Towards an AI-driven soft toy for automatically detecting and classifying infant-toy interactions using optical force sensors.

Introduction: It is crucial to identify neurodevelopmental disorders in infants early on for timely intervention to improve their long-term outcomes. Combining natural play with quantitative measurements of developmental milestones can be an effective way to swiftly and efficiently detect infants who are at risk of neurodevelopmental delays. Clinical studies have established differences in toy interaction behaviors between full-term infants and pre-term infants who are at risk for cerebral palsy and other developmental disorders. Methods: The proposed toy aims to improve the quantitative assessment of infant-toy interactions and fully automate the process of detecting those infants at risk of developing motor delays. This paper describes the design and development of a toy that uniquely utilizes a collection of soft lossy force sensors which are developed using optical fibers to gather play interaction data from infants laying supine in a gym. An example interaction database was created by having 15 adults complete a total of 2480 interactions with the toy consisting of 620 touches, 620 punches-"kick substitute," 620 weak grasps and 620 strong grasps. Results: The data is analyzed for patterns of interaction with the toy face using a machine learning model developed to classify the four interactions present in the database. Results indicate that the configuration of 6 soft force sensors on the face created unique activation patterns. Discussion: The machine learning algorithm was able to identify the distinct action types from the data, suggesting the potential usability of the toy. Next steps involve sensorizing the entire toy and testing with infants.

Synaptic vesicle glycoprotein 2C enhances vesicular storage of dopamine and counters dopaminergic toxicity.

Dopaminergic neurons of the substantia nigra exist in a persistent state of vulnerability resulting from high baseline oxidative stress, high-energy demand, and broad unmyelinated axonal arborisations. Impairments in the storage of dopamine compound this stress because of cytosolic reactions that transform the vital neurotransmitter into an endogenous neurotoxicant, and this toxicity is thought to contribute to the dopamine neuron degeneration that occurs Parkinson's disease. We have previously identified synaptic vesicle glycoprotein 2C (SV2C) as a modifier of vesicular dopamine function, demonstrating that genetic ablation of SV2C in mice results in decreased dopamine content and evoked dopamine release in the striatum. Here, we adapted a previously published in vitro assay utilising false fluorescent neurotransmitter 206 (FFN206) to visualise how SV2C regulates vesicular dopamine dynamics and determined that SV2C promotes the uptake and retention of FFN206 within vesicles. In addition, we present data indicating that SV2C enhances the retention of dopamine in the vesicular compartment with radiolabelled dopamine in vesicles isolated from immortalised cells and from mouse brain. Further, we demonstrate that SV2C enhances the ability of vesicles to store the neurotoxicant 1-methyl-4-phenylpyridinium (MPP+) and that genetic ablation of SV2C results in enhanced 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced vulnerability in mice. Together, these findings suggest that SV2C functions to enhance vesicular storage of dopamine and neurotoxicants and helps maintain the integrity of dopaminergic neurons.

Motor Learning in Robot-Based Haptic Dyads: A Review.

Rehabilitation robots have the potential to alleviate the global burden of neurorehabilitation. Robot-based multiplayer gaming with virtual and haptic interaction may improve motivation, engagement, and implicit learning in robotic therapy. Over the past few years, there has been growing interest in robot mediated haptic dyads, or human-robot-robot-human interaction. The effect of such a paradigm on motor learning in general and specifically for individuals with motor and/or cognitive impairments is an open area of research. We reviewed the literature to investigate the effect of a robot-based haptic dyad on motor learning. Thirty-eight articles met the inclusion criteria for this review. We summarize study characteristics including device, haptic rendering, and experimental task. Our main findings indicate that dyadic training's impact on motor learning is inconsistent in that some studies show significant improvement of motor training while others show no influence. We also find that the relative skill level of the partner and interaction characteristics such as stiffness of connection and availability of visual information influence motor learning outcomes. We discuss implications for neurorehabilitation and conclude that additional research is needed to determine optimal interaction characteristics for motor learning and to extend this research to individuals with cognitive and motor impairments.

Epidemiology and factors associated with mortality among pediatric major trauma patients in Nova Scotia: A 17-year retrospective analysis.

