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Historically, in vitro cardiac function assays for drug screening have predominantly utilized electrophysiological techniques, employing electrodes and fluorescence microscopy. However, the patch-clamp technique entails potential cellular trauma and relies heavily on the operator’s proficiency. Microelectrode arrays (MEAs) necessitate specialized culture dishes owing to their sensitivity to cell adhesion on electrodes. In fluorescent imaging application, the loading of fluorescent dyes into cells may elicit stress, inflict damage, and disrupt cellular homeostasis. Compared to electrophysiological assays, magnetic measurements, which are advantageous for yielding vector data and being unaffected by the tissue microenvironment, remain unutilized in high-throughput drug screening in vitro owing to challenges in detecting faint magnetic signals. Therefore, we developed an in vitro noninvasive real-time magnetic recording system based on magneto-impedance (MI) sensors by providing correlated double sampling (CDS) and avoidance from singularity points of sensor noises, in MI sensor as simple, small, and highly sensitive drug screening tool. Our proposed system demonstrates high field detection sensitivity, maintaining excellent linearity and a noise level of approximately 2 pT/Hz1/2 at room temperature. This innovative MI sensor system effectively distinguishes the beat rate alterations of induced pluripotent stem cell-derived cardiomyocytes treated with positive and negative chronotropic drugs from the steady state, correlating with the MEA recordings and fluorescence imaging using standard culture dishes. The presented data suggest that our system has the potential to replace conventional methods, enabling the acquisition of diverse biometric data across cellular, tissue, and organ levels for drug screening and diagnostics.

Epidemiological trends and clinical relevance of NTM species in Japan following the adoption of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry remain unclear.

Previous studies reported mixed results on associations between dietary potassium intake and hyperkalemia in patients with chronic kidney disease (CKD). This study investigated the association between potassium intake from different food sources and hyperkalemia in patients with non–dialysis-dependent CKD.

Adenosine deaminase (ADA) in pleural fluid is a useful marker for diagnosing tuberculous pleurisy. However, recent studies have reported a lower specificity of pleural fluid ADA levels. We previously developed a diagnostic flowchart for patients with pleural fluid ADA ≥40 U/L, incorporating variables such as pleural fluid lactate dehydrogenase <825 U/L, predominant pleural fluid neutrophils or cell degeneration, and a pleural fluid ADA/total protein ratio <14. This flowchart was effective in distinguishing between tuberculous pleurisy and other diseases. Here, we conducted a validation analysis of this flowchart.

The global incidence of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing. The primary aim of pharmacotherapeutic treatment for NTM-PD is to achieve negative bacterial conversion, but this goal is challenging, especially in cases with poor prognosis factors. Moreover, recurrence frequently occurs following successful treatment. Consequently, patient-reported outcomes (PROs) have attracted an increasing amount of attention due to their potential to elucidate the pathophysiology of NTM-PD. The current review article aimed to describe the current understanding of PROs related to health-related quality of life (HRQoL). HRQoL is influenced by a variety of factors; notably, those factors associated with the prognosis of NTM-PD significantly impair HRQoL. In patients with refractory NTM-PD, HRQoL tends to worsen over time. Assessing HRQoL through PROs involves short-term or long-term evaluation tools, which are selected based on their relevance to the patient's condition and the clinician's goals. Understanding the nuances of PROs can be helpful for delivering empathetic care tailored to patients in even the most complex treatment scenarios.

Perovskite solar cells garnered commercial interest due to their device’s impressive photon conversion efficiencies and improvements in long-term stabilities. The critical indicators of high-quality perovskite solar cells are often associated with morphological characteristics, such as grain size, compact packing, surface smoothness, and formation of suitable interfaces with charge transport layers. In the present study, the linear electroabsorption spectral signals emanating from the interface of methylammonium lead triiodide perovskite films grown on different electrodes and charge transport layers are shown to be sensitive to surface roughness. The polymeric hole transporting layers PEDOT:PSS on FTO/ITO substrates as underlayers were shown to produce smoother films with weaker linear electroabsorption signals compared with the tin oxide electron transporting layer on the FTO substrate as an underlayer, thereby highlighting the potential of linear electroabsorption spectroscopy to screen the quality of perovskite solar cells.

Human pancreatic cancer is characterized by the molecular diversity encompassing native duct-like and squamous cell-like identities, but mechanisms underlying squamous transdifferentiation have remained elusive. To comprehensively capture the molecular diversity of human pancreatic cancer, we here profiled 65 patient-derived pancreatic cancer organoid lines, including six adenosquamous carcinoma lines. H3K27me3-mediated erasure of the ductal lineage specifiers and hijacking of the TP63-driven squamous-cell programme drove squamous-cell commitment, providing survival benefit in a Wnt-deficient environment and hypoxic conditions. Gene engineering of normal pancreatic duct organoids revealed that GATA6 loss and a Wnt-deficient environment, in concert with genetic or hypoxia-mediated inactivation of KDM6A, facilitate squamous reprogramming, which in turn enhances environmental fitness. EZH2 inhibition counterbalanced the epigenetic bias and curbed the growth of adenosquamous cancer organoids. Our results demonstrate how an adversarial microenvironment dictates the molecular and histological evolution of human pancreatic cancer and provide insights into the principles and significance of lineage conversion in human cancer.

