Multi-State Gene Cluster Switches Determine the Adaptive Mitochondrial And Metabolic Landscape of Breast Cancer.

Adaptive metabolic switches are proposed to underlie conversions between cellular states during normal development as well as in cancer evolution. Metabolic adaptations represent important therapeutic targets in tumors, highlighting the need to characterize the full spectrum, characteristics, and regulation of the metabolic switches. To investigate the hypothesis that metabolic switches associated with specific metabolic states can be recognized by locating large alternating gene expression patterns, we developed a method to identify interspersed gene sets by massive correlated biclustering (MCbiclust) and to predict their metabolic wiring. Testing the method on breast cancer transcriptome datasets revealed a series of gene sets with switch-like behavior that could be used to predict mitochondrial content, metabolic activity, and central carbon flux in tumors. The predictions were experimentally validated by bioenergetic profiling and metabolic flux analysis of 13C-labelled substrates. The metabolic switch positions also distinguished between cellular states, correlating with tumor pathology, prognosis, and chemosensitivity. The method is applicable to any large and heterogeneous transcriptome dataset to discover metabolic and associated pathophysiological states.

Emphysematous epididymo-orchitis: imaging plays a vital part in active management: case report and literature review.

We hereby present a rare cause of acute scrotum secondary to emphysematous epididymo-orchitis (EEO). It is often not diagnosed until crepitus is palpable in the scrotal wall with spreading cellulitis, at which point it has reached an advanced stage. This case report details a 55-year-old man with poorly controlled diabetes who presented with an acute scrotum that failed to resolve with oral antibiotics in primary care. Following rapid detection of EEO on an early scrotal ultrasound scan, the patient had surgical debridement and a near-total orchidectomy with only a small stump of testis and tunica albuginea left behind. This case highlights the importance of timely imaging, particularly in diabetic men with an acute scrotum with a high clinical suspicion of intratesticular abscess. An incidental but significant finding of EEO would warrant early surgical intervention to prevent a catastrophic sequelae i.e. Fournier's gangrene.