Metabolic stress-induced long ncRNA transcription governs the formation of meiotic DNA breaks in the fission yeast fbp1 gene.

Meiotic recombination is a pivotal process that ensures faithful chromosome segregation and contributes to the generation of genetic diversity in offspring, which is initiated by the formation of double-strand breaks (DSBs). The distribution of meiotic DSBs is not uniform and is clustered at hotspots, which can be affected by environmental conditions. Here, we show that non-coding RNA (ncRNA) transcription creates meiotic DSBs through local chromatin remodeling in the fission yeast fbp1 gene. The fbp1 gene is activated upon glucose starvation stress, in which a cascade of ncRNA-transcription in the fbp1 upstream region converts the chromatin configuration into an open structure, leading to the subsequent binding of transcription factors. We examined the distribution of meiotic DSBs around the fbp1 upstream region in the presence and absence of glucose and observed several new DSBs after chromatin conversion under glucose starvation conditions. Moreover, these DSBs disappeared when cis-elements required for ncRNA transcription were mutated. These results indicate that ncRNA transcription creates meiotic DSBs in response to stress conditions in the fbp1 upstream region. This study addressed part of a long-standing unresolved mechanism underlying meiotic recombination plasticity in response to environmental fluctuation.

Applicability evaluation of the TRS-483 protocol for the determination of small-field output factors using different multi-leaf collimator and field-shaping types.

PURPOSE: To evaluate the applicability of TRS-483 output correction factors (CFs) for small-field output factors (OFs) using different multi-leaf collimators (MLC) and field-shaping types. METHODS: All measurements were performed on TrueBeam, TrueBeam STx, and Halcyon using 6 MV flattening filter-free energy. Four detectors, including CC01, CC04, microDiamond, and EDGE, were used. Nominal field sizes ranging from 1 × 1 to 4 × 4, and 10 × 10 cm2 were used to measure small-field OFs at source-to-axis distance of 100 cm with a 0° gantry angle in a 3D water phantom. Further, the field-shaping types were defined using jaw collimator or MLC (five different configurations). A field size of 10 × 10 cm2 was used as the reference for calculation of OFs obtained as ratio of detector readings (OFdet). The percentage difference and coefficient of variation of OFdet and OFdet corrected by applying CF were compared for each field size and configuration. RESULTS: For OFdet corrected by applying CF, the ranges of percentage difference and coefficient of variation in all configurations for ≥ 2 × 2 cm2 fields were reduced from 1.2-2.2 to 0.8-1.3 percentage points (%pt) and from 0.5-1.0 to 0.4-0.7%, respectively. For 1 × 1 cm2 field, the ranges of percentage difference and coefficient of variation were reduced from 3.3-5.7 to 1.2-2.2 %pt and from 2.2-3.7 to 0.8-1.1%, respectively. CONCLUSIONS: The CFs described in TRS-483 dosimetry protocol have broad applicability in reducing OF variations between detectors under different MLC and field-shaping types.

Stepwise Sulfite Reduction on a Dinuclear Ruthenium Complex Leading to Hydrogen Sulfide.

Sulfite reduction by dissimilatory sulfite reductases is a key process in the global sulfur cycle. Sulfite reductases catalyze the 6e- reduction of SO32- to H2S using eight protons (SO32- + 8H+ + 6e- → H2S + 3H2O). However, detailed research into the reductive conversion of sulfite on transition-metal-based complexes remains unexplored. As part of our ongoing research into reproducing the function of reductases using dinuclear ruthenium complex {(TpRu)2(µ-Cl)(µ-pz)} (Tp = HB(pyrazolyl)3), we have targeted the function of sulfite reductase. The isolation of a key SO-bridged complex, followed by a sulfite-bridged complex, eventually resulted in a stepwise sulfite reduction. The reduction of a sulfite to a sulfur monoxide using 4H+ and 4e-, which was followed by conversion of the sulfur monoxide to a disulfide with concomitant consumption of 2H+ and 2e-, proceeded on the same platform. Finally, the production of H2S from the disulfide-bridged complex was achieved.

Effect of angular dependence for small-field dosimetry using seven different detectors.