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Asthma is characterized by phenotypes of different clinical, demographic, and pathological characteristics. Identifying the profile of exhaled volatile organic compounds (VOCs) in asthma phenotypes may facilitate establishing biomarkers and understanding asthma background pathogenesis. This study aimed to identify exhaled VOCs that characterize severe asthma phenotypes among patients with asthma.

The synthesis of a spirolactone analogue of xylapyrraside B1, a potent antioxidant agent, is described. The key step is the stereoselective formation of the spirolactone skeleton via the formal [3+2] annulation of the isopropylidene-protected glyceraldehyde and δ-methylene lactone, mediated by trifluoroborane etherate. This study addresses the stereoselective synthesis of pyrrolomorpholine spiroketal alkaloids, enabling the production of these bioactive compounds and their analogues.

Nanostructured lead telluride PbTe is among the best-performing thermoelectric materials, for both p- and n-types, for intermediate temperature applications. However, the fabrication of power-generating modules based on nanostructured PbTe still faces challenges related to the stability of the materials, especially nanoprecipitates, and the bonding of electric contacts. In this study, in situ high-temperature transmission electron microscopy observation confirmed the stability of nanoprecipitates in p-type Pb0.973Na0.02Ge0.007Te up to at least ∼786 K. Then, a new architecture for a packaged module was developed for improving durability, preventing unwanted interaction between thermoelectric materials and electrodes, and for reducing thermal stress-induced crack formation. Finite element method simulations of thermal stresses and power generation characteristics were utilized to optimize the new module architecture. Legs of nanostructured p-type Pb0.973Na0.02Ge0.007Te (maximum zT∼ 2.2 at 795 K) and nanostructured n-type Pb0.98Ga0.02Te (maximum zT∼ 1.5 at 748 K) were stacked with flexible Fe-foil diffusion barrier layers and Ag-foil-interconnecting electrodes forming stable interfaces between electrodes and PbTe in the packaged module. For the bare module, a maximum conversion efficiency of ∼6.8% was obtained for a temperature difference of ∼480 K. Only ∼3% reduction in output power and efficiency was found after long-term operation of the bare module for ∼740 h (∼31 days) at a hot-side temperature of ∼673 K, demonstrating good long-term stability.

We study the quantum improvement of Kerr black holes with mass-dependent scale identifications in asymptotically safe gravity. We find that a physically sensible identification can only be a function of Mrand the area A=4π(r2+a2)where Mis the mass of the black hole and ais an angular momentum parameter. We then discuss various properties of the rotating quantum black holes for a simple choice of the identification. We show that the resulting regular rotating black holes have the following nice properties: (i) admitting a consistent black hole thermodynamics at the horizon, (ii) resolving the ring singularity, (iii) partially eliminating closed time-like curves present in the classical Kerr black holes.

Previously, we have shown that pyrogallol alleviated nasal symptoms and suppressed IL-9 gene up-regulation in allergy model rats by inhibiting calcineurin/NFAT signaling. As pyrogallol has antioxidative activity, it may be responsible for inhibiting calcineurin/NFAT signaling-mediated IL-9 gene expression. However, the relationship between antioxidative activity and suppression of IL-9 gene expression has not been elucidated yet. Here, we conducted the structure-activity relationship studies of pyrogallol and its structurally related compounds to understand the mechanism of IL-9 gene suppression by pyrogallol. 2, 2-Diphenyl-1-picrylhydrazyl radical scavenging assay showed that the antioxidative activity of catechol, resorcinol, phloroglucinol, and gallic acid is 60.1%, 10.4%, 18.8%, and 113.5% of pyrogallol, respectively. Catechol, resorcinol, and phloroglucinol did not suppress NFAT dephosphorylation. Gallic acid suppressed dephosphorylation of NFAT. Gallic acid also suppressed ionomycin-induced up-regulation of IL-9 gene expression with the IC50value of 82.6 μM. However, catechol, resorcinol and phloroglucinol showed no suppressive activity. In addition, using gallic acid-immobilized beads, we isolated and identified Poly(U)-binding-splicing factor 60 (PUF60) as a pyrogallol binding protein. These results suggest that the antioxidative activity of pyrogallol is not likely to be the mechanism of IL-9 gene suppression. Data also suggest that PUF60 is one of its target molecules responsible for the suppression of calcineurin/NFAT signaling by pyrogallol.

