Publications by authors named "Rohan Gala"

Alzheimer's disease (AD) is the leading cause of dementia in older adults. Although AD progression is characterized by stereotyped accumulation of proteinopathies, the affected cellular populations remain understudied. Here we use multiomics, spatial genomics and reference atlases from the BRAIN Initiative to study middle temporal gyrus cell types in 84 donors with varying AD pathologies.

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Reproducible definition and identification of cell types is essential to enable investigations into their biological function and to understand their relevance in the context of development, disease and evolution. Current approaches model variability in data as continuous latent factors, followed by clustering as a separate step, or immediately apply clustering on the data. We show that such approaches can suffer from qualitative mistakes in identifying cell types robustly, particularly when the number of such cell types is in the hundreds or even thousands.

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Neuronal anatomy is central to the organization and function of brain cell types. However, anatomical variability within apparently homogeneous populations of cells can obscure such insights. Here, we report large-scale automation of neuronal morphology reconstruction and analysis on a dataset of 813 inhibitory neurons characterized using the Patch-seq method, which enables measurement of multiple properties from individual neurons, including local morphology and transcriptional signature.

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The mammalian brain is composed of diverse neuron types that play different functional roles. Recent single-cell RNA sequencing approaches have led to a whole brain taxonomy of transcriptomically-defined cell types, yet cell type definitions that include multiple cellular properties can offer additional insights into a neuron's role in brain circuits. While the Patch-seq method can investigate how transcriptomic properties relate to the local morphological and electrophysiological properties of cell types, linking transcriptomic identities to long-range projections is a major unresolved challenge.

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Reproducible definition and identification of cell types is essential to enable investigations into their biological function, and understanding their relevance in the context of development, disease and evolution. Current approaches model variability in data as continuous latent factors, followed by clustering as a separate step, or immediately apply clustering on the data. We show that such approaches can suffer from qualitative mistakes in identifying cell types robustly, particularly when the number of such cell types is in the hundreds or even thousands.

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Introduction: Rosai-Dorfman Disease (RDD) is a rare benign histiocytic disease that infrequently affects the spine. We report two cases of spinal RDD and review the relevant literature. This report addresses the various diagnostic dilemmas related to the evaluation of Spinal RDD and its treatment.

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Alzheimer's disease (AD) is the most common cause of dementia in older adults. Neuropathological and imaging studies have demonstrated a progressive and stereotyped accumulation of protein aggregates, but the underlying molecular and cellular mechanisms driving AD progression and vulnerable cell populations affected by disease remain coarsely understood. The current study harnesses single cell and spatial genomics tools and knowledge from the BRAIN Initiative Cell Census Network to understand the impact of disease progression on middle temporal gyrus cell types.

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A prominent trend in single-cell transcriptomics is providing spatial context alongside a characterization of each cell's molecular state. This typically requires targeting an a priori selection of genes, often covering less than 1% of the genome, and a key question is how to optimally determine the small gene panel. We address this challenge by introducing a flexible deep learning framework, PERSIST, to identify informative gene targets for spatial transcriptomics studies by leveraging reference scRNA-seq data.

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Reference cell atlases powered by single cell and spatial transcriptomics technologies are becoming available to study healthy and diseased tissue at single cell resolution. One important use of these data resources is to compare cell types from new dataset with cell types in the reference atlases to evaluate their phenotypic similarities and differences, for example, for identifying novel cell types under disease conditions. For this purpose, rigorously-validated computational algorithms are needed to perform these cell type matching tasks that can compare datasets from different experiment platforms and sample types.

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Introduction: Leiomyomas are benign epithelial tumors with a female preponderance usually in the uterus, gastro-intestinal tract and skin. They are well-capsulated tumors with no mitotic activity and little pleomorphism. Primary leiomyoma in the upper cervical spine region is rare and the occurrence of these lesions in young immunocompetent males is extremely rare.

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Introduction: Vertebral hemangiomas although benign vascular lesions few of these may be ag-gressive causing osseous, extra-osseous and/or epidural expansions with recurrence rate as low as 3%. It should be considered as one of the important differentials while dealing with lytic lesions in the dorsal spine causing compressive myelopathy.

Case Report: A 16-year-old female came with an acute history of paraparesis with bladder in-volvement.

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Purpose: We retrospectively analyzed a cohort of patients treated at our Centre with bone marrow concentrated (BMC) injection for aneurysmal bone cyst (ABC) of the spine, in order to propose this treatment as a valid alternative for the management of ABCs.

Methods: Fourteen patients (6 male, 8 female) were treated between June 2014 to December 2019 with BMC injection for ABC of the spine. The mean age was 15.

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Purpose: Management of vertebral and discovertebral lesions depends on highly specific modalities like biopsy and histopathology. The transpedicular and transforaminal routes have gained popularity for obtaining samples for diagnosing these lesions. Sample inadequacy plays an important part in lowering the diagnostic accuracy.