BACKGROUND: Major traumatic injury in the pediatric population requires further evaluation to improve patient outcomes. Relatively few Canadian studies have investigated pediatric trauma using population-based data. Our objectives were to describe the epidemiology of pediatric major trauma in Nova Scotia and identify factors associated with in-hospital mortality. METHODS: Retrospective cohort study of pediatric major trauma patients (age <18 years) injured in Nova Scotia over a 17-year period (April 2001-March 2018). Data were collected from the Nova Scotia Trauma Registry. Characteristics were compared between patient subgroups using t-tests, chi-square analyses and Fisher's exact test. Temporal trends were evaluated using the Mann-Kendall test. Incidence and mortality rates were mapped using ArcGIS Pro. A multivariate logistic regression model was created to assess for factors associated with in-hospital mortality. RESULTS: A total of 1258 injuries were observed over the 17-year study period. The incidence of pediatric major trauma was 41.7 per 100,000 person-years. Most patients were male (819/1258; 65.1 %) and resided in urban areas (764/1258; 60.7 %). Blunt trauma accounted for 86.2 % (1084/1258) of injuries, and motor vehicle collisions were the most common cause (448/1258; 35.6 %). Incidence and mortality rates were highest in the 15-17 year age group, with a trend towards increasing incidence among females (p = 0.011). Mortality was 17.2 % (217/1258) of patients; 10.9 % (137/1258) died pre-hospital. No trends were detected in mortality rates. The regression model showed increased odds of in-hospital mortality for every point increase in the ISS (OR 1.05; 95 % CI 1.02 to 1.09) and for every unit decrease in scene GCS (OR 0.63; 95 % CI 0.56-0.71). Rural patients were 2 times more likely to die in-hospital versus urban patients (OR 2.40; 95 % CI 1.01-5.69), and patients injured at home were 6 times more likely to die compared to those injured in other locations (OR 6.19; 95 % CI 1.01-38.11). CONCLUSION: Pediatric trauma remains a major public health issue in Canada and beyond. Greater efforts are required to expand our understanding of trauma epidemiology and develop targeted injury prevention strategies, especially for rural inhabitants.

with Rare Kidney Disease.

Chronic kidney disease (CKD) affects more than 35 million people in the United States, many of whom are undiagnosed. Included in this number are individuals with many types of rare kidney diseases, affecting 20,000 to 200,000 individuals nationwide. There is a major need to educate these individuals on the disease and its progression, especially since many individuals are not aware they have the disease. Descriptive correlational research was conducted in a nationwide sample of adult individuals living with rare glomerular kidney disease. Patient activation and quality of life were the concepts studied across the five CKD stages. New findings included statistically significant differences between participants' self-reported mental health quality of life and CKD Stage 1, with CKD Stages 4 and 5 in the rare kidney disease population. Nurses are essential for educating and supporting patients with rare kidney disease to preserve kidney function and slow disease progression.

ALS-related p97 R155H mutation disrupts lysophagy in iPSC-derived motor neurons.

Mutations in the AAA+ ATPase p97 cause multisystem proteinopathy 1, which includes amyotrophic lateral sclerosis; however, the pathogenic mechanisms that contribute to motor neuron loss remain obscure. Here, we use two induced pluripotent stem cell models differentiated into spinal motor neurons to investigate how p97 mutations perturb the motor neuron proteome. Using quantitative proteomics, we find that motor neurons harboring the p97 R155H mutation have deficits in the selective autophagy of lysosomes (lysophagy). p97 R155H motor neurons are unable to clear damaged lysosomes and have reduced viability. Lysosomes in mutant motor neurons have increased pH compared with wild-type cells. The clearance of damaged lysosomes involves UBXD1-p97 interaction, which is disrupted in mutant motor neurons. Finally, inhibition of the ATPase activity of p97 using the inhibitor CB-5083 rescues lysophagy defects in mutant motor neurons. These results add to the evidence that endo-lysosomal dysfunction is a key aspect of disease pathogenesis in p97-related disorders.

Addressing Structural Racism Through Public Policy Advocacy: A Policy Statement From the American Heart Association.

