Haspin kinase binds to a nucleosomal DNA supergroove.

Phosphorylation of histone H3 threonine 3 (H3T3) by Haspin recruits the chromosomal passenger complex to the inner centromere and ensures proper cell cycle progression through mitosis. The mechanism by which Haspin binds to nucleosomes to phosphorylate H3T3 is not known. We report here cryo-EM structures of the Haspin kinase domain bound to a nucleosome. In contrast with previous structures of histone-modifying enzymes, Haspin solely contacts the nucleosomal DNA, inserting into a supergroove formed by apposing major grooves of two DNA gyres. This unique binding mode provides a plausible mechanism by which Haspin can bind to nucleosomes in a condensed chromatin environment to phosphorylate H3T3. We identify key basic residues in the Haspin kinase domain that are essential for phosphorylation of nucleosomal histone H3 and binding to mitotic chromatin. Our structure is the first of a kinase domain bound to a nucleosome and is the first example of a histone-modifying enzyme that binds to nucleosomes solely through DNA contacts.

Promising therapeutic targets for ischemic stroke identified from plasma and cerebrospinal fluid proteomes: a multicenter Mendelian randomization study.

BACKGROUND: Ischemic stroke (IS) is more common every year, the condition is serious, and have a poor prognosis. New, efficient, and safe therapeutic targets are desperately needed as early treatment especially prevention and reperfusion is the key to lowering the occurrence of poorer prognosis. Generally circulating proteins are attractive therapeutic targets, this study aims to identify potential pharmacological targets among plasma and cerebrospinal fluid (CSF) proteins for the prevention and treatment of IS using a multicenter Mendelian randomization (MR) approach. METHODS: First, the genetic instruments of 734 plasma and 151 CSF proteins were assessed for causative connections with IS from MEGASTROKE consortium by MR to identify prospective therapeutic targets. Then, for additional validation, plasma proteins from the deCODE consortium and the Fenland consortium, as well as IS GWAS data from the FinnGen cohort, the ISGC consortium and UK biobank, were employed. A thorough evaluation of the aforementioned possible pharmacological targets was carried out using meta-analysis. The robustness of MR results was then confirmed through sensitivity analysis using several techniques, such as bidirectional MR analysis, Steiger filtering, and Bayesian colocalization. Finally, methods like Protein-Protein Interaction (PPI) Networking were utilized to investigate the relationship between putative drug targets and therapeutic agents. RESULTS: The authors discovered three proteins that may function as promising therapeutic targets for IS and meet the Bonferroni correction ( P <0.05/885=5.65×10 -5 ). Prekallikrein (OR=0.41, 95% CI: 0.27-0.63, P =3.61×10 -5 ), a protein found in CSF, has a 10-fold protective impact in IS, while the plasma proteins SWAP70 (OR=0.85, 95% CI: 0.80-0.91, P =1.64×10 -6 ) and MMP-12 (OR=0.92, 95% CI: 0.89-0.95, P =4.49×10 -6 ) of each SD play a protective role in IS. Prekallikrein, MMP-12, SWAP70 was replicated in the FinnGen cohort and ISGC database. MMP-12 (OR=0.93, 95% CI: 0.91-0.94, P <0.001), SWAP70 (OR=0.92, 95% CI: 0.90-0.94, P <0.001), and prekallikrein (OR=0.53, 95% CI: 0.33-0.72, P <0.001) may all be viable targets for IS, according to the combined meta-analysis results. Additionally, no evidence of reverse causality was identified, and Bayesian colocalization revealed MMP-12 (PPH 4 =0.995), SWAP70 (PPH 4 =0.987), and prekallikrein (PPH 4 =0.894) shared the same variant with IS, supporting the robustness of the aforementioned causation. Prekallikrein and MMP-12 were associated with the target protein of the current treatment of IS. Among them, Lanadelumab, a new drug whose target protein is a prekallikrein, may be a promising new drug for the treatment of IS. CONCLUSION: The prekallikrein, MMP-12, and SWAP70 are causally associated with the risk of IS. Moreover, MMP-12 and prekallikrein may be treated as promising therapeutic targets for medical intervention of IS.

