Evolution of pathologic B-cell subsets and serum environment-specific sIgEs in patients with atopic dermatitis and controls, from infancy to adulthood.

BACKGROUND: While B-cells have historically been implicated in allergy development, a growing body of evidence supports their role in atopic dermatitis (AD). B-cell differentiation across ages in AD, and its relation to disease severity scores, has not been well defined. OBJECTIVE: To compare the frequency of B-cell subsets in blood of 0-5, 6-11, 12-17, and ≥18 years old patients with AD versus age-matched controls. METHODS: Flow cytometry was used to measure B-cell subset frequencies in the blood of 27 infants, 17 children, 11 adolescents, and 31 adults with moderate-to-severe AD and age-matched controls. IgD/CD27 and CD24/CD38 core gating systems and an 11-color flow cytometry panel were used to determine frequencies of circulating B-cell subsets. Serum total and allergen-specific IgE (sIgEs) levels were measured using ImmunoCAP®. RESULTS: Adolescents with AD had lower frequencies of major B-cells subsets (p < .03). CD23 expression increased with age and was higher in AD compared to controls across all age groups (p < .04). In AD patients, multiple positive correlations were observed between IL-17-producing T-cells and B-cell subsets, most significantly non-switched memory (NSM) B-cells (r = .41, p = .0005). AD severity positively correlated with a list of B-cell subsets (p < .05). IL-9 levels gradually increased during childhood, reaching a peak in adolescence, paralleling allergen sensitization, particularly in severe AD. Principal component analysis of the aggregated environmental sIgE data showed that while controls across all ages tightly clustered together, adolescents with AD demonstrated distinct clustering patterns relative to controls. CONCLUSIONS: Multiple correlations between B-cells and T-cells, as well as disease severity measures, suggest a complex interplay of immune pathways in AD. Unique B-cell signature during adolescence, with concurrent allergen sensitization and IL-9 surge, point to a potentially wider window of opportunity to implement interventions that may prevent the progression of the atopic march.

Immune-Targeted Therapies for Depression: Current Evidence for Antidepressant Effects of Monoclonal Antibodies.

Importance: Increasing evidence suggests a potential role of immune-modulatory drugs for treatment-resistant depression. This scoping review explores the emerging evidence regarding the antidepressant effects of monoclonal antibodies (mAbs), a relatively newer class of immune therapeutics with favorable safety profile.Observations: PubMed was searched up to November 2023 for English publications addressing the antidepressant effects of mAbs, including meta-analyses, randomized controlled trials, open-label, single-arm studies, and case series. Several mAbs have shown potential antidepressant effects, but most studies in primary inflammatory disorders included patients with mild depression. Only infliximab and sirukumab were directly examined in individuals with primary depression. mAbs that do not require laboratory monitoring, such as ixekizumab and dupilumab, could hold potential promise if future studies establish their safety profile regarding suicide risk.Conclusions and Relevance: The use of several mAbs for the treatment of primary inflammatory disorders has been associated with improvement of comorbid depressive symptoms. Given their unique mechanisms of action, mAbs may offer a new hope for depressed patients who do not respond to currently available antidepressants. Further research addressing individuals with more severe depressive symptoms is essential. Direct examination of antidepressant effects of mAbs in people with primary depressive disorders is also crucial to refine their clinical use in the treatment of depression.

Integrating Upper-Limb Prostheses with the Human Body: Technology Advances, Readiness, and Roles in Human-Prosthesis Interaction.

Significant advances in bionic prosthetics have occurred in the past two decades. The field's rapid expansion has yielded many exciting technologies that can enhance the physical, functional, and cognitive integration of a prosthetic limb with a human. We review advances in the engineering of prosthetic devices and their interfaces with the human nervous system, as well as various surgical techniques for altering human neuromusculoskeletal systems for seamless human-prosthesis integration. We discuss significant advancements in research and clinical translation, focusing on upper limbprosthetics since they heavily rely on user intent for daily operation, although many discussed technologies have been extended to lower limb prostheses as well. In addition, our review emphasizes the roles of advanced prosthetics technologies in complex interactions with humans and the technology readiness levels (TRLs) of individual research advances. Finally, we discuss current gaps and controversies in the field and point out future research directions, guided by TRLs.

