Furthermore, single-shot FOCUSED-xSPEN and LASER profiles covered limited off-resonance ranges. This could be extended to bands covering arbitrary off-resonance values with uniform slice widths, by looping the experiments over a number of scans possessing suitable transmission and reception offsets. CONCLUSIONS A series of novel approaches were introduced to select slices near metals, delivering robustness against Bo and B1+ field inhomogeneities. Lung cancer metastases comprise most of all brain metastases in adults and most brain metastases are diagnosed by magnetic resonance (MR) scans. The purpose of this study was to conduct an MR imaging-based radiomic analysis of brain metastatic lesions from patients with primary lung cancer to classify mutational status of the metastatic disease. We retrospectively identified lung cancer patients with brain metastases treated at our institution between 2009 and 2017 who underwent genotype testing of their primary lung cancer. Brain MR Images were used for segmentation of enhancing tumors and peritumoral edema, and for radiomic feature extraction. The most relevant radiomic features were identified and used with clinical data to train random forest classifiers to classify the mutation status. Of 110 patients in the study cohort (mean age 57.51 ± 12.32 years; M F = 3773), 75 had an EGFR mutation, 21 had an ALK translocation, and 15 had a KRAS mutation. One patient had both ALK translocation and EGFR mutation. Majority of radiomic features most relevant for mutation classification were textural. Model building using both radiomic features and clinical data yielded more accurate classifications than using either alone. For classification of EGFR, ALK, and KRAS mutation status, the model built with both radiomic features and clinical data resulted in area-under-the-curve (AUC) values based on cross-validation of 0.912, 0.915, and 0.985, respectively. Our study demonstrated that MR imaging-based radiomic analysis of brain metastases in patients with primary lung cancer may be used to classify mutation status. This approach may be useful for devising treatment strategies and informing prognosis. BACKGROUND & AIMS Intestinal epithelial homeostasis depends on a tightly regulated balance between intestinal epithelial cell (IEC) death and proliferation. Disruption of factors that promote IEC death result in intestinal inflammation, whereas loss of anti-apoptotic proteins, such as BCL2 or its family member BCL2L1, has no effect on intestinal homeostasis in mice. We investigated the functions of the anti-apoptotic protein MCL1, another member of the BCL2 family, in intestinal homeostasis in mice. METHODS We generated mice with IEC-specific disruption of Mcl1 (Mcl1ΔIEC mice) or tamoxifen-inducible IEC-specific disruption of Mcl1 (i-Mcl1ΔIEC mice); these mice and mice with full-length Mcl1 (controls) were raised under normal or germ-free conditions. Some mice were given antibiotics in their drinking water or the PORCUPINE WNT inhibitor WNT974. Mice were analyzed by endoscopy and for intestinal epithelial barrier permeability. Intestinal tissues were analyzed by histology, in situ hybridization, proliferationss of MCL1 results in development of intestinal carcinomas, even under germ-free conditions, and therefore does not involve microbe-induced chronic inflammation. Mcl1ΔIEC mice might be used to study apoptotic enterocolopathy and inflammatory bowel diseases. BACKGROUND & AIMS Estimates of absolute risk of colorectal cancer (CRC) are needed to facilitate communication and better inform the public about the potentials and limits of cancer prevention. METHODS Using data from a large population-based case-control study in Germany (DACHS study, which began in 2003) and population registry data, we calculated 30-year absolute risk estimates for development of CRC, based on a healthy lifestyle score (derived from 5 modifiable lifestyle factors smoking, alcohol consumption, diet, physical activity, and body fatness), a polygenic risk score (based on 90 single nucleotide polymorphisms), and colonoscopy history. RESULTS We analyzed data from 4220 patients with CRC and 3338 individuals without CRC. Adherence to a healthy lifestyle and colonoscopy in the preceding 10 y were associated with a reduced relative risk of CRC in men and women.  https://www.selleckchem.com/products/l-monosodium-glutamate-monohydrate.html  We observed a higher CRC risk in participants with high or intermediate genetic risk scores. For 50-year-old men and women without a colonoscopy, the absolute risk of CRC varied according to the polygenic risk score and the healthy lifestyle score (men, 3.5%-13.4% and women, 2.5%-10.6%). For 50-year-old men and women with a colonoscopy, the absolute risk of developing CRC was much lower but still varied according to the polygenic risk score and the healthy lifestyle score (men, 1.2%-4.8% and women, 0.9%-4.2%). Among all risk factor profiles, the 30-y absolute risk estimates consistently decreased with adherence to a healthy lifestyle. CONCLUSIONS In a population-based study, we found that a colonoscopy can drastically reduce the absolute risk of CRC and that the genetically predetermined risk of CRC can be further reduced by adherence to a healthy lifestyle. Our results show the magnitude of CRC prevention possible through colonoscopy and lifestyle at a predefined genetic risk. BACKGROUND & AIMS A significant proportion of colorectal cancer (CRC) cases have familial aggregation but little is known about the genetic factors that contribute to these cases. We performed an exhaustive functional characterization of genetic variants associated with familial CRC. METHODS We performed whole-exome sequencing analyses of 75 patients from 40 families with a history of CRC (including early-onset cases) of an unknown germline basis (discovery cohort). We also sequenced specific genes in DNA from an external replication cohort of 473 families, including 488 patients with colorectal tumors that had normal expression of mismatch repair proteins (validation cohort). We disrupted the Fas associated factor 1 gene (FAF1) in DLD-1 CRC cells using CRISPR/Cas9 gene editing; some cells were transfected with plasmids that express FAF1 missense variants. Cells were analyzed by immunoblots, quantitative real-time PCR, and functional assays monitoring apoptosis, proliferation, and assays for Wnt signaling or NF-κB activity.