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The modified Attitudes Toward Health Care Teams Scale (mATHCTS) is a self-administered questionnaire with 14 items to assess participants' perceptions of the impact of interprofessional collaboration. Its validity and reliability have been widely evaluated. The effect of interprofessional education (IPE) has been evaluated using changes in mATHCTS factor scores. However, several aspects of the scale require clarification: the difficulty of correctly answering each item; how well each item discriminates between respondents' abilities; and whether the mATHCTS is better at identifying those with higher/lower abilities. We investigated the mATHCTS's item characteristics such as difficulty, discrimination, and measurement accuracy using item-response theory (IRT) analysis. Health and welfare university students were administered a questionnaire prior to starting IPE in 2021. The results for 180 participants were analyzed based on IRT. The test-response (TRF) and test-information (TIF) functions, discrimination, and difficulty were estimated. All items' discrimination and difficulty were adequate. The TRF, which shows the relationship between scores and ability, increased monotonically. The TIF, which shows the relationship between ability and measurement accuracy, decreased as the total score increased. The mATHCTS effectively assessed participants' attitudes toward health care teams as a one-dimensional ability. The mATHCTS performed well in identifying participants with relatively low scores.

Our research focuses on elucidating the crystallographic structure of Japanese swords in a nondestructive manner using the neutron imaging instrument RADEN at the Materials and Life Science Experimental Facility of the Japan Proton Accelerator Research Complex (J-PARC). We developed an analysis method combining wavelength-resolved Bragg-edge imaging and wavelength-selective neutron tomography with a new strategy and applied it to an approximately 45-cm blade length Japanese sword signed by Bishu Osafune Norimitsu. Computed tomography was performed, and the three-dimensional analysis captured the characteristic internal structure of Kobuse. Kobuse is the most famous steel-combining structure of Japanese swords, where an outer steel with high-carbon content (Kawagane) covers a core steel with low-carbon content (Shingane). The crystallite size distribution obtained through Bragg-edge analysis could consistently explain the internal structure of two steels observed in neutron tomograms. Our nondestructive imaging revealed deep hardening, forming a wavy pattern more than 5 mm from the cutting edge., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

This study presents a significant development in the Energy-Resolved Neutron Imaging System RADEN, in the Japan Proton Accelerator Research Complex, Japan. Through a systematic study, the collimation power of the facility was reevaluated. What was initially considered to be values of 230, 420, and 760 have been proven to be much higher. To perform the calculation of the L/D factor of the beam, a state-of-the-art method has been used, along with a standard reference sample to measure the resolution of neutron images. To add robustness to the results, the study compares five different scintillators of different composition and thickness [6LiF:ZnS(Ag) of 50, 100, 200, and 300 μm and Gd2O2S of 50 μm]. The calculated collimating power of the beam ranges between 470 and 1520. These results place a spotlight on an existing discrepancy between the geometrically calculated L/D and the actual measurable quantity, as well as highlight the superior performance of the RADEN beamline., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).)

Most elements of filamentous fungi seen in human tissue by pathologists are hyphae, and encountering other elements may interfere with diagnosis. Sporangia and chlamydospores are such elements that have been described in only a few case reports. We present an autopsy case with the extremely rare coexistence of Mucorales sporangia and chlamydospores in the lung. These fungal elements must be recognized and identified accurately because they can easily be mistaken for other fungi, microorganisms, or degenerated tissue structures., (© 2024 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Thallium bromide (TlBr) semiconductor detectors are being developed as promising candidates for high-detection-efficiency, high-energy-resolution, and room-temperature gamma-ray spectrometers. This study presents methods for evaluating TlBr crystal quality and carrier transport characteristics using neutron Bragg-dip imaging and the time-of-flight method for pulsed-laser-induced carriers, respectively. Neutron Bragg-dip imaging effectively determines the crystal orientation distribution, revealing crystal imperfections and grain boundaries. Time-of-flight measurements provide a spatial distribution of carrier mobility. In this study, two samples obtained from both the upstream and downstream region in the crystal ingot were evaluated. Although both samples show similar crystal quality, the upstream sample showed high carrier mobility across all areas, whereas the downstream sample exhibits low mobility in some areas. These findings suggest that, at least within the range of carrier mobility currently obtained, the effect of crystal integrity on carrier mobility is less significant than that of impurities. In conclusion, combining neutron Bragg-dip imaging with carrier mobility measurements offers a comprehensive approach to evaluating and improving TlBr detectors., (© 2024. The Author(s).)

Introduction: Catheter ablation for atrial fibrillation (AF) reduces heart failure (HF) hospitalization in patients with HF with preserved ejection fraction (HFpEF). However, the long-term outcomes and subclinical HF after nonparoxysmal AF ablation in HFpEF patients have not been fully evaluated., Methods and Results: One-hundred-ninety nonparoxysmal AF patients with left ventricular ejection fraction ≥50% who underwent first-time AF ablation were studied. HFpEF was diagnosed from a history of congestive HF and/or combined criteria of N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and transthoracic echocardiogram parameters, including average septal-lateral E/e' and tricuspid regurgitation peak velocity. Ninety-five patients with HFpEF (HFpEF group) were compared with 95 patients without HF (CNT group). Low voltage area (LVA) was defined as an area with a bipolar electrogram of <0.5 mV covering >5% of the total left atrial surface. The primary endpoint was a composite of death from any cause or hospitalization for worsening HF. The secondary endpoint was subclinical HFpEF defined from NT-proBNP concentration and average septal-lateral E/e' or tricuspid regurgitation peak velocity at 6-12 months after the procedure irrespective of the rhythm. Kaplan-Meier curves showed that the primary composite endpoint did not differ between the two groups (mean follow-up period 707 ± 75 days, log-rank p = 0.5330). However, significantly more patients in the HFpEF group reached the secondary endpoint (42 [44%] vs. 13 [14%], p < 0.0001). Multivariate analysis revealed that a high preablation NT-proBNP (odds ratio [OR] 1.001, 95% confidence interval [CI] 1.001-1.002, p = 0.0040) and the existence of LVA (OR 5.983, 95% CI 1.463-31.768, p = 0.0194) independently predicted the secondary endpoint in HFpEF patients., Conclusion: After nonparoxysmal AF ablation, mortality of HFpEF patients was not inferior compared to patients without coexisting HF. However, subclinical HF occasionally persisted especially in HFpEF patients with a high preprocedure NT-proBNP concentration and LVA., (© 2024 Wiley Periodicals LLC.)

