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Chiharu Wada-Koike,1,&ast; Ryo Terauchi,1,&ast; Kota Fukai,2 Kei Sano,1 Euido Nishijima,1 Koji Komatsu,1 Kyoko Ito,3 Tomohiro Kato,3 Masayuki Tatemichi,2 Yoshiaki Kabata,4,&ast; Tadashi Nakano1 1Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan; 2Department of Preventive Medicine, Tokai University School of Medicine, Isehara, Japan; 3Centre for Preventive Medicine, The Jikei University School of Medicine, Tokyo, Japan; 4Department of Ophthalmology, Jikei University School of Medicine, Daisan Hospital, Tokyo, Japan&ast;These authors contributed equally to this workCorrespondence: Yoshiaki Kabata, Department of Ophthalmology, Jikei University School of Medicine, Daisan Hospital, 4-11-1 Izumihontyou, Komae-si, Tokyo, 125-8506, Japan, Tel +81 3 3480 1151, Fax +81 3 3480 5700, Email kabata22122@gmail.comPurpose: To examine the variability in glaucoma screening using fundus images among physicians, including non-ophthalmologists.Patients and Methods: Sixty-nine eyes from 69 patients, including 25 eyes with glaucoma, were included from the Jikei University Hospital from July 2019 to December 2022. Fundus images were captured using TRC-NW8 (Topcon Corporation, Tokyo, Japan), and were interpreted by 10 non-ophthalmologists, 10 non-specialist ophthalmologists, and 9 specialists for diagnostic accuracy. We analyzed differences in diagnostic accuracy among the three groups. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Kappa coefficient were compared, using the Kruskal–Wallis test followed by a post hoc Dunn’s test.Results: The sensitivity and specificity were 0.22 and 0.92 for non-ophthalmologists, 0.49 and 0.83 for non-specialist ophthalmologists, and 0.68 and 0.87 for specialists, respectively. Both specialists and non-specialist ophthalmologists showed significantly higher sensitivity than non-ophthalmologists (Dunn’s test, P< 0.001 and P=0.031). There was no significant difference in specificity among the three groups (Kruskal–Wallis test, P=0.086). The PPV did not differ significantly between the groups (Kruskal–Wallis test, P=0.108), while the NPV was significantly higher in specialists compared to non-ophthalmologists (Dunn’s test, P< 0.001). Specialists also had a significantly higher Kappa coefficient than non-ophthalmologists and non-specialist ophthalmologists (Dunn’s test, P< 0.001 and P=0.024).Conclusion: Diagnostic accuracy varied significantly based on the physician’s background.Keywords: glaucoma, fundus images, sensitivity, specificity, health checkup

The external quantum efficiency (EQE) and internal quantum efficiency (IQE) of radiation are quantified by omnidirectional photoluminescence measurements using an integrating sphere for two types of GaN crystals with different carbon concentrations ([C] = 1 × 10 14 cm − 3 , 2 × 10 15 cm − 3 ). In the sample with lower [C], when the excitation density is 140 W cm − 2 , the EQE and IQE for near-band-edge (NBE) emission are 0.787% and 21.7%, respectively. The relationship between [C] and the IQE for NBE emission indicates that carbon impurities work as effective nonradiative recombination centers (NRCs) in n-type GaN, and major NRCs switch from carbon impurities to intrinsic NRCs, such as vacancies, when [C] falls below 3.5 × 10 14 cm − 3 . [ABSTRACT FROM AUTHOR]

In this study, thermosensitive liposomes (TSLs) encapsulating urinary excretable radiolabeled compounds were developed. We considered that the release of the radiolabeled compounds from the TSLs in the blood by heating the blood in peripheral tissues can achieve rapid clearance of radioactivity, resulting in improved imaging contrast. To demonstrate the hypothesis, classical TSLs mainly composed of 1,2-dipalmitoyl- sn -glycero-3-phosphocholine with a phase transition temperature of 41 °C were used. The optimal composition of TSLs was determined by an in vitro release test using [ 111 In]In-diethylenetriaminepentaacetic acid (DTPA)-encapsulated liposomes, which showed that the cholesterol content drastically changed the release characteristics of classical TSLs. In the biodistribution experiments, [ 111 In]In-DTPA was significantly released from the TSLs in the blood when the tails of mice were heated at 43 °C. The tumor-to-blood ratio of the heated group was three times higher than that of the nonheated group, and accumulation in normal tissues of the heated group was lower than that of the nonheated group. These results demonstrate the usefulness of the method using TSLs to encapsulate urinary excretable radiolabeled compounds for improving imaging contrast.

Background: Major hepatectomy (MH) can increase the risk of adverse events (AEs) owing to impaired drug metabolism due to decreased liver volume and surgical injury. Thus, we performed this subgroup analysis using data from JCOG1113, a phase III trial comparing gemcitabine plus S-1 (GS) and gemcitabine plus cisplatin (GC) in patients with advanced and recurrent biliary tract cancer (BTC), to evaluate the effect of MH on the safety and efficacy of GC and GS regimens in patients with recurrent BTC., Methods: Of the 354 patients with advanced BTC enrolled in JCOG1113, 76 patients with postoperative recurrence (30 in the MH group and 46 in the non-MH group) were analyzed., Results: Grade ≥ 3 platelet count decreased in both arms was more frequent in the MH group than in non-MH group (GC, 0.0 vs. 17.6%; GS, 3.9 vs. 15.4%). However, in the MH group, the white blood cell decreased (GC, 55.0 vs. 38.5%; GS, 23.1 vs. 7.7%) and anemia (GC, 15.0 vs. 11.8%; GS, 23.1 vs. 7.7%) were less common than in the non-MH group. The MH and non-MH groups showed no significant difference in overall survival (OS) in both GC [median OS, 23.0 in MH vs. 16.9 months in non-MH (hazard ratio, 0.857; 95% CI 0.387-1.899)], and GS [median OS, 21.5 vs. 14.9 months (hazard ratio, 0.670; 95% CI 0.310-1.447)] arms., Conclusions: The safety and efficacy of gemcitabine-based chemotherapy were comparable between patients who underwent MH and those who underwent other surgeries., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Up to seven doses of coronavirus disease 2019 (COVID-19) mRNA vaccines (BNT162b2) were administered to Japanese healthcare workers, until February 2024. The monovalent Omicron XBB.1.5 vaccine (hereafter called XBB.1.5 vaccine) was used for dose 7., Objective: Although the XBB.1.5 vaccine has been reported to induce a robust increase in neutralizing antibodies against the currently circulating Omicron variant BA.2.86, little is known about its serological effects in Japan, where the BNT162b2 mRNA vaccine is the most frequently administered in the world., Study Design: Twenty-five recipients of the XBB.1.5 vaccine, categorized as seronegative (n = 18) or seropositive (n = 7) based on their recent history of COVID-19, were analyzed. Neutralizing antibody titers against Omicron subvariants, receptor binding domain (RBD) IgG levels, IgG subclass distribution, and T-cell responses were assessed., Results: We found a significant increase in neutralizing antibody titers against XBB.1.5 and BA.2.86 variants following XBB.1.5 vaccination, particularly in seropositive individuals. No significant change in total RBD IgG levels was observed, indicating efficient induction of antibodies targeting regions outside the RBD by XBB.1.5 vaccination. IgG subclass analysis demonstrated no significant subclass switching after vaccination. T-cell responses against the virus were comparable between seropositive and seronegative groups., Conclusions: The study suggests that XBB.1.5 vaccination enhances humoral immunity against Omicron variants without significant IgG subclass switching. However, some individuals with low pre-vaccination IgG titers did not exhibit increased antibody levels post-vaccination, raising concerns about potential immune tolerance., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To develop a job-exposure matrix for sedentary behavior and assess its relationship with non-communicable diseases., Methods: We constructed a job-exposure matrix using occupational and industry classifications combined with data on daily average sitting durations from 41,718 individuals. This matrix was then applied to a cohort of 706,939 participants in a case-control study to explore the link between sedentary behavior and non-communicable disease risks., Results: The matrix effectively identified sedentary behavior across different occupational groups. Using the matrix to assess sedentary behavior, associations were found between increased sedentary activity and heightened risks of diabetes, acute myocardial infarction, and endometrial cancer, while a reduced risk was observed for stroke., Conclusions: The job-exposure matrix provides valuable insights into the health impacts of sedentary behavior in the workplace, underscoring significant disease risks associated with prolonged inactivity., Competing Interests: Conflicts of interest: N.K. received grant from the Industrial Disease Clinical Research Grants from the Ministry of Health, Labour and Welfare (No. 170201-01). M.T. received founding from the Ministry of Health, Labour and Welfare in Japan., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

Background: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common encephalopathy syndrome among Japanese children. We report, for the first time, a case of AESD, in which magnetic resonance imaging (MRI) showed no diffusion abnormalities, but hyperperfusion was detected by arterial spin labelling (ASL)., Case Report: A previously healthy Japanese 1-year and 5-month-old boy was transferred to our hospital due to a consciousness disorder after >60 min of status epilepticus on the first day of fever. Brain MRI on the first day revealed no abnormal findings. On the fourth day, focal seizures of the left upper and lower limbs were observed. Thereafter, the patient's condition progressed without seizures. Diffusion-weighted imaging (DWI) on day 6 showed no abnormal findings, including a bright tree appearance. However, ASL showed hyperperfusion in the frontoparietal lobes. MRI scans on days 19 and 39 revealed that the hyperperfusion lesions on day 6 had transitioned to hypoperfusion on ASL and displayed high signal intensity on T2-weighted and fluid-attenuated inversion recovery imaging. Cerebral atrophy was also observed. Based on the clinical course and imaging findings during the chronic phase, a diagnosis of AESD was made., Conclusion: ASL may be more sensitive than DWI for detecting AESD lesions and should be performed in children with suspected AESD., 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. Published by Elsevier B.V.)

