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Background: Active transportation (AT), described as self-powered modes of travel (eg, walking and cycling), is an important source of health-promoting physical activity. While AT behaviors have been measured on national health surveys in Canada for over 2 decades, historic prevalence has not been previously reported. We aimed to document the measures of AT on Canada's various national health surveys, examine AT over time, and interpret them within the context of evolving methods of assessment. Methods: We compiled and summarized the questions used to measure AT among Canadians on 4 national health surveys: National Population Health Survey (1994–1998), Canadian Community Health Survey (2000–2020), Canadian Health Measures Survey (2007–2019), and the Health Behaviour in School-aged Children Study (2010–2018). Among youth and adults (12+ y), we summarized over time: (1) the prevalence of AT participation and (2) time spent in AT (in hours per week) among those who report any AT participation. Where possible, we reported separate estimates of walking and cycling and produced an aggregate estimate of total AT. We stratified results by age group and sex. Results: Changes in AT survey questions over time and between surveys limit the interpretation and comparability of temporal trends. Nevertheless, a consistently higher proportion of females report walking, while a higher proportion of males report cycling. Irrespective of mode, males report spending more total time in AT. Participation in AT tends to decrease with age, with youth reporting the highest rates of AT and young adults often spending the most time in AT. Conclusions: Monitoring trends in AT can help assess patterns of behavior and identify whether promotion strategies are needed or whether population interventions are effective. Our evaluation of AT over time is limited by questions surveyed; however, consistent differences in AT by age and sex are evident over time. Moving forward, ensuring consistency of AT measurement over time is essential to monitoring this important behavior. [ABSTRACT FROM AUTHOR]

Data-driven interatomic potentials (IPs) trained on large collections of first principles calculations are rapidly becoming essential tools in the fields of computational materials science and chemistry for performing atomic-scale simulations. Despite this, apart from a few notable exceptions, there is a distinct lack of well-organized, public datasets in common formats available for use with IP development. This deficiency precludes the research community from implementing widespread benchmarking, which is essential for gaining insight into model performance and transferability, and also limits the development of more general, or even universal, IPs. To address this issue, we introduce the ColabFit Exchange, the first database providing open access to a large collection of systematically organized datasets from multiple domains that is especially designed for IP development. The ColabFit Exchange is publicly available at https://colabfit.org, providing a web-based interface for exploring, downloading, and contributing datasets. Composed of data collected from the literature or provided by community researchers, the ColabFit Exchange currently (September 2023) consists of 139 datasets spanning nearly 70 000 unique chemistries, and is intended to continuously grow. In addition to outlining the software framework used for constructing and accessing the ColabFit Exchange, we also provide analyses of the data, quantifying the diversity of the database and proposing metrics for assessing the relative diversity of multiple datasets. Finally, we demonstrate an end-to-end IP development pipeline, utilizing datasets from the ColabFit Exchange, fitting tools from the KLIFF software package, and validation tests provided by the OpenKIM framework. [ABSTRACT FROM AUTHOR]

This study investigates an axial extension mode magnetoelectric antenna designed for near-field communication in dielectric cluttered environments. The antenna configuration consists of two magnetostrictive Metglas-polymer composites bonded on opposite sides of a PZT-5A actuator, creating a dumbbell configuration. Operating at its 88 kHz mechanical resonance, the antenna emits electromagnetic radiation in the near field by applying an AC voltage to the piezoelectric material, generating an acoustic wave that propagates through the volume and induces oscillating magnetizations. The design uses a system of uncoupled models: an electrostatic finite element model to predict strain that feeds into a Landau–Lifshitz–Gilbert micromagnetic model to predict magnetic moment changes and, subsequently, a dipole model to forecast near-field radiation characteristics. Measurements were conducted on the antenna's impedance, quality factor, mechanical resonance, transmitted magnetic signal strength, and radiation patterns, with variations in the bias magnetic field, frequency, and applied voltage. The results exhibit a strong correlation with model predictions, and the radiated signal strengths compare favorably with those of state-of-the-art pacemaker communication devices. Computational parametric studies using Galfenol and Terfenol-D suggest the potential for up to a three order of magnitude reduction in the antenna's volume, which is critical for implanted medical devices. [ABSTRACT FROM AUTHOR]

Background: Functional cell processes (e.g., molecular signaling, response to stimuli, mitosis, etc.) impact cell phenotypes, which scientists can measure with cell morphology. However, linking these measurements with phenotypes remains challenging because it requires manually annotated labels. We propose that nuclear morphology can be a predictive marker for cell phenotypes that are generalizable across contexts. Methods: We reanalyzed a pre-labeled, publicly-available nucleus microscopy dataset from the MitoCheck consortium. We extracted single-cell morphology features using CellProfiler and DeepProfiler, which provide robust processing pipelines. We trained multinomial, multi-class elastic-net logistic regression models to classify nuclei into one of 15 phenotypes such as 'Anaphase,' 'Apoptosis', and 'Binuclear'. We rigorously assessed performance using F1 scores, precision-recall curves, and a leave-one-image-out (LOIO) cross-validation analysis. In LOIO, we retrained models using cells from every image except one and predicted phenotype in the held-out image, repeating this procedure for all images. We evaluated each morphology feature space, a concatenated feature space, and several feature space subsets (e.g., nuclei AreaShape features only). We applied models to the Joint Undertaking in Morphological Profiling (JUMP) data to assess performance using a different dataset. Results: In a held-out test set, we observed an overall F1 score of 0.84. Individual phenotype scores ranged from 0.64 (moderate performance) to 0.99 (high performance). Phenotypes such as 'Elongated', 'Metaphase', and 'Apoptosis' showed high performance. While CellProfiler and DeepProfiler features were generally equally effective, concatenation yielded the best results for 9/15 phenotypes. LOIO showed a performance decline, indicating our model could not reliably predict phenotypes in new images. Poor performance was unrelated to illumination correction or model selection. Applied to the JUMP data, models trained using nuclear AreaShape features only increased alignment with the annotated MitoCheck data (based on UMAP space). This approach implicated many chemical and genetic perturbations known to be associated with specific phenotypes. Discussion: Poor LOIO performance demonstrates challenges of single-cell phenotype prediction in new datasets. We propose several strategies that could pave the way for more generalizable methods in single-cell phenotype prediction, which is a step toward morphology representation ontologies that would aid in cross-dataset interpretability. [ABSTRACT FROM AUTHOR]