NSF DARE-Transforming modeling in neurorehabilitation: Four threads for catalyzing progress.

We present an overview of the Conference on Transformative Opportunities for Modeling in Neurorehabilitation held in March 2023. It was supported by the Disability and Rehabilitation Engineering (DARE) program from the National Science Foundation's Engineering Biology and Health Cluster. The conference brought together experts and trainees from around the world to discuss critical questions, challenges, and opportunities at the intersection of computational modeling and neurorehabilitation to understand, optimize, and improve clinical translation of neurorehabilitation. We organized the conference around four key, relevant, and promising Focus Areas for modeling: Adaptation & Plasticity, Personalization, Human-Device Interactions, and Modeling 'In-the-Wild'. We identified four common threads across the Focus Areas that, if addressed, can catalyze progress in the short, medium, and long terms. These were: (i) the need to capture and curate appropriate and useful data necessary to develop, validate, and deploy useful computational models (ii) the need to create multi-scale models that span the personalization spectrum from individuals to populations, and from cellular to behavioral levels (iii) the need for algorithms that extract as much information from available data, while requiring as little data as possible from each client (iv) the insistence on leveraging readily available sensors and data systems to push model-driven treatments from the lab, and into the clinic, home, workplace, and community. The conference archive can be found at (dare2023.usc.edu). These topics are also extended by three perspective papers prepared by trainees and junior faculty, clinician researchers, and federal funding agency representatives who attended the conference.

Contributions of University of Toronto Dentistry Alumni to China's Early Dental Education.

University of Toronto Dentistry alumni have made valuable contributions to the evolution of dentistry and the dental profession not only in Canada but also internationally. The founder and some of the early faculty members of West China College of Stomatology at Sichuan University (formerly the Dental School of West China Union University), known as the birthplace of China's modern dental science education, were alumni from the University of Toronto. With their excellent dental background, skills, and dedication, those pioneers laid a firm foundation for modern dental education in China and their contributions to this effort will be addressed in this paper.

Modified motor unit properties in residual muscle following transtibial amputation.

Objective.Neural signals in residual muscles of amputated limbs are frequently decoded to control powered prostheses. Yet myoelectric controllers assume muscle activities of residual muscles are similar to that of intact muscles. This study sought to understand potential changes to motor unit (MU) properties after limb amputation.Approach.Six people with unilateral transtibial amputation were recruited. Surface electromyogram (EMG) of residual and intacttibialis anterior(TA) andgastrocnemius(GA) muscles were recorded while subjects traced profiles targeting up to 20% and 35% of maximum activation for each muscle (isometric for intact limbs). EMG was decomposed into groups of MU spike trains. MU recruitment thresholds, action potential amplitudes (MU size), and firing rates were correlated to model Henneman's size principle, the onion-skin phenomenon, and rate-size associations. Organization (correlation) and modulation (rates of change) of relations were compared between intact and residual muscles.Main results.The residual TA exhibited significantly lower correlation and flatter slopes in the size principle and onion-skin, and each outcome covaried between the MU relations. The residual GA was unaffected for most subjects. Subjects trained prior with myoelectric prostheses had minimally affected slopes in the TA. Rate-size association correlations were preserved, but both residual muscles exhibited flatter decay rates.Significance.We showed peripheral neuromuscular damage also leads to spinal-level functional reorganizations. Our findings suggest models of MU recruitment and discharge patterns for residual muscle EMG generation need reparameterization to account for disturbances observed. In the future, tracking MU pool adaptations may also provide a biomarker of neuromuscular control to aid training with myoelectric prostheses.

Enthusiastic and Grounded, Avoidant and Cautious: Understanding Public Receptivity to Data and Visualizations.

