Artificial intelligence can regulate light and climate systems to reduce energy use in plant factories and support sustainable food production.

Plant factories with artificial lighting (PFALs) can boost food production per unit area but require resources such as carbon dioxide and energy to maintain optimal plant growth conditions. Here we use computational modelling and artificial intelligence (AI) to examine plant-environment interactions across ten diverse global locations with distinct climates. AI reduces energy use by optimizing lighting and climate regulation systems, with energy use in PFALs ranging from 6.42 kWh kg-1 in cooler climates to 7.26 kWh kg-1 in warmer climates, compared to 9.5-10.5 kWh kg-1 in PFALs using existing, non-AI-based technology. Outdoor temperatures between 0 °C and 25 °C favour ventilation-related energy use reduction, with outdoor humidity showing no clear pattern or effect on energy use. Ventilation-related energy savings negatively impact other resource utilization such as carbon dioxide use. AI can substantially enhance energy savings in PFALs and support sustainable food production.

Amphiphilic shuttle peptide delivers base editor ribonucleoprotein to correct the CFTR R553X mutation in well-differentiated airway epithelial cells.

Base editing could correct nonsense mutations that cause cystic fibrosis (CF), but clinical development is limited by the lack of delivery methods that efficiently breach the barriers presented by airway epithelia. Here, we present a novel amphiphilic shuttle peptide based on the previously reported S10 peptide that substantially improved base editor ribonucleoprotein (RNP) delivery. Studies of the S10 secondary structure revealed that the alpha-helix formed by the endosomal leakage domain (ELD), but not the cell penetrating peptide (CPP), was functionally important for delivery. By isolating and extending the ELD, we created a novel shuttle peptide, termed S237. While S237 achieved lower delivery of green fluorescent protein, it outperformed S10 at Cas9 RNP delivery to cultured human airway epithelial cells and to pig airway epithelia in vivo, possibly due to its lower net charge. In well-differentiated primary human airway epithelial cell cultures, S237 achieved a 4.6-fold increase in base editor RNP delivery, correcting up to 9.4% of the cystic fibrosis transmembrane conductance regulator (CFTR) R553X allele and restoring CFTR channel function close to non-CF levels. These findings deepen the understanding of peptide-mediated delivery and offer a translational approach for base editor RNP delivery for CF airway disease.

4D ultrasound-based strain assessment of cardiac dysfunction in male rats with reperfused and nonreperfused myocardial infarction.

Two-dimensional ultrasound (2DUS) echocardiography is the main noninvasive method used to evaluate cardiac function in animal models of myocardial infarction (MI). However, 2DUS echocardiography does not capture regional differences in cardiac contractility since it relies on planar images to estimate left ventricular (LV) geometry and global function. Thus, the current study was designed to evaluate the efficacy of a newly developed 4-dimensional ultrasound (4DUS) method in detecting cardiac functional differences between two models of MI, permanent ligation (PL), and ischemia/reperfusion (I/R) in rats. We found that only 4DUS was able to detect LV global functional differences between the two models and that 4DUS-derived surface area strain accurately detected infarcted regions within the myocardium that correlated well with histological infarct size analysis. We also found that 4DUS-derived strain, which includes circumferential, longitudinal, and surface area strain, correlated with the peak positive of the first derivative of left ventricular pressure (+dP/dtmax). In conclusion, 4DUS strain echocardiography effectively assesses myocardial mechanics following experimentally induced ischemia in rats and accurately estimates infarct size as early as 1 day after injury. 4DUS also correlates well with +dP/dtmax, a widely used marker of cardiac contractility.

Prospective, international, multisite comparison of platelet isolation techniques for genome-wide transcriptomics: communication from the SSC of the ISTH.

