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  A Feasibility Study Performing Formative Evaluation on Two Components of a Pilot Study: Demand/Utilization and Practicality

  Kayla R. Johannes, Kathryn Fiandt, and Breanna Hetland

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  Alcohol and Cigarette Smoke Decrease Lung Epithelial Cell Proliferation

  Destiny Jordan, Deanna Mosley, Carmen Ochoa, Christopher Bauer, Claire Nissen, Art J. Heires, Debra J. Romberger, and Todd A. Wyatt

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  Investigating Neural Plasticity and Cortical Reorganization via fMRI Following Tumor Resection

  Esther Jung, David G. Ellis, Matthew A. Garlinghouse, and Michele R. Aizenberg

  The brain is known to dynamically repair and reorganize itself after sustaining damage. Patients undergoing tumor resection display cortical reorganization, but the specific processes remain relatively unknown. Our longitudinal study investigates the effectiveness of task-based functional magnetic resonance imaging (fMRI) in detecting recovery of eloquent function in brain tumor patients. We assessed the changes in brain activity as the brain recovers from tumor growth and surgery through the correlations between neuropsychological analysis and changes in fMRI activation.

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  Estimated Incidence of Sjögren-Larsson Syndrome Using Bioinformatics Databases and Software Prediction Programs

  Emily Kassing, Edward Siefker, and William B. Rizzo

  Background: Sjögren-Larsson Syndrome (SLS) is a rare autosomal recessive disease characterized by ichthyosis, neurological retardation, spastic diplegia and a distinctive retinopathy. It is caused by bi-allelic mutations in the ALDH3A2 gene, which result in decreased activity of fatty aldehyde dehydrogenase (FALDH). Although known to be a rare disease, the incidence of SLS is not established. We therefore used a bioinformatics approach to determine the incidence of SLS.

  Methods: To estimate the incidence of SLS, we used mutation prediction programs PROVEAN, SIFT, and PolyPhen-2 to identify potential disease-causing DNA variants in the ExAC and NHLBI databases of >70,000 individual exomes. Missense variants were produced in a ALDH3A2 cDNA mammalian expression vector using site-directed mutagenesis, transfected into CHO cells, and FALDH activity was measured to determine residual enzyme activity.

  Results: In the ExAC and NHLBI exome databases, we identified 696 ALDH3A2 variants consisting of missense (295), insertions/deletions/frameshifts (28), nonsense (7), intronic/splice-site (319) and others (47). Among SLS patients, 124 pathogenic ALDH3A2 variants have been reported; of the 55 missense variants, 40 were correctly predicted to be pathogenic by all 3 mutation analysis programs, indicating only 73% accuracy. Among the ALDH3A2 variants in the exome databases, we selected 23 missense variants predicted by all 3 software programs to be pathogenic for expression in mammalian cells and measured FALDH enzyme activity. Only 10/23 missense variants coded for an enzyme that had

  Conclusions: Based on the US population (330 million) and normal life expectancy of SLS, we estimate that 733-1,031 SLS patients reside in the US, indicating that SLS is an ultra-rare disease.

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  Spinal Cord Disease in HIV Infection

  Zoe Keese, Amanda Fernandes, Lili Guo, Edward Makarov, Saumi Mathews, and Santhi Gorantla

  HIV infection is associated with numerous spinal cord diseases, such as vacuolar myelopathy, primary HIV-associated acute transverse myelitis, and primary CNS lymphoma, amongst others. These diseases had a much higher prevalence in the pre-cART era, however, some individuals are still affected despite cART treatment. Moreover, a previous study has shown that HIV-1 gp120 induces synaptic degeneration in the spinal pain neural circuit, which is likely a critical step in neuropathogenesis of the spinal cord in HIV. Further study is needed to better understand how HIV patients are affected by spinal cord disease, and to develop therapeutic strategies.

  To study HIV in its relation to spinal cord disease, we used a recently developed humanized mouse model that has human microglial cell reconstitution. This model allows for the HIV infection in central nervous system and the observation of resulting pathology.