Background: Gastroschisis is a rare congenital anomaly in which abdominal organs herniate through a defect in the abdominal wall. Managing gastroschisis in extremely low birth weight (ELBW) infants presents significant challenges because of their immature physiologies and increased risk of complications., Case Presentation: This report discusses the case of a female ELBW infant born via an emergency cesarean section at 29 weeks of gestation, weighing 768 g, who had a prenatal diagnosis of gastroschisis. Postnatal management included immediate surgical intervention using a hand-made silo manufactured from expanded polytetrafluoroethylene (ePTFE) sheets that were sutured to the patient's abdominal wall to accommodate her small abdominal cavity and preserve mesenteric blood flow. Necrotizing enterocolitis with bowel perforation emerged as a complication, which led to the excision of a 10 cm segment of the ileum and the creation of an ileostomy. The infant experienced insufficient weight gain and liver dysfunction. However, she was eventually discharged on day 142 of life, weighing 2774 g, on oral feeding, without significant complications., Conclusions: This case emphasizes how prematurity significantly affected the patient's clinical outcomes, and highlights the importance of individualized management strategies. Our experience demonstrates that custom silo placement allows for the size to be adapted to the abdominal defect, and highlights the critical need to prioritize postnatal bowel perfusion in ELBW infants with gastroschisis., (© 2024. The Author(s).)

Endothelial dysfunction may trigger coronary spastic angina (CSA). However, the risk factors for CSA in young patients remain unclear. This study aimed to investigate the age-dependent role of serum uric acid levels in patients with CSA. We enrolled 423 patients who underwent an ergonovine tolerance test during coronary angiography for the CSA evaluation. We categorized the patients as (1) young (age ≤ 65 years) CSA-positive (n = 33), (2) young CSA-negative (n = 138), (3) elderly (age > 66 years) CSA-positive (n = 42), and (4) elderly CSA-negative (n = 210) groups. In the young groups, the smoker proportion (57.6 vs. 38.4%, p = 0.04) and serum uric acid levels (6.3 ± 1.4 vs. 5.4 ± 1.5 mg/dl, p = 0.006) were significantly higher in the CSA-positive compared with the CSA-negative group. Conversely, in the elderly group, the male proportion (66.6 vs. 47.1%, p = 0.02) and alcohol consumption level (40.5 vs. 21.0%, p = 0.01) were significantly higher in the CSA-positive compared with the CSA-negative group. The multivariate analysis in young groups revealed the independent association between the serum uric acid level (p = 0.02) and the presence of CSA. Our results indicate that elevated serum uric acid levels may affect CSA development in young patients., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Background: Risk stratification in patients with Brugada syndrome (BrS) is challenging, especially in those at intermediate risk. The Predicting Arrhythmic evenT (PAT) score has recently been demonstrated to be excellent for predicting future arrhythmic events in patients without prior ventricular fibrillation (VF). However, validation studies are lacking., Objective: This study aimed to assess the performance of a novel risk stratification model in predicting future VF events in patients with BrS in a Japanese multicenter cohort., Methods: The PAT score was calculated for 413 patients with BrS (mean age, 50.9 ± 13.6 years; 395 men) from 59 hospitals in Japan, including 314 patients without prior VF. The incidence of developing VF during the follow-up period was investigated., Results: During the 106.8-month follow-up period, 54 patients (13.1%) experienced VF events. Of the 314 patients without prior VF at enrollment, 14 (4.5%) experienced VF events. The incidence of VF events during the follow-up period was significantly higher in patients with PAT scores ≥ 10 than in those with scores < 10 (41/173 [23.7%] vs 13/240 [5.4%]; P < .0001) in the total cohort. No difference was observed in the incidence of VF events between patients with PAT scores ≥ 10 and < 10 among the 314 patients without prior VF (6/86 [7.0%] vs 8/228 [3.5%]; P = .22). PAT scores ≥ 10 predicted future VF events with a sensitivity and specificity of 42.9% and 73.3%, respectively., Conclusion: This Japanese multicenter registry demonstrated that the novel risk stratification model could not accurately predict future VF events in patients with BrS but without prior VF., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Current infertility treatment strategies focus on mature gametes, leaving a significant proportion of cases with gamete progenitors that stopped complete differentiation. On the other hand, recent advancements in next-generation sequencing have identified many candidate genes that may promote maturation of germ cells. Although gene therapy has shown success in mice, concerns about the integration of DNA vectors into oocytes hinder clinical applications. Here, we present the restoration of fertility in female mice through Sendai virus (SeV)-mediated RNA delivery. Ovaries lacking Kitl expression exhibit only primordial follicles due to impaired signaling to oocytes expressing the KIT tyrosine kinase. Despite SeVs being immunogenic and larger than the blood-follicle barrier, the administration of Kitl -expressing SeVs reinitiated oogenesis in genetically infertile mice that have only primordial follicles, resulting in the birth of normal offspring through natural mating. This virus also effectively addressed iatrogenic infertility induced by busulfan, a widely used cancer chemotherapy agent. Offspring born through SeV administration and natural mating displayed normal genomic imprinting patterns and fertility. Since SeVs pose no genotoxicity risk, the successful restoration of fertility by SeVs represents a promising approach for treating congenital infertility with somatic cell defects and protecting fertility of cancer patients who may become infertile due to loss of oocytes during cancer therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Purpose: Controlled ovarian stimulation (COS) is vital for IVF. We have developed an AI system to support the implementation of COS protocols in our clinical group., Methods: We developed two models as AI algorithms of the AI system. One was the oocyte retrieval decision model, to determine the timing of oocyte retrieval, and the other was the prescription inference model, to provide a prescription similar to that of an expert physician. Data was obtained from IVF treatment records from the In Vitro Fertilization (IVF) management system at the Asada Ladies Clinic, and these models were trained with this data., Results: The oocyte retrieval decision model achieved superior sensitivity and specificity with 0.964 area under the curve (AUC). The prescription inference model achieved an AUC value of 0.948. Four models, namely the hCG prediction model, the hMG prediction model, the Cetrorelix prediction model, and the Estradiol prediction model included in the prescription inference model, achieved AUC values of 0.914, 0.937, 0.966, and 0.976, respectively., Conclusion: The AI algorithm achieved high accuracy and was confirmed to be useful. The AI system has now been implemented as a COS tool in our clinical group for self-funded treatments., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Our study highlights the discovery of recurrent copy number alterations in noncoding regions, specifically blood enhancer cluster (BENC-CNA), in B-precursor acute lymphoblastic leukemia (BCP-ALL) cell lines. We demonstrate that BENC-CNA acts as a super-enhancer, driving MYC expression and possibly contributing to the immortalization and proliferative advantage of BCP-ALL cells in vitro., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Rechargeable Ca batteries offer the advantages of high energy density, low cost, and earth-abundant constituents, presenting a viable alternative to lithium-ion batteries. However, using polymer electrolytes in practical Ca batteries is not often reported, despite its potential to prevent leakage and preserve battery flexibility. Herein, a Ca(BH 4 ) 2 -based gel-polymer electrolyte (GPE) is prepared from Ca(BH 4 ) 2 and poly(tetrahydrofuran) (pTHF) and tested its performance in Ca batteries. The electrolyte demonstrates excellent stability against Ca-metal anodes and high ionic conductivity. The results of infrared spectroscopy and 1 H and 11 B NMR indicate that the terminal ─OH groups of pTHF reacted with BH 4 - anions to form B─H─(pTHF) 3 moieties, achieving cross-linking and solidification. Cyclic voltammetry measurements indicate the occurrence of reversible Ca plating/stripping. To improve the performance at high current densities, the GPE is supplemented with LiBH 4 to achieve a lower overpotential in the Ca plating/stripping process. An all-solid-state Ca-metal battery with a dual-cation (Ca 2+ and Li + ) GPE, a Ca-metal anode, and a Li 4 Ti 5 O 12 cathode sustained >200 cycles, confirming their feasibility. The results pave the way for further developing lithium salt-free Ca batteries by developing electrolyte salts with high oxidation stability and optimal electrochemical properties., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Several patients treated with osimertinib experience progressive disease. The aim was to clarify the mechanisms underlying resistance to osimertinib., Methods: ELUCIDATOR: A multi-centre, prospective, observational study involved chemotherapy-naive patients with advanced non-small cell lung cancer receiving osimertinib. Mutations in cancer-associated genes, detected via ultrasensitive next-generation sequencing of circulating tumour deoxyribonucleic acid samples, were collected at baseline and after progressive disease detection. These paired plasma samples were compared., Results: Of 188 patients enrolled (May 2019-January 2021), 178 (119 females [67 %]) median age 74 years, were included. Patients, n = 95 (53 %) had epidermal growth factor receptor exon 19 deletion mutations. Among 115 patients with progressive disease, circulating tumour deoxyribonucleic acid levels of 85 patients were analysed. MET amplification (n = 4), TP53 mutations (n = 4), PIK3CA mutations (n = 3), BRINP3 mutation (n = 2), BRAF mutation (n = 2), APC mutation (n = 1), RET mutation (n = 1) and epidermal growth factor receptor (EGFR) resistance mutation, and C797S (n = 1) were detected. Patients with baseline TP53 mutations, with MET or EGFR amplification had shorter progression-free (PFS) and overall survival. Patients with PIK3CA mutations tended to shorter PFS., Conclusion: MET amplification and PIK3CA mutation mechanisms underly resistance to osimertinib in patients. Patients with coexisting mutations or amplifications at baseline had shorter PFS and overall survival., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare no competing interests.

