Oncocytoma-Related Gene Signature to Differentiate Chromophobe Renal Cancer and Oncocytoma Using Machine Learning

Publicly available gene expression datasets were analyzed to develop a chromophobe and oncocytoma related gene signature (COGS) to distinguish chRCC from RO. The datasets GSE11151, GSE19982, GSE2109, GSE8271 and GSE11024 were combined into a discovery dataset. The transcriptomic differences were identified with unsupervised learning in the discovery dataset (97.8% accuracy) with density based UMAP (DBU). The top 30 genes were identified by univariate gene expression analysis and ROC analysis, to create a gene signature called COGS. COGS, combined with DBU, was able to differentiate chRCC from RO in the discovery dataset with an accuracy of 97.8%. The classification accuracy of COGS was validated in an independent meta-dataset consisting of TCGA-KICH and GSE12090, where COGS could differentiate chRCC from RO with 100% accuracy. The differentially expressed genes were involved in carbohydrate metabolism, transcriptomic regulation by TP53, beta-catenin-dependent Wnt signaling, and cytokine (IL-4 and IL-13) signaling highly active in cancer cells. Using multiple datasets and machine learning, we constructed and validated COGS as a tool that can differentiate chRCC from RO and complement histology in routine clinical practice to distinguish these two tumors.

Can vena cava ultrasound-guided volume repletion prevent general induced hypotension in elderly patients? A mini-fluid challenge

Background Hypotension is often occurring after induction of general anesthesia (IGA) and can cause organ hypoperfusion and ischemia which associated with adverse outcomes in patients having both cardiac and non-cardiac surgery. Elderly patients are particularly more vulnerable and at increased risk to the depressant effect of anesthetic drugs. So, recognition and prevention of such event are of clinical importance. This study recruited patients aged above 60 years, with ASA physical status classification I-II-III who were scheduled for surgery under general anesthesia with the aim to assess the effectiveness of preoperative IVC ultrasonography in predicting hypotension which develops following IGA and its association with the volume status in elderly patients receiving general anesthesia, through measurements of the maximum inferior vena cava diameter (dIVCmax), minimum inferior vena cava diameter (dIVCmin), inferior vena cava collapsibility index (IVC-CI), and basal and post-induction mean arterial pressure (MAP). Results Thirty-nine (44.3%) of the 88 patients developed hypotension after IGA, and it was significantly more in patients who did not receive preoperative fluid (p = 0.045). The cut-off for dIVCmax was found as 16.250 mm with the ROC analysis. Specificity and sensitivity for the cut-off value of 16.250 mm were calculated as 61.2% and 76.9%, respectively. The cut-off for IVC-CI was found as 33.600% with the ROC analysis. Specificity and sensitivity for the cut-off value of 33.600% were calculated as 68.7% and 87.2%, respectively. Conclusions IVC ultrasonography may be helpful in the prediction of preoperative hypovolemia in elderly patients in the form of high IVC-CI and low dIVCmax. The incidence of hypotension was lower in patients who received fluid infusion before IGA.

Immune infiltration and a ferroptosis-related gene signature for predicting the prognosis of patients with cholangiocarcinoma

Background Cholangiocarcinoma (CHOL) is a digestive tract tumor with high malignancy and poor prognosis and is extremely challenging to treat. At present, induced cell death holds great promise in tumor therapy. Ferroptosis is a recently proposed pattern of programmed cell death, and numerous studies have shown that it is intimately involved in tumors. However, the roles of differentially expressed ferroptosis-related genes (DEFRGs) in CHOL have not been investigated. Methods Our study was based on the The Cancer Genome Atlas (TCGA) database, DEFRGs were obtained to construct a prognostic riskScore model of CHOL by univariate and multivariate Cox regression analyses. Subsequently, the model was evaluated by nomogram construction, survival analysis, receiver operating characteristic (ROC) analysis and exploration of the immune microenvironment, and the mRNA and protein expression levels of each gene in the model were validated by Gene Expression Omnibus (GEO) database and quantitative real-time PCR (qRT-PCR). Results We screened four DEFRGs from the TCGA database to construct a prognostic model. The construction of a nomogram confirmed the predictive value of the model for overall survival (OS), and it was confirmed to have high diagnostic value by ROC analysis. The GSEA results suggested that these genes were mainly enriched in ferroptosis- and metabolism-related pathways. Finally, our experimental results validated the expression levels of the four DEFRGs, which were almost consistent with our bioinformatics results. Conclusion Our study found that the prognostic model showed extremely high diagnostic and prognostic value and could predict the possibility of immunotherapy, thus providing a new direction for individualized treatment of patients with CHOL.

