LET Dependence of 8-Hydroxy-2'-deoxyguanosine (8-OHdG) Generation in Mammalian Cells under Air-Saturated and Hypoxic Conditions: A Possible Experimental Approach to the Mechanism of the Decreasing Oxygen Effect in the High-LET Region.

One of the most distinguished features in biological effects of heavy ions would be the decrease of oxygen effect in the high-LET region. This feature has been referred to as the radiobiological basis for the control of hypoxic fraction in cancer radiotherapy. However, mechanisms to explain this phenomenon have not been fully understood. One of the explanations was given by the oxygen in the track hypothesis, which proposes that oxygen is produced along ion tracks even in the hypoxic irradiation condition. In the present study, we designed an experimental approach to support this hypothesis by using 8-hydroxy-2'-deoxyguanosine (8-OHdG) as DNA damage requiring oxygen to produce. The LET dependence of 8-OHdG under hypoxic condition revealed that with increasing LET 8-OHdG yield seems to increase, despite that the yield of OH radical, which is also required for the production of 8-OHdG, decreases in the high-LET region. This result is consistent with the explanation that the local generation of oxygen along ion tracks contributes to the increase of 8-OHdG yield.

Efficient NMR measurement and data analysis supported by the Bayesian inference: The case of the heavy fermion compound YbCo2Zn20.

We propose a data-driven technique to infer microscopic physical quantities from nuclear magnetic resonance (NMR) spectra, in which the data size and quality required for the Bayesian inference are investigated. The 59Co-NMR measurement of YbCo2Zn20 single crystal generates complex spectra with 28 peaks. By exploiting the site symmetry in the crystal structure, the isotropic Knight shift Kiso and nuclear quadrupole resonance (NQR) frequency νQ were respectively estimated to be Kiso=0.7822±0.0090% and νQ=2.008±0.016 MHz (T=20 K and H≃10.2 T) by analyzing only 30 data points from one spectrum. The estimated νQ is consistent with the precise value obtained in the NQR experiment. Our method can significantly reduce the measurement time and the computational cost of data analysis in NMR experiments.

Erratum: Search for Cosmic-Ray Boosted Sub-GeV Dark Matter Using Recoil Protons at Super-Kamiokande [Phys. Rev. Lett. 130, 031802 (2023)].

This corrects the article DOI: 10.1103/PhysRevLett.130.031802.

Vulnerable newborn types: analysis of subnational, population-based birth cohorts for 541 285 live births in 23 countries, 2000-2021.

OBJECTIVE: To examine prevalence of novel newborn types among 541 285 live births in 23 countries from 2000 to 2021. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Subnational, population-based birth cohort studies (n = 45) in 23 low- and middle-income countries (LMICs) spanning 2000-2021. POPULATION: Liveborn infants. METHODS: Subnational, population-based studies with high-quality birth outcome data from LMICs were invited to join the Vulnerable Newborn Measurement Collaboration. We defined distinct newborn types using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight, LBW [<2500 g], nonLBW) as ten types (using all three outcomes), six types (by excluding the birthweight categorisation), and four types (by collapsing the AGA and LGA categories). We defined small types as those with at least one classification of LBW, PT or SGA. We presented study characteristics, participant characteristics, data missingness, and prevalence of newborn types by region and study. RESULTS: Among 541 285 live births, 476 939 (88.1%) had non-missing and plausible values for gestational age, birthweight and sex required to construct the newborn types. The median prevalences of ten types across studies were T+AGA+nonLBW (58.0%), T+LGA+nonLBW (3.3%), T+AGA+LBW (0.5%), T+SGA+nonLBW (14.2%), T+SGA+LBW (7.1%), PT+LGA+nonLBW (1.6%), PT+LGA+LBW (0.2%), PT+AGA+nonLBW (3.7%), PT+AGA+LBW (3.6%) and PT+SGA+LBW (1.0%). The median prevalence of small types (six types, 37.6%) varied across studies and within regions and was higher in Southern Asia (52.4%) than in Sub-Saharan Africa (34.9%). CONCLUSIONS: Further investigation is needed to describe the mortality risks associated with newborn types and understand the implications of this framework for local targeting of interventions to prevent adverse pregnancy outcomes in LMICs.

