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Abstract Drug discovery is an intricate and costly process. Repurposing existing drugs and active compounds offers a viable pathway to develop new therapies for various diseases. By leveraging publicly available biomedical information, it is possible to predict compounds’ activity and identify their potential targets across diverse organisms. In this study, we aimed to assess the antiplasmodial activity of compounds from the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) library using in vitro and bioinformatics approaches. We assessed the in vitro antiplasmodial activity of the compounds using blood-stage and liver-stage drug susceptibility assays. We used protein sequences of known targets of the ReFRAME compounds with high antiplasmodial activity (EC50

The central Arctic cryosphere is influenced by the Arctic amplification (AA) and is warming faster than the lower latitudes. AA affects the formation, loss, and transport of aerosols. Efforts to assess the underlying processes determining aerosol variability are currently limited due to the lack of ground-based and space-borne aerosol observations with high spatial coverage in this region. This study addresses the observational gap by making use of total aerosol optical depth (AOD) datasets retrieved by the AEROSNOW algorithm over the vast cryospheric region of the central Arctic during Arctic spring and summer. GEOS-Chem (GC) simulations combined with AEROSNOW-retrieved data are used to investigate the processes controlling aerosol loading and distribution at different temporal and spatial scales. For the first time, an integrated study of AOD over the Arctic cryosphere during sunlight conditions was possible with the AEROSNOW retrieval and GC simulations. The results show that the spatial patterns observed by AEROSNOW differ from those simulated by GC. During spring, which is characterized by long-range transport of anthropogenic aerosols in the Arctic, GC underestimates the AOD in the vicinity of Alaska in comparison with AEROSNOW retrieval. At the same time, it overestimates the AOD along the Bering Strait, northern Europe, and the Siberian central Arctic sea-ice regions, with differences of −12.3 % and 21.7 %, respectively. By contrast, GC consistently underestimates AOD compared with AEROSNOW in summer, when transport from lower latitudes is insignificant and local natural processes are the dominant source of aerosol, especially north of 70° N. This underestimation is particularly pronounced over the central Arctic sea-ice region, where it is −10.6 %. Conversely, GC tends to overestimate AOD along the Siberian and Greenland marginal sea-ice zones by 19.5 % but underestimates AOD along the Canadian Archipelago by −9.3 %. The differences in summer AOD between AEROSNOW data products and GC-simulated AOD highlight the need to integrate improved knowledge of the summer aerosol process into existing models in order to constrain its effects on cloud condensation nuclei, on ice nucleating particles, and on the radiation budget over the central Arctic sea ice during the developing AA period.

Abstract Non-invasive neuromodulation of non-compressible internal organs has significant potential for internal organ bleeding and blood-shift in aero/space medicine. The present study aims to investigate the potential influences of the non-invasive transcutaneous electrical nerve stimulation (TENS) on multiple non-compressible internal organs’ blood flow. Porcine animal model (n = 8) was randomized for a total of 48 neuromodulation sessions with two different TENS stimulation frequencies (80 Hz, 10 Hz) and a placebo stimulation. A combination of two different electrode configurations (Abdominal-only or Abdominal and hind limb) were also performed. Intraarterial blood flow measurements were taken during pre and post-stimulation periods at the left renal artery, common hepatic artery, and left coronary artery. Intracranial, and extracranial arterial blood flows were also assessed with digital subtraction angiography. TENS with abdominal-only electrode configurations at 10 Hz demonstrated significant reductions in average peak blood flow velocity (APV) of the common hepatic artery (p = 0.0233) and renal arteries (p = 0.0493). Arterial pressures (p = 0.0221) were also significantly lower when renal APV was reduced. The outcome of the present study emphasises the potential use of TENS in decreasing the blood flow of non-compressible internal organs when the correct combination of electrodes configuration and frequency is used.

