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Abstract We present X‐ray observations of the upper atmospheric density disturbance caused by the explosive eruption of the Hunga Tonga‐Hunga Ha'apai (HTHH) volcano on 15 January 2022. From 14 January to 16 January, the Chinese X‐ray astronomy satellite, Insight‐HXMT, was observing the supernova remnant Cassiopeia A. The X‐ray data obtained during Earth's atmospheric occultations allowed us to measure neutral densities in the altitude range of ∼90–150 km. The density profiles above 110 km altitude obtained before the major eruption are in reasonable agreement with expectations by both GAIA and NRLMSIS 2.0 models. In contrast, after the HTHH eruption, a severe density depletion was found up to 1,000 km away from the epicenter, and a relatively weak depletion extending up to ∼7,000 km for over 8 hr after the eruption. In addition, density profiles showed wavy structures with a typical length scale of either ∼20 km (vertical) or ∼1,000 km (horizontal). This may be caused by Lamb waves or gravity waves triggered by the volcanic eruption.

Key Clinical Message CYP3A4 and CYP3A5 are the most abundant and important enzymes of the CYP3A subfamily, distributed in the liver, intestinal mucosa and kidney, and involved in tacrolimus metabolism. Here, we report a case of tacrolimus dosage refractoriness due to a genetic polymorphism of CYP3A5.

Key Clinical Message Recently, hypoxia‐inducible factor prolyl hydroxylase (HIF‐PH) inhibitors have been used for renal anemia, but side effects have also been reported. We report on the association of central hypothyroidism and cholesterol with roxadustat. Based on this case and previous reports, we believe that patients receiving roxadustat should have their thyroid function and cholesterol levels checked regularly.

Abstract Therapeutic benefits and underlying biomechanism(s) of antibody drug conjugates (ADC) in combination with other targeted therapeutics are largely unknown. Here, the synergy between ADC and epigenetic drug decitabine (DAC), a clinically approved DNA methylation inhibitor, in multiple preclinical models of melanoma specifically investigated. Mechanistically, the underlying biomechanisms of how DAC cooperatively worked with ICAM1 antibody conjugated DNA topoisomerase I inhibitor DXd (I1‐DXd) is elucidated. DAC treatment significantly enhanced anti‐tumor efficacy of I1‐DXd by upregulating antigen expression, enhancing antibody internalization and potentiating tumor sensitivity by epigenetically reprogramming of melanoma. Meanwhile, I1‐DXd/DAC combination also exerted regulatory effects on tumor microenvironment (TME) by enhancing tumor infiltration of innate and adaptive immune cells and improving penetration of ADCs with a boosted antitumor immunity. This study provides a rational ADC combination strategy for solid tumor treatment.

Background Observational studies have reported associations between primary aldosteronism (PA) and cardiovascular outcomes, including coronary artery diseases (CAD), congestive heart failure (CHF), and stroke. However, establishing causality remains a challenge due to the lack of randomized controlled trial data on this topic. We thus aimed to investigate the causal relationship between PA and the risk of developing CAD, CHF, and stroke. Methods and Results Cross‐ancestry meta‐analysis of genome‐wide association studies combining East Asian and European ancestry (1560 PA cases and 742 139 controls) was conducted to identify single‐nucleotide variants that are associated with PA. Then, using the identified genetic variants as instrumental variables, we conducted the 2‐sample Mendelian randomization analysis to investigate the causal relationship between PA and incident CAD, CHF, and stroke among both East Asian and European ancestry. Summary association results were extracted from large genome‐wide association studies consortia. Our cross‐ancestry meta‐analysis of East Asian and European populations identified 7 genetic loci significantly associated with the risk of PA, for which the genes nearest to the lead variants were CASZ1, WNT2B, HOTTIP, LSP1, TBX3, RXFP2, and NDP. Among the East Asian population, the pooled odds ratio estimates using these 7 genetic instruments of PA were 1.07 (95% CI, 1.03–1.11) for CAD, 1.10 (95% CI, 1.01–1.20) for CHF, and 1.13 (95% CI, 1.09–1.18) for stroke. The results were consistent among the European population. Conclusions Our 2‐sample Mendelian randomization study revealed that PA had increased risks of CAD, CHF, and stroke. These findings highlight that early and active screening of PA is critical to prevent future cardiovascular events.

Abstract Research on predator–prey interactions between sharks and cetaceans remain limited. Here, we report on a video of a shortfin mako shark circling a finless porpoise with a damaged caudal fin in the Seto Inland Sea, Japan. The finless porpoise was neither emaciated nor inactive, but unable to swim effectively due to the complete lack of a caudal fin. Some circumstantial evidence, including a bite mark on the porpoise's head, strongly suggests that the mako shark attacked it. Furthermore, the possible time difference between the two injuries the porpoise sustained may reflect the shark's hunting tactics. While mako sharks primarily feed on small fish and cephalopods, this observation suggests they also may prey on live cetaceans more often than previously thought.

Abstract Objective We retrospectively analyzed breast cancer patients who received adjuvant radiotherapy to determine the incidence of lymphocytopenia and its risk factors. Methods We reviewed 812 patients with breast cancer who received postoperative radiotherapy. Patients were divided into two groups based on the use of chemotherapy, and a generalized linear regression model was used to explore predictive factors for grade 2 or higher lymphocytopenia. We also examined the effect of lymphocytopenia on overall survival. Results Grade 2 or higher lymphocytopenia was observed in 19.4% of patients who did not receive chemotherapy and 45.1% of patients who received chemotherapy. In multivariate analysis, bilateral disease, regional lymph node irradiation, and baseline lymphocytopenia were associated with lymphocytopenia in patients who did not receive cytotoxic chemotherapy. Regional lymph node irradiation, baseline lymphocytopenia, use of antimetabolites, and use of molecular‐targeted agents were associated with lymphocytopenia in patients treated with chemotherapy. In the survival analysis, lymphocytopenia was associated with worse overall survival only in patients treated with cytotoxic chemotherapy (p = 0.039), and not in patients who did not receive chemotherapy (p = 0.77). Conclusion The analysis revealed the incidence and risk factors of lymphocytopenia after postoperative radiotherapy in patients with breast cancer.

