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The influences of particle size in dye-sensitized solar cells on diffusion coefficient of electrons and electron recombination lifetime were calculated. The implications of particle size to solar cell efficiency are discussed.

Objective: This study undertook neuropharmacological research on the clinical course of controlled medication discontinuation to guide practitioners who are considering stopping medications for youths with attention-deficit hyperactivity disorder (ADHD)., Methods: This study analyzed the data for 14 ADHD children (12 male and 2 female) in two datasets: The children prescribed methylphenidate (MPH) were at an initial mean age of 7.5 years (SD = 1.70, range: 6-11) with a mean ADHD-Rating Score (ADHD-RS) of 26.6 (SD = 8.64, range 15-40). The children who discontinued MPH based on clinical judgment were at a mean age of 12.21 years (SD = 2.12, range: 8-15) with a mean ADHD-RS of 15.9 (SD = 6.86, range 5-27). The go/no-go task was used to assess response inhibition, while functional near-infrared spectroscopy (fNIRS) was used to measure cerebral hemodynamics. Oxygenated hemoglobin (Oxy-Hb) values from fNIRS data were analyzed for each subject, focusing on past and current measurements. Baseline was set at 10 s pre-task, with interval means from 4 to 24 s analyzed. One-sample t-tests were used to evaluate brain activity magnitude., Results: The results of the study demonstrate that the children who had discontinued the medication exhibited activation in specific brain regions including the frontopolar cortex and the right ventrolateral prefrontal cortex. Activation (t = 2.363, p = 0.034, Cohen's d = 0.632) was found especially in the right dorsolateral prefrontal cortex during the performance of the go/no-go task. These activated areas were consistent with those observed in a previous study comparing brain activity during a go/no-go task between children with ADHD and healthy children., Conclusion: The present study showed differences in cerebral hemodynamics before and after discontinuation of MPH in ADHD children whose ADHD symptoms did not recur after MPH was discontinued. In the near future, further investigations that include control groups will be conducted to demonstrate the effects of MPH prior to discontinuation based on the changes in cerebral blood flow in the right prefrontal cortex, which is involved in behavioral inhibition, as observed in this study. This and future research will facilitate the development of criteria for discontinuing treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced or appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Amino acid transporters play a vital role in cellular homeostasis by maintaining protein synthesis. L-type amino acid transporter 1 (LAT1/SLC7A5/CD98lc) is a major transporter of large neutral amino acids in cancer cells because of its predominant expression. Although amino acid restriction with various amino acid analog treatments is known to induce mitotic defects, the involvement of amino acid transporters in cell division remains unclear. In this study, we identified that LAT1 is responsible for mitotic progression in a transport activity-independent manner. LAT1 knockdown activates the spindle assembly checkpoint, leading to a delay in metaphase. LAT1 maintains proper spindle orientation with confinement of the lateral cortex localization of the NuMA protein, which mediates the pulling force against the mitotic spindle toward the lateral cortex. Unexpectedly, JPH203, an inhibitor of LAT1 amino acid transport activity, does not affect mitotic progression. Moreover, the transport activity-deficient LAT1 mutant maintains the proper spindle orientation and mitotic progression. LAT1 forms a heterodimer with CD98 (SLC3A2/CD98hc) both in interphase