The fungus Wickerhamiella pararugosa (Candida pararugosa) has been detected in various human organs but has rarely caused bloodstream infections. This report presents a case of central venous catheter-related bloodstream infection (CRBSI) of W. pararugosa in an adult. A female patient in her 80s was admitted to our facility for intestinal obstruction caused by colorectal cancer. The patient's ability to consume food was hindered, necessitating the insertion of a central venous catheter (CVC) into the internal jugular vein. On day 3 after admission, the patient developed a fever, prompting blood and CVC tip cultures to be performed. On day 5, yeast-like fungi were discovered in the blood cultures, and fosfluconazole (fluconazole [FLCZ] pro-drug) treatment was initiated. On day 8, yeast-like fungi were identified in both the blood and CVC tip cultures, leading to a diagnosis of CRBSI. The fungus was identified as W. pararugosa through biochemical and genetic characterization. This finding justified the use of micafungin (MCFG) for combination therapy. On day 17, the minimum inhibitory concentrations (MIC) for FLCZ and MCFG were 4-8 and 0.06 μg/mL, respectively. Accordingly, the treatment was changed to monotherapy with MCFG. After a 21-day treatment regimen, the patient was discharged on day 31. We present a case of CRBSI caused by W. pararugosa in an adult with intestinal obstruction. The notable increase in the MIC of FLCZ necessitated monotherapy with MCFG, which resulted in successful recovery of the patient., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background/aim: For patients treated with osimertinib as first-line therapy, there have been no studies comparing both progression-free survival (PFS) and overall survival (OS) according to performance status (PS). Furthermore, no studies have examined differences in baseline genetic abnormalities between patients with poor and good PS. Therefore, we aimed to investigate differences in baseline genetic abnormalities and treatment effects between patients with poor and good PS who received osimertinib as the primary treatment., Patients and Methods: This is a secondary analysis of the ELUCIDATOR study, which is a multi-center prospective observational study in Japan that assessed mechanisms underlying resistance to osimertinib as first-line treatment for advanced non-small cell lung cancer with epidermal growth factor receptor mutations., Results: There were 153 and 25 patients in the good and poor PS groups, respectively. Multivariate analysis revealed no significant between-group differences in PFS (hazards ratio [HR]: 0.98, 95% confidence interval [CI]: 0.52-1.72, p = 0.946). Multivariate analysis of OS revealed that poor PS was a poor prognostic factor (HR: 2.67, 95% CI: 1.43-4.73, p = 0.003). Regarding baseline genetic abnormalities, there was a significant increase in APC-positive cases (20.0% vs. 2.2%, p = 0.009) and a trend toward more CTNNB1-positive cases in the poor PS group than in the good PS group (14.3% vs. 2.9%, p = 0.062)., Conclusion: There was no between-group difference in PFS, although OS was significantly inferior in the poor PS group. Additionally, there was a significant increase in APC-positive cases and a trend toward more CTNNB1-positive cases in the poor PS group., (© 2024. The Author(s).)