Short-chain enoyl-CoA hydratase, encoded by ECHS1, plays a major role in the valine catabolic pathway and mitochondrial fatty acid β-oxidation. Deficiency of this enzyme causes Leigh syndrome. Herein, we report a case of ECHS1 -related Leigh syndrome with a prominent ketone body spectrum on magnetic resonance spectroscopy during acute exacerbation. A 6-month-old boy with mild motor developmental delay presented with disturbances of consciousness and hypercapnia without prior infection or feeding failure. Upon admission, investigations revealed prominent ketosis and elevated 2,3-dihydroxy-2-methylbutyric acid excretion. Brain magnetic resonance imaging revealed symmetrical T2 prolongation with restricted diffusion in the basal ganglia. Magnetic resonance spectroscopy showed a prominent ketone body spectrum in the cerebral white matter, and prominent ketone bodies, elevated lactate and markedly decreased N-acetylaspartate levels in the basal ganglia. Genetic analysis identified compound heterozygous variants of ECHS1 . Short-chain enoyl-CoA hydratase deficiency is a disease for which a valine-restricted diet is reported to be beneficial, and early diagnosis is desirable. Severe ketosis and the ketone body magnetic resonance spectroscopy spectrum during acute exacerbation may aid in the diagnosis of this disease., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Reactive oxygen species generated via reperfusion cause lipid damage and induce lipid peroxidation, leading to cerebral ischemia/reperfusion injury and exacerbation of cerebral infarction. Lipid radicals are key molecules generated during lipid peroxidation. Therefore, understanding the spatiotemporal behavior of lipid radicals is important to improve the therapeutic outcomes of cerebral infarction. However, the behaviors of lipid radicals in the brain remain unclear. In this study, we aimed to evaluate the distribution of radioactivity in a transient middle cerebral artery occlusion (tMCAO) model using lipid radical detection probe [ 125 I]1 to assess the behaviors of lipid radicals after cerebral ischemia/reperfusion. The tMCAO model administered [ 125 I]1 exhibited significant differences in the timing and location of radioactivity accumulation between the ischemic and non-ischemic regions. Liquid chromatography/mass spectrometry analysis identified the lipid radical adducts formed by the reaction of 1 with the lipid radicals generated after reperfusion. More adducts were detected in the ischemic region samples than in the non-ischemic region samples. Therefore, 1 successfully detected the lipid radicals generated after cerebral ischemia/reperfusion. Overall, this study demonstrates the potential of nuclear medical imaging using radiolabeled 1 to detect the lipid radicals generated after cerebral ischemia/reperfusion. Our approach can aid in the development of new therapeutic agents scavenging lipid radicals after cerebral reperfusion by facilitating the determination of therapeutic efficacy and optimal administration period., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The sexual receptivity of female mice, shown as lordosis response, is mainly regulated by estradiol action on estrogen receptor alpha (ERα) and beta (ERβ), depending on the day of the estrous cycle. Previous studies revealed that ERα in the ventromedial nucleus of the hypothalamus (VMH) plays an essential role in the induction of lordosis on the day of estrus (Day 1). However, the mechanisms of the transition to non-receptive states on the day after estrus (Day 2) are not completely understood. In the present study, we investigated the possible role of ERβ, which is highly expressed in the dorsal raphe nucleus (DRN), in lordosis expression. We found that ERβ-Cre female mice, which were ovariectomized and primed with estradiol and progesterone to mimic the estrous cycle, showed high levels of lordosis on Day 2 when ERβ-expressing DRN (DRN-ERβ+) neuronal activity was chemogenetically suppressed. This finding suggests that excitation of DRN-ERβ+ neurons is necessary for the decline of lordosis on Day 2. Fiber photometry recordings during female-male behavioral interactions revealed that DRN-ERβ+ neuronal activation in response to male intromission was significantly more prolonged on Day 2 compared to Day 1. Chemogenetic over-stimulation of DRN-ERβ+ neurons induced c-Fos expression in brain areas known to be inhibitory for lordosis expression, even though they did not express anterogradely labeled fibers of DRN-ERβ+ cells. These findings collectively suggest that DRN-ERβ+ neuronal excitation serves as an inhibitory modulator and is responsible for the decline in receptivity during non-estrus phases. Significance Statement In females, switching from a sexually receptive state to a non-receptive phase during the estrous cycle is essential for effective behavioral interactions with males and successful reproduction. Here, we delineate the possible brain regions that regulate the decline in receptive behavioral responses, such as lordosis, from those shown on the day of estrus to those on the day after estrus. We found that excitation of neurons expressing estrogen receptor (ER) β in the midbrain dorsal raphe nucleus is crucial for the suppression of lordosis during the day after estrus. This is contrasted with the facilitatory action of ERα, another type of ER, and provides new insights for understanding the neural basis of the adaptive expression of female reproductive behavior., (Copyright © 2024 the authors.)