Abstract Background Bone morphogenetic protein 4 (BMP4) is a potent inhibitor of breast cancer metastasis. However, a tumor-promoting effect of BMP4 is reported in other tumor types, especially when SMAD4 is inactive. Methods To assess the requirement for SMAD4 in BMP4-mediated suppression of metastasis, we knocked down SMAD4 in two different breast tumors and enforced SMAD4 expression in a third line with endogenous SMAD4 deletion. In addition, we assessed the requirement for SMAD4 in tumor cell-specific BMP signalling by expression of a constitutively active BMP receptor. Delineation of genes regulated by BMP4 in the presence or absence of SMAD4 was assessed by RNA sequencing and a BMP4-induced gene, MYO1F was assessed for its role in metastasis. Genes regulated by BMP4 and/or SMAD4 were assessed in a publicly available database of gene expression profiles of breast cancer patients. Results In the absence of SMAD4, BMP4 promotes primary tumor growth that is accompanied by increased expression of genes associated with DNA replication, cell cycle, and MYC signalling pathways. Despite increased primary tumor growth, BMP4 suppresses metastasis in the absence of tumor cell expression of SMAD4. Consistent with the anti-metastatic activity of BMP4, enforced signalling through the constitutively active receptor in SMAD4 positive tumors that lacked BMP4 expression still suppressed metastasis, but in the absence of SMAD4, the suppression of metastasis was largely prevented. Thus BMP4 is required for suppression of metastasis regardless of tumor SMAD4 status. The BMP4 upregulated gene, MYO1F, was shown to be a potent suppressor of breast cancer metastasis. Gene signature upregulated by BMP4 in the absence of SMAD4 was associated with poor prognosis in breast cancer patients, whereas gene signature upregulated by BMP4 in the presence of SMAD4 was associated with improved prognosis. Conclusions BMP4 expression is required for suppression of metastasis regardless of the SMAD4 status of the tumor cells. Since BMP4 is a secreted protein, we conclude that it can act both in an autocrine manner in SMAD4-expressing tumor cells and in a paracrine manner on stromal cells to suppress metastasis. Deletion of SMAD4 from tumor cells does not prevent BMP4 from suppressing metastasis via a paracrine mechanism.

Abstract Major depressive disorder (MDD) is associated with interoceptive processing dysfunctions, but the molecular mechanisms underlying this dysfunction are poorly understood. This study combined brain neuronal-enriched extracellular vesicle (NEEV) technology and serum markers of inflammation and metabolism with Functional Magnetic Resonance Imaging (fMRI) to identify the contribution of gene regulatory pathways, in particular micro-RNA (miR) 93, to interoceptive dysfunction in MDD. Individuals with MDD (n = 41) and healthy comparisons (HC; n = 35) provided blood samples and completed an interoceptive attention task during fMRI. EVs were separated from plasma using a precipitation method. NEEVs were enriched by magnetic streptavidin bead immunocapture utilizing a neural adhesion marker (L1CAM/CD171) biotinylated antibody. The origin of NEEVs was validated with two other neuronal markers - neuronal cell adhesion molecule (NCAM) and ATPase Na+/K+ transporting subunit alpha 3 (ATP1A3). NEEV specificities were confirmed by flow cytometry, western blot, particle size analyzer, and transmission electron microscopy. NEEV small RNAs were purified and sequenced. Results showed that: (1) MDD exhibited lower NEEV miR-93 expression than HC; (2) within MDD but not HC, those individuals with the lowest NEEV miR-93 expression had the highest serum concentrations of interleukin (IL)-1 receptor antagonist, IL-6, tumor necrosis factor, and leptin; and (3) within HC but not MDD, those participants with the highest miR-93 expression showed the strongest bilateral dorsal mid-insula activation during interoceptive versus exteroceptive attention. Since miR-93 is regulated by stress and affects epigenetic modulation by chromatin re-organization, these results suggest that healthy individuals but not MDD participants show an adaptive epigenetic regulation of insular function during interoceptive processing. Future investigations will need to delineate how specific internal and external environmental conditions contribute to miR-93 expression in MDD and what molecular mechanisms alter brain responsivity to body-relevant signals.

Abstract This study aimed to compare the prevalence of somnolence and hypersomnolence between a higher education student and non-student sample. Hershner and Chervin [Hershner in Nat sci sleep 10.2147/NSS.S62907, 2014] defined somnolence as lapses into drowsiness, consequently leading to the inability to maintain alertness. This definition aligns with the American Academy of Sleep Medicine's (AASM) definition [Berry in Am Acad Sleep Med 176:2012, 2012]. Hypersomnolence differs from this, as suggested by Lammers et al. [Lammers in Sleep Med Rev 52, 101306, 2020], and refers to the experience of excessive daytime sleepiness. It is commonly observed that individuals enrolled in higher education courses often experience somnolence and hypersomnolence; however, it is currently unclear whether this is more prevalent in students compared to the general population. An online survey was administered to 202 participants measuring somnolence, hypersomnolence, sleep quality, sleep efficiency, sleep disturbance, sleep duration, circadian preference, and daytime dysfunction. 94 participants were non-students, and 108 were enrolled in higher education. Significant differences were found between student and non-student samples for somnolence but not for hypersomnolence. Furthermore, within the non-student sample a multiple linear regression demonstrated that hypersomnolence was predicted by daytime dysfunction. The results suggest that there are differences in the predictors of somnolence and hypersomnolence between a student and non-student sample. Consequently, this study highlights that students experience hypersomnolence and somnolence differently to their non-student counterparts. Thus, warranting the need for further investigating within this unique population.

