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There is a growing interest in using pulsed high magnetic field as a controlling parameter of physical phenomena in various scientific disciplines, such as condensed matter physics, particle physics, plasma physics, chemistry, and biological studies. We devised a concise and portable pulsed magnetic field generator that produces a 40 T field with a pulse duration of 2 ms. It is assembled using only off-the-shelf components and a homemade coil that leverages small computers, Raspberry Pi, and Python codes. It allows for straightforward modification for general purposes. As working examples, we show representative applications in condensed matter experiments of magnetoresistance, magnetization, and magnetostriction measurements for graphite, NdNi 2 P 2 , and NdCo 2 P 2 , respectively, with the maximum magnetic field of 41 T and the lowest temperature of 4.2 K. [ABSTRACT FROM AUTHOR]

Optical image stabilization (OIS) systems maintain the three-dimensional focal position of a lens through mechanical actuation systems. This paper examines an optical lens for OIS that utilizes ultrasound vibration to alter the focal position, not only in the depth direction but also in the radial direction. The lens has a simple structure with no mechanical moving parts and consists of an ultrasound transducer divided into four pieces, a glass disk, and a transparent viscoelastic gel film that functions as a lens. The acoustic radiation force generated by the resonant flexural vibration of the glass disk can alter the surface profile of the gel film, allowing for a variable-focus function. The concave and convex lenses can be interchanged using two resonant vibration modes: the standing-wave mode, in which the vibration loop appears at the center, and the traveling-wave mode, in which the vibration node appears at the center. The positions of ultrasound vibrations on the lens can be controlled in a two-dimensional plane by adjusting the driving amplitudes of each channel, thereby achieving focus control in the radial direction. The focusing characteristics of the lens are evaluated through ray-tracing simulation. [ABSTRACT FROM AUTHOR]

Although high-temperature superconducting induction motors have a simple structure, they are distinguished by their high efficiency and high power density. However, an accurate theoretical model that defines the primary electrical characteristics controlling the motor has not been established because of the nonlinear characteristics of high-temperature superconducting squirrel-cage rotor winding. As part of establishing such a model, an experiment was conducted to analyze the relationship between the induced voltage of the rotor bar in a high-temperature superconducting squirrel-cage rotor winding and stator-side quantities (voltage and transport current), as well as its rotation characteristics. A subject was a 1.5 kW class induction motor using Bi–Sr–Ca–Cu–O high-temperature superconducting rotor bars and the experiment was performed at a temperature and a frequency of 77 K and 60 Hz, respectively. The induced voltages of the rotor bars were measured by applying a rotating magnetic field and exhibited a distorted waveform characterized by a third-order harmonic in a magnetic flux flow state. Despite the distorted voltage waveform of the rotor bar, the stator transport current responsible for driving the induction motor remained unaffected and the motor initiated rotation in a slip rotation mode. From the above results, it was experimentally clarified that a stator voltage exceeding the critical current of the rotor bar must be applied when starting the induction motor. It was also shown that the rotor bar can be regarded as a constant resistance for a constant effective value of the stator current when transitioning the motor into a slip rotation state. [ABSTRACT FROM AUTHOR]

Purpose: There are multiple postexercise recovery technologies available in the market based on the assumption of blood-flow enhancement. Lower-limb intermittent pneumatic compression (IPC) has been widely used, but the available scientific evidence supporting its effectiveness remains scarce, requiring a deeper investigation into its underlying mechanisms. The aim of this study was to assess the hemodynamic effects caused by the use of IPC at rest. Methods: Twenty-two soccer and track and field athletes underwent two 15-minute IPC protocols (moderate- [80 mm Hg] and high-pressure [200 mm Hg]) in a randomized order. Systolic peak velocity, end-diastolic peak velocity, arterial diameter, and heart rate were measured before, during (at the eighth minute), and 2 minutes after each IPC protocol. Results: Significant effects were observed between before and during (eighth minute) the IPC protocol for measures of systolic (P <.001) and end-diastolic peak velocities (P <.001), with the greater effects observed during the high-pressure protocol. Moreover, 2 minutes after each IPC protocol, hemodynamic variables returned to values close to baseline. Arterial diameter presented significant differences between pressures during the IPC protocols (P <.05), while heart rate remained unaltered. Conclusion: IPC effectively enhances transitory blood flow of athletes, particularly when applying high-pressure protocols. [ABSTRACT FROM AUTHOR]

The efficiency of multiple quantum well (QW) light emitting diodes (LEDs) to a large degree depends on uniformity of hole distribution between the QWs. Typically, transport between the QWs takes place via carrier capture into and thermionic emission out of the QWs. In InGaN/GaN QWs, the thermionic hole transport is hindered by the high quantum confinement and polarization barriers. To overcome this drawback, hole injection through semipolar QWs located at sidewalls of V-defects had been proposed. However, in the case of the V-defect injection, strong lateral emission variations take place. In this work, we explore the nature of these variations and the impact of the V-defects on the emission spectra and carrier dynamics. The study was performed by mapping electroluminescence (EL) and photoluminescence (PL) with a scanning near-field optical microscope in LEDs that contain a deeper well that can only be populated by holes through the V-defects. Applying different excitation schemes (electrical injection and optical excitation in the far- and near-field), we have shown that the EL intensity variations are caused by the lateral nonuniformity of the hole injection. We have also found that, in biased structures, the PL intensity and decay time in the V-defect regions are only moderately lower that in the V-defect-free regions thus showing no evidence of an efficient Shockley-–Read–Hall recombination. In the V-defect regions, the emission spectra experience a red shift and increased broadening, which suggests an increase of the In content and well width in the polar QWs close to the V-defects. [ABSTRACT FROM AUTHOR]

Ultra-thin solar cells display high intrinsic radiation tolerance, making them interesting for space applications. This study investigates the dependence of the open-circuit voltage degradation and overall current–voltage behavior of devices with 80 nm thick GaAs absorber layers, on their absorber layer doping concentration and the radiation type used to introduce damage. The radiation types used were 1 MeV electrons and 20 keV, 100 keV, and 1 MeV protons. It is shown that the open-circuit voltage degradation rate increases with absorber layer doping concentration. This is linked to the increase in trap-assisted tunneling enhancement of the recombination rate, facilitated by the increase in electric field strength in the absorber layer with doping concentration. Trap-assisted tunneling is also found to contribute to the high local ideality factors observed in these devices, exceeding values of 2, and to be responsible for the trend of an increasing ideality factor with doping concentration. The significant role of trap-assisted tunneling in the devices is established through fitting of dark current–voltage data using a custom recombination–generation model. An open-circuit voltage degradation rate and local ideality factor curves are also shown to vary with radiation type, despite accounting for their differences in non-ionizing energy loss. This is corroborated by corresponding trends in carrier lifetime damage constants, extracted from the fitting of the dark current–voltage curves. This suggests that the introduction or behavior of radiation damage differs between ultra-thin and conventional, thicker solar cells, where non-ionizing energy loss theory tends to be reliable, especially over the studied proton energy range. [ABSTRACT FROM AUTHOR]