Life-space mobility (LSM) in older adults is influenced by physical, cognitive, and psychological states. However, the relationship between LSM and personality traits remains unclear. Thus, our cross-sectional study investigated this correlation, which included 144 participants aged ≥60 years. LSM was assessed using the life-space assessment (LSA), and personality traits were evaluated using the Japanese version of the Ten-Item Personality Inventory (TIPI-J). Physical data were also collected. Univariate analyses revealed that among young-older adults, extroversion in the TIPI-J showed a significant association with LSA scores in addition to handgrip strength. Among old-older adults, openness to experience in the TIPI-J demonstrated a significant association with LSA scores in addition to quadriceps strength. This study revealed correlations between personality traits (extroversion and openness to experience) and LSM, in addition to physical function. Considering older adults' personality traits is crucial for designing support and interventions to maintain and expand LSM., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Intracytoplasmic sperm injection (ICSI) is clinically used to treat obstructive/nonobstructive azoospermia. This study compared the efficacy of ICSI with cauda epididymal and testicular sperm in Wistar (WI) and Brown-Norway (BN) rats. The transfer of ICSI oocytes with cryopreserved epididymal and testicular WI sperm resulted in offspring production of 26.2% and 3.7%-4.7%, respectively (P < 0.05). Treatments for artificial oocyte activation (AOA) and acrosome removal improved pronuclear formation in BN-ICSI oocytes; however, only AOA treatment was effective in producing offspring (3.7%-6.5%). In the case of ICSI with testicular sperm (TESE-ICSI), one offspring (0.6%) was derived from the BN-TESE-ICSI oocytes. The application of AOA or a hypo-osmotic sperm suspension did not improve the production of TESE-ICSI offspring. Thus, outbred WI rat offspring can be produced by using ICSI and less efficiently by using TESE-ICSI. Challenges in producing offspring by using ICSI/TESE-ICSI in inbred BN strain require further investigation.

Background: We have reported that a prehospital 12-lead electrocardiography system (P-ECG) contributed to transport of suspected acute coronary syndrome (ACS) patients to appropriate institutes and in this study, we compared its usefulness between urban and rural areas, and between weekday daytime and weekday nighttime/holiday., Methods and results: Consecutive STEMI patients who underwent successful primary percutaneous coronary intervention after using P-ECG were assigned to the P-ECG group (n=123; 29 female, 70±13 years), and comparable STEMI patients without using P-ECG were assigned to the conventional group (n=117; 33 females, mean age 70±13 years). There was no significant difference in door-to-reperfusion times between the rural and urban cases (70±32 vs. 69±29 min, P=0.73). Door-to-reperfusion times in the urban P-ECG group were shorter than those in the urban conventional group for weekday nighttime/holiday (65±21 vs. 83±32 min, P=0.0005). However, there was no significance different between groups for weekday daytime. First medical contact to reperfusion time (90±22 vs. 105±37 min, P=0.0091) in the urban P-ECG group were significantly shorter than in the urban conventional groups for weekday nighttime/holiday, but were not significantly different between the groups for weekday daytime., Conclusions: P-ECG is useful even in urban areas, especially for patients who develop STEMI during weekday nighttime or while on a holiday.

We encountered an extremely low birth weight infant with breast milk-transmitted cytomegalovirus (CMV) infection. To determine the transmission route, we conducted direct sequence analysis of two variable CMV genes, UL139, and UL146. When utilizing breast milk, the possibility of acquired CMV infection should be considered and tested for prompt diagnosis and treatment., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

We aimed to verify the characteristics of lifestyles and frailty among older adults during and after the COVID-19 pandemic. This two-point cross-sectional study conducted a baseline survey (BL) in 2020 and a follow-up survey (FU) in 2023 with community-dwelling individuals aged ≥65 years in Japan. The 700 and 572 participants in the BL and FU were analyzed. We compared frailty occurrence and lifestyle characteristics between both surveys. In the BL and FU, 38.3 %, 52.4 %, and 9.3 % and 29.4 %, 59.4 %, and 11.2 % of the individuals were classified as robust, pre-frail, and frail, respectively, showing a significant decrease in the number of robust, and an increase in the number of pre-frail. A significant decrease in dietary intake was observed among robust individuals in the FU, with an overall significant decrease in communication opportunities in the BL. Therefore, lifestyle changes due to infection control measures may have a delayed impact on frailty., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Epicardial adipose tissue (EAT) have been shown to be associated with several heart disease, including coronary artery disease (CAD), atrial fibrillation (AF), and heart failure (HF). It is reported that the quality of EAT, represented by fat attenuation determined using computed tomography (CT) imaging, can detect the histologically-assessed remodeled EAT. We tested the hypothesis that quality of EAT would predict major adverse cerebral and cardiovascular events (MACCE) following transcatheter aortic valve implantation (TAVI) in patients with aortic stenosis (AS). A total of 125 consecutive severe AS patients who underwent TAVI were enrolled (39 male, mean 85.4 ± 4.0 years). Using CT imaging before TAVI, we measured the average CT fat attenuation of EAT (EAT attenuation) and investigated the association with MACCE. During the mean follow up period of 567 ± 371 days, 21 cases of MACCE were observed. Patients with MACCE had greater levels of EAT attenuation compared to those without (- 74 ± 3.7 Hounsfield Units (HU) vs - 77 ± 5.5 HU, p = 0.010). Based on the ROC curves, the high EAT attenuation was defined as > - 74.3 HU. According to this cut-off index, 44 patients were classified into the high EAT attenuation group (28 female, mean age 87 ± 3.6 years), whereas 81 patients were classified into the low EAT attenuation group (13 female, 85 ± 4.1 years). Kaplan-Meier survival curve demonstrated that the patients in the high EAT attenuation group showed greater prevalence of MACCE (log-rank 6.64, p = 0.010). Cox proportional hazards regression analysis revealed that EAT attenuation and Logistic EuroSCORE were independently associated with the incidence of MACCE. Our results suggest that quality of EAT, assessed by EAT attenuation detected by CT imaging, can predict the cerebral and cardiovascular events after TAVI in patients with AS., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Background: The prevalence of transthyretin amyloid cardiomyopathy (ATTR-CM) in atrial fibrillation (AF) patients remains unclear. We explored the efficacy of computed tomography-based myocardial extracellular volume (CT-ECV) combined with red flags for the early screening of concealed ATTR-CM in AF patients undergoing catheter ablation., Methods and results: Patients referred for AF ablation at Oita University Hospital were prescreened using the red-flag signs defined by echocardiographic or electrocardiographic findings, medical history, symptoms, and blood biochemical findings. Myocardial CT-ECV was quantified in red flag-positive patients using routine pre-AF ablation planning cardiac CT with the addition of delayed-phase cardiac CT scans. Patients with high (>35%) ECV were evaluated using technetium pyrophosphate ( 99 m Tc-PYP) scintigraphy. A cardiac biopsy was performed during the planned AF ablation procedure if 99 m Tc-PYP scintigraphy was positive. Between June 2022 and June 2023, 342 patients were referred for AF ablation. Sixty-seven (19.6%) patients had at least one of the red-flag signs. Myocardial CT-ECV was evaluated in 57 patients because of contraindications to contrast media, revealing that 16 patients had high CT-ECV. Of these, 6 patients showed a positive 99 m Tc-PYP study, and 6 patients were subsequently diagnosed with wild-type ATTR-CM via cardiac biopsy and genetic testing., Conclusions: CT-ECV combined with red flags could contribute to the systematic early screening of concealed ATTR-CM in AF patients undergoing catheter ablation.