The Anthropogenic Carbon Dioxide Monitoring (CO2M) mission is a constellation of satellites currently planned to be launched in 2026. CO2M is planned to be a core component of a Monitoring and Verification Support (MVS) service capacity under development as part of the Copernicus Atmosphere Monitoring Service (CAMS). The CO2M radiance measurements will be used to retrieve column-averaged dry-air mole fractions of atmospheric carbon dioxide (XCO2), methane (XCH4) and total columns of nitrogen dioxide (NO2). Using appropriate inverse modelling, the atmospheric greenhouse gas (GHG) observations will be used to derive United Nations Framework Convention on Climate Change (UNFCCC) COP 21 Paris Agreement relevant information on GHG sources and sinks. This challenging application requires highly accurate XCO2 and XCH4 retrievals. Three different retrieval algorithms to derive XCO2 and XCH4 are currently under development for the operational processing system at EUMETSAT. One of these algorithms uses the heritage of the FOCAL (Fast atmOspheric traCe gAs retrievaL) method, which has already successfully been applied to measurements from other satellites. Here, we show recent results generated using the CO2M version of FOCAL, called FOCAL-CO2M. To assess the quality of the FOCAL-CO2M retrievals, a large set of representative simulated radiance spectra has been generated using the radiative transfer model SCIATRAN. These simulations consider the planned viewing geometry of the CO2 instrument and corresponding geophysical scene data (including different types of aerosols and varying surface properties), which were taken from model data for the year 2015. We consider instrument noise and systematic errors caused by the retrieval method but have not considered additional error sources due to, for example, instrumental issues, spectroscopy or meteorology. On the other hand, we have also not taken advantage in this study of CO2M's MAP (multi-angle polarimeter) instrument, which will provide additional information on aerosols and cirrus clouds. By application of the FOCAL retrieval to these simulated data, confidence is gained that the FOCAL method is able to fulfil the challenging requirements for systematic errors for the CO2M mission (spatio-temporal bias ≤ 0.5 ppm for XCO2 and ≤ 5 ppb for XCH4).

2D and 3D ultrasonic imaging has so far not been demonstrated in pure molten lead in the open literature. In this study the development of such an ultrasonic device for imaging is outlined and results from testing at 380 °C in lead are presented. The main difficulties were found to be achieving then maintaining suitable wetting while ensuring suitable durability of the device, both due to the harsh nature of molten lead and the elevated temperatures. The successful detection and imaging (2D and 3D), of differently shaped targets, where the features were above the size of the transmitted ultrasound beam was demonstrated.

A tropospheric ozone column (TrOC) dataset from the Ozone Mapping and Profiler Suite (OMPS) observations was generated by combining the retrieved total ozone column from OMPS – Nadir Mapper (OMPS-NM) and limb profiles from OMPS – Limb Profiler (OMPS-LP) data. All datasets were generated at the University of Bremen, and the TrOC product was obtained by applying the limb–nadir matching technique (LNM). The retrieval algorithm and a comprehensive analysis of the uncertainty budget are presented here. The OMPS-LNM-TrOC dataset (2012–2018) is analysed and validated through comparison with ozonesondes, tropospheric ozone residual (TOR) data from the combined Ozone Monitoring Instrument/Microwave Limb Sounder (OMI/MLS) observations, and the TROPOspheric Monitoring Instrument (TROPOMI) Convective Cloud Differential technique (CCD) dataset. The OMPS-LNM TrOC is generally lower than the other datasets. The average bias with respect to ozonesondes is −1.7 DU with no significant latitudinal dependence identified. The mean difference with respect to OMI/MLS TOR and TROPOMI CCD is −3.4 and −1.8 DU, respectively. The seasonality and inter-annual variability are in good agreement with all comparison datasets.

Abstract Biofilms are surface-associated communities of bacteria that grow in a self-produced matrix of polysaccharides, proteins, and extracellular DNA (eDNA). Sub-minimal inhibitory concentrations (sub-MIC) of antibiotics induce biofilm formation, potentially as a defensive response to antibiotic stress. However, the mechanisms behind sub-MIC antibiotic-induced biofilm formation are unclear. We show that treatment of Pseudomonas aeruginosa with multiple classes of sub-MIC antibiotics with distinct targets induces biofilm formation. Further, addition of exogenous eDNA or cell lysate failed to increase biofilm formation to the same extent as antibiotics, suggesting that the release of cellular contents by antibiotic-driven bacteriolysis is insufficient. Using a genetic screen for stimulation-deficient mutants, we identified the outer membrane porin OprF and the ECF sigma factor SigX as important. Similarly, loss of OmpA – the Escherichia coli OprF homolog – prevented sub-MIC antibiotic stimulation of E. coli biofilms. Our screen also identified the periplasmic disulfide bond-forming enzyme DsbA and a predicted cyclic-di-GMP phosphodiesterase encoded by PA2200 as essential for biofilm stimulation. The phosphodiesterase activity of PA2200 is likely controlled by a disulfide bond in its regulatory domain, and folding of OprF is influenced by disulfide bond formation, connecting the mutant phenotypes. Addition of reducing agent dithiothreitol prevented sub-MIC antibiotic biofilm stimulation. Finally, activation of a c-di-GMP-responsive promoter follows treatment with sub-MIC antibiotics in the wild-type but not an oprF mutant. Together, these results show that antibiotic-induced biofilm formation is likely driven by a signaling pathway that translates changes in periplasmic redox state into elevated biofilm formation through increases in c-di-GMP.