Genome-wide platelet transcriptomics is increasingly used to uncover new aspects of platelet biology and as a diagnostic and prognostic tool. Nevertheless, platelet isolation methods for transcriptomic studies are not standardized, introducing challenges for cross-study comparisons, data integration, and replication. In this prospective multicenter study, called "Standardizing Platelet Transcriptomics for Discovery, Diagnostics, and Therapeutics in the Thrombosis and Hemostasis Community (STRIDE)" by the International Society on Thrombosis and Haemostasis Scientific and Standardization Committees, we assessed how 3 of the most commonly used platelet isolation protocols influence metrics from next-generation bulk RNA sequencing and functional assays. Compared with washing alone, more stringent removal of leukocytes by anti-CD45 beads or PALL filters resulted in a sufficient quantity of RNA for next-generation sequencing and similar quality of RNA sequencing metrics. Importantly, stringent removal of leukocytes resulted in the lower relative expression of known leukocyte-specific genes and the higher relative expression of known platelet-specific genes. The results were consistent across enrolling sites, suggesting that the techniques are transferrable and reproducible. Moreover, all 3 isolation techniques did not influence basal platelet reactivity, but agonist-induced integrin αIIbß3 activation is reduced by anti-CD45 bead isolation compared with washing alone. In conclusion, the isolation technique chosen influences genome-wide transcriptional and functional assays in platelets. These results should help the research community make informed choices about platelet isolation techniques in their own platelet studies.

Developmental Programming of the Fetal Immune System by Maternal Western-Style Diet: Mechanisms and Implications for Disease Pathways in the Offspring.

Maternal obesity and over/undernutrition can have a long-lasting impact on offspring health during critical periods in the first 1000 days of life. Children born to mothers with obesity have reduced immune responses to stimuli which increase susceptibility to infections. Recently, maternal western-style diets (WSDs), high in fat and simple sugars, have been associated with skewing neonatal immune cell development, and recent evidence suggests that dysregulation of innate immunity in early life has long-term consequences on metabolic diseases and behavioral disorders in later life. Several factors contribute to abnormal innate immune tolerance or trained immunity, including changes in gut microbiota, metabolites, and epigenetic modifications. Critical knowledge gaps remain regarding the mechanisms whereby these factors impact fetal and postnatal immune cell development, especially in precursor stem cells in bone marrow and fetal liver. Components of the maternal microbiota that are transferred from mothers consuming a WSD to their offspring are understudied and identifying cause and effect on neonatal innate and adaptive immune development needs to be refined. Tools including single-cell RNA-sequencing, epigenetic analysis, and spatial location of specific immune cells in liver and bone marrow are critical for understanding immune system programming. Considering the vital role immune function plays in offspring health, it will be important to understand how maternal diets can control developmental programming of innate and adaptive immunity.

Evidence-Based Therapist-Supported Digital Mental Health Intervention for Patients Experiencing Medical Multimorbidity: A Retrospective Cohort Intent-to-Treat Study.

OBJECTIVE: Multimorbidity or the co-occurrence of multiple health conditions is increasing globally and is associated with significant psychological complications. It is unclear whether digital mental health (DMH) interventions for patients experiencing multimorbidity are effective, particularly given that this patient population faces more treatment resistance. The goal of the current study was to examine the impact of smartphone-delivered DMH interventions for patients presenting with elevated internalizing symptoms that have reported multiple lifetime medical conditions. METHODS: This preregistered (see https://osf.io/vh2et/ ) retrospective cohort intent-to-treat study with 2819 patients enrolled in a therapist-supported DMH intervention examined the associations between medical multimorbidity (MMB) and mental health outcomes. RESULTS: Results indicated that more MMB was significantly associated with greater presenting mental health symptom severity. MMB did not have a deleterious influence on depressive symptom trajectories across treatment, although having one medical condition was associated with a steeper decrease in anxiety symptoms compared to patients with no medical conditions. Finally, MMB was not associated with time to dropout, but was associated with higher dropout and was differentially associated with fewer beneficial treatment outcomes, although this is likely attributable to higher presenting symptom severity, rather than lesser symptom reductions during treatment. CONCLUSIONS: Overall, the Meru Health Program was associated with large effect size decreases in depressive and anxiety symptoms regardless of the number of MMB. Future DMH treatments and research might investigate tailored barrier reduction and extended treatment lengths for patients experiencing MMB to allow for greater treatment dose to reduce symptoms below clinical outcome thresholds.

Daily links between objective smartphone use and sleep among adolescents.