Heterochromatin is an organizational property of eukaryotic chromosomes, characterized by extensive DNA and histone modifications, that is associated with the silencing of transposable elements and repetitive sequences. Maintaining heterochromatin is crucial for ensuring genomic integrity and stability during the cell cycle. During meiosis, heterochromatin is important for homologous chromosome synapsis, recombination, and segregation, but our understanding of meiotic heterochromatin formation and condensation is limited. In this review, we focus on the dynamics and features of heterochromatin and how it condenses during meiosis in plants. We also discuss how meiotic heterochromatin influences the interaction and recombination of homologous chromosomes during prophase I. [ABSTRACT FROM AUTHOR]

Aim: Automated insulin delivery (AID) systems have demonstrated improved glycaemic outcomes in people with type 1 diabetes (T1D), yet limited data exist on these systems in very young children and their impact on caregivers. We evaluated psychosocial outcomes following use of the tubeless Omnipod® 5 AID System in caregivers of very young children. Materials and Methods: This 3‐month single‐arm, multicentre, pivotal clinical trial enrolled 80 children aged 2.0–5.9 years with T1D to use the Omnipod 5 AID System. Caregivers completed questionnaires assessing psychosocial outcomes—diabetes distress (Problem Areas in Diabetes), hypoglycaemia confidence (Hypoglycemia Confidence Scale), well‐being (World Health Organization 5 Well‐Being Index), sleep quality (Pittsburgh Sleep Quality Index), insulin delivery satisfaction (Insulin Delivery Satisfaction Survey) and system usability (System Usability Scale) at baseline with standard therapy and after 3 months of AID use. Results: Following 3 months of Omnipod 5 use, caregivers experienced significant improvements across all measures, including diabetes‐related psychosocial outcomes (Problem Areas in Diabetes; p < 0.0001, Hypoglycemia Confidence Scale; p < 0.01), well‐being (World Health Organization 5 Well‐Being Index; p < 0.0001) and perceived system usability (System Usability Scale; p < 0.0001). Significant improvements were seen in the Pittsburgh Sleep Quality Index total score and the overall sleep quality, sleep duration and efficiency subscales (all p < 0.05). Insulin Delivery Satisfaction Survey scores improved on all subscales (greater satisfaction, reduced burden and reduced inconvenience; all p < 0.0001). Conclusions: Caregivers face unique challenges when managing T1D in very young children. While glycaemic metrics have unquestioned importance, these results evaluating psychosocial outcomes reveal additional meaningful benefits and suggest that the Omnipod 5 AID System alleviates some of the burdens caregivers face with diabetes management. [ABSTRACT FROM AUTHOR]

The RUNT‐related transcription factor RUNX2 plays a critical role in osteoblast differentiation, and alterations to gene dosage cause distinct craniofacial anomalies. Uniquely amongst the RUNT‐related family, vertebrate RUNX2 encodes a polyglutamine/polyalanine repeat (Gln23‐Glu‐Ala17 in humans), with the length of the polyalanine component completely conserved in great apes. Surprisingly, a frequent 6‐amino acid deletion polymorphism, p.(Ala84_Ala89)del, occurs in humans (termed 11A allele), and a previous association study (Cuellar et al. Bone137:115395;2020) reported that the 11A variant was significantly more frequent in non‐syndromic sagittal craniosynostosis (nsSag; allele frequency [AF] = 0.156; 95% confidence interval [CI] 0.126–0.189) compared to non‐syndromic metopic craniosynostosis (nsMet; AF = 0.068; 95% CI 0.045–0.098). However, the gnomAD v.2.1.1 control population used by Cuellar et al. did not display Hardy–Weinberg equilibrium, hampering interpretation. To re‐examine this association, we genotyped the RUNX2 11A polymorphism in 225 individuals with sporadic nsSag as parent–child trios and 164 singletons with sporadic nsMet, restricting our analysis to individuals of European ancestry. We compared observed allele frequencies to the non‐transmitted alleles in the parent–child trios, and to the genome sequencing data from gnomAD v.4, which display Hardy–Weinberg equilibrium. Observed AFs (and 95% CI) were 0.076 (0.053–0.104) in nsSag and 0.082 (0.055–0.118) in nsMet, compared with 0.062 (0.042–0.089) in non‐transmitted parental alleles and 0.065 (0.063–0.067) in gnomAD v.4.0.0 non‐Finnish European control genomes. In summary, we observed a non‐significant excess, compared to gnomAD data, of 11A alleles in both nsSag (relative risk 1.18, 95% CI 0.83–1.67) and nsMet (relative risk 1.29, 95% CI 0.87–1.92), but we did not replicate the much higher excess of RUNX2 11A alleles in nsSag previously reported (p = 0.0001). [ABSTRACT FROM AUTHOR]

The European Union's General Data Protection Regulation (GDPR) of 2016 is widely recognised as the benchmark global standard for data-privacy law. In recent years, countries across Southeast Asia have enacted or updated data-privacy laws with provisions that align with the GDPR. This paper explores the balance of internal and external forces driving these regulatory changes. It argues that a nuanced understanding of diffusion in the policymaking process allows us to see beyond the 'Brussels Effect' and how the increasing digitalistion of Southeast Asian societies has created increasing local demand for regulatory change. While an analytical focus on scripting in the drafting of GDPR-like laws focuses attention on the extraterritorial reach of the EU's regulatory power, an analytical focus on problematisation points to different pathways of domestic learning regarding data privacy, especially in response to rising data-security threats. [ABSTRACT FROM AUTHOR]

