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Search Methodologies in Systematic Reviews: The Rigor in Adding 'Cited by' to Our Searches
Get PDFOBJECTIVE: Search methodologies are such an important step in conducting Systematic Reviews. Researchers rely heavily on librarian expertise in both conducting the search strategy and then implementing them. Are librarians missing a crucial step in ensuring that all the evidence available is found? By adding this step to the process could librarians close the loop on searching and ensure we have not missed both vital research that relates to their review, but also newer research on the subject? METHODS: A comprehensive search of articles found surrounding keywords. No articles were obtained that met the criteria. There is a gap in our knowledge on the effectiveness of this strategy. RESULTS: Primary research needs to be conducted on this search strategy to ascertain the effectiveness of this method. Librarians could implement this strategy into their searches and they should note this added step within the Search Strategy portion of the Review. CONCLUSIONS: In conclusion, this search strategy step of searching 'Cited by' after the 'Full Text' review has been conducted and before the 'hand searching' of the articles selected could be very advantageous in ensuring all relevant articles will be found. More research needs to be conducted to see if this step is necessary for the rigor of the search methodology
Dreaming of a Modern Print Collection: Revitalizing Health Sciences Library Resources
Get PDFLibrarians curated an opening day book collection for a new health sciences library in 2018. The collection consisted of previously held books along with new purchases, and covered content areas including general health and medicine, nursing, optometry, and pharmacy. In the intervening years, the library system transformed its approach to collections, opened a new library location dedicated to medicine, and experienced a pandemic. With these changes, the print collection needed to be assessed and updated. After discussions with collections, acquisitions, and cataloging personnel, librarians devised a plan to assess the collection with the following factors for consideration: year of publication, circulation statistics, existence of a new edition, existence of an ebook format, cost of new edition/ebook, curricular needs, and research priorities. Librarians then carried out this plan, withdrawing, updating, and refreshing the print collection with new priorities in mind. They also kept detailed records of the process in order to plan and budget for more timely and consistent future collection updates. This presentation will outline the collection update project, including the decision-making process for individual books, the staff time involved, and the budget required for new books
Overcoming Vulnerabilities of Machine Learning in Neuroimaging Applications
No full textNeuroimaging has been widely used to non-invasively probe the structural and functional changes in many neurological and psychiatric diseases. Techniques such as functional magnetic resonance imaging (fMRI) generate a wealth of dense and high-dimensional measurements of the brain. Through machine learning, a powerful class of statistical methods, such measurements can be used to make personalized predictions that inform clinical care, such as diagnoses, prognoses, or treatment outcome trajectories. However, applications of machine learning must meet two critical requirements: 1) there must be sufficient training data and 2) data samples should be independent and identically distributed (iid). In this dissertation, I propose two novel methods to overcome these vulnerabilities in neuroimaging and other biomedical data, and I develop two promising applications of machine learning and neuroimaging to address critical needs in neurological and psychiatric disease.
