Development and evaluation of a BCI-neurofeedback system with real-time EEG detection and electrical stimulation assistance during motor attempt for neurorehabilitation of children with cerebral palsy.

In the realm of motor rehabilitation, Brain-Computer Interface Neurofeedback Training (BCI-NFT) emerges as a promising strategy. This aims to utilize an individual's brain activity to stimulate or assist movement, thereby strengthening sensorimotor pathways and promoting motor recovery. Employing various methodologies, BCI-NFT has been shown to be effective for enhancing motor function primarily of the upper limb in stroke, with very few studies reported in cerebral palsy (CP). Our main objective was to develop an electroencephalography (EEG)-based BCI-NFT system, employing an associative learning paradigm, to improve selective control of ankle dorsiflexion in CP and potentially other neurological populations. First, in a cohort of eight healthy volunteers, we successfully implemented a BCI-NFT system based on detection of slow movement-related cortical potentials (MRCP) from EEG generated by attempted dorsiflexion to simultaneously activate Neuromuscular Electrical Stimulation which assisted movement and served to enhance sensory feedback to the sensorimotor cortex. Participants also viewed a computer display that provided real-time visual feedback of ankle range of motion with an individualized target region displayed to encourage maximal effort. After evaluating several potential strategies, we employed a Long short-term memory (LSTM) neural network, a deep learning algorithm, to detect the motor intent prior to movement onset. We then evaluated the system in a 10-session ankle dorsiflexion training protocol on a child with CP. By employing transfer learning across sessions, we could significantly reduce the number of calibration trials from 50 to 20 without compromising detection accuracy, which was 80.8% on average. The participant was able to complete the required calibration trials and the 100 training trials per session for all 10 sessions and post-training demonstrated increased ankle dorsiflexion velocity, walking speed and step length. Based on exceptional system performance, feasibility and preliminary effectiveness in a child with CP, we are now pursuing a clinical trial in a larger cohort of children with CP.

NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice.

Circulating monocytes participate in pain chronification but the molecular events that cause their deployment are unclear. Using a mouse model of hyperalgesic priming (HP), we show that monocytes enable progression to pain chronicity through a mechanism that requires transient activation of the hydrolase, N-acylethanolamine acid amidase (NAAA), and the consequent suppression of NAAA-regulated lipid signaling at peroxisome proliferator-activated receptor-α (PPAR-α). Inhibiting NAAA in the 72 hours following administration of a priming stimulus prevented HP. This effect was phenocopied by NAAA deletion and depended on PPAR-α recruitment. Mice lacking NAAA in CD11b+ cells - monocytes, macrophages, and neutrophils - were resistant to HP induction. Conversely, mice overexpressing NAAA or lacking PPAR-α in the same cells were constitutively primed. Depletion of monocytes, but not resident macrophages, generated mice that were refractory to HP. The results identify NAAA-regulated signaling in monocytes as a control node in the induction of HP and, potentially, the transition to pain chronicity.

Testing the Capability of AI Art Tools for Urban Design.

This study aimed to evaluate the performance of three artificial intelligence (AI) image synthesis models, Dall-E 2, Stable Diffusion, and Midjourney, in generating urban design imagery based on scene descriptions. A total of 240 images were generated and evaluated by two independent professional evaluators using an adapted sensibleness and specificity average metric. The results showed significant differences between the three AI models, as well as differing scores across urban scenes, suggesting that some projects and design elements may be more challenging for AI art generators to represent visually. Analysis of individual design elements showed high accuracy in common features like skyscrapers and lawns, but less frequency in depicting unique elements such as sculptures and transit stops. AI-generated urban designs have potential applications in the early stages of exploration when rapid ideation and visual brainstorming are key. Future research could broaden the style range and include more diverse evaluative metrics. The study aims to guide the development of AI models for more nuanced and inclusive urban design applications, enhancing tools for architects and urban planners.

Effects of the Toxic Non-Protein Amino Acid ß-Methylamino-L-Alanine (BMAA) on Intracellular Amino Acid Levels in Neuroblastoma Cells.

The cyanobacterial non-protein amino acid (AA) ß-Methylamino-L-alanine (BMAA) is considered to be a neurotoxin. BMAA caused histopathological changes in brains and spinal cords of primates consistent with some of those seen in early motor neuron disease; however, supplementation with L-serine protected against some of those changes. We examined the impact of BMAA on AA concentrations in human neuroblastoma cells in vitro. Cells were treated with 1000 µM BMAA and intracellular free AA concentrations in treated and control cells were compared at six time-points over a 48 h culture period. BMAA had a profound effect on intracellular AA levels at specific time points but in most cases, AA homeostasis was re-established in the cell. The most heavily impacted amino acid was serine which was depleted in BMAA-treated cells from 9 h onwards. Correction of serine depletion could be a factor in the observation that supplementation with L-serine protects against BMAA toxicity in vitro and in vivo. AAs that could potentially be involved in protection against BMAA-induced oxidation such as histidine, tyrosine, and phenylalanine were depleted in cells at later time points.

