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The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs.

In recent years, commercially available dexterous upper limb prostheses for children have begun to emerge. These devices derive control signals from surface electromyography (measure of affected muscle electrical activity, sEMG) to drive a variety of grasping motions. However, the ability for children with congenital upper limb deficiency to actuate their affected muscles to achieve naturalistic prosthetic control is not well understood, as compared to adults or children with acquired hand loss. To address this gap, we collected sEMG data from 9 congenital one-handed participants ages 8-20 years as they envisioned and attempted to perform 10 different movements with their missing hands. Seven sEMG electrodes were adhered circumferentially around the participant's affected and unaffected limbs and participants mirrored the attempted missing hand motions with their intact side. To analyze the collected sEMG data, we used time and frequency domain analyses. We found that for the majority of participants, attempted hand movements produced detectable and consistent muscle activity, and the capacity to achieve this was not dissimilar across the affected and unaffected sides. These data suggest that children with congenital hand absence retain a degree of control over their affected muscles, which has important implications for translating and refining advanced prosthetic control technologies for children.

Children with a unilateral congenital below elbow deficiency (UCBED) have one typical upper limb and one that lacks a hand, ending below the elbow at the proximal/mid forearm. UCBED is an isolated condition, and affected children otherwise develop normal sensorimotor control. Unlike adults with upper limb absence, the majority of whom have an acquired loss, children with UCBED never developed a hand, so their residual muscles have never actuated an intact limb. Their ability to purposefully modulate affected muscle activity is often assumed to be limited, and this assumption has influenced prosthetic design and prescription practices for this population as many modern devices derive control signals from affected muscle activity. To better understand the motor capabilities of the affected muscles, we used ultrasound imaging to study 6 children with UCBED. We examined the extent to which subjects activate their affected muscles when performing mirrored movements with their typical and missing hands. We demonstrate that all subjects could intentionally and consistently enact at least five distinct muscle patterns when attempting different missing hand movements (e.g., power grasp) and found similar performance across affected and typically developed limbs. These results suggest that although participants had never actuated the missing hand they could distinctively and consistently activate the residual muscle patterns associated with actions on the unaffected side. These findings indicate that motor control still develops in the absence of the normal effector, and can serve as a guide for developing prostheses that leverage the full extent of these children's motor control capabilities.

We identified a de novo heterozygous transient receptor potential cation channel subfamily M (melastatin) member 3 (TRPM3) missense variant, p.(Asn1126Asp), in a patient with developmental delay and manifestations of cerebral palsy (CP) using phenotype-driven prioritization analysis of whole-genome sequencing data with Exomiser. The variant is localized in the functionally important ion transport domain of the TRPM3 protein and predicted to impact the protein structure. Our report adds TRPM3 to the list of Mendelian disease-associated genes that can be associated with CP and provides further evidence for the pathogenicity of the variant p.(Asn1126Asp).

MOTIVATION: Methods for concept recognition (CR) in clinical texts have largely been tested on abstracts or articles from the medical literature. However, texts from electronic health records (EHRs) frequently contain spelling errors, abbreviations, and other nonstandard ways of representing clinical concepts. RESULTS: Here, we present a method inspired by the BLAST algorithm for biosequence alignment that screens texts for potential matches on the basis of matching k-mer counts and scores candidates based on conformance to typical patterns of spelling errors derived from 2.9 million clinical notes. Our method, the Term-BLAST-like alignment tool (TBLAT) leverages a gold standard corpus for typographical errors to implement a sequence alignment-inspired method for efficient entity linkage. We present a comprehensive experimental comparison of TBLAT with five widely used tools. Experimental results show an increase of 10% in recall on scientific publications and 20% increase in recall on EHR records (when compared against the next best method), hence supporting a significant enhancement of the entity linking task. The method can be used stand-alone or as a complement to existing approaches. AVAILABILITY AND IMPLEMENTATION: Fenominal is a Java library that implements TBLAT for named CR of Human Phenotype Ontology terms and is available at https://github.com/monarch-initiative/fenominal under the GNU General Public License v3.0.

