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The article focuses on Japan Environment and Children's Study (JECS) and small for gestational age (SGA) is associated with significant perinatal outcomes, such as foetal and neonatal distress with insulin resistance and cardiovascular disease. It mentions inflammatory reactions caused by allergic diseases might increase the risk of intrauterine growth retardation (IUGR). It also mentions Maternal allergic features included the history of asthma, allergic rhinitis and atopic dermatitis (AD).

To determine the in vivo effects of a zinc oxide-eugenol mixture (ZOE) on the cyclo-oxygenase system in dental pulp, we used radioimmunoassay to measure the levels of prostaglandin E2 (PGE2), 13,14-dihydro-15-keto-PG (DHK-PG), thromboxane B2 (TXB2), and 6-keto-PGF1α, in the dental pulp of rats. When the dental pulp was irritated by a hole made in the dentin of the mandibular incisors without use of any coolants, the levels of these cyclo-oxygenase products in the pulp were increased to, respectively, 2.8, 1.7, 10.0, and 2.6 times those in the normal pulp at six hr after treatment. In contrast, these increases in cyclo-oxygenase products disappeared immediately when the artificial cavity in the dentin was filled with ZOE (P/L; 1 g/0.25 mL), but were not altered when the cavity was filled with zinc oxide-water (ZOW, 1 g/1.5 mL). Most of the eugenol portion of ZOE was released into the pulp within two hr after the cavity was filled with ZOE. The maximal eugenol content was 35 pmol per mg of pulp. Furthermore, when the cavity was filled either with ZOE or by the addition of 10 µmol/L eugenol to the pulp homogenate, biosynthesis of 14C-6-keto-PGF1α, PGF2α, and PGE2 from 14C-arachidonic acid in the homogenate was inhibited. These results suggest that eugenol released from ZOE in the cavity prepared in the dentin inhibited the biosynthesis of cyclo-oxygenase products during pulp irritation. [ABSTRACT FROM AUTHOR]

Background: Few treatment options exist for patients with non-Hodgkin lymphoma, and outcomes remain poor for relapsed or refractory disease. We evaluated the safety and preliminary clinical activity of valemetostat, a novel inhibitor of EZH2 and EZH1, in patients with relapsed or refractory non-Hodgkin lymphomas., Methods: This first-in-human, multicentre, open-label, single-arm, phase 1, dose-escalation and dose-expansion trial was done in 19 hospitals across Japan and the USA. Patients were included if they were aged 18 years or older in the USA or 20 years or older in Japan with a primary diagnosis of relapsed or refractory non-Hodgkin lymphoma and an Eastern Cooperative Oncology Group performance status of 0 or 1. In the dose-escalation part, patients received oral valemetostat at doses of 150 mg per day, 200 mg per day, 250 mg per day, and 300 mg per day continuously in 28-day cycles until progressive disease or unacceptable toxicities. All patients received 200 mg per day in the dose-expansion part. The primary endpoints were safety, pharmacokinetics, and the recommended phase 2 dose; the secondary endpoints were the maximum tolerated dose and the antitumour activity of valemetostat. Responses were assessed in patients who received at least one dose, with measurable lesions at baseline according to the International Working Group 2007 revised criteria for malignant lymphoma (peripheral T-cell lymphoma and B-cell non-Hodgkin lymphoma) and the modified 2009 criteria for adult T-cell leukaemia/lymphoma. The trial is registered with ClinicalTrials.gov, NCT02732275, and is currently active, but not recruiting., Findings: Between April 7, 2016, and June 10, 2021, 90 patients (53 [59%] males and 37 [41%] females; 49 [54%] Asian, 33 [37%] White, and eight [9%] Black) were enrolled and treated with valemetostat and included in the safety analysis set. 57 (63%) patients had peripheral T-cell lymphoma, 14 (16%) had adult T-cell leukaemia/lymphoma, and 19 (21%) had B-cell non-Hodgkin lymphoma. Seven (8%) patients received valemetostat 150 mg per day, 74 (82%) received 200 mg per day, seven received 250 mg per day, and two received 300 mg per day. Median follow-up was 7·4 months (IQR 3·4-17·6). All patients had at least one treatment-emergent adverse event; the most common