Evaluation of QSAR models for predicting mutagenicity: outcome of the Second Ames/QSAR international challenge project.

Quantitative structure-activity relationship (QSAR) models are powerful in silico tools for predicting the mutagenicity of unstable compounds, impurities and metabolites that are difficult to examine using the Ames test. Ideally, Ames/QSAR models for regulatory use should demonstrate high sensitivity, low false-negative rate and wide coverage of chemical space. To promote superior model development, the Division of Genetics and Mutagenesis, National Institute of Health Sciences, Japan (DGM/NIHS), conducted the Second Ames/QSAR International Challenge Project (2020-2022) as a successor to the First Project (2014-2017), with 21 teams from 11 countries participating. The DGM/NIHS provided a curated training dataset of approximately 12,000 chemicals and a trial dataset of approximately 1,600 chemicals, and each participating team predicted the Ames mutagenicity of each trial chemical using various Ames/QSAR models. The DGM/NIHS then provided the Ames test results for trial chemicals to assist in model improvement. Although overall model performance on the Second Project was not superior to that on the First, models from the eight teams participating in both projects achieved higher sensitivity than models from teams participating in only the Second Project. Thus, these evaluations have facilitated the development of QSAR models.

A potent allele marker related to low bull conception rate in Japanese Black bulls.

Over the years, there has been considerable variation in the bull conception rate (BCR) of Japanese Black cattle; moreover, several Japanese Black bulls with a low BCR of ≤10% have been identified. However, the alleles responsible for the low BCR are not determined yet. Therefore, in this study, we aimed to identify single-nucleotide polymorphisms (SNPs) for predicting low BCR. To this end, the genome of Japanese Black bulls was comprehensively examined by a genome-wide association study with whole-exome sequencing (WES), and the effect of the identified marker regions on BCR was determined. The WES analysis of six sub-fertile bulls with a BCR of ≤10% and 73 normal bulls with a BCR of ≥40% identified a homozygous genotype for low BCR in Bos taurus autosome 5 in the region between 116.2 and 117.9 Mb. The g.116408653G > A SNP in this region had the most significant effect on the BCR (P-value = 1.0 × 10-23), and the GG (55.4 ± 11.2%) and AG (54.4 ± 9.4%) genotypes in the SNP had a higher phenotype than the AA (9.5 ± 6.1%) genotype for the BCR. The mixed model analysis revealed that g.116408653G > A was related to approximately 43% of the total genetic variance. In conclusion, the AA genotype of g.116408653G > A is a useful index for identifying sub-fertile Japanese Black bulls. Some positive and negative effects of SNP on the BCR were presumed to identify the causative mutations, which can help evaluate bull fertility.

Post-Disaster Mental Health and Dietary Patterns among Older Survivors of an Earthquake and Tsunami.

OBJECTIVES: Research suggests that cardiometabolic disease risks are elevated among survivors of natural disasters, possibly mediated by changes in diet. Using the Brief Dietary History Questionnaire, we examined (1) dietary patterns among older survivors of the 2011 Great East Japan Earthquake and Tsunami, and (2) the contribution of posttraumatic stress symptoms (PTSS)/depressive symptoms, as well as relocation to temporary housing on dietary patterns and (3) gender differences in the associations. DESIGN, SETTING AND PARTICIPANTS: Data came from a prospective cohort study of 1,375 survivors aged 65-89 years (44.6% male). MEASUREMENTS: PTSS/depression onset was evaluated in 2013, 2.5 years after the disaster. Dietary data was collected with a self-administered brief-type diet history questionnaire in 2020. A principal component analysis identified three posterior dietary patterns. RESULTS: Diet 1 consisted of high intake of vegetables, soy products, and fruits; Diet 2 consisted of carbohydrate-rich foods and snacks/sweets; Diet 3 consisted of high intake of alcoholic beverages, meat, and seafood. Least-squares linear regression revealed that individuals with PTSS/depression were less likely to exhibit Diet 1, while individuals with PTSS were more likely to exhibit Diet 2 and 3. Especially, males who had depression showed an unhealthy dietary pattern. Those who have lived in a trailer-style temporary housing reported less consumption of Diet 3. CONCLUSION: Survivors of disaster with symptoms of mental illness tended to exhibit less healthy dietary patterns after 9 years. Diet varied by type of post-disaster mental illness, gender, and current social circumstances. We lacked pre-disaster BDHQ data, which is a limitation.