Introduction: In emergency medicine, triage encompasses more than the initial prioritization of treatment; it also includes decisions about the most suitable level of care and disposition for each patient. However, the increasing use of mobile technology by patients in the emergency department (ED) introduces a new factor. This study aims to explore the relationship between patients' cellphone use at the time of initial assessment and final disposition in the ED. Methods: A prospective, cross-sectional study was conducted on 292 patients who presented to the ED between 9/1/2021 and 8/9/2022. Patients were stratified into two cohorts based on their behavior during the initial assessment: actively using a cell phone (n = 32) or not using a cell phone (n = 259). Final disposition was dichotomously recorded as admission or discharge. Hospital admission, hospital observation, and admission to the ED observation unit were consolidated into the combined category of admission. Results: Patients not actively using their cell phone on initial assessment exhibited a discharge rate of 64%, while those engaged with their cellphones displayed notably higher dismissal rates at 94%. The calculated odds ratio (OR) of 8.4 (95% confidence interval: 1.96-36.0, p = 0.004) underscores a significantly heightened likelihood of dismissal among individuals actively using their cellphones, suggesting a potential association between cellphone use and a reduced probability of hospital admission. Conclusion: The study suggests an association between cellphone use during initial ED assessment and higher discharge rates. While this introduces a novel concept, the study's potential contribution to more informed and efficient triage decisions warrants careful consideration in future research and clinical applications. [ABSTRACT FROM AUTHOR]

What is this summary about? This plain language summary shares results from a clinical study called INTEGRIS-IPF that was published in the American Journal of Respiratory and Critical Care Medicine in 2024. This study looked at a medicine called bexotegrast (beck-so-teh-grast) as a possible treatment for idiopathic pulmonary fibrosis (i-dee-uh-pa-thick pul-muh-ner-ee fie-bro-sis; IPF). Bexotegrast is an investigational medicine, which means that it is being studied and has not yet been approved by the US Food and Drug Administration (FDA), for people with IPF to take as a treatment. IPF is a chronic, progressive lung disease that makes it hard to breathe and gets worse over time. There is no cure for IPF, treatment includes symptom management and consideration for the use of nintedanib or pirfenidone, which may decrease the pace of disease progression. The study compared bexotegrast to a placebo (a treatment that looks identical to the medicine but has no medicinal effect) to look at how well it works and how safe it is in treating people with IPF. Most people in the study also took one of two medicines that are already approved by the FDA for IPF, pirfenidone or nintedanib. [ABSTRACT FROM AUTHOR]

Premise of research. A self-fertilizing mating system can be important for colonization and persistence in diverse habitats. This study uses life history theory to generate hypotheses and compare mixed mating strategies in two caespitose grass species native to eastern North America: the annual Triplasis purpurea , which colonizes sandy beaches, and the perennial Danthonia compressa , which colonizes woodland edges. Methodology. Both species produce open, potentially outcrossed chasmogamous (CH) spikelets on emergent panicles and self-fertilizing, axillary cleistogamous (CL) spikelets enclosed by leaf sheaths along flowering tillers. Individuals from three populations per species were collected. Fecundity and mass of seeds from CH and CL panicles were determined. Plant parts were separated and dried to constant mass. Aboveground allocation to CH and CL seeds as a proportion of shoot mass and investment into cleistogamy based on its proportion of total fecundity or reproductive allocation was calculated. Pivotal results. Both species had similar sizes in the field based on tiller numbers and shoot mass. However, CL fecundity and allocation were much greater in T. purpurea than in D. compressa. Axillary CL seeds weighed more than CH seeds but only in D. compressa. Populations of T. purpurea showed phenotypic variation in CH and CL fecundity and allocation-based CL investment. Danthonia compressa populations varied in allocation to chasmogamy and cleistogamy and in fecundity- and allocation-based CL investment; a young experimental population (27 mo) had the highest CL investment. There was no evidence of a trade-off between CH and CL fecundity or allocation in either species. Conclusions. Colonizing annual grasses such as T. purpurea rely on CL seed production as reproductive assurance in sparsely populated, recently disturbed habitats. Although fecundity and reproductive allocation to chasmogamy and cleistogamy are lower in perennial D. compressa , heavier axillary CL seeds that are minimally dispersed maintain populations within less disturbed, more vegetated competitive habitats. [ABSTRACT FROM AUTHOR]

This study considers an aspect of the work experience material to an individual employee's happiness—their relationship with their supervisor—through the lens of expanding journalism studies scholarship on personal well-being. Considered through field theory, the present study reflects on interviews with U.S. journalists (n = 27) on their relationship with their supervisor and their perceptions of what constitutes an effective leader in journalism. Journalists largely attributed great leadership to a combination of strong cultural capital and strong symbolic capital within the field. [ABSTRACT FROM AUTHOR]

The safety of casirivimab + imdevimab (CAS + IMD) (anti-severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] monoclonal antibodies [mAbs]) in pediatric outpatients with coronavirus disease 2019 (COVID-19) was evaluated in a randomized phase 1/2/3 trial. Consistent with adults, CAS + IMD was generally well tolerated with low drug-induced immunogenicity rates. The findings support the development of next-generation anti-SARS-CoV-2 mAbs for at-risk pediatric patients. [ABSTRACT FROM AUTHOR]

Background and Hypothesis: The Cognitive Model of Negative Symptoms is a prominent model that posits that defeatist performance beliefs (DPB) are a key psychological mechanism underlying negative symptoms in those with schizophrenia (SZ). However, the ecological validity of the model has not been established, and temporally specific evaluations of the model's hypotheses have not been conducted. This study tested the model's key hypotheses in real-world environments using ecological momentary assessment (EMA). Study Design: Fifty-two outpatients with SZ and 55 healthy controls (CN) completed 6 days of EMA. Multilevel models examined concurrent and time-lagged associations between DPB and negative symptoms in daily life. Study Results: SZ displayed greater DPB in daily life than CN. Furthermore, greater DPB were associated with greater concurrently assessed negative symptoms (anhedonia, avolition, and asociality) in daily life. Time-lagged analyses indicated that in both groups, greater DPB at time t led to elevations in negative symptoms (anhedonia, avolition, or asociality) at t  + 1 above and beyond the effects of negative symptoms at time t. Conclusions: Results support the ecological validity of the Cognitive Model of Negative Symptoms and identify a temporally specific association between DPB and subsequent negative symptoms that is consistent with the model's hypotheses and a putative mechanistic pathway in Cognitive Behavioral Therapy for negative symptoms. Findings suggest that DPB are a psychological factor contributing to negative symptoms in real-world environments. Implications for measuring DPB in daily life and providing just-in-time mobile health-based interventions to target this mechanism are discussed. [ABSTRACT FROM AUTHOR]

