Miracle-dz/UniFAR-FTUs huggingface dataset:
Mediation of 6‐year mid‐childhood follow‐up outcomes after pre‐school social communication (PACT) therapy for autistic children: randomised controlled trial

Background There are very few mechanistic studies of the long‐term impact of psychosocial interventions in childhood. The parent‐mediated Paediatric Autism Communication Therapy (PACT) RCT showed sustained effects on autistic child outcomes from pre‐school to mid‐childhood. We investigated the mechanism by which the PACT intervention achieved these effects. Methods Of 152 children randomised to receive PACT or treatment as usual between 2 and 5 years of age, 121 (79.6%) were followed 5–6 years after the endpoint at a mean age of 10.5 years. Assessors, blind to the intervention group, measured Autism Diagnostic Observation Scale Calibrated Severity Score (ADOS CSS) for child autistic behaviours and Teacher Vineland (TVABS) for adaptive behaviour in school. Hypothesised mediators were child communication initiations with caregivers in a standard play observation (Dyadic Communication Measure for Autism, DCMA). Hypothesised moderators of mediation were baseline child non‐verbal age equivalent scores (AE), communication and symbolic development (CSBS) and ‘insistence on sameness’ (IS). Structural equation modelling was used in a repeated measures mediation design. Results Good model fits were obtained. The treatment effect on child dyadic initiation with the caregiver was sustained through the follow‐up period. Increased child initiation at treatment midpoint mediated the majority (73%) of the treatment effect on follow‐up ADOS CSS. A combination of partial mediation from midpoint child initiations and the direct effect of treatment also contributed to a near‐significant total effect on follow‐up TVABS. No moderation of this mediation was found for AE, CSBS or IS. Conclusions Early sustained increase in an autistic child's communication initiation with their caregiver is largely responsible for the long‐term effects from PACT therapy on autistic and adaptive behaviour outcomes. This supports the theoretical logic model of PACT therapy but also illuminates fundamental causal processes of social and adaptive development in autism over time: early social engagement in autism can be improved and this can have long‐term generalised outcome effects.
Burden of disease of spinal muscular atrophy linked to chromosome 5q (5q-SMA) in Colombia

ABSTRACT Objective This article estimates the disease burden of 5q-SMA in Colombia by using the disability-adjusted life years (DALYs) metric. Methods Epidemiological data were obtained from local databases and medical literature and were adjusted in the DisMod II tool. DALYs were obtained by adding years of life lost due to premature death (YLL) and years lived with disability (YLD). Results The modeled prevalence of 5q-SMA in Colombia was 0.74 per 100,000 population. The fatality rate for all types was 14.1%. The disease burden of 5q-SMA was estimated at 4,421 DALYs (8.6 DALYs/100,000), corresponding to 4,214 (95.3%) YLLs and 207 (4.7%) YLDs. Most of the DALYs were accounted in the 2–17 age group. Of the total burden, 78% correspond to SMA type 1, 18% to type 2, and 4% to type 3. Conclusions Although 5q-SMA is a rare disease, it is linked to a significant disease burden due to premature mortality and severe sequelae. The estimates shown in this article are important inputs to inform public policy decisions on how to ensure adequate health service provision for patients with 5q-SMA.
A meta‐analysis of human disturbance effects on glucocorticoid hormones in free‐ranging wild vertebrates