Pelagic clay with high concentrations of rare-earth elements (REE), called REE-rich mud, is considered to be a promising REE resource. To decipher the formation mechanism of REE-rich mud and the paleoenvironments recorded in pelagic clay, reliable age constraints are required. However, it is difficult to apply conventional biostratigraphy and magnetostratigraphy to pelagic clays because they lack calcareous and siliceous microfossils, and erosional events and depositional hiatuses interrupt continuous chronological records such as magnetic polarity. Here, we combined Sr isotope chemostratigraphy and ichthyolith biostratigraphy to obtain precise ages for samples from three drilling cores from the pelagic realms of the North and South Pacific Ocean (Ocean Drilling Program Hole 777B, and Integrated Ocean Drilling Program Holes U1366C and U1370D). This composite approach enabled us to constrain the depositional ages of REE-enriched layers with high reliability: the sediments with REE-concentration maxima were deposited at 23.0–28.2 Ma in Hole 777B; at 32.4 Ma, 61.0–65.4 Ma, and 74.6–78.8 Ma in Hole U1366C; and at 60.5–65.7 Ma in Hole U1370D. This study also confirmed that, in several horizons, reworking due to bioturbation or diagenesis and silicate alteration may have led to imprecise Sr isotope dates. Our new age model suggests that the sediments in all three holes have large chronological gaps due to erosion and hiatus events.

Two-dimensional tiling manners as cross-sectional views of cylindrical domain assembly formed by pentablock quarterpolymers of the AB1CB2D type in bulk were investigated. Several binary and ternary blends from three mother polymers having different ϕB1/ϕB2ratios (ϕB1and ϕB2are the volume fractions of the B1and B2blocks, respectively) represent nonperiodic but ordered triangle/square tilings, where the N3/N4ratios (N3and N4are the numbers of triangles and squares in the observed area, respectively) are all close enough to the theoretical value of 4/√3 ≑ 2.31 for the dodecagonal quasicrystalline (DDQC) state, irrespective of the total number of polygons. The TEM images, having almost the same N3/N4ratios, were proved to show 4- and 6-fold symmetries in terms of the angular appearance of equilateral polygon sides via image analyses. Among them, a ternary blend showed a nearly ideal random tiling pattern that is almost equivalent to the theoretically predicted tiling by SCFT. Moreover, the magnitude of phason strain estimated for a TEM image from the ternary blend was proved to be quite small when the observing area is narrow, while it deviates from the ideal quasicrystalline tiling with an increasing number of vertices in the observing area.

This study analyzes self-enforcing climate agreements in a repeated-game framework in which asymmetric countries emit greenhouse gases over time. In particular, we consider a novel burden-sharing scheme that makes an agreement self-enforcing even when a relatively less patient country participates in the agreement. The long-term stable emission quota that makes the agreement self-enforcing for the largest set of discount factors equalizes the compliance thresholds across countries. We then show that the long-term stable quota satisfies grandfathering as an equity criterion when countries are asymmetric. This implies that low-emitting countries that have developed clean technologies will be reluctant to agree to the scheme, while countries that have invested in adaptation and brown technology are likely to accept the emission quota. Furthermore, an ambitious target level deteriorates the compliance incentives of countries that are allowed to have low emission reduction rates.

Nintedanib is generally safe and well tolerated and can improve prognosis in patients with various interstitial lung diseases (ILDs). Appropriate management of adverse events of nintedanib is important to ensure its long-term persistent use. Weight loss is a routinely assessed adverse event in clinical practice. This study aimed to elucidate whether body weight change in the first year of nintedanib therapy can indicate prognosis and predict tolerability in patients with ILD.

An improved algorithm for computing multiphase flows is presented in which the multimaterial Moment-of-Fluid (MOF) algorithm for multiphase flows, initially described by Li et al. (2015), is enhanced addressing existing MOF difficulties in computing solutions to problems in which surface tension forces are crucial for understanding salient flow mechanisms. The Continuous MOF (CMOF) method is motivated in this article. The CMOF reconstruction method inherently removes the “checkerboard instability” that persists when using the MOF method on surface tension driven multiphase (multimaterial) flows. The CMOF reconstruction algorithm is accelerated by coupling the CMOF method to the level set method and coupling the CMOF method to a decision tree machine learning (ML) algorithm. Multiphase flow examples are shown in the two-dimensional (2D), three-dimensional (3D) axisymmetric “RZ”, and 3D coordinate systems. Examples include two material and three material multiphase flows: bubble formation, the impingement of a liquid jet on a gas bubble in a cryogenic fuel tank, freezing, and liquid lens dynamics.

Pt-supported SPEEK (sulfonated poly(ether ether ketone)) thin films, mimicking the ionomer–electrode interface in polymer electrolyte fuel cells (PEFCs), were synthesized with thicknesses from 12 to 105 nm. Their glass transition temperature (Tg) was analyzed via in situ thermal ellipsometry, revealing a thickness-dependent decrease in Tg, indicative of confinement effects. Particularly, a 30 nm film, typical of practical ionomer films, exhibited surface crystallization preceding that at the buried interface, a phenomenon linked to higher mobility at the free surface, as confirmed by grazing incidence wide-angle X-ray scattering (GIWAXS) at both subcritical (0.09°) and supercritical (0.14°) angles. This study elucidates the dynamic interplay between the high-mobility-free surface and the interaction-intensive buried interface in confined SPEEK thin films. It was observed that below 30 nm thickness, interfacial interactions become the primary factor influencing transition temperature. Additionally, spatially heterogeneous crystallization, more pronounced in the out-of-plane direction, correlates with reduced proton conduction, underscoring the impact of membrane electrolyte assembly (MEA) hot-pressing on the functional properties of Nafion alternatives.

