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Biomedical subjects

Christopher Wilson

Publications and source records attributed to Christopher Wilson.

11 recordsLinked to original sources

iModMix: integrative module analysis for multi-omics data.

SUMMARY: Integrative Module Analysis for Multi-omics Data (iModMix) is a biology-agnostic framework that enables the discovery of novel associations across any type of quantitative abundance data, including but not limited to transcriptomics, proteomics, and metabolomics. Instead of relying on pathway annotations or prior biological knowledge, iModMix constructs data-driven modules using graphical lasso to estimate sparse networks from omics features. These modules are summarized into eigenfeatures and correlated across datasets for horizontal integration, while preserving the distinct feature sets and interpretability of each omics type. iModMix operates directly on matrices containing expression or abundances for a wide range of features, including but not limited to genes, proteins, and metabolites. Because it does not rely on annotations (e.g., KEGG identifiers), it can seamlessly incorporate both identified and unidentified metabolites, addressing a key limitation of many existing metabolomics tools. iModMix is available as a user-friendly R Shiny application requiring no programming expertise (https://imodmix.moffitt.org), and as a Bioconductor R package for advanced users (https://bioconductor.org/packages/release/bioc/html/iModMix.html). The tool includes several public and in-house datasets to illustrate its utility in identifying novel multi-omics relationships in diverse biological contexts. AVAILABILITY AND IMPLEMENTATION: iModMix is freely available from Bioconductor (https://bioconductor.org/packages/release/bioc/html/iModMix.html), and the example dataset package (iModMixData) is also available from Bioconductor (https://bioconductor.org/packages/release/ data/experiment/html/iModMixData.html). The R package source code and Docker are available from GitHub: https://github.com/biodatalab/iModMix. Shiny application can be accessed at: https://imodmix.moffitt.org.

Multiomics↗

Investigation of a Mycobacterium fortuitum prosthetic joint infection outbreak at two ambulatory surgery centers in Tennessee.

OBJECTIVE: This study outlines the investigation into an outbreak of Mycobacterium fortuitum infections involving 17 cases undergoing hip or knee surgeries at two ambulatory surgery centers (ASCs) in Tennessee from January 2023 to November 2024. Notably, the outbreak could not be attributed to contaminated water sources, which are typically associated with non-tuberculous mycobacteria (NTM) outbreaks, presenting a unique challenge. METHODS: Outbreak investigation steps included Infection Prevention (IP) assessments, case-control study, environmental sampling, whole genome sequencing, and a healthcare personnel (HCP) exposure questionnaire. RESULTS: IP assessment highlighted several concerns, including no formal facility water management program (WMP), a lack of dedicated IP personnel and certified sterile processing staff, the absence of a formalized system for tracking surgical site infections, and a notable gap in understanding the requirements for reporting diseases. The case-control findings revealed a significant association between the presence of a surgical technologist in the operating room during the procedures and the occurrence of NTM infections, indicated by an odds ratio of 55.77 (95% CI [3.16-985.44]; P = 0.0097). Thirteen clinical isolates collected at one ASC and three additional isolates collected at a second ASC were highly related by whole genome sequencing. CONCLUSION: The study further elucidates valuable insights gained from the outbreak response, including the gaps in surveillance within the ambulatory surgical setting and systematic collection of cultures from environmental sources. It emphasizes the importance of thorough vetting, onboarding, continuing education, and practice monitoring for HCP.

Humans↗

Repetitive transcranial magnetic stimulation may induce language switching in bilingual patients.

The dorsolateral prefrontal cortex (DLPFC) may participate in the process of language switching in multilingual individuals. We present two cases of bilingual patients who experienced unexpected language switching after receiving high-frequency, repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC as a treatment for major depression. These preliminary findings support the role of the DLPFC in language switching in polyglots and highlight the potential value of rTMS for non-invasively investigating language function in humans. Further investigation is warranted.

Adult↗

Naloxone increases ketamine-induced hyperactivity in the open field in female rats.

In considering possible effects of ketamine, and its interactions with drugs that might be administered following ketamine abuse, researchers investigated the effects of administering combinations of saline, naloxone, and/or ketamine on open-field activity levels and frequencies of turning, reverse locomotion, head weaving, and rearing in 50-day-old rats. Female subjects having received ketamine combined with saline showed significant increases in open-field activity as compared with male subjects and subjects having received combinations of saline and/or naloxone. When combined with ketamine, naloxone caused an increase in the aforementioned ketamine-induced hyperactivity in female rats. In addition, ketamine caused increases in turning in female rats and increases in reverse locomotion and head weaving in male and female rats. Decreases in rearing were reported in both males and females with administration of ketamine. In general, naloxone had little, if any, effect on these behaviors. Thus, the primary effect of administration of naloxone reported in this study is an exacerbation of ketamine-induced open-field hyperactivity. The authors discuss the results with respect to indirect effects of ketamine on endogenous opiate and dopamine systems on the aforementioned behaviors. The researchers also consider sex differences and possible precautions when dealing with individuals having ingested psychedelic anesthetics.

Animals↗

Melanoma chondroitin sulfate proteoglycan enhances FAK and ERK activation by distinct mechanisms.

