Search

Background: Photoimmunotherapy (PIT) is a potent modality for cancer treatment. The conventional PIT regimen involves the systemic delivery of an antibody-photoabsorber conjugate, followed by a 24-h waiting period to ensure adequate localisation on the target cells. Subsequent exposure to near-infrared (NIR) light selectively damages the target cells. We aimed to improve the efficacy of PIT in vivo by evaluating the effects of the different routes of conjugate administration on treatment outcomes., Methods: Subcutaneous Lewis lung carcinoma tumours were established in mice, targeting cluster of differentiation (CD)44 with an anti-CD44 antibody conjugated to IRDye700DX (IR700). The conjugate was administered via the intravenous or intratumoural route followed by the assessment of antibody binding and therapeutic effects of PIT., Findings: Compared to intravenous administration, intratumoural delivery of the CD44-IR700 conjugate significantly increased the number of cells binding to the conjugate by >five-fold. This method, combined with NIR light irradiation, halved tumour growth when compared to intravenous delivery. Reducing the interval between intratumoural injection and NIR light exposure to 30 min did not diminish efficacy, thereby demonstrating the feasibility of a 1-h procedure., Interpretation: Intratumoural administration of the antibody-photoabsorber conjugate enhanced the efficacy of PIT in vivo. A simplified, 1-h procedure involving conjugate tumour injection followed by irradiation emerged as a potent cancer treatment strategy., Funding: This study was supported by the Japan Society for the Promotion of Science, the Japan Agency for Medical Research and Development, Japan Science and Technology Agency, and the Osaka Medical Research Foundation for Intractable Diseases., Competing Interests: Declaration of interests 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 © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Regional anesthesia techniques that provide analgesia to the entire lateral abdomen are limited. We present a modified external oblique intercostal block for complete lateral abdominal analgesia with a single injection., Case: We performed a modified version of the external oblique intercostal block unilaterally at the tenth rib along the mid-axillary line in three patients undergoing robot-assisted partial nephrectomy (two single injections, one catheter placement) and tested the technique on a cadaver with 20 ml of dye bilaterally. All patients reported good postoperative pain relief without complications and had consistent sensory coverage of the T8-T12 dermatomes from the anterior-to-posterior axillary line. Anatomical assessment confirmed consistent bilateral staining of the lateral cutaneous branches T8-T12., Conclusions: The initial clinical success and anatomical findings of the modified approach to the external oblique intercostal block suggest that this technique may be an effective option for lateral abdominal analgesia.

Background: Fungus gardens of the termite Odontotermes formosanus, excavated from Iriomote Island, Okinawa Prefecture, Japan, were subsequently incubated under laboratory conditions. A Xylaria species emerging from these fungus gardens was initially identified as X. angulosa, a species originally described from North Sulawesi, Indonesia. The Iriomote fungus is now described as a distinct species, X. iriomotensis., Results: Xylaria iriomotensis is peculiar in producing the teleomorph in culture but lacking an anamorph. Cultures of X. angulosa were obtained from two Taiwan specimens, which agree with the holotype from BO and the isotypes from NY and WSP in their stromata being repeatedly dichotomously branched and possessing a black core. In contrast to X. iriomotensis, X. angulosa does not form the teleomorph in culture but a typical Xylaria anamorph with conidiophores densely arranged in palisades. The ITS sequence obtained from the WSP isotype shared high similarities with those two Taiwan specimens as well as an Indian specimen, reconfirming the latter three specimens as X. angulosa. These four specimens shared 98.28-99.66% similarities at ITS sequences among themselves but only 84.25-85.01% similarities with X. iriomotensis. Molecular phylogenetic studies based on sequences of multiple protein-coding loci indicate that, while X. iriomotensis is grouped with three soil-dwelling species of the X. guepini cluster, X. angulosa belongs to the X. nigripes cluster, which includes all known species capable of producing massive sclerotia., Conclusion: Xylaria iriomotensis has the teleomorph known only in culture, remaining to be rediscovered in its natural habitat where the stromatal morphology may be somewhat varied. The geographic distribution of X. angulosa, previously known only in Indonesia, has been expanded to Taiwan and India. Xylaria angulosa grouping with the X. nigripes cluster in our phylogenetic analyses indicates its potential to form massive sclerotia within termite nests., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: Y-MJ, the corresponding author of this paper, serves as the Editor -in- Chief of Botanical Studies. To ensure an unbiased evaluation and strict adherence to ethical guidelines, he was blinded to this paper during the review and decision-making process., (© 2025. The Author(s).)