Face-to-face annealed and sputter-deposited aluminum nitride (FFA Sp-AlN) has potential in deep-ultraviolet light-emitting devices. Herein, the effects of the substrate off-cut angle (θsub) from an r-plane sapphire toward the c-axis projection direction and sputtering temperature (Tsp) on the crystallinity and surface morphology of a-plane AlN films are investigated. Increasing θsub in the minus-off direction, which occurs when the substrate surface approaches the sapphire c-plane, and lowering Tsp suppress the mixing of anomalous non-a-direction oriented domains. This reduced mixing enhances the surface flatness and crystallinity of a-plane FFA Sp-AlN. Moreover, the c-axis direction of the a-plane AlN film is inverted depending on the substrate off-cut angle. Ab initio calculations indicate that the interface stability between the r-plane sapphire substrate and the a-plane AlN film can explain the dependence of the crystallinity and c-axis orientation of FFA Sp-AlN on the surface off-cut of the r-plane sapphire. [ABSTRACT FROM AUTHOR]

In nonequilibrium statistical physics, quantifying the nearest (and higher-order) neighbors and free volumes of particles in many-body systems is crucial to elucidating the origin of macroscopic collective phenomena, such as glass/granular jamming transitions and various aspects of the behavior of active matter. However, conventional techniques (based on a fixed-distance cutoff or the Voronoi construction) have mainly been applied to equilibrated, homogeneous, and monodisperse particle systems. In this paper, we implement simple and efficient methods for local structure analysis in nonequilibrium, inhomogeneous, and polydisperse hard disk systems. We show how these novel methods can overcome the difficulties encountered by conventional techniques as well as demonstrate some applications. [ABSTRACT FROM AUTHOR]

The small-angle neutron scattering (SANS) and small-angle x-ray scattering (SAXS) measurements were performed for deuterated and non-deuterated poly(ethylene glycol) (d-PEG and h-PEG, respectively) in D2O and a D2O/H2O mixed solvent (Mix) to compare the scattering profiles. To determine the coherent scattering intensity of SANS, a 3He spin filter was utilized. The scattering profiles determined by the SANS measurements were analyzed in terms of the wormlike chain model with touched beads along the contour of the chain. However, the SAXS profiles were not explained by the same model with uniform beads but with beads each consisting of a core and a shell having different electron densities. To explore the chain thickness determined from the SANS profile, the scattering intensities for different combinations of d-PEG/D2O, d-PEG/Mix, h-PEG/D2O, and h-PEG/Mix were also examined. [ABSTRACT FROM AUTHOR]

This article discusses a new fabrication process for colloidal silicon quantum dots (SiQDs) that allows for the tuning of their luminescence color from red to green. The process involves low-temperature thermal cracking of electrochemically prepared meso-porous silicon flakes in a mixture of 10-undecen-1-ol and aqueous hydrogen fluoride solution. The size of the SiQDs and their luminescence color can be controlled by adjusting the content of hydrogen fluoride. The article also explores the properties and potential applications of SiQDs in various fields, such as photovoltaic devices, light emitting devices, bio-imaging, and sensing. The document discusses the size-dependent radiative recombination processes of SiQDs, including factors that can affect their photoluminescence properties. It also explains the formation mechanisms of SiQDs and how they can result in different photoluminescence colors and peak wavelengths. The document concludes by discussing the relationship between the size of SiQDs and their photoluminescence peak energies, as well as the effect of surface passivation on quantum confinement. The article presents a novel method for producing SiQDs with tunable emission colors and suggests potential applications for SiQD devices. [Extracted from the article]

We energetically predict the morphology of Pd, Ag, Au, and Pt nanoparticles on (0001) sapphire substrates, using density functional theory (DFT) simulations and the well-known Young–Dupre equation. In all cases, the contact angles exceed 90 ° , indicating that the nanoparticles are spherical. Notably, Au nanoparticles exhibit a higher contact angle than those of their counterparts. The validity of the proposed a b i n i t i o nanoparticle morphology prediction approach based on DFT simulations was assessed in comparison with our previous experimental findings pertaining to the time variation of the full width at half maximum (FWHM) of the resonant peak. Furthermore, the diffusivities of single Pd, Ag, Au, and Pt atoms on the substrate were evaluated by calculating the activation energy, offering insights into the underlying physics governing the timing of FWHM peaks. The analysis confirms a higher diffusivity of Au and Ag compared with Pd and Pt. According to the comparison between DFT and experiment results, although no clear relation is observed between the contact angles and timing of FWHM peaks, the diffusivity of sputtered atoms may influence the timing of FWHM peaks. Thus, timing can help to clarify the nanoparticle size, rather than shape. [ABSTRACT FROM AUTHOR]

In this study, several methods for a novel binderless technology were explored, the effects of treatment conditions on the adhesive performance were examined and the surface was characterized during adhesion. The method entailed a three-step process for bonding solid wood, which involved immersion in sodium hypochlorite–containing treatment solutions, surface scratching, and drying with pressing. Various treatment conditions were investigated, including solution types, immersion durations, scratch treatment materials, and pressing methods. The resulting shear strength was 9.7 MPa, which is well above the Japanese Agricultural Standards value for laminated wood (6 MPa). In this method, the specimens were immersed in a bleach solution containing a surfactant for 16 h, followed by pressurization at 1 MPa for 24 h at 60 ℃ using a pressure-controlled press. Around the bonding area in the specimens, the cells in the immersed area were significantly compressed, and the aldehyde groups of the coniferyl aldehyde in the lignin were denatured or lost. Based on these findings, a new binderless technology was developed for solid wood without a high-temperature, high-pressure pressing step. [ABSTRACT FROM AUTHOR]