A 68-year-old Japanese man developed a fever, headache, hiccups, and altered consciousness. Brain magnetic resonance imaging (MRI) revealed a hemorrhagic lesion in the right temporal lobe and multiple high-intensity white matter lesions. A brain biopsy showed pathological findings consistent with acute disseminated encephalomyelitis (ADEM), suggesting a diagnosis of acute hemorrhagic leukoencephalitis (AHLE), an aggressive ADEM variant. The patient also developed myodesopsia and was diagnosed with retinal vasculitis, likely due to a hyperimmune state caused by AHLE. Corticosteroids enabled full recovery. Although AHLE is uncommon in elderly individuals, clinicians should be aware of its occurrence in this patient subgroup and recognize potential retinal manifestations associated with AHLE.

Spermatogonial stem cells (SSCs) undergo self-renewal division to sustain spermatogenesis. Although it is possible to derive SSC cultures in most mouse strains, SSCs from a 129 background never proliferate under the same culture conditions, suggesting they have distinct self-renewal requirements. Here, we established long-term culture conditions for SSCs from mice of the 129 background (129 mice). An analysis of 129 testes showed significant reduction of GDNF and CXCL12, whereas FGF2, INHBA and INHBB were higher than in testes of C57BL/6 mice. An analysis of undifferentiated spermatogonia in 129 mice showed higher expression of Chrna4, which encodes an acetylcholine (Ach) receptor component. By supplementing medium with INHBA and Ach, SSC cultures were derived from 129 mice. Following lentivirus transduction for marking donor cells, transplanted cells re-initiated spermatogenesis in infertile mouse testes and produced transgenic offspring. These results suggest that the requirements of SSC self-renewal in mice are diverse, which has important implications for understanding self-renewal mechanisms in various animal species., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

CD4 + T cells induced from human iPSCs (iCD4 + T cells) offer a therapeutic opportunity for overcoming immune pathologies arising from hematopoietic stem cell transplantation. However, most iCD4 + T cells are conventional helper T cells, which secrete inflammatory cytokines. We induced high-level expression of FOXP3, a master transcription factor of regulatory T cells, in iCD4 + T cells. Human iPSC-derived, FOXP3-induced CD4 + T (iCD4 + Treg-like) cells did not secrete inflammatory cytokines upon activation. Moreover, they showed demethylation of the Treg-specific demethylation region, suggesting successful conversion to immunosuppressive iCD4 + Treg-like cells. We further assessed these iCD4 + Treg-like cells for CAR-mediated immunosuppressive ability. HLA-A2 CAR-transduced iCD4 + Treg-like cells inhibited CD8 + cytotoxic T cell (CTL) division in a mixed lymphocyte reaction assay with A2 + allogeneic CTLs and suppressed xenogeneic graft-versus-host disease (GVHD) in NSG mice treated with A2 + human PBMCs. In most cases, these cells suppressed the xenogeneic GvHD progression as much as natural CD25 + CD127 - Tregs did., Competing Interests: Declaration of interests S.K. is a director and shareholder at Shinobi Tx and received research funding from Shinobi Tx, Takeda Pharmaceutical, and Astellas. H.K received research funding from Chugai, Kyowa Kirin, Zenyaku Kogyo, Sumitomo Pharma, Eisai, Daiichi Sankyo, Otsuka Pharmaceutical, Perseus Proteomics, CURED, Astellas Pharma, Asahi Kasei, AbbVie, Nippon Shinyaku, JCR Pharmaceuticals, and Takeda Pharmaceutical. S.K. has patent applications related to the research (patent no. WO/2023/182328). T. Sato., T. Shinohara., K.K., A.M., K.N., M.S., and Y.K. are employees of Takeda Pharmaceutical Co. Ltd., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The development of next-generation sequencing (NGS) has enabled the discovery of cancer-specific driver gene alternations, making precision medicine possible. However, accurate genetic testing requires a sufficient amount of tumor cells in the specimen. The evaluation of tumor content ratio (TCR) from hematoxylin and eosin (H&E)-stained images has been found to vary between pathologists, making it an important challenge to obtain an accurate TCR. In this study, three pathologists exhaustively labeled all cells in 41 regions from 41 lung cancer cases as either tumor, non-tumor or indistinguishable, thus establishing a "gold standard" TCR. We then compared the accuracy of the TCR estimated by 13 pathologists based on visual assessment and the TCR calculated by an AI model that we have developed. It is a compact and fast model that follows a fully convolutional neural network architecture and produces cell detection maps which can be efficiently post-processed to obtain tumor and non-tumor cell counts from which TCR is calculated. Its raw cell detection accuracy is 92% while its classification accuracy is 84%. The results show that the error between the gold standard TCR and the AI calculation was significantly smaller than that between the gold standard TCR and the pathologist's visual assessment (p<0.05). Additionally, the robustness of AI models across institutions is a key issue and we demonstrate that the variation in AI was smaller than that in the average of pathologists when evaluated by institution. These findings suggest that the accuracy of tumor cellularity assessments in clinical workflows is significantly improved by the introduction of robust AI models, leading to more efficient genetic testing and ultimately to better patient outcomes.