BACKGROUND: Small-field dosimetry is challenging for radiotherapy dosimetry because of the loss of lateral charged equilibrium, partial occlusion of the primary photon source by the collimating devices, perturbation effects caused by the detector materials and their design, and the detector size relative to the radiation field size, which leads to a volume averaging effect. Therefore, a suitable tool for small-field dosimetry requires high spatial resolution, tissue equivalence, angular independence, and energy and dose rate independence to achieve sufficient accuracy. Recently, with the increasing use of combinations of coplanar and non-coplanar beams for small-field dosimetry, there is a need to clarify angular dependence for dosimetry where the detector is oriented at various angles to the incident beam. However, the effect of angular dependence on small-field dosimetry with coplanar and non-coplanar beams has not been fully clarified. PURPOSE: This study clarified the effect of angular dependence on small-field dosimetry with coplanar and non-coplanar beams using various detectors. METHODS: Seven different detectors were used: CC01, RAZOR, RAZOR Nano, Pinpoint 3D, stereotactic field diode (SFD), microSilicon, and microDiamond. All measurements were taken using a TrueBeam STx with 6 MV and 10 MV flattening filter-free (FFF) energies using a water-equivalent spherical phantom with a source-to-axis distance of 100 cm. The detector was inserted in a perpendicular orientation, and the gantry was rotated at 15° increments from the incidence beam angle. A multi-leaf collimator (MLC) with four field sizes of 0.5 × 0.5, 1 × 1, 2 × 2, and 3 × 3 cm2 , and four couch angles from 0°, 30°, 60°, and 90° (coplanar and non-coplanar) were adopted. The angular dependence response (AR) was defined as the ratio of the detector response at a given irradiation gantry angle normalized to the detector response at 0°. The maximum AR differences were calculated between the maximum and minimum AR values for each detector, field size, energy, and couch angle. RESULTS: The maximum AR difference for the coplanar beam was within 3.3% for all conditions, excluding the maximum AR differences in 0.5 × 0.5 cm2 field for CC01 and RAZOR. The maximum AR difference for non-coplanar beams was within 2.5% for fields larger than 1 × 1 cm2 , excluding the maximum AR differences for RAZOR Nano, SFD, and microSilicon. The Pinpoint 3D demonstrated stable AR tendencies compared to other detectors. The maximum difference was within 2.0%, except for the 0.5 × 0.5 cm2 field and couch angle at 90°. The tendencies of AR values for each detector were similar when using different energies. CONCLUSION: This study clarified the inherent angular dependence of seven detectors that were suitable for small-field dosimetry. The Pinpoint 3D chamber had the smallest angular dependence of all detectors for the coplanar and non-coplanar beams. The findings of this study can contribute to the calculation of the AR correction factor, and it may be possible to adapt detectors with a large angular dependence on coplanar and non-coplanar beams. However, note that the gantry sag and detector-specific uncertainties increase as the field size decreases.

Evaluation of correlation between intrafractional residual setup errors and accumulation of delivered dose distributions in single isocenter volumetric modulated arc therapy for multiple brain metastases.

PURPOSE: To evaluate the displacement of gross tumor volume (GTV) positions caused by intrafractional residual setup errors (RSEs) and to accumulate delivered dose distributions considering intrafraction RSEs in fractionated-stereotactic radiotherapy (f-SRT) with single isocenter volumetric modulated arc therapy (SI-VMAT) for multiple brain metastases. METHODS: Overall, 72 consecutive patients who underwent f-SRT with SI-VMAT for multiple brain metastases were included. For all patients, 6D correction was performed using the ExacTrac X-ray (ETX) system. GTV displacement (ΔD) was calculated considering the intrafractional RSEs measured by the ETX system during irradiation. The correlation between ΔD and the distance from the isocenter to each GTV (d) was analyzed. Computed tomography (CT) images considering the intrafractional RSEs were generated for five patients with ΔD > 1 mm. The delivered dose distributions for all fractions were reconstructed on the corresponding CT, followed by their accumulation. RESULTS: The 95th percentile of ΔD from 7,270 resultant center positions of 417 GTVs was 0.92 mm. No correlation was observed between ΔD and d. For 53 GTVs from five patients with ΔD > 1 mm, the difference of GTV D99.5% and D0.5% between the planned and accumulated values was -0.4 ± 2.5% and -1.0 ± 0.8%, respectively. There was no correlation between d and the difference of GTV D99.5% and D0.5%. CONCLUSIONS: We found no significant difference in GTV D99.5% and D0.5%, despite the location of GTVs far from the isocenter. However, it should be noted that this result was because the intrafractional RSEs were reduced to a clinically acceptable level.

