Prediction of plan adaptation in head and neck cancer proton therapy using clinical, radiographic, and dosimetric features.

PURPOSE: Because proton head and neck (HN) treatments are sensitive to anatomical changes, plan adaptation (re-plan) during the treatment course is needed for a significant portion of patients. We aim to predict re-plan at plan review stage for HN proton therapy with a neural network (NN) model trained with patients' dosimetric and clinical features. The model can serve as a valuable tool for planners to assess the probability of needing to revise the current plan. METHODS AND MATERIALS: Mean beam dose heterogeneity index (BHI), defined as the ratio of the maximum beam dose to the prescription dose, plan robustness features (clinical target volume (CTV), V100 changes, and V100 > 95% passing rates in 21 robust evaluation scenarios), as well as clinical features (e.g., age, tumor site, and surgery/chemotherapy status) were gathered from 171 patients treated at our proton center in 2020, with a median age of 64 and stages from I-IVc across 13 HN sites. Statistical analyses of dosimetric parameters and clinical features were conducted between re-plan and no-replan groups. A NN was trained and tested using these features. Receiver operating characteristic (ROC) analysis was conducted to evaluate the performance of the prediction model. A sensitivity analysis was done to determine feature importance. RESULTS: Mean BHI in the re-plan group was significantly higher than the no-replan group (p < .01). Tumor site (p < .01), chemotherapy status (p < .01), and surgery status (p < .01) were significantly correlated to re-plan. The model had sensitivities/specificities of 75.0%/77.4%, respectively, and an area under the ROC curve of .855. CONCLUSION: There are several dosimetric and clinical features that correlate to re-plans, and NNs trained with these features can be used to predict HN re-plans, which can be used to reduce re-plan rate by improving plan quality.

Role of TnrA in nitrogen source-dependent repression of Bacillus subtilis glutamate synthase gene expression.

Synthesis of glutamate, the cell's major donor of nitrogen groups and principal anion, occupies a significant fraction of bacterial metabolism. In Bacillus subtilis, the gltAB operon, encoding glutamate synthase, requires a specific positive regulator, GltC, for its expression. In addition, the gltAB operon was shown to be repressed by TnrA, a regulator of several other genes of nitrogen metabolism and active under conditions of ammonium (nitrogen) limitation. TnrA was found to bind directly to a site immediately downstream of the gltAB promoter. As is true for other genes, the activity of TnrA at the gltAB promoter was antagonized by glutamine synthetase under certain growth conditions.

Stationary-phase-inducible "gearbox" promoters: differential effects of katF mutations and role of sigma 70.

Many of the changes in gene expression observed when Escherichia coli cells enter stationary phase are regulated at the level of transcription initiation. A group of stationary-phase-inducible promoters, known as "gearbox" promoter, display a characteristic sequence in the -10 region which differs greatly from the consensus sequence for sigma 70-dependent promoters. Here we describe our studies on the gearbox promoters bolAp1 and mcbAp, responsible for the temporally regulated transcription of bolA and the genes involved in the synthesis of the peptide antibiotic microcin B17, respectively. Deletion analysis of mcbAp demonstrated that the stationary-phase-inducible properties of this promoter are found in a DNA fragment extending from -54 to +11 bp, surrounding the transcriptional start site, and are separable from DNA sequences responsible for the OmpR-dependent stimulation of transcription of mcbAp. In vitro transcription studies indicate that the RNA polymerase holoenzyme involved in the transcription of mcbAp contains sigma 70. In this and an accompanying paper (R. Lange and R. Hengge-Aronis, J. Bacteriol. 173: 4474-4481, 1991), experiments are described which show that the product of katF, a global regulator of stationary-phase gene expression and a putative sigma factor, is required for the expression of bolAp1 fused to the reporter gene lacZ. In contrast, mcbAp appears to be negatively regulated by katF. We discuss the implications of these results for postexponential gene expression and the role of gearbox sequences in the regulation of promoter activity.

Positive regulation of glutamate biosynthesis in Bacillus subtilis.

Nitrogen source regulation of glutamate synthase activity in Bacillus subtilis occurs at the level of transcription of the gltA and gltB genes, which encode the two subunits of the enzyme. We show here that transcription of gltA requires the product of gltC, a gene whose transcription is divergent from that of gltA and whose transcriptional control sequences overlap those of gltA. gltC mutants had decreased, aberrantly regulated levels of glutamate synthase activity and decreased gltA mRNA. The gltC gene product could act in trans to complement both these defects. In addition, the gltC gene product repressed its own transcription. The DNA sequence of gltC revealed that its putative product is very similar to a number of positive regulatory proteins from gram-negative bacteria (the LysR family).