Purpose: Sagging eye syndrome (SES), esotropia with high myopia including heavy eye syndrome, and age-related esotropia (ARE)-collectively termed orbital pulley degeneration syndrome (OPDS)-are characterized by strabismus with orbital pulley lateral rectus-superior rectus band impairment. Herein, we examined body mass index (BMI) in OPDS to determine SES-associated anthropometric characteristics., Design: Retrospective cohort study., Methods: We compiled and analyzed the BMI of patients aged ≥50 years who underwent strabismus surgery at a single center in Shizuoka, Japan, between July 2020 and March 2023. BMI (kg/m 2 ) was categorized into 4 groups: <18.5, 18.5 to 21.9, 22 to 24.9, and ≥25. As the boundary between OPDS and SES is ambiguous, we assumed a pure SES group by excluding patients with ARE and esotropia with high myopia from the OPDS group. Overall, 204 patients (age: 67.7 ± 9.7 years) were included in the study., Results: There were 78/126 and 49/119 patients in the OPDS/non-OPDS and SES/non-SES groups (age: 70.4 ± 9.5/66.0 ± 9.6 years, P = .002 and 75.0 ± 6.0/66.6 ± 9.5 years, P < .001; BMI: 21.2 ± 3.3/23.2 ± 3.0 kg/m 2 , P < .001 and 21.2 ± 3.3/23.1 ± 3.0 kg/m 2 , P = .003), respectively. In the BMI-stratified analysis, OPDS and SES were more prevalent in the <18.5 BMI group than in the 22 to 24.9 and ≥25 BMI groups (P < .001 and P = .006, respectively). Logistic regression analysis, adjusted for age and sex, showed that lower BMI was associated with a higher prevalence of OPDS and SES., Conclusions: Patients with OPDS, including SES, had lower BMI than other patients with strabismus. Therefore, BMI may be a clinical clue to SES., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Infantile traumatic brain injury (TBI) with a biphasic clinical course and late reduced diffusion (TBIRD) has recently been reported as a distinct type of TBI in infancy. However, the pathological and prognostic factors of TBIRD remain unknown. We aimed to compare patients with and without TBIRD and evaluate the pathomechanism of TBIRD using magnetic resonance spectroscopy (MRS)., Methods: Ten Japanese patients with TBI were admitted to our hospital and underwent MRS between September 2015 and September 2022 (age range, 3-15 months; median age, 8.5 months). TBIRD was diagnosed in six patients. MRS data were compared among patients with TBIRD, patients without TBIRD, and controls. Neurological prognosis was classified into grades 1 (normal) to 3 (severe)., Results: In patients with TBIRD, MRS revealed an increase in the glutamine (Gln) level on days 3-29, which subsequently became close to normal. The degree of Gln elevation in the non-TBIRD group was smaller (117-158 % of controls) than that in the TBIRD group (210-337 %) within 14 days. MRS in the TBIRD group showed decreased N-acetyl aspartate (NAA) concentrations. The degree of NAA decrease was more prominent in grade 3 than in grades 1 and 2. NAA levels in the non-TBIRD group were almost normal., Conclusions: Patients with TBI and markedly elevated Gln levels on MRS may develop TBIRD. Neuro-excitotoxicity is a possible pathological mechanism of TBIRD. Decreased NAA levels may be useful for predicting the prognosis of patients with TBIRD., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Early tumor shrinkage (ETS) is a prognostic predictor for patients treated with chemotherapy in colorectal cancer, although scarce studies evaluated its potential in locally advanced pancreatic cancer (LAPC). In this exploratory analysis of JCOG1407, a randomized phase II study comparing modified 5-fluorouracil, levofolinate, irinotecan, and oxaliplatin (mFOLFIRINOX) and gemcitabine plus nab-paclitaxel (GnP), we evaluated whether ETS can predict prognosis of patients with LAPC., Methods: Of the 126 patients enrolled in JCOG1407, 112 with measurable lesions were included in this study. ETS was defined as a ≥20 % reduction in tumor diameter compared with baseline at the initial imaging assessment 6-10 weeks after initiating chemotherapy. Patients were divided into the ETS (achieved ETS) and non-ETS (failed to achieve ETS) groups based on their ETS status. The impact of ETS on overall survival (OS) was compared using multivariable Cox regression analysis., Results: Fourteen of 55 (25.5 %) and 24 of 57 (42.1 %) patients in the mFOLFIRINOX and GnP arms, respectively, achieved ETS. In the overall population, mFOLFIRINOX arm, and GnP arm, the median OS in the ETS and non-ETS groups was 27.1 and 20.4, 29.8 and 20.6, and 24.1 and 20.4, months, respectively. The adjusted hazard ratios of OS for the ETS group in the overall population, mFOLFIRINOX arm, and GnP arm were 0.451 (95 % confidence interval [CI]: 0.270-0.754), 0.371 (95 % CI: 0.149-0.926), and 0.508 (95 % CI: 0.255-1.004), respectively., Conclusions: ETS may be a prognostic predictor in chemotherapy-naïve patients with LAPC treated with mFOLFIRINOX or GnP., Competing Interests: Declaration of competing interest JF reports grants from the Japan Agency for Medical Research and Development (AMED) and the National Cancer Center Research and Development Fund, during the study, as well as grants from Ono Pharmaceutical, MSD, J-Ph arma, Taiho Pharmaceutical, Takeda Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Eisai, Daiichi Sankyo, Sanofi, Sumitomo Dainippon, Astellas, Delta-Fly-Pharma, and Incyte Biosciences Japan and personal fees from Fujifilm, Delta-Fly-Pharma, Onco Therapy Science, Merck Biopharma, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Chugai Pharmaceutical, Astellas, AstraZeneca, Incyte Biosciences Japan, J-Pharma, Eisai, Daiichi Sankyo, Eli Lilly Japan, Yakult Honsha, Nihon Servier, Novartis Pharma, Takeda Pharmaceutical, Bayer, Teijin Pharma, Terumo, and Incyte Biosciences Japan outside the submitted work. KN reports personal fees from Ono Pharmaceutical, Yakult Honsha, Chugai Pharmaceutical, AstraZeneca, and Taiho Pharmaceutical outside the submitted work. HI reports grants from Ono Pharmaceutical and Nihon Servier and personal fees from Nihon Servier, Yakult Honsha, Boston Scientific, Kaneka Medix, Medico's Hirata, and SB KAWASUMI LABORATORIES outside the submitted work. SS reports grants from AstraZeneca, Incyte Corporation, and Delta-Fly-Pharma outside the submitted work. SK reports personal fees from Yakult Honsha outside the submitted work. CM reports grants from Eisai, Yakult Honsha, Ono Pharmaceutical, Taiho Pharmaceutical, J-Pharma, AstraZeneca, Merck Biopharma, Daiichi Sankyo, HITACHI, and Boehringer Ingelheim and personal fees from Yakult Honsha, MSD, Nihon Servier, Boehringer Ingelheim, Taiho Pharmaceutical, Novartis Pharma, Teijin Pharma, Eisai, and AstraZeneca outside the submitted work. MU reports grants from Japan AMED and the National Cancer Center Research and Development Fund, during the study, as well as grants from Ono Pharmaceutical, Taiho Pharmaceutical, J-Pharma, AstraZeneca, Merck Biopharma, MSD, Astellas, Eisai, Boehringer Ingelheim, Delta-Fly-Pharma, Incyte Biosciences Japan, Chugai Pharmaceutical, and Novartis Pharma and personal fees from Yakult Honsha, MSD, Nihon Servier, Ono Pharmaceutical, Chugai Pharmaceutical, Boehringer Ingelheim, Taiho Pharmaceutical, Novartis Pharma, J-Pharma, Incyte Biosciences Japan, Daiichi Sankyo, and AstraZeneca outside the submitted work. All other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: Japan started the Diabetic Nephropathy Aggravation Prevention Program. Its early impact was assessed in this study., Methods: This study used the Kokuho Database of patients with type 2 diabetes from program-implementing and non-implementing municipalities (fiscal years [FYs] 2015-2021). Implementing municipalities facilitated clinic visits and provided education to eligible patients. Average treatment effects on the treated in FYs 2016 and 2018 were evaluated using the inverse probability of treatment weighting. Comparison included intervened vs. non-intervened patients in program-implementing municipalities (Comparison A), intervened patients in program-implementing vs. eligible patients in non-implementing municipalities (Comparison B), and eligible patients in implementing and non-implementing municipalities (Comparison C)., Results: Overall, 89,611/89,685 patients from FY 2016/2018 were eligible. Among 68,125/68,170 patients in program-implementing municipalities, 1,470/1,819 were intervened. In Comparison A, the estimated effect of the program on ΔeGFR at 3 years were -0.4 (95 % confidence interval; -1.0, 0.2)/-0.4 (-0.9, 0.1) mL/min/1.73 m 2 in FY 2016/2018. Comparisons B and C demonstrated similar tendency; distribution of %change in eGFR varied between municipalities., Conclusions: Early in the program, renal function did not improve in the intervened patients or program-implementing municipalities. Diverse eGFR changes across municipalities highlighted diverse intervention outcomes, emphasizing the need of program refinement., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Takehiro Sugiyama reports financial support was provided by Government of Japan Ministry of Health, Labour and Welfare. Kazuyo Tsushita reports financial support was provided by Government of Japan Ministry of Health, Labour and Welfare. If there are other authors, they 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 Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic neoplasm with few previous imaging case reports. We report multiparametric MRI findings in four cases of PSTT with special emphasis on the "pseudo-myometrial thinning" underlying the tumor., Methods: We reviewed multiparametric MRI and pathologic findings in four cases of PSTT from four institutions. Signal intensity, enhancement pattern, margins, and location of the tumors were evaluated, and myometrial thickness underlying the tumor and normal myometrial thickness contralateral to the tumor were measured on MRI. The myometrial thickness underlying the tumor was also measured in the resected specimen and compared with the myometrial thickness measured on MRI using the Friedman test., Results: All tumors showed heterogeneous signal intensity on T1-weighted imaging, T2-weighted imaging (T2WI), and diffusion-weighted imaging. Three of the four tumors had a hypervascular area on dynamic contrast-enhanced (DCE) MRI. A hypointense rim on T2WI and DCE-MRI was seen in all tumors. All tumors protruded into the uterine cavity to varying degrees and extended into the myometrium close to the serosa. The myometrial thickness underlying the tumor measured on MRI (median thickness, 1.2 mm) was significantly thinner than that measured on pathology (median thickness, 9.5 mm) and normal myometrial thickness contralateral to the tumor on MRI (median thickness, 10.3 mm) (P = 0.02), and there was no significant difference between the latter two., Conclusions: The thickness of the myometrium underlying the tumor on MRI was approximately one tenth of the thickness on pathology. Thus, the tumors appeared to have almost transmural invasion even when pathologically located within the superficial myometrium. This "pseudo-thinning" of the underlying myometrium and the hypointense rim on MRI could be caused by focal compression of the myometrium by the tumor, possibly due to the fragility of the myometrium at the placental site., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Occupational therapy (OT) studies of delirium have attempted to test the effectiveness of interventions to reduce the incidence and duration of delirium. Although some cognitive stimulation appears to be important, appropriate approaches to delirium characterized by cognitive dysfunction remain unclear. This study aimed to determine the incidence and duration of delirium in postoperative cardiovascular surgery patients at the initial time of OT to identify characteristics of patient demographics and cognitive function according to the presence or absence of delirium., Methods: This retrospective study included patients judged to have delirium by the Confusion Assessment Method at the first postoperative OT session (after extubation) in the intensive care unit (ICU). Patient data included age, sex, days until extubation, type of hospitalization, outcome at discharge, Sequential Organ Failure Assessment score and Glasgow Coma Scale (GCS) score at the first OT session, presence or absence of delirium, duration of delirium, and Mini-Mental State Examination-Japanese (MMSE-J) score. The Mann-Whitney U test was used to test differences between the delirium and the non-delirium groups, and a binomial generalized linear model (logistic regression model) with Bayesian estimation was adopted to investigate factors characterizing delirium., Results: A Bayesian logistic regression model with delirium as the dependent variable and "days until extubation" and "spatial orientation" as adjustment variables suggested that "spatial orientation" was a significant factor in delirium., Conclusions: For ICU patients with delirium, the provision of information tailored toward spatial orientation during the first day of OT may improve delirium., Competing Interests: CONFLICTS OF INTEREST: The authors declare no conflict of interest., (2024 The Japanese Association of Rehabilitation Medicine.)

