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OBJECTIVES: Childhood cancer survivors may experience complex health issues during transition and long-term follow-up (LTFU); therefore, high-quality healthcare is warranted. Care coordination is one of the essential concepts in advanced healthcare. Care coordination models vary among childhood cancer survivors in transition and LTFU. This study aimed to identify care coordination models for childhood cancer survivors in transition and LTFU and synthesise essential components of the models. DESIGN: This scoping review was guided by the methodological framework from Arksey and OMalley and was reported with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. A systematic literature search was conducted on six databases using possible combinations of terms relevant to childhood cancer survivors, transition/LTFU and care coordination model. Data were analysed by descriptive and content analysis. DATA SOURCES: The literature search was first conducted in May 2023 and updated in May 2024. Six databases including Medline, PubMed, Embase, Web of Science, CINAHL and Cochrane Library were searched; meanwhile, a hand search was also conducted. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies relevant to describing any models, interventions or strategies about care coordination of transition or LTFU healthcare services among childhood cancer survivors were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened and included studies. Basic information as well as care coordination model-related data in the included studies were extracted. Descriptive summary and content analysis were used for data analysis. RESULTS: In the 20 545 citations generated by the search strategy, seven studies were identified. The critical determinants of the models in the included studies were the collaboration of the multidisciplinary team, integration of the navigator role and the provision of patient-centred, family-involved, needs-oriented clinical services. The main functions of the models included risk screening and management, primary care-based services, psychosocial support, health education and counselling, and financial assistance. Models of care coordination were evaluated at patient and clinical levels. Based on this review, core concepts of successful care coordination models for childhood cancer survivors in transition or LTFU were synthesised and proposed as the 3 I framework: individualisation, interaction and integration. CONCLUSION: This scoping review summarised core elements of care coordination models for childhood cancer survivors transition and LTFU. A proposed conceptual framework to support and guide the development of care coordination strategies for childhood cancer survivors transition and LTFU care was developed. Future research is needed to test the proposed model and develop appropriate care coordination strategies for providing high-quality healthcare for childhood cancer survivors transition and LTFU.

BACKGROUND AND AIM[|]Traffic-Related Air Pollution (TrAP) adversely impacts human health, disproportionately harming disadvantaged communities. New technologies and infrastructure offer opportunities to reduce TrAP, but the health outcomes of individuals are not fully understood due to a lack of high-resolution models that grasp the complexities of transportation systems and their health implications amid evolving policies and technologies.[¤]METHOD[|]We introduce BEAM CORE (beam.lbl.gov), a high-resolution, agent-based transportation framework that simulates detailed passenger and freight activities. It captures interactions between transportation, land use, demographic and vehicle ownership changes at various scales. Validating crucial factors of emission modeling, including link-level VMT, speed and regional fleet in the San Francisco Bay Area’s nine counties, demonstrates its potential to be extended for assessing health outcomes from changes in TrAP.[¤]RESULTS[|]All major outputs from the BEAM CORE 2018 baseline have been calibrated and validated. Mode split and demographics align closely with census and survey data. Passenger and freight activities were validated against public and private data, with CO2 emissions corresponding to 3.67Mt/yr for medium/heavy-duty (MHD) and 22.79Mt/yr for all vehicles, demonstrating the model’s alignment with empirical data. The NOx, PM2.5 and PM10 from MHD exhaust, PM brake and tire wear are 14.8kt/yr, 424t/yr and 606.9t/yr under the 2018 baseline with high fractions of conventional vehicles, while the wide adoption of clean truck technologies under 2050 resulted in 87\%, 75\% and 56\% reductions respectively. BEAM CORE generates detailed fleet and activity data at high spatiotemporal resolution, enabling the integration with air quality models, including InMAP/AERMOD, to explore the causal pathway of health impacts from transport policy changes.[¤]CONCLUSIONS[|]We developed a sophisticated multi-dimensional transportation model for integration with advanced air quality, and health assessment models. It enables a thorough analysis of health impacts of transportation policies and technologies across diverse communities. It supports similar analyses in any area using local data.[¤]