Pulmonary disease from exposure to an artificial aluminium silicate: further observations.

A cross sectional analysis of the relation between exposure to an artificial aluminium silicate (alunite residue) and pulmonary function changes has been made in 32 subjects, 17 of whom had been previously reported and in whom there was suggestive evidence of a dose response relation between gas transfer and total silicate exposure. Longitudinal data were also available for nine subjects. No dose effect relation was observed in either analysis and only one of the three subjects previously observed to have an abnormal chest radiograph (the index subject) had deteriorated appreciably. Respirable particles of alunite residue were injected intratracheally into Syrian hamsters. No evidence of pulmonary toxicity was seen as judged by bronchoalveolar lavage measurements of the concentrations lactic dehydrogenase, albumin, and the lambda fraction of gold, and the numbers of macrophages, polymorphonuclear cells, and red blood cells (alpha-quartz and ferrous oxide were used as positive and negative controls). These results do not support a significant toxic effect of this aluminium silicate on the lungs.

Regulation of Bacillus subtilis glutamate synthase genes by the nitrogen source.

The wild-type alleles of the gltA292 and gltB1 mutations of Bacillus subtilis have been identified in banks of B. subtilis DNA cloned in phage lambda. These mutations are thought to define the genes for the two subunits of glutamate synthase. Sequences having transforming activity for each allele were subcloned in plasmids and used as hybridization probes for measurements of the rates of synthesis and steady-state levels of glt mRNAs under different growth conditions. For both gltA and gltB, the level of mRNA varied according to the nitrogen source in the growth medium, to an extent sufficient to explain the variation in glutamate synthase activity under the same conditions. Two start points for mRNA synthesis were detected within the cloned DNA, one of which corresponded to the gltA locus. The other start point appears to define a transcription unit, separate from gltA and gltB, within which mutations cause loss of glutamate synthase activity.

Poly(ADP-ribose) metabolism appears normal in EM9, a mutagen-sensitive mutant of CHO cells.

EM9 is a mutagen-sensitive CHO cell whose phenotype resembles that of normal CHO cells exposed to 3-aminobenzamide, an inhibitor of poly(ADP-ribose) synthesis. This phenotype suggested that EM9 might be defective in poly(ADP-ribose) metabolism, but we now cannot find any abnormality in the synthesis or in the degradation of poly(ADP-ribose) in permeabilized EM9 cells. Thus the effects of 3-aminobenzamide on wild-type cells may be due to the inhibition of processes other than poly(ADP-ribose) synthesis. 3-Aminobenzamide enhances the cytotoxicity of EMS toward EM9 and control cells to the same degree.

The pulmonary toxicity of an ash sample from the MT. St. Helens Volcano.

Volcanic ash was collected from the Moses Lake region of Washington State after the 18 May 1980 eruption of Mt. St. Helens. The ash was tested in a short-term bioassay system using hamsters exposed by intratracheal instillation. One day after exposure the lungs were lavaged and the fluid collected was characterized using several parameters that represent different manifestations of lung injury: (a) in situ phagocytic ability of pulmonary macrophages; (b) the inflammatory response, as shown by polymorphonuclear neutrophil numbers and albumin levels in lung lavage fluid; and (c) release of cytoplasmic and lysosomal enzymes into the cell-free supernatant of lung-lavage fluid. The response to volcanic ash was elevated compared to controls, but was similar to the response to Al2O3, a dust considered to be relatively inert. In contrast, the response to alpha-quartz, a highly toxic fibrogenic dust, was significantly greater than the response to either volcanic ash or Al2O3 for most parameters measured.

The response of the acute-phase plasma protein alpha2-macroglobulin to vitamin A deficiency in the rat.

Alpha2-macroglobulin (alpha2-M) was determined in the sera of vitamin A-deficient and pair-fed control rats. Alpha2-macroglobulin levels were assayed by radial immunodiffusion using a purified standard sample from sera from turpentine-stressed rats. There was no significant increase in the serum level of alpha2-M in vitamin A-deficient rats relative to pair-fed controls, indicating that there was no acute response to the stress of the deficiency. When turpentine was injected to elicit an acute response, the serum level of alpha2-M rose equally (by almost 100-fold) in both deficient and normal rats. It was concluded that the response to vitamin A deficiency of serum glycoprotein synthesis shows some specificity in that the synthesis of alpha2-M in response to stress was not affected by vitamin A, whereas we previously found that levels of alpha1-M, which is very similar to alpha2-M, decline with vitamin A deficiency.