Live imaging visualizes the structure, dynamics, and function of cells and tissues to reveal the molecular mechanisms, and has contributed to the advancement of life science. In live imaging, it has been well known that there is a trade-off between higher-resolution analysis and cell damage caused by light illumination, i.e., phototoxicity. However, despite the risk of unknowingly distorting experimental results, phototoxicity is an unresolved issue in live imaging because overall consequences occurring inside cells due to phototoxicity remains unknown. Here, we determined the molecular process of phototoxicity-induced cell damage systematically under low- and high-dose light illumination conditions by analyzing differential gene expression using RNA-sequencing in a three-dimensional organoid of small intestinal epithelial cells, enteroid. The low-dose light illumination already induced various abnormalities in functional molecules involved in the response to reactive oxygen species generated by the excitation of fluorescent dyes, intracellular metabolism, mitosis, immune responses, etc., at mRNA expression level. Together with the behavior toward apoptosis caused by high-dose light illumination, the light dose-dependent progression of intracellular damage was revealed. About visible impairment of intestinal epithelial function, failures in both the structure-forming ability of enteroids and Paneth cell granule secretion were observed under high-dose light illumination, while the drug efflux was not disturbed despite abnormal drug efflux transporter mRNA expression. Based on the gene expression profiles, we comprehensively clarified phenomena in the cells at mRNA level that cannot be recognized both morphologically and functionally during live imaging, further providing a new insight into the risk of phototoxicity. This study warns from the aspect of mRNA expression that awareness of phototoxic artifacts is needed when analyzing cellular function and the mechanism in live imaging. [ABSTRACT FROM AUTHOR]

Aim: Genome‐wide association studies (GWAS) of postpartum depression (PPD) based on accumulated cohorts with multiple ethnic backgrounds have failed to identify significantly associated loci. Herein, we conducted a GWAS of Japanese perinatal women along with detailed confounding information to uncover PPD‐associated loci. Methods: The first and second cohorts (n = 9260 and n = 8582 perinatal women enrolled in the Tohoku Medical Megabank Project) and the third cohort (n = 997), recruited at Nagoya University, underwent genotyping. Of them, 1421, 1264, and 225 were classified as PPD based on the Edinburgh Postnatal Depression Scale 1 month after delivery. The most influential confounding factors of genetic liability to PPD were selected, and logistic regression analyses were performed to evaluate genetic associations with PPD after adjusting for confounders. Results: A meta‐analysis of GWAS results from the three cohorts identified significant associations between PPD and the following loci (P < 5 × 10−8) by integrating the number of deliveries and the number of family members living together as the most influential confounders: rs377546683 at DAB1, rs11940752 near UGT8, rs141172317, rs117928019, rs76631412, rs118131805 at DOCK2, rs188907279 near ZNF572, rs504378, rs690150, rs491868, rs689917, rs474978, rs690118, rs690253 near DIRAS2, rs1435984417 at ZNF618, rs57705782 near PTPRM, and rs185293917 near PDGFB. Pathway analyses indicated that SNPs suggestively associated with PPD were mostly over‐represented in categories including long‐term depression, GnRH signaling, glutamatergic synapse, oxytocin signaling, and Rap1 signaling. Conclusion: The current GWAS study identified eight loci significantly associated with PPD, which may clarify the genetic structure underlying its pathogenesis. [ABSTRACT FROM AUTHOR]

Background: This single center prospective observational study was conducted to evaluate the acute toxicity of hypo-fractionated radiotherapy for Japanese breast cancer patients after surgery. Methods: This study recruited patients who were scheduled for moderately hypo-fractionated radiotherapy including supraclavicular lymph node area (Cohort M) or ultra-hypo-fractionated radiotherapy for the conserved breast (Cohort U) as postoperative treatment for breast cancer. Radiotherapy plans were generated using automated planning system. Irradiation of 42.5 Gy/16 fractions (Cohort M) or 26 Gy/5 fractions (Cohort U) was delivered, and boost irradiation of 10 Gy/5 fractions was added as needed. The primary endpoint was the proportion of grade ≥ 2 acute adverse events within 90 days. The toxicities were evaluated using CTCAE ver 5.0. Results: Between January 2023 and December 2023, 123 patients (81 in Cohort M and 42 in Cohort U) were enrolled. All the included patients were Japanese and completed their planned radiotherapy and were also able to be evaluated for acute adverse events. Grade 1/2/3–5 acute adverse events were observed in 67/12/0 for Cohort M and 31/4/0 for Cohort U. The proportion of grade ≥ 2 acute adverse events within 90 days was 15% (95% confidence interval 8–24%) for Cohort M and 10% (95% confidence interval 3–23%) for Cohort U. Conclusions: The proportion of acute toxicity of hypo-fractionated radiotherapy for Japanese breast cancer patients after surgery was shown to be acceptable in this study. [ABSTRACT FROM AUTHOR]

Objective: Previous studies suggest older patients with multiple health conditions and medications may experience adverse interactions, leading to negative outcomes. However, there's limited research on this in older adults receiving home medical care. This study assesses whether polypharmacy is linked to falls or other clinical outcomes. Methods: The study population included 217 participants, aged ≥65 years, receiving home medical care, who consented to participate in the Osaka Home Care Registry (OHCARE) study in Japan. The survey examined the association between polypharmacy and clinical outcomes. We defined "polypharmacy" as six or more medications taken regularly. Results: Of the participants, 135 (62.6%) had polypharmacy and were significantly more likely to have hypertension or diabetes. Common medications included those for hypertension, diabetes, and mental disorders. Participants with polypharmacy experienced significantly more falls. Multivariate analysis showed an association between polypharmacy and falls (odds ratio: 2.81, 95% confidence interval [1.34, 5.92]). Conclusion: Even in older patients receiving home health care, the use of six or more medications poses a risk of falls. Careful observations and life support by medical stuffs are necessary to prevent falls in older patients with polypharmacy receiving home medical care. [ABSTRACT FROM AUTHOR]

Background: Segregated-nucleus-containing atypical monocytes have recently been identified in mice. Segregated-nucleus-containing atypical monocytes are thought to originate from the bone marrow and induce fibrosis in the drug-injured lung. The Lyc6c− murine monocyte subset is the counterpart to human CD14−CD16++ non-classical monocytes; however, the human counterpart to murine segregated-nucleus-containing atypical monocytes has not yet been identified. Primary myelofibrosis is a well-known disease of progressive marrow fibrosis, and atypical megakaryocytes are thought to be closely related to fibrosis in primary myelofibrosis bone marrow. However, recently, monocytes have been reported to play an important role in marrow fibrosis in primary myelofibrosis. We speculated that, if there is a human counterpart to murine segregated-nucleus-containing atypical monocytes, it would present the same markers as murine segregated-nucleus-containing atypical monocytes, such as CD14−CD16+ macrophage-1 antigen (CD11b/CD18 complex)+, MSR1+, and CEACAM1+, and it might exist in the bone marrow of patients with primary myelofibrosis. Case presentation: A 74-year-old Japanese male visited our hospital for clinical follow-up after total prostatectomy for prostatic cancer. Anemia, thrombocytosis, and elevated lactate dehydrogenase were suddenly observed in a periodic examination. CALR mutation type 2 (p.K385fs*47) was observed. The histological features of the patient's bone marrow were consistent with fibrotic primary myelofibrosis. We immunohistochemically studied the bone marrow in an attempt to identify a human counterpart to murine segregated-nucleus-containing atypical monocytes. We detected a few CD16+MSR1+CEACAM1+ cells, but not CD14+MSR1+CEACAM1+ cells, by triple immunostaining. The patient is in a good condition and does not require treatment for primary myelofibrosis. Conclusion: There is a possibility that human segregated-nucleus-containing atypical monocytes exist in the bone marrow of primary myelofibrosis patients and might be related to marrow fibrosis. [ABSTRACT FROM AUTHOR]