Abstract Background An understanding of the prevalence of gestational diabetes mellitus among pregnant women is essential at local, national and international level so that appropriate health care interventions can be planned, financed and delivered. Methods A systematic review and meta-analysis of primary research reporting the prevalence of gestational diabetes mellitus in Canada or the United States were carried out according to Meta-analysis of Observational Studies in Epidemiology guidelines. Four electronic databases were systematically searched in June 2023 to identify articles that reported gestational diabetes mellitus prevalence using universal screening in pregnant women from eligible general population samples. Estimates were combined using a random effects model, and the effects of moderator variables analysed. Results There were 36 separate samples of women or deliveries (total sample size 1,550,917). Overall mean prevalence of gestational diabetes mellitus was 6.9% (95% CI: 5.7–8.3); 13.7% (95% CI: 10.7–17.3) in studies using a one-step screening strategy, and 5.2% (95% CI: 4.4–6.1) in those using a two-step strategy. Heterogeneity in technical methods between studies produced differences in estimates, as did different diagnostic thresholds used. Conclusions The meta-analysis suggests a slightly higher prevalence of gestational diabetes mellitus in Canada and the United States, compared to Europe, but highlights the need for standardised protocols for estimating gestational diabetes mellitus prevalence.

Whilst automated analysis of immunostains in pathology research has focused predominantly on the epithelial compartment, automated analysis of stains in the stromal compartment is challenging and therefore requires time-consuming pathological input and guidance to adjust to tissue morphometry as perceived by pathologists. This study aimed to develop a robust method to automate stromal stain analyses using 2 of the commonest stromal stains (SMA and desmin) employed in clinical pathology practice as examples. An effective computational method capable of automatically assessing and quantifying tumour-associated stromal stains was developed and applied on cores of colorectal cancer tissue microarrays. The methodology combines both mathematical models and deep learning techniques with the former requiring no training data and the latter as many inputs as possible. The novel mathematical model was used to produce a digital double marker overlay allowing for fast automated digital multiplex analysis of stromal stains. The results show that deep learning methodologies in combination with mathematical modelling allow for an accurate means of quantifying stromal stains whilst also opening up new possibilities of digital multiplex analyses.

We connect evidence that 20 oC is the most stable temperature for cellular processes with macroecological observations. Examples show that temperatures warmer than ~20 oC result in decreases in: aquatic species’ tolerance to low oxygen; marine pelagic and benthic algal productivity; pelagic and benthic predation rates; global species richness in pelagic fishes, plankton and benthic invertebrates; and genetic diversity; but increased extinctions in the fossil record. The realised thermal niche of reef fishes and invertebrates globally is narrowest among species with distributions centred on 20 oC, as also seen in microbes. While many species have evolved to live at warmer and colder temperatures, most species live at, and extinctions in the fossil record across seven phyla were lower at, 20 oC. The mathematical “Corkrey” model, which predicts that thermal breadth should be minimized and species richness maximised at 20 oC across all Domains of life, provides an explanation for this “20 oC effect”. A literature search found highest species richness at ~20 oC across life in air and water, including animals, plants and microbes. That life seems centred around ~20 oC implies fundamental constraints that compromise the ability of extant tropical species to adapt to higher temperatures.

Research experience provides critical training for new biomedical research scientists. Students from underrepresented populations studying science, technology, engineering, and mathematics (STEM) are increasingly recruited into research pathways to diversify STEM fields. However, support structures outside of research settings designed to help these students navigate biomedical research pathways are not always available; nor are program support components outside the context of laboratory technical skills training and formal mentorship well understood. This study leveraged a multi-institutional research training program, Enhancing Cross-Disciplinary Infrastructure and Training at Oregon (EXITO), to explore how nine institutions designed a new curricular structure (Enrichment) to meet a common goal of enhancing undergraduate research training and student success. EXITO undergraduates participated in a comprehensive, 3-year research training program with the Enrichment component offered across nine sites: three universities and six community colleges, highly diverse in size, demographics, and location. Sites' approaches to supporting students in the training program were studied over a 30-month period. All sites independently created their own nonformal curricular structures, implemented interprofessionally via facilitated peer groups. Site data describing design and implementation were thematically coded to identify essential programmatic components across sites, with student feedback used to triangulate findings. Enrichment offered students time to critically reflect on their interests, experiences, and identities in research; network with peers and professionals; and support negotiation of hidden and implicit curricula. Students reported the low-pressure setting and student-centered curriculum balanced the high demands associated with academics and research. Core curricular themes described Enrichment as fostering a sense of community among students, exposing students to career paths and skills, and supporting development of students' professional identities. The non-formal, interprofessional curricula enabled students to model diverse biomedical identities and pathways for each other while informing institutional structures to improve diverse undergraduate students' success in academia and research.