Search for Cosmic-Ray Boosted Sub-GeV Dark Matter Using Recoil Protons at Super-Kamiokande.

We report a search for cosmic-ray boosted dark matter with protons using the 0.37 megaton×years data collected at Super-Kamiokande experiment during the 1996-2018 period (SKI-IV phase). We searched for an excess of proton recoils above the atmospheric neutrino background from the vicinity of the Galactic Center. No such excess is observed, and limits are calculated for two reference models of dark matter with either a constant interaction cross section or through a scalar mediator. This is the first experimental search for boosted dark matter with hadrons using directional information. The results present the most stringent limits on cosmic-ray boosted dark matter and exclude the dark matter-nucleon elastic scattering cross section between 10^{-33}cm^{2} and 10^{-27}cm^{2} for dark matter mass from 1 MeV/c^{2} to 300 MeV/c^{2}.

Search for the Majorana Nature of Neutrinos in the Inverted Mass Ordering Region with KamLAND-Zen.

The KamLAND-Zen experiment has provided stringent constraints on the neutrinoless double-beta (0νßß) decay half-life in ^{136}Xe using a xenon-loaded liquid scintillator. We report an improved search using an upgraded detector with almost double the amount of xenon and an ultralow radioactivity container, corresponding to an exposure of 970 kg yr of ^{136}Xe. These new data provide valuable insight into backgrounds, especially from cosmic muon spallation of xenon, and have required the use of novel background rejection techniques. We obtain a lower limit for the 0νßß decay half-life of T_{1/2}^{0ν}>2.3×10^{26} yr at 90% C.L., corresponding to upper limits on the effective Majorana neutrino mass of 36-156 meV using commonly adopted nuclear matrix element calculations.

Preoperative evaluation of pleural adhesions with dynamic chest radiography: a retrospective study of 146 patients with lung cancer.

AIM: To assess the utility of dynamic chest radiography (DCR) during the preoperative evaluation of pleural adhesions. MATERIALS AND METHODS: Sequential chest radiographs of 146 patients with lung cancer were acquired during forced respiration using a DCR system. The presence of pleural adhesions and their grades were determined by retrospective surgery video assessment (absent: 121, present: 25). The maximum inspiration to expiration lung area ratio was used as an index for air intake volume. A ratio of ≥0.65 was regarded as insufficient respiration. Two radiologists assessed the images for pleural adhesions based on motion findings. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were compared for each adhesion grade and patient group (patients with sufficient/insufficient respiration). Pearson's chi-squared test compared the group. Statistical significance was set at p<0.05. RESULTS: DCR correctly identified 22/25 patients with pleural adhesions, with 20 false-positive results (sensitivity, 88%; specificity, 83.5%; PPV, 52.4%; NPV, 97.12%). Although the diagnostic performances for the various adhesion grades were similar, specificity in patients with sufficient respiration increased to 93.9% (31/33), identifying all cases except for those with loose adhesions. CONCLUSIONS: DCR images revealed restricted and/or distorted motions in lung structures and structural tension in patients with pleural adhesions. DCR could be a useful technique for routine preoperative evaluation of pleural adhesions. Further development of computerised methods can assist in the quantitative assessment of abnormal motion findings.

CD9-positive cells in the intermediate lobe migrate into the anterior lobe to supply endocrine cells.