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Consistent identification of neurons in different experimental modalities is a key problem in neuroscience. Although methods to perform multimodal measurements in the same set of single neurons have become available, parsing complex relationships across different modalities to uncover neuronal identity is a growing challenge. Here we present an optimization framework to learn coordinated representations of multimodal data and apply it to a large multimodal dataset profiling mouse cortical interneurons.

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Neurons are frequently classified into distinct types on the basis of structural, physiological, or genetic attributes. To better constrain the definition of neuronal cell types, we characterized the transcriptomes and intrinsic physiological properties of over 4,200 mouse visual cortical GABAergic interneurons and reconstructed the local morphologies of 517 of those neurons. We find that most transcriptomic types (t-types) occupy specific laminar positions within visual cortex, and, for most types, the cells mapping to a t-type exhibit consistent electrophysiological and morphological properties.

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Background: Osteoid osteomas (OOs) are benign bone forming tumors that, usually, occur in the extremities, with about 10% of them arising in the spine more commonly in the posterior elements. The aim of this study is to evaluate the long-term results of patients suffering from spinal OO treated with surgery and radiofrequency ablation.

Methods: This was a retrospective comparison analysis of data prospectively collected from 2 cohorts of consecutive patients diagnosed with OO of the spine treated at the same Institute from November 2002 to February 2019.

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Article Synopsis
  • The study analyzes a large single-cell RNA-seq dataset from mouse neocortical neurons, revealing insights into the complex networks that help maintain and adapt cortical function.
  • Researchers found numerous unique neuropeptidergic systems interconnecting nearly all cortical neurons, indicating extensive local signaling mechanisms.
  • The findings provide a foundation for predicting the roles of 37 specific neuropeptide signaling networks in regulating cortical homeostasis and plasticity.
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Study Design: Cadaveric, observational study.

Purpose: Atlantoaxial instability (AAI) is characterized by excessive movement at the C1-C2 junction between the atlas and axis. An anterior surgical approach to expose the upper cervical spine for internal fixation and bone grafting has been developed to fix AAI.

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A 70 years old lady presented to us with history of a fall 3 months prior. She had suffered a type 2 odontoid fracture with atlantoaxial dislocation, that was not reducible by traction. She had symptoms of neck pain with inability to hold the neck upright.

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Introduction: Pseudoaneurysms of arteries are not uncommon complications of vessel handling during surgery. Early identification and management is important to prevent disastrous complications such as rupture and thrombosis.

Case Report: We describe a case of a 28-year-old male who developed a pseudoaneurysm of the radial artery after being operated by plating for a mid-shaft radius fracture.

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The ability to measure minute structural changes in neural circuits is essential for long-term in vivo imaging studies. Here, we propose a methodology for detection and measurement of structural changes in axonal boutons imaged with time-lapse two-photon laser scanning microscopy (2PLSM). Correlative 2PLSM and 3D electron microscopy (EM) analysis, performed in mouse barrel cortex, showed that the proposed method has low fractions of false positive/negative bouton detections (2/0 out of 18), and that 2PLSM-based bouton weights are correlated with their volumes measured in EM ( = 0.

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Objective: To determine the entry for the dorsal pedicular screw in relation to the notch present at the junction of base of the lateral margin of superior articular process with superior border of transverse process in dorsal spine. The advantage of this technique is a constant and easily identifiable entry point which does not involve partial resection of the inferior facet, thus maintaining stability and maintaining the well defined transverse and sagittal screw angles and decreasing the incidence of medial and inferior pedicle violation.

Materials And Methods: The study was carried out using ten cadavers (four male and six female).

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The impact of learning and long-term memory storage on synaptic connectivity is not completely understood. In this study, we examine the effects of associative learning on synaptic connectivity in adult cortical circuits by hypothesizing that these circuits function in a steady-state, in which the memory capacity of a circuit is maximal and learning must be accompanied by forgetting. Steady-state circuits should be characterized by unique connectivity features.

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Synopsis of recent research by authors named "Rohan Gala"

  • - Rohan Gala’s recent research emphasizes the application of multimodal and single-cell approaches to study complex neurodegenerative diseases like Alzheimer's, aiming to build detailed cell atlases that elucidate cellular heterogeneity and functional roles within the brain.
  • - Gala's work critically addresses methodological challenges in identifying cell types and their variability in large datasets, introducing novel frameworks like MMIDAS and PERSIST to enhance robustness in cell classification and gene selection for spatial transcriptomics.
  • - The integration of transcriptomic, spatial, and anatomical data through advanced techniques such as Patch-seq in his studies is paving the way for better understanding of neuronal morphology, aiding in linking cellular identities to their functional projections in brain circuitry.

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