Multichannel magnetogastrogram: a clinical marker for pediatric chronic nausea.

Chronic nausea is a widespread functional disease in children with numerous comorbidities. High-resolution electrogastrogram (HR-EGG) has shown sufficient sensitivity as a noninvasive clinical marker to objectively detect distinct gastric slow wave properties in children with functional nausea. We hypothesized that the increased precision of magnetogastrogram (MGG) slow wave recordings could provide supplementary information not evident on HR-EGG. We evaluated simultaneous pre- and postprandial MGG and HR-EGG recordings in pediatric patients with chronic nausea and healthy asymptomatic subjects, while also measuring nausea intensity and nausea severity. We found significant reductions in postprandial dominant frequency and normogastric power, and higher levels of postprandial bradygastric power in patients with nausea in both MGG and HR-EGG. MGG also detected significantly lower preprandial normogastric power in patients. A significant difference in the mean preprandial gastric slow wave propagation direction was observed in patients as compared with controls in both MGG (control: 180 ± 61°, patient: 34 ±72°; P < 0.05) and HR-EGG (control: 240 ± 39°, patient: 180 ± 46°; P < 0.05). Patients also showed a significant change in the mean slow wave direction between pre- and postprandial periods in MGG (P < 0.05). No statistical differences were observed in propagation speed between healthy subjects and patients in either MGG or HR-EGG pre/postprandial periods. The use of MGG and/or HR-EGG represents an opportunity to assess noninvasively the effects of chronic nausea on gastric slow wave activity. MGG data may offer the opportunity for further refinement of the more portable and economical HR-EGG in future machine-learning approaches for functional nausea.NEW & NOTEWORTHY Pediatric chronic nausea is a difficult-to-measure subjective complaint that requires objective diagnosis, clinical assessment, and individualized treatment plans. Our study demonstrates that multichannel MGG used in conjunction with custom HR-EGG detects key pathological signatures of functional nausea in children. This quantifiable measure may allow more personalized diagnosis and treatment in addition to minimizing the cost and potential radiation associated with current diagnostic approaches.

Magnetoenterography for the Detection of Partial Mesenteric Ischemia.

BACKGROUND: Acute mesenteric ischemia represents a life-threatening gastrointestinal condition. A noninvasive diagnostic modality that identifies mesenteric ischemia patients early in the disease process will enable early surgical intervention. Previous studies have identified significant changes in the small-bowel electrical slow-wave parameters during intestinal ischemia caused by total occlusion of the superior mesenteric artery. The purpose of this study was to use noninvasive biomagnetic techniques to assess functional physiological changes in intestinal slow waves in response to partial mesenteric ischemia. METHODS: We induced progressive intestinal ischemia in normal porcine subjects (n = 10) by slowly increasing the occlusion of the superior mesenteric artery at the following percentages of baseline flow: 50%, 75%, 90%, and 100% while simultaneous transabdominal magnetoenterogram (MENG) and serosal electromyogram (EMG) recordings were being obtained. RESULTS: A statistically significant serosal EMG amplitude decrease was observed at 100% occlusion compared with baseline, whereas no significant change was observed for MENG amplitude at any progressive occlusion levels. MENG recordings showed significant changes in the frequency and percentage of power distributed in bradyenteric and normoenteric frequency ranges at 50%, 75%, 90%, and 100% vessel occlusions. In serosal EMG recordings, a similar percent power distribution (PPD) effect was observed at 75%, 90%, and 100% occlusion levels. Serosal EMG showed a statistically significant increase in tachyenteric PPD at 90% and 100% occlusion. We observed significant increase in tachyenteric PPD only at the 100% occlusion level in MENG recordings. CONCLUSIONS: Ischemic changes in the intestinal slow wave can be detected early and noninvasively even with partial vascular occlusion. Our results suggest that noninvasive MENG may be useful for clinical diagnosis of partial mesenteric ischemia.

Integrated, High-Throughput, Multiomics Platform Enables Data-Driven Construction of Cellular Responses and Reveals Global Drug Mechanisms of Action.

An understanding of how cells respond to perturbation is essential for biological applications; however, most approaches for profiling cellular response are limited in scope to pre-established targets. Global analysis of molecular mechanism will advance our understanding of the complex networks constituting cellular perturbation and lead to advancements in areas, such as infectious disease pathogenesis, developmental biology, pathophysiology, pharmacology, and toxicology. We have developed a high-throughput multiomics platform for comprehensive, de novo characterization of cellular mechanisms of action. Platform validation using cisplatin as a test compound demonstrates quantification of over 10 000 unique, significant molecular changes in less than 30 days. These data provide excellent coverage of known cisplatin-induced molecular changes and previously unrecognized insights into cisplatin resistance. This proof-of-principle study demonstrates the value of this platform as a resource to understand complex cellular responses in a high-throughput manner.

Electroanatomical mapping of the stomach with simultaneous biomagnetic measurements.

