Technical note: Institutional solution of clinical cine MRI for tumor motion evaluation in radiotherapy

PURPOSE: Since 4D-MRI is inadequate to capture dynamic respiratory variations, real-time cinematographic (cine) MRI is actively used in MR-guided radiotherapy (MRgRT) for tumor motion evaluation, delineation, and tracking. However, most radiotherapy imaging platforms do not support the format of cine MRI from clinical MRI systems. This study developed an institutional solution of clinical cine MRI for tumor motion evaluation in radiotherapy applications. METHODS: Cine MRI manipulation software (called Cine Viewer) was developed within a commercial Treatment Planning System (TPS). It consists of (1) single/orthogonal viewers, (2) display controllers, (3) measurement grids/markers, and (4) manual contouring tools. RESULTS: The institutional solution of clinical cine MRI incorporated with radiotherapy application was assessed through case presentations (liver cancer). Cine Viewer loaded cine MRIs from 1.5T Philips Ingenia MRI, handling MRI DICOM format. The measurement grids and markers were used to quantify the displacement of anatomical structures in addition to the tumor. The contouring tool was utilized to localize the tumor and surrogates on the designated frame. The stacks of the contours were exhibited to present the ranges of tumor and surrogate motions. For example, the stacks of the tumor contours from case-1 were used to determine the ranges of tumor motions (∼8.17 mm on the x-direction [AP-direction] and ∼14 mm on the y-direction [SI-direction]). In addition, the patterns of the displacement of the contours over frames were analyzed and reported using in-house software. In the case-1 review, the tumor was displaced from +146.0 mm on the x-direction and +125.0 mm on the y-direction from the ROI of the abdominal surface. CONCLUSION: We demonstrated the institutional solution of clinical cine MRI in radiotherapy. The proposed tools can streamline the utilization of cine MRI for tumor motion evaluation using Eclipse for treatment planning

Participation in the Georgia Food for Health program and cardiovascular disease risk factors: A longitudinal observational study

Abstract Objective To assess the relationship between program attendance in a produce prescription program and changes in cardiovascular risk factors. Design The Georgia Food for Health (GF4H) program provided 6 monthly nutrition education sessions, 6 weekly cooking classes, and weekly produce vouchers. Participants became program graduates attending at least 4 of the 6 of both the weekly cooking classes and monthly education sessions. We used a longitudinal, single-arm approach to estimate the association between the number of monthly program visits attended and changes in health indicators. Setting GF4H was implemented in partnership with a large safety-net health system in Atlanta, GA. Participants 331 participants living with or at-risk of chronic disease and food insecurity were recruited from primary care clinics. Over three years, 282 participants graduated from the program. Results After adjusting for program site, year, participant sex, age, race & ethnicity, SNAP participation, and household size, we estimated that each additional program visit attended beyond 4 visits was associated with a 0.06 kg/m2 reduction in BMI (95% CI: -0.12, -0.01; p=0.02), a 0.37 inch reduction in waist circumference (95% CI: -0.48, -0.27; p<0.001), a 1.01 mmHg reduction in systolic blood pressure (95% CI: -1.45, -0.57; p<0.001), and a 0.43 mmHg reduction in diastolic blood pressure (95% CI: -0.69, -0.17; p=0.001). Conclusions Each additional cooking and nutrition education visit attended beyond the graduation threshold was associated with modest but significant improvements in cardiovascular disease risk factors, suggesting that increased engagement in educational components of a produce prescription program improves health outcomes

Correlation between Targeted qPCR Assays and Untargeted DNA Shotgun Metagenomic Sequencing for Assessing the Fecal Microbiota in Dogs

DNA shotgun sequencing is an untargeted approach for identifying changes in relative abundances, while qPCR allows reproducible quantification of specific bacteria. The canine dysbiosis index (DI) assesses the canine fecal microbiota by using a mathematical algorithm based on qPCR results. We evaluated the correlation between qPCR and shotgun sequencing using fecal samples from 296 dogs with different clinical phenotypes. While significant correlations were found between qPCR and sequencing, certain taxa were only detectable by qPCR and not by sequencing. Based on sequencing, less than 2% of bacterial species (17/1190) were consistently present in all healthy dogs (n = 76). Dogs with an abnormal DI had lower alpha-diversity compared to dogs with normal DI. Increases in the DI correctly predicted the gradual shifts in microbiota observed by sequencing: minor changes (R = 0.19, DI 2, DI > 5, and DI > 8, respectively), compared to dogs with a normal DI (DI < 0, all targets within the RI), as higher R-values indicated larger dissimilarities. In conclusion, the qPCR-based DI is an effective indicator of overall microbiota shifts observed by shotgun sequencing in dogs

Genome-wide association study of cerebral small vessel disease reveals established and novel loci