The periosteum is the layer of cells that covers nearly the entire surface of every bone. Upon infection, injury or malignancy the bone surface undergoes new growth—the periosteal reaction—but the mechanism and physiological role of this process remain unknown1,2. Here we show that the periosteal reaction protects against cancer invasion into the bone. Histological analyses of human lesions of head and neck squamous cell carcinomas (HNSCCs) show that periosteal thickening occurs in proximity to the tumour. We developed a genetically dissectible mouse model of HNSCC and demonstrate that inducible depletion of periosteal cells accelerates cancerous invasion of the bone. Single-cell RNA sequencing reveals that expression of the gene encoding the protease inhibitor TIMP1 is markedly increased in the periosteum at the pre-invasive stage. This increase is due to upregulation of HIF1α expression in the tumour microenvironment, and increased TIMP1 inactivates matrix-degrading proteases, promoting periosteal thickening to inhibit cancer invasion. Genetic deletion of Timp1 impairs periosteal expansion, exacerbating bone invasion and decreasing survival in tumour-bearing mice. Together, these data show that the periosteal reaction may act as a functional stromal barrier against tumour progression, representing a unique example of tissue immunity mediated by stromal cells.Experiments in mouse models and histology of human head and neck squamous cell carcinomas show that TIMP1-mediated periosteal thickening in proximity to tumours acts as a barrier to cancer invasion of the bone. [ABSTRACT FROM AUTHOR]

This document is a guideline on endoscopic surgery for qualified surgeons, specifically focusing on the pancreas. It provides a historical overview of laparoscopic pancreatectomy and discusses the insurance coverage for this procedure in Japan. The document also evaluates the use of laparoscopic distal pancreatectomy (LDP) and laparoscopic pancreatoduodenectomy (LPD) for pancreatic tumors, comparing them to open surgery. The guideline recommends LDP for benign or low-grade lesions and LPD for benign and low-grade tumors in facilities with experience in this surgery. However, further research is needed, particularly for LPD in pancreatic cancer. [Extracted from the article]

Background: Low-grade systemic inflammation may be a key player in the immune activation that has been reported for mental health deterioration. We hypothesised that elevated serum levels of inflammatory cytokines increase neuroinflammation and exacerbate depressive symptoms. Methods: The participants were part of a cohort study for whom data was available for both 2015 and 2019. In 2015, blood samples were collected from 232 participants. Their depressive symptoms were assessed both 2015 and 2019 using the Centre for Epidemiologic Studies Depression Scale (CES-D) (n = 33). The multiplex immunoassay system (Luminex® 200) was used to measure the serum concentrations of IL-6, IL-10, IL-12, IL-17A and TNFα. Data were analysed using linear models with the level of significance considered to be p < 0.05. Results: After controlling for age, BMI, smoking and alcohol consumption, in 2015 the serum concentrations of IL-17A and TNFα in 2015 were significantly positively associated with the CES-D scores of women (standardised β (B) =.027, p < 0.01 and B = 0.26, p < 0.01, respectively). The serum concentrations of IL-17A and TNFα of men were significantly positively associated with the CES-D scores of 2019 (B = 0.62, p = 0.02 and B = 0.59, p = 0.02, respectively). Conclusions: In this cross-sectional study, we found a significant positive correlation between the depressive symptoms and serum TNFα and IL-17A levels of women. In addition, our longitudinal findings suggest the possibility that TNFα and IL-17A could elevate the depressive symptoms of men. [ABSTRACT FROM AUTHOR]

Bitter taste receptors (TAS2Rs) are not only expressed in the oral cavity but also in skin. Extraoral TAS2Rs are thought to be involved in non‐taste perception and tissue‐specific functions. Keratinocytes that express TAS2Rs in the skin provide a first‐line defense against external threats. However, the functional roles of these receptors in host defense remain unclear. Here, we demonstrated the sensory role of intracellularly located TAS2Rs against toxic substances in keratinocytes. Although many G protein‐coupled receptors elicit signals from the surface, TAS2Rs were found to localize intracellularly, possibly to the ER, in human keratinocytes and HaCaT cells. TAS2R38, one of the TAS2R members, activated the Gα12/13/RhoA/ROCK/p38 MAP kinase/NF‐κB pathway upon stimulation by phenylthiocarbamide (PTC), an agonist for this receptor, leading to the production of ABC transporters, such as ABCB1, in these cells. Notably, treatment with bitter compounds, such as PTC and saccharin, induced the upregulation of ABCB1 in HaCaT cells. Mechanistically, intracellular TAS2R38 and its downstream signaling Gα12/13/RhoA/ROCK/p38 MAP kinase/NF‐κB pathway were identified to be responsible for the above effect. Pretreatment with PTC prevented the accumulation of rhodamine 123 because of its excretion via ABCB1. Furthermore, pretreatment with PTC or saccharin counteracted the effect of the toxic compound, diphenhydramine, and pretreated HaCaT cells were found to proliferate faster than untreated cells. This anti‐toxic effect was suppressed by treatment with verapamil, an ABCB1 inhibitor, indicating that enhanced ABCB1 helps clear toxic substances. Altogether, harmless activators of TAS2Rs may be promising drugs that enhance the excretion of toxic substances from the human skin. [ABSTRACT FROM AUTHOR]

Positive peritoneal washing cytology is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC); however, its sensitivity is relatively low. This study evaluated the performance of peptide nucleic acid (PNA)-directed PCR clamping as a molecular-based peritoneal washing cytology for sensitive detection of KRAS mutation in PDAC. Intraoperative peritoneal washing fluid (IPWF) obtained from patients with PDAC who underwent surgery was analyzed. PNA-directed PCR clamping was performed on DNA extracted from IPWF. Among 54 patients enrolled, threshold cycle (Ct) was significantly lower in patients with positive peritoneal washing cytology than in those with negative peritoneal washing cytology (P < 0.001) and in patients with peritoneal dissemination than in those without peritoneal dissemination (P < 0.01). The optimal Ct cut-off to predict KRAS mutations in IPWF was 36.42 based on a receiver operating characteristic curve. The sensitivity, specificity, and accuracy for molecular diagnosis were 100%, 80.0%, and 85.2%, respectively. Peritoneal dissemination recurrence was significantly more frequent in patients with a positive molecular diagnosis than in those with a negative diagnosis (38.9 vs. 8.0%, P = 0.013). The genomic approach might be clinically valuable for a more precise tumor cell detection in IPWF. [ABSTRACT FROM AUTHOR]