Children With Bilateral Cerebral Palsy Exhibit Bimanual Asymmetric Motor Deficits and EEG Evidence of Dominant Sensorimotor Hemisphere Overreliance During Reaching.

BACKGROUND: Reaching is a fundamental motor skill often impaired in cerebral palsy (CP). Studies on manual function, intervention, and underlying brain mechanisms largely focus on unilateral CP. This first electroencephalography (EEG) evaluation of reaching exclusively in bilateral CP aims to quantify and relate brain activation patterns to bimanual deficits in this population. METHODS: A total of 15 children with bilateral CP (13.4 ± 2.9 years) and 13 with typical development (TD: 14.3 ± 2.4 years) performed 45 reaches per hand while recording motion capture and EEG data. The Box and Blocks test was administered bilaterally. Cortical sources were identified using independent component analysis and clustered using k-means. Alpha (8-12 Hz) and beta (13-30 Hz) band event-related desynchronization (ERD) values were compared across groups and hands within clusters, between dominant and non-dominant sensorimotor clusters, and related to reach kinematics and the Box and Block test. RESULTS: The group with CP demonstrated bimanual motor deficits with slower reaches, lower Box and Blocks scores, and stronger hand preference than in TD. Beta ERD, representing motor execution, was notably higher in the dominant sensorimotor cluster in CP compared to TD. Both groups demonstrated more contralateral than ipsilateral activity in both hands and clusters, with CP showing a less lateralized (more bilateral) alpha response. Higher brain activation was generally related to better function. CONCLUSION: Bimanual deficits in bilateral CP and related EEG differences warrant more clinical and research attention particularly earlier in life when greater potential for neural and functional recovery exists.

Introduction to a Twin Dual-Axis Robotic Platform for Studies of Lower Limb Biomechanics.

This paper presents a twin dual-axis robotic platform system which is designed for the characterization of postural balance under various environmental conditions and quantification of bilateral ankle mechanics in 2 degrees-of-freedom (DOF) during standing and walking. Methods: Validation experiments were conducted to evaluate performance of the system: 1) to apply accurate position perturbations under different loading conditions; 2) to simulate a range of stiffness-defined mechanical environments; and 3) to reliably quantify the joint impedance of mechanical systems. In addition, several human experiments were performed to demonstrate the system's applicability for various lower limb biomechanics studies. The first two experiments quantified postural balance on a compliance-controlled surface (passive perturbations) and under oscillatory perturbations with various frequencies and amplitudes (active perturbations). The second two experiments quantified bilateral ankle mechanics, specifically, ankle impedance in 2-DOF during standing and walking. The validation experiments showed high accuracy of the platform system to apply position perturbations, simulate a range of mechanical environments, and quantify the joint impedance. Results of the human experiments further demonstrated that the platform system is sensitive enough to detect differences in postural balance control under challenging environmental conditions as well as bilateral differences in 2-DOF ankle mechanics. This robotic platform system will allow us to better understand lower limb biomechanics during functional tasks, while also providing invaluable knowledge for the design and control of many robotic systems including robotic exoskeletons, prostheses and robot-assisted balance training programs. Clinical and Translational Impact Statement- Our robotic platform system serves as a tool to better understand the biomechanics of both healthy and neurologically impaired individuals and to develop assistive robotics and rehabilitation training programs using this information.

Understanding Hesitation to Use Nicotine Replacement Therapy: A Content Analysis of Posts in Online Tobacco-Cessation Support Groups.

PURPOSE: We aimed to better understand hesitancy to use nicotine replacement therapy (NRT) to quit smoking. DESIGN: We content coded and analyzed NRT-related posts in online quit smoking support groups to understand NRT-use hesitancy and to examine associations with health outcomes. SETTING: NRT posts were analyzed in unmoderated social-media support groups with free NRT. SAMPLE: Adults who smoked daily (n = 438) and posted about NRT were studied, 339 of whom reported on NRT usage and 403 reported on smoking abstinence. MEASURES: Surveys at 1-month post-quit date assessed NRT usage and smoking abstinence. ANALYSIS: Relationships among NRT posts, NRT usage and smoking abstinence were analyzed using GEE models accounting for support group and covariates. RESULTS: Nearly all (96.17%) participants reported using the study-provided NRT once, most (70.21%) used NRT during the past week, but less than half (45.72%) used NRT daily for the full month as recommended. Nearly two-thirds (65.34%) of NRT posts were negative. Posts reflecting dislike or no longer needing NRT were associated with a lower likelihood of using NRT in the past week at least once (B = -.66, P = .005 and B = -.37, P = .045), use occasions (B = -1.86, P = .018 and B = -1.10, P = .016) and used daily for full month (B = -.56, P = .044 and B = -.53, P = .009). Posts related to the effectiveness of NRT related to past-week NRT used at least once (B = .15, P = .023), used daily for full month (B = .25, P = .001), and smoking abstinence (B = .27, P = .002). CONCLUSION: Strategies are needed to address dislike of NRT and strengthen perceptions of NRT efficacy, especially on social media where posts may be amplified.