The adenohypophysis is composed of the anterior and intermediate lobes (AL and IL), and secretes important hormones for growth, sexual development, metabolism, and reproduction. In the marginal cell layer (MCL) facing Rathke's cleft between the IL and AL, cluster of differentiation (CD) 9-, CD81-, S100ß-, and SOX2-quadruple positive (CD9/CD81/S100ß/SOX2-positive) cells in the adult IL are settled as tissue-resident stem/progenitor cells supplying hormone-producing cells to the AL. However, it is unclear how CD9/CD81/S100ß/SOX2-positive cells in the IL-side MCL migrate into the AL across Rathke's cleft. In the present study, we performed chimeric pituitary tissue culture using S100ß/GFP-transgenic rats and Wistar rats, and traced the footprint of S100ß/GFP-expressing cells. We detected IL-side S100ß/GFP-expressing cells in the AL tissue, demonstrating that these cells migrate from the IL to the AL. However, the cells failed to migrate in the opposite direction. Consistently, scanning electron microscopic analysis revealed well-developed cytoplasmic protrusions in the IL-side MCL, but not in the AL-side MCL, suggesting that IL-side CD9/CD81/S100ß/SOX2-positive cells had higher migratory activity. We also searched for a specific marker for IL-side CD9/CD81/S100ß/SOX2-positive cells and identified tetraspanin 1 (TSPAN1) from microarray analysis. Downregulation of Tspan1 by specific siRNA impaired cell migration and significantly reduced expression of snail family transcriptional repressor 2 (Slug), a marker of epithelial-mesenchymal transition (EMT). Therefore, CD9/CD81/S100ß/SOX2-positive cells in the IL-side MCL can be stem/progenitor cells that provide stem/progenitor cells to the AL-side MCL via SLUG-mediated EMT and cell migration.

Spermatogonial asynchrony in Tex14 mutant mice lacking intercellular bridges.

The existence of cytoplasmic passages between germ cells and their potential function in the control of the spermatogenic process has long been an intriguing question. Evidence of the important role of such structures, known as intercellular bridges (ICB), in spermatogenesis has been implicated by the failure of spermatogenesis in testis-expressed gene 14 (Tex14) mutant mice, which lack the ICBs, to progress past the pachytene spermatocyte stage. Using these Tex14 mutants, the present study evaluated, for the first time, the behavior and synchrony of the spermatogonial lineage in the absence of ICBs. Our data suggest that the absence of these cytoplasmic connections between cells affects the expansion of the undifferentiated type A (Aundiff) spermatogonia compartment and their transition to A1, resulting in a significant numerical reduction of differentiating A1 spermatogonia, but did not interfere with cell amplification during subsequent mitotic steps of differentiating spermatogonia from A1 through intermediate (In). However, beginning at the type B spermatogonia, the synchrony of differentiation was impaired as some cells showed delayed differentiation compared to their behavior in a normal seminiferous epithelium cycle. Thus although spermatogonial development is able to proceed, in the absence of ICBs in Tex14-/- mutants, the yield of cells, specific steps of differentiation, the synchrony of the cell kinetics, and the subsequent progression in meiosis are quantitatively lower than normal.

Nanostructuring with Structural-Compositional Dual Heterogeneities Enhances Strength-Ductility Synergy in Eutectic High Entropy Alloy.

A lamellar (L12 + B2) AlCoCrFeNi2.1 eutectic high entropy alloy (EHEA) was severely deformed by a novel hybrid-rolling process. During hybrid-rolling, the deformation was carried out in two stages, namely cryo-rolling followed by warm-rolling at 600 °C. The strain (ε) imparted in each of these steps was identical ~1.2, resulting in a total strain of ε~2.4 (corresponding to 90% reduction in thickness). The novel processing strategy resulted in an extremely heterogeneous microstructure consisting of retained lamellar and transformed nanocrystalline regions. Each of these regions consisted of different phases having different crystal structures and chemical compositions. The novel structure-composition dual heterogeneous microstructure originated from the stored energy of the cryo-rolling which accelerated transformations during subsequent low temperature warm-rolling. The dual heterogeneous microstructure yielded an unprecedented combination of strength (~2000 MPa) and ductility (~8%). The present study for the first time demonstrated that dual structure-composition heterogeneities can be a novel microstructural design strategy for achieving outstanding strength-ductility combination in multiphase high entropy alloys.