Social motivation--the psychobiological predisposition for social orienting, seeking social contact, and maintaining social interaction--manifests in early infancy and is hypothesized to be foundational for social communication development in typical and atypical populations. However, the lack of infant social-motivation measures has hindered delineation of associations between infant social motivation, other early-arising social abilities such as joint attention, and language outcomes. To investigate how infant social motivation contributes to joint attention and language, this study utilizes a mixed longitudinal sample of 741 infants at high (HL = 515) and low (LL = 226) likelihood for ASD. Using moderated nonlinear factor analysis (MNLFA), we incorporated items from parent-report measures to establish a novel latent factor model of infant social motivation that exhibits measurement invariance by age, sex, and familial ASD likelihood. We then examined developmental associations between 6- and 12-month social motivation, joint attention at 12-15 months, and language at 24 months of age. On average, greater social-motivation growth from 6-12 months was associated with greater initiating joint attention (IJA) and trend-level increases in sophistication of responding to joint attention (RJA). IJA and RJA were both positively associated with 24-month language abilities. There were no additional associations between social motivation and future language in our path model. These findings substantiate a novel, theoretically driven approach to modeling social motivation and suggest a developmental cascade through which social motivation impacts other foundational skills. These findings have implications for the timing and nature of intervention targets to support social communication development in infancy.

Background Adoptive T-cell therapy targeting antigens expressed in glioblastoma has emerged as a potential therapeutic strategy to prevent or delay recurrence and prolong overall survival in this aggressive disease setting. Ephrin receptor A3 (EphA3), which is highly expressed in glioblastoma; in particular, on the tumor vasculature and brain cancer stem cells, is an ideal target for immune-based therapies.Methods We have designed an EphA3-targeted chimeric antigen receptor (CAR) using the single chain variable fragment of a novel monoclonal antibody, and assessed its therapeutic potential against EphA3-expressing patient-derived glioblastoma neurospheres, organoids and xenografted glioblastoma tumors in immunodeficient mice.Results In vitro expanded EphA3 CAR T cells from healthy individuals efficiently recognize and kill EphA3-positive glioblastoma cells in vitro. Furthermore, these effector cells demonstrated curative efficacy in an orthotopic xenograft model of glioblastoma. EphA3 CAR T cells were equally effective in targeting patient-derived neurospheres and infiltrate, disaggregate, and induce apoptosis in glioblastoma-derived organoids.Conclusions This study provides compelling evidence supporting the therapeutic potential of EphA3 CAR T-cell therapy against glioblastoma by targeting EphA3 associated with brain cancer stem cells and the tumor vasculature. The ability to target patient-derived glioblastoma underscores the translational significance of this EphA3 CAR T-cell therapy in the pursuit of effective and targeted glioblastoma treatment strategies.

Abstract Parenting practices such as parental monitoring are known to positively impact dietary behaviours in offspring. However, links between adolescent‐perceived parental monitoring and dietary outcomes have rarely been examined and never in an Australian context. This study investigated whether adolescent‐perceived parental monitoring is associated with more fruit and vegetable, and less sugar‐sweetened beverages (SSB) and junk food consumption in Australian adolescents. Cross‐sectional data was collected as part of baseline measurement for a randomised controlled trial in 71 Australian schools in 2019. Self‐reported fruit, vegetable, SSB and junk food intake, perceived parental monitoring and sociodemographic factors were assessed. Each dietary variable was converted to “not at risk/at risk” based on dietary guidelines, binary logistic regressions examined associations between dietary intake variables and perceived parental monitoring while controlling for gender and socio‐economic status. The study was registered in ANZCTR clinical trials. The sample comprised 6053 adolescents (Mage = 12.7, SD = 0.5; 50.6% male‐identifying). The mean parental monitoring score was 20.1/24 (SD = 4.76) for males and 21.9/24 (SD = 3.37) for females. Compared to adolescents who perceived lower levels of parental monitoring, adolescents reporting higher parental monitoring had higher odds of insufficient fruit (OR = 1.03; 95% CI = 1.02–1.05) and excessive SSB (OR = 1.07; 95% CI = 1.06–1.09) intake, but lower odds of excessive junk food (OR = 0.96; 95% CI = 0.95–0.98) and insufficient vegetable (OR = 0.97, 95% CI = 0.96–0.99) intake. Adolescent dietary intake is associated with higher perceived parental monitoring; however, these associations for fruit and SSB differ to junk food and vegetable intake. This study may have implications for prevention interventions for parents, identifying how this modifiable parenting factor is related to adolescent diet has highlighted how complex the psychological and environmental factors contributing to dietary intake are.

