Architecture of the human regulatory network derived from ENCODE data.

Transcription factors bind in a combinatorial fashion to specify the on-and-off states of genes; the ensemble of these binding events forms a regulatory network, constituting the wiring diagram for a cell. To examine the principles of the human transcriptional regulatory network, we determined the genomic binding information of 119 transcription-related factors in over 450 distinct experiments. We found the combinatorial, co-association of transcription factors to be highly context specific: distinct combinations of factors bind at specific genomic locations. In particular, there are significant differences in the binding proximal and distal to genes. We organized all the transcription factor binding into a hierarchy and integrated it with other genomic information (for example, microRNA regulation), forming a dense meta-network. Factors at different levels have different properties; for instance, top-level transcription factors more strongly influence expression and middle-level ones co-regulate targets to mitigate information-flow bottlenecks. Moreover, these co-regulations give rise to many enriched network motifs (for example, noise-buffering feed-forward loops). Finally, more connected network components are under stronger selection and exhibit a greater degree of allele-specific activity (that is, differential binding to the two parental alleles). The regulatory information obtained in this study will be crucial for interpreting personal genome sequences and understanding basic principles of human biology and disease.

Supratentorial CAPNON associated with WHO grade II meningioma: A case report.

Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare benign tumor of uncertain etiology, arising in the craniospinal axis. CAPNON typically arises in isolation, with only two prior reports of a concurrent second neoplasm. Here, we report the case of a male 17-year-old who presented with new-onset seizures. MRIs revealed a 2 cm extra-axial solid-cystic mass, arising at the left temporo-occipital junction and abutting the dura with marked surrounding parenchymal vasogenic edema. The solid components demonstrated dense calcification and avid enhancement. Gross total surgical resection was performed. Histopathological examination revealed central regions showing characteristic features of CAPNON. Toward the periphery, the CAPNON was intimately associated with and sharply demarcated from a meningioma, which showed up to five mitoses per 10 high-power fields and had invasion into the adjacent brain parenchyma, warranting a WHO grade II designation. This is the first report of CAPNON arising in association with a meningioma. The coexistence of these two tumors raises the possibility of a reactive/dysplastic etiology for CAPNON.

Risk factors associated with significant bleeding events after ultrasound-guided percutaneous native renal biopsies: a review of 2204 cases.

OBJECTIVE: To review the incidence of significant bleeding complications after ultrasound-guided percutaneous core native renal biopsies at a single center using a standardized technique. MATERIALS AND METHODS: A retrospective review of ultrasound (US)-guided percutaneous native renal core biopsies done at our institution from September 2005 to December 2015 was performed. Demographic and clinical data were collected at the time of biopsy, with additional clinical information recorded 24 h and 3 months after the biopsy. Bleeding complications were defined using the Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) created by the National Institutes of Health. RESULTS: 2204 US-guided native renal core biopsies were performed during the study period, with 37 hemorrhages (1.64%) that were CTCAE grade 3 or higher. The rate of inadequate sampling as reported by pathology was extremely low (1.1%). Factors demonstrating a significant association with bleeding risk included estimated glomerular filtration rate (eGFR), specifically when the eGFR was less than 60 (p = 0.025), platelet count (p = 0.002), including a statistically significant decreased risk of bleeding with a platelet count greater than 100 (109/L) (p = <0.001), and performing four or more needle passes (p = 0.012). While female gender was also associated with an increased bleeding risk (p = 0.05), there was a significant association between females with a BMI ≥ 25 and a decreased bleeding risk (0.034). No statistically significant association between post-biopsy hemorrhage and aspirin use within 10 days prior to biopsy or a prior diagnosis of amyloidosis was demonstrated. CONCLUSION: US-guided native renal biopsy is a safe procedure with a low rate of significant bleeding complications and a high tissue adequacy rate using an 18-gage spring-loaded biopsy device. Factors associated with increased bleeding risk include female gender, lower platelet counts, decreased eGFR and performing four or more needle passes, which has not been reported previously. Interestingly, females with a BMI ≥ to 25 demonstrated a decreased bleeding risk, and aspirin (81 mg or 325 mg) within 10 days of the procedure did not demonstrate a significant effect. While not shown in this current study, the relationship of very recent aspirin therapy with bleeding is yet to be defined. Similarly, the statistically significant decreased risk of bleeding complications in overweight or obese females requires further investigation.