GAiN: An integrative tool utilizing generative adversarial neural networks for augmented gene expression analysis.

Big genomic data and artificial intelligence (AI) are ushering in an era of precision medicine, providing opportunities to study previously under-represented subtypes and rare diseases rather than categorize them as variances. However, clinical researchers face challenges in accessing such novel technologies as well as reliable methods to study small datasets or subcohorts with unique phenotypes. To address this need, we developed an integrative approach, GAiN, to capture patterns of gene expression from small datasets on the basis of an ensemble of generative adversarial networks (GANs) while leveraging big population data. Where conventional biostatistical methods fail, GAiN reliably discovers differentially expressed genes (DEGs) and enriched pathways between two cohorts with limited numbers of samples (n = 10) when benchmarked against a gold standard. GAiN is freely available at GitHub. Thus, GAiN may serve as a crucial tool for gene expression analysis in scenarios with limited samples, as in the context of rare diseases, under-represented populations, or limited investigator resources.

Symptomatic cholelithiasis in an ectopic retrocolic retroduodenal subhepatic duplicated gallbladder.

Gallbladder duplication is a rare anatomic variant of biliary anatomy, which can present diagnostic and treatment challenges. In this case, a 49-year-old male presented with classic symptoms of biliary colic to his primary care physician, and while computed tomography (CT) noted the presence of gallstones, neither CT nor ultrasound was able to locate a gallbladder within the gallbladder fossa. Initial surgery found and cauterized a rudimentary gallbladder, but symptoms persisted, requiring a second surgery and secondary analysis of CT, ultrasound, and magnetic resonance imaging with magnetic resonance cholangiopancreatography. Imaging helped clarify the diagnosis of gallbladder duplication (ductular type), where the first gallbladder's cystic duct inserted high on the common hepatic duct, and the second retroplaced gallbladder's cystic duct inserted into the midportion of the common bile duct. Thorough understanding of the numerous gallbladder duplication variants, careful interpretation of modern imaging, and close collaboration between surgeon and radiologist are essential for optimal management of patients with gallbladder duplications.

Temporomandibular Joint Internal Derangement Score (TIDS): novel magnetic resonance imaging assessment score and its relation to invasive treatment in patients with clinical temporomandibular joint pathology.

PURPOSE: A new magnetic resonance imaging (MRI) based scoring system for temporomandibular joint (TMJ) internal derangement was developed to predict disease severity and the likelihood of invasive treatment. PATIENTS AND METHODS: Reports and images from bilateral TMJ MRI studies of 100 consecutive patients with TMJ pain were retrospectively reviewed. A Temporomandibular Joint Internal Derangement Score (TIDS) score was composed of 6 MRI characteristics: joint effusion, disc displacement, disc nonrecapture, disc degenerative changes, abnormal condyle translation, and condyle arthritis. The primary endpoint was whether disease severity merited invasive treatment (arthrocentesis, arthroscopy, arthroplasty, or discectomy). Primary analyses were conducted as univariate regression, with the level of significance set at p < .05. Multivariate regression was also used to assess the impacts of each variable upon the need for invasive treatment. RESULTS: Invasive treatment was performed in 29 patients and planned in an additional 9 patients. Patients with clinical bilateral pathology were no more likely to undergo invasive treatment than those with unilateral clinical pathology. Statistically significant correlations were found between bilateral invasive treatment and the presence of bilateral joint effusions (p = 0.0037) and disc displacement (p = 0.014), as well as with increasing values of right TIDS (p = 0.0015) and bilateral TIDS (p = 0.0090). Bilateral TIDS of greater than 6 was correlated with both bilateral invasive treatment (p = 0.0033) and with invasive treatment of any kind (p = 0.041). In each instance of TIDS > 6, the patient demonstrated multiple signs of bilateral TMJ pathology. On multivariate regression, only disc recapture failed to trend towards statistical significance in both the six and twelve component regressions, which trended towards significance only in the twelve component analysis. CONCLUSION: A TIDS score was developed to serve as an adjunct to the clinical assessment of TMJ pathology. Bilateral TIDS score greater than 6 was statistically significantly correlated with the severity of TMJ pathology.

Association of heterozygous hemochromatosis C282Y gene mutation with hand osteoarthritis.

OBJECTIVE: To determine if there is an association between radiographic osteoarthritis (OA) of the hand and the presence of hemochromatosis HFE gene mutations. METHODS: One hundred seventy-six patients with radiographic OA of the hand were randomly selected from an academic rheumatology practice. We measured serum transferrin saturation (TS) and ferritin levels, and genotyped for the presence of the 2 common HFE mutations, C282Y and H63D. The prevalences of HFE mutations in these patients were compared to those in a hemochromatosis screening study from the same primary care patient base. RESULTS: There was a significantly increased prevalence of the C282Y mutation in the OA population compared to the unselected controls (12.5 vs 7.8%; p = 0.029). The prevalence of C282Y in OA was higher among older patients: 15.75% in the group older than 65 years versus 4.08% in the younger group. The mean TS level was higher among OA patients who were heterozygous for C282Y compared to those who lacked both HFE mutations (35.75 vs 25.93%; p < 0.0001). This difference was also found in the general population. CONCLUSION: This is the first report to show an increased risk of OA among individuals who are heterozygous for the C282Y HFE mutation. The increase in this mutation in patients older than 65 suggests that this is associated with a late onset subset of OA. If this association is substantiated by larger randomized controlled studies, it could have major therapeutic implications in the development of specific therapy directed at individuals heterozygous for C282Y HFE mutation.