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  Characterization of MAS1-86 Activity in Malaria Parasites

  Leah A. Keim, Tessa M. Firestone, Emily K. Bremers, Sukhithasri Vijayrajratnam, Mohamed A. Seleem, Martin Conda-Sheridan, and Caroline L. Ng

  In 2019, ~ 229 million malaria cases were reported globally, causing 409,000 deaths. Malaria is caused by the Plasmodium parasite with cyclical infection in human and Anopheles mosquito host. P. falciparum is the most common species, causing approximately 75% of malaria. Asexual, blood stage parasites cause malaria symptoms. The lifecycle begins with merozoites that invade red blood cells and they develop into rings, then trophozoite, and mature into schizonts. Artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated falciparum malaria. Resistance to all artemisinin (ART) is a widespread problem, which is conferred by point mutations in Kelch 13. The K13C580Y mutation is the most abundant in SE Asia. P. falciparum’s apicoplast, an essential organelle that generates fatty acids, heme, and isoprenoid precursors, is a promising drug target since humans lack this organelle. The apicoplast’s primary function in asexual life stages is to produce isoprenoid precursor isopentenyl phosphate (IPP) via the methylerythritol phosphate (MEP) pathway. IPP supplementation has been shown to chemically rescue MEP inhibited cultures. Delayed death phenotype is defined as growth of treated parasite is unaffected, but growth arrest is observed in the progeny. This is seen when apicoplast biosynthesis and apicoplast metabolic pathways are inhibited. The apicoplast-located PfClpC/P complex degrades proteins and has chymotrypsinlike proteolytic activity. PfClpC is a chaperone to the PfClpP protease. P. falciparum 26S proteasome is a cytoplasmic protease with β1, β2, and β5 subunits that have caspase-like, trypsin-like and chymotrypsin-like activity, respectively. WLL, a proteasome inhibitor, targets the β2 and β5 subunits. An analog of MAS1-86 effectively inhibited multi-drug resistant Staphylococcus aureus ClpX, a homolog of PfClpC, in multi-drug resistant S. aureus. Analogs of MAS1-86 were then tested against P. falciparum and MAS1-86 was identified as the most potent inhibitor. We show that MAS1-86 selected parasites display a 6 - 23-fold increase in resistance to MAS1-86. IPP failed to rescue MAS1-86 parasite inhibition nor did MAS1-86 inhibition display a delayed death phenotype, defined as a 10-fold reduction in IC50 values at 120 hours compared to72 hours. We conclude that MAS1-86 does not target the MEP pathway. MAS1-86 inhibition caused a delay in late trophozoite stages through schizont stages, with fewer nuclei observed in schizonts. This observation is of interest since aberrant scizont morphology with fewer nuclei has been reported in auto-inhibited ClpC P. falciparum. There was no shift in the K13 mutant dose response curves, thus K13 haplotype does not influence parasite susceptibility to MAS1-86. MAS1-86-resistant parasites did not show cross-resistance to proteasome β2 and β5 subunit inhibitor, WLL, which has the same chymotrypsin-like activity as ClpP.

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  Long Term Outcome of Childhood Bicuspid Aortic Valve

  Anna E. Kotula, Angela Yetman, David A. Danford, Camille L. Hancock-Friesen, and Ali N. Ibrahimiye

  The most common congenital heart defect is a bicuspid aortic valve (BAV), which is often genetic and the cause is unknown. The defect occurs in only 1% of the general population. A BAV is not able to fully stop blood from leaking back into the heart, which is known as aortic regurgitation. Another common issue with a BAV is that it may be too stiff to fully open, which is known as aortic stenosis. In early childhood, children with aortic stenosis often need palliation with a balloon or surgical valvotomy. As these children develop, they may need subsequent, more definitive procedures such as a Ross procedure, insertion of a tissue valve or mechanical valve, or a valve repair. These definitive operations are used to address recurrent aortic stenosis or regurgitation. As a result, comparing the long-term complications of valve interventions in infancy was an area of considerable interest. The goal of this study was to compare whether one procedure is more effective in providing a more functional status in adulthood since comparative data on the morbidity and mortality associated with each definitive repair in a contemporaneous cohort is lacking. Clinical evidence suggests that repeat surgical procedures are very common in all surgical interventions for bicuspid aortic valve with aortic stenosis in childhood. Incidences of a greater number of aortic valve surgery is associated with a higher incidence of surgical complications and endocarditis. Long-term follow up on the odds of a composite adverse outcome are less with a Ross procedure.