Broadening gene therapy applications requires manufacturable vectors that efficiently transduce target cells in humans and preclinical models. Conventional selections of adeno-associated virus (AAV) capsid libraries are inefficient at searching the vast sequence space for the small fraction of vectors possessing multiple traits essential for clinical translation. Here, we present Fit4Function, a generalizable machine learning (ML) approach for systematically engineering multi-trait AAV capsids. By leveraging a capsid library that uniformly samples the manufacturable sequence space, reproducible screening data are generated to train accurate sequence-to-function models. Combining six models, we designed a multi-trait (liver-targeted, manufacturable) capsid library and validated 88% of library variants on all six predetermined criteria. Furthermore, the models, trained only on mouse in vivo and human in vitro Fit4Function data, accurately predicted AAV capsid variant biodistribution in macaque. Top candidates exhibited production yields comparable to AAV9, efficient murine liver transduction, up to 1000-fold greater human hepatocyte transduction, and increased enrichment relative to AAV9 in a screen for liver transduction in macaques. The Fit4Function strategy ultimately makes it possible to predict cross-species traits of peptide-modified AAV capsids and is a critical step toward assembling an ML atlas that predicts AAV capsid performance across dozens of traits.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a life-saving treatment for adolescents and young adults (ages 15-39) with hematologic malignancy. Given the significant developmental milestones usually achieved during this unique life stage, this population is especially vulnerable to the interruption caused by a cancer diagnosis and its treatment. HSCT is a particularly invasive form of cancer therapy with many negative physical, social, and psychological sequelae. The long-term impact of HSCT in adolescents and young adults with hematologic malignancies warrants a systematic investigation of its effects to best shape clinical care and health policy. METHODS: This protocol for a systematic review will focus on the long-term physical, psychological, social, spiritual, and health behavior effects experienced by adolescents and young adults who undergo HSCT for hematologic malignancy. We have constructed a specific search strategy that queries these five domains, which will be applied to five databases-Embase, PubMed, Cochrane Trials and Reviews, PsychInfo, and CINAHL-to identify the key literature. Two independent reviewers will perform a title/abstract screen followed by a full-text screen using standard screening templates to ensure the inclusion of outcomes in the post-acute HSCT period. Risk of bias will be assessed using the University of Adelaide Joanna Briggs Institute Collaboration Critical Appraisal Tools. Data from included studies will be abstracted on study characteristics, study setting, sample characteristics, and outcomes. Given the broad scope of the research question, data synthesis will focus on qualitative methods in accordance with Institute of Medicine standards. DISCUSSION: While adolescents and young adults undergoing hematopoietic stem cell transplantation for hematologic malignancy are understood to have a unique survivorship experience, the sequelae of this treatment approach in this population have not been previously aggregated. This systematic review intends to expand insight into the adolescent and young adult experiences with HSCT in order to inform age-appropriate survivorship care and deliver this life-saving intervention with the best possible outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022361663.

Protein tyrosine phosphatases (PTPs) play major roles in cancer and are emerging as therapeutic targets. Recent reports suggest low-molecular weight PTP (LMPTP)-encoded by the ACP1 gene-is overexpressed in prostate tumors. We found ACP1 up-regulated in human prostate tumors and ACP1 expression inversely correlated with overall survival. Using CRISPR-Cas9-generated LMPTP knockout C4-2B and MyC-CaP cells, we identified LMPTP as a critical promoter of prostate cancer (PCa) growth and bone metastasis. Through metabolomics, we found that LMPTP promotes PCa cell glutathione synthesis by dephosphorylating glutathione synthetase on inhibitory Tyr270. PCa cells lacking LMPTP showed reduced glutathione, enhanced activation of eukaryotic initiation factor 2-mediated stress response, and enhanced reactive oxygen species after exposure to taxane drugs. LMPTP inhibition slowed primary and bone metastatic prostate tumor growth in mice. These findings reveal a role for LMPTP as a critical promoter of PCa growth and metastasis and validate LMPTP inhibition as a therapeutic strategy for treating PCa through sensitization to oxidative stress.