Free‐ranging wild vertebrates need to cope with natural and anthropogenic stressors that cause short and/or long‐term behavioural and physiological responses. In areas of high human disturbance, the use of glucocorticoid (GC) hormones as biomarkers to measure stress responses is an increasingly common tool for understanding how animals cope with human disturbance. We conducted a meta‐analysis to investigate how human disturbances such as habitat conversion, habitat degradation, and ecotourism influence baseline GC hormones of free‐ranging wild vertebrates, and we further test the role of protected areas in reducing the impact of such disturbances on these hormones. A total of 58 studies met the inclusion criteria, providing 152 data points for comparing levels of GC hormones under disturbed and undisturbed conditions. The overall effect size suggests that human disturbance does not cause a consistent increase in levels of GC hormones (Hedges' g = 0.307, 95% CI = −0.062 to 0.677). However, when the data were analysed by disturbance type, living in unprotected areas or in areas with habitat conversion were found to increase GC hormone levels compared to living in protected or undisturbed areas. By contrast, we found no evidence that ecotourism or habitat degradation generates a consistent increase in baseline GC hormone levels. Among taxonomic groups, mammals appeared more sensitive to human disturbance than birds. We advocate the use of GC hormones for inferring major human‐caused contributors to the stress levels of free‐ranging wild vertebrates – although such information needs to be combined with other measures of stress and interpreted in the context of an organism's life history, behaviour, and history of interactions with human disturbance.
Procedural anxiety among children and adolescents with cystic fibrosis and their parents

Procedural anxiety involves acute distress around medical procedures and may lead to avoidance or resistance behaviors that interfere with effective cystic fibrosis (CF) care and health outcomes. While individuals with CF commonly endure uncomfortable and/or distressing medical procedures, procedural anxiety among children and adolescents with CF has received little research attention. This study investigated the prevalence and correlates of procedural anxiety among individuals with CF aged 6–18 and their parents.
Sample size considerations for micro‐randomized trials with binary proximal outcomes

Micro‐randomized trials (MRTs) are a novel experimental design for developing mobile health interventions. Participants are repeatedly randomized in an MRT, resulting in longitudinal data with time‐varying treatments. Causal excursion effects are the main quantities of interest in MRT primary and secondary analyses. We consider MRTs where the proximal outcome is binary and the randomization probability is constant or time‐varying but not data‐dependent. We develop a sample size formula for detecting a nonzero marginal excursion effect. We prove that the formula guarantees power under a set of working assumptions. We demonstrate via simulation that violations of certain working assumptions do not affect the power, and for those that do, we point out the direction in which the power changes. We then propose practical guidelines for using the sample size formula. As an illustration, the formula is used to size an MRT on interventions for excessive drinking. The sample size calculator is implemented in R package MRTSampleSizeBinary and an interactive R Shiny app. This work can be used in trial planning for a wide range of MRTs with binary proximal outcomes.
Historical DNA from a rediscovered nineteenth-century paratype reveals genetic continuity of a Bahamian hutia (Geocapromys ingrahami) population

Past and ongoing human activities have shaped the geographical ranges and diversity of species. New genomic techniques applied to degraded samples, such as those from natural history collections, can uncover the complex evolutionary consequences of human pressures and generate baselines for interpreting magnitudes of species loss or persistence relevant to conservation. Here we integrate mitogenomic data with historical records from a recently rediscovered Bahamian hutia (Geocapromys ingrahami; (FMP Z02816)) specimen at the Fairbanks Museum & Planetarium (Vermont, USA) to determine when and where the specimen was collected and to place it in a phylogenetic context with specimens that both predate (palaeontological) and postdate (archaeological) human arrival in The Bahamas. We determined that this specimen was part of the same population as the named holotype specimen in 1891 on East Plana Cay (EPC). Bahamian hutia populations were widely extirpated following European colonization. Today, EPC hosts the last remaining natural Bahamian hutia population. Mitogenomic data places the focal specimen within the southern Bahamian hutia population, which is now largely restricted to EPC. The results reveal previously undocumented genetic continuity among the EPC population for at least the past 500 years, highlighting how ‘dark’ museum specimens inform new conservation-relevant understandings of diversity.
Variables Selection using the Wald Test and a Robust Cp