Nitrogen-based fertilizers are crucial in agriculture for maintaining soil health and increasing crop yields. Soil microorganisms transform nitrogen from fertilizers into NO3--N, which is absorbed by crops. However, some nitrogen is converted to nitrous oxide (N 2 O), a greenhouse gas with a warming potential about 300-times greater than carbon dioxide (CO 2 ). Agricultural activities are the main source of N 2 O emissions. Monitoring N 2 O can enhance soil health and optimize nitrogen fertilizer use, thereby supporting precision agriculture. To achieve this, we developed ionic liquid-gated graphene field-effect transistor (FET) sensors to measure N 2 O concentrations in agricultural soil. We first fabricated and tested the electrical characteristics of the sensors. Then, we analyzed their transfer characteristics in our developed N 2 O evaluation system using different concentrations of N 2 O and air. The sensors demonstrated a negative shift in transfer characteristic curves when exposed to N 2 O, with a Dirac point voltage difference of 0.02 V between 1 and 10 ppm N 2 O diluted with pure air. These results demonstrate that the ionic liquid-gated graphene FET sensor is a promising device for N 2 O detection for agricultural soil applications.

Ascidian larval muscle cells present a classic example of autonomous development. A regulatory mechanism for these cells has been extensively investigated, and the regulatory gene circuit has been documented from maternal factors to a muscle-specific gene. In the present study, we comprehensively identified genes expressed specifically in ascidian muscle cells, and found that all of them are under control of a positive regulatory loop of Tbx6-r.b and Mrf, the core circuit identified previously. We also found that several transcription factors under control of the Tbx6-r.b/Mrf regulatory loop exhibited various temporal expression profiles, which are probably important for creating functional muscle cells. These results, together with results of previous studies, provide an exhaustive view of the regulatory system enabling autonomous development of ascidian larval muscle cells. It shows that the Tbx6-r.b/Mrf regulatory loop, but not a single gene, serves a 'master' regulatory function. This master regulatory loop not only controls spatial gene expression patterns, but also governs temporal expression patterns in ascidian muscle cells., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2025. Published by The Company of Biologists.)

A dense glycocalyx, composed of the megaDalton-sized membrane mucin MUC17, coats the microvilli in the apical brush border of transporting intestinal epithelial cells, called enterocytes. The formation of the MUC17-based glycocalyx in the mouse small intestine occurs at the critical suckling-weaning transition. The glycocalyx extends 1 µm into the intestinal lumen and prevents the gut bacteria from directly attaching to the enterocytes. To date, the mechanism behind the positioning of MUC17 to the brush border is not known. Here, we show that the actin-based motor proteins MYO1B and MYO5B, and the sorting nexin SNX27, regulate apical targeting of MUC17 in enterocytes. We demonstrate that MUC17 turnover at the brush border is slow and controlled by MYO1B and SNX27. Furthermore, we report that MYO1B regulates MUC17 protein levels in enterocytes, whereas MYO5B specifically governs MUC17 levels at the brush border. Together, our results extend our understanding of the apical targeting of membrane mucins and provide mechanistic insights into how defective positioning of MUC17 renders enterocytes sensitive to bacterial challenges., (© 2025 The Author(s).)

