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Dark field x-ray microscopy (DXFM) can visualize microstructural distortions in bulk crystals. Using the femtosecond x-ray pulses generated by x-ray free-electron lasers (XFELs), DFXM can achieve sub-μm spatial resolution and <100 fs time resolution simultaneously. In this paper, we demonstrate ultrafast DFXM measurements at the European XFEL to visualize an optically driven longitudinal strain wave propagating through a diamond single crystal. We also present two DFXM scanning modalities that are new to the XFEL sources: spatial 3D and 2D axial-strain scans with sub-μm spatial resolution. With this progress in XFEL-based DFXM, we discuss new opportunities to study multi-timescale spatiotemporal dynamics of microstructures. [ABSTRACT FROM AUTHOR]

The high-entropy alloy with composition AlCoCrFeNi2.1, additively manufactured with the laser powder-bed fusion technique, has a far-from-equilibrium BCC/FCC eutectic nanolamellar structure. We studied the high-pressure response of this alloy under both static compression and high-strain rate shock compression. The response to static compression using a diamond anvil cell was studied at pressures up to 302 GPa with synchrotron x-ray diffraction at the advanced photon source. The high-pressure FCC-only phase of the EHEA previously observed by Pope et al. [AIP Adv. 13, 035124 (2023)] is found to be stable up to the highest pressure achieved in this study with a volume compression of V/V0 = 0.587 at ambient temperature. The shock experiments were performed by using GEKKO XII lasers at the Institute of Laser Engineering, Osaka University. The principal Hugoniot equation-of-state of the EHEA was measured up to a pressure of 515 GPa and a compression of V/V0 = 0.613. Additionally, the thermal equation of state of the EHEA was measured up to 6.2 GPa and 1623 K using a large-volume Paris–Edinburgh cell to obtain the temperature dependence of bulk modulus and thermal expansion coefficients. The melting temperature for EHEA AlCoCrFeNi2.1 at a pressure of 5.6 GPa was measured to be 1648 ± 25 K. These results can be used to refine stochastic (or special) quasi-random structure (SQS) models for high-pressure high-temperature behavior of high-entropy alloys. [ABSTRACT FROM AUTHOR]

Background: There are scarce data on risk factors for epithelial ovarian cancer (EOC) in Asian populations. Our goal was to advance knowledge on reproductive -related risk factors for EOC in a large population of Asian women. Methods: This study used pooled individual data from baseline questionnaires in 11 prospective cohorts (baseline years, 1958–2015) in the Asia Cohort Consortium. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for age, parity and cohort. Results: After a mean = 17.0 years (SD = 6.3) of follow-up, 674 incident invasive EOC cases were identified among 325,626 women. In multivariable adjusted models we observed an inverse association with parity (5+ children vs. 0, HR = 0.44, 95% CI = 0.28–0.68, Ptrend < 0.001), and a positive association with increasing menopausal age (55+ years vs. <45, HR = 1.77, 95% CI = 1.05–3.01, Ptrend = 0.02) for risk of all EOC. Conclusions: In this large study of Asian women we identified an inverse association with parity and a positive association with higher menopausal age in relation to EOC risk. Further work is needed to understand EOC risk factors for rare histologic subtypes that occur more frequently in Asian populations. [ABSTRACT FROM AUTHOR]

Reproducible control of tissue delivery and retention of a therapeutic agent facilitates the maximization of the efficacy of pharmacotherapy. Despite the proposal of various chemical and physical methods for modulating drug delivery and retention, the choice of the physical modality for this purpose has been limited in clinical practice. Thus, this study proposes a novel strategy for modulating the retention of a model antigen in tissues by using non-tissue-damaging high-frequency ultrasoundAfter the injection of a fluorescently labeled model antigen, followed by brief treatment with high-frequency ultrasound (5–20 MHz), the clearance of the antigen was monitored using a real-time near-infrared (NIR) fluorescence imaging system in vivo. Further, ultrasound treatment increased tissue retention at the site of model antigen administration. The results suggested that high-frequency ultrasound could change the response to a macromolecule injected into the tissue, such as a vaccine, thereby modulating the immune response. The proposed ultrasound-based technology is translatable to clinical settings and benefits from well-established ultrasound technologies that have been employed in various medical applications for decades. Moreover, this approach can be broadly applied to enhance the therapeutic effects of current and future immune-mediated therapeutic systems. [ABSTRACT FROM AUTHOR]

Objective: To study the effect on biomaterial degradation and bone formation of different ratios between α-tricalcium phosphate (α-TCP) and deproteinized bovine bone mineral (DBBM) using various gelatins as a carrier. Materials and methods: Thirty-six critical-sized calvarial bone defects were randomly treated in 18 animals. Four biomaterials with different compositional relations of DBBM to α-TCP and granules to carrier were investigated: (1) 40 ± 10% DBBM/40 ± 10% α-TCP with 20 ± 10% gelatin type 1 in ratio 4:1 (B1/G1), (2) 20 ± 10% DBBM/60 ± 10% α-TCP with 20 ± 10% gelatin type 1 in ratio 4:1 (B2/G1), (3) 20 ± 10% DBBM/60 ± 10% α-TCP with 15 ± 10%/5 ± 5% gelatin type 2/ glycerine (B2/G2) and 4), 10 ± 10% DBBM/60 ± 10% α-TCP with 20 ± 10%/10 ± 10% gelatin type 2/ glycerine (B3/G2). As a positive control 50 ± 10% DBBM/50 ± 10% α-TCP without gelatin (PC, B1/G0) and as a negative control (NC) empty defects were chosen. All defects were covered with a collagen membrane. The samples were harvested 4 weeks post-surgically and examined by micro-CT and histomorphometric analysis. Results: New bone formation was evident in all defects. The mineralized tissue volume was significantly higher in the four tested biomaterials than in the NC group, but lower compared to the PC group. Histomorphometry showed similar levels of bone formation in all groups, whereas only the PC group reached a significantly higher total augmentation area than that of the NC. The PC group showed significantly higher mineralized tissue density and residual material area compared to the B3/G2 group, and more residual DBBM than the four tested biomaterials. Conclusions: New bone formation was not significantly affected either by different DBBM:α-TCP compositional ratios nor the presence of various gelatin carriers. Clinical relevance: Similar levels of osteoconductivity indicates the presumptive use of combined products in alveolar ridge augmentation to support bone formation. Gelatin with or without glycerine may be considered for its use as a carrier to the biomaterials frequently applied in peri-implant surgery. [ABSTRACT FROM AUTHOR]

Cell lines derived from fish tissues are resistant to premature senescence under typical culture conditions. Previously, we demonstrated that fish genomes do not have a p16INK4a/Arf locus and that the absence of this locus underlies the lack of senescence in cultured fish cells. However, other factors may also contribute to this resistance. In amniotes, promyelocytic leukemia (PML)-IV proteins are involved in the generation of PML nuclear bodies (PML NBs), which are connected with premature senescence. The lack of a pml gene in fish genomes may be involved in the mechanism of resistance to cellular senescence. Heterologous expression of human PML-IV in an Epithelioma papulosum cyprini cell line induced the formation of PML NB-like speckled structures. The cells displayed characteristic features of cellular senescence, namely, growth suppression, a large, flattened morphology, and increased SA-β-gal activity. Additionally, the levels of proinflammatory senescence-associated secretory phenotype (SASP) factors increased in the cells, suggesting a link between the absence of PML NBs and cellular resistance to senescence. Expression of the CCAT enhancer binding protein beta gene, which encodes a transcription factor of proinflammatory SASPs, was not increased, nor was there any elevation in the activity of NF-κB, a transcription factor for proinflammatory SASP factors and C/EBPβ. Epigenetic regulatory mechanisms may contribute to the induction of proinflammatory SASP factors by PML NBs. [ABSTRACT FROM AUTHOR]

