North Carolina macular dystrophy (MCDR1) caused by a novel tandem duplication of the PRDM13 gene

PURPOSE: To identify the underlying cause of disease in a large family with North Carolina macular dystrophy (NCMD). METHODS: A large four-generation family (RFS355) with an autosomal dominant form of NCMD was ascertained. Family members underwent comprehensive visual function evaluations. Blood or saliva from six affected family members and three unaffected spouses was collected and DNA tested for linkage to the MCDR1 locus on chromosome 6q12. Three affected family members and two unaffected spouses underwent whole exome sequencing (WES) and subsequently, custom capture of the linkage region followed by next-generation sequencing (NGS). Standard PCR and dideoxy sequencing were used to further characterize the mutation. RESULTS: Of the 12 eyes examined in six affected individuals, all but two had Gass grade 3 macular degeneration features. Large central excavation of the retinal and choroid layers, referred to as a macular caldera, was seen in an age-independent manner in the grade 3 eyes. The calderas are unique to affected individuals with MCDR1. Genome-wide linkage mapping and haplotype analysis of markers from the chromosome 6q region were consistent with linkage to the MCDR1 locus. Whole exome sequencing and custom-capture NGS failed to reveal any rare coding variants segregating with the phenotype. Analysis of the custom-capture NGS sequencing data for copy number variants uncovered a tandem duplication of approximately 60 kb on chromosome 6q. This region contains two genes, CCNC and PRDM13. The duplication creates a partial copy of CCNC and a complete copy of PRDM13. The duplication was found in all affected members of the family and is not present in any unaffected members. The duplication was not seen in 200 ethnically matched normal chromosomes. CONCLUSIONS: The cause of disease in the original family with MCDR1 and several others has been recently reported to be dysregulation of the PRDM13 gene, caused by either single base substitutions in a DNase 1 hypersensitive site upstream of the CCNC and PRDM13 genes or a tandem duplication of the PRDM13 gene. The duplication found in the RFS355 family is distinct from the previously reported duplication and provides additional support that dysregulation of PRDM13, not CCNC, is the cause of NCMD mapped to the MCDR1 locus

DNA-nanoparticle superlattices formed from anisotropic building blocks

Directional bonding interactions in solid-state atomic lattices dictate the unique symmetries of atomic crystals, resulting in a diverse and complex assortment of three-dimensional structures that exhibit a wide variety of material properties. Methods to create analogous nanoparticle superlattices are beginning to be realized, but the concept of anisotropy is still largely underdeveloped in most particle assembly schemes. Some examples provide interesting methods to take advantage of anisotropic effects, but most are able to make only small clusters or lattices that are limited in crystallinity and especially in lattice parameter programmability. Anisotropic nanoparticles can be used to impart directional bonding interactions on the nanoscale, both through face-selective functionalization of the particle with recognition elements to introduce the concept of valency, and through anisotropic interactions resulting from particle shape. In this work, we examine the concept of inherent shape-directed crystallization in the context of DNA-mediated nanoparticle assembly. Importantly, we show how the anisotropy of these particles can be used to synthesize one-, two- and three-dimensional structures that cannot be made through the assembly of spherical particles. Includes Supplementary Information (44 pp.)

Brightfield for the Bright Future

In Spring 2021, ten second-year urban planning major students, Adam Coleson, Lauren Doppke, Michael Grossniklaus, Elise Jones, Kaelyn Leach, Enzo Lundy, Mattew Pytel, Kaylie Slate, Eric Snowden, and Christian Terrell, in PLAN 203 Regional Analysis and Design of Ball State University conducted solar potential analysis for brownfields in Muncie, Indiana. In collaboration with Sierra Club Hoosier Chapter with the generous support from Ball State University’s Immersive Learning Office, students applied Geographic Information Systems (GIS) to study the ownership of the brownfields, current land use and zoning ordinances, preexisting conditions, and then analyzed solar PV potentials using publicly available PV watts tool developed by the US Department of Energy

NIMG-56. USING RADIOMIC FEATURES FROM DAILY MAGNETIC RESONANCE IMAGING TO PREDICT RESPONSE TO RADIATION THERAPY IN GLIOBLASTOMA PATIENTS: A PILOT STUDY