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  Long Term Outcome of Childhood Bicuspid Aortic Valve

  Anna E. Kotula, Anji Yetman, D. Danford, K. Duncan, Camille L. Hancock-Friesen, and Ali N. Ibrahimiye

  The most common congenital heart defect is a bicuspid aortic valve (BAV), which is often genetic and the cause is unknown. The defect occurs in only 1% of the general population. A BAV is not able to fully stop blood from leaking back into the heart, which is known as aortic regurgitation. Another common issue with a BAV is that it may be too stiff to fully open, which is known as aortic stenosis. In early childhood, children with aortic stenosis often need palliation with a balloon or surgical valvotomy. As these children develop, they may need subsequent, more definitive procedures such as a Ross procedure, insertion of a tissue valve or mechanical valve, or a valve repair. These definitive operations are used to address recurrent aortic stenosis or regurgitation. As a result, comparing the long-term complications of valve interventions in infancy was an area of considerable interest. The goal of this study was to compare whether one procedure is more effective in providing a more functional status in adulthood since comparative data on the morbidity and mortality associated with each definitive repair in a contemporaneous cohort is lacking. Clinical evidence suggests that repeat surgical procedures are very common in all surgical interventions for bicuspid aortic valve with aortic stenosis in childhood. Incidences of a greater number of aortic valve surgery is associated with a higher incidence of surgical complications and endocarditis. Long-term follow up on the odds of a composite adverse outcome are less with a Ross procedure.

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  Long Term Outcome of Childhood Bicuspid Aortic Valve

  Anna Kotula and Angela Yetman

  The most common congenital heart defect is a bicuspid aortic valve (BAV), which is often genetic and the cause is unknown. The defect occurs in only 1% of the general population. A BAV is not able to fully stop blood from leaking back into the heart, which is known as aortic regurgitation. Another common issue with a BAV is that it may be too stiff to fully open, which is known as aortic stenosis. In early childhood, children with aortic stenosis often need palliation with a balloon or surgical valvotomy. As these children develop, they may need subsequent, more definitive procedures such as a Ross procedure, insertion of a tissue valve or mechanical valve, or a valve repair. These definitive operations are used to address recurrent aortic stenosis or regurgitation. As a result, comparing the long-term complications of valve interventions in infancy was an area of considerable interest. The goal of this study was to compare whether one procedure is more effective in providing a more functional status in adulthood since comparative data on the morbidity and mortality associated with each definitive repair in a contemporaneous cohort is lacking. Clinical evidence suggests that repeat surgical procedures are very common in all surgical interventions for bicuspid aortic valve with aortic stenosis in childhood. Incidences of a greater number of aortic valve surgery is associated with a higher incidence of surgical complications and endocarditis. Long-term follow up on the odds of a composite adverse outcome are less with a Ross procedure.

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  Linguistic Biases in Letters of Recommendation Written for Rheumatology Fellowship Applicants

  Margaret A. Kramer, Michelene Hearth-Holmes, Harlan Sayles, and Amy Cannella

  Our study aimed to investigate for implicit linguistic biases in letters of recommendation written for applicants applying to our rheumatology program, and to determine if differences in gender and race exist between the applicants. Additionally, we wanted to compare these results to the gender, race, academic rank, and position of the letter writers. We found that among the preliminary 50 letters, they showed that our letters seemed to show the opposite trends than other published studies. We anticipate the need for further study, and look forward to the results.

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  Ethanol-HIV Stimulates Macrophage-derived Extracellular Vesicles to Promote a Profibrotic Phenotype in Hepatic Stellate Cells