During the COVID-19 pandemic, the American Heart Association created a new 2024 Impact Goal with health equity at its core, in recognition of the increasing health disparities in our country and the overwhelming evidence of the damaging effect of structural racism on cardiovascular and stroke health. Concurrent with the announcement of the new Impact Goal was the release of an American Heart Association presidential advisory on structural racism, recognizing racism as a fundamental driver of health disparities and directing the American Heart Association to advance antiracist strategies regarding science, business operations, leadership, quality improvement, and advocacy. This policy statement builds on the call to action put forth in our presidential advisory, discussing specific opportunities to leverage public policy in promoting overall well-being and rectifying those long-standing structural barriers that impede the progress that we need and seek for the health of all communities. Although this policy statement discusses difficult aspects of our past, it is meant to provide a forward-looking blueprint that can be embraced by a broad spectrum of stakeholders who share the association's commitment to addressing structural racism and realizing true health equity.

Pre-hospital mortality among pediatric trauma patients in Nova Scotia.

OBJECTIVES: Limited data exist on pre-hospital pediatric trauma mortality in Canada. The Nova Scotia Trauma Registry is a provincial population-based registry that captures data from the Medical Examiner Service. This study examined the characteristics of pediatric trauma patient mortality in the pre-hospital and in-hospital settings. METHODS: We conducted a cohort study of major pediatric traumas recorded in our provincial database from April 1, 2001 to March 31, 2018. Characteristics of pre-hospital and in-hospital deaths were compared with t tests and Chi-square analyses. Multivariate regression modeling was used to identify predictors of pre-hospital mortality. The geographic distribution of pre-hospital trauma was assessed using choropleth maps. RESULTS: We identified 1,258 pediatric traumas, resulting in 217 deaths (137 pre-hospital, 80 in-hospital). Males accounted for 62.7% of fatalities. The 15-17 age group accounted for most deaths in both groups (pre-hospital 61.3%; in-hospital 41.3%). Injuries sustained in rural areas resulted in 74.7% of all deaths. For both groups, blunt trauma was the predominant injury type and motor vehicle collisions, the most prevalent injury mechanism. Patients who died pre-hospital had a higher mean age (13.3 vs. 10.7, p = 0.002) and a greater proportion were intentional injuries (23.4% vs. 15%; p = 0.02). Urban residency was more frequently observed in in-hospital deaths (57.5% vs. 36.5%, p < 0.001). Pre-hospital mortality was associated with increasing age (OR 1.1), higher injury severity score (OR 1.1), and intentional injury (OR 15.6). CONCLUSION: Over 10% of major pediatric traumas resulted in pre-hospital death, primarily from motor vehicle collisions in rural areas. Compared to in-hospital mortality, patients who died pre-hospital were older with more severe injuries and more likely to have intentionally injured themselves. These results underscore the importance for emergency physicians and EMS systems to consider geographic factors and injury patterns, advocate for improved injury prevention programs, mental health supports, and delivery of on-scene critical care services.