We evaluated the role of Helicobacter pylori (H. pylori)-related chronic gastritis in the development of osteoporosis in a population-based study. A total of 1690 subjects in the cohort of the Research on Osteoarthritis/ osteoporosis Against Disability (ROAD) were investigated, and the association between gastritis and osteoporosis was evaluated by the presence of serologically assessed H. pylori-related chronic gastritis and its stage, based on H. pylori antibody titer and pepsinogen. The presence of the gastritis was associated with significantly lower bone mineral density (BMD) assessed by dual-energy x-ray absorptiometry and a significant risk of lower BMD was observed in femoral neck (adjusted odds ratio [OR]: 0.78, 95% confidence interval [CI]: 061-0.99). The progression of the gastritis appeared to further increase the risk. In the stage of non-atrophic gastritis, the risk of lower BMD was significantly high, especially in a subgroup with higher gastritis activity in the femoral neck (adjusted OR: 0.61, 95% CI: 0.42-0.89). Meanwhile, in the stage of atrophic gastritis, the highest and significant risk of lower BMD was observed in a subgroup with the most extensive and severe atrophy in femoral neck (adjusted OR: 0.62, 95% CI: 0.42-0.91). These results suggest that H. pylori-related chronic gastritis is involved in the risk of osteoporosis, with higher activity of gastritis and more extensive atrophy leading to further increased risk. The serologically assessed stage of the gastritis could be used to identify a high-risk group for osteoporosis in H. pylori-infected subjects from general population., Competing Interests: Declarations. Competing Interests: The authors declare that they have no competing interests. Izumi Inoue, Noriko Yoshimura, Toshiko Iidaka, Chiaki Horii, Shigeyuki Muraki, Hiroyuki Oka, Hiroshi Kawaguchi, Toru Akune, Takao Maekita, Kanae Mure, Kozo Nakamura, Sakae Tanaka, Satoshi Mochida, and Masao Ichinose declare no conflicts of interest. Ethical Approval: This study was performed in accordance with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Human and Animal Rights: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed Consent: Informed consent was obtained from all individual participants included in the study. Consent to Participate: Not applicable., (© 2024. The Author(s).)

We have previously used the Roter Interaction Analysis System (RIAS) to analyze differences between online and face-to-face medication counseling. In our previous research, students have commented that the built-in camera on their laptops makes it difficult to make eye contact and communicate effectively. Furthermore, there is a lack of research on the impact of eye contact in online medical communication. Therefore, this study aimed to investigate the effects of eye contact on online medication counseling. Two simulated patients (SPs) and 10 pharmacy students acting as pharmacists were enrolled in this clinical study (ID:2022-001). Participants were divided into 2 groups: one using cameras designed to naturally align eye contact and another using standard device cameras. The dialogues were segmented into meaningful minimal units (utterances), categorized using RIAS according to their nature, and analyzed. Scenarios with aligned eye contact significantly increased the total number of SP utterances and the occurrence and proportion of "Check" utterances by students, confirming their understanding. The increase in the total utterance count of SPs was associated with a corresponding increase in the number of "Agree" utterances indicating agreement and understanding. Thus, eye contact enhances the clarity of patient responses and proactively confirms patient understanding, thereby mitigating the difficulty of assessing comprehension and conducting bidirectional communication online. This study's findings quantitatively suggested that eye contact in online medication counseling enhances proactive engagement in communication for pharmacy students and SPs.