In the quest for sustainable energy solutions, perovskite solar cells have emerged as a promising avenue due to their remarkable efficiency and cost-effectiveness. However, their widespread adoption is hampered by performance degradation issues primarily attributed to ion migration and vacancy formation within halide perovskite films. To mitigate the impact of ion defects, a passivation layer, which typically acts as a barrier for carriers, is employed. Nonetheless, the requirement for extreme thinness to avoid increasing series resistance complicates the manufacturing process. In this study, we introduced gallium phthalocyanine hydroxide (OHGaPc), a p-type organic semiconductor with Lewis base functionality, as a passivation layer to mitigate performance degradation in perovskite solar cells. We demonstrated that this material passivates halide vacancies by being a Lewis base and promotes efficient charge transport as a p-type semiconductor. This dual functionality of OHGaPc not only enhances the stability and performance of perovskite solar cells but also simplifies the manufacturing process by obviating the need for ultra-thin insulating films. Our findings underscore the significance of leveraging the properties of Lewis bases and p-type semiconductors in improving charge extraction and overall cell efficiency, setting a new direction in the development of durable and efficient perovskite solar cells. [ABSTRACT FROM AUTHOR]

γ-Tocopherol (γT) is the major form of vitamin E contained in plants and seed oils. Although it is readily metabolized in the liver, the function of the metabolites is not fully understood. This study investigated the antioxidant activities of the γT metabolite 2,7,8-trimethyl-2-(2′-carboxyethyl)-6-hydroxychroman (γCEHC) in comparison to its parent compound. The pretreatment of mouse hepatoma Hepa1c1c7 cells with γCEHC showed a cytoprotective effect on the hydrogen peroxide-induced cytotoxicity to a lesser extent than that of γT. A mechanistic investigation revealed that both γ-CEHC and γT significantly up-regulated the gene and protein expressions of heme oxygenase-1 (HO-1) via the promotion of the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Furthermore, the combination of γCEHC and γT significantly increased the gene and protein levels of HO-1 and the nuclear translocation of Nrf2, suggesting that it was an additive effect. Tin protoporphyrin IX (SnPP), a representative HO-1 inhibitor, significantly impaired the cytoprotection of γCEHC and γT against the hydrogen peroxide-induced cytotoxicity. These results suggested that not only γT but also its metabolite, γCEHC, are a promising cytoprotective factor against oxidative stress-induced cytotoxicity and that the cytoprotective effect is attributable to the cooperation of both compounds. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3-4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). Results: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/ day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4-78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9-26.9) and the disease control rate was 90.0% (95% CI=68.3-98.8). The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. Conclusion: The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified. [ABSTRACT FROM AUTHOR]

Illumination stress (IS) and negative bias under illumination stress (NBIS) cause considerable device instability in thin-film transistors based on amorphous In–Ga–Zn–O (a-IGZO). Models using in-gap states are suggested to explain device instability. Therefore, to provide reliably their density of states (DOS), this study investigated the valence band, conduction band, and in-gap states of an a-IGZO thin film. The DOS of in-gap states was directly determined in a dynamic range of six orders of magnitude through constant final state yield spectroscopy (CFS-YS) using low-energy and low-flux photons. Furthermore, light irradiation irreversibly induced extra in-gap states near the Fermi level and shifted the Fermi level to the vacuum level side, which should be related to the device instability due to IS and NBIS. Hard x-ray photoemission spectroscopy and ultraviolet photoemission spectroscopy using synchrotron radiation observed the large DOS of in-gap states near the Fermi level as in previous works. Here, we reveal that they are not intrinsic electronic states of undamaged a-IGZO, but induced by the intense measurement light of synchrotron radiation. This study demonstrates that CFS-YS is useful for determining the reliable DOS of the in-gap states for samples that are sensitive to light irradiation. The absorption spectrum measured through photothermal deflection spectroscopy is interpreted based on DOS directly determined via photoemission spectroscopies. This indicates that the line shape in the energy region below the region assigned to the Urbach tail in previous works actually roughly reflects the DOS of occupied in-gap states. [ABSTRACT FROM AUTHOR]

Phonon diffraction and interference patterns are observed at the atomic scale, using molecular dynamics simulations in systems containing crystalline silicon and nanometric obstacles, such as voids or amorphous inclusions. The diffraction patterns due to these nano-architectured systems of the same scale as the phonon wavelengths are similar to the ones predicted by the simple Fresnel–Kirchhoff integral. The few differences between the two approaches are attributed to the nature of the interface and the anisotropy of crystalline silicon. Based on the wave description of phonons, these findings can provide insights into the interaction of phonons with nano-objects and can have applications in smart thermal energy management. [ABSTRACT FROM AUTHOR]

Context: Nordic hamstring strength (NH strength) and single leg bridge test (SLBT) scores are used to predict the risk of hamstring strain injury. Although NH strength and SLBT scores may be related, the relationship between NH strength and SLBT score remains unknown. Objectives: This study investigated the relationship between NH strength and SLBT scores in university soccer players. Design: Cross-sectional study. Setting: Research laboratory. Participants: 38 male university soccer players. Main Outcome Measures: NH strength and SLBT scores. Interventions: A participant was instructed to lean forward gradually at the slowest possible speed from a kneeling posture with the knee joint flexed 90° for the NH strength measurement. Participants in the SLBT crossed their arms over their chests, pushed down from their heels, and lifted their hips off the ground as many times as they could until they failed. We investigated the relationship between NH strength and SLBT scores in the left and right sides using Spearman rank correlation coefficient. Additionally, we calculated the percentage of left–right asymmetry in NH strength and SLBT scores and investigated the relationship between these variables using Pearson correlation coefficient. Results: There were no significant correlations between NH strength and SLBT scores in the right (rs =.239, P =.16) and left (rs =.311, P =.065) legs. Furthermore, there was no significant relationship between NH strength and SLBT between-limb asymmetry (r =.073, P =.671). Conclusions: NH strength and SLBT scores could be different indexes, indicating either maximal muscle strength or muscle endurance. Thus, the findings suggested that when assessing risk factors for hamstring strain injury, both NH strength and SLBT scores should be measured. [ABSTRACT FROM AUTHOR]

