld smartphone with PCA functional alignment vs. a smartphone placed in a strap with assumed alignment, and to analyze acceleration score differences across balance poses of increasing difficulty. The handheld and body strap smartphones exhibited moderately to strongly correlated angular velocity scores in the calibration maneuver (r = 0.487-0.983, p < 0.001). Additionally, the handheld smartphone with PCA functional calibration successfully detected significant variance between pose type scores for anteroposterior, mediolateral, and superoinferior acceleration data (p < 0.001).

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Academic engagement was recognized as a crucial predictor to measure the effectiveness of online teaching of international students. Therefore, this study established a mediating model to explore the mechanism underlying of interaction and information technology accessibility on academic engagement of international students, as well as the impact of learning interest on these mechanisms with the context of online teaching. Using a stratified random sampling method, 1895 international students from 32 Chinese universities were selected. These international students had completed the academic engagement scale, interaction scale, information technology accessibility scale, and learning interest scale. The study variables were analyzed in sequence for reliability and validity, common method biases test, correlation analysis, structural equation model testing, and bias-corrected percentile Bootstrap testing. The results revealed that online interaction positively affected the academic engagement of international students in Chinese universities (ß= 0.35, p < 0.001), and learning interest played a partial mediating role between online interaction and academic engagement (indirect effect = 0.10, 95 % Boot CI = [0.06, 0.13], p < 0.001). Information technology accessibility did not have a direct impact on academic engagement (ß= 0.06, p > 0.05); but learning interest played a complete mediating role between information technology accessibility and academic engagement (indirect effect = 0.09, 95 % Boot CI = [0.05, 0.11], p < 0.001). The results of Bootstrap showed that the mediating effects within the model were significant. The findings of this study explored the potential mechanism underlying the online academic engagement of international students in Chinese universities, and provided empirical evidence for universities and educators to implement differentiated learning support, assist international students in adapting to online learning styles, and stimulate the endogenous motivation of students' learning.

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BACKGROUND: Refugees resettled in Australia may experience significant physical, mental and emotional health issues on arrival and difficulty accessing mainstream healthcare that often demands specialised services. It is not known if and how refugee health needs and service use change over time and generations, how this compares with the broader Australian population and what level of resourcing is required to maintain specialised services. There is also a significant knowledge gap concerning the resources and skills of refugees that can be harnessed to sustain the health and well-being of individuals and communities. Such knowledge gaps impede the ability of the health system to deliver responsive, efficient, acceptable and cost-effective care and services and limit the engagement of refugees in the coproduction of these services. METHODS: This study will be the first to provide comprehensive, longitudinal, population-based evidence of refugee health, service use and the accumulated resources or assets related to positive health and well-being (compared with data on deficits, illness and death) across the lifespan and generations. This will enable a comprehensive understanding of the relationships among assets, health status, service gaps and behaviours. We will identify the assets contributing to increased capacities to protect and promote health. This evidence is essential for planning health prevention programmes.This project has three phases: (1) employ national linked datasets to examine the health and social outcomes of refugees in Australia; (2) engage with refugees in a participatory manner to map the social, economic, organisational, physical and cultural assets in their communities and deliver an integrated model of health; and (3) codesign a roadmap of agreed actions required to attain health and well-being in communities and indicators to assess outcomes. ETHICS AND DISSEMINATION: Ethics and procedures-phase I:Ethical approval for phase I was gained from the Australian Bureau of Statistics (ABS) for Person Level Integrated Data Asset microdata (unit record data) via the ABS DataLab and the NSW Population and Health Services Research Ethics Committee (2023ETH01728), which can provide a single review of multijurisdictional data linkage research projects under the National Mutual Acceptance Scheme. This will facilitate approval for the Victorian and ACT datasets. The ABS will be the integrating/linkage authority. The Centre for Health Record Linkage (CHeReL) and the Victorian Data Linkage Unit will prepare a data extract representing all data records from the dataset to provide to the ABS for linkage.Ethics and procedures-phases 2 and 3:Written consent will be obtained from all participants, as well as consent to publish. We have obtained ethical approval from the University of Technology Sydney Medical Research Ethics Committee; however, as we deepen our consultation with community members and receive input from expert stakeholders, we will likely seek amendments to hone the survey and World Café questions. We will also need to provide flexible offerings that may extend to individual interviews and online interactions. DISCUSSION: This innovative approach will empower refugees and put them at the centre of their health and decision-making.

