Is head-shaft angle a valuable continuous risk factor for hip migration in cerebral palsy?

BACKGROUND: Reimer's migration percentage (MP) is the most established radiographic risk factor for hip migration in cerebral palsy (CP), and it assists surgical decision-making. The head-shaft angle (HSA) measures the valgus of the head and neck in relation to the shaft and may also be a useful predictor of hip migration at a young age. This study first defined normal values and investigated whether the head-shaft angle (HSA) is a continuous risk factor for hip migration in CP. METHODS: Three hundred and fifty AP pelvic radiographs of 100 consecutive children comprising the hip surveillance programme in our region were analysed for MP and HSA. Inclusion criteria were children with spastic CP and Gross Motor Function Classification System (GMFCS) levels of III-V, along with a minimum follow-up of 5 years. The mean age was 8.8 (range 3-18) years and the mean follow-up time was 7.5 (range 5-10) years. Radiographs of 103 typically developing children (TDC) were selected for the control group. The reliability of the measurements was determined. A random effects analysis was used to assess the relationship between MP and HSA for all data and for MP > 40 %. RESULTS: The TDC cohort had a mean HSA of 157.7° whilst that for the CP cohort was 161.7°. The value declined with age in both groups but remained consistently higher in the CP group. A random effects analysis considering the longitudinal data showed that there was no significant effect of HSA on MP. Similarly, when excluding CP patients with MP < 40 %, there was no significant effect of HSA on MP. CONCLUSIONS: This study found no correlation between HSA and hip migration in children with CP in this age group. Using the HSA as a routine radiographic measure in the management pathway across childhood does not offer any added value. Early enrolment onto the hip surveillance programme could offer a better prediction of hip migration using the HSA at a very young age. LEVEL OF EVIDENCE: II retrospective prognostic study

Enhanced Anticancer Activity of Gemcitabine in Combination with Noscapine via Antiangiogenic and Apoptotic Pathway against Non-Small Cell Lung Cancer

BACKGROUND:The aim of this investigation was to evaluate the anticancer activity of Noscapine (Nos) and Gemcitabine (Gem) combination (NGC) against non-small cell lung cancer (NSCLC) and to elucidate the underlying mechanism of action. METHODS:Isobolographic method was used to calculate combination index values from cytotoxicity data. In vitro antiangiogenic and apoptotic activity of Nos, Gem and NGC was evaluated. For in vivo studies, female athymic Nu/nu mice were xenografted with H460 tumors and the efficacy of Nos, Gem, or NGC was determined. Protein expressions by immunohistochemical staining were evaluated in harvested tumor tissues. RESULTS:The CI values (<0.59) were suggestive of synergistic behavior between Nos and Gem. NGC treatment showed significantly inhibited tube formation and increased percentage of apoptotic cells. NGC, Gem and Nos treatment reduced tumor volume by 82.9±4.5 percent, 39.4±5.8 percent and 34.2±5.7 percent respectively. Specifically, NGC treatment decreased expression cell survival proteins; VEGF, CD31 staining and microvessel density and enhanced DNA fragmentation and cleaved caspase 3 levels compared to single agent treated and control groups. CONCLUSION:Nos potentiated the anticancer activity of Gem in an additive to synergistic manner against lung cancer via antiangiogenic and apoptotic pathways. These findings suggest potential benefit for use of NGC chemotherapy for treatment of lung cancer

Variant phasing and haplotypic expression from long-read sequencing in maize

Haplotype phasing maize genetic variants is important for genome interpretation, population genetic analysis and functional analysis of allelic activity. We performed an isoform-level phasing study using two maize inbred lines and their reciprocal crosses, based on single-molecule, full-length cDNA sequencing. To phase and analyze transcripts between hybrids and parents, we developed IsoPhase. Using this tool, we validated the majority of SNPs called against matching short-read data from embryo, endosperm and root tissues, and identified allele-specific, gene-level and isoform-level differential expression between the inbred parental lines and hybrid offspring. After phasing 6907 genes in the reciprocal hybrids, we annotated the SNPs and identified large-effect genes. In addition, we identified parent-of-origin isoforms, distinct novel isoforms in maize parent and hybrid lines, and imprinted genes from different tissues. Finally, we characterized variation in cis- and trans-regulatory effects. Our study provides measures of haplotypic expression that could increase accuracy in studies of allelic expression