and mitosis. Although CD98 knockdown decreases the plasma membrane localization of LAT1, it does not affect mitotic progression. LAT1 is localized to the Golgi and ER not only at the plasma membrane in interphase, and promotes Golgi unlinking during the mitotic entry, leading to centrosome maturation. These results suggest that LAT1 supports mitotic progression in an amino acid transport activity-independent manner and that Golgi-localized LAT1 is important for mitotic progression through the acceleration of Golgi unlinking and centrosome maturation. These findings reveal a novel LAT1 function in mitosis., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer., Methods: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3-4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs)., Results: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4-78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9-26.9) and the disease control rate was 90.0% (95% CI=68.3-98.8). The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively., Conclusion: The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified., Trial Registration: ClinicalTrials.gov Identifier: NCT03759600., Competing Interests: Daisuke Aoki declares the receipt of consulting fees from AstraZeneca, Chugai, MSD, and Takeda Pharmaceutical Company Ltd, and honoraria from AstraZeneca, Chugai, MSD, Myriad Genetics, and Takeda Pharmaceutical Company Ltd. Tsutomu Tabata declares the receipt of lecture fees from AstraZeneca, Chugai, and Takeda Pharmaceutical Company Ltd. Satoshi Yanagida, Toshiaki Nakamura and Hidekatsu Nakai declare the receipt of lecture fees from Takeda Pharmaceutical Company Ltd. Kenichi Harano declares the receipt of grants from AstraZeneca, Chugai, Daiichi Sankyo, MSD, and Takeda Pharmaceutical Company Ltd, and speaker fees from Astra Zeneca, Chugai, Eisai, MSD, Taiho, and Takeda Pharmaceutical Company Ltd. Kenichi Harano also declares an advisory role for AstraZeneca, Chugai, Taiho and Takeda Pharmaceutical Company Ltd, and receipt of institutional research funding from Takeda Pharmaceutical Company Ltd. Kosei Hasegawa declares the receipt of research grants from Daiichi Sankyo, Eisai, MSD, and Takeda Pharmaceutical Company Ltd, honoraria from AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Genmab, Kaken, Kyowa Kirin, MSD, Sanofi, and Takeda Pharmaceutical Company Ltd, and travel expenses from Regeneron. Kosei Hasegawa is also on the advisory board of Chugai, Eisai, Genmab, MSD, Roche, Sanofi, and Takeda Pharmaceutical Company Ltd. Shinichi Komiyama declares the receipt of consulting fees from AstraZeneca, Chugai, Daiichi Sankyo, Eisai, and MSD, and honoraria from AstraZeneca, Chugai, Eisai, and Takeda Pharmaceutical Company Ltd. Kazuhiro Takehara declares the receipt of speaker bureaus fees from AstraZeneca, MSD, and Takeda Pharmaceutical Company Ltd, and manuscript writing fees from MSD. Yoichi Kase and Ai Kato are employees of, and hold stocks in Takeda Pharmaceutical Company Ltd. Shuuji Sumino and Junpei Soeda are employees of Takeda Pharmaceutical Company Ltd. Ajit Suri is an employee of Millennium Pharmaceuticals, part of Takeda, and holds stocks in Takeda Pharmaceutical Company Ltd. Aikou Okamoto declares the receipt of honoraria from ASKA Pharmaceutical Co., Ltd, AstraZeneca, Bayer Holding Ltd, Chugai, Covidien Japan Inc., Eisai, Fuji Pharma Co., Ltd, Johnson & Johnson K.K., Kaken Pharmaceutical Co., Ltd, Kissei Pharmaceutical Co., Ltd, MSD, Mochida Pharmaceutical Co., Ltd, Myriad Genetics G.K., Otsuka Pharmaceutical Co., Ltd, Sanofi, Takeda Pharmaceutical Company Ltd, and Zeria Pharmaceutical Co., Ltd. Aikou Okamoto also declares the receipt of institutional grants from ASKA Pharmaceutical Co., Ltd, AstraZeneca, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Fuji Pharma Co., Ltd, Gyne