INTRODUCTION: Concerns abound on how digital technology such as smartphone use may impair adolescent sleep. Although these linkages are supported in cross-sectional studies, research involving intensive longitudinal assessments and objective measures has called into question the robustness of associations. METHODS: In this study, a sample of ethnically diverse U.S. adolescents (N = 71; Mage = 16.49; 56% girls) wore Fitbit devices and submitted screenshots of their smartphone screen time, pickups, and notifications over a 14-day period in 2021. The Fitbits recorded nightly sleep quality and sleep onset. Adolescents also completed daily diaries reporting the previous night's sleep onset time and sleep quality. RESULTS: On days when adolescents engaged in greater nighttime screen time and, to some extent, pickups relative to their own average, they also had poorer sleep outcomes that night. Greater screen time was associated with later self-reported and Fitbit-recorded sleep onset and poorer self-reported sleep quality. Greater pickups was associated with later self-reported and Fitbit-recorded sleep onset. Smartphone use during the day did not relate to sleep outcomes, indicating the importance of distinguishing nighttime from daytime use. CONCLUSIONS: Parents and clinicians should help adolescents develop healthy digital skills to avoid exacerbating sleep problems that are known to occur during this developmental period.

Stiffness anisotropy coordinates supracellular contractility driving long-range myotube-ECM alignment.

The ability of cells to organize into tissues with proper structure and function requires the effective coordination of proliferation, migration, polarization, and differentiation across length scales. Skeletal muscle is innately anisotropic; however, few biomaterials can emulate mechanical anisotropy to determine its influence on tissue patterning without introducing confounding topography. Here, we demonstrate that substrate stiffness anisotropy coordinates contractility-driven collective cellular dynamics resulting in C2C12 myotube alignment over millimeter-scale distances. When cultured on mechanically anisotropic liquid crystalline polymer networks (LCNs) lacking topography, C2C12 myoblasts collectively polarize in the stiffest direction. Cellular coordination is amplified through reciprocal cell-ECM dynamics that emerge during fusion, driving global myotube-ECM ordering. Conversely, myotube alignment was restricted to small local domains with no directional preference on mechanically isotropic LCNs of the same chemical formulation. These findings provide valuable insights for designing biomaterials that mimic anisotropic microenvironments and underscore the importance of stiffness anisotropy in orchestrating tissue morphogenesis.

Digital mental health interventions as stand-alone vs. augmented treatment as usual.

BACKGROUND: Smartphone-based digital mental health interventions (DMHI) have been described as a purported solution to meet growing healthcare demands and lack of providers, but studies often don't account for whether patients are concurrently in another treatment modality. METHODS: This preregistered quasi-experimental intent-to-treat study with 354 patients enrolled in a therapist-supported DMHI examined the treatment effectiveness of the Meru Health Program (MHP) as a stand-alone treatment as compared to the MHP in combination with any other form of treatment, including (1) in-person therapy, (2) psychotropic medication use, and (3) in-person therapy and psychotropic medication use. RESULTS: Patients with higher baseline depressive and anxiety symptoms were more likely to self-select into multiple forms of treatment, an effect driven by patients in the MHP as adjunctive treatment to in-person therapy and psychotropic medication. Patients in combined treatments had significantly higher depressive and anxiety symptoms across treatment, but all treatment groups had similar decreasing depressive and anxiety symptom trajectories. Exploratory analyses revealed differential treatment outcomes across treatment combinations. Patients in the MHP in combination with another treatment had higher rates of major depressive episodes, psychiatric hospitalization, and attempted death by suicide at baseline. CONCLUSIONS: Patients with higher depressive and anxiety symptoms tend to self-select into using DMHI in addition to more traditional types of treatment, rather than as a stand-alone intervention, and have more severe clinical characteristics. The use the MHP alone was associated with improvement at a similar rate to those with higher baseline symptoms who are in traditional treatments and use MHP adjunctively.

Utility of Thermal Imaging in Predicting Superficial Infections in Transfemoral Osseointegrated Implants.

