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Evaluating the role of sphingolipid signaling in paclitaxel-induced neurotoxicity of SH-SY5Y cells
(2025-04) Casper, Alex; Kulkarni, Chetan; Dib, Patrick; Patel, Mayuri; Shinde, Abhijit; Kroetz, Deanna
Chemotherapies like paclitaxel and other similar microtubule targeting agents commonly used in breast cancer treatment can induce sensory peripheral neuropathy in patients, limiting dosage and impacting quality of life. One pathway implicated in chemotherapy induced peripheral neuropathy (CIPN) is sphingolipid signaling. To study the impact of microtubule targeting medications on sphingolipid signaling, SH-SY5Y cells were differentiated into neuron-like cells and treated with different concentrations of paclitaxel, both in the absence and presence of PF543, an inhibitor of sphingosine-kinase 1, the enzyme involved in the production of sphingosine-1-phosphate. Neurite degeneration was assessed using βIII-tubulin staining and high-content imaging. Imaging of paclitaxel-treated SH-SY5Y cells demonstrated neurotoxicity and a reduction in neuronal network complexity. However, PF543 did not exhibit neuroprotective effects under the tested conditions. Future studies may explore optimizing PF543 treatment parameters, such as preincubation, to assess potential protective effects. Additionally, liquid chromatography- mass spectrometry (LC-MS) is being employed to detect levels of ceramide, sphingosine, and sphingosine-1-phosphate. The impact of paclitaxel on sphingolipid signaling is being quantified to evaluate the involvement of this signaling pathway in neurotoxicity.
Unlocking the potential of nutrient-dependent regulation of Wnt signaling pathway and lipid metabolism in intestinal cells
(The Ohio State University, 2025-05) Gupta, Khushi; Mihaylova, Maria
Aging diminishes the body's ability to regenerate tissues, a decline particularly significant in the gastrointestinal tract where it increases susceptibility to damage and chronic diseases like colorectal cancer. Effective tissue regeneration is crucial for maintaining intestinal homeostasis and preventing disease, yet the underlying regulatory mechanisms, especially how they are influenced by nutrient availability, remain only partly understood. The Wnt signaling pathway plays a key role in driving cell proliferation and is essential for stem cell function. This study explores the role of Stearoyl-CoA desaturase (Scd) enzymes, which may mediate the Wnt signaling. Understanding these interactions may offer new therapeutic avenues for age-related regenerative decline and colorectal cancer. To examine how the inhibition of Scd enzymes affects stem cell function and proliferation, both pharmacological inhibition in vitro and in vivo approaches were utilized, including studies on intestinal crypts, organoids, and fibroblast cell lines. Nutrient availability and dietary content were also varied to assess the role of dietary modulation on the regulation of Scds and Wnt signaling. The key findings of this study indicate that pharmacological inhibition of Scds in vitro in fibroblast cells reduces the proliferation and function of intestinal stem cells, as evidenced by a decrease in organoid formation from the intestinal crypt cells. Additionally, deletion of Scd genes in mice resulted in decreased β-catenin activation, which impaired Wnt signaling. This emphasizes the potential role of Scd enzymes in the modulation of the Wnt signaling pathway. Specifically, the inhibition of Scd specifically reduced the activation of the Wnt-2b and Wnt-3a ligands, indicating that Scd has a selective effect on these Wnt ligands. Dietary modulation further revealed that a monounsaturated fatty acid-rich diet enhanced Wnt signaling in vivo, while nutrient deprivation suppressed Wnt signaling, highlighting a dietary link to regulation of Wnt activity.
Predicting MUOS Satellites' Radio Noise in ANITA-IV Recordings
(The Ohio State University, 2025-05) Hogrefe, Leandra; Beatty, James
The Antarctic Impulsive Transient Antenna (ANITA) was a long-duration balloon experiment looking to detect Askaryan radio emission coming from ultrahigh energy neutrinos interacting with the Antarctic ice. Its fourth flight, ANITA-IV, took place in December 2016. The payload’s antenna band overlaps with parts of the frequency range of the Mobile User Objective System (MUOS). MUOS is a satellite communications system made up of five Navy satellites. When a satellite is in the payload’s field of view, its continuous wave signal is picked up as noise. The noise triggers signal recording where there is no interesting signal and could possibly overshadow real events. To prevent either issue from majorly affecting the recording of data, the specific frequency band must be filtered for certain sectors at certain times. To effectively determine when to block what, it is important to have a way of telling where the satellites are with respect to the payload. In the following, I describe a method of determining the satellites’ positions relative to the payload’s sectors using Two Line Elements of the satellites and positional data of the payload. Using this method, noise could be identified in the past ANITA-IV recordings. Additionally, it could be used in real-time during the upcoming flight of the Payload for Ultrahigh Energy Observations to determine when to apply filters.