AimTo assess the accuracy, reliability, and discriminatory ability of a mobile app for measurement of migration percentage in hip surveillance radiographs of children with cerebral palsy (CP).MethodThe free mobile app HipScreen (www.hipscreen.org) was utilized by a diverse group of users to measure the migration percentage of 40 hips at two time points after completing an online tutorial and competency test. The mean absolute error (MAE) was calculated against the reference standard obtained on a radiology workstation. Statistical analyses included linear regression, intraclass correlation coefficient (ICC), and area under receiver-operating characteristic curve (AUC).ResultsThirty-seven users completed the study, with 30 having a healthcare professional background, but only 15 with x-ray interpretation expertise. The overall MAE of migration percentage measurement using the HipScreen app was 5.72% (95% confidence interval [CI]: 5.38-6.06), with good reliability between time points (ICC = 0.83). With a migration percentage less than 30% considered as a positive case, the HipScreen app had a sensitivity of 94% (95% CI: 87-97), specificity of 66% (95% CI: 61-77), and an AUC of 0.92 (95% CI: 0.88-0.96).InterpretationUsers from a broad range of backgrounds can utilize the HipScreen app to measure hip surveillance radiographs with clinically acceptable accuracy, reliability, and discriminatory ability.What this paper addsThe HipScreen app can accurately and reliably measure migration percentage. As a screening tool, HipScreen has excellent sensitivity and discriminatory ability. A broad range of HipScreen users achieve clinically acceptable performance.

Cerebral palsy (CP) is the most common pediatric motor disability in the United States of America today and has been associated with many etiologies. Literature on Cerebral Palsy and Social Determinants of Health (SDoH) is lacking, even though it is a crucial component of medicine. There is little evidence analyzing that the effect of socioeconomic status (SES) based on area-based analysis and the prevalence and severity of CP. The relationship between zip code tabulation areas and CP prevalence or severity is unknown.

Neurotypically developing children who toe walk usually spontaneously resolve by school age, those who do not are considered to have Persistent Idiopathic Toe Walking (ITWp) and may develop ankle contractures and foot skeletal deformities. Alvarez et al. proposed a classification scheme in 2006. When it was applied to our cohort, it failed to classify many subjects due to ambiguity in the classification scheme definitions

Cerebral Palsy• Cerebral palsy (CP) is the most common motor disability of childhood.• CP patients often experience motor disorders causing activity limitation along with disturbances of sensation, perception, cognition, communication, and behavior. Patients may also experience epilepsy and secondary musculoskeletal issues.• The clinical manifestations of CP vary greatly from patient to patient and there is a wide array of development, level of functioning, and social comfort among the CP population.

It has been noted that tripping and falling are the greatest source of accidental injury in children with motor disabilities[1]. Tripping most commonly occurs due to a decrease in foot clearance or ineffective limb shortening during the swing phase of gait. Moosabhoy and Gard developed equations based on a planar model of the leg to look directly at joint contributions to foot clearance in the adult population (Fig. 1)[2]. We modified and applied the analytical techniques used by Moosabhoy and Gard to analyze a new population of patients.

By the age of 3, most children develop a mature gait pattern, defined as plantigrade use of the foot with weightbearing through both the heel and metatarsal heads.Children with idiopathic toewalking (ITW) are otherwise neurologically normal but preferentially walk on their tiptoes. ITW resolves in most cases by 6 years of age.Children with persistent ITW (ITWp) may develop ankle contractures and foot skeletal deformities.The Alvarez criteria was established in 2006 and has since been the standard classification for ITWp based

BackgroundClinical assessment of thumb motion is challenging, due to the complex anatomy and motion of the thumb. It is especially difficult to measure hand movement during activity, and to measure the effects of surgery that changes the morphology of the thumb. A three-dimensional model of the hand may enable clinicians to better assess prehension and thumb motion at baseline, and following surgical intervention.MethodsA kinematic model of the hand was developed to measure thumb and finger position during functional tasks, enabling the calculation of the volume of space in which prehension could occur. This method was validated by application to a mechanical model of the hand, and then applied to ten adult participants, using three-dimensional motion analysis with a marker array developed for the purpose of this study.FindingsThis method can be used to accurately measure three-dimensional thumb joint range of motion (RoM) and predicted functional workspace during functional activities. The thumb carpometacarpal joint was predominantly responsible for thumb position during functional tasks. Predicted functional workspace is proportional to hand morphometric measurements.InterpretationA kinematic model of the hand measures thumb RoM and predicts functional workspace during functional activities.