Issue of Waist Circumference for the Diagnosis of Metabolic Syndrome Regarding Arterial Stiffness: Possible Utility of a Body Shape Index in Middle-Aged Nonobese Japanese Urban Residents Receiving Health Screening

<b><i>Introduction:</i></b> Abdominal obesity as a risk factor for diagnosing metabolic syndrome (MetS) is evaluated using waist circumference (WC), although WC does not necessarily reflect visceral adiposity. This cross-sectional study aimed to clarify whether replacing WC with “A Body Shape Index (ABSI),” an abdominal obesity index, in MetS diagnosis detects individuals with arterial stiffening assessed by cardio-ankle vascular index (CAVI). <b><i>Methods:</i></b> A retrospective cross-sectional study was conducted in 46,872 Japanese urban residents (median age 40 years) who underwent health screening. Exclusion criteria were current treatments and a past history of cardiovascular disease (CVD). The Japanese, International Diabetes Federation, and NCEP-ATPIII criteria were used to diagnose MetS. High CAVI was defined as CAVI ≥9.0. <b><i>Results:</i></b> CAVI correlated positively with ABSI (β = 0.127), but negatively with WC (β = −0.186), independent of age, sex, systolic blood pressure, fasting plasma glucose, and high-density lipoprotein--cholesterol. Receiver operating characteristic (ROC) analysis showed that ABSI had a stronger contribution to high CAVI (area under the ROC curve [AUC] = 0.730) than WC (AUC = 0.595) and body mass index (AUC = 0.520). ABSI ≥0.080 was defined as abdominal obesity based on the results of ROC analysis for high CAVI and estimated glomerular filtration rate &#x3c;60 mL/min/1.73 m². Logistic regression analysis revealed that replacing high WC with ABSI ≥0.080 in MetS diagnosis enhanced the detection of subjects with high CAVI. <b><i>Discussion/Conclusion:</i></b> Use of ABSI can detect subjects with arterial stiffening, which may lead to efficient stratification of CVD risk. Further studies are needed to confirm whether MetS diagnosis using ABSI predicts CVD morbidity and mortality.

Ophthalmic manifestations are associated with reduced tear lymphotoxin-α levels in chronic ocular graft-versus-host disease

Purpose To determine the role tear lymphotoxin-α (LT-α) in chronic ocular graft-versus-host disease (oGVHD). Methods Twenty-two chronic oGVHD and 17 control tear samples were collected, and commercial test strips were used to detect LT-α concentrations. Concentration differences between patients with and without oGVHD were determined via Mann-Whitney U test. The correlation between LT-α levels and ophthalmic parameters was analyzed using Spearman’s test. Results The concentration of LT-α was significantly lower in oGVHD patients than in controls. LT-α levels were significantly correlated with OSDI, NIH eye score, T-BUT, and CFS among all participants. ROC analysis revealed that the area under the curve of LT-α was 0.847, and the cutoff value for chronic oGVHD diagnosis was 0.203 ng/mL. Conclusion Our study revealed the significant decrease of tear LT-α in oGVHD, and suggested LT-α as a promising marker for chronic oGVHD diagnosis.