The development of a selective separation and recovery method for platinum-group metals (PGMs) is in high demand to establish efficient and practical recycling technologies for different secondary materials such as industrial automobile catalysts. In this study, the highly selective precipitation of Pt(IV) from hydrochloric acid (HCl) solutions containing Pd(II), Pt(IV), and Rh(III) was successfully achieved using m-phenylenediamine dihydrochloride (MPDA) as a precipitant. Pt(IV) selectivity was observed at HCl concentrations higher than 7 M, whereas the co-precipitation of Rh(III) could not be suppressed using 3–7 M HCl solutions. Successful recovery of Pt(IV)-containing precipitates with high Pt yield (94.6%) and Pt purity (98.5%) was also achieved using an actual catalyst leaching solution with a complex composition containing PGMs, base metals, and rare metals. Structural analyses revealed that the Pt(IV)-containing precipitate forms ionic crystals composed of [PtCl6]2−/protonated m-phenylenediamine (MPDA-2H+) in a 1:1 ratio. The high stability and insolubility of the Pt(IV)-containing ionic crystals, owing to their highly packed structure, resulted in the highly selective precipitation of Pt(IV) at high HCl concentrations. [ABSTRACT FROM AUTHOR]

Background: Pharmaceutical formularies play a crucial role in guiding medication use by balancing clinical effectiveness and cost efficiency. Although formulary implementation has been increasing in Japan, comprehensive evaluations of its impact on both clinical and economic outcomes are limited. This study aimed to assess the effect of introducing an antimicrobial formulary at Yokohama City University Hospital on antibiotic usage and treatment outcomes in intra-abdominal infections. Methods: We conducted a segmented time-series analysis to evaluate changes in carbapenem usage, including doripenem, before and after formulary implementation in October 2018. Monthly antibiotic consumption was measured by antibiotic use density (AUD). The primary outcomes were changes in doripenem use and treatment efficacy for intra-abdominal infections. To assess treatment efficacy, we used non-inferiority analysis with propensity score matching based on age, sex, body mass index, cancer status, and baseline blood test results. The treatment outcomes were evaluated using predefined clinical indicators. Results: Following the formulary intervention, doripenem use significantly decreased from 10.8 to 4.9%, meropenem use slightly increased, and imipenem/cilastatin usage remained stable. Overall, carbapenem use significantly decreased during the study period. Treatment effectiveness for intra-abdominal infections remained non-inferior, with a higher proportion of patients classified as having an "effective" response post-intervention (86.6% vs. 79.4% pre-intervention). The confidence interval confirmed the non-inferiority margin, indicating no clinically significant reduction in treatment effectiveness following the formulary introduction. Conclusions: The introduction of an antibiotic formulary at Yokohama City University Hospital effectively reduced the use of doripenem without compromising the effectiveness of treatment of intra-abdominal infections. These findings suggest that formulary management can be a valuable strategy for optimizing antibiotic use while maintaining clinical outcomes and contributing to improved antimicrobial stewardship in healthcare settings. Further research is warranted to explore the broader implications of formulary implementation in Japanese healthcare practices. [ABSTRACT FROM AUTHOR]

We have developed transition-metal-free synthetic methodologies for dibenzoxazepinones utilizing salicylamides as starting materials and employing two distinct types of successive hypervalent iodine-mediated arylocyclizations. This synthetic protocol encompasses selective phenol O-arylation of salicylamides with diaryliodonium salts, followed by electrophilic aromatic amination utilizing chemically or electronically generated hypervalent iodine reagents in the second stage of the process. [ABSTRACT FROM AUTHOR]

The unique architecture of the liver consists of hepatic lobules, dividing the hepatic features of metabolism into 2 distinct zones, namely the pericentral and periportal zones, the spatial characteristics of which are broadly defined as metabolic zonation. R-spondin3 (Rspo3), a bioactive protein promoting the Wnt signaling pathway, regulates metabolic features especially around hepatic central veins. However, the functional impact of hepatic metabolic zonation, regulated by the Rspo3/Wnt signaling pathway, on whole-body metabolism homeostasis remains poorly understood. In this study, we analyze the local functions of Rspo3 in the liver and the remote actions of hepatic Rspo3 on other organs of the body by using murine models. Rspo3 expression analysis shows that Rspo3 expression patterns are spatiotemporally controlled in the murine liver such that it locates in the pericentral zones and converges after feeding, and the dynamics of these processes are disturbed in obesity. We find that viral-mediated induction of Rspo3 in hepatic tissue of obesity improves insulin resistance and prevents body weight gain by restoring attenuated organ insulin sensitivities, reducing adipose tissue enlargement and reversing overstimulated adaptive thermogenesis. Denervation of the hepatic vagus suppresses these remote effects, derived from hepatic Rspo3 induction, toward adipose tissues and skeletal muscle, suggesting that signals are transduced via the neuronal communication consisting of afferent vagal and efferent sympathetic nerves. Furthermore, the non-neuronal inter-organ communication up-regulating muscle lipid utilization is partially responsible for the ameliorations of both fatty liver development and reduced skeletal muscle quality in obesity. In contrast, hepatic Rspo3 suppression through Cre-LoxP-mediated recombination system exacerbates diabetes due to glucose intolerance and insulin resistance, promotes fatty liver development and decreases skeletal muscle quality, resulting in obesity. Taken together, our study results reveal that modulation of hepatic Rspo3 contributes to maintaining systemic glucose metabolism and body composition via a newly identified inter-organ communication mechanism. Metabolism in the liver is divided between the pericentral and periportal zones, but how does this zonation affect whole body physiology? This study shows that proper liver zonation, which is regulated by Rspo3, contributes to glucose metabolism homeostasis. [ABSTRACT FROM AUTHOR]