Dosiomic feature comparison between dose-calculation algorithms used for lung stereotactic body radiation therapy.

To evaluate the reproducibility of dose-based radiomic (dosiomic) features between dose-calculation algorithms for lung stereotactic body radiation therapy (SBRT). We analyzed 105 patients with early-stage non-small cell lung cancer who underwent lung SBRT between March 2011 and December 2017. Radiation doses of 48, 60, and 70 Gy were prescribed to the isocenter in 4-8 fractions. Dose calculations were performed using X-ray voxel Monte Carlo (XVMC) on the iPlan radiation treatment planning system (RTPS). Thereafter, the radiation doses were recalculated using the Acuros XB (AXB) and analytical anisotropic algorithm (AAA) on the Eclipse RTPS while maintaining the XVMC-calculated monitor units and beam arrangements. A total of 6808 dosiomic features were extracted without preprocessing (112 shape, 144 first-order, and 600 texture features) or with wavelet filters to eight decompositions (1152 first-order and 4800 texture features). Features with absolute pairwise concordance correlation coefficients-|CCcon|-values exceeding or equaling 0.85 were considered highly reproducible. Subgroup analyses were performed considering the wavelet filters and prescribed doses. The numbers of highly reproducible first-order and texture features were 34.8%, 26.9%, and 31.0% for the XVMC-AXB, XVMC-AAA, and AXB-AAA pairs, respectively. The maximum difference between the mean |CCcon| values was 0.70 and 0.11 for the subgroup analyses of wavelet filters and prescribed dose, respectively. The application of wavelet filter-based dosiomic analyses may be limited when using different types of dose-calculation algorithms for lung SBRT.

Geometric and dosimetric impact of 3D generative adversarial network-based metal artifact reduction algorithm on VMAT and IMPT for the head and neck region.

BACKGROUND: We investigated the geometric and dosimetric impact of three-dimensional (3D) generative adversarial network (GAN)-based metal artifact reduction (MAR) algorithms on volumetric-modulated arc therapy (VMAT) and intensity-modulated proton therapy (IMPT) for the head and neck region, based on artifact-free computed tomography (CT) volumes with dental fillings. METHODS: Thirteen metal-free CT volumes of the head and neck regions were obtained from The Cancer Imaging Archive. To simulate metal artifacts on CT volumes, we defined 3D regions of the teeth for pseudo-dental fillings from the metal-free CT volumes. HU values of 4000 HU were assigned to the selected teeth region of interest. Two different CT volumes, one with four (m4) and the other with eight (m8) pseudo-dental fillings, were generated for each case. These CT volumes were used as the Reference. CT volumes with metal artifacts were then generated from the Reference CT volumes (Artifacts). On the Artifacts CT volumes, metal artifacts were manually corrected for using the water density override method with a value of 1.0 g/cm3 (Water). By contrast, the CT volumes with reduced metal artifacts using 3D GAN model extension of CycleGAN were also generated (GAN-MAR). The structural similarity (SSIM) index within the planning target volume was calculated as quantitative error metric between the Reference CT volumes and the other volumes. After creating VMAT and IMPT plans on the Reference CT volumes, the reference plans were recalculated for the remaining CT volumes. RESULTS: The time required to generate a single GAN-MAR CT volume was approximately 30 s. The median SSIMs were lower in the m8 group than those in the m4 group, and ANOVA showed a significant difference in the SSIM for the m8 group (p < 0.05). Although the median differences in D98%, D50% and D2% were larger in the m8 group than the m4 group, those from the reference plans were within 3% for VMAT and 1% for IMPT. CONCLUSIONS: The GAN-MAR CT volumes generated in a short time were closer to the Reference CT volumes than the Water and Artifacts CT volumes. The observed dosimetric differences compared to the reference plan were clinically acceptable.

Evaluation of intrafractional head motion for intracranial stereotactic radiosurgery with a thermoplastic frameless mask and ceiling-floor-mounted image guidance device.