  Alyssa M. Lawrence, Natalia Osna, and Raghubendra S. Dagur

  Liver fibrosis is the scarring process where excessive extracellular matrix proteins occur and can be caused by exposure to certain toxins or compounds such as alcohol. Alcohol can lead to increased fibrosis and cirrhosis in people living with HIV due to its ability to influence the liver’s microenvironment. Extracellular vesicles (EVs) communicate between cells by transferring their cargo. Under stress, macrophages can communicate with hepatic cells by releasing EVs and potentially progressing liver disease. The current study examines how ethanol affects EVs production from HIV-infected macrophages and how macrophage-derived EVs modulate profibrotic phenotype in hepatic stellate cells. Monocyte-derived macrophages (MDM) were infected with HIV and then exposed to 50 mM EtOH during incubation. The THP-1 monocytes were differentiated to macrophages with PMA (5 ng/mL) before alcohol and HIV treatment. The medium from the macrophages was collected for ultracentrifugation to isolate the EVs. The EVs were quantified using Nanoparticle tracking analysis (NTA). Transcriptional expression of genes was performed with qPCR. LX-2 hepatic stellate cells were exposed to macrophage-derived EVs from different treatment groups to assess profibrotic activation. Ethanol treatment in HIV-infected macrophages increased the production of EVs compared to their respective controls. The majority of the EVs from the MDM cells were in the range of small EVs (50-200 nm). Exposure of EtOH-HIV-induced macrophage EVs to LX2 cells significantly increased the transcriptional expression of profibrotic genes Col1A1, ACTA2, and CTGF. Combined treatment of EtOH and HIV in macrophages downregulated the hsa-miR92a-3p expression in macrophage-derived EVs that binds with its putative target Col1A1 to increase fibrotic changes in recipient LX-2 cells. The findings of this study lead to the conclusion that a combination of ethanol and HIV stimulates macrophage derived EVs with the downregulation of miR92a, which will activate the profibrotic phenotype in hepatic stellate cells. This activation will contribute to the progression of liver disease.

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  Combined Effects of Drugs of Abuse and HIV Infection Comorbidity on Primary Pericytes

  Jennifer Li, Michellie Thurman, Arpan Acharya, and Siddappa N. Byrareddy

  Background: Pericyte cells are an integral component of the vascular system and blood-brain barrier. HIV infection has been shown to impact both pericytes and the blood-brain barrier. Similarly, drugs of abuse have been found to alter blood-brain barrier permeability. Drugs of abuse and HIV infection comorbidity may affect pericyte function and viral replication.

  Methods: Pericyte cells were treated with varying concentrations of either morphine, cocaine, or methamphetamine to determine cytotoxicity. Next, two concentrations were chosen and infected with macrophage tropic SHIV-BORI159N4. Viral supernatant was collected every three days for analysis viral titer using qPCR and other inflammatory markers.

  Results: Drug treatment appeared to impact viral replication in pericyte cells. Most drug treatments produced lower viral titers, except for the methamphetamine at 10μM concentration treatment.

  Conclusion: Drugs of abuse may impact how HIV infection affects pericyte cells, though underlying mechanisms are still not well-defined. Various classes of drugs may differentially alter viral replication within pericyte cells.

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  Evaluation of FOXM1 inhibitor (FDI-6) as a potential therapeutic molecule for small cell lung cancer

  Aida J. Mohammed, Parvez Khan, Mahek Fatima, Jawed A. Siddiqui, Shailendra K. Maurya, Surinder K. Batra, and Mohd W. Nasser

  Lung cancer is the leading cause of cancer deaths accounting for about 22% of all cancer related cases in both males and females. Lung cancers are broadly grouped into two types mainly small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) with SCLC accounting for about 15% of all lung cancer cases. SCLC is different from NSCLC because in most cases it originates centrally in the bronchi and is frequently seen in smokers. SCLC is aggressive and one of the most malignant forms of tumor characterized by uncontrolled rapid growth of certain cells in the lungs. SCLC displays poor prognosis because of early-stage metastasis, acquisition of chemoresistance, and has a high rate of recurrence. One of major drivers of chemoresistance is the transcription factor Forkhead box protein M1 (FOXM1) that is responsible for modulating cell cycle proliferation, maintenance of genomic stability, DNA damage response, and cell differentiation in numerous tumor entities. In order to explore properties of SCLC cancer cell lines, human non-bone metastatic SBC3, bone metastatic SBC5, H1688, and murine (RPM) cells were treated with a FOXM1 inhibitor known as FDI-6. As a transcription factor FOXMI binds sequence-specific motifs on DNA through its DNA-binding domain activating proliferation and differentiation-associated genes. Anomalous overexpression of FOXMI is a crucial characteristic in oncogenesis and the development of SCLC. FDI-6 is a novel small molecule inhibitor of FOXM1, and it works by binding directly to FOXM1 protein, to displace FOXM1 from genomic targets in SCLC cells prompting concomitant translational downregulation. Functional assays performed confirm that FDI-6 is a viable FOXMI inhibitor showing therapeutic efficacies in SCLC.

