Histogram showing time to renal recovery for the entire cohort and for those patients with ATN – for those patients who do have sustained recovery of renal function.

<p>Histogram showing time to renal recovery for the entire cohort and for those patients with ATN – for those patients who do have sustained recovery of renal function.</p

Maps demonstrating the significant geographical variation in the overall rates of renal recovery and the rates of renal recovery for patients initiated on hemodialysis with a diagnosis of “tubular necrosis”.

<p>Maps demonstrating the significant geographical variation in the overall rates of renal recovery and the rates of renal recovery for patients initiated on hemodialysis with a diagnosis of “tubular necrosis”.</p

DataSheet_1_Genomic landscape of advanced prostate cancer patients with BRCA1 versus BRCA2 mutations as detected by comprehensive genomic profiling of cell-free DNA.docx

BRCA1-mutated prostate cancer has been shown to be less responsive to poly (ADP-ribose) polymerase (PARP) inhibitors as compared to BRCA2-mutated prostate cancer. The reason for this differential response is not clear. We hypothesized this differential sensitivity to PARP inhibitors may be explained by distinct genomic landscapes of BRCA1 versus BRCA2 co-segregating genes. In a large dataset of 7,707 men with advanced prostate cancer undergoing comprehensive genomic profiling (CGP) of cell-free DNA (cfDNA), 614 men harbored BRCA1 and/or BRCA2 alterations. Differences in the genomic landscape of co-segregating genes was investigated by Fisher’s exact test and probabilistic graphical models (PGMs). Results demonstrated that BRCA1 was significantly associated with six other genes, while BRCA2 was not significantly associated with any gene. These findings suggest BRCA2 may be the main driver mutation, while BRCA1 mutations tend to co-segregate with mutations in other molecular pathways contributing to prostate cancer progression. These hypothesis-generating data may explain the differential response to PARP inhibition and guide towards the development of combinatorial drug regimens in those with BRCA1 mutation.</p

Discovery and Synthesis of C‑Nucleosides as Potential New Anti-HCV Agents

Nucleoside analogues have long been recognized as prospects for the discovery of direct acting antivirals (DAAs) to treat hepatitis C virus because they have generally exhibited cross-genotype activity and a high barrier to resistance. C-Nucleosides have the potential for improved metabolism and pharmacokinetic properties over their N-nucleoside counterparts due to the presence of a strong carbon–carbon glycosidic bond and a non-natural heterocyclic base. Three 2′CMe-C-adenosine analogues and two 2′CMe-guanosine analogues were synthesized and evaluated for their anti-HCV efficacy. The nucleotide triphosphates of four of these analogues were found to inhibit the NS5B polymerase, and adenosine analogue <b>1</b> was discovered to have excellent pharmacokinetic properties demonstrating the potential of this drug class