Simple Quantification of Surface Uptake in F-18 Florapronol PET/CT Imaging for the Validation of Alzheimer’s Disease

We developed a novel quantification method named shape feature using F-18 florapronol positron emission tomography–computed tomography (PET/CT) and evaluated its sensitivity and specificity for discriminating between patients with Alzheimer’s disease (AD) and patients with mild cognitive impairment or other precursors dementia (non-AD). We calculated the cerebral amyloid smoothing score (CASS) and brain atrophy index (BAI) using the surface area and volume of the region of interest in PET images. We calculated gray and white matter from trained CT data, prepared using U-net. Shape feature was calculated by multiplying CASS with BAI scores. We measured region-based standard uptake values (SUVr) and performed receiver operating characteristic (ROC) analysis to compare SUVr, shape feature, CASS, and BAI score. We investigated the relationship between shape feature and neuropsychological tests. Fifty subjects (23 with AD and 27 with non-AD) were evaluated. SUVr, shape feature, CASS, and BAI score were significantly higher in patients with AD than in those with non-AD. There was no statistically significant difference between shape feature and SUVr in ROC analysis. Shape feature correlated well with mini-mental state examination scores. Shape feature can effectively quantify beta-amyloid deposition and atrophic changes in the brain. These results suggest that shape feature is useful in the diagnosis of AD.

Metabolomics of a cell line-derived xenograft model reveals circulating metabolic signatures for malignant mesothelioma

Background Malignant mesothelioma (MM) is a rare and highly aggressive cancer. Despite advances in multidisciplinary treatments for cancer, the prognosis for MM remains poor with no effective diagnostic biomarkers currently available. The aim of this study was to identify plasma metabolic biomarkers for better MM diagnosis and prognosis by use of a MM cell line-derived xenograft (CDX) model. Methods The MM CDX model was confirmed by hematoxylin and eosin staining and immunohistochemistry. Twenty female nude mice were randomly divided into two groups, 10 for the MM CDX model and 10 controls. Plasma samples were collected two weeks after tumor cell implantation. Gas chromatography-mass spectrometry analysis was conducted. Both univariate and multivariate statistics were used to select potential metabolic biomarkers. Hierarchical clustering analysis, metabolic pathway analysis, and receiver operating characteristic (ROC) analysis were performed. Additionally, bioinformatics analysis was used to investigate differential genes between tumor and normal tissues, and survival-associated genes. Results The MM CDX model was successfully established. With VIP > 1.0 and P-value < 0.05, a total of 23 differential metabolites were annotated, in which isoleucine, 5-dihydrocortisol, and indole-3-acetamide had the highest diagnostic values based on ROC analysis. These were mainly enriched in pathways for starch and sucrose metabolism, pentose and glucuronate interconversions, galactose metabolism, steroid hormone biosynthesis, as well as phenylalanine, tyrosine and tryptophan biosynthesis. Further, down-regulation was observed for amino acids, especially isoleucine, which is consistent with up-regulation of amino acid transporter genes SLC7A5 and SLC1A3 in MM. Overall survival was also negatively associated with SLC1A5, SLC7A5, and SLC1A3. Conclusion We found several altered plasma metabolites in the MM CDX model. The importance of specific metabolic pathways, for example amino acid metabolism, is herein highlighted, although further investigation is warranted.

Meckel’s Diverticulum in Children: A Monocentric Experience and Mini-Review of Literature

Vitelline duct anomalies (VDA, including Meckel’s diverticulum (MD)) result from failed embryologic obliteration. This study aimed for characteristics in symptomatic versus asymptomatic VDA, analyzing clinico-laboratory data from 73 children, aged 1 day to 17 years, treated at a tertiary Pediatric Surgery Institution from 2002–2017. A male preponderance was obtained (ratio 3.6:1). MD accounted for 85% of VDA. Incidence of symptomatic VDA decreased with older age. Leading symptoms were intestinal obstruction and hemorrhage. Mucosal heterotopia (present in 39% of symptomatic MD) was associated with anemia and lowered CRP-levels. On ROC-analysis, hemoglobin < 8.6 g/dL, CRP < 0.6 mg/dL and MD distance to ileocecal valve >40 cm were predictors of ectopic tissue in symptomatic MD. Our data confirmed known characteristics as male preponderance, declined incidence of symptomatic cases with age and predominance of gastric ectopia in symptomatic MD. Moreover, anemia and prolonged distance of MD to ileocecal valve were predictors of ectopic mucosa in symptomatic MD.