treatment-emergent adverse events of any grade were decreased platelet count (52 [58%] of 90 patients), dysgeusia (45 [50%]), and anaemia (38 [42%]). The most common grade 3-4 adverse events were decreased neutrophil count (21 [23%]), decreased platelet count (18 [20%]), and decreased lymphocyte count (17 [19%]). The most common serious adverse event of any grade was Pneumocystis jirovecii pneumonia (four [4%]). No treatment-related deaths occurred. The overall response rate was 54·5% (48 of 88; 95% CI 43·6-65·2) for patients in the efficacy analysis set. The maximum tolerated dose was not reached; the recommended phase 2 dose of 200 mg per day was determined. Valemetostat exposure was variable between patients and was overlapped over the dose range of 150-250 mg per day., Interpretation: The safety profile of valemetostat monotherapy was acceptable in these patients with relapsed or refractory non-Hodgkin lymphoma. Favourable clinical activity was observed. These findings support a new indication for valemetostat in this setting., Funding: Daiichi Sankyo., Competing Interests: Declaration of interests DM reports research funding from Ono, Janssen, Eisai, Chugai, Kyowa Kirin, MSD, Zenyaku, Sanofi, SymBio Pharmaceuticals, Takeda, AbbVie, AstraZeneca, Bristol Myers Squibb (BMS), Genmab, Novartis, Otsuka, Taiho, Pfizer, and Astellas; honoraria from Ono, Nippon Shinyaku, Janssen, Mundipharma, Eisai, Chugai, Kyowa Kirin, MSD, Zenyaku, Sanofi, SymBio Pharmaceuticals, Takeda, AbbVie, AstraZeneca, BMS, Genmab, and Novartis; and advisory board participation for Janssen, AstraZeneca, Chugai, AbbVie, Genmab, Sanofi, BMS, and Pfizer. EJ reports research funding from Celgene, Merck, Pharmacyclics, and F Hoffman-La Roche, unrelated to this work; honoraria from Merck, Daiichi, BMS, and Bayer, unrelated to this work; and planned patents, issued or pending with UpToDate, unrelated to this work. PP reports research funding from Ono; consulting fees from Dren Bio, Lilly-LOXO, Ono, Kiowa, and Daiichi Sankyo; honoraria from Viracta, Innate Pharma, Daiichi Sankyo, Kiowa, and Dren Bio; travel support from Dren Bio; participation in data and safety monitoring boards or advisory boards for Viracta, Innate Pharma, BeiGene, Kiowa, ADCT, Ono, and Lilly-LOXO. PA reports support from Daiichi Sankyo for the current work, and participation on an advisory board for Daiichi Sankyo. KIs reports manuscript support from Daiichi Sankyo, related to this work; research funding from Ono and Kyowa Kirin to their institutions, unrelated to this work; honoraria from Kyowa Kirin, Takeda, Chugai Pharmaceutical, Celgene, BMS, Daiichi Sankyo, Ono, Astellas, Eisai, Pfizer, Otsuka, Sanofi, CSL Behring, AbbVie, Yakult, Janssen, and Nippon Shinyaku, unrelated to this work; participation on data safety monitoring boards or advisory boards for Meiji Seika Pharma and Daiichi Sankyo, unrelated to this work; and items of value from Ono to their institution, unrelated to this work. SK has received support from Daiichi Sankyo, related to this work; research funding from Chugai, Kyowa Kirin, and Janssen, unrelated to this work; and honoraria from Daiichi Sankyo, Chugai, Kyowa Kirin, and Janssen, unrelated to this work. TN reports support from Daiichi Sankyo for the current work and institutional research support from Daiichi Sankyo. KTo reports consulting fees and honoraria from HUYA Bioscience, Daiichi Sankyo, and SymBio Pharmaceuticals. FF reports honoraria from Seagen, Acrotech, and Kyowa; participation on data safety monitoring boards and advisory boards for ASTX; and leadership or fiduciary roles on the US Cutaneous Lymphoma Consortium executive committee. KTs reports institutional support from Daiichi Sankyo for the current work; grants or contracts given to their institution from Kyowa Kirin, Meiji Seika Pharma, BMS, Bayer, Daiichi Sankyo, and HUYABIO; consulting fees from Meiji Seika Pharma, Daiichi Sankyo, HUYABIO, Ono, Solasia Pharma, and Yakuruto; honoraria from Chugai Pharma, Eisai, Takeda, Meiji Seika Pharma, and Sekisui Medical. TF reports research funding from ADCT, AstraZeneca, BMS, Corvus, Daiichi Sankyo, Genmab, Kymera, Merck, Seagen, Tessa, Trillium, Alexion, and Portola; consulting fees from ADCT, AstraZeneca, BMS, Epizyme, Genmab, Seagen, Phamacyclics, and