First, I demonstrate how standard machine learning approaches can be applied to predict future Parkinson's Disease severity from resting-state fMRI. By generating personalized prognoses for this debilitating neurodegenerative disease, better care decisions can be made. Next, I address the requirement for sufficient training data in machine learning, without which models tend to overfit and generalize poorly to new data. I propose a method to perform data augmentation, where additional data is simulated by transforming existing data, for 4D fMRI timeseries. Using this augmentation method, I develop predictors of antidepressant response from pre-treatment task-based fMRI. This targets a pressing need for individualized treatment selection tools in depression care, where it currently takes weeks to months to test various medications until adequate relief is found. Finally, I propose a method to construct neural networks, a potent class of machine learning models, that can specially handle non-iid data. This is of broad importance in biomedical data, which is frequently non-iid with samples clustered by experimental batch, study site, etc. Inadequate handling of cluster effects leads to confounding biases and poor generalization in conventional models. My method, tested across several biomedical applications, improves both performance and generalization while affording greater interpretability of cluster effects in the data
Medical ethics related to child abuse: evaluations, diagnoses, and reporting
Get PDFTuesday, February 13, 2024; noon to 1 p.m. (Central Time); Room NB2.100A or via Zoom. "Medical Ethics Related to Child Abuse: Evaluations, Diagnoses, and Reporting." Deborah E. Lowen, M.D., Former Deputy Commissioner of Child Health, Tennessee Department of Children's Services, and Senior Medical Editor, Child Abuse Pediatrics Sub-board, American Board of Pediatrics.For medical practitioners encountering situations of child abuse or neglect, the subject matter itself can be difficult and even traumatizing. The ethical issues that arise add to the discomfort for those involved with these cases. Through case vignettes, this webinar will discuss some of the more common ethical dilemmas, such as determining a plan for medical evaluations related to abuse, formulating medical diagnoses, and responding to mandatory reporting laws. The relationship of these ethical issues to concerns about the roles and functioning of child welfare agencies will also be addressed.UT Southwestern--Program in Ethic
Targeting Cilia Initiation & Maintenance in Shh-MB
Get PDFThe 62nd Annual Medical Student Research Forum at UT Southwestern Medical Center (Tuesday, January 30, 2024, 3-6 p.m., D1.700 Lecture Hall)Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Of the four molecular subtypes, Sonic Hedgehog Medulloblastoma (SHH-MB) involves aberrant growth signaling between SHH mitogen and its receptors on primary cilium in cerebellar granule cells. We hypothesized that in mouse models genetically engineered to induce SHH-MB, additional genetic modifications dysregulating primary cilium would inhibit the cancer phenotype, either decreasing severity or preventing it altogether.
We established breeding cages with conditional knockouts of Gpr161 (GPR161 normally represses SHH signaling, knockout promotes SHH-MB), knockouts of Ptch1 (a SHH receptor with more aggressive tumors upon haploinsufficiency), and Pcm1 knockouts (centriolar satellite protein critical for primary cilia stability). Our methods included: PCR and gel electrophoresis to assess genotype, BrdU injections, cerebellum dissection, cryo-sectioning, antibody staining, and immunofluorescence imaging using confocal microscopy.
We immunostained cerebellar tissues from various genotypes with cell cycle (CyclinD1), primary cilia (ARL13B), mitotic (pHH3), and proliferative markers (BrdU). We found that mice with Gpr161 or Ptch1 deletion develop SHH-MB and "persistent" external granular layers with increased cilia density versus controls. There is also a large presence of BrdU (-) and CyclinD1 (-) cells with cilia, begging the question of where in the cell cycle these cells belong. Heterozygous deletion of Pcm1 (+/ko) does not appear to diminish cancer phenotype, as a Ptch1 +/ko; Pcm1 +/ko mouse demonstrated SHH-MB and increased cilia density. A full knockout of Pcm1, however, does seem to rescue the cancer phenotype, as a Gpr161 f/f; Pcm1 ko/ko; Nestin-Cre mouse did not have any tumor, and it had low cilia density. We demonstrate that in mice with SHH-MB-predisposing genetic mutations, additional mutation of proteins regulating stability of primary cilia might prevent cancer phenotype. These results could open an avenue for investigating therapeutic inhibition or downregulation of cerebellar primary cilia in human patients with genetic predisposition for SHH-MB.Southwestern Medical Foundatio
62nd Annual Medical Student Research Forum
Get PDFThe 62nd Annual Medical Student Research Forum at UT Southwestern Medical Center (Tuesday, January 30, 2024, 3-6 p.m., D1.700 Lecture Hall)This 140-page booklet includes a list of oral presentations, a table of contents to the abstracts, and the abstracts divided into three categories: Basic Research and Disease Models; Clinical Research; and Quality Improvement, Global Health, Medical Education, Community Health, and Research Design.Southwestern Medical Foundatio