Nanoparticles (NPs) are anticipated to be used for various biomedical applications in which their aggregation has been an important issue. However, concerns regarding slightly aggregated but apparently monodispersed NPs have been difficult to address because of a lack of appropriate evaluation methods. Here, we report centrifugal field-flow fractionation (CF3) as a powerful method for analyzing the slight aggregation of NPs, using antibody-modified gold NPs (Ab-AuNPs) prepared by a conventional protocol with centrifugal purification as a model. While common evaluation methods such as dynamic light scattering cannot detect significant signs of aggregation, CF3 successfully detects distinct peaks of slightly aggregated NPs, including dimers and trimers. Their impact on biological interactions was also demonstrated by a cellular uptake study: slightly aggregated Ab-AuNPs exhibited 1.8 times higher cellular uptake than monodispersed Ab-AuNPs. These results suggest the importance of aggregate evaluation via CF3 as well as the need for careful attention to the bioconjugation procedures for NPs.

Hexagonal rare-earth iron oxides (h-RFeO3) exhibit spontaneous magnetization and room-temperature ferroelectricity simultaneously. However, achieving a large magnetoelectric coupling necessitates further exploration. Herein, we report the impact of the magnetic phase transition on the ferroelectric properties of epitaxial h-RFeO3(R= Tb and Ho) films prepared by pulsed laser deposition. The metastable h-RFeO3phase is successfully stabilized with high crystallinity and low leakage current due to the ITO buffer layer, making it possible to investigate the ferroelectric properties. The h-TbFeO3film exhibits a magnetic-field-induced transition from antiferromagnetic (AFM) to weak ferromagnetic (wFM) phases below 30 K, while also exhibiting ferroelectricity at 300 K. The dielectric constants change with the magnetic phase transition, demonstrating hysteresis in the magnetocapacitance. In contrast, the h-HoFeO3film exhibits antiferroelectric-like behavior and an AFM–wFM phase transition. Notably, the h-HoFeO3film shows a rapid increase in the remnant polarization during the AFM–wFM phase transition accompanied by an increase in the ferroelectric component. Considering the strong connection between the antiferroelectric behavior in the h-RFeO3system and the ferroelectric domain wall motion, this considerable modification of ferroelectric properties during the magnetic phase transition is probably due to the faster movement of the ferroelectric domain walls in the wFM phase induced by the clamping effect. Our findings indicate the effectiveness of magnetic phase transitions in enhancing the magnetoelectric coupling, particularly when utilizing domain wall clamping properties.

End‐functionalized linear poly(ether sulfone) (PES) free from cyclic PES (CPES) was obtained by reversible transetherification of CPESwith bis(aryloxyphenyl) sulfone 1in the presence of base catalyst. Initially, transetherification of CPESwith bis(phenoxyphenyl) sulfone 1ain the presence of a catalytic amount of CsF in N‐methylpyrrolidone (NMP) at 145 °C afforded not the desired linear PES (LPES), but CPESwith decreased molecular weight. However, when PhOSiMe3/K2CO3was used instead of CsF at 180 °C, the desired LPESwith a phenoxy group derived from 1aat both ends was obtained. Under the established conditions, the transetherification of CPESwith bis(bromophenoxyphenyl) sulfone 1binstead of 1aafforded not only LPESwith a bromophenoxy group at both ends, but also LPESwith a bromophenoxy group at one end and a phenoxy group at the other. Since the phenoxy group might be introduced from PhOSiMe3, the reaction was conducted with BrPhOSiMe3instead of PhOSiMe3along with K2CO3as a catalyst, and in this case, the desired LPESwith a bromophemoxy group at both ends was obtained.

Strobilurins A and X, isolated from Mucidula venosolamellataculture extracts, demonstrated potent inhibition of human melanoma G-361 cell proliferation. Strobilurin X exhibited milder inhibitory effects on human fibroblast cells (NB1RGB) compared to strobilurin A. Additional strobilurin-related compounds were isolated from the other mushroom species. Oudemansins A and B displayed weaker activities on G-361 cells than strobilurins A and B, respectively, emphasizing the importance of a conjugated double-bond structure. Among isolated compounds, strobilurin G showed the lowest IC50value for G-361 cells. Additional strobilurins bearing various substituents on the benzene ring were synthesized. Synthetic intermediates lacking the methyl β-methoxyacrylate group and a strobilurin analogue bearing modified β-methoxyacrylate moiety showed almost no inhibitory activity against G-361 cells. The introduction of long or bulky substituents at the 4′ position of the benzene ring of strobilurins enhanced the activity and selectivity, suggesting differential recognition of the benzene ring by G-361 and NB1RGB cells.Graphical AbstractNatural strobilurins isolated from mushrooms and their synthetic analogues revealed structural factors that enhance selective activity against human melanoma cells.