Neural signals-based respiratory motion tracking: a proof-of-concept study.

Objective.Respiratory motion tracking techniques can provide optimal treatment accuracy for thoracoabdominal radiotherapy and robotic surgery. However, conventional imaging-based respiratory motion tracking techniques are time-lagged owing to the system latency of medical linear accelerators and surgical robots. This study aims to investigate the precursor time of respiratory-related neural signals and analyze the potential of neural signals-based respiratory motion tracking.Approach.The neural signals and respiratory motion from eighteen healthy volunteers were acquired simultaneously using a 256-channel scalp electroencephalography (EEG) system. The neural signals were preprocessed using the MNE python package to extract respiratory-related EEG neural signals. Cross-correlation analysis was performed to assess the precursor time and cross-correlation coefficient between respiratory-related EEG neural signals and respiratory motion.Main results.Respiratory-related neural signals that precede the emergence of respiratory motion are detectable via non-invasive EEG. On average, the precursor time of respiratory-related EEG neural signals was 0.68 s. The representative cross-correlation coefficients between EEG neural signals and respiratory motion of the eighteen healthy subjects varied from 0.22 to 0.87.Significance.Our findings suggest that neural signals have the potential to compensate for the system latency of medical linear accelerators and surgical robots. This indicates that neural signals-based respiratory motion tracking is a potential promising solution to respiratory motion and could be useful in thoracoabdominal radiotherapy and robotic surgery.

Isolation, identification, and pathogenicity of a NADC30-like porcine reproductive and respiratory disorder syndrome virus strain affecting sow production.

Since it was first reported in 1987, porcine reproductive and respiratory syndrome virus (PRRSV) has caused several economic crises worldwide. The current prevalence of PRRSV NADC30-like stains causing clinical disease outbreaks in Chain is highly concerning. Immunization against and the prevention of this infection are burdensome for farming organizations as the pathogen frequently mutates and undergoes recombination. Herein, the genetic characterization of a NADC30-like strain (termed BL2019) isolated from a farm in Guangdong Province, China, was analyzed and its pathogenicity for piglets and sows was assessed. Results revealed that BL2019 exhibits a nucleotide homology of 93.7% with NADC30 PRRSV and its NSP2 coding region demonstrates the same 131aa deletion pattern as that of NADC30 and NADC30-like. Furthermore, we identified two recombination breakpoints located nt5804 of the NSP5-coding region and nt6478 of NSP2-coding region, the gene fragment between the two breakpoints showed higher homology to the TJ strain(a representative strain of highly pathogenic PRRSV) compared to the NADC30 strain. In addition, BL2019 infection in piglets caused fever lasting for 1 week, moderate respiratory clinical signs and obvious visual and microscopic lung lesions; infection in gestating sows affected their feed intake and increased body temperature, abortion rates, number of weak fetuses, and other undesirable phenomena. Therefore, we report a NADC30-like PRRSV strain with partial recombination and a representative strain of HP-PRRSV, strain TJ, that can provide early warning and support for PRRS immune prevention and control.

Beneficial Effects of Bacillus amyloliquefaciens D1 Soy Milk Supplementation on Serum Biochemical Indexes and Intestinal Health of Bearded Chickens.

This study investigated the effects of dietary supplementation with Bacillus amyloliquefaciens D1 (B. amyloliquefaciens D1) on growth performance, serum anti-inflammatory cytokines, and intestinal microbiota composition and diversity in bearded chickens. To investigate the effects of Bacillus amyloliquefaciensa and fermented soy milk, 7-day-old broilers were orally fed different doses of Bacillus amyloliquefaciens D1 fermented soy milk for 35 days, with the unfermented soy milk group as the Placebo group. This study found that B. amyloliquefaciens D1 fermented soy milk improved the intestinal microbiota of broilers, significantly increasing the abundance of beneficial bacteria and decreasing the abundance of harmful bacteria in the gut. B. amyloliquefaciens D1 fermented soy milk also significantly reduced the serum lipopolysaccharide (LPS) content. The body weight and daily weight gain of broilers were increased. In conclusion, the results of this study are promising and indicate that supplementing the diets of bearded chickens with B. amyloliquefaciens D1 fermented soy milk has many beneficial effects in terms of maintaining intestinal microbiota balance and reducing inflammation in chickens.