SUMMARY A new variables selection criterion is presented. It is based on the Wald test statistic and is defined by Tp = Wp- K + 2p where K and p are the numbers of parameters in the full and submodel respectively, and Wp is theWald statistic for testing whether the coefficients of the variables not in the submodel are 0. 'Good' submodels will have Tp-values that are close to or smaller than p, and, as with Mallows's Cp, they will be selected by graphical rather than stepwise methods. We first consider an application to the linear regression of the heat evolved in a cement mix on four explanatory variables; we use robust methods and obtain the same results as those from the more computer-intensive methods of Ronchetti and Staudte. Our later applications are to previously published data sets which use logistic regression to predict participation in the US federal food stamp program, myocardial infarction and prostatic cancer. The first data set was shown in previous analysis to contain an outlier and is considered for illustration. In the last two data sets our criterion applied to the maximum likelihood estimates selects the same model as do previously published stepwise analyses. However, for the food stamp data set, the application of our criterion using the robust logistic regression estimates of Carroll and Pederson suggests more parsimonious models than those arising from the likelihood analysis, and further suggests that interactions previously regarded as important may be due to outliers.
Parameterisation of small-scale random forcing in β-plane turbulence

Abstract Zonal jet formation in $\beta$-plane turbulence is investigated with the focus on whether an accurate closure can be developed for the eddy momentum fluxes due to small-scale random forcing. The approach of Srinivasan and Young (J. Atmos. Sci., vol. 71, 2014, pp. 2169–2185) is developed to give a relatively simple expression for the local Reynolds stress, due to a white-in-time random forcing with characteristic length scale much less than the jet spacing. In typical jet flows, however, it is demonstrated that the Srinivasan–Young flux is not the full story because momentum fluxes due to jet-scale waves, present as a result of distinct barotropic instabilities of the eastward and westward jets, respectively, also play a key role in the momentum balance. Numerical simulations that explicitly include the random forcing are then compared with those in which the Srinivasan–Young closure is applied. For typical jet flows, good agreement of the equilibrium zonal flow is found provided that the closure simulation is not truncated to be purely zonal, i.e. jet-scale secondary barotropic instabilities are allowed to develop. Flows in which the geometry or external forcing acts to suppress the development of secondary instabilities are also simulated, and for these flows the Srinivasan–Young closure is shown to be successful as a purely zonal closure. It is argued that vortex condensates in isotropic forced-dissipative 2D turbulence are an example of this latter situation.
Buried-regrown-implant-structure diode lasers with ultra-thick epitaxy for resistance to mounting stress without loss in efficiency

Epi-down mounting can degrade performance in broad area lasers when the stress field extends into the active region. Thick p-side epitaxial layers have the potential to isolate the device from external stress, but add electrical resistance and losses from current spreading. Therefore, we use two-step epitaxy to combine highly-doped p-side epitaxial layers (2x thicker than conventional) with a resistive oxygen-implanted layer located close to the active region to block lateral current spreading. The resulting buried-regrown-implant-structure (BRIS) lasers with 100 μm stripes and lasing wavelength of 915 nm show high efficiency (peak of 67%, 55% at 20 W) and high lateral brightness (3.3 W/mm·mrad up to 17.5 W output power), improved over reference devices, in spite of the thick p-side.
Large Eddy Simulation of Flow Pasta Twisted Cylinder

The wavy cylinder has a sinusoidal variation incross sectional area along the spanwise direction and the twistedcylinder has been newly designed by rotating the elliptic crosssection along the spanwise direction, so that the cylinder surfacehas a twisted spiral pattern. A twisted cylinder is investigated toobserve the effect of twisted spiral pattern of the flow fields. Itguarantees the accuracy of the present numerical methods thatthe excellent comparisons with previous studies for the cases of asmooth circular cylinder. The effect of surface torsion which isnewly designed in here has been predicted and assessed in termsof the mean drag and root-mean-square (RMS) value offluctuating lift at the subcritical Reynolds number of 3000.Subsequently, the mechanisms of enhancing the aerodynamicperformance and passive control of vortex-induced vibrations arealso investigated by careful analysis with the flow structures. Theiso-surface of swirling strength has been imposed to identify thevortical structures in the turbulent wake
Informing Volunteer Water Quality Monitoring Program Design and Watershed Planning: Case Study of StreamSmart Data Analysis in the Upper White River Basin, Arkansas