Melanoma chondroitin sulfate proteoglycan (MCSP) is an early cell surface melanoma progression marker implicated in stimulating tumor cell proliferation, migration, and invasion. Focal adhesion kinase (FAK) plays a pivotal role in integrating growth factor and adhesion-related signaling pathways, facilitating cell spreading and migration. Extracellular signal-regulated kinase (ERK) 1 and 2, implicated in tumor growth and survival, has also been linked to clinical melanoma progression. We have cloned the MCSP core protein and expressed it in the MCSP-negative melanoma cell line WM1552C. Expression of MCSP enhances integrin-mediated cell spreading, FAK phosphorylation, and activation of ERK1/2. MCSP transfectants exhibit extensive MCSP-rich microspikes on adherent cells, where it also colocalizes with alpha4 integrin. Enhanced activation of FAK and ERK1/2 by MCSP appears to involve independent mechanisms because inhibition of FAK activation had no effect on ERK1/2 phosphorylation. These results indicate that MCSP may facilitate primary melanoma progression by enhancing the activation of key signaling pathways important for tumor invasion and growth.

Amino Acid Sequence↗

PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity.

The regulated incorporation of AMPA receptors into synapses is important for synaptic plasticity. Here we examine the role of protein kinase A (PKA) in this process. We found that PKA phosphorylation of the AMPA receptor subunits GluR4 and GluR1 directly controlled the synaptic incorporation of AMPA receptors in organotypic slices from rat hippocampus. Activity-driven PKA phosphorylation of GluR4 was necessary and sufficient to relieve a retention interaction and drive receptors into synapses. In contrast, PKA phosphorylation of GluR1 and the activity of calcium/calmodulin-dependent kinase II (CaMKII) were both necessary for receptor incorporation. Thus, PKA phosphorylation of AMPA receptor subunits contributes to diverse mechanisms underlying synaptic plasticity.

Amino Acid Sequence↗

Pure mucinous carcinoma of the breast: is axillary staging necessary?

BACKGROUND: Mucinous carcinoma of the breast (MCB) may be associated with a low risk of axillary metastases. METHODS: To evaluate the incidence of axillary nodal metastasis in MCB, a review of all cases from January 1990 to July 2000 was performed. Pure MCB was defined as all tumor cells being completely surrounded by mucin. Patient demographics, tumor size, estrogen receptor status, total number of dissected lymph nodes, and incidence of nodal metastasis were studied. Deeper sections on the lymph nodes from the pure tumors were performed and stained with low-molecular cytokeratin. RESULTS: Nineteen cases of pure MCB and 41 cases of mixed MCB were identified. Patients with pure MCB were older than those with mixed MCB. Tumor size and estrogen receptor status showed no statistically significant differences between the two groups. None of the patients with pure MCB demonstrated lymph node metastases, whereas 12 of 41 cases with mixed MCB demonstrated metastatic lymph node involvement. CONCLUSIONS: Because pure MCB seems unlikely to metastasize, axillary lymph node staging in these patients may not be necessary. The presence of lymph node metastases strongly indicates the presence of a mixed MCB.

Adenocarcinoma, Mucinous↗

Effects of the dopamine antagonist PD 152255 on juvenile rats' responses to dorsal stimulation, the transport response, and related behaviors.

The authors gave 23- and 40-day-old rats doses of the dopamine D3 antagonist PD 152255 and tested them on transport response intensity, vertical cling catalepsy duration, and dorsal immobility duration. Administration of PD 152255 resulted in dose-dependent increases in transport response intensity in 40-day-old rats but was without effect in 23-day-old rats. Administration of PD 152255 caused increases in dorsal immobility durations in both 23- and 40-day-old subjects. The drug was without effect on vertical cling catalepsy. Results are discussed with respect to the role of D3 receptors in the transport response and the nature of D2-D3 receptor interactions.

Animals↗

Spine behavior caudal to instrumentation in King II and IV curves.

This retrospective review of children surgically treated for King Type II or IV curvature of the spine required a minimum lumbar Cobb angle of 40 degrees and a minimum lumbar inclination (the angle formed between a line through the spinous processes of the three most caudal lumbar vertebrae and a line perpendicular to the floor) of 10 degrees. Twenty children had combined anterior thoracolumbar and posterior instrumentations whereas 20 had only posterior instrumentation. Children who had combined surgery had significantly better corrections of their lumbar Cobb angles. They had a mean correction of 43.3 degrees compared with 26.7 degrees in children with posterior instrumentation only. These superior corrections of the lumbar Cobb angles did not result in significantly better improvements in the lumbar inclinations. Patients who had the combined procedures had a mean improvement of 10.1 degrees, whereas patients who had posterior instrumentation only had a mean improvement of 8.0 degrees in lumbar inclination. Instead of having superior corrections of the lumbar inclinations, the combined surgeries resulted in a significant worsening of the angle between the end plates of the last instrumented vertebra and the next most caudal end plate. In patients who had combined surgery this angle averaged 8.4 degrees, whereas in patients who had posterior instrumentation only this angle averaged 4.1 degrees.

Adolescent↗