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OBJECTIVE: Although voice therapy is a highly effective treatment for voice disorders, benefits are diminished by poor adherence to appointments. Remote telehealth delivery of therapy may address this problem by improving access. This study investigates attendance at remote telehealth voice therapy and evaluates potential correlation with patient demographics and socioeconomic status. METHODS: Retrospective review of all adult patients referred for telehealth voice therapy between April 2020-November 2021. Evaluated patient demographics including referral diagnosis, health insurance status and interpreter use, were obtained from medical records. Area Deprivation Index scores served as proxy for socioeconomic status. Multivariate analysis examined relationships between patient factors and attendance. RESULTS: Of 423 patients referred for telehealth voice therapy, 220 (52%) attended more than one therapy session, 98 (23%) attended one, and 105 (25%) never attended therapy. Multivariate analysis did not identify significant correlations between telehealth attendance and sociodemographic factors including interpreter use, insurance status, and socioeconomic status, even after adjusting for ethnicity and primary language. CONCLUSION: Over half of patients referred to telehealth voice therapy participated in multiple sessions and 75% attended at least one session. Telehealth voice therapy attendance was not negatively impacted by public health insurance and patient race and socioeconomic status did not impact attendance. Telehealth voice therapy may minimize potential barriers to care in susceptible populations. LEVEL OF EVIDENCE: IV.

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The need for equitable access to primary healthcare services in the current global context has attracted widespread attention, prompting nations to continuously enhance their grassroots medical service levels. In response, China launched the "Healthy China" initiative, which prioritizes the enhancement of national health as a core goal of the healthcare system and uses this opportunity to deepen reforms aimed at strengthening primary care. However, in remote and rural areas, the optimization of medical resource allocation and the achievement of balanced service development remain critical challenges owing to limited resources. This study selected Liannan Yao Autonomous County, which is situated in the northwestern corner of Guangdong Province, as a case study due to its remote mountainous location, underdeveloped economy, and minority region characteristics. Through field research and interviews, this study thoroughly explored the needs of both supply and demand, factoring in elements such as the service capability of healthcare facilities and residents' travel thresholds to enhance the two-step floating catchment area model, thus making it more applicable to remote villages. By integrating electric bikes and cars, which are the primary means of transportation in rural areas, this study conducted a thorough analysis and comparison of the accessibility of medical services in Liannan Yao Autonomous County (Liannan County) . The results reveal significant disparities in healthcare accessibility, an uneven distribution of medical resources, and varying impacts of transportation conditions and facility service capabilities on accessibility. Notably, the study revealed that improving transportation conditions alone has limited effects in rural areas; the key lies in balancing medical service capabilities and the rationality of overall layouts. From the perspectives of equity and efficiency, this study employs the equitable coverage model and the efficiency-driven model to construct two scenarios, comparing accessibility changes in Liannan County under both conditions and proposing strategies to improve the spatial layout of local healthcare facilities. This research not only deepens the understanding of healthcare service accessibility in rural areas but also provides a scientific basis for optimizing resource allocation and enhancing primary medical services, offering valuable guidance and reference for Liannan County and other similar rural regions.

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BACKGROUND: SMS text messages through mobile phones are a common means of interpersonal communication. SMS text message surveys are gaining traction in health care and research due to their feasibility and patient acceptability. However, challenges arise in implementing SMS text message surveys, especially when targeting marginalized populations, because of barriers to accessing phones and data as well as communication difficulties. In primary care, traditional surveys (paper-based and online) often face low response rates that are particularly pronounced among disadvantaged groups due to financial limitations, language barriers, and time constraints. OBJECTIVE: This study aimed to investigate the potential of SMS text message-based patient recruitment and surveys within general practices situated in lower socioeconomic areas. This study was nested within the Reducing Alcohol-Harm in General Practice project that aimed to reduce alcohol-related harm through screening in Australian general practice. METHODS: This study follows a 2-step SMS text message data collection process. An initial SMS text message with an online survey link was sent to patients, followed by subsequent surveys every 3 months for consenting participants. Interviews were conducted with the local primary health network organization staff, the participating practice staff, and the clinicians. The qualitative data were analyzed using constructs from the Consolidated Framework for Implementation Research. RESULTS: Out of 6 general practices, 4 were able to send SMS text messages to their patients. The initial SMS text message was sent to 8333 patients and 702 responses (8.2%) were received, most of which were not from a low-income group. This low initial response was in contrast to the improved response rate to the ongoing 3-month SMS text message surveys (55/107, 51.4% at 3 months; 29/67, 43.3% at 6 months; and 44/102, 43.1% at 9 months). We interviewed 4 general practitioners, 4 nurses, and 4 administrative staff from 5 of the different practices. Qualitative data uncovered barriers to engaging marginalized groups including limited smartphone access, limited financial capacity (telephone, internet, and Wi-Fi credit), language barriers, literacy issues, mental health conditions, and physical limitations such as manual dexterity and vision issues. Practice managers and clinicians suggested strategies to overcome these barriers, including using paper-based surveys in trusted spaces, offering assistance during survey completion, and offering honoraria to support participation. CONCLUSIONS: While SMS text message surveys for primary care research may be useful for the broader population, additional efforts are required to ensure the representation and involvement of marginalized groups. More intensive methods such as in-person data collection may be more appropriate to capture the voice of low-income groups in primary care research. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.3399/BJGPO.2021.0037.