Celgene; honoraria from Takeda, Seagen, Genmab, Epizyme, ADCT, AstraZeneca, BMS, Pharmacyclics, AbbVie, and Pfizer; and stock in OMI and Genomic Testing Cooperative. YI reports support for travel from Chugai, Meiji Seika Pharma, Sanofi, AstraZeneca, Daiichi Sankyo, BMS, SymBio Pharmaceuticals, and Kyowa Kirin. KIz has received manuscript support from Daiichi Sankyo to their institution, related to this work; research funding from Chugai, BMS, Incyte, Genmab, LOXO Oncology, Daiichi Sankyo, Beigene, AbbVie, AstraZeneca, Regeneron, Yakult, Chugai, Otsuka, Novartis, Pfizer, MSD, Bayer, Kyowa Kirin, Eisai, Janssen, Ono, Gilead, Astellas, and Amgen to their institution, unrelated to this work; consulting fees from AstraZeneca, Ono, Mitsubishi Tanabe, Eisai, Chugai, BMS, AbbVie, Takeda, Zenyaku, Genmab, Kyowa Kirin, MSD, Carna Biosciences, Novartis, Yakult, Nihon Shinyaku, Novartis, and Beigene, unrelated to this work; and honoraria from AstraZeneca, Ono, Eisai, Chugai, Janssen, SymBio Pharmaceuticals, BMS, Daiichi Sankyo, Otsuka, AbbVie, Takeda, Eli Lilly, Genmab, Kyowa Kirin, MSD, Astellas, Pfizer, Meiji Seika Pharma, Novartis, Nihon Kayaku, and Gilead, unrelated to this work. JR reports clinical trial support from Daiichi Sankyo, related to the current work. KN reports honoraria from Meiji Seika, Chugai, BMS, Kyowa Kirin, AbbVie, Daiichi Sankyo, Eisai, and Ohara. AU reports consulting fees from JIMRO and Otsuka Medical Devices, and honoraria from Meiji Seika Pharma, Kyowa Kirin, and BMS. JZ reports grand or contracts from Secura Bio, Astex, CRISPR, Myeloid, and Daiichi Sankyo; consulting fees from Seattle Genetics, Secura Bio, Kiyowa Kirin, and Myeloid; and honoraria from Kiowa Kirin. YK, HY, NB, and AI report employment with Daiichi Sankyo. MT and YH report employment with Daiichi Sankyo and stock options with Daiichi Sankyo. SMH received research funding from US National Cancer Institute Cancer Center Support Grant (P30 CA008748); research funding from ADC Therapeutics, Affimed, Aileron, Celgene, Crispr Therapeutics, Daiichi Sankyo, Forty Seven, Kyowa Kirin, Takeda, Seattle Genetics, Trillium Therapeutics, and SecuraBio; and honoraria from Abcuro, Autolus, Auxilius Pharma, Corvus, Cimeio Therapeutics, Daiichi Sankyo, DrenBio, Kyowa Kirin, March, Bio, Ono, SecuraBio, Shoreline, Biosciences, Takeda, Tubulis, and Yingli Pharma. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Peripheral T-cell lymphomas are aggressive non-Hodgkin lymphomas with few treatment options for relapsed or refractory disease. Valemetostat tosylate (valemetostat) is a potent, novel, dual inhibitor of EZH2 and EZH1. We investigated the clinical activity and safety of valemetostat in patients with relapsed or refractory peripheral T-cell lymphoma, and its safety in patients with relapsed or refractory adult T-cell leukaemia/lymphoma., Methods: VALENTINE-PTCL01 was a multicentre, open-label, single-arm, phase 2 trial performed at 47 hospitals in 12 countries across Asia, Europe, North America, and Oceania. Patients with either peripheral T-cell lymphoma or adult T-cell leukaemia/lymphoma, aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-2 received oral valemetostat at 200 mg per day in continuous 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint for patients with peripheral T-cell lymphoma was the CT-based objective response rate by blinded independent central review (BICR) using 2014 Lugano response criteria. Patients who received valemetostat and had a confirmed eligible peripheral T-cell lymphoma subtype on central review were included in the efficacy analysis. The primary endpoint for patients with adult T-cell leukaemia/lymphoma was the safety and tolerability of valemetostat. Safety in both cohorts was assessed in all patients who received at least one dose of valemetostat. The trial is registered with ClinicalTrials.gov, NCT04703192, and EudraCT, 2020-004954-31, and is closed to enrolment., Findings: Between June 16, 2021, and Aug 10, 2022, 133 patients with relapsed or refractory peripheral T-cell lymphoma (median age 69·0 years [IQR 58·0-74·0]; 91 [68%] were male, and 42 [32%] were female) and 22 patients with adult T-cell leukaemia/lymphoma (66·5 years [54·0-73·0]; 15 [68%] were male, and seven [32%] were female) were enrolled. The median follow-up time was 12·3 months (95% CI 11·8-13·8). 