A magnetically responsive photonic crystal of colloidal nanosheets can exhibit a controllable structural color, offering diverse potential applications. In this study, we systematically investigated how the lateral sizes of graphene oxide (GO) nanosheets affect their magnetic responsiveness in a photonic system. Contrary to the prediction that larger lateral sizes of nanosheets would be more responsive to an applied magnetic field based on the magnetic energy of anisotropic materials, we discovered that GO nanosheets with larger lateral sizes in the photonic system scarcely responded to a 12 T magnetic field. The lack of magnetic response may be due to the strongly restricted rotational motion of GO nanosheets by mutual electrostatic forces. In contrast, GO nanosheets with medium lateral sizes readily responded to the 12 T magnetic field, forming a uniaxially oriented structure that resulted in a vivid structural color. However, smaller GO nanosheets displayed a less vivid structural color, possibly because of less structural ordering of GO nanosheets. Finally, we found that the photonic crystal of GO nanosheets with optimized lateral sizes responded effectively to the 12 T magnetic field across various GO concentrations, resulting in a vivid and tunable structural color., (© 2024 Wiley-VCH GmbH.)

Purpose: This study sought to identify the most effective testing program for detecting visual-field defects in mild-stage glaucoma with central visual-field defects., Design: A multicenter, retrospective diagnostic testing evaluation., Participants: The study involved 93 eyes (83 patients) with mild-stage glaucoma (median mean deviation [interquartile range]: -1.79 [2.16] dB) with central visual-field defects and 69 eyes (63 patients; median mean deviation, -1.38 [2.31] dB) with mild-stage glaucoma without central visual-field defects, from Jikei University School of Medicine and Tajimi Iwase Eye Clinic., Methods: Patients underwent 10-2 Swedish Interactive Thresholding Algorithm (SITA) Standard, 24-2 SITA Standard, and 24-2C SITA Faster tests. Central visual-field defects were defined using 10-2 SITA Standard and optical coherence tomography (OCT). A detection power of 4 points in the 24-2 that coincided with 10-2 (Center4), 12 points that lie within 10° (24-2-12), and 22 points that lie within 10° of 24-2C (24-2C-22) were analyzed using receiver operating characteristic (ROC) curves based on logistic regression analysis, using total deviation (TD) and pattern deviation (PD) probability plots., Main Outcome Measures: Area under the receiver operating characteristic curve (AUC) of the Center4, 24-2-12, and 24-2C-22 tests., Results: In the upper-central visual field, AUCs of the TD plot were 0.50 (0.40-0.58) for the Center4, 0.75 (0.67-0.83) for 24-2-12, and 0.85 (0.78-0.91) for 24-2C-22, with 24-2C-22 AUC significantly exceeding 24-2-12 AUC. For the PD plot, AUCs were 0.53 (0.44-0.63), 0.81 (0.74-0.89), and 0.84 (0.77-0.90), respectively. In the lower-central visual field, using a total plot, AUCs were 0.27 (0.18-0.36), 0.57 (0.47-0.69), and 0.57 (0.46-0.68) for the Center4, 24-2-12, and 24-2C-22, respectively. Using the PD plot in the upper field, AUCs were 0.27 (0.19-0.36), 0.64 (0.53-0.75), and 0.81 (0.72-0.90), respectively, with the AUC of the 24-2C-22 significantly exceeding that of 24-2-12. The 24-2C test was significantly faster than both the 24-2 and 10-2 tests, reducing testing duration by 46% and 52%, respectively., Conclusions: The 24-2C SITA Faster test is highly effective and efficient for detecting mild-stage glaucoma with central visual-field defects. This, and its reduced duration, makes it a valuable tool in clinical settings., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: "Batch effect" in MR images, due to vendor-specific features, MR machine generations, and imaging parameters, challenges image quality and hinders deep learning (DL) model generalizability., Purpose: We aim to develop a DL model using contrast adjustment and super-resolution to reduce diffusion-weighted images (DWIs) diversity across magnetic field strengths and imaging parameters., Study Type: Retrospective., Subjects: The DL model was built using an open dataset from one individual. The MR machine identification model was trained and validated on a dataset of 1134 adults (54% females, 46% males), with 1050 subjects showing no DWI abnormalities and 84 with conditions like stroke and tumors. The 21,000 images were divided into 80% for training, 20% for validation, and 3500 for testing., Field Strength/sequence: Seven MR scanners from four manufacturers with 1.5 T and 3 T magnetic field strengths. DWIs were acquired using spin-echo sequences and high-resolution T2WIs using the T2-SPACE sequence., Assessment: An experienced, board-certified radiologist evaluated the effectiveness of restoring high-resolution T2WI and harmonizing diverse DWI with metrics such as PSNR and SSIM, and the texture and frequency attributes were further analyzed using gray-level co-occurrence matrix and 1-dimensional power spectral density. The model's impact on machine-specific characteristics was gauged through the performance metrics of a ResNet-50 model. Comprehensive statistical tests were employed for statistical robustness, including McNemar's test and the Dice index., Results: Our DL protocol reduced DWI contrast and resolution variation. ResNet-50 model's accuracy decreased from 0.9443 to 0.5786, precision from 0.9442 to 0.6494, recall from 0.9443 to 0.5786, and F1 score from 0.9438 to 0.5587. The t-SNE visualization indicated more consistent image features across multiple MR devices. Autoencoder halved learning iterations; Dice coefficient >0.74 confirmed signal reproducibility in 84 lesions., Conclusion: This study presents a DL strategy to mitigate batch effects in diffusion MR images, improving their quality and generalizability., Evidence Level: 3 TECHNICAL EFFICACY: Stage 1., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: We aimed to preliminarily compare the glaucoma detection accuracy of a head-mounted binocular visual perimeter "imo" screening program (ISP) with that of frequency doubling technology (FDT)., Methods: This multicenter, diagnostic accuracy study based on prospectively collected data included 76 non-glaucoma (including pre-perimetric glaucoma) eyes and 92 glaucomatous eyes from patients visiting two hospitals. Patients underwent ISP and FDT (C-20-1 screening program) on the same day. Diagnostic efficacy was evaluated using receiver operating characteristic curves and areas under the curve (AUCs). In addition, we compared the ISP and FDT testing times., Results: AUC values for ISP versus FDT were as follows: (1) mild-stage glaucoma (mean deviation [MD] > -6 dB), 0.82 (95% confidence interval [CI], 0.75-0.88) versus 0.76 (95% CI, 0.68-0.83); moderate-stage glaucoma (-6 dB ≥ MD ≥ -12 dB), 0.98 (95% CI, 0.95-1.00) versus 0.96 (95% CI, 0.93-1.00); and advanced-stage glaucoma (-12 dB > MD), 1.00 (95% CI, 1.00-1.00) versus 0.99 (95% CI, 0.98-1.00). In addition, mild-stage glaucoma was classified into two stages (MD > -3 D) and (-3 D ≥ MD > -6 D). AUC values were 0.81 (95% CI, 0.73-0.88) versus 0.76 (95% CI, 0.68-0.84) for MD > -3 D and 0.86 (95% CI, 0.77-0.94) versus 0.73 (95% CI, 0.61-0.86) for -3 D ≥ MD > -6 D. The testing time for the ISP was significantly shorter than that of FDT for all glaucoma stages (P < 0.001)., Conclusions: The ISP demonstrates non-inferiority in detecting glaucoma and has a shorter testing time compared with FDT. These findings provide evidence for applied further studies on large-scale population-based glaucoma screening., Translational Relevance: Our study provides a non-inferior and quicker glaucoma screening than existing tools.

Background: Helicobacter pylori ( H. pylori ), a bacterium which chronically infects the stomach of approximately half the world's population, is a risk factor for the development of gastric cancer (GC). However, the underlying mechanism whereby H. pylori infection induces GC development remains unclear. Intermittent injection of the H. pylori cytotoxin-associated gene A antigen (CagA) protein into its host cell inhibits nuclear translocation of BRCA1/BRCA2, DNA repair proteins involved in the development of breast cancer/ovarian cancer. Interestingly, hereditary breast and ovarian cancer (HBOC) syndrome is associated with GC development. Here, we aimed to clarify the molecular link between H. pylori infection, BRCA1/2 pathogenic variants (PVs), GC and higher GC incidence in HBOC families., Methods: We retrospectively reviewed data from Japanese patients undergoing precision treatment using cancer genomic medicine., Results: We found a higher GC incidence in HBOC families having germline pathogenic variants (GPVs) of BRCA1/2 (2.95% vs. 0.78% in non-HBOC families). Next, we found that 96.1% of H. pylori -infected patients received cancer genomic medicine for advanced GC, and > 16% advanced GC patients had gBRCA2 PVs. Furthermore, expressing wild-type BRCA1/2 in Gan mice (a mouse model of human GC) inhibited GC development. Thus, gBRAC1/2 PVs and H. pylori infection synergistically increase the risk of GC development., Conclusion: Our study highlights the need to investigate the potential of therapeutic agents against BRCA1/2 PVs to avoid the development of GC in HBOC families. In addition, our results suggest that poly (ADP-ribose) polymerase (PARP) inhibitors could potentially inhibit GC development and progression with gBRCA1/2 PVs., Competing Interests: The authors state no competing interest., (Copyright 2024, Hayashi et al.)