Mom Co., Ltd, Kaken Pharmaceutical Co., Ltd, Linical Co., Ltd, Meiji Holdings Co., Ltd, Merck BioPharma Japan, Mochida Pharmaceutical Co., Ltd, MSD, Nippon Shinyaku Co., Ltd, Taiho Pharmaceutical Co., Ltd, and Tsumura & Co. Other authors have no conflict of interest to disclose., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Introduction: Cardiac safety assessment, such as lethal arrhythmias and contractility dysfunction, is critical during drug development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been shown to be useful in predicting drug-induced proarrhythmic risk through international validation studies. Although cardiac contractility is another key function, fit-for-purpose hiPSC-CMs in evaluating drug-induced contractile dysfunction remain poorly understood. In this study, we investigated whether alignment of hiPSC-CMs on nanopatterned culture plates can assess drug-induced contractile changes more efficiently than non-aligned monolayer culture., Methods: Aligned hiPSC-CMs were obtained by culturing on 96-well culture plates with a ridge-groove-ridge nanopattern on the bottom surface, while non-aligned hiPSC-CMs were cultured on regular 96-well plates. Next-generation sequencing and qPCR experiments were performed for gene expression analysis. Contractility of the hiPSC-CMs was assessed using an imaging-based motion analysis system., Results: When cultured on nanopatterned plates, hiPSC-CMs exhibited an aligned morphology and enhanced expression of genes encoding proteins that regulate contractility, including myosin heavy chain, calcium channel, and ryanodine receptor. Compared to cultures on regular plates, the aligned hiPSC-CMs also showed both enhanced contraction and relaxation velocity. In addition, the aligned hiPSC-CMs showed a more physiological response to positive and negative inotropic agents, such as isoproterenol and verapamil., Discussion: Taken together, the aligned hiPSC-CMs exhibited enhanced structural and functional properties, leading to an improved capacity for contractility assessment compared to the non-aligned cells. These findings suggest that the aligned hiPSC-CMs can be used to evaluate drug-induced cardiac contractile changes., 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 Inc. All rights reserved.)

Recently, an astatine-labeled prostate-specific membrane antigen (PSMA) ligand ([ 211 At]PSMA-5) has been developed for the targeted alpha therapy of patients with prostate cancer. This manual delineates its physicochemical characteristics to assist healthcare professionals in understanding the α-ray-emitting drug of [ 211 At]PSMA-5 when administered to patients. The safety considerations regarding the handling and use of this drug in clinical trials are outlined, based on the proper usage manual of previous studies. The dose limits, as defined by the guidelines of the International Commission on Radiological Protection (ICRP) and the International Atomic Energy Agency (IAEA), are assessed for patients' caregivers and the general public. According to the calculations provided in this manual, clinical trials involving [ 211 At]PSMA-5 can be safely conducted for these populations even if patients are released after its administration. Moreover, this manual provides comprehensive guidance on the handling of [ 211 At]PSMA-5 for healthcare facilities, and compiles a list of precautionary measures to be distributed among patients and their caregivers. While this manual was created by a research team supported by Ministry of Health, Labour, and Welfare in Japan and approved by Japanese Society of Nuclear Medicine, its applicability extends to healthcare providers in other countries. This manual aims to facilitate conducting clinical trials using [ 211 At]PSMA-5 in patients with prostate cancer., (© 2024. The Author(s).)