Innovative solutions are needed to reduce the amount of high-level waste generated by used nuclear fuel recycling strategies to support the widespread adoption of sustainable nuclear fission energy technologies. To this end, a new sulfur chloride-based process has been developed to recycle zirconium alloy-based materials, which make up a significant fraction of high-level radioactive waste. To support the continued development of this process, we present new data on the potential reaction pathways over time of the products arising from the gamma and electron beam radiolysis of neat thionyl chloride (SOCl2). Interrogation of the gamma irradiated liquid by Raman spectroscopy provided more conclusive identification of the SOCl2 degradation products, specifically sulfur dichloride (SCl2), molecular chlorine (Cl2), sulfur dioxide (SO2), and sulfuryl chloride (SO2Cl2). In comparison, the high dose rate (∼107 Gy s−1) electron beam irradiations formed significantly more degradation products. For both cobalt-60 gamma and electron beam irradiations, the observed degradation products were found to evolve as a function of time post-irradiation via the same reaction pathways, with indication of a solvent regeneration mechanism. These findings are fortuitous for process development, as such a mechanism would be beneficial for process longevity and cost effectiveness. [ABSTRACT FROM AUTHOR]

Habitat structural complexity is an emergent property of ecosystems that directly shapes their biodiversity, functioning and resilience to disturbance. Yet despite its importance, we continue to lack consensus on how best to define structural complexity, nor do we have a generalised approach to measure habitat complexity across ecosystems. To bridge this gap, here we adapt a geometric framework developed to quantify the surface complexity of coral reefs and apply it to the canopies of tropical rainforests. Using high‐resolution, repeat‐acquisition airborne laser scanning data collected over 450 km2 of human‐modified tropical landscapes in Borneo, we generated 3D canopy height models of forests at varying stages of recovery from logging. We then tested whether the geometric framework of habitat complexity – which characterises 3D surfaces according to their height range, rugosity and fractal dimension – was able to detect how both human and natural disturbances drive variation in canopy structure through space and time across these landscapes. We found that together, these three metrics of surface complexity captured major differences in canopy 3D structure between highly degraded, selectively logged and old‐growth forests. Moreover, the three metrics were able to track distinct temporal patterns of structural recovery following logging and wind disturbance. However, in the process we also uncovered several important conceptual and methodological limitations with the geometric framework of habitat complexity. We found that fractal dimension was highly sensitive to small variations in data inputs and was ecologically counteractive (e.g. higher fractal dimension in oil palm plantations than old‐growth forests), while rugosity and height range were tightly correlated (r = 0.75) due to their strong dependency on maximum tree height. Our results suggest that forest structural complexity cannot be summarised using these three descriptors alone, as they overlook key features of canopy vertical and horizontal structure that arise from the way trees fill 3D space. Keywords: Forest disturbance, LiDAR, logging, recovery, remote sensing, structural complexity [ABSTRACT FROM AUTHOR]

Objectives: Study objectives were to: 1) iteratively adapt the Transdiagnostic Sleep and Circadian Intervention (TranS-C) for patients in cardiac rehabilitation (CR; Phase 1) and 2) conduct a preliminary single group pre-post intervention test to a) evaluate procedural feasibility and intervention acceptability and b) to explore preliminary pre-post changes in self-reported sleep, disability, and health-related quality of life (HRQoL; Phase 2). Method: In Phase 1, 12 individuals in CR and six content experts completed interviews to inform TranS-C adaptations. Interviews were analyzed using rapid qualitative analysis. In Phase 2, eight individuals in CR completed a baseline assessment, the adapted TranS-C intervention, and a post-intervention assessment. Intervention acceptability was assessed via questionnaire and interview. Sleep, disability, and HRQoL outcomes were assessed using questionnaires. Descriptive statistics were calculated for quantitative measures; interviews were analyzed using rapid qualitative analysis. Results: Phase 1 participants were receptive to the premise and structure of the adapted intervention. In Phase 2, participants endorsed positive attitudes toward the intervention. Seven of eight participants demonstrated improvements in sleep outcomes. Disability and HRQoL results did not consistently improve. Conclusion: The adapted TranS-C intervention was acceptable to CR patients and could yield improvements in subjective sleep outcomes. Larger-scale testing in CR is warranted. [ABSTRACT FROM AUTHOR]

BACKGROUND: Disparities in school attendance exist for children with medical complexity (CMC) due to COVID‐19. Longitudinal changes in family‐reported school safety perceptions and predictors of full‐time, in‐person school attendance are unknown. METHODS: This was a prospective, longitudinal cohort study with 3 survey waves (June 2021‐June 2022) among English‐ and Spanish‐speaking families of CMC aged 5 to 17 years and pre‐pandemic school attendance. Changes in Health Belief Model perceptions and full‐time in‐person school attendance were estimated using multivariate generalized linear modeling with repeated measures. RESULTS: Among 1601 respondents (52.9% of 3073 invited), 86.8% participated in all 3 surveys. School safety perceptions improved with time; however, perceived susceptibility to COVID‐19 increased. Full‐time in‐person school attendance rose from 48.4% to 90.0% from wave 1 to 3 (p <.0001), and was associated with motivation, benefits, and cues. For example, families with low compared to high motivation for in‐person attendance had 76% versus 98% predicted probability for child's school attendance, respectively at wave 3 (p <.0001). IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: Probability of full‐time in‐person school attendance was associated with several health belief model perceptions. School health policy and programs may benefit from promoting family motivation, benefits, and cues during future respiratory illness epidemics including COVID‐19. CONCLUSIONS: In‐person school attendance improved for CMC over time. Opportunities exist to continue optimizing in‐person attendance and family‐perceived safety for CMC at school. [ABSTRACT FROM AUTHOR]

The document is a reply to a comment regarding research on the Magallanes Fault System (MFS) in Tierra del Fuego, Patagonia. The authors address criticisms of their work and discuss overlapping results with another study on fault slip rates in Argentina. They highlight the importance of fieldwork, drone photography, and data integration in determining fault slip rates. The study emphasizes the need for further research on other active faults in the MFS and the implications for seismic hazard and neotectonics. [Extracted from the article]