Introduction Patients with translocation renal cell carcinoma (tRCC) have a poor prognosis without standardized treatment. Case presentation The first case was of a 72‐year‐old woman who underwent robot‐assisted partial nephrectomy for a left renal tumor and was pathologically diagnosed with tRCC. Recurrence was observed in the left retroperitoneal soft tissue. After treatment with avelumab–axitinib, continued progression‐free survival was confirmed at the 90‐week follow‐up. The second case was of a 41‐year‐old woman referred to our hospital and presented with translocation renal cell carcinoma metastasis to a para‐aortic lymph node. After treatment with avelumab–axitinib, continued progression‐free survival was confirmed at the 43‐week follow‐up. Conclusion The outcomes of these cases indicate that avelumab–axitinib therapy has a long‐term antitumor effect in some patients with tRCC.

Abstract This study examined the effects of exercise and detraining at a young age on fat accumulation in various organs. Four‐week‐old male Otsuka Long‐Evans Tokushima Fatty (OLETF) rats were assigned to either the non‐exercise sedentary (OLETF Sed) or exercise groups. The exercise group was subdivided into two groups: exercise between 4 and 12 weeks of age (OLETF Ex) and exercise between 4 and 6 weeks of age followed by non‐exercise between 6 and 12 weeks of age (OLETF DT). Body weight was significantly lower in the OLETF Ex group than in the OLETF Sed group at 12 weeks of age. Fat accumulation in the epididymal white adipose tissue, liver, and brown adipose tissue was suppressed in the OLETF Ex group. During the exercise period, body weight and food intake in the OLETF DT group were significantly lower than those in the OLETF Sed group. However, food intake was significantly higher in the OLETF DT group than in the OLETF Sed group after exercise cessation, resulting in extreme obesity with fatty liver and brown adipose tissue whitening. Detraining after early‐onset exercise promotes hyperphagia, causing extreme obesity. Overeating should be avoided during detraining periods in cases of exercise cessation at a young age.

Abstract A 76‐year‐old woman with cT1bN2M1b stage IVA spindle cell carcinoma of the right lower lobe of the lung, no driver gene mutation, and programmed death ligand 1

Key Clinical Message Squamous cell papilloma with elongated villous projections may occur in the hypopharynx and present with symptoms observable on physical examination.

Background Few prediction models for individuals with early‐stage out‐of‐hospital cardiac arrest (OHCA) have undergone external validation. This study aimed to externally validate updated prediction models for OHCA outcomes using a large nationwide dataset. Methods and Results We performed a secondary analysis of the JAAM‐OHCA (Comprehensive Registry of In‐Hospital Intensive Care for Out‐of‐Hospital Cardiac Arrest Survival and the Japanese Association for Acute Medicine Out‐of‐Hospital Cardiac Arrest) registry. Previously developed prediction models for patients with cardiac arrest who achieved the return of spontaneous circulation were updated. External validation was conducted using data from 56 institutions from the JAAM–OHCA registry. The primary outcome was a dichotomized 90‐day cerebral performance category score. Two models were updated using the derivation set (n=3337). Model 1 included patient demographics, prehospital information, and the initial rhythm upon hospital admission; Model 2 included information obtained in the hospital immediately after the return of spontaneous circulation. In the validation set (n=4250), Models 1 and 2 exhibited a C‐statistic of 0.945 (95% CI, 0.935–0.955) and 0.958 (95% CI, 0.951–0.960), respectively. Both models were well‐calibrated to the observed outcomes. The decision curve analysis showed that Model 2 demonstrated higher net benefits at all risk thresholds than Model 1. A web‐based calculator was developed to estimate the probability of poor outcomes (https://pcas‐prediction.shinyapps.io/90d_lasso/). Conclusions The updated models offer valuable information to medical professionals in the prediction of long‐term neurological outcomes for patients with OHCA, potentially playing a vital role in clinical decision‐making processes.

Abstract Plexiform fibromyxoma is a rare mesenchymal tumor identified in recent years and presents as a gastrointestinal submucosal tumor that is typically located in the gastric antrum. We report a case of gastric plexiform fibromyxoma in which the diagnosis was difficult despite repeated tissue sampling. Before visiting our hospital, the patient had been followed up for 3 years without a definitive diagnosis despite serial examinations, including computed tomography, endoscopy, endoscopic ultrasound, and endoscopic ultrasound‐guided fine‐needle aspiration. Endoscopic ultrasound‐guided fine‐needle aspiration was reperformed, and endoscopic submucosal dissection for deep biopsy was conducted for differential diagnosis of the tumor. However, histological analysis with immunostaining of tumor samples obtained using these techniques cannot provide a reliable diagnosis. Finally, the tumor was resected surgically because of its increasing size, and subsequent microscopic analysis revealed a multinodular plexiform growth pattern of spindle‐like cells with myxoid stroma. Immunohistochemically, the tumor cells were positive for smooth muscle actin but negative for c‐kit, CD34, and S100. Based on these findings, the patient was diagnosed with plexiform fibromyxoma. No evidence of residual or recurrent tumors was observed at 24 months postoperatively.