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The use of computers in everyday life has moved from hobby and technical professional use to being essential to almost all activities in people's lives. However, not everyone has a computer themselves or access to the internet at home. To address this, society provides computers that people can use at school, in libraries, at job centers, in community centers, and at government service centers. However, these are not accessible to those who need assistive technologies (AT), and they are not allowed to install the AT they need to use the computers. This puts people who need to use AT at a severe disadvantage to their peers at best and, at worst, prevents them from participating at all where computer use is required. This is a problem when a person is required to use a particular computer instead of their own and is a total barrier to computer use for those who do not own their own computer. Proposed is the installation of a free utility on all public or shared use computers that both a) exposes the built-in accessibility features in computers to make them easier to discover and use, and b) allows AT users to have any AT the need automatically installed on any computer they encounter, and then set up just for them. When they are done, the AT disappears.

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With advances in AI, computer vision, and interface understanding, there is the potential to offload much of the work currently spent by companies' developers in making products accessible. There is also the potential to move our major accessibility approach from an 'inclusively-designed-products-plus-AT focus to a 'universal-interface-transformer focus. This would be a major reversal of approach and have significant ramifications for legislation, regulation, and the established large-scale accessibility industries that have grown up around them. Such a disruption would require concrete evidence that such a change would, in fact, be better for people with disabilities. It would also require a path from the former to the latter. This paper presents the case for such a shift, some of the benefits and ramifications, and the developments necessary to make the shift. It also outlines a hybrid approach between inclusive design and bespoke custom interfaces.

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Accessibility has always played catch-up to the detriment of people with disabilities - and this appears to be exacerbated by the rapid advancements in technology. A key question becomes, can we better predict where technology will be in 10 or 20 years and develop a plan to be better positioned to make these new technologies accessible when they make it to market? To attempt to address this question, a "Future of Interface Workshop" was convened in February 2023, chaired by Vinton Cerf and Gregg Vanderheiden that brought together leading researchers in artificial intelligence, brain-computer interfaces, computer vision, and VR/AR/XR, and disability to both a) identify barriers these new technologies might present and how to address them, and b) how these new technologies might be tapped to address current un- or under-addressed problems and populations. This paper provides an overview of the results of the workshop as well as the current version of the R&D Agenda work that was initiated at the conference. It will also present an alternate approach to accessibility that is being proposed based on the new emerging technologies.

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There is growing attention to community-based services for preventing adverse health care outcomes among people aging with dementia. We explored whether the availability of dementia-centered programming within older adult centers (ie, senior centers)-specifically, adult day services (ADS), social adult day centers (SADCs), memory cafes, and caregiver support-is associated with reduced hospitalization, emergency room use, and total Medicare costs for community-dwelling individuals ages 75 and older with Alzheimer's disease and related dementias (ADRD), and whether associations differ by the relative size of the local jurisdiction. We used a novel dataset that links Medicare claims data with data from an organizational census of municipally based Massachusetts older adult centers. Living in a community with an older adult center that facilitates access to ADS and/or SADCs was associated with reduced hospital utilization and costs among residents in smaller jurisdictions. We found no evidence for associations concerning memory cafes or support groups. These findings underscore the potential of older adult centers in curbing health care costs and acute care usage among individuals with ADRD, particularly in smaller communities with centers that provide access to ADS.