Modulating inflammation is critical to enhance nerve regeneration after injury. However, clinically applicable regenerative therapies that modulate inflammation have not yet been established. Here, we demonstrate synergistic effects of the combination of an HMG-CoA reductase inhibitor, statin/fluvastatin and critical components of the extracellular matrix, Matrix-Bound Nanovesicles (MBV) to enhance axon regeneration and neuroprotection after mouse optic nerve injury. Mechanistically, co-intravitreal injections of fluvastatin and MBV robustly promote infiltration of monocytes and neutrophils, which lead to RGC protection and axon regeneration. Furthermore, monocyte infiltration is triggered by elevated expression of CCL2, a chemokine, in the superficial layer of the retina after treatment with a combination of fluvastatin and MBV or IL-33, a cytokine contained within MBV. Finally, this therapy can be further combined with AAV-based gene therapy blocking anti-regenerative pathways in RGCs to extend regenerated axons. These data highlight novel molecular insights into the development of immunomodulatory regenerative therapy. [ABSTRACT FROM AUTHOR]

Background: Two-drug regimens (2DRs) have been introduced in recent years to potentially reduce antiretroviral therapy (ART) toxicities and drug-drug interactions while demonstrating comparable efficacy to three-drug regimens (3DRs) for people with HIV (PWH). The objective of this study was to compare the real-world effectiveness and durability of a single-tablet 2DR of dolutegravir/lamivudine (DTG/3TC) with that of commonly prescribed 3DRs in ART-experienced, virologically suppressed PWH during the first 24 months of DTG/3TC availability in the United States. Methods: Virologically suppressed (viral load [VL] < 200 copies/mL) adult PWH initiating DTG/3TC 2DR, bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), or a DTG-based 3DR between 01MAY2019 and 31OCT2020 were identified in the OPERA® cohort and followed through 30APR2021. Univariate Poisson regression (incidence rates) and marginal structural Cox proportional hazards models with inverse probability of treatment weights (hazard ratios) were used to quantify relationships between regimen type and confirmed virologic failure (2 consecutive VLs ≥ 200 copies/mL) or regimen discontinuation. Reasons for discontinuation were examined. Results: A total of 8,037 ART-experienced, virologically suppressed PWH met the inclusion criteria and switched to DTG/3TC (n = 1,450), BIC/FTC/TAF (n = 5,691), or a DTG-based 3DR (n = 896). Incidence rates of confirmed virologic failure were low for all groups, at 0.66 (DTG/3TC), 0.84 (BIC/FTC/TAF), and 1.78 (DTG 3DR) per 100 person-years (py). Compared to DTG/3TC, only the DTG 3DRs were associated with a statistically significant increased hazard of confirmed virologic failure (hazard ratio: 5.21, 95% confidence interval: 1.85, 14.67). Discontinuation rates per 100 py were highest in the DTG 3DR group (24.90), followed by the DTG/3TC group (17.69) and the BIC/FTC/TAF group (8.30). Regardless of regimen, discontinuations were infrequently attributed to effectiveness (VL ≥ 200 copies/mL; 4%) or tolerability (adverse diagnoses, side effects, or lab abnormalities; 6%). Conclusions: Among virologically suppressed PWH initiating a new regimen, few individuals experienced virologic failure in real-world clinical care. While rates of regimen discontinuation were high, most discontinuations could not be attributed to a lack of virologic control or poor tolerability. These findings suggest that DTG/3TC is an effective option for ART-experienced, virologically suppressed PWH. [ABSTRACT FROM AUTHOR]

Many disease-causing proteins have multiple pathogenic mechanisms, and conventional inhibitors struggle to reliably disrupt more than one. Targeted protein degradation (TPD) can eliminate the protein, and thus all its functions, by directing a cell's protein turnover machinery towards it. Two established strategies either engage catalytic E3 ligases or drive uptake towards the endolysosomal pathway. Here we describe CYpHER (CatalYtic pH-dependent Endolysosomal delivery with Recycling) technology with potency and durability from a catalytic mechanism that shares the specificity and straightforward modular design of endolysosomal uptake. By bestowing pH-dependent release on the target engager and using the rapid-cycling transferrin receptor as the uptake receptor, CYpHER induces endolysosomal delivery of surface and extracellular targets while re-using drug, potentially yielding increased potency and reduced off-target tissue exposure risks. The TfR-based approach allows targeting to tumors that overexpress this receptor and offers the potential for transport to the CNS. CYpHER function was demonstrated in vitro with EGFR and PD-L1, and in vivo with EGFR in a model of EGFR-driven non-small cell lung cancer. Targeted protein degradation (TPD) can be employed to eliminate disease-causing proteins. Here, the authors present CYpHER, a TPD tool that uses molecules engineered for intracellular target release with drug recycling via transferrin receptor. CYpHER induces depletion of extracellular targets in vitro and in xenograft tumours. [ABSTRACT FROM AUTHOR]

Reward processing impairments are a key factor associated with negative symptoms in those with severe mental illnesses. However, past findings are inconsistent regarding which reward processing components are impaired and most strongly linked to negative symptoms. The current study examined the hypothesis that these mixed findings may be the result of multiple reward processing pathways (i.e., equifinality) to negative symptoms that cut across diagnostic boundaries and phases of illness. Participants included healthy controls (n = 100) who served as a reference sample and a severe mental illness-spectrum sample (n = 92) that included psychotic-like experiences, clinical high-risk for psychosis, bipolar disorder, and schizophrenia participants. All participants completed tasks measuring four RDoC Positive Valence System constructs: value representation, reinforcement learning, effort–cost computation, and hedonic reactivity. A k-means cluster analysis of the severe mental illness-spectrum samples identified three clusters with differential reward processing profiles that were characterized by: (1) global reward processing deficits (22.8%), (2) selective impairments in hedonic reactivity alone (40.2%), and (3) preserved reward processing (37%). Elevated negative symptoms were only observed in the global reward processing cluster. All clusters contained participants from each clinical group, and the distribution of these groups did not significantly differ among the clusters. Findings identified one pathway contributing to negative symptoms that was transdiagnostic and transphasic. Future work further characterizing divergent pathways to negative symptoms may help to improve symptom trajectories and personalized treatments. [ABSTRACT FROM AUTHOR]