RéSUMé: OBJECTIFS: Il existe peu de données sur la mortalité liée aux traumatismes pédiatriques pré-hospitaliers au Canada. La Nouvelle-Écosse. Le registre des traumatismes est un registre provincial fondé sur la population qui saisit les données du Medical Examiner Service. Cette étude a examiné les caractéristiques des traumatismes pédiatriques la mortalité des patients en milieu pré-hospitalier et hospitalier. MéTHODES: Nous avons mené une étude de cohorte des traumatismes pédiatriques majeurs enregistrés dans notre province base de données du 1er avril 2001 au 31 mars 2018. Caractéristiques des services pré-hospitaliers et les décès hospitaliers ont été comparés aux tests-t et aux analyses du chi carré. La modélisation multivariée de régression a été utilisée pour identifier les prédicteurs de la mortalité pré-hospitalière. La répartition géographique des traumatismes pré-hospitaliers a été évaluée à l'aide de cartes choroplèthes. RéSULTATS: Nous avons identifié 1258 traumatismes pédiatriques, entraînant 217 décès (137 pré-hospitaliers, 80 hospitalier les hommes représentaient 62,7% des décès. Le groupe des 15 à 17 ans représentait la plupart des décès dans les deux groupes (avant l'hôpital 61,3%; à l'hôpital 41,3%). Blessures subies dans les régions rurales ont entraîné 74,7% de tous les décès. Pour les deux groupes, le traumatisme contondant était le type de blessure prédominant et les collisions de véhicules à moteur, les blessures les plus fréquentes. Les patients décédés avant l'hospitalisation avaient un âge moyen plus élevé (13,3 vs 10,7, p = 0,002) et une plus grande proportion étaient des blessures intentionnelles (23,4% contre 15%; p = 0,02). La résidence en milieu urbain était plus fréquemment observée dans les décès à l'hôpital (57,5% contre 36,5%, p < 0.001). La mortalité pré-hospitalière était associée à une augmentation de l'âge (CP 1.1) le score de gravité des blessures (CP 1.1) et les blessures intentionnelles (CP 15.6). CONCLUSIONS: Plus de 10% des traumatismes pédiatriques majeurs ont entraîné un décès avant l'hôpital, principalement à cause de troubles moteurs les collisions de véhicules dans les régions rurales. Comparativement à la mortalité à l'hôpital, les patients qui sont décédés avant. les établissements de soins palliatifs étaient plus âgés et plus susceptibles d'avoir intentionnellement subi des blessures plus graves. Ces résultats soulignent l'importance pour les médecins d'urgence et les systèmes de SMU pour tenir compte des facteurs géographiques et des tendances en matière de blessures, préconiser amélioration des programmes de prévention des blessures, du soutien en santé mentale et de la prestation sur place services de soins intensifs.

The Viability and Acceptability of a Virtual Wound Care Command Centre in Australia.

The objective of this study was to assess the viability and acceptability of an innovative Virtual Wound Care Command Centre where patients in the community, and their treating clinicians, have access to an expert wound specialist service that comprises a digital wound application (app) for wound analysis, decision-making, remote consultation, and monitoring. Fifty-one patients with chronic (42.6%) wounds were healed, with a median time to healing of 66 (95% CI: 56-88) days. All patients reported high satisfaction with their wound care, 86.4% of patients recommended the Virtual Wound Care Command Centre with 84.1% of patients reporting the app as easy to use. The data revealed that the Virtual Wound Care Command Centre was a viable and acceptable patient-centred expert wound consultation service for chronic wound patients in the community.

Reshaping Wound Care: Evaluation of an Artificial Intelligence App to Improve Wound Assessment and Management.

This study evaluated the usability and effectiveness of an artificial intelligence application for wound assessment and management from a clinician-and-patient perspective. A quasi-experimental design was conducted in four settings in an Australian health service. Data were collected from patients in the standard (n=166,243 wounds) and intervention (n=124,184 wounds) group, at baseline and post-intervention. Clinicians completed a survey (n=10) and focus group (n=13) and patients were interviewed (n=4). Wound documentation were analysed descriptively, bivariate statistics determined between-group differences, and interviews were thematically analysed. Compared with the standard group, wound documentation in the intervention group improved significantly (<2 items documented 24% vs 70%, P < .001). During the intervention, 101/132 wounds improved (mean wound size reduction=53.99%). Positive evaluations included instantaneous objective wound assessment, shared wound plans increased patient adherence and enhanced efficiency in providing virtual care. Application use facilitated remote patient monitoring and reduced patient travel time while maintaining optimal wound care.

Cleave and Rescue gamete killers create conditions for gene drive in plants.

Gene drive elements promote the spread of linked traits, even when their presence confers a fitness cost to carriers, and can be used to change the composition or fate of wild populations. Cleave and Rescue (ClvR) drive elements sit at a fixed chromosomal position and include a DNA sequence-modifying enzyme such as Cas9/gRNAs (the Cleaver/Toxin) that disrupts endogenous versions of an essential gene, and a recoded version of the essential gene resistant to cleavage (the Rescue/Antidote). ClvR spreads by creating conditions in which those lacking ClvR die because they lack functional versions of the essential gene. We demonstrate the essential features of ClvR gene drive in the plant Arabidopsis thaliana through killing of gametes that fail to inherit a ClvR that targets the essential gene YKT61, whose expression is required in male and female gametes for their survival. Resistant (uncleavable but functional) alleles, which can slow or prevent drive, were not observed. Modeling shows plant ClvRs are likely to be robust to certain failure modes and can be used to rapidly drive population modification or suppression. Possible applications in plant breeding, weed control, and conservation are discussed.