BackgroundBreast cancer survivorship guidelines with specific recommendations on managing long-term effects are available, but uptake in clinical practice remains low. Using the lens of the Theoretical Domains Framework, we aimed to understand key factors in guideline-concordant management of long-term effects to inform future implementation efforts in clinical practice contexts.MethodsAs part of a broader survey of oncologists, a theory-guided questionnaire was developed. Oncologists were asked to report level of agreement with Theoretical Domains Framework-based statements, current usage and perceived value of survivorship resources, and frequency of managing long-term effects in routine care. Data analyses included psychometric assessment of the questionnaire, descriptive summaries of theoretical domains and survivorship resources, and multivariable logistic regression models.ResultsIn total, 217 oncologists completed the Theoretical Domains Framework-based questionnaire; 54% of oncologists reported "always or almost always" evaluating physical effects at routine survivorship appointments, while 34% did so for psychosocial effects. In regression models, Environmental Context and Resources was the only theoretical domain found to be statistically significantly associated with "always or almost always" evaluating both physical (odds ratio = 0.29, 95% confidence interval = 0.09 to 0.80) and psychosocial (odds ratio = 0.09, 95% confidence interval = 0.02 to 0.35) effects.ConclusionsFindings support application of the Theoretical Domains Framework in understanding oncologists' behaviors and perceived barriers in managing long-term effects in breast cancer survivors. In future implementation efforts, this theory-informed approach can be used to target relevant domains and strategies focused on embedding guideline recommendations in the clinical context through structured resources and environmental supports.

Abstract In a series of large-scale studies (N = 5,448) we show that Americans across many different demographic categories vastly underestimate their fellow Americans’ support for diversity and inclusion. Trump voters were particularly inaccurate when their task was to estimate prevalent attitudes among Biden voters. Our results show that the degree of underestimation of others’ support for diversity and inclusion predicts the frequency of conversations about diversity, reduced intentions to behave inclusively, and a smaller likelihood of confronting discrimination. Our last two studies (N = 723) demonstrate that it is possible to correct people’s misperceptions through “social norms messaging,” i.e., communications about statistics from national opinion polls highlighting that a majority of Americans are pro diversity. Our findings suggest that once people form accurate impressions of the high percentage of Americans who support diversity and inclusion, they will be more likely to be in favor of pro-diversity initiatives, behave more inclusively, and endorse policies aimed at reducing racial disparities.

Abstract Background Infliximab therapy is effective in controlling symptoms and attaining clinical remission of immune-mediated inflammatory diseases. However, treatment adherence is essential to achieve the therapeutic objective. This study aimed to determine the rate of adherence to infliximab treatment in patients treated at a referral center at a university hospital. Method This ambispective cohort study included patients treated at the Professor Edgard Santos University Hospital (HUPES) referral center of our university hospital between March 2022 and February 2023. Sociodemographic, clinical, and pharmacotherapeutic data were collected from 101 patients through interviews and medical record reviews using a structured form. The adherence rate was defined as the proportion of days covered in a year. Patients who achieved an adherence rate > 80% were considered adherent. Results The treatment adherence rate was 91.04%. Individuals with inflammatory bowel diseases had a 39.1% higher risk of non-adherence to treatment compared with other patients in our sample (p

Abstract Climate change is currently one of humanity’s greatest threats. To help scholars understand the psychology of climate change, we conducted an online quasi-experimental survey on 59,508 participants from 63 countries (collected between July 2022 and July 2023). In a between-subjects design, we tested 11 interventions designed to promote climate change mitigation across four outcomes: climate change belief, support for climate policies, willingness to share information on social media, and performance on an effortful pro-environmental behavioural task. Participants also reported their demographic information (e.g., age, gender) and several other independent variables (e.g., political orientation, perceptions about the scientific consensus). In the no-intervention control group, we also measured important additional variables, such as environmentalist identity and trust in climate science. We report the collaboration procedure, study design, raw and cleaned data, all survey materials, relevant analysis scripts, and data visualisations. This dataset can be used to further the understanding of psychological, demographic, and national-level factors related to individual-level climate action and how these differ across countries.