Blunted affect is associated with severe mental illness, particularly schizophrenia. Mechanisms of blunted affect are poorly understood, potentially due to a lack of phenomenological clarity. Here, we examine clinician rated blunted affect and computerized facial metrics derived from ambulatory video assessment using machine learning. With high predictive accuracy (80–82%), we found that head orientation, eye movement, and facets of mouth movement were associated with clinical ratings of blunted affect. Features denoting larger muscle movements were associated with social cognition (R2 = 0.37) and cognition (R2 = 0.40). Findings provide potential insights on psychological and pathophysiological contributors to blunted affect. [ABSTRACT FROM AUTHOR]

Objectives: Body image adjustment is a crucial issue for patients with facial cancer, but body image–specific interventions are scarce. We report results of a novel psychotherapeutic intervention to address body image concerns during acute postoperative recovery following facial reconstructive surgery. Our primary aims were to evaluate the intervention's feasibility, acceptability, and efficacy on body image concerns, psychological distress, and quality of life (QOL). Methods: Adults with facial cancers who endorsed body image concerns were recruited to participate in a randomized controlled trial. The intervention group participated in 4 in-person counseling sessions. The control group received an educational booklet and a brief phone call. Participants completed measures of body image, distress, and QOL at baseline and at the 4-week follow-up to assess the impact of the intervention. Intervention outcomes were assessed with 2 sample t- tests or Mann–Whitney U tests as appropriate. Results: Twenty-nine participants completed both the baseline and follow-up assessments. The intervention demonstrated good feasibility with a high retention rate (79%), visit completion rate (81%), and high satisfaction scores (75% reported mean satisfaction score of >3). Intervention did not result in an observed statistically significant difference in reduction in body image dissatisfaction and disturbance, psychological distress, or improvement in QOL compared with the control group. However, intervention resulted in statistically significant difference in perceived social impact (−1 vs. −8.3, p  = 0.033) compared to control group. Significance of results: Our study highlights the potential clinical benefits of a novel psychotherapeutic intervention that targets body image concerns and suggests the need for further evaluation. [ABSTRACT FROM AUTHOR]

Military veterans are at increased risk for headache disorders compared to the general population, yet the prevalence and burden associated with headache disorders among veterans is not yet well understood. In this electronic medical record study, we examined the prevalence of headache disorders among veterans seen in a northeastern network of Veterans Health Administration (VHA) primary care during 2017–2018. We also examined rates of psychiatric comorbidity and health care utilization of veterans with headache disorders for the year following the date of the first headache code in the medical record. Of the total population of veterans in the network, 1.3% had a headache disorder and another 3.5% had a possible headache disorder. Migraine and chronic migraine represented the majority of cases. Posttraumatic stress disorder was the most frequent psychiatric comorbidity. Having a headache disorder was associated with higher rates of primary care, neurology, pain clinic, and mental health service use but not higher rates of emergency department or Whole Health (e.g., patient-centered, holistic health services) use. Prevalence findings are comparable to those previously found among veterans, but a substantial proportion of veterans may have been misdiagnosed. Veterans with headache disorders have high rates of psychiatric comorbidity and use several types of health services at higher rates. Findings highlight the need for interdisciplinary care and further education and support for primary care providers. Primary care settings that integrate evidence-based behavioral and Whole Health services may be an optimal way of providing more holistic care for headache disorders. [ABSTRACT FROM AUTHOR]

Introduction Personalized and tumor-informed circulating tumor DNA (ctDNA) testing is feasible and allows for molecular residual disease (MRD) identification in patients with pancreatic ductal adenocarcinoma (PDAC). Methods In this retrospective analysis of commercial cases from multiple US institutions, personalized, tumor-informed, whole-exome sequenced, and germline-controlled ctDNA levels were quantified and analyzed in patients with PDAC. Plasma samples (n  = 1329) from 298 clinically validated patients were collected at diagnosis, perioperatively (MRD-window; within 2-12 weeks after surgery, before therapy), and during surveillance (>12 weeks post-surgery if no ACT or starting 4 weeks post-ACT) from November 2019 to March 2023. Results Of the initially diagnosed patients with stages I-III PDAC who went for resection, the median follow-up time from surgery was 13 months (range 0.1-214). Positive ctDNA detection rates were 29% (29/100) and 29.6% (45/152) during the MRD and surveillance windows, respectively. Positive ctDNA detection was significantly associated with shorter DFS within the MRD window (median DFS of 6.37 months for ctDNA-positive vs 33.31 months for ctDNA-negative patients; HR: 5.45, P  < .0001) as well as during the surveillance period (median DFS: 11.40 months for ctDNA-positive vs NR for ctDNA-negative; HR: 12.38, P  < .0001). Additionally, DFS was significantly better with KRAS wildtype status followed by KRAS G12R (HR: 0.99, P  = .97), KRAS G12D (HR: 1.42, P  = .194), and worse with KRAS G12V (HR: 2.19, P  = .002) status. In multivariate analysis, ctDNA detection at surveillance was found to be the most significant prognostic factor for recurrence (HR: 24.28, P  < .001). Conclusions Perioperative tumor-informed ctDNA detection in PDAC is feasible across all stages and is associated with patient survival outcomes. [ABSTRACT FROM AUTHOR]

An interview-informed synthesized contingency analysis (IISCA; Hanley et al. in J Appl Behav Anal 47:16–36, 2014) and related skill-based treatment process can result in socially valid outcomes for clients exhibiting severe challenging behavior when implemented by professionals and then transferred to parents (e.g., Santiago et al. in J Autism Dev Disord 46:797–811, 2016). However, many families do not have access to professionals trained to implement functional analyses or function-based treatments (Deochand & Fuqua Behav Anal Pract 9:243–252, 2016). Experimenters in the present study coached three parents of children with autism exhibiting severe challenging behavior through implementing an IISCA and resulting skill-based treatment process through distance-based collaborative consulting. All parents achieved differentiated functional analyses, taught their children to emit functional replacement skills, and reduced challenging behavior relative to baseline. [ABSTRACT FROM AUTHOR]

Abiogenesis is frequently envisioned as a linear, ladder-like progression of increasingly complex chemical systems, eventually leading to the ancestors of extant cellular life. This "pre-cladistics" view is in stark contrast to the well-accepted principles of organismal evolutionary biology, as informed by paleontology and phylogenetics. Applying this perspective to origins, I explore the paradigm of "Stem Life," which embeds abiogenesis within a broader continuity of diversification and extinction of both hereditary lineages and chemical systems. In this new paradigm, extant life's ancestral lineage emerged alongside and was dependent upon many other complex prebiotic chemical systems, as part of a diverse and fecund prebiosphere. Drawing from several natural history analogies, I show how this shift in perspective enriches our understanding of Origins and directly informs debates on defining Life, the emergence of the Last Universal Common Ancestor (LUCA), and the implications of prebiotic chemical experiments. [ABSTRACT FROM AUTHOR]