A Novel C Doped MoS2 /CoP/MoO2 Ternary Heterostructure Nanoflower for Hydrogen Evolution Reaction at Wide pH Range and Efficient Overall Water Splitting in Alkaline Media.

The development of low-cost and high-efficiency bifunctional catalysts is still a challenge for hydrogen production through overall water splitting. This paper reports the in-situ synthesis of C-doped MoS2 /CoP/MoO2 using bacterial cellulose (BC) as the reducing agent and the source of C and using BC (MoS2 /Co1.2 MoO4.2 ⋅ 1.2H2 O/BC) as the template. Heterogeneous structure for hydrogen evolution reaction (HER) and alkaline water electrolysis in a wide pH range. Due to the large number of defect sites caused by C doping and the synergy between these three active components (MoS2 , CoP and MoO2 ), the HER and oxygen evolution reaction (OER) activities of the catalyst have been greatly improved. Therefore, during HER, a small initial overpotential (27 mV) was achieved in 1.0 M KOH. In 0.5 M H2 SO4 , 0.1 M PBS and 1.0 M KOH, the current density reached 10 mA cm-2 at overpotentials of 123.4, 150, and 139 mV, respectively. For OER, an overpotential of 268 mV was required to achieve 10 mA cm-2 . The alkaline two-electrode device composed of C doped MoS2 /CoP/MoO2 delivers 10 mA cm-2 at a low potential of 1.51 V and can be easily driven by a single AA battery. This work provides a new design strategy of C doped ternary heterostructures for electrocatalysis and related energy applications.

Epidemiological investigations and multilocus sequence typing of Mycoplasma synoviae isolates from chicken farms in China.

Mycoplasma synoviae (M. synoviae) is an important pathogen in poultry industry and has led to major economic losses. Understanding the epidemiology is crucial to improve control and eradication program of M. synoviae. In this study, 487 samples suspected with M. synoviae infection were collected from August 2020 to June 2021 in China. Among 487 samples, 324 samples were MS positive, the positive rate was 66.53%, and 104 strains were isolated from 324 positive samples. The multilocus sequence typing (MLST) method based on seven housekeeping genes was used to conduct genotyping 104 M. synoviae strains isolated, and the 104 isolates belonged to 8 sequence types (STs) after MLST genotyping, and ST-34 had the highest proportion. After BURST analysis, all 104 isolates were divided into group 12 with other 56 strains isolated from China. Phylogenetic tree constructed by neighbor-joining method showed that nearly all of Chinese isolates (160 isolates) clustered together and separated from other reference isolates (217 isolates) in the PubMLST database. In conclusion, this study suggested that the M. synoviae strains in China were highly similar and independent of abroad strains.

Guaranteed performance of individual control chart used in gamma passing rate-based patient-specific quality assurance.

PURPOSE: To assess the effect of sampling variability on the performance of individual charts (I-charts) for PSQA and provide a robust and reliable method for unknown PSQA processes. MATERIALS AND METHODS: A total of 1327 pretreatment PSQAs were analyzed. Different datasets with samples in the range of 20-1000 were used to estimate the lower control limit (LCL). Based on the iterative "Identify-Eliminate-Recalculate" and direct calculation without any outlier filtering procedures, five I-charts methods, namely the Shewhart, quantile, scaled weighted variance (SWV), weighted standard deviation (WSD), and skewness correction (SC) method, were used to compute the LCL. The average run length (ARL0) and false alarm rate (FAR0) were calculated to evaluate the performance of LCL. RESULTS: The ground truth of the values of LCL, FAR0, and ARL0 obtained via in-control PSQAs were 92.31%, 0.135%, and 740.7, respectively. Further, for in-control PSQAs, the width of the 95% confidence interval of LCL values for all methods tended to decrease with the increase in sample size. In all sample ranges of in-control PSQAs, only the median LCL and ARL0 values obtained via WSD and SWV methods were close to the ground truth. For the actual unknown PSQAs, based on the "Identify-Eliminate-Recalculate" procedure, only the median LCL values obtained by the WSD method were closest to the ground truth. CONCLUSIONS: Sampling variability seriously affected the I-chart performance in PSQA processes, particularly for small samples. For unknown PSQAs, the WSD method based on the implementation of the iterative "Identify-Eliminate-Recalculate" procedure exhibited sufficient robustness and reliability.