LEVERAGING EVIDENCE-BASED PRACTICE MENTORS THROUGH THE CREATION OF AN EBP MENTOR FELLOWSHIP: AN EVIDENCE-BASED QUALITY IMPROVEMENT INITIATIVE
(The Ohio State University, 2025-05) Adkins, Erica; Zellefrow, Cindy
Background: The evidence-based practice (EBP) mentor is vital to the success of translating evidence into practice through EBP. Although EBP experts possess a higher level of EBP competency than most, many feel they lack the skills to mentor others through the process. A large, academic medical center identified an unfortunate trend of many Doctor of Nursing Practice (DNP) EBP and evidence-based quality improvement (EBQI) projects being implemented but not sustained once the DNP student graduated, wasting organization resources and leaving them still dealing with quality and safety issues that were addressed by these initiatives. Sustainability plans were underdeveloped and initiatives were not always continued as originally implemented, if at all.
Aim: The aim of this initiative was to create a cadre of EBP mentors who could be leveraged to assist guiding current DNP students wishing to implement and sustain their EBP/EBQI projects within the health system.
Methods: An EBP Mentor Fellowship was created in an academic medical center based on synthesis of the literature around best practices. Resources within the enterprise were leveraged to engage in course work to provide evidence-based mentor training. Three tiers of EBP mentors were established, distinguishing between level of expertise and comfort in mentoring EBP. Fifteen nurses took part in the initial EBP Mentor Fellowship. The EBP Competency Scale and the Mentor Competency Assessment were administered to measure the impact of the EBP Mentor Fellowship.
Results: Data collected suggests the mentor education sessions had a positive effect on the self-perceived competence of both EBP and mentorship skills.
Linking Evidence to Action: The development and use of these already established EBP experts will further facilitate EBP implementation and sustainability for an organization that has a strong EBP infrastructure and foundation. In addition, a robust mentorship program can increase clinician satisfaction, quality and safety, and positively influence outcomes.
Flexible Multimodal Prediction of Alzheimer's Disease Progression with Deep Learning
(The Ohio State University, 2025-05) Burns, Benjamin; Ning, Xia
Background: Alzheimer’s disease (AD) is a neurodegenerative disease with no known cure. AD progression has a high inter-patient variance, with some patients slowly progressing from mild cognitive impairment (MCI) to dementia while others demonstrate more rapid cognitive decline. AD progression prediction with deep learning is best informed by multiple medical data modalities, but existing multimodal models are limited by their inability to make accurate predictions when some modalities are missing during inference.
Methods: The state of the art in flexible multimodal fusion, Flex-MoE, was modified by replacing its single gating network in the sparse mixture-of-experts layer with independent gating networks for each neuroimaging modality. The resulting method is referred to as Per-Modality Mixture-of-Experts, abbreviated as PerMod-MoE. T1-weighted MRI, FLAIR, amyloid beta PET, and tau PET neuroimaging data were obtained for 469 patients with MCI from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. Flex-MoE and PerMod-MoE were evaluated along with unimodal neuroimaging models on predicting two-year change in Clinical Dementia Rating-Sum of Boxes (CDR-SB).
Results: PerMod-MoE achieves 8%, 4%, and 4% improvements in RMSE over Flex-MoE when evaluated on observations with only FLAIR, amyloid beta PET, and tau PET, respectively. Further, per-modality routing demonstrates competitive performance with Flex-MoE when more modalities are available. PerMod-MoE boasts an average 13% improvement in RMSE for patients with an initial CDR-SB greater than five and an average 16% improvement for patients with an observed two-year CDR-SB change of 0.5 or 1.
Conclusions: PerMod-MoE, with its addition of independent, modality-specific routers in a sparse mixture-of-experts layer, improves performance on AD progression prediction when modality availability is limited during inference.