Knowledge of the spin state of space objects is critical for effectively planning operations such as collision avoidance and debris removal. One such passive method for assessing the spin rate and spin-axis of debris is through the use of passive brightness measurements known as “light curves.” Astronomers have derived physics-based algorithms for retrieving spin state via light curve analysis. These algorithms convert the relative spin state into an inertial spin state by accounting for the motions of the observation telescope, the space object, and the sun. A major downside of these theories, however, is that the resulting cost functions for operational deployment are highly non-linear. The intractable nature of the spin state estimation problem opens the door for solution via Machine Learning (ML) models. Typical “black box” ML algorithms do not rely on scientific theory, but rather are trained on large data-bases to learn how to solve a task in a manner that is obscured from the operator. While ML models can be effective for making predictions that out-perform human-derived algorithms, they also have the potential to derive solutions that either violate known physical constraints or are non-generalizable to new data instances. This is in particular a concern for many Space Domain Awareness (SDA) problems that are rooted in the physical theory of the motions of orbiting bodies. To overcome the limitations of both physical theory and “black box” ML models for spin state retrieval, we leverage a hybrid approach: the physics-guided ML model. This concept uses a physics-based loss function in the learning objective of the ML model in order to guide the model towards making predictions that not only exhibit low prediction error with respect to training data but are also physically consistent with astronomer-derived theories. Towards this end, we introduce a new physically derived equation for relating the inertial spin state to observations of relative spin rates. We then show that this equation can be used as a loss function for training ML models. We present a time-variant ML model for the retrieval of spin state that substantially outperforms both randomized numerical optimization approaches as well as temporally-invariant ML methods such as Convolutional Neural Networks. Finally, we provide initial evidence that training of the time-variant ML model with our physics-based loss function is more stable and generalizes more effectively to unseen (i.e. “out-of-distribution”) data instances. We believe that this paper provides promising avenues for merging big-data ML approaches with the robust physical theory of the SDA field. [ABSTRACT FROM AUTHOR]

Knowledge of the maneuver axis of actively controlled satellites and the rotation axes of uncontrolled satellites is critical for maintaining Space Situational Awareness (SSA) and predicting satellite motions. Estimates of the spin rate and spin-axis of rotating satellites have been shown to be retrievable via passively collected time series of satellite brightness, otherwise known as light curves. Retrieval of satellite spin state parameters from light curves is accomplished by application of a physically derived relationship, the “Epoch Method," that explains the difference between the apparent spin rate and the inertial spin rate using the known relative motion between the observation telescope, the satellite, and the sun. There are two major challenges for retrieving the inertial spin rate from relative spin rate measurements operationally via the Epoch Method. One challenge is that satellites can have complex rotation states in the sense that they rotate about multiple axes with varying angular velocities. A second challenge is that the apparent difference between the inertial and relative spin rate is a direct function of the observer-to-solar geometry, meaning that geographical sites must be tasked optimally in order to maximize their ability to collect useful measurements for spin state retrieval. In order to overcome these challenges we derive an information metric that can both (1) explain the rotation axis that was maximally observable for a collected light curve from a geographic site, and (2) be utilized to task a diverse network of geographic sites for collecting maximally useful light curve measurements for monitoring the spin axis of an uncontrolled satellite. This is accomplished by deriving the observability of the inertial spin axis information according to the Fisher Information Matrix (FIM). We assume that the state vector that is being tracked is the inertial spin axis and that the measurement is an apparent spin rate measurement. We then derive a sensitivity matrix that utilizes the physical theory of the Epoch Method in deriving the partial derivatives of the measurement with respect to the state vector. We present several examples of how this metric can be applied towards tasking satellite networks across the continental United States for monitoring the inertial spin axis of Low Earth Orbit (LEO) and Geostationary (GEO) satellites. [ABSTRACT FROM AUTHOR]

The global obesity epidemic, with its associated comorbidities and increased risk of early mortality, underscores the urgent need for enhancing our understanding of the origins of this complex disease. It is increasingly clear that metabolism is programmed early in life and that metabolic programming can have life-long health consequences. As a critical metabolic organ sensitive to early-life stimuli, proper development of adipose tissue (AT) is crucial for life-long energy homeostasis. Early-life nutrients, especially fatty acids (FAs), significantly influence the programming of AT and shape its function and metabolism. Of growing interest are the dynamic responses during pre- and postnatal development to proinflammatory omega-6 (n6) and anti-inflammatory omega-3 (n3) FA exposures in AT. In the US maternal diet, the ratio of "pro-inflammatory" n6- to "anti-inflammatory" n3-FAs has grown dramatically due to the greater prevalence of n6-FAs. Notably, AT macrophages (ATMs) form a significant population within adipose stromal cells, playing not only an instrumental role in AT formation and maintenance but also acting as key mediators of cell-to-cell lipid and cytokine signaling. Despite rapid advances in ATM and immunometabolism fields, research has focused on responses to obesogenic diets and during adulthood. Consequently, there is a significant gap in identifying the mechanisms contributing metabolic health, especially regarding lipid exposures during the establishment of ATM physiology. Our review highlights the current understanding of ATM diversity, their critical role in AT, their potential role in early-life metabolic programming, and the broader implications for metabolism and health. [ABSTRACT FROM AUTHOR]