Background:Education regarding death diagnosis is not often included in the medical education. Objective:To investigate the change minds at the time of death diagnosis among residents after lectures based on our guidebook. Design:Uncontrolled, open-label, multi-center trial. Subjects:A total of 131 doctors undergoing their initial training were enrolled this study. Measurements:Questionnaires were administered to volunteers before and after the lecture by the clinical training instructor presented information regarding doctors’ behaviors at the death diagnosis based on our guidebook at each hospital. Results:The subjects had an average age of 27.1 years and comprised 76 men (58.0%) and 54 women (41.2%). A total of 83 subjects (63.4%) had learned how to diagnose death as medical students, and 52 subjects (39.7%) had experienced death diagnosis scenes as medical students. Among those who had difficulties related to death diagnoses, the highest number (88.4%) indicated that “I do not know what to say to the family after a death diagnosis”. Self-evaluation significantly increased after the lecture for many items concerning explanations to and considerations of the family: the effect size for “Give words of comfort and encouragement to family” increased significantly after the lecture to 0.9. Conclusions:Few of the residents felt that they had received education regarding death diagnoses; they reported difficulties with diagnosing death and responding to patients’ families. After the lecture using our guidebook, residents’ mind changed significantly for death diagnosis, suggesting that the guidebook at the time of death diagnosis may be useful.

In clinical research on multifactorial diseases such as atopic dermatitis, data-driven medical research has become more widely used as means to clarify diverse pathological conditions and to realize precision medicine. However, modern clinical data, characterized as large-scale, multimodal, and multi-center, causes difficulties in data integration and management, which limits productivity in clinical data science.

Mesenchymal stem cells (MSCs) express tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) following activation by various molecules and have antitumor effects against several cancer types. In particular, preactivation of MSCs with tumor necrosis factor-α (TNF-α) enhances TRAIL expression. We focused on the application of human periodontal ligament-derived stem cells (hPDLSCs) to stem cell-based cancer therapy, and evaluated their effects on head and neck squamous cell carcinoma (HNSCC) cells.

A direct asymmetric reductive amination of α-keto acids catalyzed by Cp*Ir complexes bearing a chiral N-(2-picolyl)sulfonamidato ligand is described. The combined use of optically active 2-phenyglycinol as an aminating agent is effective for the chemo- and stereoselective transfer hydrogenation using formic acid. The subsequent elimination of the hydroxyethyl moiety by orthoperiodic acid can afford various unprotected α-amino acids in satisfactory isolated yields (20 examples) with excellent optical purities (up to >99% ee).

Imidazole derivatives are promising building blocks for the construction of hydrogen-bonded organic frameworks (HOFs); however, imidazole-based HOFs are still much less explored than HOFs based on more prominent building blocks, such as carboxy-group-containing organic compounds and 2,4-diaminotriazine moieties. Here, we report a HOF based on phenylbis(benzimidazol-2-yl)methanol (1). The porous framework of the 1-based HOF is mainly constructed by intermolecular O–H···N and N–H···N hydrogen bonds, with ethyl acetate (EtOAc) solvate molecules occupying the pores. The EtOAc guest molecules can be removed by heating (100 °C) the as-synthesized 1-based HOF under reduced pressure or by treating it with supercritical carbon dioxide via a single-crystal-to-single-crystal transformation involving a large framework motion. The desolvated HOF can adsorb the vapors of EtOAc, 2-pentanone, 3-pentanone, 2-butanone, diethyl ether, and diethylamine even under high-humidity conditions, which renders the 1-based HOF a promising material for organic-vapor adsorption in the context of industrial applications.

AbstractThis paper presents the results of the Power To Melt and Maneuverability (P2M) Simulation Exercise on past fuel melting irradiation experiments, organized within the Organisation for Economic Co-operation and Development/Nuclear Energy Agency Framework for IrraDiation ExperimentS (FIDES) framework by the Core Group (CEA, EDF, and SCK‧CEN) and open to all FIDES members. The exercise consisted in simulating two past power ramps where fuel melting was detected: (1) the xM3 staircase power transient [ramp terminal level (RTL) 70 kW‧m−1, average burnup 27 GWd‧tU−1], carried out in 2005 in the R2 reactor at Studsvik (Sweden), where the rodlet maintained its integrity, and (2) the HBC4 fast power transient (RTL 66 kW‧m−1, average burnup 48 GWd‧tU−1), carried out in 1987 in the BR2 reactor at SCK‧CEN (Belgium), where the cladding failed during the experiment. The exercise was joined by 13 organizations from 9 countries using 11 different fuel performance codes. In this paper, the main results of the Simulation Exercise are presented and compared to available postirradiation examinations (PIE) or on-line measurements during the power ramps (fuel and clad diameters, rod elongation, pellet-clad gap, and fission gas release). Since the focus of the Simulation Exercise is on fuel melting assessment, determination of the boundary between melted/nonmelted fuel and the consequent definition of a melting radius from PIE are first discussed. During the HBC4 ramp, fuel melting was predicted by most of the codes despite differences in the melting models. Higher discrepancies were observed for the xM3 rod that can be attributed partly to power uncertainty and partly to the limited capability of the models to describe partial melting of the fuel during this ramp. Finally, possible code developments to improve simulation results are presented.

