Smart Self-Assembly Amphiphilic Cyclopeptide-Dye for Near-Infrared Window-II Imaging.

Development of novel nanomaterials for disease theranostics represents an important direction in chemistry and precision medicine. Fluorescent molecular probes in the second near-infrared window (NIR-II, 1000-1700 nm) show high promise because of their exceptional high detection sensitivity, resolution, and deep imaging depth. Here, a sharp pH-sensitive self-assembling cyclopeptide-dye, SIMM1000, as a smart nanoprobe for NIR-II imaging of diseases in living animals, is reported. This small molecule assembled nanoprobe exhibits smart properties by responding to a sharp decrease of pH in the tumor microenvironment (pH 7.0 to 6.8), aggregating from small nanoprobe (80 nm at pH 7.0) into large nanoparticles (>500 nm at pH 6.8) with ≈20-30 times enhanced fluorescence compared with the non-self-assembled CH-4T. It yields micrometer-scale resolution in blood vessel imaging and high contrast and resolution in bone and tumor imaging in mice. Because of its self-aggregation in acidic tumor microenvironments in situ, SIMM1000 exhibits high tumor accumulation and extremely long tumor retention (>19 days), while being excretable from normal tissues and safe. This smart self-assembling small molecule strategy can shift the paradigm of designing new nanomaterials for molecular imaging and drug development.

Exploring a Third Confirmed Case of Hemoperitoneum following Open Inguinal Hernia Repair Caused by Sampson Artery Hemorrhage.

Hemoperitoneum is a rare complication of open inguinal hernia repair. This is the third reported case of this complication attributed to the same bleeding source: Sampson's artery. Sampson's artery courses along the round ligament of the uterus in the inguinal canal of females, originating from the arcade formed between the uterine and ovarian arteries. Usually obliterated in postembryonic development, this artery can persist in some adult female patients. Disruption of Sampson's artery can lead to hemoperitoneum following ligation of the uterine round ligament during open inguinal hernia repair in females. This case report describes a third confirmed case of hemoperitoneum complicating an open inguinal hernia repair. We review all three reported cases to date and discuss the recurring signs, symptoms, epidemiologic factors, and diagnostic findings associated. Our review suggests that females of childbearing age, particularly those in the peripartum period, are most at risk of developing this rare complication.

Curation-free biomodules mechanisms in prostate cancer predict recurrent disease.

MOTIVATION: Gene expression-based prostate cancer gene signatures of poor prognosis are hampered by lack of gene feature reproducibility and a lack of understandability of their function. Molecular pathway-level mechanisms are intrinsically more stable and more robust than an individual gene. The Functional Analysis of Individual Microarray Expression (FAIME) we developed allows distinctive sample-level pathway measurements with utility for correlation with continuous phenotypes (e.g. survival). Further, we and others have previously demonstrated that pathway-level classifiers can be as accurate as gene-level classifiers using curated genesets that may implicitly comprise ascertainment biases (e.g. KEGG, GO). Here, we hypothesized that transformation of individual prostate cancer patient gene expression to pathway-level mechanisms derived from automated high throughput analyses of genomic datasets may also permit personalized pathway analysis and improve prognosis of recurrent disease. RESULTS: Via FAIME, three independent prostate gene expression arrays with both normal and tumor samples were transformed into two distinct types of molecular pathway mechanisms: (i) the curated Gene Ontology (GO) and (ii) dynamic expression activity networks of cancer (Cancer Modules). FAIME-derived mechanisms for tumorigenesis were then identified and compared. Curated GO and computationally generated "Cancer Module" mechanisms overlap significantly and are enriched for known oncogenic deregulations and highlight potential areas of investigation. We further show in two independent datasets that these pathway-level tumorigenesis mechanisms can identify men who are more likely to develop recurrent prostate cancer (log-rank_p = 0.019). CONCLUSION: Curation-free biomodules classification derived from congruent gene expression activation breaks from the paradigm of recapitulating the known curated pathway mechanism universe.