Global Dynamics of Porcine Enteric Coronavirus PEDV Epidemiology, Evolution, and Transmission.

With a possible origin from bats, the alphacoronavirus Porcine epidemic diarrhea virus (PEDV) causes significant hazards and widespread epidemics in the swine population. However, the ecology, evolution, and spread of PEDV are still unclear. Here, from 149,869 fecal and intestinal tissue samples of pigs collected in an 11-year survey, we identified PEDV as the most dominant virus in diarrheal animals. Global whole genomic and evolutionary analyses of 672 PEDV strains revealed the fast-evolving PEDV genotype 2 (G2) strains as the main epidemic viruses worldwide, which seems to correlate with the use of G2-targeting vaccines. The evolving pattern of the G2 viruses presents geographic bias as they evolve tachytely in South Korea but undergo the highest recombination in China. Therefore, we clustered six PEDV haplotypes in China, whereas South Korea held five haplotypes, including a unique haplotype G. In addition, an assessment of the spatiotemporal spread route of PEDV indicates Germany and Japan as the primary hubs for PEDV dissemination in Europe and Asia, respectively. Overall, our findings provide novel insights into the epidemiology, evolution, and transmission of PEDV, and thus may lay a foundation for the prevention and control of PEDV and other coronaviruses.

Abnormalities in electroencephalographic microstates among violent patients with schizophrenia.

Schizophrenia is often associated with a remarkably increased risk of violence, which has become a public health concern and brought a great economic burden. Recent studies have reported changes in the electroencephalograms (EEG) of patients with schizophrenia. The evidence for an association between EEG and violence in patients with schizophrenia is not conclusive. This study aimed to investigate EEG microstates in violent patients with schizophrenia. Forty-three violent patients with schizophrenia (the VS group) and 51 non-violent patients with schizophrenia (the NVS group) were included, and their EEG microstates were recorded using 21-Channel EEG recordings. The two groups were compared for differences of four microstate classes (A-D) with regards to three microstate parameters (duration, occurrence, and coverage). Compared with the NVS group, the VS group exhibited increased duration, occurrence, and coverage of microstate class A and decreased occurrence of microstate class B. The VS group also had lower probabilities of transitions from "B to C" and from "C to B", as compared with the NVS group. In addition, the MOAS score was positively correlated with the duration, occurrence, and coverage of microstate A. The present study found an abnormal pattern of EEG microstates in violent patients with schizophrenia, which might help clinicians identify patients with schizophrenia who might engaged in violence as well as develop intervention strategies at an early stage.

Ultrahigh Polarization Response along Large Energy Storage Properties in BiFeO3-BaTiO3-Based Relaxor Ferroelectric Ceramics under Low Electric Field.

BiFeO3-BaTiO3 (BF-BT) dielectric ceramics are receiving more and more concern for advanced energy storage devices owing to their excellent ferroelectric properties and environmental sustainability. However, the energy density and efficiency are limited in spite of the large remanent polarization. Herein, we proposed a multiscale optimization strategy via a local compositional disorder with a Birich content and nanodomain engineering by introducing the Sr0.7Bi0.2Ca0.1TiO3 (SBCT) into BF-BT ceramics. Interestingly, an extraordinary energy storage property (ESP) with a high reversible energy storage density (Wrec) of ∼3.79 J/cm3 and an ultrahigh polarization discrepancy (ΔP) of ∼58.5 µC/cm2 were obtained in the SBCT-modified BF-BT ceramics under 160 kV/cm. The boosted ESP should be attributed to the fact that the replacement of A/B-sites cations could transform the long-range ferroelectric order of the BF-BT system into polar nanoregions (PNRs) along with the refined grain size, decreased leakage current, and broadened energy band gap. Moreover, good frequency (1-103 Hz) and temperature (25-125 °C) stabilities, high fatigue resistance (× 105), large power density (∼31.1 MW/cm3), and fast discharge time (∼97 ns) were also observed for the optimized ceramics. These results illustrate a potentially effective method for creating high ESP lead-free ceramics at a low electric field.