PURPOSE: To evaluate intrafractional head motion (IFM) in patients who underwent intracranial stereotactic radiosurgery with the ExacTrac X-ray system (ETX) and a frameless mask. METHODS: A total of 143 patients who completed a pre-treatment examination for IFM were eligible for this study. The frameless mask type B R408 (Klarity Medical & Equipment Co., Ltd., Guangzhou, China), which covers the back of the head, and the entire face, was used for patient immobilization. After the initial 6D correction and first X-ray verification (IFM1), X-ray verification was performed every 3 min for a duration of 15 min. The IFMp (2 ≤ p ≤ 6) was calculated as the positional difference from IFM1. In addition, the inter-phase IFM (IP-IFM) and IFMm were calculated. The IP-IFM was defined as |IFMp - IFMp-1|, and IFMm as the difference between the values after all patients were asked to move their heads intentionally with the frameless mask on. RESULTS: Both translational IFMp and IP-IFM exceeded 1 mm for a single patient, whereas, for all patients, the translational IFMm values were kept to within 1 mm in all directions. The proportions of the rotational IFMp, IP-IFM, and IFMm values within 0.5° were greater than 94.4%, 98.6%, and 90.2% for all of the rotational axes, respectively. CONCLUSIONS: A frameless mask achieved highly accurate patient positioning in combination with ETX and a 6°-of-freedom robotic couch; however, a deviation over 1 mm and 0.5° was observed with low frequency. Therefore, X-ray verification and correction are required during treatment.

Independent calculation-based verification of volumetric-modulated arc therapy-stereotactic body radiotherapy plans for lung cancer.

This study aimed to investigate the feasibility of independent calculation-based verification of volumetric-modulated arc therapy (VMAT)-stereotactic body radiotherapy (SBRT) for patients with lung cancer using a secondary treatment planning system (sTPS). In all, 50 patients with lung cancer who underwent VMAT-SBRT between April 2018 and May 2019 were included in this study. VMAT-SBRT plans were devised using the Collapsed-Cone Convolution in RayStation (primary TPS: pTPS). DICOM files were transferred to Eclipse software (sTPS), which utilized the Eclipse software, and the dose distribution was then recalculated using Acuros XB. For the verification of dose distribution in homogeneous phantoms, the differences among pTPS, sTPS, and measurements were evaluated using passing rates of a dose difference of 5% (DD5%) and gamma index of 3%/2 mm (γ3%/2 mm). The ArcCHECK cylindrical diode array was used for measurements. For independent verification of dose-volume parameters per the patient's geometry, dose-volume indices for the planning target volume (PTV) including D95% and the isocenter dose were evaluated. The mean differences (± standard deviations) between the pTPS and sTPS were then calculated. The gamma passing rates of DD5% and γ3%/2 mm criteria were 99.2 ± 2.4% and 98.6 ± 3.2% for pTPS vs. sTPS, 92.9 ± 4.0% and 94.1 ± 3.3% for pTPS vs. measurement, and 93.0 ± 4.4% and 94.3 ± 4.1% for sTPS vs. measurement, respectively. The differences between pTPS and sTPS for the PTVs of D95% and the isocenter dose were -3.1 ± 2.0% and -2.3 ± 1.8%, respectively. Our investigation of VMAT-SBRT plans for lung cancer revealed that independent calculation-based verification is a time-efficient method for patient-specific quality assurance.

Use of a second-dose calculation algorithm to check dosimetric parameters for the dose distribution of a first-dose calculation algorithm for lung SBRT plans.