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  Wastewater-Based Epidemiology as a Predictor of SARS-CoV-2 Positive Case Rates

  Matthew Muellner, Michael Wiley, Catherine Pratt, Shannon Bartelt-Hunt, Teresa Anderson, and James Lawler

  The global response to the SARS-CoV-2 pandemic has demonstrated several limitations, including personal protective equipment (PPE) shortages and absence of sufficient medical personnel in outbreak zones₁. These problems may be alleviated through the use of new testing methods, such as wastewater-based epidemiology (WBE), to predict potential viral outbreaks in advance of standard testing and hospital admission rates data. SARS-CoV-2 RNA is shed in the waste of infected individuals and is detected by easy and comparatively cheap sampling of communal wastewater 5-8 days post symptom onset₂. RT-qPCR of communal wastewater has been suggested as a 7-day leading indicator of compiled testing data and a 3-day leading indicator of hospital entry data₃.

  Analysis of 67 grab samples taken from 3 sites in Grand Island, Nebraska with Central District Health Department data further establishes viral concentration in wastewater as a significant 7-day leading indicator of positive cases (r = 0.441). The data supports WBE as a simple predictor of outbreaks in small communities, allowing for better communication with health supply centers and general preparedness in the face of rising cases.

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  Cell death mechanism in an isolated wood smoke inhalation induced-ARDS large animal model

  Panashe T. Muendesi, Hannah R. Weber MFS, Premila D. Leiphrakpam PhD, and Keely L. Buesing MD

  Acute respiratory distress syndrome (ARDS) is a lethal disease condition in critically ill patients with a reported mortality rate reaching 45%. The current treatment modalities available for severe ARDS are invasive and carry significant risk for patients. Most published studies involving smoke inhalation utilize another simultaneous injury (such as cutaneous burn) to increase pathology burden of their animal models. This introduces confounding variables to investigations which aim to concentrate on inhalation injury. In this study, we evaluated the potential molecular targets associated with isolated smoke inhalation-induced ARDS.

  We observed an increase in lung injury score and wet/dry ratio 48h post smoke inhalation together with upregulation of inflammatory markers, IL-1βand IL-6 levels. Furthermore, there was a decrease in phosphorylation of cell survival marker Akt and an increase in pro-apoptotic protein BAX at 48h post smoke inhalation. These results indicate that smoke inhalation induced inflammatory processes resulting in increased apoptosis and decreased cell survival in lung parenchymal cells. Use of this unique model may be of benefit in studying the pathophysiology of inhalation injury and for the development of novel therapeutic strategies.

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  Phosphatidylethanolamine N-methyltransferase (PEMT) Knockout Mice Exhibit Worse Alcohol-Induced Liver Injury than Wildtype Mice

  Ireland M. Murphy, Matthew C. Paal, Srinivas Chava, Madan Kumar Arumugam, and Kusum K. Kharbanda

  Phosphatidylethanolamine N-methyltransferase (PEMT) is an enzyme that catalyzes the successive transfer of 3 methyl groups from S-adenosylmethionine (SAM) to phosphatidylethanolamine (PE) to generate phosphatidylcholine (PC). PC is vital for exporting fat out of the liver, ultimately preventing hepatic steatosis. Alcohol also induces steatosis partly through damaging this pathway, so the purpose of this study was to investigate the relationship between alcohol and PEMT in the liver. PEMT -/- (KO) and wild-type (WT) mice were subjected to a chronic + binge alcohol treatment, and both serum and liver samples were analyzed. Triglyceride quantification, SAM and S-adenosylhomocysteine (SAH) levels, and histological analyses were performed on liver samples, while ALT levels were determined from serum samples. Our study showed that ethanol-fed PEMT KO mice exhibited worse liver injury compared to other treatment groups. Our results show increased triglyceride levels, increased ALT levels, decreased SAM:SAH ratio, and increased liver to body weight ratio. From these findings, we conclude that additional liver damage is observed with the combination of alcohol feeding and absence of the PEMT enzyme. The mechanism by which these two factors affect one another is a key area of future study.