Abstract Background Immune checkpoint inhibitors (ICIs) can cause severe immune‐related adverse events (irAEs). However, biomarkers for irAEs common to different types of ICIs and cancers have not been reported. This study examined whether eosinophils can be used as a predictor of irAEs. Methods Six hundred fourteen patients with cancer (esophageal, gastric, head and neck, lung, melanoma, renal cell, urothelial, and other cancer) received anti‐PD‐1, anti‐PD‐L1, or anti‐CTLA‐4 plus anti‐PD‐1 therapy. The patients were divided into two groups depending on whether they experienced irAEs (irAE group) or not (non‐irAE group). Eosinophils were examined before the two‐course treatment. Results Patients in the irAE group who received anti‐PD‐1 or anti‐CTLA‐4 plus anti‐PD‐1 therapy had higher eosinophils before the two‐course treatment than those in the non‐irAE group (p

Abstract Background There is little evidence of abiraterone acetate (AA) plus prednisone for patients with non‐metastatic castration‐resistant prostate cancer (nmCRPC). In this study, we conducted a comparative analysis of real‐world survival outcomes between AA plus prednisone and enzalutamide (Enz) in patients with nmCRPC, utilizing our consortium dataset. Materials and Methods The clinical records of 133 nmCRPC patients treated with first‐line Enz or AA plus prednisone were analyzed. The primary endpoints of the study were overall survival (OS) and cancer‐specific survival (CSS). Cumulative incidence function (CIF) using Fine and Gray models was also utilized to assess non‐cancer‐caused death considering the competing risk of cancer‐caused death. Results During a median follow‐up of 36 months, 34 patients (25.6%) had deceased, with a median OS of 99 months in the entire cohort. There were no significant differences in comorbidities between the Enz and AA groups. Time to PSA progression (TTPP: HR 0.81, 95% CI 0.51–1.30, P = 0.375) and CSS (HR 1.32, 95% CI 0.55–3.44, P = 0.5141) were comparable between the two groups. However, intriguingly, there was a trend towards shorter OS in patients treated with AA plus prednisone compared to Enz (HR 0.57, 95% CI 0.29–1.12, P = 0.0978, median of 99 and 69 months in Enz and AA groups, respectively). CIF analysis revealed that nmCRPC patients treated with AA plus prednisone were more likely to result in non‐cancer‐caused death than those treated with Enz (HR 5.22, 95% CI 1.88–14.50, P = 0.0014). Conclusions Our real‐world survival analysis suggests that while AA plus prednisone may demonstrate comparable treatment efficacy to Enz in the context of nmCRPC, there may be an increased risk of non‐cancer‐caused death. Physicians should take into consideration this information when making treatment decisions for patients with nmCRPC.

Abstract This study reviews the current methods of numerical simulations for crystalline‐Si (c‐Si) photovoltaic (PV) cells. The increased demand for PV devices has led to significant improvements in the performance of solar cell devices. The main contribution comes from c‐Si solar cells, which constitute 90% of the industry. Numerical analysis is effective for predicting, developing, and optimizing cell performances as the cell structures become more complex and include several parameters. However, conventional methods cannot simulate improved device structures with complex configurations. Additional physics is necessary to evaluate these cell structures. This study introduces methods for evaluating these cell structures using physical modeling and highlights the latest examples of simulations of c‐Si solar cells.

Abstract Introduction Combined treatment using anti‐programmed death‐ligand 1 antibody (anti‐PD‐L1) and platinum‐etoposide is the current standard first‐line treatment for patients with extensive‐stage (ES) small cell lung cancer (SCLC). However, the best treatment for relapsed ES‐SCLC after the first‐line treatment remains unclear. There are some approved chemotherapeutic agents that can be used against ES‐SCLC, and treatment with irinotecan is well established as both a monotherapy and a combined therapy, in combination with platinum. Therefore, we conduct a phase II study with irinotecan in the second‐ or later‐line setting for patients with ES‐SCLC who have been previously treated with combined treatment. Methods Our study will enroll total 30 patients who are diagnosed with ES‐SCLC and have experienced disease progression after the combined treatment. Patients will receive irinotecan on days 1, 8, and 15, which will be repeated every 4 weeks. Doses of irinotecan (100/80/60 mg/m2) will be determined according to the type of UGT1A1 gene polymorphism, and the treatment will be discontinued following disease progression, intolerance, withdrawal of patient consent, and based on the investigator's decision. The primary endpoint of the study is the response rate, and the secondary endpoints are overall survival, progression‐free survival, and safety. Discussion Since the present first‐line treatment has been changed to the combined treatment, the second‐ or later‐line treatment should be re‐evaluated for patients with relapsed SCLC. Irinotecan is a major chemotherapeutic agent used for SCLC. This study demonstrates and re‐evaluates the clinical benefits of irinotecan after combined treatment with anti‐PD‐L1 and platinum‐etoposide for patients with ES‐SCLC. Registration details This study was registered in the Japan Registry of Clinical Trials (no. jRCT s071210090) on November 4, 2021.