It has been argued that SDSS J1430+2303 possesses a supermassive black hole binary that has been predicted to merge within a few months or three years from 2022 January. We have conducted follow-up optical spectroscopic observations of SDSS J1430+2303 with the KOOLS-IFU on the Seimei Telescope in 2022 May, June, and July, and 2023 April. The observed spectrum around Hα shows a central broad component ∼103km s−1blueshifted from the narrow Hα line, as well as a broader double-peaked component with a separation of ∼± 5 × 103km s−1, similar to the spectrum reported in 2022 January. We investigate the variability of the complex broad Hα emission line relative to the continuum over the observation period. The continuum-normalized relative flux of the central broad component shows an increasing trend from 2022 May to July, which is interpreted to be caused by the decrease of the continuum; this is also supported by damping of the X-ray, UV, and optical light curves observed for the same period. From 2022 July to 2023 April, however, the central broad component decreased significantly. For the relative flux of the broader double-peaked component, no significant change appears at any epoch. These results suggest that the complicated broad line profile of SDSS J1430+2303 is generated from at least two distinct regions. While the central broad component originates from a broad-line region, the broader double-peaked component arises in the vicinity of the continuum source.

Goreisan is a Kampo medicine used to treat headaches associated with climate change. Here, by using an implantable complementary metal-oxide-semiconductor (CMOS) device, we evaluated the effects of Goreisan and loxoprofen on cerebral blood flow (CBF) dynamics associated with barometric pressure fluctuations in freely moving mice. In the vehicle group, decreasing barometric pressure increased CBF that was prevented by Goreisan and loxoprofen. Notably, Goreisan, but not loxoprofen, reduced CBF after returning to atmospheric pressure. These results indicate that, unlike the mechanism of action of antipyretic analgesics, Goreisan normalizes CBF abnormalities associated with barometric pressure fluctuations by actively reducing CBF increase.

Introduction:Portal annular pancreas (PAP) is a congenital anomaly resulting from aberrant fusion of the ventral and dorsal pancreatic buds around the portal vein (PV). PAP was classified into three types by Joseph et al., based on the location of the main pancreatic duct around the PV. The presence of PAP is important for the surgical procedure because it is associated with the postoperative pancreatic fistula. There are no standardized surgical procedures of resection and reconstruction for PAP. Case Presentation:We report 2 cases of subtotal stomach-preserving pancreatoduodenectomy in patients with PAP. One case of PAP was discovered coincidentally intraoperatively, and the other case was diagnosed before surgery. The first case was an 84-year-old male patient who underwent surgery for distal bile duct cancer. PAP was noticed intraoperatively when the uncinate process of the pancreas was detached from behind the PV. The second case was an 84-year-old female patient who also underwent surgery for distal bile duct cancer. We recognized PAP from preoperative computed tomography images. In both cases, the ductal anatomy was consistent with type IIIA PAP, and the dorsal pancreas was resected using a stapling device. During the postoperative period, there was no clinically relevant postoperative pancreatic fistula. Conclusion:PAP is rarely encountered intraoperatively; however, it is important to recognize it before surgery and take it into consideration when deciding upon the procedures for resection and reconstruction.

Inconsistent interface control in devices based on two-dimensional materials (2DMs) has limited technological maturation. Astounding variability of 2D/three-dimensional (2D/3D) interface properties has been reported, which has been exacerbated by the lack of direct investigations of buried interfaces commonly found in devices. Herein, we demonstrate a new process that enables the assembly and isolation of device-relevant heterostructures for buried interface characterization. This is achieved by implementing a water-soluble substrate (GeO2), which enables deposition of many materials onto the 2DM and subsequent heterostructure release by dissolving the GeO2substrate. Here, we utilize this novel approach to compare how the chemistry, doping, and strain in monolayer MoS2heterostructures fabricated by direct deposition vary from those fabricated by transfer techniques to show how interface properties differ with the heterostructure fabrication method. Direct deposition of thick Ni and Ti films is found to react with the monolayer MoS2. These interface reactions convert 50% of MoS2into intermetallic species, which greatly exceeds the 10% conversion reported previously and 0% observed in transfer-fabricated heterostructures. We also measure notable differences in MoS2carrier concentration depending on the heterostructure fabrication method. Direct deposition of thick Au, Ni, and Al2O3films onto MoS2increases the hole concentration by >1012cm–2compared to heterostructures fabricated by transferring MoS2onto these materials. Thus, we demonstrate a universal method to fabricate 2D/3D heterostructures and expose buried interfaces for direct characterization.