Gastric motility is coordinated by bioelectric slow waves (SWs) and dysrhythmic SW activity has been linked with motility disorders. Magnetogastrography (MGG) is the non-invasive measurement of the biomagnetic fields generated by SWs. Dysrhythmia identification using MGG is currently challenging because source models are not well developed and the impact of anatomical variation is not well understood. A novel method for the quantitative spatial co-registration of serosal SW potentials, MGG, and geometric models of anatomical structures was developed and performed on two anesthetized pigs to verify feasibility. Electrode arrays were localized using electromagnetic transmitting coils. Coil localization error for the volume where the stomach is normally located under the sensor array was assessed in a benchtop experiment, and mean error was 4.2±2.3mm and 3.6±3.3° for a coil orientation parallel to the sensor array and 6.2±5.7mm and 4.5±7.0° for a perpendicular coil orientation. Stomach geometries were reconstructed by fitting a generic stomach to up to 19 localization coils, and SW activation maps were mapped onto the reconstructed geometries using the registered positions of 128 electrodes. Normal proximal-to-distal and ectopic SW propagation patterns were recorded from the serosa and compared against the simultaneous MGG measurements. Correlations between the center-of-gravity of normalized MGG and the mean position of SW activity on the serosa were 0.36 and 0.85 for the ectopic and normal propagation patterns along the proximal-distal stomach axis, respectively. This study presents the first feasible method for the spatial co-registration of MGG, serosal SW measurements, and subject-specific anatomy. This is a significant advancement because these data enable the development and validation of novel non-invasive gastric source characterization methods.

Automated Machine Learning Pipeline Framework for Classification of Pediatric Functional Nausea Using High-Resolution Electrogastrogram.

OBJECTIVE: Pediatric functional nausea is challenging for patients to manage and for clinicians to treat since it lacks objective diagnosis and assessment. A data-driven non-invasive diagnostic screening tool that distinguishes the electro-pathophysiology of pediatric functional nausea from healthy controls would be an invaluable aid to support clinical decision-making in diagnosis and management of patient treatment methodology. The purpose of this paper is to present an innovative approach for objectively classifying pediatric functional nausea using cutaneous high-resolution electrogastrogram data. METHODS: We present an Automated Electrogastrogram Data Analytics Pipeline framework and demonstrate its use in a 3x8 factorial design to identify an optimal classification model according to a defined objective function. Low-fidelity synthetic high-resolution electrogastrogram data were generated to validate outputs and determine SOBI-ICA noise reduction effectiveness. RESULTS: A 10 parameter support vector machine binary classifier with a radial basis function kernel was selected as the overall top-performing model from a pool of over 1000 alternatives via maximization of an objective function. This resulted in a 91.6% test ROC AUC score. CONCLUSION: Using an automated machine learning pipeline approach to process high-resolution electrogastrogram data allows for clinically significant objective classification of pediatric functional nausea. SIGNIFICANCE: To our knowledge, this is the first study to demonstrate clinically significant performance in the objective classification of pediatric nausea patients from healthy control subjects using experimental high-resolution electrogastrogram data. These results indicate a promising potential for high-resolution electrogastrography to serve as a data-driven screening tool for the objective diagnosis of pediatric functional nausea.

Processes in DNA damage response from a whole-cell multi-omics perspective.

Technological advances have made it feasible to collect multi-condition multi-omic time courses of cellular response to perturbation, but the complexity of these datasets impedes discovery due to challenges in data management, analysis, visualization, and interpretation. Here, we report a whole-cell mechanistic analysis of HL-60 cellular response to bendamustine. We integrate both enrichment and network analysis to show the progression of DNA damage and programmed cell death over time in molecular, pathway, and process-level detail using an interactive analysis framework for multi-omics data. Our framework, Mechanism of Action Generator Involving Network analysis (MAGINE), automates network construction and enrichment analysis across multiple samples and platforms, which can be integrated into our annotated gene-set network to combine the strengths of networks and ontology-driven analysis. Taken together, our work demonstrates how multi-omics integration can be used to explore signaling processes at various resolutions and demonstrates multi-pathway involvement beyond the canonical bendamustine mechanism.

The effect of chronic nausea on gastric slow wave spatiotemporal dynamics in children.

BACKGROUND: Chronic nausea in adolescents with functional gastrointestinal disorders is an increasingly reported but poorly understood symptom that negatively affects quality of life. Functional gastrointestinal disorders are known to correlate closely with slow wave rhythm disturbances. The ability to characterize gastric electrophysiologic perturbations in functional nausea patients could provide potential diagnostic and therapeutic tools for nausea patients. METHODS: We used high-resolution electrogastrograms (HR-EGG) to measure gastric slow wave parameters in pediatric chronic nausea patients and healthy subjects both pre- and postprandial. We computed the dominant frequency, percentage power distribution, gastric slow wave propagation direction, and speed from HR-EGG. KEY RESULTS: We observed significant differences in the dominant frequency and power distributed in normal and bradyarrhythmia frequency ranges when comparing patients and healthy subjects. Propagation patterns in healthy subjects were predominantly anterograde, while patients exhibited a variety of abnormalities including retrograde, anterograde, and disrupted patterns. There was a significant difference in the preprandial mean slow wave direction between healthy subjects (222° ± 22°) and patients (103° ± 66°; p Ë‚ 0.01), although the postprandial mean direction between healthy subjects and patients was similar (p = 0.73). No significant difference in slow wave propagation speed was found between patients and healthy subjects in either pre- (p = 0.21) or postprandial periods (p = 0.75). CONCLUSIONS AND INFERENCES: The spatiotemporal characterization of gastric slow wave activity using HR-EGG distinguishes symptomatic chronic nausea patients from healthy subjects. This characterization may in turn inform and direct clinical decision-making and lead to further insight into its pathophysiology.