Background: Nonpharmaceutical interventions for coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, during the pandemic altered the epidemiology of respiratory viruses. This study aimed to determine the changes in respiratory viruses among children hospitalized from 2018 to 2023., Methods: Nasopharyngeal specimens were collected from children aged under 15 years with fever and/or respiratory symptoms admitted to a medical institution in Fukushima Prefecture between January 2018 and December 2023. Eighteen respiratory viruses were detected using real-time reverse transcription-polymerase chain reaction., Results: Overall, 1933 patients were included. Viruses were detected in 1377 (71.2%); of these, a single virus was detected in 906 (46.9%) and multiple viruses in 471 (24.3%). Among the viruses whose epidemics were temporarily suppressed, the epidemics of respiratory syncytial virus A and human parainfluenza virus type 3 (HPIV3) started earlier, and the epidemics of human metapneumovirus, HPIV1, and influenza A and C viruses resumed as behavioral restrictions for preventing COVID-19 eased. The median age of children with airway infection was significantly higher in the postpandemic group than in the prepandemic group (18.0 months vs. 21.0 months, p < 0.01). The median age of children infected with HPIV3 and human rhinovirus was significantly higher in the postpandemic group than in the prepandemic group., Conclusions: Strengthening of nonpharmaceutical interventions changed the epidemic dynamics of pediatric infectious diseases, with a trend toward older hospitalized children. Continuous monitoring of pediatric infectious disease outbreaks in hospitalized children can help prepare for the emergence of future viruses and pandemics., (© 2025 The Author(s). Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: Although specific biomarkers for primary sclerosing cholangitis (PSC) are required, no such biomarkers have been identified. We previously reported that patients with PSC had anti-integrin αvβ6 autoantibodies at only two hospitals. In this study, we aimed to validate the accuracy of the autoantibodies in diagnosing PSC using the newly developed Anti-integrin αvβ6 enzyme-linked immunosorbent assay (ELISA) Kit, which enables quantitation and comparison of antibodies among different facilities., Methods: Overall, 81 patients with PSC in a Japanese PSC registry recruited from 17 medical centers and hospitals, and 358 controls were enrolled. We retrospectively assessed anti-integrin αvβ6 autoantibodies using the Anti-integrin αvβ6 ELISA Kit and in-house ELISA., Results: Anti-Integrin αvβ6 ELISA Kit and in-house ELISA exhibited a significant correlation (r = 0.97, P < 0.001). Anti-integrin αvβ6 autoantibodies were detected in 67 of 81 (82.7%) patients with PSC and 20 of 358 (5.6%) controls, resulting in a sensitivity of 82.7% and specificity of 94.4% for PSC, using the anti-integrin αvβ6 ELISA Kit. When focusing on the presence or absence of inflammatory bowel disease (IBD), the sensitivities for PSC with ulcerative colitis, Crohn's disease, unclassified-IBD, and without IBD were 97.8% (43/44), 100% (1/1), 80.0% (8/10), and 53.8% (7/13), respectively. Antibody concentrations were significantly higher in PSC patients without IBD than in controls (P < 0.001)., Conclusions: We validated that anti-integrin αvβ6 autoantibodies have high sensitivity and specificity for diagnosing PSC. This study provides further evidence that anti-integrin αvβ6 autoantibodies are a useful biomarker for diagnosing PSC., (© 2024. The Author(s).)