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  Reliability of a Revised Social Comparison Motive Scale (SCMS) in Two different Adult Populations

  Hoai Tam P. Nguyen and Sheri Rowland

  This research focuses on establishing reliability of a revised Social Comparison Motive Scale (SCMS) and subscales in two different adult populations, and to compare demographics of the two populations. The results correspond to Tigges (2016) original SCMS, which was developed to measure motives for comparison thinking about teen pregnancy prevention. One sample was recruited from Midwestern Health System, while the other sample was recruited in two rural Midwestern communities. The total sample was 122, in which 52 were inactive women employees of Midwestern Health System, and 70 were Hispanics with hypertension, obesity, dyslipidemia, or type II diabetes, living in either of the two rural Midwestern communities. SPSS was used to determine Cronbach’s alpha of the revised SCMS total scale and subscale. There are 5 subscales to measure motives, including distancing (three items), similarity identification (three items), enhancement (four items), modeling (three items), and future self (six items). Each subscale was revised to measure motives for social comparison related to increasing physical activity. The revised SCMS internal consistency reliability of the total scale (Cronbach's α = 0.968) and the subscales (Cronbach’s α = 0.806-0.897) were both high, indicating that each item/question measures motives for comparing themselves with others about physical activity. Although the two population differ in income and ethnicity, both samples had acceptable reliability. Future research is needed to evaluate the validity of the tool, including content, criterion, and construct validity.

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  Uncertainty Analysis of Radiomic Features in Normal and Pancreatic Cancer Patients

  Meredith Ollerich; Shuo Wang; and Chi Lin M.D., Ph.D

  Medical imaging is an essential component of clinical cancer treatment, with Computer Tomography scans being the most popular type of imaging used for such diagnostic purposes. Currently, the analysis of these scans is mainly done to interpret areas of concern, as well as to determine the size of the lesion or tumor. Experimentation with these scans and their corresponding computer programs has led to recent success in quantitative imaging analysis. This type of analysis is redefining the role of medical imaging as a new source of biomarker data. Radiomics is a method of high-throughput extraction on hundreds of features encrypted in these scans and images based on the delineation of boundary of a 3D volume of interest (VOI), called segmentation. These features include the shape, and the first-, second-, and higher-order statistics of a 3D VOI. The features provide a comprehensive and quantitative description of a tumor’s phenotype and are more in-depth than qualitative descriptors from doctors. This is an active area of research because of the advantages for biomarker development, which focus on risk assessment, treatment response predictions, and the relationship between image features and genomics. The inconsistency and variability of segmentation and extraction negatively affects the robustness of the predictive model and its ability to generate with a different dataset. Patient positioning and image acquisition also affect each feature to varying degrees by introducing different perturbations such as image rotation. In this study, we attempt to evaluate the uncertainties introduced by the image perturbation (e.g., rotation or translation) as well as image resampling

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  Investigating the Anti-tumorigenic Properties of Synthetic Inhibitors of B7-H3 in Group 3 Medulloblastoma

  Sonia Patel, Naveenkumar Perumal, Ranjana K. Kanchan, David J. Doss, Paul C. Trippier, and Sidharth Mahapatra

  Medulloblastomas (MB) are devastating brain tumors originating in the cerebellum most commonly in children. There are four distinct subgroups of medulloblastoma: WNT (wingless), SHH (sonic hedgehog), group 3, and group 4. The most malignant tumors possess an aggressive phenotype characterized by c-Myc amplification and deletions to chromosome 17p; they belong to group 3. Prior investigations into the significance of genes on 17p revealed that miR-1253, which is found on locus 17p13.3, is significantly downregulated in medulloblastoma and has important tumor suppressive properties. Amongst its oncogenic targets is B7-H3 (CD276), a highly deregulated oncoprotein that attenuates the immune response to MB tumors. We chose to elucidate the oncogenic properties of B7-H3 in group 3 MB using synthetic inhibitors. After screening 100,000 different compounds for: 1) docking ability, 2) oral bioavailability, 3) potential CNS activity, and 4) number of metabolic side reactions, we selected two N-terminal inhibitors: B7-H3-Ni1 and B7-H3-Ni3. In HDMB03 cells (with c-Myc amplification and i17q), we found an IC50 of 3.7 𝛍M for B7-H3-Ni1 and no discernible effect of B7-H3-Ni3. We confirmed CD276 expression inhibition using B7-H3-Ni1 via Western blotting and concurrently noted elevations in cleaved PARP (apoptosis) and reduction in p-Akt (proliferation marker), providing us preliminary insights into the mechanism of inhibition. Notably, a remarkable decline in migration and wound healing and abrogation of colony formation were observed with B7-H3-Ni1. Collectively, our findings substantiate the inhibitory properties of B7-H3-Ni1 in vitro, potentially serving as a therapeutic agent for in vivo group 3 MB tumors.