Background: Superficial infection is a common minor complication of transcutaneous implants that can be challenging to predict or diagnose. Although it remains unclear whether superficial infections progress to deep infections (which may require implant removal), predicting and treating any infection in these patients is important. Given that flap thinning during stage II surgery requires compromising vascularity for stability of the skin penetration aperture, we hypothesized that early skin temperature changes predict long-term superficial infection risk. Methods: We obtained standardized thermal imaging and recorded surface temperatures of the aperture and overlying flaps 2 weeks postoperatively for the first 34 patients (46 limbs) treated with the Osseointegrated Prosthesis for the Rehabilitation of Amputees transfemoral implant system. We used two-sided t tests to compare temperatures surrounding the aperture and adjacent soft tissues in patients with and without subsequent infection. Results: During median follow-up of 3 years, 14 limbs (30.4%) developed 23 superficial infections. At patients' initial 2-week visit, mean skin temperature surrounding the aperture was 36.3ºC in limbs that later developed superficial infections and 36.7ºC in uninfected limbs (P = 0.35). In four patients with bilateral implants who later developed superficial infection in one limb, average temperature was 1.5ºC colder in the infected limb (P = 0.12). Conclusions: Superficial infections remain a frequent complication of transfemoral osseointegration surgery. We did not find differences in early heat signatures between limbs subsequently complicated and those not complicated by superficial infection. Further research should explore more objective measures to predict, diagnose, and prevent infections after osseointegration surgery.

Therapist-supported digital mental health intervention for depressive symptoms: A randomized clinical trial.

Depression is a chronic and debilitating mental disorder. Despite the existence of several evidence-based treatments, many individuals suffering from depression face myriad structural barriers to accessing timely care which may be alleviated by digital mental health interventions (DMHI). Accordingly, this randomized clinical trial (ClinicalTrials.gov: NCT04738084) investigated the efficacy of a newer version of the therapist-supported and guided DMHI, the Meru Health Program (MHP), which was recently enhanced with heart rate variability biofeedback and lengthened from 8- to 12-weeks duration, among people with elevated depression symptoms (N = 100, mean age 37). Recruited participants were randomized to the MHP (n = 54) or a waitlist control (n = 46) condition for 12 weeks. The MHP group had greater decreases in depression symptoms compared to the waitlist control (d = -0.8). A larger proportion of participants in the MHP group reported a minimal clinically important difference (MCID) in depression symptoms than participants in the waitlist control group (39.1 % vs. 9.8 %, χ2(1) = 9.90, p = .002). Similar effects were demonstrated for anxiety symptoms, quality of life, insomnia, and resilience. The results confirm the utility of the enhanced MHP in reducing depression symptoms and associated health burdens.

Longitudinal outcomes of a therapist-supported digital mental health intervention for depression and anxiety symptoms: A retrospective cohort study.

PURPOSE: This study examined treatment outcomes (depression and anxiety symptoms) up to 24 months after completion of a therapist-supported digital mental health intervention (DMHI). METHODS: The sample consisted of 380 participants who participated in an eight-week DMHI from February 6, 2017 to May 20, 2019. Participants reported depression and anxiety symptoms at eight timepoints from baseline to 24 months. Mixed-effects modelling was used to investigate symptom changes over time. The proportion of participants meeting criteria for treatment response, clinically significant change, and remission of depression and anxiety symptoms were calculated, including proportions demonstrating each outcome sustained up to each timepoint. RESULTS: Multivariate analyses yielded statistically significant reductions in depression (ß = -5.40) and anxiety (ß = -3.31) symptoms from baseline to end of treatment (8 weeks). Symptom levels remained significantly reduced from baseline through 24 months. The proportion of participants meeting criteria for clinical treatment outcomes remained constant over 24 months, although there were linear decreases in the proportions experiencing sustained clinical outcomes. CONCLUSIONS: Treatment gains were made for depression and anxiety symptoms at the end of treatment and up to 24 months. Future studies should determine the feasibility of integrating post-treatment programmes into DMHIs to address symptom deterioration.

Links Between Objectively-Measured Hourly Smartphone Use and Adolescent Wake Events Across Two Weeks.

PURPOSE: Psychosocial and bioregulatory pressures threaten sleep during adolescence. Although recent work suggests that the ubiquity of smartphone use throughout adolescence may also relate to poorer sleep outcomes, most existing research relies upon self-report and retrospective measures. This study drew upon objective measures of smartphone use and sleep at the hourly level to understand how smartphone use was associated with the duration of wake events during sleeping hours. METHODS: Across a 14-day daily study, 59 racially and ethnically diverse adolescents ages 15 to 18 had their sleep assessed via Fitbit Inspire 2 devices and uploaded screenshots of their screen time, pickups, and notifications as logged by their iPhone's iOS. Multi-level modeling was performed to assess hourly level associations between adolescent smartphone use and wake-events during their sleep sessions (N = 4,287 hourly cases). RESULTS: In hours during adolescents' sleep session with more screen time or pickups, adolescents had longer wake event duration. More notifications in a given hour were not associated with wake event duration in the same hour. CONCLUSIONS: Using objectively measured smartphone and sleep data collected at the hourly level, we found that during sleeping hours, when adolescents are actively engaging with their smartphones, their sleep is disrupted, such that their wake events are longer in that hour.