The watershed group H2Ozarks founded the StreamSmart Citizen Science Program to establish baseline and long‐term water quality data for the Upper White River Basin, Arkansas. StreamSmart volunteers collect water samples and conduct habitat and macroinvertebrate community assessments at >20 sites across a land use‐land cover (LULC) gradient. Since 2020, H2Ozarks has adaptively assessed the program to ensure that the investment in water quality data meets core goals, with particular interest in planning tools and aligning expectations of volunteer effort with the level of training and support. Study objectives were to use StreamSmart data to 1) facilitate understanding of water quality response to stressors in the basin using a range of methods (Spearman rank correlation, non‐parametric changepoint analysis, and categorical and regression tree analysis) and 2) explore implications for program design and watershed planning. Water chemistry‐LULC relationships were in‐line with prior regional studies, as well as global patterns. Detected thresholds and hierarchy provide potential targets for managing LULC change to protect water quality, but further analysis is warranted to refine these relationships. Macroinvertebrate stressor‐response was most detectable for sensitive and less sensitive taxa and for habitat index components, suggesting potential to streamline these programmatic elements. Study findings for StreamSmart should also be informative for other small‐scale volunteer monitoring programs with limited resources, but which actively evaluate the types of data and program activities that yield a maximum scientific return on investment.
Environmental impacts of cultured meat: A cradle-to-gate life cycle assessment

Interest in animal cell-based meat (ACBM) or cultured meat as a viable environmentally conscious replacement for livestock production has been increasing, however a life cycle assessment for the current production methods of ACBM has not been conducted. Currently, ACBM products are being produced at a small scale and at an economic loss, however ACBM companies are intending to industrialize and scale-up production. This study assesses the potential environmental impact of near term ACBM production. Updated findings from recent technoeconomic assessments (TEAs) of ACBM and a life cycle assessment of Essential 8™ were utilized to perform a life cycle assessment of near-term ACBM production. A scenario analysis was conducted utilizing the metabolic requirements examined in the TEAs of ACBM and a purification factor from the Essential 8™ life cycle assessment was utilized to account for growth medium component processing. The results indicate that the environmental impact of near-term ACBM production is likely to be orders of magnitude higher than median beef production if a highly refined growth medium is utilized for ACBM production.
Scabrous is distributed via signaling filopodia to modulate Notch response during bristle patterning in Drosophila

During development, tissues must be patterned correctly in order to support tissue function and shape. The sensory bristles of the peripheral nervous system on the thorax of Drosophila melanogaster self-organize from an unpatterned epithelial tissue to a regular spot pattern during pupal stages. Wild type patterning requires Notch-mediated lateral inhibition. Scabrous is a protein that can bind to and modify Notch receptor activity. Scabrous can be secreted, but it is also known to be localized to basal signaling filopodia, or cytonemes, that play a role in long-range Notch signaling. Consistent with previous work, we show that Scabrous is primarily distributed basally, within the range of signaling filopodia extension. We show that signaling filopodia are required for the distribution of Scabrous protein during sensory bristle patterning stages. We show that the Notch response of epithelial cells is sensitive to the level of Scabrous protein being expressed by the sensory bristle precursor cell. Our findings at the cell-level suggest a model for how epithelial cells engaged in lateral inhibition at a distance are sensitive local levels of Scabrous protein.
Pavlovian-to-instrumental transfer after human threat conditioning