Prevention of postoperative splenic infarction in the robotic Warshaw technique requires rigorous evaluation of blood flow to the spleen. Shibuya and colleagues recommend checking: (1) conventional splenic color change, (2) intrasplenic artery waveform by ultrasound Doppler examination, (3) blood flow using indocyanine green, and (4) pulsatile regurgitation from the splenic artery., (© 2024 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Porphyromonas gingivalis is the most pathogenic periodontal bacterium in the world. Recently, P. gingivalis has been considered responsible for dysbiosis during the development of periodontitis. This study aimed to evaluate a novel immunochromatographic device using monoclonal antibodies against P. gingivalis in subgingival plaques. A total of 72 patients with chronic periodontitis and 53 periodontally healthy volunteers underwent clinical and microbiological examinations. Subgingival plaque samples were analyzed for the presence of P. gingivalis and compared using real-time polymerase chain reaction (PCR). In the periodontitis group, a significant positive correlation was observed between the test device scores and the real-time PCR results. The specificity, positive predictive value, negative predictive value, and accuracy of the test device for P. gingivalis , as determined by real-time PCR, were 98%, 94%, 89%, and 90%, respectively. There were significant differences in bacterial counts by real-time PCR among the groups with different ranges of device scores. Additionally, there was a significant positive correlation between the device scores for P. gingivalis and periodontal parameters. These results suggest that this novel immunochromatographic device can be effectively used for rapid detection and semi-quantification of P. gingivalis in subgingival plaques.

Background and Objectives: Integrating large language models (LLMs) such as GPT-4 Turbo into diagnostic imaging faces a significant challenge, with current misdiagnosis rates ranging from 30-50%. This study evaluates how prompt engineering and confidence thresholds can improve diagnostic accuracy in neuroradiology., Methods: We analyze 751 neuroradiology cases from the American Journal of Neuroradiology using GPT-4 Turbo with customized prompts to improve diagnostic precision., Results: Initially, GPT-4 Turbo achieved a baseline diagnostic accuracy of 55.1%. By reformatting responses to list five diagnostic candidates and applying a 90% confidence threshold, the highest precision of the diagnosis increased to 72.9%, with the candidate list providing the correct diagnosis at 85.9%, reducing the misdiagnosis rate to 14.1%. However, this threshold reduced the number of cases that responded., Conclusions: Strategic prompt engineering and high confidence thresholds significantly reduce misdiagnoses and improve the precision of the LLM diagnostic in neuroradiology. More research is needed to optimize these approaches for broader clinical implementation, balancing accuracy and utility.

Reports indicate that an interaction between TRPV4 and anoctamin 1 (ANO1) could be widely involved in water efflux of exocrine glands, suggesting that the interaction could play a role in perspiration. In secretory cells of sweat glands present in mouse foot pads, TRPV4 clearly colocalized with cytokeratin 8, ANO1, and aquaporin-5 (AQP5). Mouse sweat glands showed TRPV4-dependent cytosolic Ca 2+ increases that were inhibited by menthol. Acetylcholine-stimulated sweating in foot pads was temperature-dependent in wild-type, but not in TRPV4-deficient mice and was inhibited by menthol both in wild-type and TRPM8KO mice. The basal sweating without acetylcholine stimulation was inhibited by an ANO1 inhibitor. Sweating could be important for maintaining friction forces in mouse foot pads, and this possibility is supported by the finding that wild-type mice climbed up a slippery slope more easily than TRPV4-deficient mice. Furthermore, TRPV4 expression was significantly higher in controls and normohidrotic skin from patients with acquired idiopathic generalized anhidrosis (AIGA) compared to anhidrotic skin from patients with AIGA. Collectively, TRPV4 is likely involved in temperature-dependent perspiration via interactions with ANO1, and TRPV4 itself or the TRPV4/ANO 1 complex would be targeted to develop agents that regulate perspiration., Competing Interests: MK, SD, RY, KS, JL, MK, MT No competing interests declared, (© 2024, Kashio, Derouiche et al.)

Purpose: To assess the effects of intraocular lens (IOL) decentration and tilt, as well as age, on postoperative visual function (corrected distance visual acuity [CDVA] and contrast sensitivity) by comparing an extended depth-of-focus IOL using higher order aspheric optics against a monofocal IOL from the same platform., Methods: This retrospective observational study targeted patients without other eye diseases who underwent surgery to implant the Tecnis Eyhance OptiBlue or the monofocal IOL Tecnis OptiBlue 1-Piece (J&J Vision) during cataract surgery from November 2021 to December 2022. The effects of age, axial length, IOL decentration, tilt, and corneal higher order aberrations (HOAs) on the postoperative 5 m CDVA and area under log contrast sensitivity function (AULCSF) under photopic and scotopic conditions were evaluated within 3 months of surgery., Results: No significant difference was found in postoperative CDVA between the Tecnis Eyhance OptiBlue group (n = 61 eyes) and the Tecnis OptiBlue 1-Piece group (n = 35 eyes), but AULCSF was significantly better in the Tecnis Eyhance OptiBlue group for photopic (1.58 ± 0.13 vs 1.46 ± 0.18; P = .002) and scotopic (1.71 ± 0.11 vs 1.59 ± 0.19; P = .002) eyes. Multivariate analysis showed a negative correlation between AULCSF and IOL decentration and age in the Tecnis Eyhance OptiBlue group ( P < .01), with no significant correlation with tilt, axial length, and corneal HOAs., Conclusions: The Tecnis Eyhance OptiBlue yielded significantly better contrast sensitivity under photopic and scotopic conditions than the Tecnis OptiBlue 1-Piece. However, it is important to consider the effects of IOL decentration and age when evaluating the contrast sensitivity of the Tecnis Eyhance OptiBlue. [ J Refract Surg . 2024;40(7):e499-e505.] .

Background: Coronavirus disease 2019 (COVID-19) can lead to severe respiratory illness, rapid disease progression, and higher rates of intensive care unit admission in pregnant women. Infection during pregnancy is associated with an increased risk of preterm delivery, cesarean section, fetal dysfunction, preeclampsia, and perinatal death. Vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from pregnant women to their fetuses has also been observed. Although severe infections in neonates and infants are rare, newborns can experience serious consequences from COVID-19 due to their suboptimal humoral immune system protection. The amino acids in the structural proteins of SARS-CoV-2 are constantly mutating. Since around January 2023, COVID-19, caused by omicron-type SARS-CoV-2 variants, has been prevalent globally. These variants can evade the immune response triggered by traditional mRNA-based COVID-19 vaccines, such as BNT162b2. Therefore, vaccination with BNT162b2 XBB.1.5, which provides protection against omicron-type SARS-CoV-2 variants, is recommended., Methods: This retrospective cohort study included 148 pregnant women who received the BNT162b2 XBB.1.5 vaccine at 30 partner medical institutions from September 2023 to January 2024. We examined the titers of anti-spike glycoprotein SARS-CoV-2 immunoglobin G (IgG) and IgA in the blood and umbilical cord blood obtained from the participants using ELISA., Findings: Anti-spike glycoprotein SARS-CoV-2 IgG and IgA titers were highest in the blood and cord blood at late gestational age (28-34 weeks). No serious side effects or adverse events were observed in either the pregnant women or their newborns., Interpretation: Pregnant women who received the BNT162b2 XBB.1.5 vaccine during gestational weeks 28 to 34 had the highest titers of anti-omicron SARS-CoV-2 variant antibodies in their blood. Moreover, these antibodies were transferred to their umbilical cord blood. To validate our findings, large cohort clinical studies involving numerous pregnant women are warranted., Funding: This study was funded by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) and Grants-in-Aid for Medical Research from the Japan Agency for Medical Research and Development (AMED).

Objective and background This study aimed to develop a deep convolutional neural network (DCNN) model capable of generating synthetic 4D magnetic resonance angiography (MRA) from 3D time-of-flight (TOF) images, allowing estimation of temporal changes in arterial flow. TOF MRA provides static information about arterial structures through maximum intensity projection (MIP) processing, but it does not capture the dynamic information of contrast agent circulation, which is lost during MIP processing. Considering the principles of TOF, it is hypothesized that dynamic information about arterial blood flow is latent within TOF signals. Although arterial spin labeling (ASL) can extract dynamic arterial information, ASL MRA has drawbacks, such as longer imaging times and lower spatial resolution than TOF MRA. This study's primary aim is to extend the utility of TOF MRA by training a machine-learning model on paired TOF and ASL data to extract latent dynamic information from TOF signals. Methods A DCNN combining a modified U-Net and a long-short-term memory (LSTM) network was trained on a dataset of 13 subjects (11 men and two women, aged 42-77 years) using paired 3D TOF MRA and 4D ASL MRA images. Subjects had no history of cerebral vessel occlusion or significant stenosis. The dataset was acquired using a 3T MRI system with a 32-channel head coil. Preprocessing involved resampling and intensity normalization of TOF and ASL images, followed by data augmentation and arterial mask generation. The model learned to extract flow information from TOF images and generate 8-phase 4D MRA images. The precision of flow estimation was evaluated using the coefficient of determination (R²) and Bland-Altman analysis. A board-certified neuroradiologist validated the quality of the images and the absence of significant stenosis in the major cerebral arteries. Results The generated 4D MRA images closely resembled the ground-truth ASL MRA data, with R² values of 0.92, 0.85, and 0.84 for the internal carotid artery (ICA), proximal middle cerebral artery (MCA), and distal MCA, respectively. Bland-Altman analysis revealed a systematic error of -0.06, with 95% agreement limits ranging from -0.18 to 0.12. Additionally, the model successfully identified flow abnormalities in a subject with left MCA stenosis, displaying a delayed peak and subsequent flattening distal to the stenosis, indicative of reduced blood flow. Visualization of the predicted arterial flow overlaid on the original TOF MRA images highlighted the spatial progression and dynamics of the flow. Conclusions The DCNN model effectively generated synthetic 4D MRA images from TOF images, demonstrating its potential to estimate temporal changes in arterial flow accurately. This non-invasive technique offers a promising alternative to conventional methods for visualizing and evaluating healthy and pathological flow dynamics. It has significant potential to improve the diagnosis and treatment of cerebrovascular diseases by providing detailed temporal flow information without the need for contrast agents or invasive procedures. The practical implementation of this model could enable the extraction of dynamic cerebral blood flow information from routine brain MRI examinations, contributing to the early diagnosis and management of cerebrovascular disorders., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Wada et al.)