Facile Physicochemical Reprogramming of PEG-Dithiolane Microgels.

Granular biomaterials have found widespread applications in tissue engineering, in part because of their inherent porosity, tunable properties, injectability, and 3D printability. However, the assembly of granular hydrogels typically relies on spherical microparticles and more complex particle geometries have been limited in scope, often requiring templating of individual microgels by microfluidics or in-mold polymerization. Here, we use dithiolane-functionalized synthetic macromolecules to fabricate photopolymerized microgels via batch emulsion, and then harness the dynamic disulfide crosslinks to rearrange the network. Through unconfined compression between parallel plates in the presence of photoinitiated radicals, we transform the isotropic microgels are transformed into disks. Characterizing this process, we find that the areas of the microgel surface in contact with the compressive plates are flattened while the curvature of the uncompressed microgel boundaries increases. When cultured with C2C12 myoblasts, cells localize to regions of higher curvature on the disk-shaped microgel surfaces. This altered localization affects cell-driven construction of large supraparticle scaffold assemblies, with spherical particles assembling without specific junction structure while disk microgels assemble preferentially on their curved surfaces. These results represent a unique spatiotemporal process for rapid reprocessing of microgels into anisotropic shapes, providing new opportunities to study shape-driven mechanobiological cues during and after granular hydrogel assembly.

Preliminary Effectiveness of a Therapist-Supported Digital Mental Health Intervention in Reducing Suicidal Ideation.

Suicidal ideation (SI) is a significant public health concern with increasing prevalence. Therapist-supported digital mental health interventions (DMHI) are an emergent modality to address common mental health problems like depression and anxiety, although less is known about SI. This study examined SI trajectories among 778 patients who participated in a therapist-supported DMHI using multilevel models during and up to 6-months post-treatment. Estimates of associated suicide attempts and deaths by suicide were calculated using published data linking PHQ-9-assessed SI to records of suicide attempts and deaths by suicide. The proportion of participants reporting no SI significantly increased between baseline and end-of-treatment (78.02% to 91.00%). Effect sizes of SI changes between baseline and end-of-treatment, 3-month, and 6-month follow-ups were 0.33 (95%CI = 0.27-0.38), 0.32 (95%CI = 0.27-0.38), and 0.32 (95%CI = 0.27-0.38), respectively. Results also indicated an estimated 30.49% reduction (95%CI = 25.15%-35.13%) in suicide attempts and death by suicide across treatment. This study provides preliminary evidence of the effectiveness of a therapist-supported DMHI in reducing SI.

Pediatric Pulmonary Fellowship Program Size Effect on Recruitment and Workforce Distribution.

Background: Concerns about the pediatric pulmonology workforce suggest a need to improve fellowship recruitment. Program size is related to the financial health and recruitment success of pediatric subspecialty education programs, but there are few data on how program size impacts recruitment and workforce in pediatric pulmonology. Objective: Assess the impact of program size in pediatric pulmonology through examination of the distribution of applicants matching into pediatric pulmonology training programs over time and relationships to workforce distribution. Methods: Data from the National Residency Match Program from 2010 to 2022 were extracted from published documents. Positions offered, positioned filled, and match rates were calculated for each appointment year. Statewide statistics for the number of fellows matched were analyzed relative to the number of pediatric pulmonologists per capita using data from the American Board of Pediatrics. Results: From 2010 to 2018, the size and distribution of programs in pediatric pulmonology were stable, with most fellows (82.4%) matching into programs with one or two positions per cycle. Starting in 2019, programs offering three or more positions steadily increased in number and aggregate positions offered. This change was associated with an increase in total filled positions (38.9 ± 7.3 in 2010-2018 vs. 50.5 ± 8.7 in 2019-2022; P < 0.03) and an increased fraction who matched into larger programs (17.6% in 2010-2018 vs. 36.9% in 2019-2022; P < 0.001). Among states with fellowship programs, the number of fellows matched over the past 5 years correlated with the number of practicing pediatric pulmonologists per capita (r = 0.78; P < 0.001). Conclusion: The period 2019-2022 saw a marked shift of pediatric pulmonary trainees matching into a relatively small number of larger programs. This shift was associated with overall growth in the number of trainees but may have implications on geographical distribution of practicing pediatric pulmonologists.