Abstract Recent developments in environmental DNA (eDNA) analysis allow more rapid and extensive biomonitoring than traditional capture‐based surveys do. However, detection of eDNA not derived from living organisms may lead to false‐positive inferences of species presence. Such limitations may be overcome by utilizing RNA molecules present in the environment (environmental RNA [eRNA]) because of their physiochemical instability. Nevertheless, the biomonitoring performance of eRNA analysis remains unclarified because of the substantial lack of knowledge regarding basic eRNA properties, such as its persistence and degradation mechanisms. Here, we performed a factorial aquarium experiment to assess the effects of water temperature (10, 20, and 30°C) and pH (4, 7, and 10) conditions on the degradation of zebrafish (Danio rerio) eDNA and eRNA, targeting the mitochondrial cytochrome b (CytB) and nuclear beta‐2‐microglobulin (b2m) genes. A linear mixed‐model analysis showed that the degradation of eRNA was significantly faster than that of eDNA. Higher water temperatures promoted both eDNA and eRNA degradation, and alkaline conditions substantially promoted eRNA but not eDNA degradation. This might be explained by the physicochemical characteristics of DNA and RNA molecules, the membranous structure surrounding them, and their susceptibility to environmental microbial activity. Moreover, the relative concentrations of zebrafish eRNA to eDNA decreased over time, inferring that the ratio of eRNA to eDNA concentrations can be used for estimating the elapsed time since the genomic material was released and the freshness of the target eDNA signal in the field. Nevertheless, given that the confidence intervals of the eDNA and eRNA decay rates tended to overlap for each treatment level, this study indicates that fish eRNA is not always degraded rapidly and is, in fact, more abundant in water than previously expected. This result favors the application of eRNA analysis to indicate living biotic assemblages.

Abstract Aims No solid evidence‐based opinion was raised regarding predictors of the degree of ascites reduction with tolvaptan. This retrospective cohort study aimed to examine whether serum copeptin concentration is a useful predictor of this. Methods The study population consisted of 80 patients with liver cirrhosis treated with tolvaptan for hepatic ascites effusions at Nara Medical University Hospital from May 2014 to December 2018. Forty‐three patients who lost >1.5 kg of body weight in the first week after starting tolvaptan were classified as good responders and the remaining 37 as poor responders. Various laboratory parameters were measured immediately before the start of tolvaptan therapy to examine factors associated with predicting its efficacy. Results In the univariate analysis, no significant differences with respect to age (67.6 vs. 69.8 years, p > 0.05), sex, body mass index (24.8 vs. 23.7 kg/m2, p > 0.05), Child–Pugh score (9.4 vs. 9.7, p > 0.05), and Model for End‐stage Liver Disease score (11 vs. 12, p > 0.05) were found between the two groups. Conversely, aspartate transferase and alanine transaminase (ALT) levels were significantly lower in the good response group (52.9 ± 56.3 vs. 68.8 ± 50.7 U/L, p

Abstract Aims Heart failure with a preserved ejection fraction (HFpEF) is associated with chronic inflammation. We aimed to investigate the association between pericoronary adipose tissue attenuation (PCATA) on coronary computed tomography angiography as a novel noninvasive marker of pericoronary inflammation and the presence of HFpEF. Methods and results This retrospective study included 607 outpatients (median age, 65 years; 50% male) who underwent both echocardiography and coronary computed tomography angiography. Patients with obstructive coronary artery disease were excluded from this study. PCATA was compared between patients with and without HFpEF, which was diagnosed according to the Heart Failure Association (HFA)‐PEFF score. PCATA was assessed at the proximal 40‐mm segments of all three major coronary arteries on coronary computed tomography angiography. Patients with HFpEF had higher PCATA in all coronary arteries compared to the control participants: left anterior descending artery (LAD), −65.2 ± 6.9 Hounsfield units (HU) vs. −68.1 ± 6.7 HU; left circumflex artery (LCX), −62.7 ± 6.8 HU vs. −65.4 ± 6.6 HU; and right coronary artery (RCA), −63.6 ± 8.5 HU vs. −65.5 ± 7.7 HU (P

Abstract The nitrogen‐heteroatom single bonds of 1,2‐azoles and isoxazolines underwent methylene insertion in the presence of CH2I2 (6 equiv.) and diethylzinc (3 equiv.) to produce a wide variety of the ring‐expanded six‐membered heterocycles. Density functional theory calculations suggest that the methylene insertion proceeds via cleavage of nitrogen‐heteroatom single bonds followed by ring closure.

Abstract Forced vital capacity has been utilized as a parameter of disease progression in idiopathic pulmonary fibrosis (IPF); however, its measurement is difficult when patients do not understand or cooperate. Dynamic digital radiography (DDR) enables sequential chest X‐ray imaging during breathing, with lower radiation doses compared to conventional fluoroscopy or computed tomography. There is accumulating evidence showing that parameters obtained from DDR, particularly those related to diaphragmatic dynamics, are correlated with pulmonary function parameters, and are useful for pathophysiological evaluation. We herein present two cases that suggest parameters obtained from DDR during supine normal tidal breathing may predict disease progression of IPF.

Abstract Background and Aim Anticoagulant users with nonvalvular atrial fibrillation (NVAF) sometimes suffer from gastrointestinal bleeding (GIB) and have difficulty continuing the medication. Left atrial appendage closure (LAAC) has been developed for such situations. We aimed to clarify the clinical significance of a history of GIB in comparison to other factors in patients who had undergone LAAC. Methods From October 2019 to September 2023, patients with NVAF who underwent LAAC at our hospital were enrolled. We investigated the percentage of patients with a history of GIB who underwent LAAC and compared the incidence of post‐LAAC bleeding in these patients compared to those with other factors. Results A total of 45 patients were included. There were 19 patients (42%) with a history of GIB who underwent LAAC. In a Kaplan–Meier analysis, the cumulative incidence of bleeding complications after LAAC was significantly higher in patients with a history of GIB in comparison to patients with other factors. There were eight cases of post‐LAAC bleeding in total, and seven cases had GIB. Conclusions We need to recognize that GIB is a significant complication in patients who undergo LAAC. The management of GIB by gastroenterologists is essential to the success of LAAC.