Effects of Dietary Essential Oils Supplementation on Egg Quality, Biochemical Parameters, and Gut Microbiota of Late-Laying Hens.

The objective of this study was to explore the effects of adding essential oils (EO) to diets on egg quality, biochemical parameters and intestinal flora of late laying hens. The number of 252 Dawu Golden Phoenix laying hens (55 weeks old) were randomly sorted into two groups: the control group (CG) fed a basal diet and the EO group fed a basal diet with 300 mg/kg of essential oils. The average egg weight, feed-to-egg ratio, and egg production rate were determined every week. The trial started at week 55 and lasted for 8 weeks. During the experiment's last week, 36 eggs out of each group were chosen at random to test. In our study, dietary supplementation with EO considerably decreased the egg breaking rate (p = 0.01) and increased the shell-breaking strength (p = 0.04). The treatment group's alanine aminotransferase (ALT) levels were considerably lower than those of the control group (p = 0.03). The EO group had substantially higher total antioxidant capacity (T-AOC) and total superoxide dismutase (T-SOD) (p = 0.04 and p =0.03, respectively). However, there were no differences in alpha diversity indicators between the two groups. It is worth noting that Firmicutes were increased considerably (p < 0.05), while Spirochaetota and Proteobacteria were significantly reduced in the EO group. At genus levels, the EO supplementation increased the relative abundance of Intestinimonas (p < 0.05) and Megamonas (p < 0.01). In conclusion, a dietary supplementation of 300 mg/kg EO can improve the production performance of laying hens and the egg quality. It can also regulate the abundance of cecal flora and serum biochemical indicators.

Circular RNA hsa_circ_0018189 drives non-small cell lung cancer growth by sequestering miR-656-3p and enhancing xCT expression.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the cancers with a high mortality rate. CircRNAs have emerged as an important regulatory factor in tumorigenesis in recent years. However, the detailed regulatory mechanism of a circular RNA cullin 2 (hsa_circ_0018189; hsa_circ_0018189) is still unclear in NSCLC. METHODS: RNA levels of hsa_circ_0018189, microRNA (miR)-656-3p, and Solute carrier family seven member 11 (SLC7A11, xCT) were analyzed by real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR), and protein level was assessed by Western blot and immunohistochemical assay. Enzyme-linked immunosorbent assay was conducted to detect cell glutamine metabolism. Effects of hsa_circ_0018189 on cell proliferation, apoptosis, migration, and invasion were analyzed by corresponding assays. Luciferase reporter assay and RNA-immunoprecipitation assay confirmed the target relationship between miR-656-3p and hsa_circ_0018189 or xCT. The in vivo function of hsa_circ_0018189 was verified by xenograft mouse models. RESULTS: Hsa_circ_0018189 abundance was overexpressed in NSCLC cells and samples. Deficiency of hsa_circ_0018189 lowered NSCLC cell proliferative, migrating, invading, and glutamine metabolism capacities, and hsa_circ_0018189 silencing inhibited the growth of tumors in vivo. Hsa_circ_0018189 could up-regulate xCT by sponging miR-656-3p. And miR-656-3p downregulation or xCT overexpression partly overturned hsa_circ_0018189 knockdown or miR-656-3p mimic-mediated repression of NSCLC cell malignancy. CONCLUSION: Hsa_circ_0018189 drove NSCLC growth by interacting with miR-656-3p and upregulating xCT.