A gene delivery system utilizing lentiviral vectors (LVs) requires high transduction efficiency for successful application in human gene therapy. Pseudotyping allows viral tropism to be expanded, widening the usage of LVs. While vesicular stomatitis virus G (VSV-G) single-pseudotyped LVs are commonly used, dual-pseudotyping is less frequently employed because of its increased complexity. In this study, we examined the potential of phenotypically mixed heterologous dual-pseudotyped LVs with VSV-G and Sendai virus hemagglutinin-neuraminidase (SeV-HN) glycoproteins, termed V/HN-LV. Our findings demonstrated the significantly improved transduction efficiency of V/HN-LV in various cell lines of mice, cynomolgus monkeys, and humans compared with LV pseudotyped with VSV-G alone. Notably, V/HN-LV showed higher transduction efficiency in human cells, including hematopoietic stem cells. The efficient incorporation of wild-type SeV-HN into V/HN-LV depended on VSV-G. SeV-HN removed sialic acid from VSV-G, and the desialylation of VSV-G increased V/HN-LV infectivity. Furthermore, V/HN-LV acquired the ability to recognize sialic acid, particularly N-acetylneuraminic acid on the host cell, enhancing LV infectivity. Overall, VSV-G and SeV-HN synergistically improve LV transduction efficiency and broaden its tropism, indicating their potential use in gene delivery.

Background: Laparoscopic sacrocolpopexy (LSC) and robot-assisted sacrocolpopexy (RSC) using mesh are popular approaches for treating pelvic organ prolapse (POP). However, it is not uncommon that native tissue repair (NTR) should be presented as an option to patients who are expected to have extensive intraperitoneal adhesion or patients for whom LSC or RSC is difficult owing to various risk factors. Laparoscopic vaginal stump-uterosacral ligament fixation (Shull method) has been introduced as a method for NTR in case of POP. However, effective repair using this surgical procedure may not be possible in severe POPs. To solve the problems of the Shull method, we devised the laparoscopic vaginal stump-round ligament fixation (Kakinuma method) in which the vaginal stump is fixed to the uterine round ligament, a histologically strong tissue positioned anatomically higher than the uterosacral ligament. This study aimed to retrospectively and clinically compare the two methods., Methods: Of the 78 patients who underwent surgery for POP between January 2017 and June 2022 and postoperative follow-up for at least a year, 40 patients who underwent the Shull method (Shull group) and 38 who underwent the Kakinuma method (Kakinuma group) were retrospectively analyzed., Results: No significant differences were observed between the two groups in patient background variables such as mean age, parity, body mass index, and POP-Q stage. The mean operative duration and mean blood loss in the Shull group were 140.5 ± 31.7 min and 91.3 ± 96.3 ml, respectively, whereas the respective values in the Kakinuma group were 112.2 ± 25.3 min and 31.4 ± 47.7 ml, respectively. Thus, compared with the Shull group, the operative duration was significantly shorter (P < 0.001) and blood loss was significantly less (P = 0.003) in the Kakinuma group. Recurrence was observed in six patients (15.0%) in the Shull group and two patients (5.3%) in the Kakinuma group. Hence, compared with the Shull group, recurrence was significantly less in the Kakinuma group (P = 0.015). No patients experienced perioperative complications in either group., Conclusions: The results suggest that the Kakinuma method can serve as a novel and viable NTR procedure for POP., (© 2024. The Author(s).)

Spermatogonial stem cell (SSC) transplantation is a valuable tool for studying stem cell-niche interaction. However, the conventional approach requires the removal of endogenous SSCs, causing damage to the niche. Here we introduce WIN18,446, an ALDH1A2 inhibitor, to enhance SSC colonization in nonablated recipients. Pre-transplantation treatment with WIN18,446 induced abnormal claudin protein expression, which comprises the blood-testis barrier and impedes SSC colonization. Consequently, WIN18,446 increased colonization efficiency by 4.6-fold compared with untreated host. WIN18,446-treated testes remained small despite the cessation of WIN18,446, suggesting its irreversible effect. Offspring were born by microinsemination using donor-derived sperm. While WIN18,446 was lethal to busulfan-treated mice, cyclophosphamide- or radiation-treated animals survived after WIN18,446 treatment. Although WIN18,446 is not applicable to humans due to toxicity, similar ALDH1A2 inhibitors may be useful for SSC transplantation into nonablated testes, shedding light on the role of retinoid metabolism on SSC-niche interactions and advancing SSC research in animal models and humans., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Most patients with Brugada syndrome (BrS) are first diagnosed in their 40s, with sudden cardiac death (SCD) often occurring in their 50s. Ventricular fibrillation (VF) may occur in some patients with BrS despite having been asymptomatic for a long period. This study aimed to assess the incidence and risk factors for late life-threatening arrhythmias in patients with BrS., Methods: Patients with BrS (n = 523; mean age, 51 ± 13 years; male, n = 497) were enrolled. The risk of late life-threatening arrhythmia was investigated in 225 patients who had experienced no cardiac events (CEs: SCD or ventricular tachyarrhythmia) for at least 10 years after study enrollment. The incidence of CEs during the follow-up period was examined., Results: During the follow-up of the 523 patients, 59 (11%) experienced CEs. The annual incidences of CEs were 2.87%, 0.77%, and 0.09% from study enrollment to 3, 3-10, and after 10 years, respectively. Among 225 patients who had experienced no CEs for at least 10 years after enrollment, four patients (1.8%) subsequently experienced CEs. Kaplan-Meier analysis revealed significant differences in the incidence of late CEs between patients with and without a history of symptoms (p = .032). The positive and negative predictive values of late CEs for the programmed electrical stimulation (PES) test were 2.9% and 100%, respectively., Conclusion: Our results suggest that patients with BrS who are asymptomatic and have no ventricular tachycardia/VF inducibility by PES are at extremely low risk of experiencing late life-threatening arrhythmias., (© 2024 Wiley Periodicals LLC.)

