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The brain injury modeling community has recommended improving model subject specificity and simulation efficiency. Here, we extend an instantaneous (<1 sec) convolutional neural network (CNN) brain model based on the anisotropic Worcester Head Injury Model (WHIM) V1.0 to account for strain differences due to individual morphological variations. Linear scaling factors relative to the generic WHIM along the three anatomical axes are used as additional CNN inputs. To generate training samples, the WHIM is randomly scaled to pair with augmented head impacts randomly generated from real-world data for simulation. An estimation of voxelized peak maximum principal strain of the whole brain is said to be successful when the linear regression slope and Pearson’s correlation coefficient relative to directly simulated do not deviate from 1.0 (when identical) by more than 0.1. Despite a modest training dataset (N=1363 vs. ~5.7 k previously), the individualized CNN achieves a success rate of 86.2% in cross-validation for scaled model responses, and 92.1% for independent generic model testing for impacts considered as complete capture of kinematic events. Using 11 scaled subject-specific models (with scaling factors determined from pre-established regression models based on head dimensions and sex and age information, and notably, without neuroimages), the morphologically individualized CNN remains accurate for impacts that also yield successful estimations for the generic WHIM. The individualized CNN instantly estimates subject-specific and spatially detailed peak strains of the entire brain and thus, supersedes others that report a scalar peak strain value incapable of informing the location of occurrence. This tool could be especially useful for youths and females due to their anticipated greater morphological differences relative to the generic model, even without the need for individual neuroimages. It has potential for a wide range of applications for injury mitigation purposes and the design of head protective gears. The voxelized strains also allow for convenient data sharing and promote collaboration among research groups. 

Up to one of every six individuals diagnosed with one cancer will be diagnosed with a second primary cancer in their lifetime. Genetic factors contributing to the development of multiple primary cancers, beyond known cancer syndromes, have been underexplored.

To characterize genetic susceptibility to multiple cancers, we conducted a pan-cancer, whole-exome sequencing study of individuals drawn from two large multi-ancestry populations (6429 cases, 165,853 controls). We created two groupings of individuals diagnosed with multiple primary cancers: (1) an overall combined set with at least two cancers across any of 36 organ sites and (2) cancer-specific sets defined by an index cancer at one of 16 organ sites with at least 50 cases from each study population. We then investigated whether variants identified from exome sequencing were associated with these sets of multiple cancer cases in comparison to individuals with one and, separately, no cancers.

We identified 22 variant-phenotype associations, 10 of which have not been previously discovered and were significantly overrepresented among individuals with multiple cancers, compared to those with a single cancer.

Overall, we describe variants and genes that may play a fundamental role in the development of multiple primary cancers and improve our understanding of shared mechanisms underlying carcinogenesis.