Purpose: To examine the effects of a neuromuscular training program combining plyometric exercises with acceleration, deceleration, and change-of-direction drills conducted on sand or hard surfaces on the fitness qualities of young male tennis players. Methods: Thirty-one young male players were allocated to a training group performing 12 training sessions on sand or hard surfaces, during a 6-week period. Tests included linear sprint (10-m acceleration with 5-m split times), change of direction (modified 5-0-5 test), vertical jumps (countermovement jump and the 10/5 repeated-jump test), isometric hip abduction and adduction strength, and dynamic balance (Y-balance test). Perceived training loads and muscle soreness were assessed during the intervention. Results: Both training strategies were similarly effective in improving the analyzed fitness components. Group × time interaction effects were noticed, with countermovement jump (P =.032), repeated-jump test (P =.029), and reactive strength index (P =.008) favoring hard surfaces and 5-m sprint (P =.009), dynamic balance (P <.05), adduction strength (P <.05), and abduction strength (P <.001) indices favoring sand. Furthermore, the sand group promoted greater perceived training loads and muscle soreness (P <.05) than the hard group across the intervention period. Conclusion: Neuromuscular training strategies characterized by a relatively low volume (∼35 min), conducted on sand or hard surfaces, promoted similar improvements in the fitness qualities of young tennis players, with selected surface-interaction effects. Training on sand can cause transiently higher training loads and persistently higher muscle soreness, suggesting the need for an adequate familiarization period. [ABSTRACT FROM AUTHOR]

Although it plays a critical role in the photophysics and catalysis of lanthanides, spin–orbit coupling of electrons on individual lanthanide atoms in small clusters is not well understood. The major objective of this work is to probe such coupling of the praseodymium (Pr) 4f and 6s electrons in Pr2O2 and Pr2O2+. The approach combines mass-analyzed threshold ionization spectroscopy and spin–orbit multiconfiguration second-order quasi-degenerate perturbation theory. The energies of six ionization transitions are precisely measured; the adiabatic ionization energy of the neutral cluster is 38 045 (5) cm−1. Most of the electronic states involved in these transitions are identified as spin–orbit coupled states consisting of two or more electron spins. The electron configurations of these states are 4f46s2 for the neutral cluster and 4f46s for the singly charged cation, both in planar rhombus-type structures. The spin–orbit splitting due to the coupling of the electrons on the separate Pr atoms is on the order of hundreds of wavenumbers. [ABSTRACT FROM AUTHOR]

PURPOSE: To understand the mutational landscape of circulating tumor DNA (ctDNA) and tumor tissue of patients with hormone receptor–positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) metastatic breast cancer (MBC) treated with abemaciclib + endocrine therapy (ET). METHODS: Blood samples for ctDNA and/or tissue samples were collected from abemaciclib-treated patients with HR+/HER2– MBC enrolled in the SCRUM-Japan MONSTAR-SCREEN project. Blood samples were collected before abemaciclib initiation (baseline) and at disease progression/abemaciclib discontinuation (post abemaciclib treatment). Clinical and genomic characteristics including neoplastic burden (measured by shedding rate and maximum variant allele frequency [VAF]) were assessed at baseline. Genomic alterations in ctDNA were compared in paired baseline and post abemaciclib treatment samples. RESULTS: All patients (N = 97) were female (median age, 57 years [IQR, 50-67]). In baseline ctDNA (n = 77), PIK3CA (37%), TP53 (28%), ESR1 (16%), and GATA3 (11%) were the most frequently mutated genes. Baseline tissue samples (n = 79) showed similar alteration frequencies. Among patients with baseline ctDNA data, 30% had received previous ET. ESR1 alteration frequency (35% v 8%; P <.01), median shedding rate (3 v 2), and maximum somatic VAF (4 v 0.8; both P <.05) were significantly higher in ctDNA from patients with previous ET than those without previous ET. In paired ctDNA samples (n = 33), PIK3CA and ESR1 alteration frequencies were higher after abemaciclib treatment than at baseline, though not statistically significant. Among the post-treatment alterations, those newly acquired were detected most frequently in FGF3/4/19 (18%); PIK3CA , TP53 , CCND1 , and RB1 (all 15%); and ESR1 (12%). CONCLUSION: We summarized the ctDNA and cancer tissue mutational landscape, including overall neoplastic burden and PIK3CA and ESR1 hotspot mutations in abemaciclib-treated patients with HR+/HER2– MBC. The data provide insights that could help optimize treatment strategies in this population. [ABSTRACT FROM AUTHOR]

Mammalian genome research has conventionally involved mice and rats as model organisms for humans. Given the recent advances in life science research, to understand complex and higher-order biological phenomena and to elucidate pathologies and develop therapies to promote human health and overcome diseases, it is necessary to utilize not only mice and rats but also other bioresources such as standardized genetic materials and appropriate cell lines in order to gain deeper molecular and cellular insights. The Japanese bioresource infrastructure program called the National BioResource Project (NBRP) systematically collects, preserves, controls the quality, and provides bioresources for use in life science research worldwide. In this review, based on information from a database of papers related to NBRP bioresources, we present the bioresources that have proved useful for mammalian genome research, including mice, rats, other animal resources; DNA-related materials; and human/animal cells and microbes. [ABSTRACT FROM AUTHOR]

It is still unclear whether or how quercetin influences the toxic events induced by acetaldehyde in hepatocytes, though quercetin has been reported to mitigate alcohol-induced mouse liver injury. In this study, we evaluated the modulating effect of quercetin on the cytotoxicity induced by acetaldehyde in mouse hepatoma Hepa1c1c7 cells, the frequently used cellular hepatocyte model. The pretreatment with quercetin significantly inhibited the cytotoxicity induced by acetaldehyde. The treatment with quercetin itself had an ability to enhance the total ALDH activity, as well as the ALDH1A1 and ALDH3A1 gene expressions. The acetaldehyde treatment significantly enhanced the intracellular reactive oxygen species (ROS) level, whereas the quercetin pretreatment dose-dependently inhibited it. Accordingly, the treatment with quercetin itself significantly up-regulated the representative intracellular antioxidant-related gene expressions, including heme oxygenase-1 (HO-1), glutamate-cysteine ligase, catalytic subunit (GCLC), and cystine/glutamate exchanger (xCT), that coincided with the enhancement of the total intracellular glutathione (GSH) level. Tin protoporphyrin IX (SNPP), a typical HO-1 inhibitor, restored the quercetin-induced reduction in the intracellular ROS level, whereas buthionine sulphoximine, a representative GSH biosynthesis inhibitor, did not. SNPP also cancelled the quercetin-induced cytoprotection against acetaldehyde. These results suggest that the low-molecular-weight antioxidants produced by the HO-1 enzymatic reaction are mainly attributable to quercetin-induced cytoprotection. [ABSTRACT FROM AUTHOR]