The interplay between sex, time of day, fasting status, and their impact on cardiac mitochondrial structure, function, and dynamics.

Mitochondria morphology and function, and their quality control by mitophagy, are essential for heart function. We investigated whether these are influenced by time of the day (TOD), sex, and fed or fasting status, using transmission electron microscopy (EM), mitochondrial electron transport chain (ETC) activity, and mito-QC reporter mice. We observed peak mitochondrial number at ZT8 in the fed state, which was dependent on the intrinsic cardiac circadian clock, as hearts from cardiomyocyte-specific BMAL1 knockout (CBK) mice exhibit different TOD responses. In contrast to mitochondrial number, mitochondrial ETC activities do not fluctuate across TOD, but decrease immediately and significantly in response to fasting. Concurrent with the loss of ETC activities, ETC proteins were decreased with fasting, simultaneous with significant increases of mitophagy, mitochondrial antioxidant protein SOD2, and the fission protein DRP1. Fasting-induced mitophagy was lost in CBK mice, indicating a direct role of BMAL1 in regulating mitophagy. This is the first of its kind report to demonstrate the interactions between sex, fasting, and TOD on cardiac mitochondrial structure, function and mitophagy. These studies provide a foundation for future investigations of mitochondrial functional perturbation in aging and heart diseases.

Quantifying interaction with robotic toys in pre-term and full-term infants.

Infants born pre-term are at an increased risk for developmental, behavioral, and motor delay and subsequent disability. When these problems are detected early, clinical intervention can be effective at improving functional outcomes. Current methods of early clinical assessment are resource intensive, require extensive training, and do not always capture infants' behavior in natural play environments. We developed the Play and Neuro Development Assessment (PANDA) Gym, an affordable, mechatronic, sensor-based play environment that can be used outside clinical settings to capture infant visual and motor behavior. Using a set of classification codes developed from the literature, we analyzed videos from 24 pre-term and full-term infants as they played with each of three robotic toys designed to elicit different types of interactions-a lion, an orangutan, and an elephant. We manually coded for frequency and duration of toy interactions such as kicking, grasping, touching, and gazing. Pre-term infants gazed at the toys with similar frequency as full-term infants, but infants born full-term physically engaged more frequently and for longer durations with the robotic toys than infants born pre-term. While we showed we could detect differences between full-term and pre-term infants, further work is needed to determine whether differences seen were primarily due to age, developmental delays, or a combination.

Nomogram for Predicting Risk of Cancer Therapy-Related Cardiac Dysfunction in Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer.

BACKGROUND: Cancer therapy-related cardiac dysfunction (CTRCD) is an important treatment-limiting toxicity for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer that adversely affects cancer and cardiovascular outcomes. Easy-to-use tools that incorporate readily accessible clinical variables for individual estimation of CTRCD risk are needed. METHODS AND RESULTS: From 2004 to 2013, 1440 patients with stage I to III HER2-positive breast cancer treated with trastuzumab-based therapy were identified. A multivariable Cox proportional hazards model was constructed to identify risk factors for CTRCD and included the 1377 patients in whom data were complete. Nine clinical variables, including age, race, body mass index, left ventricular ejection fraction, systolic blood pressure, coronary artery disease, diabetes, arrhythmia, and anthracycline exposure were built into a nomogram estimating risk of CTRCD at 1 year. The nomogram was validated for calibration and discrimination using bootstrap resampling. A total of 177 CTRCD events occurred within 1 year of HER2-targeted treatment. The nomogram for prediction of 1-year CTRCD probability demonstrated good discrimination, with a concordance index of 0.687. The predicted and observed probabilities of CTRCD were similar, demonstrating good model calibration. CONCLUSIONS: A nomogram composed of 9 readily accessible clinical variables provides an individualized 1-year risk estimate of CTRCD among women with HER2-positive breast cancer receiving HER2-targeted therapy. This nomogram represents a simple-to-use tool for clinicians and patients that can inform clinical decision-making on breast cancer treatment options, optimal frequency of cardiac surveillance, and role of cardioprotective strategies.