Correlation of Optical Surface Respiratory Motion Signal and Internal Lung and Liver Tumor Motion: A Retrospective Single-Center Observational Study.

Purpose: Surface-guided radiation therapy (SGRT) application has limitations. This study aimed to explore the relationship between patient characteristics and their external/internal correlation to qualitatively assess the external/internal correlation in a particular patient. Methods: Liver and lung cancer patients treated with radiotherapy in our institution were retrospectively analyzed. The external/internal correlation were calculated with Spearman correlation coefficient (SCC) and SCC after support vector regression (SVR) fitting (SCCsvr). The relationship between the external/internal correlation and magnitudes of motion of the tumor and external marker (Ai, Ae), tumor volume Vt, patient age, gender, and tumor location were explored. Results: The external/internal motions of liver and lung cancer patients were strongly correlated in the S-I direction, with mean SCCsvr values of 0.913 and 0.813. The correlation coefficients between the external/internal correlations and the patients' characteristics (Ai, Ae, Vt, and age) were all smaller than 0.5; Ai, Ae and liver tumor volumes were positively correlated with the strength of the external/internal correlation, while lung tumor volumes and patient age were negative. The external/internal correlations in males and females were roughly equal, and the external/internal correlations in patients with peripheral lung cancers were stronger than those in patients with central lung cancers. Conclusion: The external/internal correlation shows great individual differences. The effects of Ai, Ae, Vt, and age are weakly to moderately correlated. Our results suggest the necessity of individualized assessment of patient's external/internal motion correlation prior to the application of SGRT technique for breath motion monitoring.

Evaluating the impact of possible interobserver variability in CBCT-based soft-tissue matching using TCP/NTCP models for prostate cancer radiotherapy.

BACKGROUND: Prostate alignment is subject to interobserver variability in cone-beam CT (CBCT)-based soft-tissue matching. This study aims to analyze the impact of possible interobserver variability in CBCT-based soft-tissue matching for prostate cancer radiotherapy. METHODS: Retrospective data, consisting of 156 CBCT images from twelve prostate cancer patients with elective nodal irradiation were analyzed in this study. To simulate possible interobserver variability, couch shifts of 2 mm relative to the resulting patient position of prostate alignment were assumed as potential patient positions (27 possibilities). For each CBCT, the doses of the potential patient positions were re-calculated using deformable image registration-based synthetic CT. The impact of the simulated interobserver variability was evaluated using tumor control probabilities (TCPs) and normal tissue complication probabilities (NTCPs). RESULTS: No significant differences in TCPs were found between prostate alignment and potential patient positions (0.944 ± 0.003 vs 0.945 ± 0.003, P = 0.117). The average NTCPs of the rectum ranged from 5.16 to 7.29 (%) among the potential patient positions and were highly influenced by the couch shift in the anterior-posterior direction. In contrast, the average NTCPs of the bladder ranged from 0.75 to 1.12 (%) among the potential patient positions and were relatively negligible. CONCLUSIONS: The NTCPs of the rectum, rather than the TCPs of the target, were highly influenced by the interobserver variability in CBCT-based soft-tissue matching. This study provides a theoretical explanation for daily CBCT-based image guidance and the prostate-rectum interface matching procedure. TRIAL REGISTRATION: Not applicable.