Abstract A coordination network containing isolated pores without interconnecting channels is prepared from a tetrahedral ligand and copper(I) iodide. Despite the lack of accessibility, CO2 is selectively adsorbed into these pores at 298 K and then retained for more than one week while exposed to the atmosphere. The CO2 adsorption energy and diffusion mechanism throughout the network are simulated using Matlantis, which helps to rationalize the experimental results. CO2 enters the isolated voids through transient channels, termed “magic doors”, which can momentarily appear within the structure. Once inside the voids, CO2 remains locked in limiting its escape. This mechanism is facilitated by the flexibility of organic ligands and the pivot motion of cluster units. In situ powder X‐ray diffraction revealed that the crystal structure change is negligible before and after CO2 capture, unlike gate‐opening coordination networks. The uncovered CO2 sorption and retention ability paves the way for the design of sorbents based on isolated voids.

Abstract Aims Current approaches to classify chronic heart failure (HF) subpopulations may be limited due to the diversity of pathophysiology and co‐morbidities in chronic HF. We aimed to elucidate the clusters of chronic patients with HF by data‐driven approaches with machine learning in a hospital‐based registry. Methods and results A total of 4649 patients with a broad spectrum of left ventricular ejection fraction (LVEF) in the CHART‐2 (Chronic Heart Failure Analysis and Registry in the Tohoku District‐2) study were enrolled to this study. Chronic HF patients were classified using random forest clustering with 56 multiscale clinical parameters. We assessed the influence of the clusters on cardiovascular death, non‐cardiovascular death, all‐cause death, and free from hospitalization by HF. Latent class analysis using random forest clustering identified 10 clusters with four primary components: cardiac function (LVEF, left atrial and ventricular diameters, diastolic blood pressure, and brain natriuretic peptide), renal function (glomerular filtration rate and blood urea nitrogen), anaemia (red blood cell, haematocrit, haemoglobin, and platelet count), and nutrition (albumin and body mass index). All 11 significant clinical parameters in the four primary components and two disease aetiologies (ischaemic heart disease and valvular heart disease) showed statistically significant differences among the 10 clusters (P 111.3 pg/mL, 0.9%) and lowest left atrial diameter (>42 mm, 37.4%), showed the best 5 year survival rate of 98.1% for cardiovascular death, 95.9% for non‐cardiovascular death, 92.9% for all‐cause death, and 91.7% for free from hospitalization by HF. Cluster 10 (6.0% of the total), which is co‐morbid disorders of all four primary components, showed the worst survival rate of 39.1% for cardiovascular death, 68.9% for non‐cardiovascular death, 23.9% for all‐cause death, and 28.1% for free from hospitalization by HF. Conclusions These results suggest the potential applicability of the machine leaning approach, providing useful clinical prognostic information to stratify complex heterogeneity in patients with HF.

Abstract Objectives This study aims to investigate whether a cribriform pattern on prostate biopsy may be a factor in suspicion of intraductal carcinoma of the prostate after radical prostatectomy. Methods This retrospective study assessed 100 men who underwent prostatectomy from 2015 to 2019. Participants were grouped as 76 patients with Gleason pattern 4 and 24 patients without this pattern. All 100 participants underwent retrograde radical prostatectomy and limited lymph node dissection. The same pathologist evaluated all specimens. The cribriform pattern was evaluated with haematoxylin and eosin counterstaining, and intraductal carcinoma of the prostate was evaluated with immunohistochemical analysis of cytokeratin 34βE12. Results Patients with intraductal carcinoma of the prostate on immunohistochemical analysis showed a significant tendency to relapse in the postoperative period, and those with the cribriform pattern on biopsy had a significant recurrence rate. In univariate and multivariate analyses, intraductal carcinoma of the prostate confirmed in biopsy tissue was an independent predictor of biochemical recurrence after prostatectomy. The rate of intraductal carcinoma of the prostate confirmation was 28% of cases with a cribriform pattern in biopsy tissue, which was increased to 62% in prostatectomy tissues. Conclusion The cribriform pattern in the biopsy tissue may be a predictor for intraductal carcinoma of the prostate.

Abstract La Niña persisted from 2020 to 2023, but its mechanisms are still unclear. In this study, atmosphere and ocean reanalysis and 100‐member initialized forecasts using a state‐of‐the‐art climate model were analyzed to identify factors contributing to the persistence of the first‐ to second‐year La Niña during 2020–2022. We found that North Pacific high pressure anomalies in the winter of 2020/2021 forced a negative phase of the Pacific meridional mode through the following spring, forming the broader structure of La Niña. The resultant broader La Niña pattern slowed down the recharge‐discharge process by Ekman transport, persisting La Niña. Ensemble forecast sensitivity analysis revealed that the meridional extent of La Niña explains its forecast spread, reaffirming the importance of La Niña spatial pattern. Advancing predictive understanding of 2020–2022 multi‐year La Niña can help to improve the extended seasonal forecast.

Abstract Human‐mediated hybridization between native and non‐native species is causing biodiversity loss worldwide. Hybridization has contributed to the extinction of many species through direct and indirect processes such as loss of reproductive opportunity and genetic introgression. Therefore, it is essential to manage hybrids to conserve biodiversity. However, specialized knowledge is required to identify the target species based on visual characteristics when two species have similar features. Although image recognition technology can be a powerful tool for identifying hybrids, studies have yet to utilize deep learning approaches. Hence, this study aimed to identify hybrids between the native Japanese giant salamander (Andrias japonicus) and the non‐native Chinese giant salamander (Andrias cf. davidianus) using EfficientNetV2 and smartphone images. We used smartphone images of 11 individuals of native A. japonicus (five training and six test images) and 20 individuals of hybrids between A. japonicus and A. cf. davidianus (five training and 15 test images). In our experimental environment, an AI model constructed with EfficientNetV2 exhibited 100% accuracy in identifying hybrids. In addition, gradient‐weighted class activation mapping revealed that the AI model was able to classify A. japonicus and hybrids between A. japonicus and A. cf. davidianus on the basis of the dorsal head spot patterning. Our approach thus enables the identification of hybrids against A. japonicus, which was previously considered difficult by non‐experts. Furthermore, since this study achieved reliable identification using smartphone images, it is expected to be applied to a wide range of citizen science projects.