The prognostic value of 18F-FDG PET/CT taken immediately after completion of radiotherapy for lung cancer treated with concurrent chemoradiotherapy: A pilot study.

PURPOSE: The prognostic value of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) taken immediately after completion of radiotherapy in lung cancer patients is not well known. The purpose of this study is to assess the prognostic value of PET/CT taken immediately after completion of radiotherapy in lung cancer patients. MATERIALS AND METHODS: Patients with primary lung cancer planned to undergo concurrent chemoradiotherapy were enrolled. Patients underwent PET/CT scans at 3 time points: before radiotherapy, within 24hours of completing radiotherapy (im-PET/CT), and 2-9 months after radiotherapy (post-PET/CT). Maximum standardized uptake value (SUVmax) was obtained. A post-PET/CT-SUVmax cut-off of 2.5 was determined as radiotherapy success. RESULTS: Nineteen patients were enrolled. im-PET/CT-SUVmax for patients in the high post-PET/CT-SUVmax group was significantly higher than that of the low group (P=0.004). Receiver operator curve analysis indicated that im-PET/CT-SUVmax of 4.35 was an optimal cut-off value to discriminate between the two groups. Multivariable analysis showed that a high im-PET/CT-SUVmax was significantly associated with a high post-PET/CT-SUVmax (P=0.003). CONCLUSION: PET/CT-SUVmax taken immediately following radiotherapy was associated with that evaluated 2-9 months after radiotherapy.

Andreev reflection of fractional quantum Hall quasiparticles.

Electron correlation in a quantum many-body state appears as peculiar scattering behaviour at its boundary, symbolic of which is Andreev reflection at a metal-superconductor interface. Despite being fundamental in nature, dictated by the charge conservation law, however, the process has had no analogues outside the realm of superconductivity so far. Here, we report the observation of an Andreev-like process originating from a topological quantum many-body effect instead of superconductivity. A narrow junction between fractional and integer quantum Hall states shows a two-terminal conductance exceeding that of the constituent fractional state. This remarkable behaviour, while theoretically predicted more than two decades ago but not detected to date, can be interpreted as Andreev reflection of fractionally charged quasiparticles. The observed fractional quantum Hall Andreev reflection provides a fundamental picture that captures microscopic charge dynamics at the boundaries of topological quantum many-body states.

S-1 and oxaliplatin versus tegafur-uracil and leucovorin as post-operative adjuvant chemotherapy in patients with high-risk stage III colon cancer: updated 5-year survival of the phase III ACTS-CC 02 trial.

BACKGROUND: The ACTS-CC 02 trial demonstrated that S-1 plus oxaliplatin (SOX) was not superior to tegafur-uracil and leucovorin (UFT/LV) in terms of disease-free survival (DFS) as adjuvant chemotherapy for high-risk stage III colon cancer (any T, N2, or positive nodes around the origin of the feeding arteries). We now report the final overall survival (OS) and subgroup analysis according to the pathological stage (TNM 7th edition) for treatment efficacy. PATIENTS AND METHODS: Patients who underwent curative resection for pathologically confirmed high-risk stage III colon cancer were randomly assigned to receive either UFT/LV (300 mg/m2 of UFT and 75 mg/day of LV on days 1-28, every 35 days, five cycles) or SOX (100 mg/m2 of oxaliplatin on day 1 and 80 mg/m2/day of S-1 on days 1-14, every 21 days, eight cycles). The primary endpoint was DFS and the patients' data were updated in February 2020. RESULTS: A total of 478 patients in the UFT/LV group and 477 patients in the SOX group were included in the final analysis. With a median follow-up time of 74.3 months, the 5-year DFS rate was 55.2% in the UFT/LV group and 58.1% in the SOX group [stratified hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.76-1.11; P = 0.3973], and the 5-year OS rates were 78.3% and 79.1%, respectively (stratified HR 0.97; 95% CI 0.76-1.24; P = 0.8175). In the subgroup analysis, the 5-year OS rates in patients with T4N2b disease were 51.0% and 64.1% in the UFT/LV and SOX groups, respectively (HR 0.72; 95% CI 0.40-1.31). CONCLUSION: Our final analysis reconfirmed that SOX as adjuvant chemotherapy is not superior to UFT/LV in terms of DFS in patients with high-risk stage III colon cancer. The 5-year OS rate was similar in the UFT/LV and SOX groups.