Stiffness anisotropy coordinates supracellular contractility driving long-range myotube-ECM alignment.

In skeletal muscle tissue, injury-related changes in stiffness activate muscle stem cells through mechanosensitive signaling pathways. Functional muscle tissue regeneration also requires the effective coordination of myoblast proliferation, migration, polarization, differentiation, and fusion across multiple length scales. Here, we demonstrate that substrate stiffness anisotropy coordinates contractility-driven collective cellular dynamics resulting in C2C12 myotube alignment over millimeter-scale distances. When cultured on mechanically anisotropic liquid crystalline polymer networks (LCNs) lacking topographic features that could confer contact guidance, C2C12 myoblasts collectively polarize in the stiffest direction of the substrate. Cellular coordination is amplified through reciprocal cell-ECM dynamics that emerge during fusion, driving global myotube-ECM ordering. Conversely, myotube alignment was restricted to small local domains with no directional preference on mechanically isotropic LCNs of same chemical formulation. These findings reveal a role for stiffness anisotropy in coordinating emergent collective cellular dynamics, with implications for understanding skeletal muscle tissue development and regeneration.

AgAnimalGenomes: browsers for viewing and manually annotating farm animal genomes.

Current genome sequencing technologies have made it possible to generate highly contiguous genome assemblies for non-model animal species. Despite advances in genome assembly methods, there is still room for improvement in the delineation of specific gene features in the genomes. Here we present genome visualization and annotation tools to support seven livestock species (bovine, chicken, goat, horse, pig, sheep, and water buffalo), available in a new resource called AgAnimalGenomes. In addition to supporting the manual refinement of gene models, these browsers provide visualization tracks for hundreds of RNAseq experiments, as well as data generated by the Functional Annotation of Animal Genomes (FAANG) Consortium. For species with predicted gene sets from both Ensembl and RefSeq, the browsers provide special tracks showing the thousands of protein-coding genes that disagree across the two gene sources, serving as a valuable resource to alert researchers to gene model issues that may affect data interpretation. We describe the data and search methods available in the new genome browsers and how to use the provided tools to edit and create new gene models.

Smartphone Photoplethysmography Pulse Rate Covaries With Stress and Anxiety During a Digital Acute Social Stressor.

OBJECTIVE: Heart rate is a transdiagnostic correlate of affective states and the stress diathesis model of health. Although most psychophysiological research has been conducted in laboratory environments, recent technological advances have provided the opportunity to index pulse rate dynamics in real-world environments with commercially available mobile health and wearable photoplethysmography (PPG) sensors that allow for improved ecologically validity of psychophysiological research. Unfortunately, adoption of wearable devices is unevenly distributed across important demographic characteristics, including socioeconomic status, education, and age, making it difficult to collect pulse rate dynamics in diverse populations. Therefore, there is a need to democratize mobile health PPG research by harnessing more widely adopted smartphone-based PPG to both promote inclusivity and examine whether smartphone-based PPG can predict concurrent affective states. METHODS: In the current preregistered study with open data and code, we examined the covariation of smartphone-based PPG and self-reported stress and anxiety during an online variant of the Trier Social Stress Test, as well as prospective relationships between PPG and future perceptions of stress and anxiety in a sample of 102 university students. RESULTS: Smartphone-based PPG significantly covaries with self-reported stress and anxiety during acute digital social stressors. PPG pulse rate was significantly associated with concurrent self-reported stress and anxiety ( b = 0.44, p = .018) as well as prospective stress and anxiety at the subsequent time points, although the strength of this association diminished the farther away pulse rate got from self-reported stress and anxiety (lag 1 model: b = 0.42, p = .024; lag 2 model: b = 0.38, p = .044). CONCLUSIONS: These findings indicate that PPG provides a proximal measure of the physiological correlates of stress and anxiety. Smartphone-based PPG can be used as an inclusive method for diverse populations to index pulse rate in remote digital study designs.