Category difference facilitates oddity learning in honeybees (Apis mellifera).

Performance of honeybees resembles that of vertebrates in a variety of associative learning experiments. Recent work has focused on relational learning phenomena not easily explained by associative principles, including same/different problems, the simplest of which is the oddity problem. Free-flying bees were trained to visit a laboratory window and were rewarded for choice of the odd stimulus among a set of stimuli. There were two stimulus categories, single-color solids and two-color patterns. The training was trial-unique, with new sets of stimuli on each trial. In Experiment 1, 4 groups were trained in a 3-stimulus oddity problem, 2 with solid odd and patterns nonodd and 2 with pattern odd and solids nonodd. For 1 group in each condition, the odd and nonodd stimuli shared a color. The performance of all groups was better than chance. The bees could solve the problem on the basis of oddity (same vs. different) or category (solid vs. pattern). These possibilities were unconfounded in Experiment 2 with 2 groups trained in a 4-stimulus oddity problem. Group 1 was trained with a category difference on each trial; the solid color was odd on half the trials and the pattern odd on the others. Group 2 was trained with no category difference; all stimuli were patterns. Both groups showed better-than-chance performance, and the irrelevant category difference facilitated oddity discrimination for Group 1. The results support previous findings of oddity learning in honeybees, the only invertebrate species for which any relational learning phenomena have been demonstrated. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Noninvasive Magnetogastrography Detects Erythromycin-Induced Effects on the Gastric Slow Wave.

OBJECTIVE: The prokinetic action of erythromycin is clinically useful under conditions associated with gastrointestinal hypomotility. Although erythromycin is known to affect the electrogastrogram, no studies have examined the effects that erythromycin has on gastric slow wave magnetic fields. METHODS: In this study, gastric slow wave activity was assessed simultaneously using noninvasive magnetogastrogram (MGG), electrogastrogram, and mucosal electromyogram recordings. Recordings were obtained for 30 min prior to and 60 min after intravenous administration of erythromycin at dosages of 3 and 6 mg/kg. RESULTS: MGG recordings showed significant changes in the percentage power distribution of gastric signal after infusion of both 3 and 6 mg/kg erythromycin at t = 1-5 min that persisted for t = 30-40 min after infusion. These changes agree with the changes observed in the electromyogram. We did not observe any statistically significant difference in MGG amplitude before or after injection of either 3 or 6 mg/kg erythromycin. Both 3 and 6 mg/kg erythromycin infusion showed retrograde propagation with a statistically significant decrease in slow wave propagation velocity 11-20 min after infusion. Propagation velocity started returning toward baseline values after approximately 21-30 min for the 3 mg/kg dosage and after 31-40 min for a dosage of 6 mg/kg. CONCLUSION: Our results showed that the magnetic signatures were sensitive to disruptions in normal slow wave activity induced by pharmacological and prokinetic agents such as erythromycin. SIGNIFICANCE: This study shows that repeatable noninvasive bio-electro-magnetic techniques can objectively characterize gastric dysrhythmias and may quantify treatment efficacy in patients with functional gastric disorders.

Relational learning in honeybees (Apis mellifera): Oddity and nonoddity discrimination.

Honeybee learning is surprisingly similar to vertebrate learning and one implication is that the basic associative learning principles are also similar. This research extends the work to more complex cognitive phenomena. Forager bees were trained individually to visit a laboratory window for sucrose. On each training trial for all experiments, bees found three stimuli, two identical and one different. In Experiments 1 and 2, stimuli were three-dimensional two-color patterns, and in Experiments 3 and 4, stimuli were two-color patterns displayed on a computer monitor. Training was trial-unique, that is, a different triad of stimuli was presented on each trial. In Experiments 1 and 3, choice of odd was rewarded and choice of nonodd was punished. In Experiments 2 and 4, choice of nonodd was rewarded and choice of odd was punished. On every trial, the initial choice was recorded and correction permitted. Honeybees learned to choose the odd stimulus in Experiments 1 and 3 and the nonodd stimuli in Experiments 2 and 4. The results provide compelling evidence of oddity and nonoddity learning, often interpreted as relational learning in vertebrates. Whether the mechanism of such learning in honeybees is similar to that of vertebrate species remains to be determined.