A genome-wide association study reveals a quantitative trait locus for calf mortality on chromosome 9 in Japanese Black cattle.

Calf mortality is a major problem affecting cattle production. To identify genetic variants associated with calf mortality in Japanese Black cattle, we evaluated calf mortality as a categorical trait using a threshold model and conducted a GWAS. We identified two SNPs between 32 549 297 and 32 606 924 bp on bovine chromosome 9 that were significantly associated with calf mortality from 61 to 180 days after birth. The SNP showing the highest association was localized at a region 624 bp downstream of exon 4 of the anti-silencing function 1A histone chaperone gene (ASF1A) that promotes DNA damage repair, and the null mice, which exhibit pre- and postnatal lethality. This association was also detected using the breeding value of 334 sires. The frequency of the risk allele in Japanese Black cattle from locations across Japan was 0.013; although the frequency of ASF1A risk allele was low, it is widespread in the Japanese Black cattle population. Thus, it may be necessary to routinely monitor the cattle population for the presence of this allele.

A highly multiplexed melt-curve assay for detecting the most prevalent carbapenemase, ESBL, and AmpC genes.

Resistance to third-generation cephalosporins and carbapenems in Gram-negative bacteria is chiefly mediated by beta-lactamases including extended-spectrum beta-lactamase (ESBL), AmpC, and carbapenemase enzymes. Routine phenotypic detection methods do not provide timely results, and there is a lack of comprehensive molecular panels covering all important markers. An ESBL/carbapenemase high-resolution melt analysis (HRM) assay (SHV, TEM, CTX-M ESBL families, and NDM, IMP, KPC, VIM and OXA-48-like carbapenemases) and an AmpC HRM assay (16S rDNA control, FOX, MOX, ACC, EBC, CIT, and DHA) were designed and evaluated on 111 Gram-negative isolates with mixed resistance patterns. The sensitivity for carbapenemase, ESBL, and AmpC genes was 96.7% (95% confidence interval [CI]: 82.8-99.9%), 93.6% (95% CI: 85.7-97.9%), and 93.8% (95% CI: 82.8-98.7%), respectively, with a specificity of 100% (95% CI: 95.6-100%), 93.9% (95% CI: 79.8-99.3%), and 93.7% (95% CI: 84.5-98.2%). The HRM assays enable the simultaneous detection of the 14 most important ESBL, carbapenemase, and AmpC genes and could be used as a molecular surveillance tool or to hasten detection of antimicrobial resistance for treatment management.

Sample collection from asteroid (162173) Ryugu by Hayabusa2: Implications for surface evolution.

The near-Earth asteroid (162173) Ryugu is thought to be a primitive carbonaceous object that contains hydrated minerals and organic molecules. We report sample collection from Ryugu's surface by the Hayabusa2 spacecraft on 21 February 2019. Touchdown images and global observations of surface colors are used to investigate the stratigraphy of the surface around the sample location and across Ryugu. Latitudinal color variations suggest the reddening of exposed surface material by solar heating and/or space weathering. Immediately after touchdown, Hayabusa2's thrusters disturbed dark, fine grains that originate from the redder materials. The stratigraphic relationship between identified craters and the redder material indicates that surface reddening occurred over a short period of time. We suggest that Ryugu previously experienced an orbital excursion near the Sun.

A high-power, high-repetition-rate THz source for pump-probe experiments at Linac Coherent Light Source II.

Experiments using a THz pump and an X-ray probe at an X-ray free-electron laser (XFEL) facility like the Linac Coherent Light Source II (LCLS II) require frequency-tunable (3 to 20 THz), narrow bandwidth (∼10%), carrier-envelope-phase-stable THz pulses that produce high fields (>1 MV cm-1) at the repetition rate of the X-rays and are well synchronized with them. In this paper, a two-bunch scheme to generate THz radiation at LCLS II is studied: the first bunch produces THz radiation in an electromagnet wiggler immediately following the LCLS II undulator that produces X-rays from the second bunch. The initial time delay between the two bunches is optimized to compensate for the path difference in THz transport. The two-bunch beam dynamics, the THz wiggler and radiation are described, as well as the transport system bringing the THz pulses from the wiggler to the experimental hall.