This study investigated the prognostic impact of vitamin D deficiency and reduced skeletal muscle mass in diffuse large B-cell lymphoma (DLBCL) patients. A retrospective analysis of 186 newly diagnosed DLBCL patients from 2012 to 2022 was conducted, measuring serum 25-hydroxyvitamin D [25(OH)D] levels and the skeletal muscle index (SMI). Decreased vitamin D levels were linked to more severe DLBCL disease, with a median 25(OH)D concentration of 13 (4.0–27) ng/mL. Males in the group with a low SMI had a considerably lower 25(OH)D concentration. The optimal threshold of 25(OH)D levels for overall survival (OS) was 9.6 ng/mL, with lower values associated with a higher likelihood of recurrence and mortality. Multivariable analysis showed hazard ratios for OS of 1.4 [95% CI 0.77–2.5] for a low SMI and 3.2 [95% CI 1.8–5.8] for low 25(OH)D concentration. The combination of a low SMI and low vitamin D concentration resulted in the worst prognosis. Thus, low levels of vitamin D associated with disease progression significantly impact DLBCL prognosis, which can be further stratified by the SMI, providing valuable insights for patient management and potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

Extramammary Paget disease (EMPD) is an intraepithelial adenocarcinoma that primarily affects the genital and axillary areas in older individuals. A limited number of paired patients with familial EMPD (i.e. parent–offspring, siblings) have been reported but the genetics have not yet been adequately studied. We report, to the best of our knowledge, the first familial cases of patients with EMPD involving three affected siblings. The tumour-only multigene panel testing using surgical specimens revealed a heterozygous c.2997A>C (p.Glu999Asp) nonsynonymous variant in the proto-oncogene MET (NM_000245.4) in the three affected siblings. The germline multigene panel testing using peripheral blood lymphocytes revealed the same missense MET variant in all five family members who were tested, including two asymptomatic offspring (51 and 37 years of age). The MET variant we identified could be involved in EMPD carcinogenesis. Further genomic analyses of patients with familial EMPD are warranted to validate the pathogenic relevance of MET variants in EMPD development. [ABSTRACT FROM AUTHOR]

Summary: This study aimed to complement the results of the REACH-2 study by prospectively evaluating the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma (HCC) in a real-world setting. This was an open-label, nonrandomized, multicenter, prospective study conducted at 13 institutions in Japan (jRCTs031190236). The study included Child–Pugh Class A patients with advanced HCC who had received pretreatment with atezolizumab plus bevacizumab (Atez/Bev) or lenvatinib. Ramucirumab was introduced as a second-line treatment after Atez/Bev or lenvatinib and as a third-line treatment after Atez/Bev and lenvatinib. Between May 2020 and July 2022, we enrolled 19 patients, including 17 who received ramucirumab. Additionally, seven patients received lenvatinib, another seven patients received Atez/Bev, and three patients received Atez/Bev followed by lenvatinib as prior treatment. The primary endpoint was a 6-month progression-free survival (PFS) rate, which was 14.3%. The median PFS and overall survival were 3.7 and 12.0 months, respectively. The most common grade ≥ 3 adverse events (AEs) were hypertension (23.5%), proteinuria (17.6%), and neutropenia (11.8%). The discontinuation rate due to AEs was 29.4%. Six patients progressed from Child–Pugh A to B after treatment with ramucirumab. Thirteen patients were eligible for post-ramucirumab treatment, including systemic therapy. Despite the limited number of patients, the efficacy of ramucirumab was comparable to that observed in the REACH-2 study when used after lenvatinib and Atez/Bev. However, the incidence of AEs was higher than that in the REACH-2 study. [ABSTRACT FROM AUTHOR]

Bioabsorbable materials have a wide range of applications, such as scaffolds for regenerative medicine and cell transplantation therapy and carriers for drug delivery systems. Therefore, although many researchers are conducting their research and development, few of them have been used in clinical practice. In addition, existing bioabsorbable materials cannot bind to the body's tissues. If bioabsorbable materials with an adhesive ability to biological tissues can be made, they can ensure the mixture remains fixed to the affected area when mixed with artificial bone or other materials. In addition, if the filling material in the bone defect is soft and uncured, resorption is rapid, which is advantageous for bone regeneration. In this paper, the development and process of a new bioabsorbable material "Phosphorylated pullulan" and its capability as a bone replacement material were demonstrated. Phosphorylated pullulan, which was developed based on the tooth adhesion theory, is the only bioabsorbable material able to adhere to bone and teeth. The phosphorylated pullulan and β-TCP mixture is a non-hardening putty. It is useful as a new resorbable bone replacement material with an adhesive ability for bone defects around implants. [ABSTRACT FROM AUTHOR]

When the velocity shear between the two plasmas separated by Earth's magnetopause is locally super‐Alfvénic, the Kelvin‐Helmholtz (KH) instability can develop. A crucial role is played by the interplanetary magnetic field (IMF) orientation, which can stabilize the velocity shear. Although, in a linear regime, the instability threshold is equally satisfied during both northward and southward IMF orientations, in situ measurements show that KH instability is preferentially excited during the northward IMF orientation. We investigate this different behavior by means of a mixing parameter which we apply to two KH events to identify both boundaries and the center of waves/vortices. During the northward orientation, the waves/vortex boundaries have stronger electrons than ions mixing, while the opposite is observed at their center. During the southward orientation, instead, particle mixing is observed predominantly at the boundaries. In addition, stronger local ion and electron non‐thermal features are observed during the northward than the southward IMF orientation. Specifically, ion distribution functions are more distorted, due to field‐aligned beams, and electrons have a larger temperature anisotropy during the northward than the southward IMF orientation. The observed kinetic features provide an insight into both local and remote processes that affect the evolution of KH structures. Plain Language Summary: Due to the velocity shear layer generated by the solar wind flowing past the Earth's magnetosphere, large surface Kelvin‐Helmholtz (KH) waves and vortices can be formed at the magnetopause. These waves and vortices play a crucial role in transporting the solar wind particles through the magnetopause into the magnetosphere, where the particles form a so‐called low‐latitude boundary layer (LLBL). The particle transport occurs due to stretching and twisting of the magnetic field lines by the KH waves/vortices, which result in plasma mixing and diffusion through the magnetopause. It appears that spacecraft observe the KH waves/vortices more often during northward orientations of the interplanetary magnetic field (IMF). During northward IMF, the induced high‐latitudes reconnection thicken the preexisting LLBL and lower the density gradient at the magnetopause, thus favoring KH instability. Conversely, higher density jump and dayside reconnection, during southward IMF, can suppress the instability development and disrupt the KH vortices. To clarify these differences in the KH wave/vortex appearance under different IMF directions, we compare the wave/vortex and particle properties during both IMF orientations. We employ a mixing parameter, which helps identify specific regions of KH waves/vortices and investigate their kinetic signatures, thus providing an insight into KH evolution. Key Points: Two Kelvin‐Helmholtz events during northward and southward interplanetary magnetic field (IMF) orientations are compared using a mixing‐parameterHigher mixing and local non‐thermal features due to field‐aligned ion beams during the northward IMF are observedKinetic features of Kelvin‐Helmholtz structures can identify both local and remote processes affecting the instability evolution [ABSTRACT FROM AUTHOR]