Abstract Human papillomavirus (HPV) infection has been suggested as a potential risk factor for Bowen's disease. Here, we report a case of a 40‐year‐old man with Bowen's disease on the finger showing a discontinuous skip lesion, in which HPV‐34 was detected. Our case is a reminder that the possibility of multiple lesions must be considered when Bowen's disease occurs on the finger.

Background Limited data exist on the prognostic factors for patients with ischemic stroke and active cancer. Methods and Results We conducted a prospective, multicenter, observational study in Japan, including patients with acute ischemic stroke and active cancer, to investigate the prognostic factors. We followed up the patients for 1 year after stroke onset. The patients were divided into 2 groups according to cryptogenic stroke and known causes (small‐vessel occlusion, large‐artery atherosclerosis, cardioembolism, and other determined cause), and survival was compared. The hazard ratios (HRs) and 95% CIs for mortality were calculated using Cox regression models. We identified 135 eligible patients (39% women; median age, 75 years). Of these patients, 51% had distant metastasis. A total of 65 (48%) and 70 (52%) patients had cryptogenic stroke and known causes, respectively. Patients with cryptogenic stroke had significantly shorter survival than those with known causes (HR [95% CI], 3.11 [1.82–5.32]). The multivariable Cox regression analysis revealed that distant metastasis, plasma D‐dimer levels, venous thromboembolism (either deep venous thrombosis or pulmonary embolism) complications at stroke onset were independent predictors of mortality after adjusting for potential confounders. Cryptogenic stroke was associated with prognosis in univariable analysis but was not significant in multivariable analysis. The plasma D‐dimer levels stratified the prognosis of patients with ischemic stroke and active cancer. Conclusions The prognosis of patients with acute ischemic stroke and active cancer varied considerably depending on stroke mechanism, distant metastasis, and coagulation abnormalities. The present study confirmed that coagulation abnormalities were crucial in determining the prognosis of such patients.

Abstract Background Etoposide plus cisplatin (EP) combined with concurrent accelerated hyperfractionated thoracic radiotherapy (AHTRT) is the standard treatment strategy for unresectable limited‐disease (LD) small cell lung cancer (SCLC), which has remained unchanged for over two decades. Based on a previous study that confirmed the non‐inferiority of amrubicin (AMR) plus cisplatin (AP) when compared with EP for extensive‐disease (ED) SCLC, we have previously conducted a phase I study assessing AP with concurrent TRT (2 Gy/time, once daily, 50 Gy in total) for LD‐SCLC therapy. Our findings revealed that AP with concurrent TRT could prolong overall survival to 39.5 months with manageable toxicities. Therefore, we plan to conduct a phase I study to investigate and determine the effect of AP combined with AHTRT, recommended dose (RD), maximum tolerated dose (MTD), and dose‐limiting toxicity (DLT) of AP in patients with LD‐SCLC. Methods Treatment‐naive patients with LD‐SCLC, age between 20 and 75 years, who had a performance status of 0 or 1 and adequate organ functions will be enrolled. For chemotherapy, cisplatin 60 mg/m2/day (day 1) and AMR (day 1 to 3) will be administered with AHTRT (1.5 Gy/time, twice daily, 45 Gy in total). The initial AMR dose is set to 25 mg/m2/day. RD and MTD will be determined by evaluating toxicities. Discussion Based on our previous study, the initial dose of AMR 25 mg/m2 is expected to be tolerated and acceptable. Here, we aim to determine whether treatment with AP and concurrent AHTRT would be an optimal choice with manageable toxicities for LD‐SCLC.

Abstract The design of crosslinking domains is a vital factor to create functional hydrogels with controlled physical, mechanical, and adhesive properties. This paper demonstrates versatile synthetic systems of micelle‐crosslinked hydrogels with highly stretchable, self‐healing, and selectively adhesive properties. For this, methacrylate‐bearing random copolymer micelles are designed as physical and covalent crosslink domains via the self‐assembly of amphiphilic random copolymers carrying hydrophilic poly(ethylene glycol) (PEG), hydrophobic butyl or dodecyl groups, and methacrylate‐terminal PEG in water. The size, aggregation number, and pendant methacrylate number of the micelles are controlled by the composition and degree of polymerization. Hydrogels are efficiently obtained from the free radical polymerization of hydrophilic monomers such as PEG acrylate and acrylamide in the presence of the micelle crosslinkers in water. Owing to the dynamic yet selective chain exchange properties of the micelle domains, the hydrogels are highly stretchable up to over 1000% and show self‐healing and selectively adhesive properties. The self‐healing of hydrogels is promoted upon heating due to the fast chain exchange of the micelle domains, whereas hydrogels consisting of micelles with different alkyl groups are never adhesive because of their self‐sorting properties.