Objective This study aims to determine the associations between specialty type and practice location at postgraduate year 10 (PGY10), matched with PGY5 and PGY8 work locations, and earlier rural exposure/experience.Design and setting A cohort study of medicine graduates from nine Australian universities.Participants 1220 domestic medicine graduates from the class of 2011.Outcome measures Practice location recorded by the Australian Health Practitioner Regulation Agency in PGY10; matched graduate movement between PGYs 5, 8 and 10 as classified by the Modified Monash Model, stratified by specialty type (predominantly grouped as general practitioner (GP) or non-GP).Results At PGY10, two-thirds (820/1220) had achieved fellowship. GPs were 2.8 times more likely to be in non-metropolitan practice (28% vs 12%; 95% CI 2.0 to 4.0, p

Abstract Background Empirical evidence regarding the development of sensory responsivity in young children at high likelihood to develop autism spectrum disorder (ASD) remains relatively limited. It is unclear how sensory responsivity behaviors may change over time and impact later developmental outcomes. The goals of this study were to (a) characterize developmental trajectories of sensory responsivity across infancy (∼12 months), toddlerhood (∼24 months), and school age (6–11 years) in children at high and low familial likelihood for ASD; and (b) determine if sensory responsivity in infancy predicts adaptive and cognitive functioning at school age among children with ASD. Methods Generalized linear mixed effects models were used to examine scores from the Sensory Experiences Questionnaire in three groups of children including high‐likelihood children later diagnosed with ASD (HL‐ASD; n = 30), high‐likelihood children without ASD (HL‐Neg; n = 150), and low‐likelihood control children not meeting ASD diagnostic criteria (LL‐Neg; n = 94). Hierarchical linear regression was then used to examine the association between sensory responsivity scores in infancy and functional adaptive and cognitive outcomes at school age for children at high likelihood of ASD. Results Development of sensory responsivity from infancy to later childhood is best estimated by the effects of chronological age and Group for Sensory Seeking and Hypo responsivity and the additional effect of the interaction of Group and chronological age for Total and Hyper responsivity. Early elevated Hypo responsivity and Sensory Seeking scores are negatively associated with later adaptive behavior but not cognitive level. Conclusion Overall, higher degrees of Sensory Seeking and Hypo sensory responsivity are detectable in autistic children's behavioral repertoires by 12 months of age and associate with reduced adaptive functioning in middle childhood. These results point to the potential importance of early detection and treatment implications of early sensory behaviors.

Green space exposure has been associated with improved mental, physical and general health. However, the underlying biological mechanisms remain largely unknown. The aim of this study was to investigate the association between green space exposure and cord and child blood DNA methylation.Data from eight European birth cohorts with a total of 2,988 newborns and 1,849 children were used. Two indicators of residential green space exposure were assessed: (i) surrounding greenness (satellite-based Normalized Difference Vegetation Index (NDVI) in buffers of 100 m and 300 m) and (ii) proximity to green space (having a green space ≥ 5,000 m2 within a distance of 300 m). For these indicators we assessed two exposure windows: (i) pregnancy, and (ii) the period from pregnancy to child blood DNA methylation assessment, named as cumulative exposure. DNA methylation was measured with the Illumina 450K or EPIC arrays. To identify differentially methylated positions (DMPs) we fitted robust linear regression models between pregnancy green space exposure and cord blood DNA methylation and between cumulative green space exposure and child blood DNA methylation. Two sensitivity analyses were conducted: (i) without adjusting for cellular composition, and (ii) adjusting for air pollution. Cohort results were combined through fixed-effect inverse variance weighted meta-analyses. Differentially methylated regions (DMRs) were identified from meta-analysed results using the Enmix-combp and DMRcate methods.There was no statistical evidence of pregnancy or cumulative exposures associating with any DMP (False Discovery Rate, FDR, p-value

This article explores technology's integration, assessment, and reflection within a single secondary education program at a Mountain West university. In light of the publication of the Teacher Education Technology Competencies (TETCs), faculty members of a secondary education program focused on existing practices and pathways for expansion to better align with the TETC standards in the future. The purpose of this study was to explore existing practices of incorporating technology into secondary methods coursework and to search for new spaces to implement the TETC guidelines and structure, as well as explore the roles faculty play in the adoption and implementation of technologies. Vignettes authored by faculty in each content area provide a rich depth of faculty experience and dispositions regarding technology integration, as well as spaces for the deeper use of technology based on the TETC recommendations. Key questions emerged about the efficacy of current technology practices, as well as the experiences and dispositions of the faculty within the secondary education program. Findings show that secondary education faculty use domain/content-specific technologies in their course; are expected to be "meta-experts", both discovering and implementing technology simultaneously; and tend to discover technologies through content-specific interactions and discussions.