PURPOSE: To verify lung stereotactic body radiotherapy (SBRT) plans using a secondary treatment planning system (TPS) as an independent method of verification and to define tolerance levels (TLs) in lung SBRT between the primary and secondary TPSs. METHODS: A total of 147 lung SBRT plans calculated using X-ray voxel Monte Carlo (XVMC) were exported from iPlan to Eclipse in DICOM format. Dose distributions were recalculated using the Acuros XB (AXB) and the anisotropic analytical algorithm (AAA), while maintaining monitor units (MUs) and the beam arrangement. Dose to isocenter and dose-volumetric parameters, such as D2, D50, D95 and D98, were evaluated for each patient. The TLs of all parameters between XVMC and AXB (TLAXB) and between XVMC and AAA (TLAAA) were calculated as the mean±1.96 standard deviations. RESULTS: AXB values agreed with XVMC values within 3.5% for all dosimetric parameters in all patients. By contrast, AAA sometimes calculated a 10% higher dose in PTV D95 and D98 than XVMC. The TLAXB and TLAAA of the dose to isocenter were -0.3±1.4% and 0.6±2.9%, respectively. Those of D95 were 1.3±1.8% and 1.7±3.6%, respectively. CONCLUSIONS: This study quantitatively demonstrated that the dosimetric performance of AXB is almost equal to that of XVMC, compared with that of AAA. Therefore, AXB is a more appropriate algorithm for an independent verification method for XVMC.

Multiple malignant epithelioid mesotheliomas of the liver and greater omentum: a case report and review of the literature.

BACKGROUND: Malignant mesothelioma commonly arises from the pleura, but can also arise from the peritoneum, pericardium, and tunica vaginalis testis. However, malignant mesothelioma of the liver is extremely rare and coexistence with malignant mesothelioma of the greater omentum has not been described in the literature. In this case report, we present a case of multiple malignant mesothelioma of the liver and greater omentum. CASE PRESENTATION: A 36-year-old woman was admitted to our hospital for the evaluation of an elastic hard mass in the right upper abdomen. Abdominal contrast computed tomography showed a cystic mass measuring 13 × 14 × 11 cm in the right liver lobe with enhanced mural nodule. Abnormal accumulation was identified in the liver and lower abdominal area on 18F-fluorodeoxyglucose positron emission tomography. The patient underwent hepatectomy of the posterior segment and partial resection of the omentum. The final pathological diagnosis was low-grade multiple malignant epithelioid mesothelioma based on characteristic immunohistochemical findings. As of 6 months postoperatively, the patient has shown no disease recurrence. CONCLUSIONS: We present the first case of a 36-year-old woman with multiple malignant mesothelioma of the liver and greater omentum.

Optimization of Couch Modeling in the Change of Dose Calculation Methods and Their Versions.

In external radiotherapy, the X-ray beam passes through the treatment couch, leading to the dose reduction by the attenuation of the couch. As a method to compensate for the reduction, radiation treatment planning systems (RTPS) support virtual couch function, namely "couch modeling method". In the couch modeling method, the computed tomography (CT) numbers assigned to each structure should be optimized by comparing calculations to measurements for accurate dose calculation. Thus, re-optimization of CT numbers will be required when the dose calculation algorithm or their version changes. The purpose of this study is to evaluate the calculation accuracy of the couch modeling method in different calculation algorithms and their versions. The optimal CT numbers were determined by minimizing the difference between measured transmission factors and calculated ones. When CT numbers optimized by Anisotropic Analytical Algorithm (AAA) Ver. 8.6 were used, the maximum and the mean difference of transmission factor were 5.8% and 1.5%, respectively, for Acuros XB (AXB) Ver. 11.0. However, when CT numbers optimized by AXB Ver. 11.0 were used, they were 2.6% and 0.6%, respectively. The CT numbers for couch structures should be optimized when changing dose calculation algorithms and their versions. From the comparison of the measured transmission to calculation, it was found that the CT numbers had high accuracy.

Dosimetric Verification around High-density Materials for External Beam Radiotherapy.

It is generally known that the dose distribution around the high-density materials is not accurate with commercially available radiation treatment planning systems (RTPS). Recently, Acuros XB (AXB) has been clinically available for dose calculation algorithm. The AXB is based on the linear Boltzmann transport equation - the governing equation - that describes the distribution of radiation particles resulting from their interactions with matter. The purpose of this study was to evaluate the dose calculation accuracy around high-density materials for AXB under three X-rays energy on the basis of measured values with EBT3 and compare AXB with various dose calculation algorithms (AAA, XVMC) in RTPS and Monte Carlo. First, two different metals, including titanium and stainless steel, were inserted at the center of a water-equivalent phantom, and the depth dose was measured with EBT3. Next, after a phantom which reproduced the geometry of measurement was virtually created in RTPS, dose distributions were calculated with three commercially available algorithms (AXB, AAA, and XVMC) and MC. The calculated doses were then compared with the measured ones. As a result, compared to other algorithms, it was found that the dose calculation accuracy of AXB at the exit side of high-density materials was comparable to that of MC and measured value with EBT3. However, note that AXB underestimated the dose up to approximately 30% at the plane of incidence because it cannot exactly estimate the impact of the backscatter.