Background/Purpose: Differential diagnosis of isolated immunoglobin (Ig)G4-related sclerosing cholangitis (IgG4-SC) and cholangiocarcinoma is challenging. We aimed to clarify the role of endoscopic retrograde cholangiography (ERCP)-related procedures in the differential diagnosis of isolated IgG4-SC and perihilar cholangiocarcinoma (PHCC). Methods: Seven patients with hilar-type isolated IgG4-SC diagnosed at Hiroshima University Hospital and sixty-five patients with surgically resected invasive PHCC were enrolled, and the diagnostic yields of intraductal ultrasonography (IDUS), peroral cholangioscopy (POCS), and pathological examinations were determined. Results: In six of seven (86%) patients with isolated IgG4-SC, the stricture was in the perihilar bile duct. IDUS showed that symmetrical wall thickening (40% vs. 5%, p = 0.04), homogeneous internal echo (80% vs. 5%, p < 0.001), and smooth outer margins (80% vs. 6%, p < 0.001) were more frequent in isolated IgG4-SC than in PHCC. POCS showed a smooth mucosal surface more frequent in isolated IgG4-SC (75% vs. 7%, p = 0.006). Only one patient had two pathological findings characteristic of IgG4-SC. The sensitivity for diagnosing PHCC was 81% using two or more combined sampling methods. Conclusions: Pathological examinations have limitations in the differential diagnosis of isolated-IgG4-SC and PHCC, and a diagnostic strategy that combines multiple ERCP-related procedures, including IDUS and POCS, is recommended. [ABSTRACT FROM AUTHOR]

The Japanese islands were originally included in the Eurasian Continent as part of the southern and northern landmasses. The two landmasses were detached from the continent 18 million years ago. After that, the former was repeatedly connected to the Korean peninsula during glacial periods, but most of the latter was under seawater. Thus, all Japanese amphibians are undoubtedly derived from this nearby continent. However, it is unclear where the amphibians moved during the formation of the Japanese islands. To address the issue, we selected Glandirana rugosa as a representative of Japanese amphibians because this frog is the only species among amphibians in which nucleotide sequences of the mitochondrial genes and sex chromosome evolution have been deeply investigated. Then, we constructed time‐calibrated and RAxML phylogenetic trees based on nucleotide sequences of the mitochondrial genes of the Glandirana frogs in Japan and South Korea. Various sites were used to select SNP data from the Glandirana species and their sex chromosome evolution, and the cladograms we obtained suggest that ancient Glandirana frogs except for one group moved along with the southern landmass, when it was separated from the continent. The movements of the Glandirana frogs in Japan and South Korea obtained as results of this study will help scientists to understand the geographical changes that took place during the formation of the Japanese islands. This strategy is applicable to studying and understanding the movements of other amphibian species of the Eurasian and other continents. [ABSTRACT FROM AUTHOR]

Thrombocytopenia frequently occurs in patients with sepsis. Disseminated intravascular coagulation (DIC) may be a possible cause of thrombocytopenia owing to its high prevalence and association with poor outcomes; however, it is important to keep the presence of other diseases in mind in sepsis practice. Thrombotic microangiopathy (TMA), which is characterized by thrombotic thrombocytopenic purpura, Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (HUS), and complement-mediated HUS, is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ damage. TMA has become widely recognized in recent years because of the development of specific treatments. Previous studies have reported a remarkably lower prevalence of TMA than DIC; however, its epidemiology is not well defined, and there may be cases in which TMA is not correctly diagnosed, resulting in poor outcomes. Therefore, it is important to differentiate DIC from TMA. Nevertheless, differentiating between DIC and TMA remains a challenge as indicated by previous reports that most patients with TMA can be diagnosed as DIC using the universal coagulation scoring system. Several algorithms to differentiate sepsis-related DIC from TMA have been suggested, contributing to improving the care of septic patients with thrombocytopenia; however, it may be difficult to apply these algorithms to patients with coexisting DIC and TMA, which has recently been reported. This review describes the disease characteristics, including epidemiology, pathophysiology, and treatment, of DIC, TMA, and other diseases with thrombocytopenia and proposes a novel practical approach flow, which is characterized by the initiation of the diagnosis of TMA in parallel with the diagnosis of DIC. This practical flow also refers to the longitudinal diagnosis and treatment flow with TMA in mind and real clinical timeframes. In conclusion, we aim to widely disseminate the results of this review that emphasize the importance of incorporating consideration of TMA in the management of septic DIC. We anticipate that this practical new approach for the diagnostic and treatment flow will lead to the appropriate diagnosis and treatment of complex cases, improve patient outcomes, and generate new epidemiological evidence regarding TMA. [ABSTRACT FROM AUTHOR]

Background: Selecting pembrolizumab monotherapy (MONO) or pembrolizumab plus platinum‐based chemotherapy (COMB) for patients with nonsmall cell lung cancer (NSCLC) and high programmed death‐ligand 1 (PD‐L1) expression is an important issue in clinical practice. We previously conducted a retrospective multicenter observational study of patients with NSCLC and high PD‐L1 expression who received MONO or COMB as a first‐line treatment. Here, we report updated data and evaluate the long‐term outcomes. Methods: We performed a retrospective multicenter study of 298 patients with NSCLC and high PD‐L1 expression who received MONO or COMB as first‐line treatment between December 2018 and January 2020. We reviewed the medical records and assessed the clinical efficacy and toxicity using a prolonged data cutoff. Results: In total, 164 (median age: 74 years) and 134 (median age: 68 years) patients received MONO and COMB, respectively; patients who received COMB were younger and had better performance statuses (0–1). At the prolonged data cutoff, the median follow‐up was 20.2 (range: 0.1–41.4) months. The median progression‐free survivals were 7.5 and 13.1 months, and overall survivals (OSs) were 17.2 and 33.7 months for MONO and COMB, respectively. Treatment discontinuation rates were 21.9% and 20.1% for the MONO and COMB, respectively. With prolonged follow‐up, although COMB demonstrated an OS benefit and higher objective response rate than MONO, in the propensity score matching analysis COMB didn't demonstrate a significant benefit compared to the MONO. Conclusions: COMB may be effective as a first‐line treatment for NSCLC with high PD‐L1 expression in a selected subset of patients. [ABSTRACT FROM AUTHOR]