Background: Typical left bundle branch block (LBBB) shows 2 peaks of the R wave, which reflect activation reaching the interventricular septum (R) and posterolateral wall (R') sequentially., Objective: The purpose of this study was to investigate the relationship among R-R' interval (RR'), mechanical dyssynchrony, extent of viable myocardium, and long-term outcomes in cardiac resynchronization therapy (CRT) candidates., Methods: The study enrolled 49 patients (34 men; mean age: 69 ± 11 years) with LBBB who received CRT. The LBBB definition used requires the presence of mid-QRS notching in leads V 1 , V 2 , V 5 , V 6 , I, and aVL. Baseline evaluations were QRS duration (QRSd) and RR' measured from the 12-lead electrocardiogram; eyeball dyssynchrony (apical rocking and septal flash) and opposing-wall delay by speckle tracking from echocardiography, and extent of viable myocardium assessed by thallium-201 single-photon emission computed tomography. Primary outcomes included the combination of all-cause death and heart failure-related hospitalization., Results: RR' predicted volumetric response better than QRSd (area under the curve 0.73 vs 0.67, respectively). The long RR' group (≥48 ms) revealed more frequent eyeball dyssynchrony and significantly greater radial (SL) and circumferential dyssynchrony (AP and SL) and %viable segment than the short RR' group. In multivariate regression analysis, only RR' ≥48 ms was independently associated with higher event-free survival rates following CRT (hazard ratio 0.21; P = .014)., Conclusion: These findings suggest that RR' in complete LBBB was associated with mechanical dyssynchrony, extent of viable myocardium, and long-term outcomes following CRT., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background & Aims: To date, no regional evidence of long-term colorectal cancer (CRC) risk reduction after endoscopic premalignant lesion removal has been established. We aimed to analyze this over a long-term follow-up evaluation., Methods: This was a prospective cohort study of participants from the Japan Polyp Study conducted at 11 Japanese institutions. Participants underwent scheduled follow-up colonoscopies after a 2-round baseline colonoscopy process. The primary outcome was CRC incidence after randomization. The observed/expected ratio of CRC was calculated using data from the population-based Osaka Cancer Registry. Secondary outcomes were the incidence and characteristics of advanced neoplasia (AN)., Results: A total of 1895 participants were analyzed. The mean number of follow-up colonoscopies and the median follow-up period were 2.8 years (range, 1-15 y) and 6.1 years (range, 0.8-11.9 y; 11,559.5 person-years), respectively. Overall, 4 patients (all males) developed CRCs during the study period. The observed/expected ratios for CRC in all participants, males, and females, were as follows: 0.14 (86% reduction), 0.18, and 0, respectively, and 77 ANs were detected in 71 patients (6.1 per 1000 person-years). Of the 77 ANs detected, 31 lesions (40.3%) were laterally spreading tumors, nongranular type. Nonpolypoid colorectal neoplasms (NP-CRNs), including flat (<10 mm), depressed, and laterally spreading, accounted for 59.7% of all detected ANs. Furthermore, 2 of the 4 CRCs corresponded to T1 NP-CRNs., Conclusions: Endoscopic removal of premalignant lesions, including NP-CRNs, effectively reduced CRC risk. More than half of metachronous ANs removed by surveillance colonoscopy were NP-CRNs. The Japan Polyp Study: University Hospital Medical Information Network Clinical Trial Registry: University Hospital Medical Information Network Clinical Trial Registry, C000000058; cohort study: UMIN000040731., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Aberrant DNA methylation is prevalent in colorectal serrated lesions. We previously reported that the CpG island of SMOC1 is frequently methylated in traditional serrated adenomas (TSAs) and colorectal cancers (CRCs) but is rarely methylated in sessile serrated lesions (SSLs). In the present study, we aimed to further characterize the expression of SMOC1 in early colorectal lesions., Methods: SMOC1 expression was analyzed immunohistochemically in a series of colorectal tumors (n = 199) and adjacent normal colonic tissues (n = 112)., Results: SMOC1 was abundantly expressed in normal colon and SSLs while it was significantly downregulated in TSAs, advanced adenomas and cancers. Mean immunohistochemistry scores were as follows: normal colon, 24.2; hyperplastic polyp (HP), 18.9; SSL, 23.8; SSL with dysplasia (SSLD)/SSL with early invasive cancer (EIC), 15.8; TSA, 5.4; TSA with high grade dysplasia (HGD)/EIC, 4.7; non-advanced adenoma, 21.4; advanced adenoma, 11.9; EIC, 10.9. Higher levels SMOC1 expression correlated positively with proximal colon locations and flat tumoral morphology, reflecting its abundant expression in SSLs. Among TSAs that contained both flat and protruding components, levels of SMOC1 expression were significantly lower in the protruding components., Conclusion: Our results suggest that reduced expression of SMOC1 is associated with progression of TSAs and conventional adenomas and that SMOC1 expression may be a biomarker for diagnosis of serrated lesions and risk prediction in colorectal tumors., (© 2024. The Author(s).)