Endovascular Treatment for Very Early Hepatic Artery Stenosis Following Living-Donor Liver Transplantation: Report of Two Cases.

BACKGROUND: Some literature has reported on endovascular treatment for very early hepatic artery stenosis (HAS; within 2 weeks after liver transplantation, and has deemed endovascular treatment to be a contraindication because out of serious complications associated with the procedure. We report on 2 cases of very early HAS successfully treated with endovascular treatment after living-donor liver transplantation (LDLT). CASE 1: A 54-year-old woman underwent LDLT with a left liver graft. The native right gastric artery and left hepatic artery (LHA) of the donor were anastomosed. On postoperative day (POD) 13, HAS was suspected and multidetector computerized tomographic angiography (MDCTA) was performed, which revealed 90% stenosis of the arterial anastomosis and 50% stenosis of the LHA in the graft. We performed percutaneous balloon arterioplasty (PBA) without any complications. The artery was patent with a postoperative follow-up of 60 months without the need for repeat intervention. CASE 2: A 67-year-old woman with a history of repeated transarterial chemoembolization for hepatocellular carcinoma underwent LDLT with a left liver graft. The native A4 and LHA of the donor were anastomosed. We performed MDCTA on POD 11, which revealed 70% stenosis of the native hepatic artery. We performed PBA followed by stent placement on POD 11 without complication. The artery was patent with a postoperative follow-up of 40 months without the need for repeated intervention. CONCLUSIONS: Endovascular treatment has the potential to avoid the need for repeated surgical interventions or retransplantation, and it can be safely performed in carefully selected patients.

Evaluation of absolute measurement using a 4π plastic scintillator for the 4πß-γ coincidence counting method.

Absolute measurement by the 4πß-γ coincidence counting method was conducted by two photomultipliers facing across a plastic scintillator to be focused on ß ray counting efficiency. The detector was held with a through-hole-type NaI(Tl) detector. The results include absolutely determined activity and its uncertainty especially about extrapolation. A comparison between the obtained and known activities showed agreement within their uncertainties.

Kinematic analysis of pressing situations in female collegiate football games: New insight into anterior cruciate ligament injury causation.

The most common events during which anterior cruciate ligament (ACL) injuries occur in football are pressing situations. This study aimed to describe the knee and hip joint kinematics during pressing situations in football games to identify kinematic patterns in actions with a high risk for ACL injuries. We filmed 5 female collegiate football matches and identified 66 pressing situations. Five situations with a large distance between the trunk and foot placements in the sagittal plane were analyzed using a model-based image-matching technique. The mean knee flexion angle at initial contact (IC) was 13° (range, 8°-28°) and increased by 11° (95% confidence interval [CI], 3°-14°) at 40 ms after IC. As for knee adduction and rotation angles, the knee positions were close to neutral at IC, and only minor knee angular changes occurred later in the sequences. The mean hip flexion was 25° (range, 8°-43°) at IC and increased by 22° (95% CI, 11°-32°) after 100 ms. The hip was also externally rotated by 7° (range, -19° to 3°) at IC, and gradually rotated internally, reaching 10° of internal rotation (range, -5° to 27°) at 100 ms after IC. This study suggests that the observed knee valgus, internal hip and knee rotation, and static hip flexion previously reported in non-contact ACL injury events are unique to injury situations. In contrast, neither rapid knee valgus nor increased internal rotation was seen in non-injury pressing maneuvers.

Crystallization and vitrification of electrons in a glass-forming charge liquid.

Charge ordering (CO) is a phenomenon in which electrons in solids crystallize into a periodic pattern of charge-rich and charge-poor sites owing to strong electron correlations. This usually results in long-range order. In geometrically frustrated systems, however, a glassy electronic state without long-range CO has been observed. We found that a charge-ordered organic material with an isosceles triangular lattice shows charge dynamics associated with crystallization and vitrification of electrons, which can be understood in the context of an energy landscape arising from the degeneracy of various CO patterns. The dynamics suggest that the same nucleation and growth processes that characterize conventional glass-forming liquids guide the crystallization of electrons. These similarities may provide insight into our understanding of the liquid-glass transition.