Abstract Background Substantial variability in response to lifestyle interventions has been recognized for many years, and researchers have begun to disentangle sources of error from inherent differences in individual responsiveness. The objective of this secondary analysis of an intensive lifestyle intervention (diet and exercise) for metabolic syndrome (MetS) was to identify potentially important differences among study completers grouped by treatment response as measured by change in a continuous metabolic syndrome score (Gurka/MetS). Methods All study completers from a 12-month primary care study were categorized into one of five groups according to change in the Gurka/MetS score. A change of 0.4 in z-score defined clinically relevant change in line with results of previous studies. Repeated measures analysis of variance was used to examine cardiovascular disease risk and individual clinical indicators of MetS over 12 months, looking for differences in response over time by the five groups. Results Of 176 participants, 50% (n = 88) had stable scores, 10% (n = 18) had relevant change scores in the first 3 months only and reverted toward baseline, 20% (n = 35) achieved meaningful change over the whole study, 11% (n = 20) had a delayed response at 3–12 months, and 9% (n = 15) demonstrated worsening scores. Significant differential patterns were noted for groups over the duration of the intervention (p

The global spread of lake hypoxia, [O2] < 2 mg L−1, during the last 2 centuries has had a severe impact on ecological systems and sedimentation processes. While the occurrence of hypoxia was observed in many lakes, a detailed quantification of hypoxia spread at centennial timescales remained largely unquantified. We track the evolution of hypoxia and its controls during the past 200 years in a lake, Tiefer See (TSK; NE Germany), using 17 gravity cores recovered from between 10 and 62 m water depth in combination with lake monitoring data. Lake hypoxia was associated with the onset of varve preservation in the TSK and has been dated by varve counting to 1918 ± 1 at 62 m water depth and reached a lake floor depth of 16 m in 1997 ± 1. This indicates that oxygen concentration fell below the threshold for varve preservation at the lake floor (> 16 m). Sediment cores at 10–12 m depth do not contain varves indicating good oxygenation of the upper-water column. Monitoring data show that the threshold for hypoxia, and the intensity and duration of hypoxia which are sufficient for varve preservation, is a period of 5 months of [O2] < 5 mg L−1 and 2 months of [O2] < 2 mg L−1. Detailed total organic carbon (TOC), δ13Corg, and X-ray fluorescence (XRF) core scanning analyses of the short cores indicate that the decline in dissolved oxygen (DO) started several decades prior to the varve preservation. This proves a change in the depositional conditions in the lake, following a transition phase of several decades during which varves were not preserved. Furthermore, varve preservation does occur at seasonal stratification and does not necessarily require permanent stratification.

Abstract Autism spectrum disorders (ASD) are complex neurodevelopmental conditions characterized by impairments in social communication, repetitive behaviors, and restricted interests. Epigenetic modifications serve as critical regulators of gene expression playing a crucial role in controlling brain function and behavior. Lysine (K)-specific demethylase 6B (KDM6B), a stress-inducible H3K27me3 demethylase, has emerged as one of the highest ASD risk genes, but the precise effects of KDM6B mutations on neuronal activity and behavioral function remain elusive. Here we show the impact of KDM6B mosaic brain knockout on the manifestation of different autistic-like phenotypes including repetitive behaviors, social interaction, and significant cognitive deficits. Moreover, KDM6B mosaic knockout display abnormalities in hippocampal excitatory synaptic transmission decreasing NMDA receptor mediated synaptic transmission and plasticity. Understanding the intricate interplay between epigenetic modifications and neuronal function may provide novel insights into the pathophysiology of ASD and potentially inform the development of targeted therapeutic interventions.

Ambient fine particulate matter (PM2.5) is the worlds leading environmental health risk factor. Quantification is needed of regional contributions to changes in global PM2.5 exposure. Here we interpret satellite-derived PM2.5 estimates over 1998-2019 and find a reversal of previous growth in global PM2.5 air pollution, which is quantitatively attributed to contributions from 13 regions. Global population-weighted (PW) PM2.5 exposure, related to both pollution levels and population size, increased from 1998 (28.3 μg/m3) to a peak in 2011 (38.9 μg/m3) and decreased steadily afterwards (34.7 μg/m3 in 2019). Post-2011 change was related to exposure reduction in China and slowed exposure growth in other regions (especially South Asia, the Middle East and Africa). The post-2011 exposure reduction contributes to stagnation of growth in global PM2.5-attributable mortality and increasing health benefits per µg/m3 marginal reduction in exposure, implying increasing urgency and benefits of PM2.5 mitigation with aging population and cleaner air.