Fluorescence is a mainstay of bioanalytical methods, offering sensitive and quantitative reporting, often in multiplexed or multiparameter assays. Perhaps the best example of the latter is flow cytometry, where instruments equipped with multiple lasers and detectors allow measurement of 15 or more different fluorophores simultaneously, but increases beyond this number are limited by the relatively broad emission spectra. Surface enhanced Raman scattering (SERS) from metal nanoparticles can produce signal intensities that rival fluorescence, but with narrower spectral features that allow a greater degree of multiplexing. We are developing nanoparticle SERS tags as well as Raman flow cytometers for multiparameter single cell analysis of suspension or adherent cells. SERS tags are based on plasmonically active nanoparticles (gold nanorods) whose plasmon resonance can be tuned to give optimal SERS signals at a desired excitation wavelength. Raman resonant compounds are adsorbed on the nanoparticles to confer a unique spectral fingerprint on each SERS tag, which are then encapsulated in a polymer coating for conjugation to antibodies or other targeting molecules. Raman flow cytometry employs a high resolution spectral flow cytometer capable of measuring the complete SERS spectra, as well as conventional flow cytometry measurements, from thousands of individual cells per minute. Automated spectral unmixing algorithms extract the contributions of each SERS tag from each cell to generate high content, multiparameter single cell population data. SERS-based cytometry is a powerful complement to conventional fluorescence-based cytometry. The narrow spectral features of the SERS signal enables more distinct probes to be measured in a smaller region of the optical spectrum with a single laser and detector, allowing for higher levels of multiplexing and multiparameter analysis.
This paper describes a new version of the mixedinitiative collaborative level designing system: Baba is Y'all, as well as the results of a user study on the system. Baba is Y'all is a prototype for AI-assisted game design in collaboration with others. The updated version includes a more user-friendly interface, a better level-evolver and recommendation system, and extended site features. The system was evaluated via a user study where participants were required to play a previously submitted level from the site and then create their own levels using the editor. They reported on their individual process creating the level and their overall experience interacting with the site. The results have shown both the benefits and limitations of a mixedinitiative system and how it can help with creating a diversity of 'Baba is You' levels that are both human and AI designed while maintaining their quality.
INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is a spectrum ranging from simple steatosis to cirrhosis. It is present in 33% of the general adult population and is more prevalent in overweight and diabetic patients. This can be explained by abnormal lipid metabolism with stressed conditions such as Cushing's disease (CD). In CD, glucocorticoids act synergistically with insulin to increase lipid accumulation. The incidence of NAFLD in CD is not well described but is thought to be greater than the general population. CD is less commonly labelled as a culprit of elevated liver chemistries. Here, we present a case of a young woman with uncharacteristically elevated liver tests found to be due to CD. CASE DESCRIPTION/METHODS: A 35-year-old woman was admitted for abdominal pain, nausea, and vomiting. Her medical history included a pituitary adenoma with subsequent CD status post three resections, diabetes insipidus, diabetes mellitus type 2, bipolar disorder, and symptomatic cholelithiasis status post cholecystectomy. Admission labs showed total bilirubin 3.70 mg/dL, ALP 480 U/L, AST 681 U/L, ALT 992 U/L, lipase 25 U/L. Workup was negative including viral hepatitis including hepatitis E, autoimmune hepatitis, hemochromatosis, alpha-1 anti-trypsin deficiency were negative. Abdominal ultrasound and MRCP showed hepatic steatosis. Liver biopsy revealed 70-80% macrovesicular hepatic steatosis and prominent cholestasis. Her liver function tests transitioned to a cholestatic pattern with total bilirubin 7.07 mg/dL, ALP 1019 U/L, AST 273 U/L, and ALT 519 U/L. She was started on ursodiol 15 mg/kg resulting in immediate symptomatic improvement. One month following hospitalization while on treatment, labs were AST 21 U/L and ALT 30 U/L. DISCUSSION: NAFLD is diagnosed by adiposity within the liver on imaging or histopathology and remains the most common cause of abnormal liver chemistries. Patients with CD have been shown to have a higher incidence of NAFLD, as much as 20%. This is thought due to an increase in visceral fat rather than a direct effect of cortisol, as often the BMI is not particularly elevated. While a majority of patients with NALFD may have normal transaminases, a study by Shirin et al found that patients with higher elevations in cholestatic enzymes were more likely to have advanced liver disease. Thus, clinicians should have a high suspicion when a patient has comorbidities predisposing them to hepatic steatosis, including metabolic syndromes such as CD.
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