Synaptic vesicle glycoprotein 2C enhances vesicular storage of dopamine and counters dopaminergic toxicity.

Dopaminergic neurons of the substantia nigra exist in a persistent state of vulnerability resulting from high baseline oxidative stress, high energy demand, and broad unmyelinated axonal arborizations. Impairments in the storage of dopamine compound this stress due to cytosolic reactions that transform the vital neurotransmitter into an endogenous neurotoxicant, and this toxicity is thought to contribute to the dopamine neuron degeneration that occurs Parkinson's disease. We have previously identified synaptic vesicle glycoprotein 2C (SV2C) as a modifier of vesicular dopamine function, demonstrating that genetic ablation of SV2C in mice results in decreased dopamine content and evoked dopamine release in the striatum. Here, we adapted a previously published in vitro assay utilizing false fluorescent neurotransmitter 206 (FFN206) to visualize how SV2C regulates vesicular dopamine dynamics and determined that SV2C promotes the uptake and retention of FFN206 within vesicles. In addition, we present data indicating that SV2C enhances the retention of dopamine in the vesicular compartment with radiolabeled dopamine in vesicles isolated from immortalized cells and from mouse brain. Further, we demonstrate that SV2C enhances the ability of vesicles to store the neurotoxicant 1-methyl-4-phenylpyridinium (MPP+) and that genetic ablation of SV2C results in enhanced 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced vulnerability in mice. Together, these findings suggest that SV2C functions to enhance vesicular storage of dopamine and neurotoxicants, and helps maintain the integrity of dopaminergic neurons.

xenoGI 3: using the DTLOR model to reconstruct the evolution of gene families in clades of microbes.

To understand genome evolution in a group of microbes, we need to know the timing of events such as duplications, deletions and horizontal transfers. A common approach is to perform a gene-tree / species-tree reconciliation. While a number of software packages perform this type of analysis, none are geared toward a complete reconstruction for all families in an entire clade. Here we describe an update to the xenoGI software package which allows users to perform such an analysis using the newly developed DTLOR (duplication-transfer-loss-origin-rearrangement) reconciliation model starting from genome sequences as input.

Impact of Squamous Histology on Clinical Outcomes and Molecular Profiling in Metastatic Urothelial Carcinoma Patients Treated With Immune Checkpoint Inhibitors or Enfortumab Vedotin.

INTRODUCTION: Urothelial carcinoma with squamous differentiation (UCS) is associated with increased resistance to chemotherapy, but outcomes associated with newer therapies approved in this space over the last 5 to 10 years are less well defined. We investigated clinical outcomes and molecular profiling of patients with UCS treated with an immune checkpoint inhibitor (ICI) and/or Enfortumab vedotin (EV). PATIENTS AND METHODS: We undertook a retrospective analysis of UC patients treated with ICI and/or EV. Objective response rate (ORR), progression free survival (PFS) and overall survival (OS) were compared between pure UC (pUC) and UCS using X2 and log-rank tests, respectively. Prevalence of the most commonly detected somatic alterations were also compared between the 2 histologic subgroups. RESULTS: A total of 160 patients (40 UCS, 120 pUC) were identified for this analysis. Among 151 patients treated with ICI (38 UCS, 113 pUC), UCS patients had a shorter mPFS (1.9 vs. 4.8 months, P < 0.01) and mOS (9.2 vs. 20.7 months, P < 0.01) compared to pUC. Among 37 patients treated with EV (12 UCS, 25 pUC), UCS patients had a lower ORR (17% vs. 70%, P < 0.01) and shorter mPFS (3.4 vs. 15.8 months, P < 0.01). UCS samples were enriched for CDKN2A, CDKN2B, PIK3CA, while pUC samples were enriched for ERBB2 alterations. CONCLUSION: In this single-center retrospective analysis, patients with UCS had a distinct somatic genomic profile relative to patients with pUC. Patients with UCS also had inferior outcomes to ICIs and EV compared to patients with pUC.