Objectives: In recent years, the incidence of invasive fungal infections has increased, resulting in considerable morbidity and mortality, particularly among immunocompromised individuals. Potential challenges in treating these infections with the few existing antifungal agents highlight the urgency of developing new ones. Here, we evaluated six alkyl polyamine compounds (APCs), not previously reported as antifungal drugs to our knowledge, that could deprive fungi of essential transition metals., Methods: The APC with confirmed antifungal activity against Candida spp. was analysed by using transcriptomics, followed by metal-addition experiments, mass spectrometric analyses and intracellular zinc quantification with a fluorescent probe., Results: A cyclic APC with three pyridylmethyl groups, APC6, had high antifungal activity against a wide range of Candida species, including MDR Candida auris . We conclusively demonstrated that APC6 was able to capture zinc within fungal cells. APC6 not only exhibited activity against C. auris as a single agent but also enhanced the efficacy of an azole antifungal agent, voriconazole, in vitro and in vivo . APC6 disrupted the biofilms formed by Candida species., Conclusions: This zinc-chelating compound has potential as an antifungal agent, and the control of zinc levels in Candida species could be a powerful approach to treating drug-resistant candidiasis., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

The frequency of falls increases with age. In Japan, the population is aging rapidly, and fall prevention measures are an urgent issue. However, assessing fall risk during the coronavirus disease pandemic was complicated by the social distancing measures implemented to prevent the disease, while traditional assessments that involve actual measurements are complicated. This prospective cohort study predicted the risk of falls in community-dwelling older adults using an assessment method that does not require actual measurements. A survey was conducted among 434 community-dwelling older adults to obtain data regarding baseline attributes (age, sex, living with family, use of long-term care insurance, and multimorbidity), Frailty Screening Index (FSI) score, and Questionnaire for Medical Checkup of Old-Old (QMCOO) score. The participants were categorized into fall ( n = 78) and non-fall ( n = 356) groups. The binomial logistic regression analysis showed that it is better to focus on the QMCOO sub-item score, which focuses on multiple factors. The items significantly associated with falls were Q5 (odds ratio [OR] 1.95), Q8 (OR 2.33), and Q10 (OR 3.68). Our results were similar to common risk factors for falls in normal times. During the pandemic, being able to gauge the risk factors for falls without actually measuring them was important.

Combination immunotherapy with multiple immune checkpoint inhibitors (ICIs) has been approved for various types of malignancies, including malignant pleural mesothelioma (MPM). Podoplanin (PDPN), a transmembrane sialomucin-like glycoprotein, has been investigated as a diagnostic marker and therapeutic target for MPM. We previously generated and developed a PDPN-targeting Ab reagent with high Ab-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). However, the effects of anti-PDPN Abs on various tumor-infiltrating immune cells and their synergistic effects with ICIs have remained unclear. In the present study, we established a novel rat-mouse chimeric anti-mouse PDPN IgG 2a mAb (PMab-1-mG 2a ) and its core-fucose-deficient Ab (PMab-1-mG 2a -f) to address these limitations. We identified the ADCC and CDC activity of PMab-1-mG 2a -f against the PDPN-expressing mesothelioma cell line AB1-HA. The antitumor effect of monotherapy with PMab-1-mG 2a -f was not sufficient to overcome tumor progression in AB1-HA-bearing immunocompetent mice. However, PMab-1-mG 2a -f enhanced the antitumor effects of CTLA-4 blockade. Combination therapy with anti-PDPN Ab and anti-CTLA-4 Ab increased tumor-infiltrating natural killer (NK) cells. The depletion of NK cells inhibited the synergistic effects of PMab-1-mG 2a -f and CTLA-4 blockade in vivo. These findings indicated the essential role of NK cells in novel combination immunotherapy targeting PDPN and shed light on the therapeutic strategy in advanced MPM., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Immune checkpoint inhibitors (ICIs) are a revolutionary paradigm in the treatment of thoracic malignancies and chemoimmunotherapy is a current standard care in this field. Chemotherapeutic agents are known to induce not only direct cytotoxic effects on tumor cells but also immune modulating effects, such as stimulating immunogenic cell death (ICD). Currently, either pemetrexed (PEM) or taxane plus platinum are combined with ICIs for patients with non-small cell lung cancer (NSCLC); however, it is still unknown whether these agents are immunologically optimal partners for ICIs., Methods: To determine the immunologically optimal chemotherapeutic agent, we first evaluated the ability of several chemotherapeutic agents, including platinum, PEM, taxane, and 5-fluorouracil (5-FU) to induce ICD using several thoracic tumor cell lines in vitro. ICD was evaluated by the cell surface expression of calreticulin (CRT) and adenosine-triphosphate (ATP) secretion. We further performed an antitumor vaccination assay in vivo., Results: 5-FU induced cell surface expression of CRT and ATP secretion most efficiently among the several chemotherapeutic agents. This effect was enhanced when it was combined with platinum. In the antitumor vaccination assay in vivo, we found that vaccination with dying-AB1-HA (a murine malignant mesothelioma cell line) cells treated with 5-FU, but neither PEM nor PTX, reduced the tumor growth of living-AB1-HA cells inoculated 1 week after vaccination by recruiting CD3 + CD8 + T cells into the tumor microenvironment., Conclusion: Our findings indicate that fluoropyrimidine can be an immunologically optimal partner of ICIs through the induction of ICD for thoracic malignancies., (© 2023 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

In patent ductus arteriosus (PDA) in preterm infants, the relationship between treatment timing and long-term developmental prognosis remains unclear. The purpose of this study was to clarify the relationship between the age in days when ductus arteriosus closure occurred and long-term development. Preterm infants with a birth weight of less than 1500 g who were admitted to our NICU over a period of 9 years (2011-2019) and were diagnosed with PDA were included. A new version of the K-type developmental test for corrected ages of 1.5 and 3 years was used as an index of development. The relationship between the duration of PDA and the developmental index was evaluated using Pearson's correlation coefficient, and multiple regression analysis was performed. Development quotient (DQ) at the ages of 1.5 and 3 years showed a correlation with the PDA closure date and the standard deviation (SD) value of the term birth weight. Multiple regression analysis showed a positive correlation of the DQ at 1.5 and 3 years with the SD value of the term birth weight and a negative correlation with the PDA closure date. In addition, a stronger correlation was found in the "posture/motor" sub-item at 3 years. On the other hand, the analysis including preterm infants without PDA showed that preterm infants with PDA closure on the 6th day or later after birth had a significantly lower 3-year-old DQ than preterm infants with a PDA exposure within 5 days. In conclusion, it is suggested that the decrease in cerebral blood flow due to PDA in preterm infants has an adverse effect on long-term neurodevelopment. Appropriate interventions, including surgical treatment for PDA in preterm infants without delay, ideally within 5 days of birth, may be effective in improving the developmental prognosis., Competing Interests: The authors declare no conflicts of interest.