Form in Darkness: Linking Visual Cortex Structure With Spontaneous Neural Function

Spontaneous neural activity within visual cortex is synchronized at varying spatial scales, from the cytoarchitecural level of individual neurons to the coarse scale of whole regions. The neural basis of this synchronicity remains ambiguous. In this thesis, we focus on the role visual experience plays in organizing the spontaneous activity within the visual system. We start in Chapter 2 by creating a means by which to analyze homologous patches of cortex between sighted and blind individuals, as lack of vision precludes the use of traditional stimulus-driven mapping techniques. We find that anatomy alone could indeed predict the retinotopic organization of an individual\u27s striate cortex with an accuracy equivalent to the length of a typical mapping experiment. Chapter 3 applies this approach to analyze the organization of spontaneous signals within the striate cortex of blind and sighted subjects. We find that lack of visual experience produces a subtle change in the pattern of corticocortico correlations only between the hemispheres, and that these correlations are best modeled as function of cortical distance, not retinotopy. Chapter 4 expands our analysis to include areas V2 and V3. Here, we find that persistent visual experience supports network-level neural synchrony between spatially distributed cortical visual areas at both a coarse (regional) and fine (topographic) scale. Together, these results allow us model the organization of spontaneous activity in visual cortex as a combination of network signals linked to visual function and intrinsic signals coupled to structural connections. In the final chapter, we examine possible top-down mediators that may further modulate this network-level correlation. Minimal change in synchronicity is observed in a subject with a corpus callosotomy, suggesting the preeminence of bottom-up inputs. Taken together, this work advances our understanding of the origins of coherent spontaneous neural activity within visual cortex

Minecraft in education benefits learning and social engagement

Empirical evidence suggests game-based learning (GBL) as a potentially engaging form of contemporary learning. With the increase in the use of Minecraft, a sandbox computer game in open-world format, there has been a concurrent rise in the level of interest in investigating the role of Minecraft in social and academic learning. Minecraft is socially interactive, and its cooperative, rather than competitive, open-world gameplay suggests that it could be used for educational purposes. This paper presents a systematic review of all published peer-reviewed research and synthesises the evidence for and against Minecraft's use in education to better understand the applicability of Minecraft in educational and psychological interventions. Forty-two papers were identified. These revealed Minecraft to be beneficial in terms of increased motivation, language development, and academic learning in subjects such as science and history. Minecraft play also supported the development of social skills, including communication, sharing, collaboration, and leadership. Concerns about age-appropriateness, safety, technology use, and learning generalisation were raised, but on balance, the evidence favours an informed and guided employment of Minecraft for improved opportunities for learning and engagement in education

Case report: Real-world experience using a personalized cancer-specific circulating tumor DNA assay in different metastatic melanoma scenarios

Circulating-tumor DNA (ctDNA) has emerged as an important biomarker for monitoring disease status in cancer patients. Different ctDNA testing platforms have shown promising results in the early detection of disease, monitoring response to treatment, and prognostication in metastatic melanoma. However, several challenges exist, including the reduced shedding of ctDNA into the bloodstream in the metastatic setting, differences in sensitivity among various ctDNA assays, and the inherent inability to distinguish tumor-specific mutations from other mutations that are not related to the cancer of interest. Using a ctDNA assay that is designed to detect multiple single-nucleotide variants (SNVs) that are specific to the tumor itself may allow for more accurate monitoring of disease status in metastatic melanoma. In this case series, we describe a real-world experience using a personalized, tumor-informed ctDNA assay to monitor the clinical trajectories of four patients with metastatic melanoma. Our report highlights potential benefits and limitations using ctDNA in this setting to inform clinical decision-making. This report provides a proof of concept of the technique using an mPCR-NGS-based ctDNA assay (Signater

Identification and management of aggressive meningiomas

Meningiomas are common primary central nervous system tumors derived from the meninges, with management most frequently entailing serial monitoring or a combination of surgery and/or radiation therapy. Although often considered benign lesions, meningiomas can not only be surgically inaccessible but also exhibit aggressive growth and recurrence. In such cases, adjuvant radiation and systemic therapy may be required for tumor control. In this review, we briefly describe the current WHO grading scale for meningioma and provide demonstrative cases of treatment-resistant meningiomas. We also summarize frequently observed molecular abnormalities and their correlation with intracranial location and recurrence rate. We then describe how genetic and epigenetic features might supplement or even replace histopathologic features for improved identification of aggressive lesions. Finally, we describe the role of surgery, radiotherapy, and ongoing systemic therapy as well as precision medicine clinical trials for the treatment of recurrent meningioma