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  The Experience of Wearing Masks in the Hospital: "We Adapt Quickly and Just Moved On"

  Mikayla Peralta, Jana Wardian PhD, and Sarah Richards MD

  Background

  As it became known that SARS-CoV-2 was spread through droplets, masks became a primary form of protection. While wearing masks was not a new in the health field, little is known about how they affect the patient-provider relationship.

  Methods

  We conducted interviews with patients and providers regarding their experience with mask-wearing in the hospital. Participants came from Internal Medicine hospitalists and patients. Interviews were recorded, transcribed, and coded for analysis and interpretation.

  Results

  Our population included 9 patients and 9 providers. The benefit of wearing masks is safety; many providers stated they did not get sick at all during the pandemic. The main challenge providers perceived was connecting with patients. The connection concern was common amongst providers. Adaptations to overcome it included showing their face, speaking louder/clearer, spending more time with patients, and being more expressive in their communication. However, some providers felt there were situations in which removing masks for a critical conversation would be the better option.

  Discussion

  While both parties welcome the safety aspect of masks, providers had concerns about the connection with their patients. However, patients did not notice a significant effect on communicating with providers or their quality of care. This difference in perception could be due to patients having no prior knowledge to compare their interactions, whereas providers recall interactions prior to the pandemic without masks. For future policy, patients and providers would favor wearing masks but providers would like to be able to remove them when necessary for patient connection.

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  Role of Oocyte-Specific cKIT on Development of Ovarian Reserve

  Amelia L. Podolny, Yi Luan, and So-Youn Kim PhD

  Many chemotherapy drugs cause female infertility by permanently shutting down the ovaries. In pre-pubescent girls, this can also result in abnormal sexual development. It is known that many of these harmful chemotherapy drugs bind to cKIT receptors throughout the body. cKIT receptors exist in particularly high concentrations in the ovaries and when they are blocked by chemotherapy drugs, premature ovarian failure results. Our experiment uses a transgenic mouse model to evaluate the effects of cKIT receptors on oocyte formation and development. This experiment is part of a larger effort to understand the mechanisms by which chemotherapy drugs cause premature ovarian failure.

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  Radiomics: Medical Imaging Can Predict Pancreatic Cancer Patient Outcome

  Kiersten M. Preuss

  Radiomics is a process that mines quantitative data from imaging techniques, including MRIs, CTs, and PET scans. In this study, radiomics is used to find associations between clinical factors such as the number of metastases in pancreatic ductal adenocarcinoma (PDAC) patients from their preoperative CT scans. PDAC patients have a five-year survival rate only barely above 10%. By the time of diagnosis over half of pancreatic cancers are metastasized, and when that is the case the five-year survival rate is only 3%. It is hypothesized that radiomics can help predict clinical factors such as the number of metastases in pancreatic patients. These predictions can lead to improved treatment plans by risk stratification. Patients with a higher risk of metastases would adopt more aggressive treatment than patients with lower risk. This study included 87 patients diagnosed with PDAC who consented to a Rapid Autopsy Program. Although results have not yet been processed, future work would include finishing developing a model to use to predict PDAC metastases.

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  TDP-43 Liquid-Liquid Phase Separation (LLPS) Deficiency Attenuates Amyloid Beta Deposition in the 5XFAD Transgenic Mouse Model of Alzheimer's Disease

  Nathan Ramachandran, Xiaojia Ren, Ju Gao, Luwen Wang, Ariele Peters, Justin Dunn, and Xinglong Wang

  Background: TAR DNA-binding protein 43 (TDP-43) can be found within the cell nucleus in most tissues and is a fundamental component to protein production, as it works to slice and reconfigure mRNA molecules. Recently, TDP-43 inclusions have been identified as a prevalent proteinopathy in the brains of individuals diagnosed with Alzheimer's Disease (AD). However, despite the growing body of evidence demonstrating the important role of TDP-43 in AD pathogenesis, whether and how TDP-43 proteinopathy and other AD pathological hallmarks interact remain largely unknown. Furthermore, TDP-43 has a high propensity to undergo liquid-liquid phase separation (LLPS), a biological process necessary for the condensation of proteins, nucleic acids, and other biomolecules.