52 (44%; 95% CI 35-53) of 119 efficacy-evaluable patients with relapsed or refractory peripheral T-cell lymphoma had an objective response. The most common grade 3-4 adverse events were thrombocytopenia (31 [23%] of 133 patients in the peripheral T-cell lymphoma group and 11 [50%] of 22 patients in the adult T-cell leukaemia/lymphoma group), anaemia (25 [19%] and ten [46%]), and neutropenia (23 [17%] and four [18%]). Serious treatment-emergent adverse events were reported in 53 (40%) patients with peripheral T-cell lymphoma and 15 (68%) patients with adult T-cell leukaemia/lymphoma; nine (7%) patients and one (5%) patient had a serious treatment-emergent adverse event considered to be treatment related, respectively. No treatment-related deaths were reported., Interpretation: These data show that treatment with valemetostat leads to durable responses in patients with relapsed or refractory peripheral T-cell lymphoma, with a manageable safety profile., Funding: Daiichi Sankyo., Competing Interests: Declaration of interests PLZ has received consulting fees from lncyte, Novartis, BeiGene, and SOBI, and honoraria from Takeda, AstraZeneca, MSD, Bristol Myers Squibb (BMS), lncyte, Roche, Gilead, Recordati, Kyowa Kirin, Novartis, BeiGene, Janssen, and SOBI, unrelated to this study. KIz has received manuscript support from Daiichi Sankyo to their institution, related to this work; research funding Chugai, BMS, Incyte, Genmab, LOXO Oncology, Daiichi Sankyo, BeiGene, AbbVie, AstraZeneca, Regeneron, Yakult, Chugai, Otsuka, Novartis, Pfizer, MSD, Bayer, Kyowa Kirin, Eisai, Janssen, Ono Pharmaceutical, Gilead, Astellas, and Amgen to their institution, unrelated to this work; consulting fees from AstraZeneca, Ono Pharmaceutical, Mitsubishi Tanabe, Eisai, Chugai, BMS, AbbVie, Takeda, Zenyaku, Genmab, Kyowa Kirin, MSD, Carna Biosicences, Novartis, Yakult, Nihon Shinyaku, Novartis, and BeiGene, unrelated to this work; and honoraria from AstraZeneca, Ono Pharmaceutical, Eisai, Chugai, Janssen, Symbio, BMS, Daiichi Sankyo, Otsuka, AbbVie, Takeda, Eli Lilly, Genmab, Kyowa Kirin, MSD, Astellas, Pfizer, Meiji Seika Pharma, Novartis, Nihon Kayaku, and Gilead, unrelated to this work. NM-S has received research funding from AstraZeneca, BMS, C4 Therapeutics, Celgene, Corvus Pharmaceuticals, Daiichi Sankyo, Dizal Pharmaceuticals, Genetech/Roche, Incyte, Innate Pharmaceuticals, Secura Bio, Verastem, and Yingli Pharmaceuticals, to their institutions, unrelated to this work; consulting fees from AstraZeneca, Kyowa Hakka Kirin, Karyopharm, Ono Pharmaceuticals, Secura Bios, Daiichi Sankyo, Genentech, and Janssen, unrelated to this work; and participated on a data safety monitoring board and an advisory board for Daiichi Sankyo, unrelated to this work. SKB received manuscript support from Daiichi Sankyo, related to this work; consulting fees and honoraria from Acrotech, Kyowa Kirin, and Seagen, unrelated to this work; and participated on a data safety monitoring board or advisory board for Janssen, unrelated to this work. KIs has received manuscript support from Daiichi Sankyo, related to this work; research funding from Ono Pharmaceutical and Kyowa Kirin to their institutions, unrelated to this work; honoraria from Kyowa Kirin, Takeda, Chugai Pharmaceutical, Celgene, BMS, Daiichi Sankyo, Ono Pharmaceutical, Astellas, Eisai, Pfizer, Otsuka, Sanofi, CSL Behring, AbbVie, Yakult, Janssen Pharmaceutical, and Nippon Shinyaku, unrelated to this work; participated on data safety monitoring board or advisory board for Meiji Seika Pharma and Daiichi Sankyo, unrelated to this work; and received materials from Ono Pharmaceutical to their institution, unrelated to this work. SK has received support from Daiichi Sankyo, related to this work; research funding from Chugai, Kyowa Kirin, and Janssen, unrelated to this work; and honoraria from Daiichi Sankyo, Chugai, Kyowa Kirin, and Janssen, unrelated to this work. EB has received research funding from Amgen and BMS, to their institution, unrelated to this work; honoraria from Novartis, Kite/Gilead, Roche, Takeda, Janssen, and AbbVie, unrelated to this work; support for attending meetings or travel from Roche and Kite/Gilead, unrelated