A high-performance computational workflow to accelerate GATK SNP detection across a 25-genome dataset

Background: Single-nucleotide polymorphisms (SNPs) are the most widely used form of molecular genetic variation studies. As reference genomes and resequencing data sets expand exponentially, tools must be in place to call SNPs at a similar pace. The genome analysis toolkit (GATK) is one of the most widely used SNP calling software tools publicly available, but unfortunately, high-performance computing versions of this tool have yet to become widely available and affordable. Results: Here we report an open-source high-performance computing genome variant calling workflow (HPC-GVCW) for GATK that can run on multiple computing platforms from supercomputers to desktop machines. We benchmarked HPC-GVCW on multiple crop species for performance and accuracy with comparable results with previously published reports (using GATK alone). Finally, we used HPC-GVCW in production mode to call SNPs on a “subpopulation aware” 16-genome rice reference panel with ~ 3000 resequenced rice accessions. The entire process took ~ 16 weeks and resulted in the identification of an average of 27.3 M SNPs/genome and the discovery of ~ 2.3 million novel SNPs that were not present in the flagship reference genome for rice (i.e., IRGSP RefSeq). Conclusions: This study developed an open-source pipeline (HPC-GVCW) to run GATK on HPC platforms, which significantly improved the speed at which SNPs can be called. The workflow is widely applicable as demonstrated successfully for four major crop species with genomes ranging in size from 400 Mb to 2.4 Gb. Using HPC-GVCW in production mode to call SNPs on a 25 multi-crop-reference genome data set produced over 1.1 billion SNPs that were publicly released for functional and breeding studies. For rice, many novel SNPs were identified and were found to reside within genes and open chromatin regions that are predicted to have functional consequences. Combined, our results demonstrate the usefulness of combining a high-performance SNP calling architecture solution with a subpopulation-aware reference genome panel for rapid SNP discovery and public deployment. © 2024, The Author(s).Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Gapless Assembly of Maize Chromosomes Using Long-Read Technologies

Creating gapless telomere-to-telomere assemblies of complex genomes is one of the ultimate challenges in genomics. We use two independent assemblies and an optical map-based merging pipeline to produce a maize genome (B73-Ab10) composed of 63 contigs and a contig N50 of 162 Mb. This genome includes gapless assemblies of chromosome 3 (236 Mb) and chromosome 9 (162 Mb), and 53 Mb of the Ab10 meiotic drive haplotype. The data also reveal the internal structure of seven centromeres and five heterochromatic knobs, showing that the major tandem repeat arrays (CentC, knob180, and TR-1) are discontinuous and frequently interspersed with retroelements

Intra-arterial chemoradiation for T3-4 oral cavity cancer: Treatment outcomes in comparison to oropharyngeal and hypopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>Surgery followed by radiotherapy is the standard of care for resectable locally advanced oral cavity squamous cell carcinoma (SCC). We report the treatment outcomes of patients with T3-T4 SCC of the oral cavity treated with chemoradiation, an alternative approach.</p> <p>Patients and methods</p> <p>From a series of 240 patients with stage III-IV carcinoma of the upper aerodigestive tract who were treated consecutively according to the RADPLAT protocol, a subset analysis of 155 patients with T3-T4 SCC (Oral cavity SCC N = 22, oropharynx SCC N = 94 and hypopharynx SCC N = 39), was performed. The goal was to test the hypothesis that oral cavity SCC treated with chemoradiation has similar outcomes to the two comparison sites.</p> <p>Results</p> <p>With a median follow-up of 58 months, local disease control was 69% and the overall survival was 37%. In comparison, local disease control for the oropharynx and hypopharynx groups was 86% and 79% respectively. The overall survival rate for the oropharyngeal and hypopharyngeal groups were 41% and 6% respectively</p> <p>Conclusion</p> <p>Patients with locally advanced oral cavity cancer treated with the chemoradiation protocol RADPLAT have outcomes that are equal or better compared to patients with similar disease involving the oropharynx and hypopharynx</p