American election results at the precinct level.

We describe the creation and quality assurance of a dataset containing nearly all available precinct-level election results from the 2016, 2018, and 2020 American elections. Precincts are the smallest level of election administration, and election results at this granularity are needed to address many important questions. However, election results are individually reported by each state with little standardization or data quality assurance. We have collected, cleaned, and standardized precinct-level election results from every available race above the very local level in almost every state across the last three national election years. Our data include nearly every candidate for president, US Congress, governor, or state legislator, and hundreds of thousands of precinct-level results for judicial races, other statewide races, and even local races and ballot initiatives. In this article we describe the process of finding this information and standardizing it. Then we aggregate the precinct-level results up to geographies that have official totals, and show that our totals never differ from the official nationwide data by more than 0.457%.

Correction: Steele et al. Misincorporation Proteomics Technologies: A Review. Proteomes 2021, 9, 2.

In the original publication, there was a mistake in Table 2 as published [...].

ß-Methylamino-L-alanine-induced protein aggregation in vitro and protection by L-serine.

The cyanobacterial non-protein amino acid α-amino-ß-methylaminopropionic acid, more commonly known as BMAA, was first discovered in the seeds of the ancient gymnosperm Cycad circinalis (now Cycas micronesica Hill). BMAA was linked to the high incidence of neurological disorders on the island of Guam first reported in the 1950s. BMAA still attracts interest as a possible causative factor in amyotrophic lateral sclerosis (ALS) following the identification of ALS disease clusters associated with living in proximity to lakes with regular cyanobacterial blooms. Since its discovery, BMAA toxicity has been the subject of many in vivo and in vitro studies. A number of mechanisms of toxicity have been proposed including an agonist effect at glutamate receptors, competition with cysteine for transport system xc_ and other mechanisms capable of generating cellular oxidative stress. In addition, a wide range of studies have reported effects related to disturbances in proteostasis including endoplasmic reticulum stress and activation of the unfolded protein response. In the present studies we examine the effects of BMAA on the ubiquitin-proteasome system (UPS) and on chaperone-mediated autophagy (CMA) by measuring levels of ubiquitinated proteins and lamp2a protein levels in a differentiated neuronal cell line exposed to BMAA. The BMAA induced increases in oxidised proteins and the increase in CMA activity reported could be prevented by co-administration of L-serine but not by the two antioxidants examined. These data provide further evidence of a protective role for L-serine against the deleterious effects of BMAA.

Misincorporation Proteomics Technologies: A Review.

Proteinopathies are diseases caused by factors that affect proteoform conformation. As such, a prevalent hypothesis is that the misincorporation of noncanonical amino acids into a proteoform results in detrimental structures. However, this hypothesis is missing proteomic evidence, specifically the detection of a noncanonical amino acid in a peptide sequence. This review aims to outline the current state of technology that can be used to investigate mistranslations and misincorporations whilst framing the pursuit as Misincorporation Proteomics (MiP). The current availability of technologies explored herein is mass spectrometry, sample enrichment/preparation, data analysis techniques, and the hyphenation of approaches. While many of these technologies show potential, our review reveals a need for further development and refinement of approaches is still required.

Facebook Recruitment Using Zip Codes to Improve Diversity in Health Research: Longitudinal Observational Study.