Aim: Children and adolescents highly value their ability to participate in relevant daily life and recreational activities. The Activities Scale for Kids-performance (ASKp) instrument measures the frequency of performance of 30 common childhood activities, and has been shown to be valid and reliable. A revised and expanded 38-item ASKp (ASKp38) version has been reported in recent literature and is currently used in clinical research. The aim of this paper is to assess the factor structure and item-level statistics of the ASKp38. Method: Our study used factor analyses and Rasch analyses to determine the item-set dimensionality and to calculate item-level statistics respectively, for existing ASKp38 data from 200 children (104 males; 96 females; mean age 12y 7mo; SD 2y 8mo; range 6-20y) with physical disabilities. The children had a variety of physical impairments including cerebral palsy (n=105; range 8-13y), limb salvage (n=18; range 11-20y), arthrogryposis (n=13; 6-17y), and other, including individuals with spina bifida and spinal cord injury (n=64; 8-19y). Results: A two-factor model, with components of activities of daily living and play, most optimally fit the data. Item-fit statistics based on this two-factor model demonstrated adequate fit and content coverage. Interpretation: The ASKp38 appears to consist of two factors, defined as (1) activities of daily living and (2) play, and may be used to measure the frequency of activity performance on two corresponding subscales.

Aim: To test a model of child, family, and service determinants of intensity of participation in leisure and recreational activities by children with cerebral palsy (CP). Method: Participants were 288 children with CP, age range 6 to 12 years (mean 9y 8mo, SD 2y), and their parents from seven children's hospitals. The sample comprised 166 (57.6%) males and 122 (42.4%) females, and between 40 (13.9%) and 74 (25.7%) children in each of the five levels of the Gross Motor Function Classification System. Children completed the Children's Assessment of Participation and Enjoyment by interview. Parents completed the Pediatric Outcomes Data Collection Instrument, Family Environment Scale, Coping Inventory, Measure of Processes of Care, and two questionnaires. Structural equation modeling was used to test the model. Results: Fit statistics indicated a good model fit. The model explains 32% of the variance in intensity of participation. Path coefficients (p less than or equal to 0.05) indicate that higher gross motor function, higher enjoyment, more effective adaptive behavior, younger age, and higher family activity orientation are associated with higher intensity of participation. The path between services and participation was not significant. Interpretation: Intensity of participation of children with CP is influenced by multiple child and family determinants. Children's gross motor function and behavior in life situations are important for participation; knowledge of activities the child and family enjoy has implications for opportunities for participation. Professionals are encouraged to address priorities for leisure and recreation identified by children with CP and their families.

Discriminatory ability of several pediatric outcome tools was assessed relative to Gross Motor Function Classification System (GMFCS) level in patients with cerebral palsy. Five hundred and sixty-two patients (400 with diplegia, 162 with hemiplegia; 339 males, 223 females; age range 4-18y, mean 11y 1mo [SD 3y 7mo]), classified as GMFCS Levels I to III, participated in this prospective multicenter, cross-sectional study. All tools were completed by parents and participants when appropriate. Effect size indices (ESIs) for parametric variables and odds ratios for non-parametric data quantified the magnitude of differences across GMFCS levels. Binary logistic regression models determined discrimination, and receiver operating characteristic curves addressed sensitivity and specificity. Between Levels I and II, the most discriminatory tools were Gross Motor Function Measure (GMFM-66), velocity, and WeeFIM Mobility. Between Levels II and III, the most discriminatory tools were GMFM Dimension E, Pediatric Functional Independence Measure (WeeFIM) Self-Care and Mobility, cadence, and Gillette Functional Assessment Questionnaire Question 1. Large ESIs were noted for Parent and Child reports of Pediatric Outcomes Data Collection Instrument (PODCI) Sports & Physical Function, Parent report of PODCI Global Function, GMFM Dimension E, and GMFM-66 across all GMFCS level comparisons. The least discriminatory tools were the Quality of Life and cognition measures; however, these are important in comprehensive assessments of treatment effects. (Contains 4 tables and 3 figures.)