The transposition of an adjacent finger following the loss of a finger due to a malignant tumor resection improves hand function. However, patients may not accept the resulting appearance of a three-finger hand. A 28-year-old male with a malignant fibroblastic tumor at the base of the ring finger underwent resection of the tumor, excising the phalanx and a portion of the metacarpal. He refused a ray amputation and subsequent fifth-finger transposition. Therefore, we reconstructed the defect with a long-vascularized subtotal second toe from the metacarpal neck to the middle phalanx base of the fourth finger. There was no tumor recurrence, and the patient was highly satisfied with hand function and cosmetic appearance at 3 years of follow-up., (© 2024 Published by Elsevier B.V. on behalf of Society for Indian Hand Surgery and Micro Surgeons.)

In ovo exposure to o,p'-dichloro-diphenyl-trichloroethane (o,p'-DDT) impairs reproduction by inducing malformation of the reproductive organs in birds, although the mechanism remains unclear. Here, we examined the effects of o,p'-DDT on the development of the reproductive organs, the expression of genes controlling sexual differentiation, and the plasma concentrations of testosterone and estradiol in Japanese quail embryos. o,p'-DDT-containing sesame oil was injected into the yolk sac on Embryonic Day (E) 3 at a dose of 500, 2,000, or 8,000 μg per egg. On E15, the reproductive organs were observed; the gonads and Müllerian ducts (MDs) were sampled to measure the mRNA of steroidogenic enzymes, sex steroid receptors, anti-Müllerian hormone (AMH), and AMH receptor 2 (AMHR2); blood samples were collected to assay plasma testosterone and estradiol levels; and the gonads were used for histological analysis. o,p'-DDT dose-dependently increased the prevalence of hypertrophic MDs in females and residual MDs in males. In female MDs, o,p'-DDT dose-dependently decreased estrogen receptor (ER) α, ERβ, and AMHR2 mRNA expression. o,p'-DDT dose-dependently induced left-biased asymmetry of testis size, and ovary-like tissue was found in the left testis after exposure to 8,000 μg per egg o,p'-DDT, although asymmetric gene expression did not occur. o,p'-DDT did not affect ovarian tissue but did decrease 17α-hydroxylase/C17-20 lyase mRNA expression and dose-dependently increased ERβ mRNA expression. o,p'-DDT decreased plasma testosterone concentrations in females. These findings suggest that o,p'-DDT induces hypertrophy of the MDs and ovarian tissue formation in the left testis. Abnormal MD development may be linked to altered gene expression for sensing estrogens and AMH signals., (© 2023 John Wiley & Sons Ltd.)

Magnetically responsive photonic crystals of colloidal nanosheets hold great promise for various applications. Here, we systematically investigated the magnetically responsive behavior of a photonic crystal consisting of graphene oxide (GO) nanosheets and water. After applying a 12 T magnetic field perpendicular and parallel to the observation direction, the photonic crystal exhibited a more vivid structural color and no structural color, respectively, based on the magnetic orientation of GO nanosheets. The reflection wavelength can be modulated by varying the GO concentration, and the peak intensity can be basically enhanced by increasing both the time and strength of the magnetic application. To improve color quality, we developed a novel approach of alternately applying a magnetic field to two orthogonal directions, instead of using a rotating magnetic field. Finally, we achieved color switching by changing the direction of applied magnetic fields.

The standard treatment for mucous cysts with Heberden nodes is excision of the dorsolateral osteophytes and capsule of the distal interphalangeal joint or thumb interphalangeal joint, including the stalk of the cyst. The skin incision varies for cases depending upon the geometry. We propose a surgical method utilizing blind lateral approaches for treating such mucous cysts., (© 2024 Published by Elsevier B.V. on behalf of Society for Indian Hand Surgery and Micro Surgeons.)

Rare sugars are known for their ability to suppress postprandial blood glucose levels. Therefore, oligosaccharides and disaccharides derived from rare sugars could potentially serve as functional sweeteners. A disaccharide [α-d-allopyranosyl-(1→2)-β-d-psicofuranoside] mimicking sucrose was synthesized from rare monosaccharides D-allose and D-psicose. Glycosylation using the intermolecular aglycon delivery (IAD) method was employed to selectively form 1,2- cis α-glycosidic linkages of the allopyranose residues. Moreover, β-selective psicofuranosylation was performed using a psicofuranosyl acceptor with 1,3,4,6-tetra- O -benzoyl groups. This is the first report on the synthesis of non-reducing disaccharides comprising only rare d-sugars by IAD using protected ketose as a unique acceptor; additionally, this approach is expected to be applicable to the synthesis of functional sweeteners.

Generally, in vertebrates, the first step toward fertilization is the ovulation of mature oocytes, followed by their binding to sperm cells outside of the ovary. Exceptionally, the oocytes of poeciliid fish are fertilized by sperm cells within the follicle, and the developmental embryo is subsequently released into the ovarian lumen before delivery. In the present study, we aimed to identify the factor(s) responsible for intrafollicular fertilization in a viviparous teleost species, Poecilia reticulata (guppy). Sperm tracking analysis in this regard indicated that in this species, sperm cells reached immature oocytes including the germinal vesicle, and the insemination assay indicated that the immature oocytes robustly adhered to the sperm cells; similar binding was not observed in Danio rerio (zebrafish) and Oryzias latipes (medaka). We also identified the Ly6/uPAR protein bouncer as the factor responsible for the observed sperm binding activity of the immature oocytes in this species. The recombinant bouncer peptide acted as an inhibitory decoy for the sperm-oocyte binding in guppy. On the other hand, ectopic expression of guppy bouncer in zebrafish oocytes resulted in interspecific sperm-oocyte binding. These results argue that bouncer is responsible for sperm-immature oocyte binding. Our findings highlight the unique reproductive strategies of guppy fish and enhance our understanding of the diverse reproductive mechanisms in vertebrates., (© 2024 Japanese Society of Developmental Biologists.)

The primary mode of transmission for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is infection of the respiratory tract through droplets and/or aerosols. Therefore, immune responses at respiratory mucosal surfaces play a significant role in the prevention of infection. Greater emphasis is now being placed on mucosal immunity induced by exposure to SARS-CoV-2 antigens through infection or vaccination. In concert with cellular immunity, humoral responses at mucosal surfaces, especially the secretory version of immunoglobulin A (sIgA), can be instrumental in preventing respiratory infections. A better understanding of mucosal immune responses can further our knowledge of immunity to SARS-CoV-2 and help inform vaccine design. Here we describe a detailed protocol for an in vitro assay based on the enzyme-linked immunosorbent assay (ELISA) to assess mucosal antibody response to SARS-CoV-2 spike protein in human saliva. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: ELISA measurement of mucosal antibodies to SARS-CoV-2 spike protein in human saliva., (© 2024 The Authors. Current Protocols published by Wiley Periodicals LLC.)