  Purpose of Research: The correlation between TDP-43 LLPS and AD deposition is an intriguing, yet currently unexplored area of interest. The purpose of this study is to investigate whether and how TDP-43 and its phase separation are involved in amyloid deposition in APP transgenic mice for Alzheimer's Disease.

  Methods: We crossed our recently generated mice expressing endogenous LLPS-deficient murine TDP-43 with the widely used 5XFAD transgenic mouse model. Different approaches were then performed to assess amyloid deposition and associated neuroinflammation.

  Results: When compared to 5XFAD mice, 5XFAD mice expressing LLPS-deficient TDP-43 showed significantly reduced amyloid deposition throughout the brain. Neuroinflammation, as evaluated by GFAP and Iba1 expression was also alleviated by LLPS-deficient TDP-43.

  Conclusion: For the first time, our study demonstrates the likely role TDP-43 LLPS plays in amyloid deposition. And, targeting TDP-43 LLPS may serve as a novel therapeutic approach to Alzheimer's Disease treatment.

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  Pediatric Acute Lymphoblastic Leukemia Patients and Potential Risk for Vincristine Side Effects with Concomitant Fluconazole

  Reyna C. Ramirez, Jill C. Beck, James B. Ford, Chittalsinh M. Raulji, Robin High, and Caleb A. Cave

  Background: Pediatric Acute Lymphoblastic Leukemia (ALL) patients undergoing intensive treatment are considered at high risk for opportunistic infections. To prevent invasive fungal infection, some patients receive antifungal prophylaxis such as fluconazole. As a consequence, an increase in vincristine toxicity has been associated with the co-administration of antifungal prophylaxis. We analyzed whether the use of fluconazole prophylaxis impacts vincristine’s side effects during induction therapy. Method: We conducted a retrospective chart review of all pediatric (age 0-18 years) patients diagnosed with ALL at Children’s Hospital and Medical Center in Omaha, Nebraska from July 2013-May 2021. Patients were divided into two groups based on whether or not they received fluconazole. Incidence of fungal infection, rate and grade of peripheral neuropathy, and prescription for gabapentin (treatment for peripheral neuropathy) were collected for both groups. Results: We had 157 ALL patients, of which 72 patients received fluconazole, and 85 patients did not receive fluconazole. There was no significant difference between fluconazole use and increased incidence of peripheral neuropathy (p value= 0.28) or incidence of hyponatremia (p value =Conclusion: We did not find a statistically significant difference that the use of concomitant fluconazole with vincristine increased the risk of peripheral neuropathy or hyponatremia.

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  Inhibitory Effects of ab initio Antiviral Peptides Efficiently Designed Based on APD3 Database

  Thomas J. Ripperda Jr, Yangsheng Yu, Atul Verma, St. Patrick Reid, and Guangshun Wang

  Natural antimicrobial peptides (AMPs) aid in many organisms innate immune defense against pathogens. Engineering new therapeutics from natural AMP templates may provide an effective treatment to emerging microbial infections such as SARS-CoV-2, Ebola viruses, and drug-resistant bacteria. One way to design antimicrobial peptides is the database filtering technology (DFT). The DFT is an ab initio design that selects the most probable parameters for an AMP by statistical analysis in the antimicrobial peptide database (https://aps.unmc.edu). To our knowledge, the DFT design has never been used to develop an antiviral peptide. We present here the improved DFT that enables a faster and more efficient design. Indeed, the peptide designed in this manner inhibits both SARS-CoV-2 and Ebola viruses. We also validated that deviations from the most probable length or amino acids led to a decrease in peptide activity. Further refinement of the peptide by introducing a disulfide bond improved peptide stability to proteases such as chymotrypsin and trypsin. Our database designed and improved peptide 1 (DDIP1) has the potential as a novel antiviral agent.