We have carried out spectral analysis of coronavirus disease 2019 (COVID-19) notifications in all 47 prefectures in Japan. The results confirm that the power spectral densities (PSDs) of the data from each prefecture show exponential characteristics, which are universally observed in the PSDs of time series generated by nonlinear dynamical systems, such as the susceptible/exposed/infectious/recovered (SEIR) epidemic model. The exponential gradient increases with the population size. For all prefectures, many spectral lines observed in each PSD can be fully assigned to a fundamental mode and its harmonics and subharmonics, or linear combinations of a few fundamental periods, suggesting that the COVID-19 data are substantially noise-free. For prefectures with large population sizes, PSD patterns obtained from segment time series behave in response to the introduction of public and workplace vaccination programs as predicted by theoretical studies based on the SEIR model. The meaning of the relationship between the exponential gradient and the population size is discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: The soil bacterium Bacillus thuringiensis (Bt) produces protein crystals during sporulation. Cry toxins, a major component of these protein crystals, are insecticidal proteins with pore-forming activity. Cry toxins are environmentally friendly biopesticides used to create Bt-incorporating genetically modified crops (BT-GMCs) that confer resistance to insect pests. However, public acceptance of BT-GMCs is lacking. A major concern over BT-GMCs is the allergenicity of Cry toxins. Specifically, the pore-forming activity of Cry toxins may directly induce intestinal mast cells to release histamine. In this study, three lepidopteran-specific Cry toxins, Cry1Aa, Cy1Ab, and Cry1Ac, were treated with simulated digestive fluids under different conditions. Cry1A toxins exhibited differing sensitivity to simulated digestive fluids, and digests of Cry1A toxins contained the α4–α5 helical hairpin of domain I, which is thought to be the transmembrane domain. To determine whether Cry1A toxins directly induce histamine release, intact and digested Cry1A toxins were applied to RBL-2H3 cultured rat mast cells. However, no histamine secretion from these mast cells was detected, even when samples were analyzed using HPLC. The results of our study provide important data supporting the safety of Cry1A toxins and potentially BT-GMCs, and reducing anxiety over their safety should help increase public acceptance. Public acceptance of genetically modified crops engineered with Bacillus thuringiensis (Bt) insecticidal protein genes (BT-GMCs), which confer resistance to various lepidopteran insect pests, is generally lacking. As a major concern over BT-GMCs is the allergenicity of insecticidal proteins, alleviating safety concerns should help increase public acceptance. In this study, three lepidopteran-specific Bt toxins, Cry1Aa, Cy1Ab, and Cry1Ac, were treated with simulated digestive fluids under various conditions. Western blotting using antiserum raised against individual segments (α-helices of domain I and β-sheets of domains II and III) of Cry1Aa showed that digestion produces a variety of polypeptides. In particular, the transmembrane α4–α5 of domain I, which may retain the ability to form pores, was the most resistant to digestion. Intact Cry1A toxins and these digests were then applied to RBL-2H3 cultured rat mast cells to determine whether the toxins directly induce histamine release. However, fluorescence microscopy revealed no specific binding of Cry1A toxins to RBL-2H3 cultured rat mast cells. In addition, neither the OPA method nor HPLC analysis detected significant histamine release from mast cells treated with Cry1A toxins and these digests. Our results provide important data supporting the safety of Cry1A toxins and potentially BT-GMCs. [ABSTRACT FROM AUTHOR]

The optical coherence tomography (OCT)-based calcium scoring system was developed to guide optimal lesion preparation strategies for percutaneous coronary intervention (PCI) of calcified lesions. However, the score was derived retrospectively, and a prospective investigation is lacking. The CORAL (UMIN000053266) study was a single-arm, prospective, multicenter study that included patients with calcified lesions with OCT-calcium score of 1–2 to investigate whether these lesions could be optimally treated with a balloon-only preparation strategy using a non-compliant/scoring/cutting balloon. The primary endpoint was strategy success (successful stent placement with a final percent diameter stenosis [%DS] < 20% and Thrombolysis In Myocardial Infarction flow grade III without crossover to rotational atherectomy/orbital atherectomy/intravascular lithotripsy [RA/OA/IVL]). A superiority analysis for the primary endpoint was performed by comparing the study cohort with a performance goal of 83.3%. One hundred and eighteen patients with 130 lesions were enrolled. The mean age was 79.0 ± 10.3 years, and 79 patients (66.9%) were male. The OCT-calcium score was 1 for 81 lesions (62.3%) and 2 for 49 lesions (37.7%). The %DS improved from 47.0 ± 14.8% preprocedure to 11.1 ± 5.6% postprocedure. Stent expansion ≥ 70% was achieved in 90.2%. The strategy success rate was 93.1% (95% confidence interval: 87.3–96.8), and superiority against the performance goal was achieved without any crossover to RA/OA/IVL (P = 0.0027). The OCT-calcium score could identify mild/moderately calcified lesions treatable by PCI with the balloon-first strategy using a non-compliant/scoring/cutting balloon for predilatation, with a high strategy success rate. These results support the intravascular imaging-based treatment algorithm for calcified lesions proposed by CVIT. [ABSTRACT FROM AUTHOR]

Taste bud cells are classified into four types by their ultrastructural features. Immunohistochemical detection of taste-signaling molecules is used to distinguish cell types of taste bud cells; however, the characteristics of taste cell types such as the immunoreactivity for taste-signaling molecules have long remained unclear. We investigated the detailed characteristics of taste cells in rat vallate taste buds by electron microscopy and immunohistochemistry for gustducin, neural cell adhesion molecule (NCAM) and vesicle-associated membrane protein 2 (VAMP2), which are known as markers of Type II cells, Type III cells and both cell types, respectively. Triple immunostaining for these molecules discriminated seven kinds of cell, including the totally immunopositive cell. Electron microscopy revealed Type III cells with a typical synaptic structure and subsurface cisterna as a specialized contact between a nerve and a Type II cell. The present study clarified the existence of cells with features of both Type II and Type III cells as a subtype of taste bud cells in the rat taste bud. [ABSTRACT FROM AUTHOR]

Background: Although durvalumab has shown promise in improving survival rates in patients with locally advanced non-small cell lung cancer (NSCLC), the ideal duration of treatment has yet to be established. Objective: The primary objective of this study was to determine the optimal number of durvalumab cycles following definitive chemoradiotherapy for locally advanced NSCLC. Patients and Methods: A total of 178 patients who received chemoradiotherapy for stage III NSCLC at 15 institutions were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were assessed according to the number of consolidation durvalumab cycles by landmark analysis. Landmark analyses were performed at 3-month intervals from the start of durvalumab treatment to 9 months. Results: The median number of durvalumab cycles was 16 (range 1–27). PFS and OS were significantly better in patients who received ≥20 cycles of durvalumab than in those who did not (p < 0.001 and p < 0.001, respectively). In landmark analysis, significant differences were observed in PFS from 0 to 6 months and OS from 3 to 6 months between patients who continued durvalumab after the time point and those who did not. However, there were no significant differences in PFS or OS between patients who received 13–19 or ≥20 cycles of durvalumab at 9 months. Conclusions: Durvalumab should be administered for more than 6 months to contribute to the main benefits of consolidation therapy following chemoradiotherapy. [ABSTRACT FROM AUTHOR]

This study used the electrodeposition resin molding method (EDRM), an easy and effective technique, to create composite materials. Because it's a new technique, consideration of the impact of various production parameters on composite qualities was necessary. The effects of altering these EDRM voltage and electrical current conditions on the static and dynamic properties of composites were examined and tuned to fit the objective. Three distinct voltage values (100, 150, and 200 V) and five different current conditions (0.5, 0.75, 1.00, 1.25, and 1.50 A) were used for the manufacturing variables. In accordance with that, the effectiveness of heat treatment was also evaluated using two distinct temperature profiles. The bending strength of composites was somewhat influenced by the voltage and current conditions of the EDRM, but not in a particularly significant way. However, the bending strength of composites was significantly impacted by the heat curing temperature as well as the heat curing time. [ABSTRACT FROM AUTHOR]