Dosimetric comparison of Acuros XB, AAA, and XVMC in stereotactic body radiotherapy for lung cancer.

PURPOSE: To compare the dosimetric performance of Acuros XB (AXB), anisotropic analytical algorithm (AAA), and x-ray voxel Monte Carlo (XVMC) in heterogeneous phantoms and lung stereotactic body radiotherapy (SBRT) plans. METHODS: Water- and lung-equivalent phantoms were combined to evaluate the percentage depth dose and dose profile. The radiation treatment machine Novalis (BrainLab AG, Feldkirchen, Germany) with an x-ray beam energy of 6 MV was used to calculate the doses in the composite phantom at a source-to-surface distance of 100 cm with a gantry angle of 0°. Subsequently, the clinical lung SBRT plans for the 26 consecutive patients were transferred from the iPlan (ver. 4.1; BrainLab AG) to the Eclipse treatment planning systems (ver. 11.0.3; Varian Medical Systems, Palo Alto, CA). The doses were then recalculated with AXB and AAA while maintaining the XVMC-calculated monitor units and beam arrangement. Then the dose-volumetric data obtained using the three different radiation dose calculation algorithms were compared. RESULTS: The results from AXB and XVMC agreed with measurements within ± 3.0% for the lung-equivalent phantom with a 6 × 6 cm(2) field size, whereas AAA values were higher than measurements in the heterogeneous zone and near the boundary, with the greatest difference being 4.1%. AXB and XVMC agreed well with measurements in terms of the profile shape at the boundary of the heterogeneous zone. For the lung SBRT plans, AXB yielded lower values than XVMC in terms of the maximum doses of ITV and PTV; however, the differences were within ± 3.0%. In addition to the dose-volumetric data, the dose distribution analysis showed that AXB yielded dose distribution calculations that were closer to those with XVMC than did AAA. Means ± standard deviation of the computation time was 221.6 ± 53.1 s (range, 124-358 s), 66.1 ± 16.0 s (range, 42-94 s), and 6.7 ± 1.1 s (range, 5-9 s) for XVMC, AXB, and AAA, respectively. CONCLUSIONS: In the phantom evaluations, AXB and XVMC agreed better with measurements than did AAA. Calculations differed in the density-changing zones (substance boundaries) between AXB/XVMC and AAA. In the lung SBRT cases, a comparative analysis of dose-volumetric data and dose distributions with XVMC demonstrated that the AXB provided better agreement with XVMC than AAA. The computation time of AXB was faster than that of XVMC; therefore, AXB has better balance in terms of the dosimetric performance and computation speed for clinical use than XVMC.

[Use of surgical clips to verify positional accuracy in image-guided accelerated partial breast irradiation].

The purpose of this study was to evaluate the accuracy of positional verification during overall radiation treatment periods in accelerated partial breast irradiation using one or more surgical clips. We first investigated the appropriate computed tomography (CT) slice thickness and detectability of clips for a matching criterion in a phantom study. Next, clinical investigations were carried on 12 patients with multiple clips positioned around the lumpectomy cavity. During radiation treatment planning, a 5-mm region of interest (5-mm ROI) was defined by adding a three dimentional (3D) margin of 5 mm to each clip. During treatment, the clips on two orthogonal kilovoltage X-ray images acquired were moved so as to be included in the corresponding 5-mm ROI on digitally reconstructed radiographs (DRRs). Positional accuracy was calculated using the displacement of each clip in the verification images. The displacements of each clip acquired in all setups were then calculated throughout the overall radiation treatment period and the factors affecting the displacement of clips were investigated. Positional accuracy was also investigated in setups using skin marks and in setups using the bone structure around the thorax. We demonstrated in a phantom study that a CT slice thickness of 2.5 mm was appropriate. In our clinical investigations, 91% of the clips were included in the 5-mm ROI. The interfractional displacement of clips was large, with a long distance between the isocenter and each clip at the time of radiation treatment planning.