A systematic framework for predictive biomarkers in immune effector cell-associated neurotoxicity syndrome

Chimeric antigen receptor (CAR)-T cell therapy has revolutionized the management of several life-threatening malignancies, often achieving durable sustained responses. The number of patients treated with this new class of cell-based therapy, along with the number of Food and Drug Association (FDA) approved indications, are growing significantly. Unfortunately Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) can often occur after treatment with CAR-T cells, and severe ICANS can be associated with significant morbidity and mortality. Current standard treatments are mainly steroids and supportive care, highlighting the need for early identification. In the last several years, a range of predictive biomarkers have been proposed to distinguish patients at increased risk for developing ICANS. In this review, we discuss a systematic framework to organize potential predictive biomarkers that builds on our current understanding of ICANS

The impact of online computer games on mental health of children with autism or hearing loss

This study examined the role of online computer games in mental health and relationships skills for children with Autism Spectrum Disorder (ASD) or Hearing Loss (HL) compare to typical developing children (TD). This study approached the role of these games on social relations, social skills development, and mental health and well-being

Idiopathic pulmonary hemosiderosis - A rare cause of chronic anemia

Idiopathic pulmonary hemosiderosis (IPH) is a rare disease marked by alveolar bleeding and accumulation of hemosiderin in the lungs. Here we present three cases of IPH. The first case is of a 26-year-old male with anemia, hemoptysis and dyspnea. Bronchoscopy confirmed diffuse alveolar hemorrhage (DAH). A diagnosis of IPH was made after ruling out other causes of DAH and observing good response to steroids. The patient\u27s condition improved with prednisolone and azathioprine. The second case is of 26-year-old female with severe anemia. Imaging suggested IPH and lung biopsy confirmed it. She died shortly afterwards. The third case is of a 7-year-old male with chronic anemia. CT was suggestive of IPH and lung biopsy confirmed the diagnosis. Later, patient developed posterior reversible encephalopathy syndrome (PRES). This patient is stable on azathioprine and prednisolone. We aim to emphasize the importance of considering IPH as a differential in patients with DAH or chronic anemia

Case Report: Stereotactic body radiation treatment for immunotherapy escaped oligometastatic progression in cutaneous melanoma and merkel cell carcinoma

Oligometastatic progression represents a unique manifestation of tumor immune-escape that can lead to disease progression during treatment with immune checkpoint inhibitor (ICI). The diagnosis and further optimal management of oligometastatic progression through ICI remains unclear. Diagnostic challenges include practical limitations due to the anatomical sites of oligometastatic progression, such as the para-aortic region, where traditional tissue biopsy carries high risk, and circulating-tumor DNA (ctDNA) could aid in diagnosis and disease monitoring as a supplement to surveillance imaging. In this report, we describe two cases of one patient with metastatic melanoma and the other with metastatic Merkel cell carcinoma (MCC) who were treated with ICI and later developed localized resistance due to oligometastatic progression. We further highlight our experience using stereotactic body radiation therapy (SBRT) as a salvage approach to treat the oligometastatic progression. In addition, we describe the temporal and dynamic relationship of circulating-tumor DNA (ctDNA) prior to, during and after SBRT, which highly suggested the diagnosis without obtaining a histological specimen. Our cases highlight a potential role for SBRT in the management of oligometastatic progression. However, large prospective trials are essential to confirm the utility of this approach

Prolonged response of recurrent IDH-wild-type glioblastoma to laser interstitial thermal therapy with pembrolizumab

Despite the improved understanding of the molecular and genetic heterogeneity of glioblastoma, there is still an unmet need for better therapeutics, as treatment approaches have remained unchanged in recent years. Research into the role of the immune microenvironment has generated enthusiasm for testing immunotherapy (specifically, immune checkpoint inhibitors). However, to date, trials of immunotherapy in glioblastoma have not demonstrated a survival advantage. Combination approaches aimed at optimally inducing response to immune checkpoint inhibitors with radiotherapy are currently being investigated. Herein, the authors describe their experience of the potential benefit and clinical outcomes of using combination pembrolizumab (an immune checkpoint inhibitor) and laser interstitial thermal therapy in a case series of patients with recurren