Multi-omics reveals specific host metabolism-microbiome associations in intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is the most devastating subtype of stroke, but effective prevention and treatment strategies are lacking. Recently, gut microbiome and its metabolitesis are considered to be an influencing factor of stroke. However, little is known about the effects of the gut microbiome on ICH and host metabolic activity. Therefore, we used 16S sequencing, macrogenomics sequencing and untargeted metabolomics to explore the differences in gut microbial-metabolome interactions between patients with intracerebral hemorrhage and healthy control populations. We found a significant decrease in the phylum of Firmicutes and a significant increase of Bacteroidetes in ICH patients. At the genus level, Streptococcus, Bifidobacterium, Akkermansia, and Lactobacillus were more abundant in ICH patients. Macrogenomic analysis revealed active glycosaminoglycan degradation, heme synthesis, galactose degradation, lipopolysaccharide core region synthesis, and beta-Lactam resistance in ICH patients. Serum untargeted metabolomic analysis combined with ROC curves showed that octanoylcarnitine, decanoylcarnitine, dodecanoylcarnitine, glyceric acid, pyruvic acid, aspartic acid, methylcysteine, pyroglutamic acid, 9E-tetradecenoic acid, N-Acetylneuraminic acid, and aconitic acid were the best markers for the diagnosis of ICH. Correlation analysis showed that microbiome enriched in the gut of ICH patients were significantly correlated with serum metabolites, revealing a close correlation between the gut microbiome of ICH patients and the host metabolome, and significant differences from the healthy population. microbiota-host co-metabolites including pyruvic acid and 9E-tetradecenoic acid is associated with the the National Institutes of Health Stroke Scale (NIHSS) scores. In conclusion, microbiome-related metabolites in ICH patients was associated with the severity of ICH, the microbiota-host co-metabolites may be a potential may be potential therapeutic targets.

A robust approach to establish tolerance limits for the gamma passing rate-based patient-specific quality assurance using the heuristic control charts.

PURPOSE: Establishing the tolerance limits of patient-specific quality assurance (PSQA) processes based on the gamma passing rate (GPR) by using normal statistical process control (SPC) methods involves certain problems. The aim of this study was threefold: (a) to show that the heuristic SPC method can replace the quantile method for establishing tolerance limits in PSQA processes and is more robust, (b) to introduce an iterative procedure of "Identify-Eliminate-Recalculate" for establishing the tolerance limits in PSQA processes with unknown states based on retrospective GPRs, and (c) to recommend a workflow to define tolerance limits based on actual clinical retrospective GPRs. MATERIALS AND METHODS: A total of 1671 volumetric-modulated arc therapy (VMAT) pretreatment plans were measured on four linear accelerators (linacs) and analyzed by treatment sites using the GPRs under the 2%/2 mm, 3%/2 mm, and 3%/3 mm criteria. Normality testing was performed using the Anderson-Darling (AD) statistic and the optimal distributions of GPRs were determined using the Fitter Python package. The iterative "Identify-Eliminate-Recalculate" procedure was used to identify the PSQA outliers. The tolerance limits of the initial PSQAs, remaining PSQAs after elimination, and in-control PSQAs after correction were calculated using the conventional Shewhart method, two transformation methods, three heuristic methods, and two quantile methods. The tolerance limits of PSQA processes with different states for the respective methods, linacs, and treatment sites were comprehensively compared and analyzed. RESULTS: It was found that 75% of the initial PSQA processes and 63% of the in-control processes were non-normal (AD test, p < 0.05). The optimal distributions of GPRs for the initial and in-control PSQAs varied with different linacs and treatment sites. In the implementation of the "Identify-Eliminate-Recalculate" procedure, the quantile methods could not identify the out-of-control PSQAs effectively due to the influence of outliers. The tolerance limits of the in-control PSQAs, calculated using the quantile of optimal fitting distributions, represented the ground truth. The tolerance limits of the in-control PSQAs and remaining PSQAs after elimination calculated using the heuristic methods were considerably close to the ground truth (the maximum average absolute deviations were 0.50 and 1.03%, respectively). Some transformation failures occurred under both transformation methods. For the in-control PSQAs at 3%/2 mm gamma criteria, the maximum differences in the tolerance limits for four linacs and different treatment sites were 3.10 and 5.02%, respectively. CONCLUSIONS: The GPR distributions of PSQA processes vary with different linacs and treatment sites but most are skewed. In applying SPC methodologies to PSQA processes, heuristic methods are robust. For in-control PSQA processes, the tolerance limits calculated by heuristic methods are in good agreement with the ground truth. For unknown PSQA processes, the tolerance limits calculated by the heuristic methods after the iterative "Identify-Eliminate-Recalculate" procedure are closest to the ground truth. Setting linac- and treatment site-specific tolerance limits for PSQA processes is necessary for clinical applications.