Ultra-small metal particles having band gaps are regarded as a new class of functional materials. We investigated the size dependencies of the band-edge energies on Cu quantum-dots in the size range of 0.7-2.1 nm. The extremely high conduction band-edge energies owing to the strong quantum-size effects were observed for sizes below 1 nm.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which is associated with various neurological symptoms, including nausea, dizziness, headache, encephalitis, and epileptic seizures. SARS-CoV-2 is considered to affect the central nervous system (CNS) by interacting with the blood-brain barrier (BBB), which is defined by tight junctions that seal paracellular gaps between brain microvascular endothelial cells (BMECs). Although SARS-CoV-2 infection of BMECs has been reported, the detailed mechanism has not been fully elucidated., Methods: Using the original strain of SARS-CoV-2, the infection in BMECs was confirmed by a detection of intracellular RNA copy number and localization of viral particles. BMEC functions were evaluated by measuring transendothelial electrical resistance (TEER), which evaluates the integrity of tight junction dynamics, and expression levels of proinflammatory genes. BMEC signaling pathway was examined by comprehensive RNA-seq analysis., Results: We observed that iPSC derived brain microvascular endothelial like cells (iPSC-BMELCs) were infected with SARS-CoV-2. SARS-CoV-2 infection resulted in decreased TEER. In addition, SARS-CoV-2 infection decreased expression levels of tight junction markers CLDN3 and CLDN11. SARS-CoV-2 infection also increased expression levels of proinflammatory genes, which are known to be elevated in patients with COVID-19. Furthermore, RNA-seq analysis revealed that SARS-CoV-2 dysregulated the canonical Wnt signaling pathway in iPSC-BMELCs. Modulation of the Wnt signaling by CHIR99021 partially inhibited the infection and the subsequent inflammatory responses., Conclusion: These findings suggest that SARS-CoV-2 infection causes BBB dysfunction via Wnt signaling. Thus, iPSC-BMELCs are a useful in vitro model for elucidating COVID-19 neuropathology and drug development., (© 2024. The Author(s).)

To evaluate the usefulness of robot-assisted total laparoscopic hysterectomy with four equally-spaced ports (RA-TLH/4e) without an assistant port. In RA-TLH/4e, four da Vinci ports were placed horizontally at a height of 4 cm above the umbilicus with 8 cm equal spacing. Poor development of the surgical field or difficult forceps manipulations were handled with the endoscope and forceps movement (port-hopping). Patient background, surgical outcomes, complications, port-hopping frequency were compared in three groups: RA-TLH/4e, RA-TLH with four unequally-spaced ports (RA-TLH/4u), and conventional RA-TLH with five ports (RA-TLH/5). There were no significant differences in patient background or surgical outcomes among the three groups except for age, preparation time, and hospital stay, and no cases of laparotomy conversion or serious complications. RA-TLH/4e had fewer port-hoppings than RA-TLH/4u. The minimum abdominal width showed a weak negative correlation with port-hopping frequency in RA-TLH/4u, but not in RA-TLH/4e. RA-TLH/4e allowed for a reduction in personnel and costs compared to RA-TLH/5. The equal placement of four ports allowed sufficient port spacing even for patients with narrow abdominal widths. In addition, the port-hopping technique was able to fully compensate for the lack of an assistant port. RA-TLH/4e is a highly useful technique that not only excels in safety but also reduces costs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Cardiotoxicity is a serious adverse effect of anti-cancer drugs. Anti-cancer drug-induced cardiotoxicity are arrhythmia, cardiac contractile dysfunction, coronary artery disease, and hypertension, which affect to the quality of life in patients with cancer. In particular, cardiac contractile dysfunction is a life-threatening symptom leading to heart failure, suggesting that it is very important to predict the risk of developing the contractile dysfunction by anti-cancer drugs. Recently, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can be used to assess the risk of drug-induced arrhythmias. This prompts us to evaluate other cardiotoxic effects such as contractility dysfunction and structural toxicity with hiPSC-CMs. Since anti-cancer drug-induced contractility dysfunction are considered to be induced by chronic exposure, we have developed a method to assess chronic contractility dysfunction by imaging analysis of hiPSC-CMs. BMS-986094, which failed in clinical trials due to the occurrence of heart failure, was used as a positive compound. We found that chronic exposure to BMS-986094 decreased the contraction and relaxation velocity in hiPSC-CMs. Doxorubicin was observed to decrease cytotoxicity and both contraction and relaxation velocities in hiPSC-CMs. We are currently further evaluating other anti-cancer drugs with different mode-of-actions using hiPSC-CMs and assess the predictivity and utility of contractile assessment using hiPSC-CMs by comparing with real-world data. Here, we introduce our novel method to assess the chronic contractility of hiPSC-CMs by imaging analysis and discuss the future perspectives for assessing the anti-cancer drug-induced cardiotoxicity.