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Patients with rare diseases often experience prolonged diagnostic delays. Ordering appropriate genetic tests is crucial yet challenging, especially for general pediatricians without genetic expertise. Recent American College of Medical Genetics (ACMG) guidelines embrace early use of exome sequencing (ES) or genome sequencing (GS) for conditions like congenital anomalies or developmental delays while still recommend gene panels for patients exhibiting strong manifestations of a specific disease. Recognizing the difficulty in navigating these options, we developed a machine learning model trained on 1005 patient records from Columbia University Irving Medical Center to recommend appropriate genetic tests based on the phenotype information. The model achieved a remarkable performance with an AUROC of 0.823 and AUPRC of 0.918, aligning closely with decisions made by genetic specialists, and demonstrated strong generalizability (AUROC:0.77, AUPRC: 0.816) in an external cohort, indicating its potential value for general pediatricians to expedite rare disease diagnosis by enhancing genetic test ordering., Competing Interests: Competing interests: W.C. is on the Board of Directors of both Prime Medicine and Rallybio. Other authors declare no financial competing interests., (© 2024. The Author(s).)

Background: Comorbidity is common and causes poor stroke outcomes. We aimed to examine the modifying impacts of physical activity (PA) and diet quality on the association between comorbidity and disability in stroke patients., Methods: A cross-sectional study was conducted on 951 stable stroke patients in Vietnam from December 2019 to December 2020. The survey questionnaires were administered to assess patients' characteristics, clinical parameters (e.g., Charlson Comorbidity Index items), health-related behaviors (e.g., PA using the International Physical Activity Questionnaire- short version), health literacy, diet quality (using the Dietary Approaches to Stop Hypertension Quality (DASH-Q) questionnaire), and disability (using the World Health Organization Disability Assessment Schedule II (WHODAS II)). Linear regression models were used to analyze the associations and interactions., Results: The proportion of comorbidity was 49.9% (475/951). The scores of DASH-Q and WHODAS II were 29.2 ± 11.8, 32.3 ± 13.5, respectively. Patients with comorbidity had a higher score of disability (regression coefficient, B, 8.24; 95% confidence interval, 95%CI, 6.66, 9.83; p < 0.001) as compared with those without comorbidity. Patients with comorbidity and higher tertiles of PA (B, -4.65 to -5.48; p < 0.05), and a higher DASH-Q score (B, -0.32; p < 0.001) had a lower disability score, as compared with those without comorbidity and the lowest tertile of PA, and the lowest score of DASH-Q, respectively., Conclusions: Physical activity and diet quality significantly modified the negative impact of comorbidity on disability in stroke patients. Strategic approaches are required to promote physical activity and healthy diet which further improve stroke rehabilitation outcomes.

Objective: Demyelination that results from disease or traumatic injury, such as spinal cord injury (SCI), can have a devastating effect on neural function and recovery. Many researchers are examining treatments to minimize demyelination by improving oligodendrocyte availability in vivo. Transplantation of stem and oligodendrocyte progenitor cells is a promising option, however, trials are plagued by undirected differentiation. Here we introduce a biomaterial that has been optimized to direct the differentiation of neural progenitor cells (NPCs) toward oligodendrocytes as a cell delivery vehicle after SCI., Approach: A collagen-based hydrogel was modified to mimic the mechanical properties of the neonatal spinal cord, and components present in the developing extracellular matrix were included to provide appropriate chemical cues to the NPCs to direct their differentiation toward oligodendrocytes. The hydrogel with cells was then transplanted into a unilateral cervical contusion model of SCI to examine the functional recovery with this treatment. Six behavioral tests and histological assessment were performed to examine the in vivo response to this treatment., Main Results: Our results demonstrate that we can achieve a significant increase in oligodendrocyte differentiation of NPCs compared to standard culture conditions using a three-component biomaterial composed of collagen, hyaluronic acid, and laminin that has mechanical properties matched to those of neonatal neural tissue. Additionally, SCI rats with hydrogel transplants, with and without NPCs, showed functional recovery. Animals transplanted with hydrogels with NPCs showed significantly increased functional recovery over six weeks compared to the media control group., Significance: The three-component hydrogel presented here has the potential to provide cues to direct differentiation in vivo to encourage regeneration of the central nervous system.

We study n-pulse interaction in fast collisions of N solitons of the cubic nonlinear Schrödinger (NLS) equation in the presence of generic weak nonlinear loss. We develop a generalized reduced model that yields the contribution of the n-pulse interaction to the amplitude shift for collisions in the presence of weak (2m+1)-order loss, for any n and m. We first employ the reduced model and numerical solution of the perturbed NLS equation to analyze soliton collisions in the presence of septic loss (m=3). Our calculations show that the three-pulse interaction gives the dominant contribution to the collision-induced amplitude shift already in a full-overlap four-soliton collision, and that the amplitude shift strongly depends on the initial soliton positions. We then extend these results for a generic weak nonlinear loss of the form G(|ψ|2)ψ, where ψ is the physical field and G is a Taylor polynomial of degree mc. Considering mc=3, as an example, we show that three-pulse interaction gives the dominant contribution to the amplitude shift in a six-soliton collision, despite the presence of low-order loss. Our study quantitatively demonstrates that n-pulse interaction with high n values plays a key role in fast collisions of NLS solitons in the presence of generic nonlinear loss. Moreover, the scalings of n-pulse interaction effects with n and m and the strong dependence on initial soliton positions lead to complex collision dynamics, which is very different from that observed in fast NLS soliton collisions in the presence of cubic loss.

We investigate the statistics of flat-top solitary wave parameters in the presence of weak multiplicative dissipative disorder. We consider first propagation of solitary waves of the cubic-quintic nonlinear Schrödinger equation (CQNLSE) in the presence of disorder in the cubic nonlinear gain. We show by a perturbative analytic calculation and by Monte Carlo simulations that the probability-density function (PDF) of the amplitude eta exhibits loglognormal divergence near the maximum possible amplitude eta(m), a behavior that is similar to the one observed earlier for disorder in the linear gain [A. Peleg, Phys. Rev. E 72, 027203 (2005)]. We relate the loglognormal divergence of the amplitude PDF to the superexponential approach of eta to eta(m) in the corresponding deterministic model with linear/nonlinear gain. Furthermore, for solitary waves of the derivative CQNLSE with weak disorder in the linear gain both the amplitude and the group velocity beta become random. We therefore study analytically and by Monte Carlo simulations the PDF of the parameter p, where p = eta/(1-epsilon(s)beta/2) and epsilon(s) is the self-steepening coefficient. Our analytic calculations and numerical simulations show that the PDF of p is loglognormally divergent near the maximum p value.