This study reported that the flow instability of the internal flow was first initiated around the leading edge of the splitter blades and finally resulted in tip-leakage flow instability at the leading edge of the main blades. The impeller stall consisted of a stall cell and rotated about 70% of the impeller rotational speed. Furthermore, a pressure disturbance occurs at the splitter blade leading edge before the main blade leading edge. The blockage within the passage of the suction side at the leading edge of the splitter blade was first increased because the leading-edge separation on the suction surface of the splitter blade was enlarged. The blockage within the passage of the pressure side was increased after that of the suction side stopped increasing. Therefore, the blockage development of both pressure and suction passage at the leading edge of the splitter blade was the main cause of the stall inception. Then, a longitudinal vortex was formed near the bleed slots and blocked the mainstream near tip side. Subsequently, the reverse flow region in the inducer was developed and extended to the impeller inlet. Finally, the flow angle to the main blade increased, the spillage occurred at a leading edge of a main blade, and the rotating stall was generated. The cause of impeller instability was the separation of the suction surface of splitter blade and the formation of a stagnation region on the pressure surface at the splitter leading edge.

This paper discusses the data informativity for continuous-time system identification. We extract a finite number of data samples from continuous-time signals using linear functionals and decide whether the data is informative for determining system matrices uniquely. We examine how and when the sampled data preserves the information of continuous-time signals enough to identify the system.

Although comprehensive genomic profiling has become standard in oncology for advanced solid tumors, the full potential of circulating tumor DNA (ctDNA)-based profiling in capturing tumor heterogeneity and guiding therapy selection remains underexploited, marked by a scarcity of evidence on its clinical impact and the assessment of intratumoral heterogeneity. The GOZILA study, a nationwide, prospective observational ctDNA profiling study, previously demonstrated higher clinical trial enrollment rates using liquid biopsy compared with tissue screening. This updated analysis of 4,037 patients further delineates the clinical utility of ctDNA profiling in advanced solid tumors, showcasing a significant enhancement in patient outcomes with a 24% match rate for targeted therapy. Patients treated with matched targeted therapy based on ctDNA profiling demonstrated significantly improved overall survival compared with those receiving unmatched therapy (hazard ratio, 0.54). Notably, biomarker clonality and adjusted plasma copy number were identified as predictors of therapeutic efficacy, reinforcing the value of ctDNA in reflecting tumor heterogeneity for precise treatment decisions. These new insights into the relationship between ctDNA characteristics and treatment outcomes advance our understanding beyond the initial enrollment benefits. Our findings advocate for the broader adoption of ctDNA-guided treatment, signifying an advancement in precision oncology and improving survival outcomes in advanced solid tumors.

Postsurgical treatment comprehensively benefits from the application of tissue-adhesive injectable hydrogels, which reduce postoperative complications by promoting wound closure and tissue regeneration. Although various hydrogels have been employed as clinical tissue adhesives, many exhibit deficiencies in adhesive strength under wet conditions or in immunomodulatory functions. Herein, we report the development of reactive oxygen species (ROS) scavenging and tissue-adhesive injectable hydrogels composed of polyamine-modified gelatin crosslinked with the 4-arm poly (ethylene glycol) crosslinker. Polyamine-modified gelatin was particularly potent in suppressing the secretion of proinflammatory cytokines from stimulated primary macrophages. This effect is attributed to its ability to scavenge ROS and inhibit the nuclear translocation of nuclear factor kappa-B. Polyamine-modified gelatin-based hydrogels exhibited ROS scavenging abilities and enhanced tissue adhesive strength on collagen casing. Notably, the hydrogel demonstrated exceptional tissue adhesive properties in a wet environment, as evidenced by its performance using porcine small intestine tissue. This approach holds significant promise for designing immunomodulatory hydrogels with superior tissue adhesion strength compared to conventional medical materials, thereby contributing to advancements in minimally invasive surgical techniques.

Abstract: Purpose: This study was designed to identify colonoscopic stigmata, indicating substantial invasion into the submucosa by T1 colorectal cancer with sessile morphology, including both flat and protruded types. Methods: A total of 111 Tis or T1 colorectal cancers were studied retrospectively. The lesions were divided into two groups: Group A (n = 83), Tis or T1 cancers with <1 mm submucosal invasion; and Group B (n = 28), T1 cancers with a ≥1 mm submucosal invasion. Printed photographs of the lesions were reviewed by five experienced colonoscopists who were blinded to histology. Deep depression, irregular surface, ulceration or erosion, fold convergence, and spontaneous bleeding were independently evaluated. Findings considered present by three or more reviewers were defined as positive. Kappa analysis was used to measure inter/intraobserver variability. Results: Positive rates of four findings but not fold convergence were significantly higher in Group B than in Group A. Irregular surface and spontaneous bleeding were significant independent predictors of ≥1 mm submucosal invasion, with diagnostic accuracies of 85.6 and 76.6 percent, respectively. Kappa analysis demonstrated fair-to-good inter/intraobserver agreement for spontaneous bleeding and fair-to-good intraobserver agreement for irregular surface. Conclusions: Irregular surface and spontaneous bleeding were colonoscopic stigmata, indicating ≥1 mm submucosal invasion in T1 colorectal cancer.