Abstract Aims The relief of congestion is essential for the prevention of worsening heart failure (HF) resulting in hospitalizations. Assessment of the degree of organ congestion in the chronic phase of HF is important for determining therapeutic strategies. The aim of this study was to evaluate the efficacy of shear wave (SW) elasticity for assessing congestion and clinical outcomes in patients with chronic HF. Methods and results We prospectively enrolled 345 consecutive patients with chronic HF who underwent SW elastography at outpatient clinic. Patients were divided into two groups according to the median value of SW elasticity: low group (SW elasticity

Abstract Purpose To evaluate the efficacy of two progestins, levonorgestrel intrauterine system (LNG‐IUS) and dienogest (DNG), for adenomyosis. Methods This study enrolled 157 women with adenomyosis, randomized to either LNG‐IUS (n = 76) or DNG (n = 81) groups as a controlled clinical trial for 72 months. Participants were classified by three different localizations of adenomyosis: diffuse, focal, and extrinsic. VAS (Visual analog scale) score, days, and amount of uterine bleeding were assessed. Uterine volume or bone mineral density (BMD) were measured by three‐dimensional ultrasonography or dual‐energy X‐ray absorptiometry. Results LNG‐IUS and DNG comparably reduced pain scores in patients with adenomyosis. With regard to pain control, DNG offered greater efficacy than LNG‐IUS in 3 months of treatment. In all types of adenomyosis, the days of bleeding after 12 months with DNG were significantly decreased compared to those with LNG‐IUS. The decrease of whole uterine body was transient in any subtypes. A comparable decrease in BMD due to age‐related changes in both groups was observed. Conclusions LNG‐IUS and DNG could be useful for long‐term management of adenomyosis. In terms of durations of uterine bleeding, DNG was superior to LNG‐IUS for 6 years.

Abstract Solution‐processed solar cells are promising for the cost‐effective, high‐throughput production of photovoltaic devices. Colloidal quantum dots (CQDs) are attractive candidate materials for efficient, solution‐processed solar cells, potentially realizing the broad‐spectrum light utilization and multi‐exciton generation effect for the future efficiency breakthrough of solar cells. The emerging quantum junction solar cells (QJSCs), constructed by n‐ and p‐type CQDs only, open novel avenue for all‐quantum‐dot photovoltaics with a simplified device configuration and convenient processing technology. However, the development of high‐efficiency QJSCs still faces the challenge of back carrier diffusion induced by the huge carrier density drop at the interface of CQDs and conductive glass substrate. Herein, an ultra‐thin atomic layer deposited tin oxide (SnOx) layer is employed to buffer this carrier density drop, significantly reducing the interfacial recombination and capacitance caused by the back carrier diffusion. The SnOx‐modified QJSC achieves a record‐high efficiency of 11.55% and a suppressed hysteresis factor of 0.04 in contrast with reference QJSC with an efficiency of 10.4% and hysteresis factor of 0.48. This work clarifies the critical effect of interfacial issues on the carrier recombination and hysteresis of QJSCs, and provides an effective pathway to design high‐performance all‐quantum‐dot devices.

Abstract A patient complained of acute right vision loss and headache. A computed tomography scan revealed ethmoidal sinus mucocele in the right ethmoid sinus that was compressing the optic nerve and emergency endoscopic sinus surgery was performed.

Abstract Adverse reactions, including the onset of diabetes, after coronavirus disease 2019 (COVID‐19) vaccination have been reported. Herein, we report a case of a man who developed anti‐glutamic acid decarboxylase (GAD) antibody‐positive fulminant type 1 diabetes 15 weeks after COVID‐19 vaccination, atypical of the previously reported anti‐GAD antibody‐negative cases.

Background Several longitudinal studies have reported that higher visit‐to‐visit blood pressure variability is associated with greater risk for developing chronic kidney disease. However, no population‐based studies have investigated the association between day‐to‐day home blood pressure variability and incident chronic kidney disease. Methods and Results A total of 2342 Japanese community‐dwelling residents aged ≥40 years without chronic kidney disease at baseline were followed up by annual health examinations for 10 years. Home blood pressure was measured 3 times every morning for 28 days. Day‐to‐day coefficients of variation of home systolic blood pressure levels were categorized into quintiles. Chronic kidney disease was defined as an estimated glomerular filtration rate

Abstract Background It has recently been suggested that concomitant medication may affect the clinical outcome of patients treated with immune checkpoint inhibitors (ICIs). However, only a few studies on the impact of concomitant medication on immune‐related adverse events (irAEs) have previously been reported. Here, we aimed to determine the impact of concomitant medication on the efficacy and safety of ICIs. Methods We retrospectively analyzed the data of 300 patients treated with nivolumab or pembrolizumab for advanced non‐small cell lung cancer (NSCLC) between January 2016 and July 2018. Multivariate logistic regression analysis was used to assess the effect of concomitant medication on treatment response or irAEs. A multivariate Cox proportional hazards model was used to evaluate concomitant medication‐related factors associated with time‐to‐treatment failure or overall survival (OS). Results A total of 70 patients responded to treatment and 137 experienced irAEs. The response rate and incidence of irAEs in patients treated with ICIs were not significantly associated with concomitant medication. Multivariate analysis showed that the use of opioids was an independent factor (time‐to‐treatment failure: hazard ratio 1.39, p = 0.021, OS: hazard ratio 1.54, p = 0.007). Conclusions The efficacy and safety of nivolumab or pembrolizumab in the treatment of patients with advanced NSCLC were not significantly influenced by concomitant medication. However, opioid usage might be associated with shorter OS in patients treated with these ICIs. Further mechanistic investigations should explore whether these associations are purely prognostic or contribute to ICI resistance.