Despite an abundance of open data initiatives aimed to inform and empower "general" audiences, we still know little about the ways people outside of traditional data analysis communities experience and engage with public data and visualizations. To investigate this gap, we present results from an in-depth qualitative interview study with 19 participants from diverse ethnic, occupational, and demographic backgrounds. Our findings characterize a set of lived experiences with open data and visualizations in the domain of energy consumption, production, and transmission. This work exposes information receptivity - an individual's transient state of willingness or openness to receive information -as a blind spot for the data visualization community, complementary to but distinct from previous notions of data visualization literacy and engagement. We observed four clusters of receptivity responses to data- and visualization-based rhetoric: Information-Avoidant, Data-Cautious, Data-Enthusiastic, and Domain-Grounded. Based on our findings, we highlight research opportunities for the visualization community. This exploratory work identifies the existence of diverse receptivity responses, highlighting the need to consider audiences with varying levels of openness to new information. Our findings also suggest new approaches for improving the accessibility and inclusivity of open data and visualization initiatives targeted at broad audiences. A free copy of this paper and all supplemental materials are available at https://OSF.IO/MPQ32.

Gelatin methacryloyl hydrogel with and without dental pulp stem cells for TMJ regeneration: An in vivo study in rabbits.

BACKGROUND: In the last decade, tissue-engineering strategies for regenerating the temporomandibular joint (TMJ) have been investigated. This may be a promising strategy for the minimally invasive restoration of joint integrity. OBJECTIVES: To evaluate whether dental pulp stem cells (DPSCs) loaded in a light-occured hydrogel made of gelatin methacryloyl (GelMA) enhance the regeneration of osteochondral defects in the rabbit TMJ. MATERIALS AND METHODS: Defects were filled with GelMA alone (control group; n = 4) or filled with GelMA loaded with rabbit DPSCs (experimental group; n = 4), In one group, the TMJ capsule was opened without creating a defect (sham group; n = 2). The following micro-CT parameters were analysed: bone volume to total volume ratio (BV/TV%) and bone mineral density (BMD). Histological evaluation was performed to assess cartilage regeneration features. A semi-quantitative scoring system was also used to evaluate the defects. RESULTS: All groups had no statistical difference regarding the micro-CT parameters. The highest mean healing score was found for the experimental group. After 4 weeks, there were no signs of hydrogel in either group or no signs of inflammation in the adjacent tissues. The tissue formed in the defect was dense fibrous connective tissue. CONCLUSION: Adding DPSCs to GelMA did not provide a regenerative enhancement in TMJ osteochondral defects. This resulted in similar micro-CT parameters after 4 weeks of healing, with improved signs of subchondral bone regeneration but no cartilage regeneration.

Intrapatient comparison of atopic dermatitis skin transcriptome shows differences between tape-strips and biopsies.

BACKGROUND: Our knowledge of etiopathogenesis of atopic dermatitis (AD) is largely derived from skin biopsies, which are associated with pain, scarring and infection. In contrast, tape-stripping is a minimally invasive, nonscarring technique to collect skin samples. METHODS: To construct a global AD skin transcriptomic profile comparing tape-strips to whole-skin biopsies, we performed RNA-seq on tape-strips and biopsies taken from the lesional skin of 20 moderate-to-severe AD patients and the skin of 20 controls. Differentially expressed genes (DEGs) were defined by fold-change (FCH) ≥2.0 and false discovery rate <0.05. RESULTS: We detected 4104 (2513 Up; 1591 Down) and 1273 (546 Up; 727 Down) DEGs in AD versus controls, in tape-strips and biopsies, respectively. Although both techniques captured dysregulation of key immune genes, tape-strips showed higher FCHs for innate immunity (IL-1B, IL-8), dendritic cell (ITGAX/CD11C, FCER1A), Th2 (IL-13, CCL17, TNFRSF4/OX40), and Th17 (CCL20, CXCL1) products, while biopsies showed higher upregulation of Th22 associated genes (IL-22, S100As) and dermal cytokines (IFN-γ, CCL26). Itch-related genes (IL-31, TRPV3) were preferentially captured by tape-strips. Epidermal barrier abnormalities were detected in both techniques, with terminal differentiation defects (FLG2, PSORS1C2) better represented by tape-strips and epidermal hyperplasia changes (KRT16, MKI67) better detected by biopsies. CONCLUSIONS: Tape-strips and biopsies capture overlapping but distinct features of the AD molecular signature, suggesting their respective utility for monitoring specific AD-related immune, itch, and barrier abnormalities in clinical trials and longitudinal studies.

