eScholarship@UMassChan
eScholarship@UMassChan is a digital archive for UMass Chan Medical School's research and scholarship, including journal articles, theses, datasets and more. We welcome submissions from our faculty, staff, and students. eScholarship@UMassChan is a service of the Lamar Soutter Library, Worcester, MA, USA. See also our open access journal publishing services.
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Recent Publications
Publication Track-Weighted Dynamic Functional Connectivity Profiles and Topographic Organization of the Human Pulvinar(2024-12-01)The human pulvinar is considered a prototypical associative thalamic nucleus as it represents a key node in several cortico-subcortical networks. Through this extensive connectivity to widespread brain areas, it has been suggested that the pulvinar may play a central role in modulating cortical oscillatory dynamics of complex cognitive and executive functions. Additionally, derangements of pulvinar activity are involved in different neuropsychiatric conditions including Lewy-body disease, Alzheimer's disease, and schizophrenia. Anatomical investigations in nonhuman primates have demonstrated a topographical organization of cortico-pulvinar connectivity along its dorsoventral and rostrocaudal axes; this specific organization shows only partial overlap with the traditional subdivision into subnuclei (anterior, lateral, medial, and inferior) and is thought to coordinate information processing within specific brain networks. However, despite its relevance in mediating higher-order cognitive functions, such a structural and functional organization of the pulvinar in the human brain remains poorly understood. Track-weighted dynamic functional connectivity (tw-dFC) is a recently developed technique that combines structural and dynamic functional connectivity, allowing the identification of white matter pathways underlying the fluctuations observed in functional connectivity between brain regions over time. Herein, we applied a data-driven parcellation approach to reveal topographically organized connectivity clusters within the human pulvinar complex, in two large cohorts of healthy human subjects. Unsupervised clustering of tw-dFC time series within the pulvinar complex revealed dorsomedial, dorsolateral, ventral anterior, and ventral posterior connectivity clusters. Each of these clusters shows functional coupling to specific, widespread cortico-subcortical white matter brain networks. Altogether, our findings represent a relevant step towards a better understanding of pulvinar anatomy and function, and a detailed characterization of his role in healthy and pathological conditions.Publication Intravenous gene therapy improves lifespan and clinical outcomes in feline Sandhoff Disease [preprint](2024-11-18)Sandhoff Disease (SD), a fatal neurodegenerative disorder, is caused by the absence of ß-hexosaminidase (Hex) and subsequent accumulation of GM2 ganglioside in lysosomes. Previous studies have led to adeno-associated virus (AAV) gene therapy for children with GM2 gangliosidosis in both expanded access and Phase I/II clinical trials via intracranial and/or cerebrospinal fluid-based delivery. The current study investigated intravenous (IV) gene therapy of SD cats, treated at one month of age with a bicistronic AAV vector. While untreated SD cats lived to 4.3±0.2 months, cats treated with low and high doses lived to 8.3±1.2 and 12.4±2.7 months, respectively. In-life assessments revealed clear clinical benefit of AAV treatment, with the most dramatic improvement seen in the reduction of overt full-body tremors. Cerebrospinal fluid levels of aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were decreased, indicating a reduction of cell damage within the central nervous system. Magnetic resonance imaging (MRI) and spectroscopy (MRS) acquired on a 7 Tesla scanner indicated that structural pathology and metabolite abnormalities are partially normalized by AAV treatment. Dose-dependent reduction of GM2 ganglioside storage and increases in Hex activity were most substantial in the caudal regions of the brain and in the spinal cord. Immunohistochemistry revealed reduction in neuroinflammatory cell populations and partial correction of myelin deficits. These results support the dose-dependent efficacy of AAV delivered IV for significant restoration of clinical metrics and Hex function in a feline model of SD.Publication Design, creation, and use of the Test Us Bank (TUB) COVID-19 sample biorepository(2024-11-12)Shortly after the first case of SARS-CoV-2 was diagnosed a public health emergency (PHE) was declared and a multi-agency response was initiated within the US federal government to create and propagate testing capacity. As part of this response, an unprecedented program designated Rapid Acceleration of Diagnostics (RADx) Tech was established by the National Institutes of Health (NIH) to facilitate the development