Experimental investigations of silica under high pressure and temperature offer crucial insights into modeling of Earth and super‐Earths' interiors. Despite extensive studies on Hugoniots of silica polymorphs like fused‐silica (2.20 g/cm3), quartz (2.65 g/cm3) and stishovite (4.29 g/cm3) up to a terapascal, unexplored region of melting and liquid of silica at high pressures is leaved because of the Hugoniots dependence on ambient density. This emphasizes the urgence to supplement the phase diagram to constrain silica properties under extreme conditions. Here, the Hugoniot and shock temperature of coesite (2.92 g/cm3) were studied by laser shock compression experiments up to 950 GPa. Our findings confirm shock‐induced superheating in coesite, revealing a higher Grüneisen parameter and lower electrical conductivity compared to those of fused‐silica and quartz along an isothermal line (<2 × 104 K). These results suggest unique properties of shocked coesite, which imply a warmer and longer‐lived silica magma ocean of earlier rocky‐planets. Plain Language Summary: Silica is a critical mineral in Earth's interior. Studying its behavior under extreme conditions offers essential insights into planetary processes, enhancing our understanding of Earth and other rocky worlds in our solar system and beyond. In our research, we focused on a particular form of silica called coesite, compressing it to extraordinarily high pressures ‐ up to 950 GPa by using the GEKKO laser's powerful laser drive. Our experiments uncovered unique properties of silica in its liquid state, such as a high Grüneisen parameter and electrical conductivity after melting, indicating potential support for dynamo processes despite retaining semi‐metallic traits. Our findings suggest that magma oceans could have formed earlier and endured longer than previously assumed, where the high Grüneisen parameter accelerates temperature rises during planetary formation processes like accretion or giant impacts. Existence of a conducting mantle of SiO2‐bearing liquid could result in complex magnetic fields on such planets, posing challenges for detecting and modeling exoplanetary magnetic fields. This research significantly advances planetary science, deepening our grasp of planetary evolution and the diverse processes shaping rocky worlds across the cosmos. Key Points: Shocked coesite exhibits superheating before melting, suggesting incomplete crystallization under rapid compressionGrüneisen parameter estimated by coesite‐quartz Hugoniot reveals higher γ, affecting thermodynamic models of rocky planetsHigh conductivity of shocked coesite after melting indicates band gap closure, with a persistent pseudo‐gap in the liquid phase [ABSTRACT FROM AUTHOR]

When plants are exposed to drought stress, there is a trade-off between plant growth and stress responses. Here, we identified a signaling mechanism for the initial steps of the drought-growth trade-off. Phosphoproteomic profiling revealed that Raf13, a B1 subgroup Raf-like kinase, is dephosphorylated under drought conditions. Raf13 and the related B1-Raf Raf15 are required for growth rather than the acquisition of osmotolerance. We also found that Raf13 interacts with B55-family regulatory subunits of protein phosphatase 2A (PP2A), which mediates hyperosmolarity-induced dephosphorylation of Raf13. In addition, Raf13 interacts with an AGC kinase INCOMPLETE ROOT HAIR ELONGATION HOMOLOG 1 (IREH1), and Raf13 and IREH1 have similar functions in regulating cellular responses that promote plant growth. Overall, our results support a model in which Raf13-IREH1 activity promotes growth under nonstressed conditions, whereas PP2A activity suppresses Raf13-IREH1 during osmotic stress to modulate the physiological "trade-off" between plant growth and stress responses. [ABSTRACT FROM AUTHOR]

Although organic light-emitting devices (OLEDs) have been commercialized for display applications, electron-injection layers (EILs) still rely on alkali metals or their compounds to lower driving voltages, and hence reactivity with atmospheric moisture is a primary concern, especially in flexible devices. As an alternative strategy, combining electron transport materials (ETMs) based on 1,10-phenanthroline (Phen) derivatives with silver (Phen/Ag) has attracted much attention for developing air-stable EILs. However, most studies have focused on Phen derivatives. Herein, we developed a non-Phen ETM named DPmPy-BP based on a 2,6-di(pyrimidin-2-yl)pyridine skeleton. Combined with Ag (DPmPy-BP/Ag) as a potentially air-stable EIL, this ETM exhibited superior electron-injection properties and remarkable stability in preliminary green phosphorescent OLEDs achieving a maximum external quantum efficiency (EQE) of 20% and an operational lifetime (LT50) of approximately 17 000 hours at 1000 cd m−2, which surpass those of Phen/Ag devices and are comparable to devices using a conventional alkali metal compound 8-hydroxyquinolinolato-lithium (Liq) as the EIL (DPmPy-BP/Liq). [ABSTRACT FROM AUTHOR]

Metabolic surgery, including laparoscopic sleeve gastrectomy (LSG), may improve hypertension (HTN) complicated by severe obesity; however, insufficient deliberation exists regarding the therapeutic effect of post-metabolic surgery on HTN. This study aimed to analyze the factors correlated with HTN remission and recurrence post-LSG in patients who have severe obesity, and to create a classification system to predict HTN remission and recurrence. Of the 102 patients who underwent LSG at Iwate Medical University Hospital between 2008 and 2020, 62 were enrolled in this study. Factors correlated with HTN remission and recurrence post-LSG were retrospectively analyzed. The HTN remission rate 12-months post-LSG was 40.3%. The remission cohort had a lower number of preoperative antihypertensive drugs (ADs) than that of the non-remission cohort (one and two tablets, respectively; p< 0.001). Additionally, the remission cohort had a statistically significantly smaller visceral fat area (VFA) than that of the non-remission cohort, at all time points. Logistic regression analysis revealed that the number of preoperative ADs and VFA were independent predictors of remission. The HTN recurrence rate 36-months post-LSG was 36.0%. In the recurrence cohort, the number of preoperative ADs and VFA were higher and larger than that in the non-recurrence cohort, respectively. Stratification, based on the number of preoperative ADs and VFA, revealed that the HTN remission and recurrence rates in the sub-cohort with a small number of preoperative ADs and small VFA (100% and 16.7%, respectively) were better than those in the sub-cohort with a large number of preoperative ADs and large VFA (5.3% and 100%, respectively). In Japanese patients with severe obesity, the number of preoperative ADs and VFA were correlated with HTN remission and recurrence post-LSG. Stratification, by combining the number of preoperative ADs and VFA, may be useful in predicting HTN remission and recurrence. [ABSTRACT FROM AUTHOR]

In eukaryotes, mRNAs with long poly(A) tails are translationally active, but deadenylation and uridylation of these tails generally cause mRNA degradation. However, the fate of uridylated mRNAs that are not degraded quickly remains obscure. Here, using tail-seq and microinjection of the 3′ region of mRNA, we report that some mRNAs in starfish are re-polyadenylated to be translationally active after deadenylation and uridylation. In oocytes, uridylated maternal cyclin B mRNAs are stable without decay, and they are polyadenylated to be translated after hormonal stimulation to resume meiosis, whereas they are deadenylated and re-uridylated at the blastula stage, followed by decay. Similarly, deadenylated and uridylated maternal ribosomal protein mRNAs, Rps29 and Rpl27a, were stable and inactive after hormonal stimulation, but they had been polyadenylated and active before hormonal stimulation. At the morula stage, uridylated maternal ribosomal protein mRNAs were re-polyadenylated, rendering them translationally active. These results indicate that uridylated mRNAs in starfish exist in a poised state, allowing them to be recycled or decayed. [ABSTRACT FROM AUTHOR]