Abstract A dilemma in treating glioblastoma is that MRI after chemotherapy and radiation therapy (chemoRT) shows areas of presumed tumor growth in up to 50% of patients. These areas can represent true progression (TP), tumor growth with tumors non-responsive to treatment, or pseudoprogression (PP), edema and tumor necrosis with favorable treatment response. On imaging, TP and PP are usually not discernable. Patients in this study undergo six weeks of chemoRT on a combination MRI/RT device, receiving daily MRIs. The goal of this study is to explore the correlation of radiomics features with progression. The tumor lesion and surrounding areas of growth/edema were manually outlined as regions of interest (ROIs) for each daily T2-weighted MRI scan. The ROIs were used to calculate texture features: statistical features based on the gray-level co-occurrence matrix (GLCM), the gray-level zone size matrix (GLZSM), the gray-level run length matrix (GLRLM), and the neighborhood gray-tone difference matrix (NGTDM). Each of these matrix classes describe the probability of spatial relationships of gray levels occurring within the ROI. Daily texture features were averaged per week of treatment for each patient. Patient response was retrospectively defined as no progression (NP), TP, or PP. A Kruskal-Wallis test was performed to identify texture features that correlated most strongly with patient response. Forty texture features were calculated for 12 patients (19 treated, 7 excluded due to no T2 lesion or progression status unknown, 6 NP, 3 TP, 3 PP). There was a trend of more texture features correlating significantly with response in weeks 4-6 of treatment, compared to weeks 1-3. A particular texture feature, GLSZM Small Zone Low Gray-Level Emphasis, showed increasing difference between PP and TP over time, with significant difference during week 6 of treatment (p=0.0495). Future directions include correlating early outcomes with greater numbers of patients and daily multiparametric MRI

North Carolina macular dystrophy (MCDR1) caused by a novel tandem duplication of the PRDM13 gene

To identify the underlying cause of disease in a large family with North Carolina macular dystrophy (NCMD). A large four-generation family (RFS355) with an autosomal dominant form of NCMD was ascertained. Family members underwent comprehensive visual function evaluations. Blood or saliva from six affected family members and three unaffected spouses was collected and DNA tested for linkage to the MCDR1 locus on chromosome 6q12. Three affected family members and two unaffected spouses underwent whole exome sequencing (WES) and subsequently, custom capture of the linkage region followed by next-generation sequencing (NGS). Standard PCR and dideoxy sequencing were used to further characterize the mutation. Of the 12 eyes examined in six affected individuals, all but two had Gass grade 3 macular degeneration features. Large central excavation of the retinal and choroid layers, referred to as a macular caldera, was seen in an age-independent manner in the grade 3 eyes. The calderas are unique to affected individuals with MCDR1. Genome-wide linkage mapping and haplotype analysis of markers from the chromosome 6q region were consistent with linkage to the MCDR1 locus. Whole exome sequencing and custom-capture NGS failed to reveal any rare coding variants segregating with the phenotype. Analysis of the custom-capture NGS sequencing data for copy number variants uncovered a tandem duplication of approximately 60 kb on chromosome 6q. This region contains two genes, and . The duplication creates a partial copy of and a complete copy of . The duplication was found in all affected members of the family and is not present in any unaffected members. The duplication was not seen in 200 ethnically matched normal chromosomes. The cause of disease in the original family with MCDR1 and several others has been recently reported to be dysregulation of the gene, caused by either single base substitutions in a DNase 1 hypersensitive site upstream of the and genes or a tandem duplication of the gene. The duplication found in the RFS355 family is distinct from the previously reported duplication and provides additional support that dysregulation of , not , is the cause of NCMD mapped to the MCDR1 locus

A Deep Learning Approach for Automatic Segmentation during Daily MRI-Linac Radiotherapy of Glioblastoma

Glioblastoma changes during chemoradiotherapy are inferred from high-field MRI before and after treatment but are rarely investigated during radiotherapy. The purpose of this study was to develop a deep learning network to automatically segment glioblastoma tumors on daily treatment set-up scans from the first glioblastoma patients treated on MRI-linac. Glioblastoma patients were prospectively imaged daily during chemoradiotherapy on 0.35T MRI-linac. Tumor and edema (tumor lesion) and resection cavity kinetics throughout the treatment were manually segmented on these daily MRI. Utilizing a convolutional neural network, an automatic segmentation deep learning network was built. A nine-fold cross-validation schema was used to train the network using 80:10:10 for training, validation, and testing. Thirty-six glioblastoma patients were imaged pre-treatment and 30 times during radiotherapy (n = 31 volumes, total of 930 MRIs). The average tumor lesion and resection cavity volumes were 94.56 ± 64.68 cc and 72.44 ± 35.08 cc, respectively. The average Dice similarity coefficient between manual and auto-segmentation for tumor lesion and resection cavity across all patients was 0.67 and 0.84, respectively. This is the first brain lesion segmentation network developed for MRI-linac. The network performed comparably to the only other published network for auto-segmentation of post-operative glioblastoma lesions. Segmented volumes can be utilized for adaptive radiotherapy and propagated across multiple MRI contrasts to create a prognostic model based for glioblastoma on multiparametric MRI