Deep Neural Network With Structural Similarity Difference and Orientation-Based Loss for Position Error Classification in the Radiotherapy of Graves' Ophthalmopathy Patients.

Identifying position errors for Graves' ophthalmopathy (GO) patients using electronic portal imaging device (EPID) transmission fluence maps is helpful in monitoring treatment. However, most of the existing models only extract features from dose difference maps computed from EPID images, which do not fully characterize all information of the positional errors. In addition, the position error has a three-dimensional spatial nature, which has never been explored in previous work. To address the above problems, a deep neural network (DNN) model with structural similarity difference and orientation-based loss is proposed in this paper, which consists of a feature extraction network and a feature enhancement network. To capture more information, three types of Structural SIMilarity (SSIM) sub-index maps are computed to enhance the luminance, contrast, and structural features of EPID images, respectively. These maps and the dose difference maps are fed into different networks to extract radiomic features. To acquire spatial features of the position errors, an orientation-based loss function is proposed for optimal training. It makes the data distribution more consistent with the realistic 3D space by integrating the error deviations of the predicted values in the left-right, superior-inferior, anterior-posterior directions. Experimental results on a constructed dataset demonstrate the effectiveness of the proposed model, compared with other related models and existing state-of-the-art methods.

[Application of Virtual Monochromatic Images Reconstructed by Dual-energy Computed Tomography in Radiotherapy Treatment Planning System].

Virtual monochromatic images (VMI) that reconstructed on dual-energy computed tomography (DECT) have further application prospects in radiotherapy, and there is still a lack of clinical dose verification. In this study, GE Revolution CT scanner was used to perform conventional imaging and gemstone spectral imaging on the simulated head and body phantom. The CT images were imported to radiotherapy treatment planning system (TPS), and the same treatment plans were transplanted to compare the CT value and the dose distribution. The results show that the VMI can be imported into TPS for CT value-relative electron density conversion and dose calculation. Compared to conventional images, the VMI varies from 70 to 140 keV, has little difference in dose distribution of 6 MV photon treatment plan.

Analysis of EPID Transmission Fluence Maps Using Machine Learning Models and CNN for Identifying Position Errors in the Treatment of GO Patients.

PURPOSE: To find a suitable method for analyzing electronic portal imaging device (EPID) transmission fluence maps for the identification of position errors in the in vivo dose monitoring of patients with Graves' ophthalmopathy (GO). METHODS: Position errors combining 0-, 2-, and 4-mm errors in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions in the delivery of 40 GO patient radiotherapy plans to a human head phantom were simulated and EPID transmission fluence maps were acquired. Dose difference (DD) and structural similarity (SSIM) maps were calculated to quantify changes in the fluence maps. Three types of machine learning (ML) models that utilize radiomics features of the DD maps (ML 1 models), features of the SSIM maps (ML 2 models), and features of both DD and SSIM maps (ML 3 models) as inputs were used to perform three types of position error classification, namely a binary classification of the isocenter error (type 1), three binary classifications of LR, SI, and AP direction errors (type 2), and an eight-element classification of the combined LR, SI, and AP direction errors (type 3). Convolutional neural network (CNN) was also used to classify position errors using the DD and SSIM maps as input. RESULTS: The best-performing ML 1 model was XGBoost, which achieved accuracies of 0.889, 0.755, 0.778, 0.833, and 0.532 in the type 1, type 2-LR, type 2-AP, type 2-SI, and type 3 classification, respectively. The best ML 2 model was XGBoost, which achieved accuracies of 0.856, 0.731, 0.736, 0.949, and 0.491, respectively. The best ML 3 model was linear discriminant classifier (LDC), which achieved accuracies of 0.903, 0.792, 0.870, 0.931, and 0.671, respectively. The CNN achieved classification accuracies of 0.925, 0.833, 0.875, 0.949, and 0.689, respectively. CONCLUSION: ML models and CNN using combined DD and SSIM maps can analyze EPID transmission fluence maps to identify position errors in the treatment of GO patients. Further studies with large sample sizes are needed to improve the accuracy of CNN.