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PURPOSE: Cancer care for lesbian, gay, bisexual, transgender, queer, intersex, asexual, and other sexuality and gender diverse (LGBTQIA +) individuals is marked by disparities stemming from a history of discrimination, stigma, and systemic inequities. For LGBTQIA + individuals seeking cancer care, cancer center websites may be a first point of contact with healthcare. Two complementary studies sought to evaluate the LGBTQIA + inclusivity of cancer centers' websites. METHODS: The authors conducted two studies in 2022-2023, reviewing the websites of National Cancer Institute (NCI)-designated cancer centers and Children's Oncology Group (COG)-designated health systems and cancer centers. Reviewers manually searched websites and coded several Yes/No criteria for LGBTQIA + inclusivity. RESULTS: Among the 65 NCI cancer centers' websites in 2023, 66% included a nondiscrimination statement, 71% mentioned LGBTQIA + health disparities, 65% included LGBTQIA + tailored resources, and 66% had articles about LGBTQIA + health. There was a trend of increased inclusivity across categories from 2022 to 2023. Among the 204 COG-designated health system websites in 2023, there were 60 pediatric care websites and 144 lifespan care websites. A total of 79.9% of COG health system websites referenced LGBTQIA + patients (80.0% of pediatric and 79.9% of lifespan sites), 16.7% of COG cancer center websites referenced LGBTQIA + patients in the context of cancer care (6.7% of pediatric and 20.8% of lifespan sites), and 82.4% yielded results when search terms were input (83.3% of pediatric and 81.9% of lifespan sites). CONCLUSIONS: Adult and pediatric cancer centers' websites have varying levels of LGBTQIA + inclusivity based on nondiscrimination statements, articles, and the availability of LGBTQIA + resources. While there have been some improvements in inclusivity on the NCI-designated cancer centers' websites between 2022 and 2023, there is a need for further improvement.

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The aim of this paper is to explore whether and how urban road transport (URT) development affects haze pollution. One of the innovations of this paper is that URT development is measured by road accessibility with novel digital elevation model datasets, which have been used by few scholars. The endogenous problem caused by revere causality issue in the relationship between URT development and haze pollution is also considered. Based on the panel data of prefecture-level cities of Yangtze River Delta (YRD) region in China from 2011 to 2018, this paper uses long-lagged values of URT development as the instrumental variable, employing the two-stage least squares (2SLS) method. The study shows that URT development leads to an increase of haze pollution. Moreover, mechanism tests based on moderating and mediating models support the finding that decreasing haze pollution resulted from better connection effects, while rising agglomeration effects tend to bring about increasing haze pollution, and the latter effect is larger in magnitude than the former. Current URT development may have long-term negative consequences for livability of YRD cities, and urban decision makers should reconsider the effectiveness of the current road transport investment and construction.

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BACKGROUND: Worldwide, children with cerebral palsy (CP) living in underserved communities face barriers to accessing motor therapy services. This study assessed the implementation and effectiveness of an 8-week, upper limb (UL) home-based intervention with a movement-tracking videogame (Bootle Blast) in Costa Rican children with CP. METHODS: Children established a weekly playtime goal and two UL activities of daily living (ADLs) that they would like to improve on. A multiple-baseline, single-case experimental design, was used with the Performance Quality Rating Scale (PQRS) as the repeated measure to track changes in performance of the selected ADLs between the baseline (usual care) and intervention (Bootle Blast) phases. The Canadian Occupational Performance Measure (COPM), the Box and Blocks Test (BBT) and the Children's Hand-Use Experience Questionnaire (CHEQ) were collected before and after the intervention. Technical barriers were documented during weekly video calls with a monitoring therapist. Treatment effect size, slope changes and percentage of non-overlapping data were identified for the PQRS. Descriptive statistics summarized results for the BBT, CHEQ, videogame logs (e.g., playtime) and technical barriers. RESULTS: Fifteen children participated and 13 completed the intervention. Both participants who dropped out did so after completing baseline assessments, but before experiencing Bootle Blast. Children's mean active playtime (i.e., mini-games targeting the UL) across the 8-weeks was 377 min, while mean total time spent engaging with Bootle Blast (active + passive play time [e.g., time navigating menus, reviewing rewards]) was 728 min. In total, eight technical issues (from five children) were reported, and all but three were resolved within 48 h. Partial effectiveness was associated with the intervention. Specifically, 85% of participants improved on the PQRS and 69% achieved clinically important improvements ≥ 2 points in performance on the COPM. Children improved by 1.8 blocks on average on the BBT, while on the CHEQ, five children had a clinically important increase of 10% of the total number of UL activities performed with both hands. CONCLUSION: Bootle Blast is a feasible and effective option to facilitate access and engage children with cerebral palsy in UL home rehabilitation. Trial registration Trial registration number: NCT05403567.

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