Threat conditioning is a common associative learning model with translational relevance. How threat-conditioned cues impact on formally unrelated instrumental behavior in humans is not well known. Such an effect is known as Pavlovian-to-instrumental transfer (PIT). While PIT with aversive primary Pavlovian reinforcers is established in nonhuman animals, this is less clear in humans, where secondary reinforcers or instructed instrumental responses are most often investigated. We modified an existing human PIT procedure to include primary reinforcers. Participants first learned to obtain (or avoid losing) appetitive instrumental reinforcement (chocolate) by appropriate approach or avoidance actions. They either had to act (Go) or to withhold an action (NoGo), and in the Go condition either to approach a reward target to collect it or to withdraw from the reward target to avoid losing it. Then they learned to associate screen color (CS) with aversive Pavlovian reinforcement (electric shock US). In the transfer phase, we conducted the instrumental task during the presence of Pavlovian CS. In a first experiment, we show that the aversive Pavlovian CS+, compared to CS−, increased response rate in Go-Withdraw trials, i.e., induce conditioned facilitation of avoidance responses. This finding was confirmed in a second and independent experiment with an increased number of Go-Withdraw trials. Notably, we observed no appreciable conditioned suppression of approach responses. Effect size to distinguish CS+/CS− in Go-Withdraw trials was d = 0.42 in the confirmation sample. This would require n = 37 participants to demonstrate threat learning with 80% power. Thus, the effect size is on a practically useful scale although smaller than for model-based analysis of autonomic measures. In summary, our results indicate conditioned facilitation of formally unrelated instrumental avoidance behavior in humans and provide a novel behavioral threat learning measure that requires only key presses.
Sensory eye dominance plasticity in the human adult visual cortex

Sensory eye dominance occurs when the visual cortex weighs one eye’s data more heavily than those of the other. Encouragingly, mechanisms underlying sensory eye dominance in human adults retain a certain degree of plasticity. Notably, perceptual training using dichoptically presented motion signal-noise stimuli has been shown to elicit changes in sensory eye dominance both in visually impaired and normal observers. However, the neural mechanisms underlying these learning-driven improvements are not well understood. Here, we measured changes in fMRI responses before and after a five-day visual training protocol to determine the neuroplastic changes along the visual cascade. Fifty visually normal observers received training on a dichoptic or binocular variant of a signal-in-noise (left-right) motion discrimination task over five consecutive days. We show significant shifts in sensory eye dominance following training, but only for those who received dichoptic training. Pattern analysis of fMRI responses revealed that responses of V1 and hMT+ predicted sensory eye dominance for both groups, but only before training. After dichoptic (but not binocular) visual training, responses of V1 and hMT+ could no longer predict sensory eye dominance. Our data suggest that perceptual training-driven changes in eye dominance are driven by a reweighting of the two eyes’ data in both primary and task-related extrastriate visual areas. These findings may provide insight into developing region-targeted rehabilitative paradigms for the visually impaired, particularly those with severe binocular imbalance.
Protein multiple conformations prediction using multi-objective evolution algorithm

Motivation With the breakthrough of AlphaFold2 and the publication of AlphaFold DB, the protein structure prediction has made remarkable progress, which may further promote many potential applications of proteomics in all areas of life. However, it should be noted that AlphaFold2 models tend to represent only a single static structure, and accurately predicting multiple conformations remains a challenge. Therefore, it is essential to develop methods for predicting multiple conformations, which enable us to gain knowledge of multiple conformational states and the broader conformational landscape to better understand the mechanism of action. Results In this work, we proposed a multiple conformational states folding method using the distance-based multi-objective evolutionary algorithm framework, named MultiSFold. First, a multi-objective energy landscape with multiple competing constraints generated by deep learning is constructed. Then, an iterative modal exploration and exploitation strategy based on multi-objective optimization, geometric optimization and structural similarity clustering is designed to perform conformational sampling. Finally, the final population is generated using a loop-specific perturbation strategy to adjust the spatial orientations. MultiSFold was compared with state-of-the-art methods on a developed benchmark testset containing 81 proteins with two representative conformational states. Based on the proposed metric, the success ratio of MultiSFold predicting multiple conformations was 70.4% while that of AlphaFold2 was 9.88%, which may indicate that conformational sampling combined with knowledge gained through deep learning has the potential to produce conformations spanned the range between two experimental structures. In addition, MultiSFold was tested on 244 human proteins with low structural accuracy in AlphaFold DB to test whether it could further improve the accuracy of static structures. The experimental results demonstrate that the TM-score of MultiSFold is 2.97% and 7.72% higher than that of AlphaFold2 and RoseTTAFold, respectively, supporting our hypothesis that multiple competing optimization objectives can further assist conformational search to improve prediction accuracy.