BACKGROUND: Facebook's advertising platform reaches most US households and has been used for health-related research recruitment. The platform allows for advertising segmentation by age, gender, and location; however, it does not explicitly allow for targeting by race or ethnicity to facilitate a diverse participant pool. OBJECTIVE: This study looked at the efficacy of zip code targeting in Facebook advertising to reach blacks/African Americans and Hispanics/Latinos who smoke daily for a quit-smoking web-based social media study. METHODS: We ran a general market campaign for 61 weeks using all continental US zip codes as a baseline. Concurrently, we ran 2 campaigns to reach black/African American and Hispanic-/Latino-identified adults, targeting zip codes ranked first by the percentage of households of the racial or ethnic group of interest and then by cigarette expenditure per household. We also ran a Spanish language campaign for 13 weeks, targeting all continental US zip codes but utilizing Facebook's Spanish language targeting. The advertising images and language were common across campaigns. Costs were compared for advertisement clicks, queries, applications, and participants, and yields were compared for the final three outcomes. We examined outcomes before and after the Cambridge Analytica scandal that broke in March 2018. Finally, we examined 2 promoted Facebook features: lookalike audiences and audience network placement. RESULTS: Zip code targeting campaigns were effective for yielding the racial or ethnic groups of interest. The black-/African American-focused versus general market campaign increased black/African American weekly queries (mean 9.48, SD 5.69 vs general market mean 2.83, SD 2.05; P<.001) and applicants (mean 1.11, SD 1.21 vs general market mean 0.54, SD 0.58; P<.001). The Hispanic-/Latino-focused versus general market campaign increased Hispanic/Latino weekly queries (mean 3.10, SD 2.16 vs general market mean 0.71, SD 0.48; P<.001) and applicants (mean 0.36, SD 0.55 vs general market mean 0.10, SD 0.14; P=.001). Cost metrics did not differ between campaigns at generating participants (overall P=.54). Costs increased post- versus prescandal for the black-/African American-focused campaign for queries (mean US $8.51, SD 3.08 vs US $5.87, SD 1.89; P=.001) and applicants (mean US $59.64, SD 35.63 vs US $38.96, SD 28.31; P=.004) and for the Hispanic-/Latino-focused campaign for queries (mean US $9.24, SD 4.74 vs US $7.04, SD 3.39; P=.005) and applicants (mean US $61.19, SD 40.08 vs US $38.19, SD 21.20; P=.001). CONCLUSIONS: Zip code targeting in Facebook advertising is an effective way to recruit diverse populations for health-based interventions. Audience network placement should be avoided. The Facebook lookalike audience may not be necessary for recruitment, with drawbacks including an unknown algorithm and unclear use of Facebook user data, and so public concerns around data privacy should be considered. TRIAL REGISTRATION: ClinicalTrial.gov NCT02823028; https://clinicaltrials.gov/ct2/show/NCT02823028.

The Use of Web-Based Support Groups Versus Usual Quit-Smoking Care for Men and Women Aged 21-59 Years: Protocol for a Randomized Controlled Trial.

BACKGROUND: Existing smoking cessation treatments are challenged by low engagement and high relapse rates, suggesting the need for more innovative, accessible, and interactive treatment strategies. Twitter is a Web-based platform that allows people to communicate with each other throughout the day using their phone. OBJECTIVE: This study aims to leverage the social media platform of Twitter for fostering peer-to-peer support to decrease relapse with quitting smoking. Furthermore, the study will compare the effects of coed versus women-only groups on women's success with quitting smoking. METHODS: The study design is a Web-based, three-arm randomized controlled trial with two treatment arms (a coed or women-only Twitter support group) and a control arm. Participants are recruited online and are randomized to one of the conditions. All participants will receive 8 weeks of combination nicotine replacement therapy (patches plus their choice of gum or lozenges), serial emails with links to Smokefree.gov quit guides, and instructions to record their quit date online (and to quit smoking on that date) on a date falling within a week of initiation of the study. Participants randomized to a treatment arm are placed in a fully automated Twitter support group (coed or women-only), paired with a buddy (matched on age, gender, location, and education), and encouraged to communicate with the group and buddy via daily tweeted discussion topics and daily automated feedback texts (a positive tweet if they tweet and an encouraging tweet if they miss tweeting). Recruited online from across the continental United States, the sample consists of 215 male and 745 female current cigarette smokers wanting to quit, aged between 21 and 59 years. Self-assessed follow-up surveys are completed online at 1, 3, and 6 months after the date they selected to quit smoking, with salivary cotinine validation at 3 and 6 months. The primary outcome is sustained biochemically confirmed abstinence at the 6-month follow-up. RESULTS: From November 2016 to September 2018, 960 participants in 36 groups were recruited for the randomized controlled trial, in addition to 20 participants in an initial pilot group. Data analysis will commence soon for the randomized controlled trial based on data from 896 of the 960 participants (93.3%), with 56 participants lost to follow-up and 8 dropouts. CONCLUSIONS: This study combines the mobile platform of Twitter with a support group for quitting smoking. Findings will inform the efficacy of virtual peer-to-peer support groups for quitting smoking and potentially elucidate gender differences in quit rates found in prior research. TRIAL REGISTRATION: ClinicalTrials.gov NCT02823028; https://clinicaltrials.gov/ct2/show/NCT02823028. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16417.