Intracerebral haemorrhage and small vessel ischaemic stroke (SVS) are the most acute manifestations of cerebral small vessel disease, with no established preventive approaches beyond hypertension management. Combined genome-wide association study (GWAS) of these two correlated diseases may improve statistical power to detect novel genetic factors for cerebral small vessel disease, elucidating underlying disease mechanisms that may form the basis for future treatments. Because intracerebral haemorrhage location is an adequate surrogate for distinct histopathological variants of cerebral small vessel disease (lobar for cerebral amyloid angiopathy and non-lobar for arteriolosclerosis), we performed GWAS of intracerebral haemorrhage by location in 1813 subjects (755 lobar and 1005 non-lobar) and 1711 stroke-free control subjects. Intracerebral haemorrhage GWAS results by location were meta-analysed with GWAS results for SVS from MEGASTROKE, using 'Multi-Trait Analysis of GWAS' (MTAG) to integrate summary data across traits and generate combined effect estimates. After combining intracerebral haemorrhage and SVS datasets, our sample size included 241 024 participants (6255 intracerebral haemorrhage or SVS cases and 233 058 control subjects). Genome-wide significant associations were observed for non-lobar intracerebral haemorrhage enhanced by SVS with rs2758605 [MTAG P-value (P) = 2.6 x 10(-8)] at 1q22;rs72932727 (P = 1.7 x 10(-8)) at 2q33;and rs9515201 (P = 5.3 x 10(-10)) at 13q34. In the GTEx gene expression library, rs2758605 (1q22), rs72932727 (2q33) and rs9515201 (13q34) are significant cis-eQTLs for PMF1 (P = 1 x 10(-4) in tibial nerve), NBEAL1, FAM117B and CARF (P<2.1 x 10(-7) in arteries) and COL4A2 and COL4A1 (P<0.01 in brain putamen), respectively. Leveraging S-PrediXcan for gene-based association testing with the predicted expression models in tissues related with nerve, artery, and non-lobar brain, we found that experiment-wide significant (P<8.5 x 10(-7)) associations at three genes at 2q33 including NBEAL1, FAM117B and WDR12 and genome-wide significant associations at two genes including ICA1L at 2q33 and ZCCHC14 at 16q24. Brain cell-type specific expression profiling libraries reveal that SEMA4A, SLC25A44 and PMF1 at 1q22 and COL4A1 and COL4A2 at 13q34 were mainly expressed in endothelial cells, while the genes at 2q33 (FAM117B, CARF and NBEAL1) were expressed in various cell types including astrocytes, oligodendrocytes and neurons. Our cross-phenotype genetic study of intracerebral haemorrhage and SVS demonstrates novel genome-wide associations for non-lobar intracerebral haemorrhage at 2q33 and 13q34. Our replication of the 1q22 locus previous seen in traditional GWAS of intracerebral haemorrhage, as well as the rediscovery of 13q34, which had previously been reported in candidate gene studies with other cerebral small vessel disease-related traits strengthens the credibility of applying this novel genome-wide approach across intracerebral haemorrhage and SVS

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Cell-type–specific eQTL of primary melanocytes facilitates identification of melanoma susceptibility genes

Most expression quantitative trait locus (eQTL) studies to date have been performed in heterogeneous tissues as opposed to specific cell types. To better understand the cell-type–specific regulatory landscape of human melanocytes, which give rise to melanoma but account for <5% of typical human skin biopsies, we performed an eQTL analysis in primary melanocyte cultures from 106 newborn males. We identified 597,335 cis-eQTL SNPs prior to linkage disequilibrium (LD) pruning and 4997 eGenes (FDR < 0.05). Melanocyte eQTLs differed considerably from those identified in the 44 GTEx tissue types, including skin. Over a third of melanocyte eGenes, including key genes in melanin synthesis pathways, were unique to melanocytes compared to those of GTEx skin tissues or TCGA melanomas. The melanocyte data set also identified trans-eQTLs, including those connecting a pigmentation-associated functional SNP with four genes, likely through cis-regulation of IRF4. Melanocyte eQTLs are enriched in cis-regulatory signatures found in melanocytes as well as in melanoma-associated variants identified through genome-wide association studies. Melanocyte eQTLs also colocalized with melanoma GWAS variants in five known loci. Finally, a transcriptome-wide association study using melanocyte eQTLs uncovered four novel susceptibility loci, where imputed expression levels of five genes (ZFP90, HEBP1, MSC, CBWD1, and RP11-383H13.1) were associated with melanoma at genome-wide significant P-values. Our data highlight the utility of lineage-specific eQTL resources for annotating GWAS findings, and present a robust database for genomic research of melanoma risk and melanocyte biology

Review of \u3ci\u3eStar Wars: A Scanimation Book\u3c/i\u3e by Rufus Butler Seder

https://digitalcommons.cedarville.edu/intern_book_reviews/1064/thumbnail.jp

Review of \u3ci\u3eThe Day-Glo Brothers\u3c/i\u3e by Chris Barton

https://digitalcommons.cedarville.edu/intern_book_reviews/1062/thumbnail.jp

Review of \u3ci\u3eDewey: There’s a Cat in the Library!\u3c/i\u3e by Vicki Myron

https://digitalcommons.cedarville.edu/intern_book_reviews/1053/thumbnail.jp