to this work; and participated on data safety monitoring board or advisory board from Novartis, Kite/Gilead, Roche, Incyte, ADC Therapeutics, and AbbVie, unrelated to this work. KC received consulting fees from Roche, Takeda, Celgene, and AbbVie, unrelated to this work; honoraria from Roche and Takeda, unrelated to this work; support for attending meetings or travel from Roche, Takeda, and BMS, to their institution; and participated on data safety monitoring board or advisory board for Daiichi Sankyo, unrelated to this work. GG received honoraria from Ideogen and Takeda, unrelated to this work; support for attending meetings or travel from Roche, Kite-Gilead, Sandoz, BeiGene, and Janssen, unrelated to this work; and participated on data safety monitoring board or advisory board for AbbVie, Roche, Takeda, Kite-Gilead, Italfarmaco, Ideogen, and Genmab, unrelated to this work. EJ received research funding from Celgene, Merck, Pharmacyclics, and F Hoffman-LaRoche, unrelated to this work; honoraria from Merck, Daiichi, BMS, and Bayer, unrelated to this work; and has patents planned, issued, or pending with UpToDate, unrelated to this work. TF has received research funding from ADCT, AstraZeneca, BMS, Corvus, Daiichi, Genmab, Kymera, Merck, Seagen, TESSA, Trillium, Alexion, and Portola, unrelated to this work; consulting fees from ADCT, AstraZeneca, BMS, Epizyme, Genmab, Seagen, Pharmacyclics, and Celgene, unrelated to this work; honoraria from Takeda, Seagen, Genmab, Epizyme, ADCT, AstraZeneca, BMS, Pharmacyclics, AbbVie, and Pfizer, unrelated to this work; and owns stock in OMI and Genomic Testing Cooperative, unrelated to this work. DE received research funding from Nippon Shinyaku Pharmaceutical, Chugai Pharmaceutical, and Eisai Pharmaceutical, to their institution, unrelated to this work; and honoraria from Eisai Pharmaceutical, Chugai Pharmaceutical, SymBio Pharmaceuticals, BMS, Kyowa Kirin Pharmaceutical, and Nippon Shinyaku Pharmaceutical, unrelated to this work. EDD received consulting fees from Takeda, unrelated to this work; honoraria from Takeda and BeiGene, unrelated to this work; and funding for attending meetings or travel from Takeda, unrelated to this work. JZ received research funding from Secura Bio, Astex, CRSPR, Myeloid Therapeutics, and Daichi Sankyo, unrelated to this work; consulting fees from Seattle genetics, Secura Bio, Kyowa Kirin, and Myeloid Therapeutics, unrelated to this work; and honoraria from Kyowa Kirin, unrelated to this work. JJ, SW, TM, AI, and KN are employed by Daiichi Sankyo. TM has received support for attending meetings or travel from Daiichi Sankyo, unrelated to this work. AI, TM, and YC own stock options in Daiichi Sankyo, unrelated to this work. KN owns stock in Daiichi Sankyo, unrelated to this work. SH received research funding from the US National Institutes of Health/National Cancer Institute Cancer Center, (support grant P30 CA008748); research funding from ADC Therapeutics, Affimed, Aileron, Celgene, Crispr Therapeutics, Daiichi Sankyo, Forty Seven, Kyowa Hakko Kirin, Takeda, Seattle Genetics, Trillium Therapeutics, and SecuraBio; and honoraria from Abcuro, Autolus, Auxilius Pharma, Corvus, Cimeio Therapeutics, Daiichi Sankyo, Dren Bio, Kyowa Hakko Kirin, March, Bio, Ono Pharmaceuticals, SecuraBio, Shore line, Biosciences, Takeda, Tubulis and Yingli Pharma. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Patients with peripheral T-cell lymphoma demonstrated a poor prognosis after obtaining a complete response with induction treatment compared to those with B-cell lymphoma. Once it relapsed, curative treatment is frequently limited to invasive treatments with significant treatment-related mortality, including allogeneic stem cell transplantation. The limitations of these treatment choices indicate the necessity for developing optimal consolidation therapies to prevent relapse. This multicenter randomized phase III trial aims to confirm the superiority of the high-dose therapy with autologous stem cell transplantation over observation alone in terms of progression-free survival for patients with newly diagnosed peripheral T-cell lymphoma who achieved complete metabolic response after induction therapy. A total of 140 patients from 52 hospitals will be enrolled