Purpose: Bladder cancer (BCa) is generally considered one of the most prevalent deadly diseases worldwide. Patients suffering from muscle-invasive bladder cancer (MIBC) possess dismal prognoses, while those with non-muscle-invasive bladder cancer (NMIBC) generally have a favorable outcome after local treatment. However, some NMIBCs relapse and progress to MIBC, with an unclarified mechanism. Hence, insight into the genetic drivers of BCa progression has tremendous potential benefits for precision therapeutics, risk stratification, and molecular diagnosis. Methods: In this study, three cohorts profile datasets (GSE13507, GSE32584, and GSE89) consisting of NMIBC and MIBC samples were integrated to address the differently expressed genes (DEGs). Subsequently, the protein-protein interaction (PPI) network and pathway enrichment analysis of DGEs were performed. Results: Six collagen members (COL1A1, COL1A2, COL5A2, COL6A1, COL6A2, and COL6A3) were up-regulated and gathered in the ECM-receptor interaction signal pathway identified by KEGG pathway analysis and GSEA. Evidence derived from the Oncomine and TCGA databases indicated that the 6 collagen genes promote the progression of BCa and are negatively associated with patient prognosis. Moreover, taking COL1A1 as a further research object, the results showed that COL1A1 was up-regulated in MIBC and its knockdown significantly inhibited the proliferation, migration, and invasion of 5637 and T24 cells by inhibiting epithelial-mesenchymal transition (EMT) process and the TGF-β signaling pathway. Conclusion: With integrated bioinformatic analysis and cell experiments, we showed that 6 collagen family members are high progression risk factors and that they can be used as independent effective diagnostic and prognostic biomarkers for BCa.

Background The psychosocial benefits of postmastectomy breast reconstruction are well established; however, health care barriers persist. The authors evaluated statewide patient population to further identify obstacles to reconstruction. Methods A linked data set combining the North Carolina Central Cancer Registry with administrative claims from Medicare, Medicaid, and private insurance plans identified women diagnosed with breast cancer from 2003 to 2006. For inclusion in the study, women must have had a mastectomy within 6 months of diagnosis and had continuous insurance enrollment at least 2 years postoperatively (n = 5381). Multivariable logistic regression was used to model odds of reconstruction. Results Approximately 20 percent underwent reconstruction (n = 1130). Distance to a plastic surgeon—10 to 20 miles (OR, 0.78) and greater than 20 miles (OR, 0.73; p < 0.05)—was significantly predictive of no reconstruction, independent of other well-known disparities, including age, race, rural location, and lower household income. Women with government-funded health care, such as Medicare (OR, 0.58) and Medicaid (OR, 0.24; p < 0.001), were also significantly less likely to undergo reconstruction. Consistent with previous study, advanced cancer stage and receipt of radiation therapy decreased the likelihood of reconstruction. Furthermore, when the authors compared immediate to delayed reconstruction, rural location, chemotherapy, and radiation therapy were significantly predictive of delay. Conclusions This is the first population-based study to demonstrate distance to care and insurance plan as significant predictors of receipt of reconstruction. Additional research is needed to understand health care barriers and to determine whether distance to a plastic surgeon can be ameliorated by outreach programs. CLINICAL QUESTION/LEVEL OF EVIDENCE Risk, III.

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CAD encodes a multifunctional enzyme involved in de novo pyrimidine biosynthesis, and pyrimidine can be alternatively recycled from uridine. Trio whole-exome sequencing identified CAD compound heterozygous mutations in a new male patient with global developmental delay (DD), refractory epilepsy, and anemia with anisopoikilocytosis. We further reviewed all published cases with CAD deficiency. Five patients were collected from two publications, including three males and two females, and all presented with DD, drug-resistant epilepsy, and anemia with anisopoikilocytosis. Four out of six patients (including the present case) were supplemented with uridine, which led to immediate cessation of seizures, resolved anemia with anisopoikilocytosis, and progress in global development. The other two patients, who were not treated with uridine, died at the ages of 4 and 5 years. In summary, CAD deficiency is probably a treatable neurometabolic disorder.

IBA57 is involved in the biogenesis of mitochondrial [4Fe-4S] proteins. Eighteen cases with IBA57 mutations have been reported to date. We described a novel phenotype in 11 children with cavitating leukoencephalopathy and summarized the phenotypic spectrum of IBA57 mutations. The median age of onset was 9 months, with an initial presentation of motor regression. Deterioration of neurological function reached its peak within 4 months. The median interval between onset and last follow-up was 2.9 years (0.4-10.0). All cases survived and remained stable. Severe motor handicap was observed in 50.0% of the patients, 52.9% to 71.4% had a delay in communication, problem solving or personal-social skills, and 20.0% had mild symptomatic fluctuations. In the peak phase, magnetic resonance imaging (MRI) lesions were mainly observed in the periventricular/central white matter, and cavitating lesions and patchy high diffusion-weighted imaging (DWI) signals were observed. The numbers and extent of restricted diffusional lesions were reduced, and atrophy was prominent in the recovery phase. Eight novel mutations in IBA57 were identified in our study. This study provided more information about the natural history and evolution of neuroimaging. Combined with previously reported patient studies, our findings suggest that defects in IBA57 can produce diverse phenotypes. IBA57 should be considered a candidate gene for cavitating leukoencephalopathy.