Precision Analysis of the

We present a precision analysis of the ^{136}Xe two-neutrino ßß electron spectrum above 0.8 MeV, based on high-statistics data obtained with the KamLAND-Zen experiment. An improved formalism for the two-neutrino ßß rate allows us to measure the ratio of the leading and subleading 2νßß nuclear matrix elements (NMEs), ξ_{31}^{2ν}=-0.26_{-0.25}^{+0.31}. Theoretical predictions from the nuclear shell model and the majority of the quasiparticle random-phase approximation (QRPA) calculations are consistent with the experimental limit. However, part of the ξ_{31}^{2ν} range allowed by the QRPA is excluded by the present measurement at the 90% confidence level. Our analysis reveals that predicted ξ_{31}^{2ν} values are sensitive to the quenching of NMEs and the competing contributions from low- and high-energy states in the intermediate nucleus. Because these aspects are also at play in neutrinoless ßß decay, ξ_{31}^{2ν} provides new insights toward reliable neutrinoless ßß NMEs.

Longitudinal changes in 18 F-THK5351 positron emission tomography in corticobasal syndrome.

BACKGROUND AND PURPOSE: Corticobasal syndrome (CBS) is pathologically characterized by tau deposits in neuronal and glial cells and by reactive astrogliosis. In several neurodegenerative disorders, 18 F-THK5351 has been observed to bind to reactive astrocytes expressing monoamine oxidase B. In this study, the aim was to investigate the progression of disease-related pathology in the brains of patients with CBS using positron emission tomography with 18 F-THK5351. METHODS: Baseline and 1-year follow-up imaging were acquired using magnetic resonance imaging and positron emission tomography with 18 F-THK5351 in 10 subjects: five patients with CBS and five age-matched normal controls (NCs). RESULTS: The 1-year follow-up scan images revealed that 18 F-THK5351 retention had significantly increased in the superior parietal gyrus of the patients with CBS compared with the NCs. The median increases in 18 F-THK5351 accumulation in the patients with CBS were 6.53% in the superior parietal gyrus, 4.34% in the precentral gyrus and 4.33% in the postcentral gyrus. In contrast, there was no significant increase in the regional 18 F-THK5351 retention in the NCs. CONCLUSIONS: Longitudinal increases in 18 F-THK5351 binding can be detected over a short interval in the cortical sites of patients with CBS. A monoamine oxidase B binding radiotracer could be useful in monitoring the progression of astrogliosis in CBS.

Risk factors for decreased teicoplanin trough concentrations during initial dosing in critically ill patients.

Aim of the study: Here, we investigated the risk factors for decreased teicoplanin plasma trough concentrations relative to the initial dosing in critically ill patients. Patients and methods: Data obtained from 80 eligible critically ill patients who received intravenous teicoplanin were retrospectively analyzed. Risk factors for decreases in teicoplanin trough concentrations 72 h after administration of teicoplanin of more than 30% relative to predicted concentrations based on initial dosing setting were identified by logistic regression analysis. Results: Although prediction trough concentration and total dose of two days no significant differences were seen between the variation group and the non-variation group, actual trough concentration was significantly different between two groups (19.9±5.6 µg/ml vs 10.3±2.2 µg/ml, p < 0.001). In multivariate analysis, serum albumin ≤ 2.2 mg/dl (odds ratio [OR] = 3.003, 95% CI 1.072-8.408; p = 0.036) and SOFA score ≥ 9 (OR = 3.498, 95% CI 1.171-10.450; p = 0.025) were significant risk factors for decreased teicoplanin plasma trough concentrations. Conclusion: In critically ill patients, high SOFA score and low serum albumin were risk factors for decreased teicoplanin plasma trough concentration during initial dosing.

Changes in the blood level, efficacy, and safety of tacrolimus in pregnancy and the lactation period in patients with systemic lupus erythematosus.