Objectives: Collagen membranes are extensively used for guided bone regeneration procedures, primarily for horizontal bone augmentation. More recently, it has been demonstrated that collagen membranes promote bone regeneration. Present study aimed at assessing if structural modifications of collagen membranes may enhance their osteoconductive capacity. Methods: Twenty‐four adult Wistar rats were used. Bilateral calvaria defects with a diameter of 5 mm were prepared and covered with prototypes of collagen membranes (P1 or P2). The P1 membrane (positive control) presented a lower onset temperature of protein denaturation and a higher solubility than the P2 membrane (test). The contralateral defects were left uncovered (NC). After 1 and 4 weeks, the animals were euthanized. A microcomputed tomography analysis of the harvested samples was performed within and above the bony defect. Undecalcified ground sections were subjected to light microscopy and morphometric analysis. Results: Bone formation was observed starting from the circumferential borders of the defects in all groups at 1‐week of healing. The foci of ossification were observed at the periosteal and dura mater sites, with signs of collagen membrane mineralization. However, there was no statistically significant difference between the groups. At 4 weeks, remnants of the collagen fibers were embedded in the newly formed bone. In the P2 group, significantly more bone volume, more new bone, and marrow spaces compared to the NC group were observed. Furthermore, the P2 group showed more bone volume ectocranially then the P1 group. Conclusions: Bone formation subjacent to a P2 membrane was superior than subjacent to the P1 membrane and significantly better compared to the control. Modifications of the physico‐chemical properties may enhance the osteoconductive competence of collagen membranes, supporting bone formation outside the bony defects. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated the incidence of lymph node metastasis and long‐term outcomes in patients with T1 colorectal cancer where endoscopic submucosal dissection (ESD) resulted in noncurative treatment. It is focused on those with deep submucosal invasion, a factor considered a weak predictor of lymph node metastasis in the absence of other risk factors. Methods: This nationwide, multicenter, prospective study conducted a post‐hoc analysis of 141 patients with T1 colorectal cancer ≥20 mm where ESD of the lesion resulted in noncurative outcomes, characterized by poor differentiation, deep submucosal invasion (≥1000 μm), lymphovascular invasion, high‐grade tumor budding, or positive vertical margins. Clinicopathologic features and patient prognoses focusing on lesion sites and additional surgery requirements were evaluated. Lymph node metastasis incidence in the low‐risk T1 group, identified by deep submucosal invasion as the sole high‐risk histological feature, was assessed. Results: Lymph node metastasis occurred in 14% of patients undergoing additional surgery post‐noncurative endoscopic submucosal dissection for T1 colorectal cancer. In the low‐risk T1 group, in the absence of other risk factors, the frequency was 9.7%. The lymph node metastasis rates in patients with T1 colon and rectal cancers did not differ significantly (14% vs. 16%). Distant recurrence was observed in one patient (2.3%) in the ESD only group and in one (1.0%) in the additional surgery group, both of whom had had rectal cancer removed. Conclusion: The risk of lymph node metastasis or distant occurrence was not negligible, even in the low‐risk T1 group. The findings suggest the need for considering additional surgery, particularly for rectal lesions (Clinical Trial Registration: UMIN000010136). [ABSTRACT FROM AUTHOR]

The principal causes of death among 68,555 patients with diabetes and 164,621 patients without diabetes who died in 208 hospitals throughout Japan between 2011 and 2020 were determined based on a survey of hospital records. The most frequent cause of death in patients with diabetes was malignant neoplasms (38.9%) (lung 7.8%, pancreas 6.5%, liver 4.1%), followed, in order of descending frequency, by infectious diseases (17.0%) and then vascular diseases (10.9%) (cerebrovascular diseases 5.2%, ischemic heart diseases 3.5%, renal failure 2.3%). The proportion of deaths from malignant neoplasms and vascular diseases has trended upward and downward, respectively. Almost all deaths from ischemic heart diseases were due to myocardial infarction, and the proportion of deaths from heart diseases other than ischemic heart diseases was relatively high (9.0%), with most cases due to heart failure. Diabetic coma associated with hyperglycemia accounted for only 0.3% of deaths. The proportion of deaths from malignant neoplasms, infectious diseases, renal failure, ischemic heart diseases, and heart failure was significantly higher in patients with diabetes than in those without diabetes, and the proportion of deaths from cerebrovascular diseases was significantly lower in patients with diabetes. With regard to the relationship between the age and cause of death in patients with diabetes, malignant neoplasms were the most frequent cause of death in all age groups, and the incidence was around 50% for those in their 50s and 60s. The incidence of death due to infectious diseases was highest in patients older than their 70s. The incidence of death due to vascular diseases for patients in their 40s and 50s was higher than that due to infectious diseases. The highest incidence of death due to ischemic heart diseases was observed for patients in their 40s, and that due to renal failure and heart failure in patients older than their 70s. Compared with patients without diabetes, patients with diabetes demonstrated a higher incidence of death due to pancreatic cancer, infectious diseases, renal failure, ischemic heart diseases, and heart failure, and a lower incidence of death due to cerebrovascular diseases in all age groups. The average age at death of patients with diabetes was 74.4 years old in men and 77.4 years old in women, which were lower than the average lifespan of the Japanese general population in 2020 by 7.2 and 10.3 years, respectively. However, these differences were smaller than in previous surveys. The average age at death due to all causes, especially due to ischemic heart diseases, cerebrovascular diseases, heart failure, infectious diseases, and diabetic coma, was lower in patients with 'poorer' glycemic control than in those with 'better' glycemic control. In the total survey population, the average age at death of patients with diabetes was significantly higher than that of patients without diabetes. The average age at death due to malignant neoplasms and cerebrovascular diseases was higher in patients with diabetes than in those without diabetes and that due to renal failure, ischemic heart diseases, and infectious diseases was lower in patients with diabetes than in those without diabetes. [ABSTRACT FROM AUTHOR]

Although various complications associated with intraductal papillary mucinous neoplasms have been reported, including acute pancreatitis, duct perforation, and fistula formation, spontaneous bleeding, especially life-threatening bleeding, is infrequent. In this case, emergency pancreatic resection might be one of the therapeutic options, which is associated with poor postoperative outcomes. An 87-year-old woman presented to our hospital with severe anemia (hemoglobin, 4.5 g/dl). Contrast-enhanced computed tomography revealed a large cystic lesion in the pancreatic head measuring 15 cm, with some solid components and an adjacent hematoma, suggestive of intra-cystic hemorrhage of the intraductal papillary mucinous neoplasm. The patient was hemodynamically unstable and had hypotension. After transcatheter arterial embolization, the patient became hemodynamically stable. Subsequently, an elective pylorus-preserving pancreaticoduodenectomy was successfully performed. Preoperative embolization was effective for subsequent elective pancreaticoduodenectomy in patients with severe intraductal papillary mucinous neoplasm bleeding. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a minimally invasive treatment that elicits tumor apoptosis using laser light exclusively applied to the tumor site. IR-783, a heptamethine cyanine (HMC) dye, impedes the proliferation of breast cancer cells, even without light. Although studies have investigated the efficacy of IR-783 in cell and animal studies, its efficacy in clinical settings remains unknown. Therefore, we aimed to determine the efficacy of PDT using IR-783 liposomes. An HMC dye, excited by long-wavelength infrared light and with high tissue permeability, was used for PDT after liposomization to enhance tumor tissue accumulation. PDT was performed using IR-783 in two patients with either tongue or breast cancer, one each. IR-783 liposomes inhibited cell proliferation in tongue cancer cells even when not excited by light. Tumor size was markedly reduced in both cases, with no significant adverse events. Furthermore, the patient with tongue cancer exhibited improved respiratory, swallowing, and speech functions, which were attributed not only to the shrinkage of the tumor but also to the improvement in airway narrowing. In conclusion, PDT using IR-783 liposomes effectively reduces tumor size in tongue and breast cancers. [ABSTRACT FROM AUTHOR]

