Coherence Resonance and Noise-Induced Synchronization in Globally Coupled Hodgkin-Huxley Neurons

The coherence resonance (CR) of globally coupled Hodgkin-Huxley neurons is studied. When the neurons are set in the subthreshold regime near the firing threshold, the additive noise induces limit cycles. The coherence of the system is optimized by the noise. A bell-shaped curve is found for the peak height of power spectra of the spike train, being significantly different from a monotonic behavior for the single neuron. The coupling of the network can enhance CR in two different ways. In particular, when the coupling is strong enough, the synchronization of the system is induced and optimized by the noise. This synchronization leads to a high and wide plateau in the local measure of coherence curve. The local-noise-induced limit cycle can evolve to a refined spatiotemporal order through the dynamical optimization among the autonomous oscillation of an individual neuron, the coupling of the network, and the local noise.Comment: five pages, five figure

Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer

We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival “neuronal” subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments. A multiplatform analysis of 412 muscle-invasive bladder cancer patients provides insights into mutational profiles with prognostic value and establishes a framework associating distinct tumor subtypes with clinical options

Genetic alterations and histopathologic findings in familial renal cell carcinoma

Renal cell carcinoma is increasing in frequency in the United States and is often detected late in the course of disease due to nonspecific symptoms. A subset of renal cell carcinoma is attributable to familial or hereditary syndromes, including von Hippel-Lindau and Birt-Hogg-Dubé syndromes, among others. Understanding of the molecular alterations in patients with familial syndromes may provide some insight into the underlying mechanisms of disease initiation and progression. This review describes the various subtypes of renal cell carcinoma and the familial syndromes associated with these tumors

Comparative gene expression profiling analysis of urothelial carcinoma of the renal pelvis and bladder

10.1186/1755-8794-3-58BMC Medical Genomics35

Bladder cancer

Bladder cancer is a global health issue with sex differences in incidence and prognosis. Bladder cancer has distinct molecular subtypes with multiple pathogenic pathways depending on whether the disease is non-muscle invasive or muscle invasive. The mutational burden is higher in muscle-invasive than in non-muscle-invasive disease. Commonly mutated genes include TERT, FGFR3, TP53, PIK3CA, STAG2 and genes involved in chromatin modification. Subtyping of both forms of bladder cancer is likely to change considerably with the advent of single-cell analysis methods. Early detection signifies a better disease prognosis; thus, minimally invasive diagnostic options are needed to improve patient outcomes. Urine-based tests are available for disease diagnosis and surveillance, and analysis of blood-based cell-free DNA is a promising tool for the detection of minimal residual disease and metastatic relapse. Transurethral resection is the cornerstone treatment for non-muscle-invasive bladder cancer and intravesical therapy can further improve oncological outcomes. For muscle-invasive bladder cancer, radical cystectomy with neoadjuvant chemotherapy is the standard of care with evidence supporting trimodality therapy. Immune-checkpoint inhibitors have demonstrated benefit in non-muscle-invasive, muscle-invasive and metastatic bladder cancer. Effective management requires a multidisciplinary approach that considers patient characteristics and molecular disease characteristics

Clinicopathologic Characteristics of 23 Cases of Invasive Low-grade Papillary Urothelial Carcinoma.

OBJECTIVE: To investigate the clinicopathologic and immunohistochemical features associated with invasive low-grade papillary urothelial carcinoma (LGPUC), an uncommon entity not previously described in published studies. METHODS: A multicenter effort originally identified 36 cases diagnosed as invasive LGPUC by urologic pathology subspecialists; after re-review, 23 cases were included. RESULTS: The average patient age was 69 years (range 46-82); 20 patients were men and 3 were women. Stage pT1 disease was present in 19 (83%) of 23 and pT2 disease in 4 patients. Of the 23 cases, 13 (57%) showed a single focus of invasion and 10 multiple foci. The invasive front showed rounded, variably sized nests in 17 cases (74%) and irregular nests with retraction artifact in 6. Additional findings in the noninvasive component included inverted growth in 23, apoptotic debris in 5, focal brisk mitotic activity in 4, dispersed chromatin in individual cells in 4, and a single atypical cell in 2. Immunohistochemical stains showed focal p53 nuclear stain in 23, patchy full-thickness cytokeratin 20 stain in 20, full-thickness CD44 expression in 17, and retention of E-cadherin in 23 cases. Clinical follow-up was available for all patients. The subsequent diagnosis included papilloma in 1 patient (4%), LGPUC in 5 (22%), and high-grade papillary urothelial carcinoma in 8 (35%) of the 23 patients, with 5 demonstrating invasion. Of the latter patients, 2 developed metastatic disease. CONCLUSION: Given the risk of progressive disease in these patients, especially the limited stage pT1 disease in most patients, additional studies investigating the molecular properties and outcomes associated with this uncommon lesion are warranted

Updated pathology reporting standards for bladder cancer: biopsies, transurethral resections and radical cystectomies

AIM: Optimal management of bladder cancer requires an accurate, standardised and timely pathological diagnosis, and close communication between surgeons and pathologists. Here, we provide an update on pathology reporting standards of transurethral resections of the bladder and cystectomies. METHODS: We reviewed recent literature, focusing on developments between 2013 and 2021. RESULTS: Published reporting standards developed by pathology organizations have improved diagnosis and treatment. Tumor sub-staging and subtyping has gained increased attention. Lymph nodes continue to be an area of debate, and their staging has seen minor modifications. Several tasks, particularly regarding specimen preparation ("grossing"), are not yet standardized and offer opportunity for improvement. Molecular classification is rapidly evolving, but currently has only limited impact on management. CONCLUSION: Pathological reporting of bladder cancer is continuously evolving and remains challenging in some areas. This review provides an overview of recent major developments, with a particular focus on published reporting standards