OBJECTIVES: We investigated the efficacy and safety of tacrolimus (TAC) by monitoring its serum concentration for mothers and infants in pregnant patients with systemic lupus erythematosus (SLE). METHODS: We measured trough concentrations of TAC in 25 pregnant patients with SLE to assess influence of TAC on the disease activity. Additionally, we measured the concentrations of TAC in umbilical arterial blood, breast milk, and breastfed infants to investigate the safety of TAC for the mothers and infants. RESULTS: The trough concentrations of TAC in the mothers significantly decreased in the second trimester as compared with those before pregnancy. However, the decrease in the trough concentrations of TAC did not lead to the deterioration of SLE. When examined, the doses of TAC were significantly lower in the second trimester and postpartum in the deteriorating group than those in the non-deteriorating group. There were no adverse events by TAC in mothers and fetuses. The concentrations of TAC in the umbilical cord blood were lower than those in the maternal blood. The relative infant dose in breastfed infants of TAC was < 1%. The level of TAC in infant bloods was below detectable limits. CONCLUSION: These findings suggest that TAC is one of the most effective and safest immunosuppressive drugs for use in pregnant patients with SLE.

Efficacy of discontinuing risedronate for patients with systemic lupus erythematosus: a prospective study.

Objective The objective of this study is to investigate the effectiveness of discontinuation of risedronate for patients with systemic lupus erythematosus (SLE) treated with glucocorticoid (GC). Methods The participants were patients with SLE treated with prednisolone (PSL) ≥ 2 mg/day and risedronate for at least three years. Lumbar spine and total hip bone mineral density (BMD) measurements were taken at baseline and 24 and 48 weeks after discontinuation of risedronate, and bone turnover markers were evaluated at baseline, 12, 24, 36, and 48 weeks. Results A total of 36 patients were enrolled, 25 of whom discontinued risedronate. The mean age was 46.8 ± 11.2 years, and 23 were female. The mean duration of GC treatment was 14.8 ± 11.4 years, the mean dose of PSL was 7.8 ± 3.9 mg/day, and the mean duration of risedronate was 5.8 ± 2.4 years. Seventeen patients showed decreased lumbar spine BMD at 48 weeks after discontinuation of risedronate, with a mean lumbar spine lumbar decrease of 1.42% ± 3.20% ( p = 0.034); 17 patients (71%) showed a decreased total hip BMD at 48 weeks after discontinuation of risedronate, with a mean total hip BMD decrease of 0.99% ± 2.10% ( p = 0.021). Serum tartrate-resistant acid phosphatase 5b (TRACP-5b) ≥ 309 mU/dl at baseline was a risk factor for decreased total hip BMD at 48 weeks compared with serum TRACP-5b < 309 mU/dl (56% vs 0%, p = 0.0098). One patient developed a clinical fracture of the lumbar spine at 20 weeks. Conclusions Discontinuation of risedronate treatment in patients with SLE who had received GC therapy led to decreases in lumbar spine and total hip BMD, particularly in patients with high baseline serum TRACP-5b levels.

Creation of Rydberg Polarons in a Bose Gas.

We report spectroscopic observation of Rydberg polarons in an atomic Bose gas. Polarons are created by excitation of Rydberg atoms as impurities in a strontium Bose-Einstein condensate. They are distinguished from previously studied polarons by macroscopic occupation of bound molecular states that arise from scattering of the weakly bound Rydberg electron from ground-state atoms. The absence of a p-wave resonance in the low-energy electron-atom scattering in Sr introduces a universal behavior in the Rydberg spectral line shape and in scaling of the spectral width (narrowing) with the Rydberg principal quantum number, n. Spectral features are described with a functional determinant approach (FDA) that solves an extended Fröhlich Hamiltonian for a mobile impurity in a Bose gas. Excited states of polyatomic Rydberg molecules (trimers, tetrameters, and pentamers) are experimentally resolved and accurately reproduced with a FDA.