Prcis: The analysis of intraocular pressure (IOP) by day of the week using the mega database showed a periodic weekly pattern with the highest value on Monday., Purpose: To evaluate IOP by the day of the week., Patients and Methods: Annual health checkup examinees between April 2014 and March 2015 were cross-sectionally evaluated. As a result, 655,818 participants [51.5±10.5 (range: 20-96) years, 40.1% women] from 103 medical centers were included. IOP was measured using a noncontact tonometer. The mean IOPs of each day of the week were compared using multiple comparison test and multiple linear regression analysis. Wednesday was set as the reference. Moreover, weekly IOP variations stratified by sex and age were also evaluated., Results: Mean IOPs from Monday to Sunday were 13.19±2.97, 13.06±2.92, 13.05±2.91, 13.05±2.92, 13.12±2.94, 13.10±2.96, and 13.16±2.78 mm Hg. IOP was significantly higher on Monday, Friday, and Saturday than those on Wednesday ( P <0.001, <0.001, 0.002). After adjusting for factors affecting IOP, the IOPs on Monday and Saturday were higher than those on Wednesday [β=0.097 (95% CI: 0.074-0.121), P <0.001; β=0.032 (95% CI: 0.005-0.059), P =0.019]. Men had significantly higher IOPs on Monday and Saturday than on Wednesday [β=0.142 (95% CI: 0.110-0.173), P <0.001; β=0.053 (95% CI: 0.017-0.089), P =0.004], whereas women did not have a significant trend. Participants aged below 65 years had higher IOPs on Monday ( P <0.001 in under 60 years; P =0.003 in 60-64 years), while those aged 65 years or older did not ( P =0.856)., Conclusion: IOP values may have a periodic weekly pattern. The high IOP on Monday was more pronounced in men aged less than 65 years., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Yolk-consuming (lecithotrophic) embryos of oviparous animals, such as those of fish, need to make do with the maternally derived yolk. However, in many cases, yolk possesses little carbohydrates and sugars, including glucose, the essential monosaccharide. Interestingly, increases in the glucose content were found in embryos of some teleost fishes; however, the origin of this glucose has been unknown. Unveiling new metabolic strategies in fish embryos has a potential for better aquaculture technologies. In the present study, using zebrafish, we assessed how these embryos obtain the glucose. We employed stable isotope ( 13 C)-labeled substrates and injected them to the zebrafish embryos. Our liquid chromatography-mass spectrometry-based isotope tracking revealed that among all tested substrate, glutamate was most actively metabolized to produce glucose in the zebrafish embryos. Expression analysis for gluconeogenic genes found that many of these were expressed in the yolk syncytial layer (YSL), an extraembryonic tissue found in teleost fishes. Generation 0 (G0) knockout of pck2 , a gene encoding the key enzyme for gluconeogenesis from Krebs cycle intermediates, reduced gluconeogenesis from glutamate, suggesting that this gene is responsible for gluconeogenesis from glutamate in the zebrafish embryos. These results showed that teleost YSL undergoes gluconeogenesis, likely contributing to the glucose supplementation to the embryos with limited glucose source. Since many other animal lineages lack YSL, further comparative analysis will be interesting., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Historically, antibody reactivity to pathogens and vaccine antigens has been evaluated using serological measurements of antigen-specific antibodies. However, it is difficult to evaluate all antibodies that contribute to various functions in a single assay, such as the measurement of the neutralizing antibody titer. Bulk antibody repertoire analysis using next-generation sequencing is a comprehensive method for analyzing the overall antibody response; however, it is unreliable for estimating antigen-specific antibodies due to individual variation. To address this issue, we propose a method to subtract the background signal from the repertoire of data of interest. In this study, we analyzed changes in antibody diversity and inferred the heavy-chain complementarity-determining region 3 (CDRH3) sequences of antibody clones that were selected upon influenza virus infection in a mouse model using bulk repertoire analysis. A decrease in the diversity of the antibody repertoire was observed upon viral infection, along with an increase in neutralizing antibody titers. Using kernel density estimation of sequences in a high-dimensional sequence space with background signal subtraction, we identified several clusters of CDRH3 sequences induced upon influenza virus infection. Most of these repertoires were detected more frequently in infected mice than in uninfected control mice, suggesting that infection-specific antibody sequences can be extracted using this method. Such an accurate extraction of antigen- or infection-specific repertoire information will be a useful tool for vaccine evaluation in the future., Importance: As specific interactions between antigens and cell-surface antibodies trigger the proliferation of B-cell clones, the frequency of each antibody sequence in the samples reflects the size of each clonal population. Nevertheless, it is extremely difficult to extract antigen-specific antibody sequences from the comprehensive bulk antibody sequences obtained from blood samples due to repertoire bias influenced by exposure to dietary antigens and other infectious agents. This issue can be addressed by subtracting the background noise from the post-immunization or post-infection repertoire data. In the present study, we propose a method to quantify repertoire data from comprehensive repertoire data. This method allowed subtraction of the background repertoire, resulting in more accurate extraction of expanded antibody repertoires upon influenza virus infection. This accurate extraction of antigen- or infection-specific repertoire information is a useful tool for vaccine evaluation., Competing Interests: The authors declare no conflict of interest.

Pungent capsaicinoid is synthesized only in chili pepper (Capsicum spp.). The production of vanillylamine from vanillin is a unique reaction in the capsaicinoid biosynthesis pathway. Although putative aminotransferase (pAMT) has been isolated as the vanillylamine synthase gene, it is unclear how Capsicum acquired pAMT. Here, we present a phylogenetic overview of pAMT and its homologs. The Capsicum genome contained 5 homologs, including pAMT, CaGABA-T1, CaGABA-T3, and two pseudogenes. Phylogenetic analysis indicated that pAMT is a member of the Solanaceae cytoplasmic GABA-Ts. Comparative genome analysis found that multiple copies of GABA-T exist in a specific Solanaceae genomic region, and the cytoplasmic GABA-Ts other than pAMT are located in the region. The cytoplasmic GABA-T was phylogenetically close to pseudo-GABA-T harboring a plastid transit peptide (pseudo-GABA-T3). This suggested that Solanaceae cytoplasmic GABA-Ts occurred via duplication of a chloroplastic GABA-T ancestor and subsequent loss of the plastid transit signal. The cytoplasmic GABA-T may have been translocated from the specific Solanaceae genomic region during Capsicum divergence, resulting in the current pAMT locus. A recombinant protein assay demonstrated that pAMT had higher vanillylamine synthase activity than those of other plant GABA-Ts. pAMT was expressed exclusively in the placental septum of mature green fruit, whereas tomato orthologs SlGABA-T2/4 exhibit a ubiquitous expression pattern in plants. These findings suggested that both the increased catalytic efficiency and transcriptional changes in pAMT may have contributed to establish vanillylamine synthesis in the capsaicinoid biosynthesis pathway. This study provides insights into the establishment of pungency in the evolution of chili peppers., (© 2023 Society for Experimental Biology and John Wiley & Sons Ltd.)

HIV-1 Gag protein is synthesized in the cytosol and is transported to the plasma membrane, where viral particle assembly and budding occur. Endosomes are alternative sites of Gag accumulation. However, the intracellular transport pathways and carriers for Gag have not been clarified. We show here that Syntaxin6 (Syx6), a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) involved in membrane fusion in post-Golgi networks, is a molecule responsible for Gag trafficking and also for tumor necrosis factor-α (TNFα) secretion and that Gag and TNFα are cotransported via Syx6-positive compartments/vesicles. Confocal and live-cell imaging revealed that Gag colocalized and cotrafficked with Syx6, a fraction of which localizes in early and recycling endosomes. Syx6 knockdown reduced HIV-1 particle production, with Gag distributed diffusely throughout the cytoplasm. Coimmunoprecipitation and pulldown show that Gag binds to Syx6, but not its SNARE partners or their assembly complexes, suggesting that Gag preferentially binds free Syx6. The Gag matrix domain and the Syx6 SNARE domain are responsible for the interaction and cotrafficking. In immune cells, Syx6 knockdown/knockout similarly impaired HIV-1 production. Interestingly, HIV-1 infection facilitated TNFα secretion, and this enhancement did not occur in Syx6-depleted cells. Confocal and live-cell imaging revealed that TNFα and Gag partially colocalized and were cotransported via Syx6-positive compartments/vesicles. Biochemical analyses indicate that TNFα directly binds the C-terminal domain of Syx6. Altogether, our data provide evidence that both Gag and TNFα make use of Syx6-mediated trafficking machinery and suggest that Gag expression does not inhibit but rather facilitates TNFα secretion in HIV-1 infection., Competing Interests: Conflict of 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 Authors. Published by Elsevier Inc. All rights reserved.)