Despite the higher prevalence of mental health disorders among serving Royal Canadian Mounted Police (RCMP) relative to the general population, RCMP cadets begin training with lower putative risk and greater perceived resilience than young adults in the general population. The current study was designed to assess the effectiveness of the Cadet Training Program—the paramilitary training RCMP recruits complete to become serving RCMP—in strengthening RCMP cadets' mental health by examining putative risk and resilience factors among post-training/pre-deployment cadets. Post-training/pre-deployment cadets (n = 492; 70.5% men) completed self-report measures of several putative risk variables (i.e., anxiety sensitivity, fear of negative evaluation, illness and injury sensitivity, intolerance of uncertainty, pain anxiety, and state anger) and perceived resilience. Cadets' post-training/pre-deployment scores were compared to their pre-training scores (see Khoury et al. in Front Psychol 14:1048573, 2023) on the same measures, and to scores from Canadian, American, Australian, and European young adult control samples. Participants had significantly lower scores on all putative risk variables with the exception of state anger, and significantly higher scores on perceived resilience, at post-training/pre-deployment compared to pre-training. Participants also had significantly lower scores on all putative risk variables, and significantly higher scores on perceived resilience, compared to scores from young adult control samples. These uncontrolled pilot findings suggest the Cadet Training Program may be beneficial for RCMP cadets' mental health and provide further evidence that the nature of policing, rather than individual differences in risk and resilience, likely explains serving RCMP's relatively higher prevalence of mental health disorders. [ABSTRACT FROM AUTHOR]

An updated version of the Particle Analysis by Laser Mass Spectrometry (PALMS) instrument, termed PALMS-NG (-Next Generation), has been designed to characterize particles in the troposphere and stratosphere. Two PALMS-NG instruments have been built: a Purdue University version, which has flown on the National Aeronautics and Space Administration (NASA) ER-2 and DC-8, and a National Oceanic and Atmospheric Administration (NOAA) version, which has flown on the NASA WB-57F. The general design and construction are nearly identical. New features and construction techniques are described here. These include a new inlet, optics for an extended size range of particle measurement, and a unique bipolar s-shaped mass spectrometer with higher resolution. These make the -NG instrument a significant improvement over the original flight PALMS which was first flown 25 years ago. Copyright © 2024 American Association for Aerosol Research [ABSTRACT FROM AUTHOR]

In frequency regions where ultra‐wide band log‐periodic antennas exhibit negative group delay (NGD), the effect of higher‐order modes upon amplitude‐modulated signals is examined using convolution theory. It is shown that in these frequency regions, the group delay and the effect of the higher order modes upon amplitude‐modulated signals vary throughout the antenna's radiation pattern. It is also shown that the signal time advances predicted by the NGD are due to signal distortion when undesired higher‐order modes are present on the antenna. [ABSTRACT FROM AUTHOR]

This study seeks to explore the motivations and labor of lifestyle, or "soft news," journalists. Rooted in the lens of discursive institutionalism and through 30 interviews with lifestyle journalists in the United States, this study reflects on the aspirational labor—the opportunity to "do what you love"—that motivates entry into journalism but also can encourage disengagement. This study finds that while lifestyle journalists are motivated to enter the profession because of their own personal connection to the topic, their desire to be embedded in the topic and their love for the people in the genre, they also have to negotiate institutional expectations. Furthermore, lifestyle journalists seemed to reflect a sort of cognitive dissonance in their practices—while drawn to the idea they would never actually work, since they were embedded in their passion—in reality what many journalists described reflected that they had difficulty leaving work, given that even their passion had become work. [ABSTRACT FROM AUTHOR]

Simple Summary: Currently, there are no effective therapies for glioblastoma. Infiltrating myeloid cells contributes significantly to the immune suppressive tumor microenvironment that is characteristic of GBM. Monocytic myeloid-derived suppressor cells are chief immune suppressive cells found in the glioma microenvironment. Understanding the mechanisms of M-MDSC differentiation and T-cell suppression is imperative for generating therapies that target this tumor-supportive cell population. In this study, we found that glioma-secreted CSF1R ligands, M-CSF and IL-34, promote M-MDSCs to suppress CD8 T cells. These M-MDSCs partially utilize nitric oxide synthase to illicit their suppressive activity. However, spatial RNAseq points to glioma microenvironment niches driving M-MDSC heterogeneity. Our findings identify key regulators of differentiation and suppressive mechanisms of M-MDSCs and confirm the importance of targeting this cell population in glioma. Glioblastoma (GBM) is the most common malignant primary brain tumor, resulting in poor survival despite aggressive therapies. GBM is characterized by a highly heterogeneous and immunosuppressive tumor microenvironment (TME) made up predominantly of infiltrating peripheral immune cells. One significant immune cell type that contributes to glioma immune evasion is a population of immunosuppressive cells, termed myeloid-derived suppressor cells (MDSCs). Previous studies suggest that a subset of myeloid cells, expressing monocytic (M)-MDSC markers and dual expression of chemokine receptors CCR2 and CX3CR1, utilize CCR2 to infiltrate the TME. This study evaluated the mechanism of CCR2+/CX3CR1+ M-MDSC differentiation and T cell suppressive function in murine glioma models. We determined that bone marrow-derived CCR2+/CX3CR1+ cells adopt an immune suppressive cell phenotype when cultured with glioma-derived factors. Glioma-secreted CSF1R ligands M-CSF and IL-34 were identified as key drivers of M-MDSC differentiation while adenosine and iNOS pathways were implicated in the M-MDSC suppression of T cells. Mining a human GBM spatial RNAseq database revealed a variety of different pathways that M-MDSCs utilize to exert their suppressive function that is driven by complex niches within the microenvironment. These data provide a more comprehensive understanding of the mechanism of M-MDSCs in glioblastoma. [ABSTRACT FROM AUTHOR]

Research has documented that socio-economically disadvantaged students (SEDSs) lag behind in reading when compared with their counterparts from privileged backgrounds. Although well-designed instructional interventions could improve students' reading achievement, what is still unknown is which pedagogical approach could improve the reading of SEDSs especially in the context of a developing nation. We compared the effects of two different approaches that contain metacognitive reading strategies with the conventional teaching method on the reading achievement (comprehension and vocabulary) of students with low socio-economic status. We adopted a non-randomized pretest–posttest control group design. One hundred and twenty-eight students from three community secondary schools participated in the study. Data were collected with a teacher-made reading achievement test. Using the mixed repeated-measures ANOVA, findings indicated no significant differences in their reading achievement across groups, though similar significant improvements were observed within groups. Gender also showed a significant main effect only on the comprehension achievement of the students showing that female students did better than their male counterparts in comprehension achievement. Results did not show a significant interaction effect between gender and method. It was concluded that the students' reading achievement could be improved in the three approaches. [ABSTRACT FROM AUTHOR]