Risky business: elevated cardiovascular risk in lupus
Get PDFDetailed formal protocol with illustrations and extensive bibliography.A recording of the protocol presentation is available on UT Southwestern's Mediasite. Note: Access to the video is restricted to authorized UT Southwestern users only.UT Southwestern--Internal Medicin
Molecular mechanisms of preeclampsia: implications for cardiovascular disease and chronic kidney disease
Get PDFDetailed formal protocol with illustrations and extensive bibliography.A recording of the protocol presentation is available on UT Southwestern's Mediasite. Note: Access to the video is restricted to authorized UT Southwestern users only.UT Southwestern--Internal Medicin
Characterization of Virulence Mechanisms in Vibrio parahaemolyticus
No full textPages xvi-xix are misnumbered as pages vi-ix.Vibrio parahaemolyticus (V. parahaemolyticus) is a Gram-negative, halophilic bacterium found in estuarine and marine environments worldwide, and is a leading cause of foodborne illness. The V. parahaemolyticus life cycle is facilitated by a broad array of virulence factors, including two type three secretion systems (T3SS). Within the T3SS1 effector repertoire, VopR induces cytoskeletal collapse, cell rounding, and actin localization to the host cell periphery, but its catalytic activity, substrate, and cognate chaperone remained uncharacterized. Herein, we investigated the catalytic mechanism of VopR, evaluated potential substrates through structural analyses and biochemical assays, and identified VP1684 as the cognate chaperone for VopR. V. parahaemolyticus also mediates an intracellular infection via the T3SS2. The T3SS2 effector VopC promotes host invasion by deamidating small host Rho GTPases. Rho GTPase deamidation is a highly conserved invasion strategy in Gram-negative bacteria, including the human pathogen uropathogenic Escherichia coli (UPEC). UPEC secretes a Rho GTPase deamidating toxin CNF1, a VopC homologue, that enters the host via endocytosis. Herein we determined that CNF1 can complement VopC activity in promoting V. parahaemolyticus invasion, but leaves many internalized bacteria confined to endosomes. We also investigated the mechanism by which V. parahaemolyticus exits the host cell, and found that a type two secretion system (T2SS)-secreted lipase VPA0226 was necessary for bacterial egress, marking the successful completion of the infection process. Finally, we utilized in silico analyses and a transposon mutagenesis screen to identify novel putative virulence factors in and outside the V. parahaemolyticus T3SS effector repertoire, and uncovered a putative GABA antiporter with a significant effect on bacterial proliferation, and possibly pH regulation. Cumulatively, these studies highlight the diversity of the virulence factors and complex networks involving an interdependency between these factors in a clinically relevant human pathogen
The Immunosuppressive Function of VEGF Signaling in the Tumor Microenvironment
No full textAngiogenesis, a hallmark of cancer, is induced by vascular endothelial growth factor-A (VEGF). As a result, anti-VEGF therapy is commonly employed for cancer treatment. However, anti-VEGF therapy generally provides modest efficacy in cancer patients and therapy-induced hypoxia results in a less differentiated mesenchymal-like tumor cell phenotype, which reinforces the need for effective companion therapies. Cyclooxygenase-2 (COX-2) inhibition has been shown to promote tumor cell differentiation and improve standard therapy response in pancreatic cancer. Here, I evaluate the efficacy of COX-2 inhibition and VEGF blockade in preclinical models of pancreatic cancer and identity it as a strategy to overcome therapy-induced resistance in pancreatic cancer. Combination therapy reverses anti-VEGF-induced epithelial-mesenchymal transition, collagen deposition and promotes an immune stimulatory microenvironment. Recent studies have also found that VEGF expression is also associated with immune suppression in cancer patients. This connection has been investigated in preclinical and clinical studies by evaluating the therapeutic effect of combining anti-angiogenic reagents with immune therapy. However, the mechanisms of how anti-VEGF strategies enhance immune therapy are not fully understood. We and others have shown selective elevation of VEGFR2 expression on tumor-associated myeloid cells in tumor-bearing animals. I further investigate the function of VEGFR2+ myeloid cells in regulating tumor immunity and find VEGF induces an immunosuppressive phenotype in VEGFR2+ myeloid cells including directly upregulating the expression of programmed cell death 1-ligand 1 (PD-L1). Moreover, I demonstrate that VEGF blockade inhibits the immunosuppressive phenotype of VEGFR2+ myeloid cells, increases T cell activation and enhances the efficacy of immune checkpoint blockade. These studies highlight the function of VEGFR2 on myeloid cells and provide mechanistic insight on how VEGF inhibition potentiates immune checkpoint blockade