Background: Approximately 1% of clinically treatable tyrosine kinase fusions, including anaplastic lymphoma kinase, neurotrophic tyrosine receptor kinase, RET proto-oncogene, and ROS proto-oncogene 1, have been identified in soft tissue sarcomas via comprehensive genome profiling based on DNA sequencing. Histologic tumor-specific fusion genes have been reported in approximately 20% of soft tissue sarcomas; however, unlike tyrosine kinase fusion genes, these fusions cannot be directly targeted in therapy. Approximately 80% of tumor-specific fusion-negative sarcomas, including myxofibrosarcoma and leiomyosarcoma, that are defined in complex karyotype sarcomas remain genetically uncharacterized; this mutually exclusive pattern of mutations suggests that other mutually exclusive driver oncogenes are yet to be discovered. Tumor-specific, fusion-negative sarcomas may be associated with unique translocations, and oncogenic fusion genes, including tyrosine kinase fusions, may have been overlooked in these sarcomas., Questions/purposes: (1) Can DNA- or RNA-based analysis reveal any characteristic gene alterations in bone and soft tissue sarcomas? (2) Can useful and potential tyrosine kinase fusions in tumors from tumor-specific, fusion-negative sarcomas be detected using an RNA-based screening system? (3) Do the identified potential fusion tumors, especially in neurotrophic tyrosine receptor kinase gene fusions in bone sarcoma, transform cells and respond to targeted drug treatment in in vitro assays? (4) Can the identified tyrosine kinase fusion genes in sarcomas be useful therapeutic targets?, Methods: Between 2017 and 2020, we treated 100 patients for bone and soft tissue sarcomas at five institutions. Any biopsy or surgery from which a specimen could be obtained was included as potentially eligible. Ninety percent (90 patients) of patients were eligible; a further 8% (8 patients) were excluded because they were either lost to follow-up or their diagnosis was changed, leaving 82% (82 patients) for analysis here. To answer our first and second questions regarding gene alterations and potential tyrosine kinase fusions in eight bone and 74 soft tissue sarcomas, we used the TruSight Tumor 170 assay to detect mutations, copy number variations, and gene fusions in the samples. To answer our third question, we performed functional analyses involving in vitro assays to determine whether the identified tyrosine kinase fusions were associated with oncogenic abilities and drug responses. Finally, to determine usefulness as therapeutic targets, two pediatric patients harboring an NTRK fusion and an ALK fusion were treated with tyrosine kinase inhibitors in clinical trials., Results: DNA/RNA-based analysis demonstrated characteristic alterations in bone and soft tissue sarcomas; DNA-based analyses detected TP53 and copy number alterations of MDM2 and CDK4 . These single-nucleotide variants and copy number variations were enriched in specific fusion-negative sarcomas. RNA-based screening detected fusion genes in 24% (20 of 82) of patients. Useful potential fusions were detected in 19% (11 of 58) of tumor-specific fusion-negative sarcomas, with nine of these patients harboring tyrosine kinase fusion genes; five of these patients had in-frame tyrosine kinase fusion genes ( STRN3-NTRK3, VWC2-EGFR, ICK-KDR, FOXP2-MET , and CEP290-MET ) with unknown pathologic significance. The functional analysis revealed that STRN3-NTRK3 rearrangement that was identified in bone had a strong transforming potential in 3T3 cells, and that STRN3-NTRK3 -positive cells were sensitive to larotrectinib in vitro. To confirm the usefulness of identified tyrosine kinase fusion genes as therapeutic targets, patients with well-characterized LMNA-NTRK1 and CLTC-ALK fusions were treated with tyrosine kinase inhibitors in clinical trials, and a complete response was achieved., Conclusion: We identified useful potential therapeutic targets for tyrosine kinase fusions in bone and soft tissue sarcomas using RNA-based analysis. We successfully identified STRN3-NTRK3 fusion in a patient with leiomyosarcoma of bone and determined the malignant potential of this fusion gene via functional analyses and drug effects. In light of these discoveries, comprehensive genome profiling should be considered even if the sarcoma is a bone sarcoma. There seem to be some limitations regarding current DNA-based comprehensive genome profiling tests, and it is important to use RNA testing for proper diagnosis and accurate identification of fusion genes. Studies on more patients, validation of results, and further functional analysis of unknown tyrosine kinase fusion genes are required to establish future treatments., Clinical Relevance: DNA- and RNA-based screening systems may be useful for detecting tyrosine kinase fusion genes in specific fusion-negative sarcomas and identifying key therapeutic targets, leading to possible breakthroughs in the treatment of bone and soft tissue sarcomas. Given that current DNA sequencing misses fusion genes, RNA-based screening systems should be widely considered as a worldwide test for sarcoma. If standard treatments such as chemotherapy are not effective, or even if the sarcoma is of bone, RNA sequencing should be considered to identify as many therapeutic targets as possible., Competing Interests: All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Association of Bone and Joint Surgeons.)

Expressed subtype of paralogous genes in functionally homologous cells sometimes show differences across species, the reasons for which have not been explained. The present study examined hypophysiotropic gonadotropin-releasing hormone (GnRH) neurons in vertebrates to investigate this mechanism. These neurons express either gnrh1 or gnrh3 paralogs, depending on the species, and apparent switching of the expressed paralogs in them occurred at least four times in vertebrate evolution. First, we found redundant expression of gnrh1 and gnrh3 in a single neuron in piranha and hypothesized that it may represent an ancestral GnRH system. Moreover, the gnrh1/gnrh3 enhancer of piranha induced reporter RFP/GFP co-expression in a single hypophysiotropic GnRH neuron in both zebrafish and medaka, whose GnRH neurons only express either gnrh3 or gnrh1 . Thus, we propose that redundant expression of gnrh1/3 of relatively recent common ancestors may be the key to apparent switching of the paralog usage among present-day species., Competing Interests: Authors declare that they have no competing interests., (© 2024 The Author(s).)

Sirt3 is a mitochondrial protein deacetylase functioning in energy metabolism, regulation of intracellular reactive oxygen species (ROS) levels, and aging. Although Sirt3 loss has negative effects on fertility of oocytes during in vitro fertilization and on progesterone production in granulosa cells, Sirt3's function in Leydig cells remains unclear. Therefore, we investigated Sirt3 activity in Leydig cells, focusing on androgen production. To do so, we performed immunohistochemistry to confirm Sirt3 localization in gonads and observed strong Sirt3 immunostaining in Leydig cells of human testes and of Sirt3+/+ and Sirt3+/- mouse testes, while Sirt3-/- mouse testis tissue was negative. In human ovary, hilus cells were strongly Sirt3-positive, theca cells showed weak positivity, and granulosa cells showed very weak or almost no immunostaining. Next, we used the murine Leydig tumor cell line MA-10 as a model. We overexpressed Sirt3 but observed no changes in proliferation, expression of Star, Cyp11a1 (p450scc gene), and Hsd3b, or progesterone production in MA-10 cells. Sirt3 knockdown significantly reduced proliferation, suppressed expressions of steroidogenic enzymes and of transcription factors Ad4bp (Sf-1 gene) and Gata4, and decreased progesterone production. Sirt3 knockdown in MA-10 cells also increased intracellular ROS levels based on CM-H2DCFDA fluorescence dye analysis and increased the proportion of both early and late apoptotic (necrotic) cells based on Annexin V/7AAD assays. These results indicate that Sirt3 has a potential function in androgen production in Leydig cells by regulating intracellular ROS levels., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A fluorescence-quenching-based assay system was constructed to determine the hydrolytic activity of endo-β-N-acetylglucosaminidases (ENGases) interacting with hybrid-type N-glycans. This was achieved using a dual-labeled fluorescent probe with a nonasaccharide structure. We produced the nonasaccharide skeleton by the stepwise glycosylation of the galactose residue on a galactosyl chitobiose derivative. Next, we introduced azido and acetoxy groups into the nonasaccharide derivative in a stepwise manner, which led to stereochemistry inversion at both the C-4 and C-2 hydroxy groups on its galactose residue. The protecting groups of the resulting nonasaccharide derivative were removed, and the derivative was labeled with an N-methylanthraniloyl group to obtain a reporter dye and a 2,4-dinitrophenyl group as a quenching molecule to obtain target probe 1. The use of this probe along with a microplate reader enabled a facile evaluation of the hydrolytic activities of ENGases Endo-H, Endo-M, Endo-F3, Endo-S, and Endo-CC. Furthermore, this probe could also assist in the search for novel ENGases that are specific to hybrid-type N-glycans., 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. Published by Elsevier Ltd.)

Background: Infantile traumatic brain injury (TBI) with a biphasic clinical course and late reduced diffusion (TBIRD) has been reported as a type of TBI. However, it remains uncertain which pediatric patients with TBI develop TBIRD., Methods: Patients with TBI who were admitted to our hospital and underwent magnetic resonance imaging (MRI) between December 2006 and October 2022 were included in this study. A diagnosis of TBIRD was made in patients with or suspected TBI, with initial symptoms being convulsions or disturbance of consciousness and late-onset subcortical reduced diffusion, the so-called bright tree appearance. Clinical features, neuroimaging (computed tomography (CT) and MRI) findings, laboratory data, and Tada score were retrospectively compared between TBIRD and non-TBIRD patients. Neurological prognosis was assessed using the Pediatric Cerebral Performance Category scale., Results: Of 21 patients who met the inclusion criteria, a diagnosis of TBIRD was made in 7 patients (median age: 8 months). The factors contributing to TBIRD development were seizures lasting over 30 min as the initial symptom (5/7 in TBIRD vs. 0/14 in non-TBIRD), tracheal intubation during initial treatment (5/7 vs. 0/14), and brain parenchymal lesions on CT (3/7 vs. 0/14), suggesting that severe TBI may progress to TBIRD. The Tada score was more positive in patients with TBIRD (6/7) than in those without (0/14)., Conclusions: It is important to monitor infant patients with severe TBI for the development of TBIRD. The Tada score can be a useful tool for TBIRD prediction., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective The Patterns of Non-adherence to Anti-platelet Regimen in Stented Patients (PARIS) and Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) thrombotic and bleeding risk scores were established to predict ischemic and bleeding events in patients undergoing percutaneous coronary intervention (PCI). However, whether or not the combination of these risk scores is predictive of clinical outcomes is unclear. Methods This bicenter registry included a total of 1,098 patients with acute myocardial infarction (MI) undergoing primary PCI. Patients were divided into three groups according to the PARIS and CREDO-Kyoto thrombotic and bleeding risk scores. The study endpoints included the rates of both ischemic (cardiovascular death, recurrent MI, and ischemic stroke) and major bleeding (Bleeding Academic Research Consortium type 3 or 5) events at two years. Results Two years after primary PCI, ischemic and major bleeding events occurred in 17.3% and 10.2% of patients, respectively. The higher-risk categories of PARIS and CREDO-Kyoto scores were associated with increased risks of ischemic and bleeding events. The rates of ischemic and major bleeding events progressively increased with the increase in risk categories in the two risk scoring systems. In the receiver operating characteristic curve analysis, the addition of CREDO-Kyoto thrombotic and bleeding risk scores to PARIS scores significantly improved diagnostic ability in predicting ischemic (area under the curve: 0.59 vs. 0.63, p=0.01) and bleeding (area under the curve: 0.65 vs. 0.68, p=0.01) events. Conclusion The combinations of the PARIS and CREDO-Kyoto risk scores might be useful for evaluating ischemic and bleeding risks in patients with acute MI undergoing primary PCI.