of point-of-care tests for the COVID-19. The RADx Tech Clinical Studies Core (CSC), located at the University of Massachusetts Chan Medical School (UMass Chan), with partnering academic, private, and non-governmental organizations around the country, was tasked with developing clinical studies to support this work. This manuscript details development of a biorepository specifically focused on the collection and storage of samples designed for diagnostic platform development. It highlights the unified collection and annotation process that enabled gathering a diverse set of samples. This diversity encompasses the geography and backgrounds of the participants as well as sample characteristics such as variant type and RT-PCR cycle threshold (CT) value of the corresponding reference sample on a uniform clinical reference platform.Publication Nucleic acid sensing in the central nervous system: Implications for neural circuit development, function, and degeneration(2024-11-06)Nucleic acids are a critical trigger for the innate immune response to infection, wherein pathogen-derived RNA and DNA are sensed by nucleic acid sensing receptors. This subsequently drives the production of type I interferon and other inflammatory cytokines to combat infection. While the system is designed such that these receptors should specifically recognize pathogen-derived nucleic acids, it is now clear that self-derived RNA and DNA can also stimulate these receptors to cause aberrant inflammation and autoimmune disease. Intriguingly, similar pathways are now emerging in the central nervous system in neurons and glial cells. As in the periphery, these signaling pathways are active in neurons and glia to present the spread of pathogens in the CNS. They further appear to be active even under steady conditions to regulate neuronal development and function, and they can become activated aberrantly during disease to propagate neuroinflammation and neurodegeneration. Here, we review the emerging new roles for nucleic acid sensing mechanisms in the CNS and raise open questions that we are poised to explore in the future.Publication Knowledge, Attitudes and Confidence in Providing Dementia Care to Older Adults Among Nurses Practicing in Hanoi, Vietnam: A Cross-Sectional Study(2024-11)Background: Nurses' competencies are crucial in providing effective dementia care in healthcare settings for older people. Understanding nurses' current knowledge, attitudes and confidence in this area is essential for developing education programmes for healthcare professionals to improve patient care. The purpose of this study was to assess the knowledge, attitudes and confidence related to providing dementia care among nurses practicing in geriatric hospital wards and nursing homes in Hanoi, Vietnam. Methods: A total of 269 out of 313 (response rate was 86%) full-time nurses working at six geriatric wards in hospitals and nursing homes in Hanoi were surveyed using three self-administered questionnaires: the Dementia Knowledge Assessment Scale (DKAS), Dementia Attitude Scale (DAS) and the Confidence in Dementia Scale (CODE). Multiple regression models were constructed to identify factors associated with dementia care knowledge, attitudes and confidence. Results: The overall mean scores of nurse's knowledge, attitudes and confidence were 28.1 ± 8.0, 102.1 ± 13.4 and 28.3 ± 6.4, respectively. A positive correlation was reported between the knowledge and attitude scores and between the attitudes and confidence scores. Greater seniority (β: 0.29; 95% CI: 0.03-0.56) and having learned information through colleagues or experts (β: 3.02; 95% CI: 0.88-5.16) were associated with better dementia knowledge. A higher level of dementia training desirability was associated with increased knowledge (β: 0.74; 95% CI: 0.28-1.20) and favourable attitudes (β: 0.94; 95% CI: 0.15-1.74), whereas frequent exposure to dementia cases was associated with higher confidence (β: 3.56; 95% CI: 1.39-5.73) and more favourable attitudes (β: 3.96; 95% CI: 0.27-7.66). Conclusion: Our study highlights deficits in knowledge, low levels of social comfort in nurses' attitudes towards people with dementia and a lack of confidence in providing effective care among nurses practicing in healthcare settings for older adults in Hanoi, Vietnam. With the ageing of the population and with increasing numbers of persons living with dementia, our findings suggest the importance of improving the training of nurses to specifically address these deficits. Implications for practice: Multidisciplinary consultation meetings need to be encouraged in the healthcare workplace setting as well as ensuring the presence of qualified counsellors for care teams working with older adults in non-hospital settings. Training about non-cognitive symptoms of dementia and demonstrating effective verbal and non-verbal communication skills is critical and should be integrated into nurse's educational training.