Intersection control systems have been actively studied in recent years as they could potentially replace traffic signals via the utilization of the communication and automatic driving capabilities of connected and autonomous vehicles (CAVs). In these studies, conflicting travel trajectories at intersections that could cause accidents and delays were safely and efficiently avoided by controlling the vehicle's speed. However, routing approaches for avoiding conflicts at intersections have only been discussed in a few studies. To investigate the feasibility of avoiding intersection conflicts through network-level route allocation, we propose a cooperative route allocation model using reinforcement learning than can model the relationship between the complex traffic environment and optimal route solutions. Models aimed at decreasing the total travel time and those with high delay importance owing to conflicts in travel times were trained and verified under multiple traffic conditions. The results indicate that our model effectively allocates vehicles to their optimal routes, reducing the number of intersection conflicts and decreasing the average travel time by up to approximately 40 s compared to random allocation, demonstrating the potential of reinforcement learning for cooperative route allocation in the management of multiple vehicles. [ABSTRACT FROM AUTHOR]

Background: The primary tumor resection (PTR) of de novo stage IV breast cancer (DnIV BC) is controversial, and previous studies have suggested that the neutrophil-to-lymphocyte ratio (NLR) could be a poor-prognosis factor for BC. We investigated PTR's surgical advantage related to clinical outcomes, the surgery timing in responders to systemic therapy, and whether the NLR can predict the benefit of surgery for DnIV BC. Patients and methods: We retrospectively analyzed the cases of the DnIV BC patients who received systemic therapies and/or underwent PTR at our institution between January 2004 and December 2022. Blood tests and NLR measurement were performed before and after each systematic therapy and/or surgery. Results: Sixty patients had undergone PTR local surgery (Surgery group); 81 patients had not undergone surgical treatment (Non-surgery group). In both groups, systemic treatment was performed as chemotherapy (95%) and/or endocrine therapy (92.5%) (p < 0.0001). The groups' respective median progression-free survival (PFS) durations were 88 and 30.3 months (p = 0.004); their overall survival (OS) durations were 100.1 and 31.8 months (p = 0.0002). The Surgery-group responders to systemic therapy lasting > 8.1-months showed significantly longer OS (p = 0.044). The PFS and OS were significantly associated with the use of postoperative systemic therapy (p = 0.0012) and the NLR (p = 0.018). A low NLR (≤ 3) was associated with significantly better prognoses (PFS and OS; p < 0.0001). Conclusions: A longer effective duration of systemic therapy (> 8.1 months) and a low pre-surgery NLR (≤ 3.0) could predict PTR's surgical advantage for DnIV BC. These variables may help guide decisions regarding the timing of surgery for DnIV BC. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine whether the 21-Gene Breast Recurrence Score® assay from primary breast tissue predicts the prognosis of patients with hormone receptor-positive and human epidermal growth factor 2-negative advanced breast cancers (ABCs) treated with fulvestrant monotherapy (Group A) and the addition of palbociclib combined with fulvestrant (Group B), which included those who had progression in Group A from the Japan Breast Cancer Research Group-M07 (FUTURE trial). Methods: Progression-free survival (PFS) and overall survival (OS) were compared using the log-rank test and Cox regression analysis based on original recurrence score (RS) categories (Low: 0–17, Intermediate: 18–30, High: 31–100) by treatment groups (A and B) and types of ABCs (recurrence and de novo stage IV). Results: In total, 102 patients [Low: n = 44 (43.1%), Intermediate: n = 38 (37.5%), High: n = 20 (19.6%)] in Group A, and 45 in Group B, who had progression in Group A were analyzed. The median follow-up time was 23.8 months for Group A and 8.9 months for Group B. Multivariate analysis in Group A showed that low-risk [hazard ratio (HR) 0.15, 95% confidence interval (CI) 0.04–0.53, P = 0.003] and intermediate-risk (HR 0.22, 95% CI 0.06–0.78) with de novo stage IV breast cancer were significantly associated with better prognosis compared to high-risk. However, no significant difference was observed among patients with recurrence. No prognostic significance was observed in Group B. Conclusion: We found a distinct prognostic value of the 21-Gene Breast Recurrence Score® assay by the types of ABCs and a poor prognostic value of the high RS for patients with de novo stage IV BC treated with fulvestrant monotherapy. Further validations of these findings are required. [ABSTRACT FROM AUTHOR]

This study examines the holographic representation of the quantum theory of transmission lines, which play a crucial role in quantum computing and quantum information. By utilizing Yurke and Denker's quantum circuit network theory within the framework of continuous Multi-scale Entanglement Renormalization Ansatz (cMERA) in AdS space, we analyze the quantization and interactions of transmission lines. The metric is revealed to be described by the inductance of the quantum circuit, which is AdS space in its 0-limit. These results provide new insights into handling and controlling complex phenomena in quantum circuits, potentially advancing the understanding of quantum computing and quantum communication. [ABSTRACT FROM AUTHOR]

Tricholoma matsutake is an important wild edible mycorrhizal mushroom in Japan. The domestic matsutake harvest has been declining for 80 y. Nagano Prefecture, a central region of Japan, is the area that has been most productive of matsutake during the past 20 y. To study how matsutake harvesting was affected by forest management, an experimental site was established in a pine forest in Nagano Prefecture in 1980. Two plots were established: a managed plot (MP) in which all trees except pine were cut, pine trees were thinned, and soil litter layer was removed; and a control plot (CP) with no forest management. The numbers of matsutake fruiting bodies were recorded annually in both plots for 41 y. The annual matsutake harvest was stable in the MP but decreased in the CP, while the number of shiro increased in the MP and was stable at the low level in the CP. These trends were suggested to be affected significantly by the thicker humus layer and large root biomass other than pines in the CP. This is the longest record of matsutake harvest in the managed forest, which reveals the importance of such long-term forest management for the sustainable matsutake harvesting. [ABSTRACT FROM AUTHOR]

The article explores the correlation between genomic alterations and clinical features of hepatitis-associated aplastic anaemia (HAAA), focusing on the loss of HLA class I allele expression in male patients. The study found a higher prevalence of certain high-risk HLA alleles, particularly HLA-B*40:02, in patients with HAAA compared to those with idiopathic aplastic anaemia (iAA). The research sheds light on the immunopathological mechanisms underlying HAAA and emphasizes the significance of HLA-B*40:02 in the development of this condition, particularly in young men. Further studies are needed to deepen our understanding of the molecular pathogenesis of HAAA. [Extracted from the article]