in Japan over 5.5 years. This trial is registered in the Japan Registry of Clinical Trials as jRCTs031240169 (https://jrct.niph.go.jp/latest-detail/jRCTs031240169)., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study retrospectively compared outcomes of various allogeneic haematopoietic cell transplantation (allo-HCT) platforms in patients with adult T-cell leukaemia/lymphoma. Platforms included human leukocyte antigen (HLA)-haploidentical-related donors using post-transplant cyclophosphamide (PTCY), HLA-matched related donors (MRD), HLA-matched unrelated donors (MUD) and cord blood transplantation (CBT). Patients who underwent their first allo-HCT between 2016 and 2021 were included. Outcomes analysed were overall survival (OS), relapse and non-relapse mortality (NRM). Seven hundred patients were included (PTCY, n = 121; MRD, n = 91; MUD, n = 160; CBT, n = 328). With a median follow-up of 794 days for survivors, 2-year OS was 48.1% (PTCY), 48.8% (MRD), 48.4% (MUD) and 34.6% (CBT); the respective 2-year cumulative incidence of relapse was 37.1%, 47.5%, 33.9% and 45.1% and that of NRM was 24.2%, 19.8%, 24.7% and 27.3%. PTCY was associated with delayed platelet engraftment relative to MRD and MUD. There was no increase in the incidence of severe acute or chronic graft-versus-host disease. In the PTCY group, poor performance status was a significant predictor of inferior OS, and infused CD34+ cell numbers of less than 5 × 10 6 /kg were associated with delayed neutrophil and platelet engraftment. These results suggest that allo-HCT with PTCY is a safe and effective platform for patients with adult T-cell leukaemia/lymphoma., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Alemtuzumab is recommended as first-line and second-line therapies for T-cell prolymphocytic leukemia (T-PLL). This study retrospectively evaluated the efficacy and safety of alemtuzumab in nine Japanese patients with T-PLL at five participating institutions who were treated between January 2015 and August 2023. The median age at first administration of alemtuzumab was 72 years (range, 39 to 78). Two patients were treatment naïve, and seven had been treated with a median of one (range, 1 to 3) prior systemic therapy. Six patients were refractory to their most recent therapy. Three patients completed 12 weeks of treatment. The overall response rate and the complete response (CR) rate were 78% and 11%, respectively. Among the six patients who achieved a partial response, two achieved clinical CR but did not undergo bone marrow examination. One patient also achieved clinical CR but did not undergo CT and bone marrow examination for response evaluation. The median progression-free survival time was 8.1 months (95% confidence interval, 0.9 to 18.6). Three patients received readministration of alemtuzumab monotherapy after disease progression. There were no treatment-related deaths. The grade 3 or 4 nonhematologic adverse events included infusion reaction (grade 3, n = 2), cytomegalovirus reactivation (grade 3, n = 2), and pulmonary edema (grade 3, n = 1). One patient experienced Epstein‒Barr virus-positive diffuse large B-cell lymphoma 15 months after the last dose of alemtuzumab. These results confirm that the efficacy and safety of alemtuzumab monotherapy in Japanese patients are comparable to those previously reported.

During the screening of novel chemotherapeutic candidates from plants against adult T-cell leukaemia/lymphoma (ATL), we found that extracts of plants in the Solanaceae, Annonaceae, Apocynaceae, and Rutaceae families showed anti-proliferative activity in the MT-1 and MT-2 cell lines. We have isolated active compounds from these plants in the present research because Cupressaceae plants showed potent anti-proliferative activity in the cell lines. We attempted to isolate the active compounds from the leaves of Juniperus rigida . Using activity-guided fractionation, we isolated 22 compounds, including seven terpenoids, three aromatic compounds, two iridoids, five lignans, and five biflavonoids. The anti-proliferative activities of five diterpenoids were moderate, and those of two biflavonoids were stronger. A lignan (compound 13 ) showed the strongest activity. These compounds are promising candidates for the treatment of ATL.