Towards Personalized Control for Powered Knee Prostheses: Continuous Impedance Functions and PCA-Based Tuning Method.

Optimizing control parameters is crucial for personalizing prosthetic devices. The current method of finite state machine impedance control (FSM-IC) allows interaction with the user but requires time-consuming manual tuning. To improve efficiency, we propose a novel approach for tuning knee prostheses using continuous impedance functions (CIFs) and Principal Component Analysis (PCA). The CIFs, which represent stiffness, damping, and equilibrium angle, are modeled as fourth-order polynomials and optimized through convex optimization. By applying PCA to the CIFs, we extract principal components (PCs) that capture common features. The weights of these PCs serve as tuning parameters, allowing us to reconstruct various impedance functions. We validated this approach using data from 10 able-bodied individuals walking. The contributions of this study include: i) generating CIFs via convex optimization; ii) introducing a new tuning space based on the obtained CIFs; and iii) evaluating the feasibility of this tuning space.

Neural prosthesis control restores near-normative neuromechanics in standing postural control.

Current lower-limb prostheses do not provide active assistance in postural control tasks to maintain the user's balance, particularly in situations of perturbation. In this study, we aimed to address this missing function by enabling neural control of robotic lower-limb prostheses. Specifically, electromyographic (EMG) signals (amplified neural control signals) recorded from antagonistic residual ankle muscles were used to drive a robotic prosthetic ankle directly and continuously. Participants with transtibial amputation were recruited and trained in using the EMG-driven robotic ankle. We studied how using the EMG-controlled ankle affected the participants' anticipatory and compensatory postural control strategies and stability under expected perturbations compared with using their daily passive devices. We investigated the similarity of neuromuscular coordination (by analyzing motor modules) of the participants, using either device in a postural sway task, to that of able-bodied controls. Results showed that, compared with their passive prosthesis, the EMG-controlled prosthesis enabled participants to use near-normative postural control strategies, as evidenced by improved between-limb symmetry in intact-prosthetic center-of-pressure and joint angle excursions. Participants substantially improved postural stability, as evidenced by a reduction in steps or falls using the EMG-controlled prosthetic ankle. Furthermore, after relearning to use residual ankle muscles to drive the robotic ankle in postural control, nearly all participants' motor module structure shifted toward that observed in individuals without limb amputations. Here, we have demonstrated the potential benefit of direct EMG control of robotic lower limb prostheses to restore normative postural control strategies (both neural and biomechanical) toward enhancing standing postural stability in amputee users.

Angle-programmed tendril-like trajectories enable a multifunctional gripper with ultradelicacy, ultrastrength, and ultraprecision.

Achieving multicapability in a single soft gripper for handling ultrasoft, ultrathin, and ultraheavy objects is challenging due to the tradeoff between compliance, strength, and precision. Here, combining experiments, theory, and simulation, we report utilizing angle-programmed tendril-like grasping trajectories for an ultragentle yet ultrastrong and ultraprecise gripper. The single gripper can delicately grasp fragile liquids with minimal contact pressure (0.05 kPa), lift objects 16,000 times its own weight, and precisely grasp ultrathin, flexible objects like 4-µm-thick sheets and 2-µm-diameter microfibers on flat surfaces, all with a high success rate. Its scalable and material-independent design allows for biodegradable noninvasive grippers made from natural leaves. Explicitly controlled trajectories facilitate its integration with robotic arms and prostheses for challenging tasks, including picking grapes, opening zippers, folding clothes, and turning pages. This work showcases soft grippers excelling in extreme scenarios with potential applications in agriculture, food processing, prosthesis, biomedicine, minimally invasive surgeries, and deep-sea exploration.

