Publications by authors named "Anish Simhal"

The rich diversity of synapses facilitates the capacity of neural circuits to transmit, process and store information. We used multiplex super-resolution proteometric imaging through array tomography to define features of single synapses in mouse neocortex. We find that glutamatergic synapses cluster into subclasses that parallel the distinct biochemical and functional categories of receptor subunits: GluA1/4, GluA2/3 and GluN1/GluN2B.

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  • Recent advancements in sequencing tech have improved how we analyze genomic and proteomic data, but we still lack efficient computational tools for large-scale data analysis.
  • To fill this gap, a new bioinformatics tool called Ollivier-Ricci curvature-omics (ORCO) has been developed, which incorporates gene interactions and omic data into a biological network.
  • ORCO calculates Ollivier-Ricci curvature (ORC) values to assess network robustness and gene signaling changes, and it's an open-source Python package available on GitHub for public use.
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  • * Researchers analyzed the MMRF CoMMpass dataset and found that WEE1 expression levels can effectively distinguish between high-risk and low-risk patients, showing a significant difference in progression-free survival (PFS).
  • * The findings suggest that WEE1 expression is an independent prognostic factor for MM and may lead to new therapeutic strategies by exploring the causes of abnormal WEE1 expression.
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  • Multiple myeloma (MM) shows significant variations in genomic traits, treatment responses, and long-term outcomes, prompting researchers to explore global interactions using a large dataset.
  • A novel analysis method, using network robustness metrics, revealed patterns in gene expression that correlate with clinical outcomes and identified high-risk subtypes with poor progression-free survival.
  • This study found 118 aberrantly expressed genes related to immune function and DNA repair, with eight identified as prognostic, highlighting complex immune dysregulation that contributes to shorter survival in MM patients.
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The advance of sequencing technologies has enabled a thorough molecular characterization of the genome in human cancers. To improve patient prognosis predictions and subsequent treatment strategies, it is imperative to develop advanced computational methods to analyze large-scale, high-dimensional genomic data. However, traditional machine learning methods face a challenge in handling the high-dimensional, low-sample size problem that is shown in most genomic data sets.

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Background: Heterogeneous mental health outcomes during the COVID-19 pandemic are documented in the general population. Such heterogeneity has not been systematically assessed in youth with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). To identify distinct patterns of the pandemic impact and their predictors in ASD/NDD youth, we focused on pandemic-related changes in symptoms and access to services.

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Introduction: Stereotactic Body Radiation Therapy (SBRT) has emerged as a definitive therapy for localized prostate cancer (PCa). However, more data is needed to predict patient prognosis to help guide which patients will benefit most from treatment. The FACIT-Fatigue (FACIT-F) is a well validated, widely used survey for assessing fatigue.

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Diffusion tensor imaging (DTI) has been used as an outcome measure in clinical trials for several psychiatric disorders but has rarely been explored in autism clinical trials. This is despite a large body of research suggesting altered white matter structure in autistic individuals. The current study is a secondary analysis of changes in white matter connectivity from a double-blind placebo-control trial of a single intravenous cord blood infusion in 2-7-year-old autistic children (1).

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  • Pediatric brain imaging is valuable for understanding neurodevelopment, but challenges like staying still in noisy MRI scanners can hinder the process.
  • This study involved 250 children with autism and/or ADHD who underwent simulator training to adapt to the scanner environment, with high initial success rates in completing scans.
  • Age emerged as the most significant predictor of success, with younger children struggling more, while sensorimotor atypicalities also played a role in outcomes.
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Ollivier-Ricci curvature is a method for measuring the robustness of connections in a network. In this work, we use curvature to measure changes in robustness of brain networks in children with autism spectrum disorder (ASD). In an open label clinical trials, participants with ASD were administered a single infusion of autologous umbilical cord blood and, as part of their clinical outcome measures, were imaged with diffusion MRI before and after the infusion.

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Fragile X Syndrome (FXS), a common inheritable form of intellectual disability, is known to alter neocortical circuits. However, its impact on the diverse synapse types comprising these circuits, or on the involvement of astrocytes, is not well known. We used immunofluorescent array tomography to quantify different synaptic populations and their association with astrocytes in layers 1 through 4 of the adult somatosensory cortex of a FXS mouse model, the FMR1 knockout mouse.

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Goal: In this paper, we propose methods for (1) automatic feature extraction and classification for acetic acid and Lugol's iodine cervigrams and (2) methods for combining features/diagnosis of different contrasts in cervigrams for improved performance.

Methods: We developed algorithms to pre-process pathology-labeled cervigrams and extract simple but powerful color and textural-based features. The features were used to train a support vector machine model to classify cervigrams based on corresponding pathology for visual inspection with acetic acid, visual inspection with Lugol's iodine, and a combination of the two contrasts.

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Application-specific validation of antibodies is a critical prerequisite for their successful use. Here we introduce an automated framework for characterization and screening of antibodies against synaptic molecules for high-resolution immunofluorescence array tomography (AT). The proposed Synaptic Antibody Characterization Tool (SACT) is designed to provide an automatic, robust, flexible, and efficient tool for antibody characterization at scale.

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Deeper exploration of the brain's vast synaptic networks will require new tools for high-throughput structural and molecular profiling of the diverse populations of synapses that compose those networks. Fluorescence microscopy (FM) and electron microscopy (EM) offer complementary advantages and disadvantages for single-synapse analysis. FM combines exquisite molecular discrimination capacities with high speed and low cost, but rigorous discrimination between synaptic and non-synaptic fluorescence signals is challenging.

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