Objectives　Resilience is the ability to navigate adversity and recover from challenging situations. Developing resilience at a young age promotes mental health and provides benefits throughout one's lifespan. Validated measures for assessing resilience at a young age are required in both clinical practice and epidemiological studies. The Child and Youth Resilience Measure-Revised (CYRM-R) is a tool used worldwide to assess resilience in children and young people. The objective of this study was to develop a Japanese version of the CYRM-R and investigate its psychometric properties.Methods　Children in grades 5-9 were recruited via a two-stage cluster random sampling taken from the Japan Adolescent and Youth (JAY) Longitudinal Cohort Study. The participants completed the Japanese version of the CYRM-R . The CYRM-R consists of two subscales, personal resilience and caregiver resilience, with a total of 17 items. The linguistic validity of the Japanese version of the CYRM-R was ensured through translation and back-translation.Cronbach's alpha coefficients were examined for the total score and the two subscales to assess the internal consistency of the Japanese version of the CYRM-R scale. In addition, correlation coefficients of the subscales were calculated. For factorial validity, a confirmatory factor analysis was conducted on the same two-factor structure as in the original version to assess the model's goodness of fit. Results　A total of 2,266 children (50.0% male) were included in the study. The overall Cronbach's alpha of the Japanese version of the CYRM-R obtained from this sample was 0.956; For the personal resilience subscale, Cronbach's alpha was 0.932; for the caregiver resilience subscale, it was 0.919. Significant positive correlations were also found between subscales (r = 0.827, p < 0.001). A confirmatory factor analysis was conducted using a two-factor structure for validity. The model fit was good (RMSEA = 0.085, SRMR = 0.041, CFI = 0.934).Conclusion　The Japanese version of the CYRM-R maintained the same two-factor structure as the original version. The study findings showed that the Japanese version of the CYRM-R had adequate internal consistency and factorial validity for assessing resilience in children and youth. Therefore, this scale is a valuable tool for identifying individuals or groups at risk in terms of children's resilience and for evaluating the effectiveness of support and interventions.

Background: The impact of parent-childbearing age on child development at 36 months of age is controversial., Aims: We used data from a large cohort study with multiple imputation and mediation analyses of variables., Methods and Procedures: A total of 72,606 parent-child pairs from the Japan Environment and Children's Study were included in the study. Parents' ages were categorized into five groups. We used five domains of the Japanese translation of the Ages and Stages Questionnaire, Third Edition (J-ASQ-3). Scores below the cutoff value at 36 months were defined as developmental delays in each domain. We used three logistic analysis models. In Model 3, we analyzed maternal and paternal age using other variables and covariates., Outcomes and Results: The outcome was a developmental delay in the five domains of J-ASQ-3. In Model 3, ORs for the developmental delay scores regarding parental age were significantly associated with all five domains of J-ASQ-3. The mediation analysis showed a significant mediation interaction effect for mothers but localized for fathers., Conclusion: Advanced paternal and maternal ages were associated with developmental delay in children. Awareness of the risks of childbearing at an advanced age is crucial., What's the Paper Adds: This manuscript used data from a large cohort study with multiple imputation and mediation analyses. With these analyses, we identified the pure effect of advanced parental age on their children's development at 36 months., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest, except the association with the Ministry of Environment, Japan., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: The COVID-19 pandemic posed tremendous challenges for children. However, the long-term effects of the pandemic on various aspects of physical health at a national level remain unclear., Methods: In this retrospective cohort study, we analysed data from nationwide health checkup records amongst children aged 7-15 years. The dataset comprised 3 544 146 records from 393 794 individuals who graduated from junior high school during fiscal years 2007 to 2022. Difference-in-differences (DID) analyses with multiple time periods were used to examine the impact of COVID-19 on physical health outcomes., Results: Compared with the pre-pandemic period, the COVID-19 pandemic was associated with excess increases in obesity for boys and girls, persisting over the 3 years (+0.42%; [95% CI, 0.23-0.61]). Also, it was associated with excess increases in underweight (+0.28% [0.25-0.32]) and poor visual acuity amongst boys in the 3rd year (+1.80% [1.30-2.30]). There were excess reductions in dental caries (-1.48% [-2.01 to -0.95]), glucosuria (-0.55 [-0.88 to -0.23]) and hematuria (-0.43% [-0.73 to -0.13]) during the 3rd year of the pandemic., Conclusions: These findings underscore the multifaceted impact of the pandemic on various health indicators for school-aged children. This information could be valuable for public health policy and paediatric healthcare planning in the post-pandemic era., (© 2024 World Obesity Federation.)