An authentic, interdisciplinary, research and problem-based integrated science, technology, engineering, and mathematics (STEM) project may be ideal for encouraging scientific inquiry and developing teamwork among undergraduate students, but it also presents challenges. The authors describe how two interdisciplinary teams (n=6) of undergraduate college students built integrated STEM projects in a research based internship setting, and then collaboratively brought the project to fruition to include designing lessons and activities shared with K-12 students in a classroom setting. Each three person undergraduate team consisted of two STEM majors and one Education major. The Education majors are a special focus for this study. Interviews, field observations, and lesson plan artifacts collected from the undergraduate college students were analyzed according to authenticity factors, the authentic scientific inquiry instrument, and an integrated STEM instrument. The authors highlight areas of strength and weakness for both teams and explore how preservice teachers contributed to integrated STEM products and lessons. Teacher educators might apply recommendations for teacher preparation and professional development when facilitating authentic scientific inquiry and integrated STEM topics with both STEM and non-STEM educators. Undergraduate college students were challenged to fully integrate the STEM disciplines, transitions between them, and the spaces between them where multiple disciplines existed. By describing the challenges of integrating the spaces between STEM, the authors offer a description of the undergraduate college students' experiences in an effort to expand the common message beyond a flat approach of try this activity because it works, to a more robust message of try this type of engagement and purposefully organize for maximum results.

Secondary and post-secondary science and engineering educators share common class arrangements with both a laboratory and lecture component, coordinating both components so they build upon each other to create meaningful learning experiences. The COVID-19 pandemic forced educators to convert lectures and exams to online delivery. Doing so came with trade-off decisions about sacrificing laboratory experience goals of hands-on practice, problem-solving, and learning concepts at a deeper, tactile level. Due to rapidly changing conditions, educators faced course redesign to accommodate social distancing and virtual learning requirements. In this study, a team of undergraduate college students including one secondary science preservice teacher planned a set of lessons for STEM outreach to a K-12 audience. The team faced challenges in planning meaningful learning experiences in the face of COVID-19 uncertainty. Options for secondary and post-secondary educators to consider are provided in this article.

This study compares three pre-collegiate teacher professional learning and development (PLD) integrated science, technology, engineering, and mathematics (STEM) experiences framed in astronomy. The study is set in the western United States (USA) and involves 60 pre-collegiate teachers (in the USA these are K-12 teachers) over the course of three years (June 2014-May 2017). During the PLDs, astronomy acted as a vehicle for pre-collegiate STEM teachers to increase their STEM content knowledge as well as create and implement integrated STEM classroom lessons. The authors collected quantitative and qualitative data to address five research questions and embraced social constructionism as the theoretical framework. Findings show that STEM pre-collegiate teachers are largely engaged with integrated STEM PLD content and embrace astronomy content and authentic science. Importantly, they need time to practice, interpret, translate, and use the integrated STEM content in classroom lessons. Recommendations for PLD STEM teacher support are provided. Implications of this study are vast, as gaps in authentic science, utilizing astronomy, PLD structure, and STEM integration are ripe for exploration.

BackgroundInflammation may affect long-term kidney function. Diet may play a role in chronic inflammation. We hypothesized that proinflammatory diets increase the risk of progression to kidney failure with replacement therapy (KFRT), and systemic inflammation is a mediator of the effect of diet on progression to KFRT.MethodsIn the 1988-1994 National Health and Nutrition Examination Survey linked to the national ESKD registry, in adults with CKD (eGFR 15-59 ml/min per 1.73 m2), aged ≥20 years, we calculated the Adapted Dietary Inflammatory Index (ADII) at baseline from a 24-hour dietary recall and an inflammation score (IS) using average of z scores of four inflammation biomarkers. We explored the association of the ADII and IS with risk of incident KFRT using Cox proportional model, adjusting for sociodemographics, physical activity, Framingham risk score, eGFR, and urinary ACR. We evaluated whether, and to what extent, IS mediated the effect of the ADII on KFRT incidence, using causal mediation analysis.ResultsOf 1084 adults with CKD, 109 (10%) developed KFRT. The ADII was associated with increased risk of KFRT (relative hazard [RH] per SD increase (2.56): 1.4 [1.04-1.78]). IS was also associated with KFRT (RH: 1.12; 95% CI, 1.02 to 1.25). Approximately 36% of the association between the ADII and KFRT was explained by IS.ConclusionsAmong adults with CKD, a proinflammatory diet was associated with risk of KFRT, and that association was partially explained by an increase in inflammatory markers. Dietary interventions that reduce inflammation may offer an approach for preventing KFRT.