Introduction: A new algorithm for causality assessment of drugs and fatal cerebral haemorrhage (ACAD-FCH) was published in 2021. However, its use in clinical practice has not been verified. Objectives: This study aimed to explore the practical value of the ACAD-FCH when applying information available in clinical practice. Methods: The medical records of patients who died at the University of Tokyo Hospital in 2020 were reviewed, and cases with intracranial haemorrhage were selected. Two evaluators independently assessed these cases using three methods (the ACAD-FCH, Naranjo algorithm, and WHO-UMC scale). The number of ‘Yes’, ‘No’, and ‘No information/Do not know’ responses to each question by both evaluators were summed and compared. Inter-rater reliability was evaluated for each method using agreement rates and kappa coefficients with 95% confidence intervals (CI). Results: Among 316 deaths, 24 cases with intracranial haemorrhage were evaluated. The proportion of ‛No information/Do not know’ responses for each question was 35.6% (95% CI 31.4–40.6%) for the ACAD-FCH and 66.9% (95% CI 62.5–71.1%) for the Naranjo algorithm. The respective agreement rates and kappa coefficients were 0.917 (0.798–1.00) and 0.867 (0.675–1.00) for the ACAD-FCH, 0.708 (0.512–0.904) and 0.139 (−0.236 to 0.513) for the Naranjo algorithm, and 0.50 (0.284–0.716) and 0.326 (0.110–0.541) for the WHO-UMC scale, respectively. Conclusion: Our findings suggest the utility of the ACAD-FCH when assessing death cases with intracranial haemorrhage. However, larger studies including intra-rater assessments are warranted for further validation of this algorithm.

Low-power wide area networks (LPWANs), such as long-range wide area networks, are increasingly adopted as a communication standard for wireless sensor networks. LPWAN has been adopted for systems that periodically collect data from sensors, such as in environmental monitoring. However, continuous packet collisions may occur in periodic traffic systems owing to the adoption of a simple random-access scheme in LPWAN. In addition, the use of low-cost nodes results in clock drift, rendering the synchronization of nodes in the system challenging. Thus, this study proposes a wireless resource allocation scheme to avoid continuous packet collisions under the adverse effect of such clock drift. In the proposed scheme, the gateway determines the transmission offset and frequency channel for each node utilizing the periodic traffic feature and clock drift. Based on computer simulation results, the proposed scheme can improve the packet delivery rate by over 20% compared with benchmark methods.

In recent years, long-range wide-area network (LoRaWAN) has attracted considerable attention due to its ability to realize massive machine-type communication (MTC); however, its throughput is limited by the duty cycle (DC). Packet-level index modulation (PLIM) can increase throughput by utilizing a data packet’s frequency channel and transmission timing as the information-bearing index. In PLIM, a node selects a specific transmission resource (frequency channel and timing) within a frame and transmits a packet. If the node cannot transmit the packet at the specific transmission resource, it discards the packet. This packet discard results in throughput degradation of each node. Thus, this paper proposes an index mapping scheme that divides a frame into multiple subframes to provide each node with multiple transmission opportunities. A node performs channel activity detection (CAD) at the selected transmission resource within a subframe; if the node cannot transmit a packet, it moves to the next subframe. The proposed scheme adaptively maps the information bit sequence onto a transmission resource within each subframe based on the wireless environment and communication quality. Computer simulation results show that the proposed scheme improves throughput by increasing the transmission opportunities and reducing the packet discard rate under the constraint of DC.

Pancreatic islet transplantation is an effective treatment for type I diabetes mellitus. However, many problems associated with pancreatic islet engraftment remain unresolved. In this study, we developed a hydrogel microwell device for islet implantation, fabricated by crosslinking gelatin-methacryloyl (GelMA) and 2-hydroxyethyl methacrylate (HEMA) in appropriate proportions. The fabricated hydrogel microwell device could be freeze-dried and restored by immersion in the culture medium at any time, allowing long-term storage and transport of the device for ready-to-use applications. In addition, due to its non-swelling properties, the shape of the wells of the device was maintained. Thus, the device allowed pancreatic β cell lines to form spheroids and increase insulin secretion. Intraperitoneal implantation of the β cell line-seeded GelMA/HEMA hydrogel microwell device reduced blood glucose levels in diabetic mice. In addition, they were easy to handle during transplantation and were removed from the transplant site without peritoneal adhesions or infiltration by inflammatory cells. These results suggest that the GelMA/HEMA hydrogel microwell device can go from spheroid and/or organoid fabrication to transplantation in a single step.