Abstract Background The overall incidence of gastric cancer in women is half that in men for most global populations. Sex hormone pathways may be involved in carcinogenesis and estrogens have been postulated to protect women against gastric cancer. Aim To evaluate associations of gastric cancer with estrogen metabolites in postmenopausal women. Methods and results We performed an analysis of 233 gastric cancer cases and 281 age‐matched controls from three prospective cohorts and two case‐control studies of early‐stage gastric cancer, mainly conducted in high‐risk Asian populations. Fifteen estrogen‐parent (estrone and estradiol) and ‐metabolite analytes (2‐hydroxyestrone, 2‐hydroxyestradiol, 2‐hydroxyestrone‐3‐methyl ether, 4‐hydroxyestrone; 4‐methoxyestrone, 4‐methoxyestradiol, 2‐methoxyestrone, 2‐methoxyestradiol, estriol, 16α‐hydroxyestrone, 16‐ketoestradiol, 16‐epiestriol, and 17‐epiestriol) were measured in spot urines using liquid chromatography–tandem mass spectrometry. Odds ratios for association with each marker were estimated by logistic regression. Heterogeneity was assessed by Cochran's Q test. Study‐specific odds ratios were pooled by fixed‐effects meta‐analysis. Urinary levels of estrogen‐related molecules were not associated with gastric cancer (adjusted odds ratios ranged from 0.87 to 1.27; p‐values >.05), with low between‐study heterogeneity (p‐values >.1) for all but two metabolites (2‐hydroxyestrone‐3‐methyl ether and 2‐methoxyestradiol). Conclusion To date, this is the first comprehensive assessment of endogenous estrogens with gastric cancer risk in women. Estrogens do not appear to have an etiologic role in gastric cancer risk among postmenopausal women. Given the complex network of sex steroid hormones and their extreme variation over the lifespan, further evaluation of this hypothesis is warranted.

Abstract Takotsubo cardiomyopathy (TCM) causes QT interval prolongation, potentially leading to a fatal arrhythmia. We report the first case of TCM associated with licorice‐induced pseudoaldosteronism causing fatal arrhythmia in an older patient on polypharmacy including yokukansan (TJ‐54) and galantamine. Polypharmacy should be resolved to prevent unexpected adverse events in older patients.

Abstract Aims/Introduction The relationship between renal function and urinary glucose is poorly understood in diabetes patients who are not using sodium–glucose cotransporter 2 inhibitors. This study aimed to investigate the association of urinary glucose excretion with renal function prognosis in such patients. Materials and Methods This retrospective cohort study included 1,172 patients with type 1 or 2 diabetes mellitus. Patients were recruited and data were collected between 1 January 2007 and 31 December 2011; follow‐up data were collected until 30 June 2015. The primary outcome was set as a 30% decline in estimated glomerular filtration rate relative to baseline. The relationship between this outcome and urinary glucose was investigated using Cox proportional hazards model. For analysis, patients were categorized into two groups: urinary glucose

Abstract Objective This study aimed to analyze the early mortality rates and patterns of relapse after stereotactic body radiotherapy (SBRT) as an initial metastasis‐directed therapy. Methods Patients with pulmonary oligometastases initially treated with SBRT were included in this retrospective multicenter study. SBRT was performed between 2004 and 2015, and the primary lesion was controlled at the time of SBRT. Multivariate logistic regression was used for early mortality analyses. Results A total of 720 patients with 793 oligometastatic tumors for whom the median follow‐up period was 24.6 months were enrolled. The median overall survival period was 53.2 months. The 90‐, 180‐, and 360‐day mortality rates were 1.1% (8 deaths), 2.4% (17 deaths), and 10.8% (71 deaths), respectively. During follow up, 422 patients relapsed. Over 329 patients had single‐site relapse, the most frequent site was the lung in 176; 49 had local failure; and 42 had lymph node metastases. The maximum tumor diameter was significantly related to 90‐day mortality. Maximum tumor diameter, biological effective dose, and performance status were significantly related to 180‐day mortality, whereas maximum tumor diameter, performance status, and pathology were significantly related to 360‐day mortality. Conclusion Our results showed good survival outcomes and low rates of early mortality after SBRT. The patterns of relapse and factors affecting early mortality were revealed.

Abstract Aims Liver dysfunction is important for prognosis in heart failure (HF). Shear wave elastography (SWE), which is a novel ultrasound technique for charactering tissues, has been used in liver diseases. However, clinical implication of SWE, including dispersion slope, remains unknown in heart diseases. This study aimed to evaluate the efficacy of SWE assessing liver function in the severity of HF. Methods and results We enrolled 316 consecutive patients with or suspected heart diseases, who were classified according to the American College of Cardiology Foundation/American Heart Association stage of HF, including 37 with Stage A, 139 with Stage B, 114 with Stage C, and 26 with Stage D, and 45 normal subjects. Elasticity and dispersion slope of shear wave were assessed according to the HF stage. Elasticity and dispersion slope were not elevated in normal subjects and patients with Stage A. Elasticity was slightly increased from Stage A to Stage C and was remarkably elevated in Stage D (normal: 5.2 ± 1.1 kPa, Stage A: 5.4 ± 1.2 kPa, Stage B: 6.4 ± 1.8 kPa, Stage C: 7.8 ± 3.5 kPa, and Stage D: 17.7 ± 12.7 kPa), whereas dispersion slope was gradually increased from Stage A to Stage D (normal: 9.7 ± 1.7m/s/kHz, Stage A: 10.4 ± 1.6m/s/kHz, Stage B: 11.7 ± 2.4m/s/kHz, Stage C: 13.2 ± 3.4m/s/kHz, and Stage D: 17.6 ± 5.6 m/s/kHz). In the early HF stage, dispersion slope was elevated. In the advanced HF stage, both elasticity and dispersion slope were elevated. Liver function test abnormalities were observed only from Stage C or Stage D. Conclusions Dispersion slope could detect early liver damage, and the combination of elasticity and dispersion slope could clarify the progression of liver dysfunction in HF. SWE may be valuable to manage therapeutic strategies in patients with HF.