Reciprocal inhibition (RI) between leg muscles is crucial for smooth movement. Pedaling is a rhythmic movement that can increase RI in healthy individuals. Transcutaneous spinal cord stimulation (tSCS) stimulates spinal neural circuits by targeting the afferent fibers. Pedaling with simultaneous tSCS may modulate the plasticity of the spinal neural circuit and alter neural activity based on movement and muscle engagement. This study investigated the RI changes after pedaling and tSCS and determined the phase of pedaling in which tSCS should be applied for optimal RI modulation in healthy individuals. Eleven subjects underwent three interventions: pedaling combined with tSCS during the early phase of lower extension (phase 1), pedaling combined with tSCS during the late phase of lower flexion (phase 4) of the pedaling cycle, and pedaling combined with sham tSCS. The RI from the tibialis anterior to the soleus muscle was assessed before, immediately after, 15 min, and 30 min after the intervention. RI increased immediately after phase 4 and pedaling combined with sham tSCS, whereas no changes were observed after phase 1. These results demonstrate that tSCS modulates RI changes induced by pedaling in a stimulus phase-dependent manner in healthy individuals. However, the mechanism involved in this intervention needs to be explored to achieve higher efficacy. [ABSTRACT FROM AUTHOR]

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Nuclear proliferation literature typically differentiates supply-side and demand-side factors influencing the spread of nuclear weapons. These distinct approaches to the proliferation puzzle raise the following empirical questions: Does nuclear supply stimulate states' demand for nuclear weapons? Conversely, does the demand for nuclear weapons really facilitate the acquisition of nuclear supply? If such endogeneity exists between the demand-side and supply-side determinants, how would it cause empirical bias in the estimation of their effects on nuclear proliferation? This article aims to unpack endogenous mechanisms of nuclear demand and nuclear supply over the course of nuclear proliferation. In particular, it examines two potential sources of endogeneity: (1) simultaneous interactions between states' nuclear development decisions and nuclear technological capability and (2) selection bias in nuclear development. To address each source of endogeneity, simultaneous equation models and the duration models with selection are estimated, respectively. Contrary to what recent supply-side literature suggests, the empirical analyses reveal that states' nuclear demand is primarily driven by external security threats instead of their existing nuclear technology, and that their successful acquisition of nuclear technology mainly follows as the result of nuclear development efforts but does not necessarily depend on individual supply-side factors. This article addresses the typical inference issues in nuclear proliferation research and contributes to our synthetic understanding of proliferation mechanisms. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Clustering-based subclassification of type 2 diabetes, which reflects pathophysiology and genetic predisposition, is a promising approach for providing personalised and effective therapeutic strategies. Ahlqvist's classification is currently the most vigorously validated method because of its superior ability to predict diabetes complications but it does not have strong consistency over time and requires HOMA2 indices, which are not routinely available in clinical practice and standard cohort studies. We developed a machine learning (ML) model to classify individuals with type 2 diabetes into Ahlqvist's subtypes consistently over time. Methods: Cohort 1 dataset comprised 619 Japanese individuals with type 2 diabetes who were divided into training and test sets for ML models in a 7:3 ratio. Cohort 2 dataset, comprising 597 individuals with type 2 diabetes, was used for external validation. Participants were pre-labelled (T2Dkmeans) by unsupervised k-means clustering based on Ahlqvist's variables (age at diagnosis, BMI, HbA1c, HOMA2-B and HOMA2-IR) to four subtypes: severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD) and mild age-related diabetes (MARD). We adopted 15 variables for a multiclass classification random forest (RF) algorithm to predict type 2 diabetes subtypes (T2DRF15). The proximity matrix computed by RF was visualised using a uniform manifold approximation and projection. Finally, we used a putative subset with missing insulin-related variables to test the predictive performance of the validation cohort, consistency of subtypes over time and prediction ability of diabetes complications. Results: T2DRF15 demonstrated a 94% accuracy for predicting T2Dkmeans type 2 diabetes subtypes (AUCs ≥0.99 and F1 score [an indicator calculated by harmonic mean from precision and recall] ≥0.9) and retained the predictive performance in the external validation cohort (86.3%). T2DRF15 showed an accuracy of 82.9% for detecting T2Dkmeans, also in a putative subset with missing insulin-related variables, when used with an imputation algorithm. In Kaplan–Meier analysis, the diabetes clusters of T2DRF15 demonstrated distinct accumulation risks of diabetic retinopathy in SIDD and that of chronic kidney disease in SIRD during a median observation period of 11.6 (4.5–18.3) years, similarly to the subtypes using T2Dkmeans. The predictive accuracy was improved after excluding individuals with low predictive probability, who were categorised as an 'undecidable' cluster. T2DRF15, after excluding undecidable individuals, showed higher consistency (100% for SIDD, 68.6% for SIRD, 94.4% for MOD and 97.9% for MARD) than T2Dkmeans. Conclusions/interpretation: The new ML model for predicting Ahlqvist's subtypes of type 2 diabetes has great potential for application in clinical practice and cohort studies because it can classify individuals with missing HOMA2 indices and predict glycaemic control, diabetic complications and treatment outcomes with long-term consistency by using readily available variables. Future studies are needed to assess whether our approach is applicable to research and/or clinical practice in multiethnic populations. [ABSTRACT FROM AUTHOR]

Effective separation of linear and branched C6 alkanes is of importance in the improvement of the research octane number of gasoline during the isomerization of linear alkanes. However, developing a novel material for this separation remains a challenge. Activated crystals with a collapsed "channel-like sorption site" by assembling p-bromothiacalix[4]arene propyl ether molecules after removing cyclohexane (CyC6) molecules that act as templates are classified as a nonporous adaptive crystal. The activated crystals are capable of storing branched alkanes such as isohexane (2-C6), 3-methylpentane (3-C6), and 2,2- and 2,3-dimethylbutane (2,2- and 2,3-C6) vapors in the single-component system. In contrast, no sorption of n-hexane (n-C6) as one of the linear alkanes was observed. In these branched alkanes, the crystals preferentially adsorbed more branched alkanes, specifically 2,2-C6 and 2,3-C6, compared to mono-branched alkanes like 2-C6 and 3-C6 in two-component systems. Surprisingly, slight adsorption of n-C6 was observed in the system. The retention capacity of mono- and di-branched and linear alkanes in the crystals follows the order: 2,2-C6 ≈ 2,3-C6 > 3-C6 > 2-C6 ≫; n-C6. [ABSTRACT FROM AUTHOR]

Helicenes, with their unique helical structures, have long captured the interest of synthetic chemists, not only as end products, but also as versatile platforms for further chemical transformations. However, transforming [6]helicene into planar coronene typically requires harsh conditions and poses significant challenges. Herein, we demonstrate that replacing the terminal benzene ring of [6]helicene with a thiophene ring enables its photochemical transformation into coronene. Sulfur oxidation of the thiophene ring enables the corresponding thermal transformation, and the terminal tetrafluorination of the opposite benzene ring further accelerates this process, yielding 1,2‐difluorocoronene, as confirmed by X‐ray crystallography. The transformation begins with an intramolecular Diels–Alder reaction, whose activation energy is significantly lowered by these structural changes. Our findings underscore the utility of strategic modifications such as sulfur oxidation and fluorination in promoting this "helix‐to‐disc" conversion and opening new avenues for synthesizing functional polycyclic aromatics. [ABSTRACT FROM AUTHOR]

