Visualization of protein sequence space with force-directed graphs, and their application to the choice of target-template pairs for homology modelling.

The protein sequence-structure gap results from the contrast between rapid, low-cost deep sequencing, and slow, expensive experimental structure determination techniques. Comparative homology modelling may have the potential to close this gap by predicting protein structure in target sequences using existing experimentally solved structures as templates. This paper presents the first use of force-directed graphs for the visualization of sequence space in two dimensions, and applies them to the choice of suitable RNA-dependent RNA polymerase (RdRP) target-template pairs within human-infective RNA virus genera.

Methotrexate pharmacokinetics in infants with acute lymphoblastic leukemia.

Purpose: We performed a pharmacokinetic evaluation of methotrexate (MTX) in infants with acute lymphoblastic leukemia enrolled on the Pediatric Oncology Group (POG) 9407 Infant Leukemia Study to evaluate the effects of age on MTX pharmacokinetics and pharmacodynamics.

Methods: A pharmacokinetic database of 61 patients was developed by combining MTX data obtained from 16 patients in a pharmacokinetic sub-study with data obtained for clinical care in other patients enrolled on the POG 9407 protocol. The data were analyzed for the first dose of MTX given to patients in induction/intensification therapy.

Value of baseline positron emission tomography for predicting overall survival in patient with nonmetastatic esophageal or gastroesophageal junction carcinoma.

Background: The value of baseline positron emission tomography (PET) for predicting overall survival (OS) or disease-free survival (DFS) is unclear in patients with nondistant metastatic (locoregional only) esophageal carcinoma. The authors tested the hypothesis that, in this setting, the number of PET abnormalities (NPA) would correlate with OS and DFS.

Methods: The authors of the current study analyzed patients with localized esophageal carcinoma (Stages II and III) who had a baseline PET and endoscopic ultrasonography (EUS) and were all treated with chemoradiotherapy followed by surgery.

BRAF mutations in aberrant crypt foci and hyperplastic polyposis.

Patients with hyperplastic polyposis have multiple hyperplastic polyps (HPs) and increased risk of colorectal carcinomas. Aberrant crypt foci (ACF) are postulated to be the earliest precursor lesions in colorectal carcinogenesis. We evaluated BRAF mutations by DNA sequencing in 53 ACF from patients with sporadic colorectal carcinomas and familial adenomatous polyposis, in 18 sporadic HPs from patients with resected colorectal cancer, and in 70 HPs, 4 serrated adenomas, 3 admixed hyperplastic-adenomatous polyps, 10 tubular adenomas, and 6 carcinomas from 17 patients with multiple/large HPs and/or hyperplastic polyposis.

Transhepatic ipsilateral right portal vein embolization extended to segment IV: improving hypertrophy and resection outcomes with spherical particles and coils.

Purpose: To analyze outcomes after right portal vein embolization extended to segment IV (right PVE + IV) before extended right hepatectomy, including liver hypertrophy, resection rates, and complications after embolization and resection, and to assess differences in outcomes with two different particulate embolic agents.

Materials And Methods: Between 1998 and 2004, transhepatic ipsilateral right PVE + IV with particles and coils was performed in 44 patients with malignant hepatobiliary disease, including metastases (n = 24), biliary cancer (n = 14), and hepatocellular carcinoma (n = 6). Right PVE + IV was considered if the future liver remnant (FLR; segments II/III with or without I) was less than 25% of the total estimated liver volume (TELV).