Plasticity of aggregation pheromones in insects.

Pheromone plasticity is widely observed in insects and enhances their survival, adaptation, and reproductive success. Aggregation pheromones, which cause notable individual aggregation and consequently impact agriculture and human life, are renowned for their special function. Here, we present a review of research progress regarding pheromone plasticity in three typical aggregative insects: locusts, bark beetles, and cockroaches. These insects are major pest species with considerable impacts on the social economy and public health. Numerous studies have demonstrated the plasticity of aggregation pheromones in different populations of these insect species. Although pheromone chemicals and compositions vary across the three groups, the plasticity of aggregation pheromones is significantly impacted by population density, location, food resources, and gut symbiotic microorganisms, indicating the complexity of pheromone plasticity regulated by multiple factors. Finally, we discuss the potential application of pheromone plasticity in basic research and pest management.

Artificial intelligence meets medical robotics.

Artificial intelligence (AI) applications in medical robots are bringing a new era to medicine. Advanced medical robots can perform diagnostic and surgical procedures, aid rehabilitation, and provide symbiotic prosthetics to replace limbs. The technology used in these devices, including computer vision, medical image analysis, haptics, navigation, precise manipulation, and machine learning (ML) , could allow autonomous robots to carry out diagnostic imaging, remote surgery, surgical subtasks, or even entire surgical procedures. Moreover, AI in rehabilitation devices and advanced prosthetics can provide individualized support, as well as improved functionality and mobility (see the figure). The combination of extraordinary advances in robotics, medicine, materials science, and computing could bring safer, more efficient, and more widely available patient care in the future. -Gemma K. Alderton.

The Impact of Dental Care Programs on Individuals and Their Families: A Scoping Review.

BACKGROUND: Despite significant global improvements in oral health, inequities persist. Targeted dental care programs are perceived as a viable approach to both improving oral health and to address inequities. However, the impacts of dental care programs on individual and family oral health outcomes remain unclear. OBJECTIVES: The purpose of this scoping review is to map the evidence on impacts of existing dental programs, specifically on individual and family level outcomes. METHODS: We systematically searched four scientific databases, MEDLINE, EMBASE, CINAHL, and Sociological Abstracts for studies published in the English language between December 1999 and November 2021. Search terms were kept broad to capture a range of programs. Four reviewers (AG, VD, AE, and KKP) independently screened the abstracts and reviewed full-text articles and extracted the data. Cohen's kappa inter-rater reliability score was 0.875, indicating excellent agreement between the reviewers. Data were summarized according to the PRISMA statement. RESULTS: The search yielded 65,887 studies, of which 76 were included in the data synthesis. All but one study assessed various individual-level outcomes (n = 75) and only five investigated family outcomes. The most common program interventions are diagnostic and preventive (n = 35, 46%) care, targeted children (n = 42, 55%), and delivered in school-based settings (n = 28, 37%). The majority of studies (n = 43, 57%) reported a significant improvement in one or more of their reported outcomes; the most assessed outcome was change in dental decay (n = 35). CONCLUSIONS: Dental care programs demonstrated effectiveness in addressing individual oral health outcomes. However, evidence to show the impact on family-related outcomes remains limited and requires attention in future research.

Toward higher-performance bionic limbs for wider clinical use.