Hyperthermia stimulates ventilation in humans. This hyperthermia-induced hyperventilation may be mediated by the activation of peripheral chemoreceptors implicated in the regulation of respiration in reaction to various chemical stimuli, including reductions in arterial pH. Here, we investigated the hypothesis that during passive heating at rest, the increases in arterial pH achieved with sodium bicarbonate ingestion, which could attenuate peripheral chemoreceptor activity, mitigate hyperthermia-induced hyperventilation. We also assessed the effect of sodium bicarbonate ingestion on cerebral blood flow responses, which are associated with hyperthermia-induced hyperventilation. Twelve healthy men ingested sodium bicarbonate (0.3 g/kg body weight) or sodium chloride (0.208 g/kg). One hundred minutes after the ingestion, the participants were passively heated using hot-water immersion (42°C) combined with a water-perfused suit. Increases in esophageal temperature (an index of core temperature) and minute ventilation (V̇E) during the heating were similar in the two trials. Moreover, when V̇E is expressed as a function of esophageal temperature, there were no between-trial differences in the core temperature threshold for hyperventilation (38.0 ± 0.3 vs. 38.0 ± 0.4°C, P = 0.469) and sensitivity of hyperthermia-induced hyperventilation as assessed by the slope of the core temperature-V̇E relation (13.5 ± 14.2 vs. 15.8 ± 15.5 L/min/°C, P = 0.831). Furthermore, middle cerebral artery mean blood velocity (an index of cerebral blood flow) decreased similarly with heating duration in both trials. These results suggest that sodium bicarbonate ingestion does not mitigate hyperthermia-induced hyperventilation and the reductions in cerebral blood flow index in resting heated humans. NEW & NOTEWORTHY: Hyperthermia leads to hyperventilation and associated cerebral hypoperfusion, both of which may impair heat tolerance. This hyperthermia-induced hyperventilation may be mediated by peripheral chemoreceptors, which can be activated by reductions in arterial pH. However, our results suggest that sodium bicarbonate ingestion, which can increase arterial pH, is not an effective intervention in alleviating hyperthermia-induced hyperventilation and cerebral hypoperfusion in resting heated humans. [ABSTRACT FROM AUTHOR]

Several epidemiologic studies have investigated the circulating levels of albumin, bilirubin, and uric acid (UA) in relation to cancer risk; however, they have provided equivocal evidence. In this prospective case-cohort study, we measured the plasma levels of albumin, bilirubin, and UA and investigated their association with cancer incidence in 3584 case patients and 4270 randomly selected participants with a median follow-up of 15.8 years. The adjusted hazard ratios (HRs) and 95% CIs of total cancer for the highest quartile (Q4) versus lowest quartile (Q1) was 0.77 (95% CI, 0.67-0.90; P <.001 for trend) for albumin. This association was attenuated after excluding liver cancer cases with lower plasma albumin levels. Plasma bilirubin levels were positively related to liver cancer but inversely to total cancer after excluding liver cancer with, for Q4 versus Q1, an adjusted HR of 0.86 (95% CI, 0.74-0.99; P  = .015 for trend). Plasma UA levels were not dose-responsively associated with total cancer risk. Higher plasma bilirubin levels were associated with a decreased risk of total cancer after excluding liver cancer, which is likely attributed to the antioxidant properties of bilirubin. [ABSTRACT FROM AUTHOR]

Pimobendan is not currently approved for use in cats, although its usefulness in feline hypertrophic cardiomyopathy has been suggested. Reports indicate an increase in arrhythmic events following oral administration to healthy cats. Given the greater potency of intravenous administration compared to oral intake, it is conceivable that the incidence of arrhythmias may be increased following pimobendan injection. Therefore, this study aimed to investigate the proarrhythmic effects of pimobendan injection in cats. Five clinically healthy cats underwent physical examination, echocardiography, blood pressure measurements, and 24-hour Holter electrocardiography immediately before and after receiving pimobendan as an intravenous bolus dose of 0.15 mg/kg twice daily for 3 days. Additionally, a 24-hour Holter electrocardiography recording was conducted on the third day of pimobendan or placebo IV administration to assess heart rate, arrhythmias, and heart rate variability. Following pimobendan administration, there was a significant increase in total 24-hour heart rate. Echocardiography revealed a significant increase in mitral valve annulus systolic velocity (S') on the ventricular septal wall side, indicative of enhanced contractility. Only one cat exhibited paroxysmal ventricular tachycardia and an increase in the frequency of arrhythmic events. Conversely, in the remaining cats, a decreasing trend in the number of arrhythmias was observed. These findings indicate that intravenous administration of pimobendan may not be implicated in the onset of arrhythmias. Nevertheless, further research is warranted to explore the effects of intravenous pimobendan administration in cats with myocardial disease. [ABSTRACT FROM AUTHOR]

The principal causes of death among 68,555 patients with diabetes and 164,621 patients without diabetes who died in 208 hospitals throughout Japan between 2011 and 2020 were determined based on a survey of hospital records. 1. The most frequent cause of death in patients with diabetes was malignant neoplasms (38.9%) (lung 7.8%, pancreas 6.5%, liver 4.1%), followed, in order of descending frequency, by infectious diseases (17.0%) and then vascular diseases (10.9%) (cerebrovascular diseases 5.2%, ischemic heart diseases 3.5%, renal failure 2.3%). The proportion of deaths from malignant neoplasms and vascular diseases has trended upward and downward, respectively. Almost all deaths from ischemic heart diseases were due to myocardial infarction, and the proportion of deaths from heart diseases other than ischemic heart diseases was relatively high (9.0%), with most cases due to heart failure. Diabetic coma associated with hyperglycemia accounted for only 0.3% of deaths. 2. The proportion of deaths from malignant neoplasms, infectious diseases, renal failure, ischemic heart diseases, and heart failure was significantly higher in patients with diabetes than in those without diabetes, and the proportion of deaths from cerebrovascular diseases was significantly lower in patients with diabetes. 3. In regard to the relationship between the age and cause of death in patients with diabetes, malignant neoplasms were the most frequent cause of death in all age groups, and the incidence was around 50% for those in their 50s and 60s. The incidence of death due to infectious diseases was highest in patients older than their 70s. The incidence of death due to vascular diseases for patients in their 40s and 50s was higher than that due to infectious diseases. The highest incidence of death due to ischemic heart diseases was observed for patients in their 40s, and that due to renal failure and heart failure in patients older than their 70s. 4. Compared to patients without diabetes, patients with diabetes demonstrated a higher incidence of death due to pancreas cancer, infectious diseases, renal failure, ischemic heart diseases and heart failure and lower incidence of death due to cerebrovascular diseases in all age groups. 5. The average age at death of patients with diabetes was 74.4 years old in men and 77.4 years old in women, which were lower than the average lifespan of the Japanese general population in 2020 by 7.2 and 10.3 years, respectively. However, these differences were smaller than in previous surveys. 6. The average age at death due to all causes, especially due to ischemic heart diseases, cerebrovascular diseases, heart failure, infectious diseases, and diabetic coma, was lower in patients with "poorer" glycemic control than in those with "better" glycemic control. 7. In the total survey population, the average age at death of patients with diabetes was significantly higher than that of patients without diabetes. The average age at death due to malignant neoplasms and cerebrovascular diseases was higher in patients with diabetes than in those without diabetes and that due to renal failure, ischemic heart diseases, and infectious diseases was lower in patients with diabetes than in those without diabetes. [ABSTRACT FROM AUTHOR]