Skipping breakfast and 5-year changes in body mass index and waist circumference in Japanese men and women.

OBJECTIVE: This study investigated the relationship between frequency of skipping breakfast and annual changes in body mass index (BMI) and waist circumference (WC). METHODS: The participants were 4,430 factory employees. BMI and WC were measured repeatedly at annual medical examinations over a 5-year period. The association between frequency of skipping breakfast at the baseline examination and annual changes in anthropometric indices was evaluated using the generalized estimating equation method. RESULTS: The mean (standard deviation) BMI was 23.3 (3.0) kg m-2 for men and 21.9 (3.6) kg m-2 for women; and the mean WC was 82.6 (8.7) cm for men and 77.8 (9.8) cm for women. During the follow-up period, mean BMI increased by 0.2 kg m-2 for men and women, and mean WC increased by 1.1 cm for men and 1.0 cm for women. The annual change in the BMI of men who skipped breakfast four to six times per week was 0.061 kg m-2 higher, and that of those who skipped breakfast seven times per week was 0.046 kg m-2 higher, compared with those who did not skip breakfast. Annual changes in the WC of male participants who skipped breakfast seven times per week was 0.248 cm higher than that of those who did not skip breakfast. Skipping breakfast was not associated with changes in BMI or WC in women. CONCLUSIONS: Skipping breakfast was closely associated with annual changes in BMI and WC among men, and eating breakfast more than four times per week may prevent the excessive body weight gain associated with skipping breakfast.

Helical Phase Structure of Radiation from an Electron in Circular Motion.

We theoretically show that a single free electron in circular motion radiates an electromagnetic wave possessing helical phase structure, which is closely related to orbital angular momentum carried by it. We experimentally demonstrate it by interference and double-slit diffraction experiments on radiation from relativistic electrons in spiral motion. Our results indicate that photons carrying orbital angular momentum should be created naturally by cyclotron/synchrotron radiations or Compton scatterings in various situations in cosmic space. We propose promising laboratory vortex photon sources in various wavelengths ranging from radio wave to gamma-rays.

MSC/ECM Cellular Complexes Induce Periodontal Tissue Regeneration.

Transplantation of mesenchymal stem cells (MSCs), which possess self-renewing properties and multipotency, into a periodontal defect is thought to be a useful option for periodontal tissue regeneration. However, developing more reliable and predictable implantation techniques is still needed. Recently, we generated clumps of an MSC/extracellular matrix (ECM) complex (C-MSC), which consisted of cells and self-produced ECM. C-MSCs can regulate their cellular functions in vitro and can be grafted into a defect site, without any artificial scaffold, to induce bone regeneration. Accordingly, this study aimed to evaluate the effect of C-MSC transplantation on periodontal tissue regeneration in beagle dogs. Seven beagle dogs were employed to generate a premolar class III furcation defect model. MSCs isolated from dog ilium were seeded at a density of 7.0 × 104 cells/well into 24-well plates and cultured in growth medium supplemented with 50 µg/mL ascorbic acid for 4 d. To obtain C-MSCs, confluent cells were scratched using a micropipette tip and were then torn off as a cellular sheet. The sheet was rolled up to make round clumps of cells. C-MSCs were maintained in growth medium or osteoinductive medium (OIM) for 5 or 10 d. The biological properties of C-MSCs were evaluated in vitro, and their periodontal tissue regenerative activity was tested by using a dog class III furcation defect model. Immunofluorescence analysis revealed that type I collagen fabricated the form of C-MSCs. OIM markedly elevated calcium deposition in C-MSCs at day 10, suggesting its osteogenic differentiation capacity. Both C-MSCs and C-MSCs cultured with OIM transplantation without an artificial scaffold into the dog furcation defect induced periodontal tissue regeneration successfully compared with no graft, whereas osteogenic-differentiated C-MSCs led to rapid alveolar bone regeneration. These findings suggested that the use of C-MSCs refined by self-produced ECM may represent a novel predictable periodontal tissue regenerative therapy.