Most prosthetic limbs can autonomously move with dexterity, yet they are not perceived by the user as belonging to their own body. Robotic limbs can convey information about the environment with higher precision than biological limbs, but their actual performance is substantially limited by current technologies for the interfacing of the robotic devices with the body and for transferring motor and sensory information bidirectionally between the prosthesis and the user. In this Perspective, we argue that direct skeletal attachment of bionic devices via osseointegration, the amplification of neural signals by targeted muscle innervation, improved prosthesis control via implanted muscle sensors and advanced algorithms, and the provision of sensory feedback by means of electrodes implanted in peripheral nerves, should all be leveraged towards the creation of a new generation of high-performance bionic limbs. These technologies have been clinically tested in humans, and alongside mechanical redesigns and adequate rehabilitation training should facilitate the wider clinical use of bionic limbs.

Chick chorioallantoic membrane model to investigate role of migrasome in angiogenensis.

The development of the vascular system is essential for embryonic development, including processes such as angiogenesis. Angiogenesis plays a critical role in many normal physiological and pathological processes. It is driven by a set of angiogenic proteins, including angiogenic growth factors, chemokines, and extracellular matrix proteins. Among various animal model systems, the chorioallantoic membrane (CAM), a specialized and highly vascularized tissue of the avian embryo, has proven to be a valuable tool for analyzing the angiogenic potential of candidate cells or factors. In this protocol, we provide detailed procedures for establishing the CAM model to evaluate the function and mechanism of migrasomes in embryonic angiogenesis. This includes the CAM nylon mesh assay and CAM ex vivo sprouting assay to assess CAM angiogenesis, as well as the observation, purification, and delivery of migrasomes. Additionally, we describe the generation of T4-KO-mCherry-KI embryos using the CRISPR system within the CAM tissue to investigate the role of migrasomes in angiogenesis.

The impact of dental care programs on healthcare system and societal outcomes: a scoping review.

BACKGROUND: Dental diseases have detrimental effects on healthcare systems and societies at large. Providing access to dental care can arguably improve health outcomes, reduce healthcare utilization costs, and improve several societal outcomes. OBJECTIVES: Our objective was to review the literature to assess the impacts of dental care programs on healthcare and societal outcomes. Specifically, to identify the nature of such programs, including the type of services delivered, who was targeted, where services were delivered, and how access to dental care was enabled. Also, what kind of societal and healthcare outcomes have been attempted to be addressed through these programs were identified. METHODS: We conducted a scoping review by searching four databases, MEDLINE, EMBASE, CINAHL, and Sociological Abstracts. Relevant articles published in English language from January 2000 to February 2022 were screened by four reviewers to determine eligibility for inclusion. RESULTS: The search resulted in 29,468 original articles, of which 25 were included in the data synthesis. We found minimal evidence that answers our proposed research question. The majority of identified programs have demonstrated effectiveness in reducing medical and dental healthcare utilization (especially for non-preventive services) and avert more invasive treatments, and to a lesser degree, resulting in cost-savings. Moreover, some promising but limited evidence about program impacts on societal outcomes such as reducing homelessness and improving employability was reported. CONCLUSION: Despite the well-known societal and economic consequences of dental problem, there is a paucity of studies that address the impacts of dental care programs from the societal and healthcare system perspectives. MESH TERMS: Delivery of Health Care, Dental Care, Outcome assessment, Patient acceptance of Health Care.

Monocytes deposit migrasomes to promote embryonic angiogenesis.

Pro-angiogenic factors are key regulators of angiogenesis. Here we report that highly migratory cells patrol the area of capillary formation in chick embryo chorioallantoic membrane. These cells deposit migrasomes on their migration tracks, creating migrasome-enriched areas. Single-cell sequencing identified these cells as monocytes. Depletion of monocytes impairs capillary formation. Quantitative mass spectrometry analysis reveals that monocyte migrasomes are enriched with pro-angiogenic factors. Purified migrasomes promote capillary formation and monocyte recruitment in vivo, and endothelial cell tube formation and monocyte chemotaxis in vitro. Knockdown or knockout of TSPAN4 reduces migrasome formation and impairs capillary formation and monocyte recruitment. Mechanistically, monocytes promote angiogenesis via VEGFA and CXCL12 in migrasomes. In summary, monocytes deposit migrasomes enriched in pro-angiogenic factors to promote angiogenesis.