Mogamulizumab is a humanized antibody targeting CC chemokine receptor 4 (CCR4). This post-marketing surveillance was conducted in Japan as a regulatory requirement from 2014 to 2020 to ensure the safety and effectiveness of mogamulizumab in patients with relapsed or refractory (r/r) CCR4-positive peripheral T-cell lymphoma (PTCL) or r/r cutaneous T-cell lymphoma (CTCL). Safety and effectiveness data were collected for up to 31 weeks after treatment initiation. A total of 142 patients were registered; safety was evaluated in 136 patients. The median number of doses was 8.0 (range, 1-18). The main reasons for treatment termination were insufficient response (22.1%) and adverse events (13.2%). The frequency of any grade adverse drug reaction was 57.4%, including skin disorders (26.5%), infections and immune system disorders (16.2%), and infusion-related reactions (13.2%). Graft-versus-host disease, grade 2, developed in one of two patients who underwent allogeneic-hematopoietic stem cell transplantation after receiving mogamulizumab. Effectiveness was evaluated in 131 patients (103 with PTCL; 28 with CTCL). The best overall response rate was 45.8% (PTCL, 47.6%; CTCL, 39.3%). At week 31, the survival rate was 69.0% (95% confidence interval, 59.8%-76.5%) [PTCL, 64.4% (54.0%-73.0%); CTCL, 90.5% (67.0%-97.5%)]. Safety and effectiveness were comparable between patients <70 and ≥ 70 years old and between those with relapsed and refractory disease. The safety and effectiveness of mogamulizumab for PTCL and CTCL in the real world were comparable with the data reported in previous clinical trials. Clinical Trial Registration., (© 2024 The Author(s). Hematological Oncology published by John Wiley & Sons Ltd.)

Teenage pregnancy increases the threat of depression because of its many factors. Pregnancy during young adulthood may also have several risk factors for depression compared to older pregnancies. However, data on depression in young adult pregnancies are lacking. This study investigated the association between teenage and young adult pregnancy and depression. Data from the Japan Environment and Children's study was used as a nationwide multicenter prospective cohort study. A multivariate logistic regression was performed to investigate the association between age groups (14-19, 20-24, 25-29, 30-34, ≥ 35 years) and depression, adjusted for behavioral and sociodemographic characteristics. Depression was assessed using the Kessler Psychological Distress Scale. In total, 96,808 pregnant women responded to the questionnaire. Teenage (14-19 years) and young adult (20-24 years) pregnancy were associated with an increased risk of depression compared to older pregnancy (≥ 35 years) (teenage: OR 4.28, 95% confidence interval, CI [3.24-5.64]; young adult: OR 3.00, 95% CI [2.64-3.41]). After adjusting for covariates, the magnitude of the risk of depression was attenuated. However, teenage and young adult pregnancy remained at a significantly increased risk of depression compared to older pregnancy (teenage: OR 2.38, 95% CI [1.77-3.21]; young adult: OR 2.14, 95% CI [1.87-2.46]). Our findings indicate that teenage and young adults' pregnancy are at an increased risk of depression compared to older pregnancy. These findings suggest prioritizing teenage and young pregnant women for prevention and interventions related to depression., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

This study investigated the potential link between early childhood allergic diseases and neurodevelopmental milestone attainment during the first 3 years of life. Utilizing data from a large-scale prospective birth cohort study in Japan, encompassing 87,986 children, we examined physician-diagnosed and caregiver-reported allergic conditions, including atopic dermatitis (AD), asthma, and food allergy (FA). Neurodevelopmental milestones were assessed using the Ages and Stages Questionnaires at 1, 1.5, 2, 2.5, and 3 years of age. Stabilized inverse probability-weighted generalized estimating equation models were employed to estimate odds ratios (ORs). Our analysis revealed no significant association of AD and asthma with delay in communication, gross motor, fine motor, problem-solving, and personal-social skills during the initial 3 years of life. However, children with FA showed an increased likelihood of experiencing gross motor delay compared with that shown by those without FA (weighted adjusted OR: 1.14). Despite this, no significant association of FA with other developmental domains was observed. Early childhood allergies may not influence neurodevelopmental delays. However, there is a potential association between FA and delays, specifically in gross motor skills, that warrants routine developmental monitoring and additional investigations., (© 2024. The Author(s).)