Growth in early infancy is hypothesized to affect chronic disease risk factors later in life. To date, most reports draw on European-ancestry cohorts with few repeated observations in early infancy. We investigated the association between infant growth before 6 months and lipid levels in adolescents in a Hispanic/Latino cohort. We characterized infant growth from birth to 5 months in male (n = 311) and female (n = 285) infants from the Santiago Longitudinal Study (1991-1996) using 3 metrics: weight (kg), length (cm), and weight-for-length (g/cm). Superimposition by translation and rotation (SITAR) and latent growth mixture models (LGMMs) were used to estimate the association between infant growth characteristics and lipid levels at age 17 years. We found a positive relationship between the SITAR length velocity parameter before 6 months of age and high-density lipoprotein cholesterol levels in adolescence (11.5, 95% confidence interval; 3.4, 19.5), indicating higher high-density lipoprotein cholesterol levels occurring with faster length growth. The strongest associations from the LGMMs were between higher low-density lipoprotein cholesterol and slower weight-for-length growth, following a pattern of associations between slower growth and adverse lipid profiles. Further research in this window of time can confirm the association between early infant growth as an exposure and adolescent cardiovascular disease risk factors.

BACKGROUND: Adverse events are often misreported in clinical trials, leading to an incomplete understanding of toxicities. We aimed to test automated laboratory adverse event ascertainment and grading (via the ExtractEHR automated package) to assess its scalability and define adverse event rates for children with acute myeloid leukaemia and acute lymphoblastic leukaemia. METHODS: For this retrospective cohort study from the Childrens Oncology Group (COG), we included patients aged 0-22 years treated for acute myeloid leukaemia or acute lymphoblastic leukaemia at Childrens Healthcare of Atlanta (Atlanta, GA, USA) from Jan 1, 2010, to Nov 1, 2018, at the Childrens Hospital of Philadelphia (Philadelphia, PA, USA) from Jan 1, 2011, to Dec 31, 2014, and at the Texas Childrens Hospital (Houston, TX, USA) from Jan 1, 2011, to Dec 31, 2014. The ExtractEHR automated package acquired, cleaned, and graded laboratory data as per Common Terminology Criteria for Adverse Events (CTCAE) version 5 for 22 commonly evaluated grade 3-4 adverse events (fatal events were not evaluated) with numerically based CTCAE definitions. Descriptive statistics tabulated adverse event frequencies. Adverse events ascertained by ExtractEHR were compared to manually reported adverse events for patients enrolled in two COG trials (AAML1031, NCT01371981; AALL0932, NCT02883049). Analyses were restricted to protocol-defined chemotherapy courses (induction I, induction II, intensification I, intensification II, and intensification III for acute myeloid leukaemia; induction, consolidation, interim maintenance, delayed intensification, and maintenance for acute lymphoblastic leukaemia). FINDINGS: Laboratory adverse event data from 1077 patients (583 from Childrens Healthcare of Atlanta, 200 from the Childrens Hospital of Philadelphia, and 294 from the Texas Childrens Hospital) who underwent 4611 courses (549 for acute myeloid leukaemia and 4062 for acute lymphoblastic leukaemia) were extracted, processed, and graded. Of the 166 patients with acute myeloid leukaemia, 86 (52%) were female, 80 (48%) were male, 96 (58%) were White, and 132 (80%) were non-Hispanic. Of the 911 patients with acute lymphoblastic leukaemia, 406 (45%) were female, 505 (55%) were male, 596 (65%) were White, and 641 (70%) were non-Hispanic. Patients with acute myeloid leukaemia had the most adverse events during induction I and intensification II. Hypokalaemia (one [17%] of six to 75 [48%] of 156 courses) and alanine aminotransferase (ALT) increased (13 [10%] of 134 to 27 [17%] of 156 courses) were the most prevalent non-haematological adverse events in patients with acute myeloid leukaemia, as identified by ExtractEHR. Patients with acute lymphoblastic leukaemia had the greatest number of adverse events during induction and maintenance (eight adverse events with prevalence ≥10%; induction and maintenance: anaemia, platelet count decreased, white blood cell count decreased, neutrophil count decreased, lymphocyte count decreased, ALT increased, and hypocalcaemia; induction: hypokalaemia; maintenance: aspartate aminotransferase [AST] increased and blood bilirubin increased), as identified by ExtractEHR. 187 (85%) of 220 total comparisons in 22 adverse events in four AAML1031 and six AALL0923 courses were substantially higher with ExtractEHR than COG-reported adverse event rates for adverse events with a prevalence of at least 2%. INTERPRETATION: ExtractEHR is scalable and accurately defines laboratory adverse event rates for paediatric acute leukaemia; moreover, ExtractEHR seems to detect higher rates of laboratory adverse events than those reported in COG trials. These rates can be used for comparisons between therapies and to counsel patients treated on or off trials about the risks of chemotherapy. ExtractEHR-based adverse event ascertainment can improve reporting of laboratory adverse events in clinical trials. FUNDING: US National Institutes of Health, St Baldricks Foundation, and Alexs Lemonade Stand Foundation.