Ypeginterferon alpha-2b (PegBeron)

Standardized, repeatable ulcerative colitis histology scoring and endpoint assessment using an automated, foundation model-based tool.

Tahir Waleed W, Shamshoian John J, Tauber John J, Clinton Lani K LK et al.

In clinical trials for ulcerative colitis (UC), pathologists assess disease severity through standardized histological indices, including the Geboes Score, Robarts Histopathology Index (RHI), and Nancy Histologic Index (NHI). Despite strong associations with clinical outcomes, histologic scoring suffers from inter- and intra-reader variability, and consensus criteria for histologic remission remain uncertain. Through a consortium approach, we developed an artificial intelligence-based measurement (AIM) tool for scoring histology in UC mucosal biopsies (AIM-HI UC). This model, trained on a large dataset of UC biopsies (N=10,230), utilizes additive multiple instance learning models leveraging PLUTO, a pathology foundation model, that predict each of the Geboes subgrades, from which the Geboes grade-level score, RHI, and NHI can be calculated. Evaluation of this model on a standalone verification set including clinical trial specimens established algorithm non-inferiority and/or superiority relative to standard qualified pathologists through comparison of algorithm-consensus and pathologist-consensus agreement metrics (non-inferior if difference >-0.1, superior if difference >0, inclusive of confidence intervals). AIM-HI UC was determined to be non-inferior to pathologists (N=3) for the prediction of all seven Geboes subgrades, grade-level Geboes, RHI, NHI, histologic improvement (GS < 3.1), 2A histologic remission (GS<2A.0), and 2B histologic remission (GS<2B.0). AIM-HI UC was superior to pathologists for several Geboes subgrades (GS 0, GS 1, GS 2B, and GS 5), as well as grade-level Geboes, RHI, and positive percent agreement of 2A histologic remission. The model was shown to be greater than 99% repeatable for all histologic scoring metrics examined. Model-derived scores were shown to strongly correlate with canonical histologic features of inflammation, including the proportion of total epithelium that is inflamed (Spearman r=0.83; p<0.01), the proportion of neutrophils localized within crypt epithelium (Spearman r=0.83, p<0.01), and the amount of mucosal area classified as erosion or ulceration (Spearman r=0.80, p<0.01). Overall, these results suggest that AIM-HI UC has the potential to improve consistency of UC histology interpretation, providing a path toward standardization of UC histology scoring in clinical trials.

Alterations in Early Alpha-band Connectivity emerge in Infancy among children later diagnosed with Autism.

Chung Haerin H, An Winko W WW, Wilkinson Carol L CL, Davila Mejia Gabriela G et al.

Autism is a heterogeneous neurodevelopmental condition, often accompanied by challenges in language and cognitive development. Although atypical functional connectivity (FC) has been reported in autism, the timing of when it first emerges and its relevance for later behavior remain poorly understood. In this study, we examined developmental trajectories of alpha-band FC and network organization across the first three years of life. We computed global alpha-band measures, including peak alpha connectivity frequency (PACF), mean FC, clustering coefficient, and modularity, to characterize nonlinear developmental trajectories from longitudinal EEGs collected from 238 children (3-36-month-olds) with (Autism; n=58) and without (LL-noAutism; n=180) autism. Network-based statistics (NBS-Predict) identified subnetworks contributing to group differences at each age. Exploratory graph analyses (EGA) examined associations among FC, network measures, and language outcomes. We observed that PACF increased linearly with age in both groups. Global alpha-band connectivity measures showed a similar developmental pattern, with mean global FC, clustering coefficient, and modularity all increasing rapidly during the first year in both groups. Thereafter, these measures declined in the Autism group but continued to gradually increase in the LL-noAutism group. Compared to LL-noAutism, NBS-Predict identified both hyper- and hypo-connectivity subnetworks in Autism at 3 months, followed by a hypo-connectivity subnetwork at 24 and 36 months. EGA indicated that early hyperconnectivity predicted later hypoconnectivity and was associated with subsequent network organization and language outcomes. These findings indicate that altered alpha-band connectivity trajectories are detectable in infancy in children later diagnosed with autism and may contribute to later differences in developmental outcomes.

Effects of Mandala Coloring on Alpha Brain Activity and Anxiety Symptoms among Students at Universiti Sains Malaysia: A Randomized Controlled Trial.

Chang Xin Ni XN, Othman Azizah A, Yusoff Nasir N, Zulkifly Mohd Faizal Mohd MFM

University students commonly experience stress and anxiety, which can negatively affect their academic performance. Mandala coloring has gained attention as a therapeutic art-based activity that may help alleviate symptoms of anxiety. Changes in brain activity, particularly in the alpha power, are known to reflect psychological states and responses to interventions. This study investigated the effects of mandala coloring on alpha brain activity and anxiety symptoms among students at Universiti Sains Malaysia. In a randomized experimental study, sixty students aged 18 to 25 years (M=22.97, SD=1.03) with moderate to high anxiety levels were randomly assigned to either an intervention group (n=30), which colored a geometric mandala for 20 minutes, or a control group (n=30), which colored a blank circle. Brain activity was recorded using electroencephalography (EEG), and anxiety levels were assessed before and after the session using the Malay version of the Beck Anxiety Inventory. Data were analyzed using a mixed-design analysis of variance (ANOVA) with group (intervention vs. control) as the between-subjects factor, and time and brain regions as the within-subjects factor. Both groups showed reductions in anxiety symptoms over time, with no significant differences between groups (F(1; 56)=0.03, p=0.87). However, EEG changes across brain regions differed between groups, with mandala coloring leading to increased frontal alpha power (F(3; 156)=3.21, p=0.03). Mandala coloring was associated with increased frontal alpha power, suggesting enhanced relaxation and focused attention. Anxiety symptoms decreased in both coloring groups, indicating that coloring in general may support emotional regulation and well-being. Taken together, these findings suggest that coloring-based activities may serve as useful therapeutic tools for reducing anxiety and improving focus among university students.

A Novel MAN2B1 Variant in a Child with a Unique Presentation of Alpha-Mannosidosis.

Mittal Payal P, Bhalla Kapil K, Acharya Rohan R, Hotwani Lipika L