For understanding trace element dynamics in tissues, methods for analyzing elemental distribution and localization without destroying tissue structures and cell arrangements are desired. Synchrotron radiation X-ray fluorescence (SR-XRF) analysis is one of the non-destructive and multi-element simultaneous analyses. The kidney is the major excretion pathway of cesium (Cs) taken into the body, and an understanding of cesium distribution in the kidney would be useful for establishing technology to facilitate the excretion of radioactive Cs from the body due to nuclear disasters. In the present study, the distribution of cesium and trace elements, such as iron (Fe) and zinc (Zn), corresponding to the kidney structure was examined in Cs-administered mice by SR-XRF imaging with high-energy excitation X-rays (40 keV). By beam scanning with a 200-µm square beam, clear Cs images corresponding to the renal layer structure were obtained for the renal specimen at the early phase after Cs administration with the mean renal Cs concentration of 24.1 ± 3.2 μg/g. Cs was distributed mainly in the medulla and the outer stripe of the outer medulla located in the center area of the kidney. Unlike the Cs distribution, endogenous Fe and Zn tended to be lower in the medulla than in the outer stripe of the outer medulla and the cortex. This method is effective for analyzing Cs distribution because it can simultaneously analyze the distribution of endogenous trace elements., Competing Interests: Declarations. Ethics Approval: Animal experiments were approved by the Animal Experimental Committee of the National Institutes for Quantum Science and Technology (22–1014). Competing of Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Anticholinergic burden, reflecting the cumulative impact of medications with anticholinergic properties, significantly predicts adverse drug reactions and geriatric syndromes in older adults. Although anticholinergic risk scales (ARS) have been developed and validated in various countries, none have been tailored specifically for Japan. The Japanese Anticholinergic Risk Scale (JARS) was developed to adapt the existing ARS frameworks to the Japanese context, considering unique medication profiles and cultural factors., Process: First, a systematic review was performed to follow the protocol registered in PROSPERO (CRD42017076510). A PubMed search from October 2017 to March 2023 was conducted to identify ARS publications post-September 2017. Based on two algorithms, average scores from the existing scores were used to develop JARS. The Delphi method, an expert consensus approach, was applied to determine the scores for medications that were not established by the algorithms. Sixteen articles identified in our systematic review contributed to JARS development. JARS categorizes 158 medications into three potency groups: 37 drugs scored as 3 (strong), 27 as 2 (moderate), and 94 as 1 (weak)., Conclusion: JARS, the newly developed ARS, could be a critical tool for anticholinergic burden assessment in older Japanese populations. Developed through a systematic review and Delphi-based expert consensus, it encompasses 158 medications, offering a comprehensive anticholinergic burden assessment. Future studies and updates should be conducted to improve the accuracy and clinical applicability of this scale. Geriatr Gerontol Int 2025; 25: 5-13., (© 2024 The Author(s). Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Over a decade has passed since the development of the Hi-C method for genome-wide analysis of 3D genome organization. Hi-C utilizes next-generation sequencing (NGS) technology to generate large-scale chromatin interaction data, which has accumulated across a diverse range of species and cell types, particularly in eukaryotes. There is thus a growing need to streamline the process of Hi-C data analysis to utilize these data sets effectively. Hi-C generates data that are much larger compared to other NGS techniques such as chromatin immunoprecipitation sequencing (ChIP-seq) or RNA-seq, making the data reanalysis process computationally expensive. In an effort to bridge this resource gap, the 4D Nucleome (4DN) Data Portal has reanalyzed approximately 600 Hi-C data sets, allowing users to access and utilize the analyzed data. In this chapter, we provide detailed instructions for the implementation of the common workflow language (CWL)-based Hi-C analysis pipeline adopted by the 4DN Data Portal ecosystem. This reproducible and portable pipeline generates standard Hi-C contact matrices in formats such as .hic or .mcool from FASTQ files. It enables users to output their own Hi-C data in the same format as those registered in the 4DN Data portal, facilitating comparative analysis using data registered in the portal. Our custom-made scripts are available on GitHub at https://github.com/kuzobuta/4dn&#95;cwl&#95;pipeline ., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Ferroptosis is a type of programmed cell death owed to an intracellular accumulation of iron resulting in the generation reactive oxygen species, which in turn can cause peroxidation of plasma membrane lipids and ultimately result in cell death. We investigated the potential involvement of VPS13A deficiency in ferroptosis. The VPS13A gene encodes for chorein, and its deficiency is a molecular cause of chorea-acanthocytosis (ChAc), a Huntington-like disease with neurodegeneration in the striatum. In our previous study, we found male infertility characterized by increased malondialdehyde staining of the spermatozoa in the testes of the ChAc model mice. Thus, in this study we performed metabolome analysis of sperm extracted from the epididymis of the ChAc model mice, which revealed decreased cystine levels, suggesting an association between chorein deficiency and ferroptosis. We then investigated the role of chorein in ferroptosis using VPS13A knockdown (VPS13A-KD) HEK293 cells. We found that VPS13A-KD cells displayed a significantly diminished resistance to tert-Butyl hydroperoxide (tBHP)-induced lipid peroxidation and cell death compared to control cells, which could be rescued by treatment with ferrostatin-1. Moreover, VPS13A-KD cells showed Fe(II) accumulation, suggesting an impaired capacity for divalent iron removal. In the cytosolic fraction of VPS13A-KD cells, the protein level of glutathione peroxidase 4 (GPX4) was significantly reduced, suggesting that dysfunction of chorein impairs GPX4 transport, thereby facilitating ferroptosis. These results suggest that ferroptosis may contribute to neurodegeneration in ChAc caused by loss of chorein function., (© 2024 The Author(s). FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Serotonin-transporter-linked polymorphic region (5-HTTLPR), a variable number of tandem repeats in the promoter region of serotonin transporter gene, is classified into short (S) and long (L) alleles. Initial case-control association studies claiming the risks of the S allele in depression and anxiety were not completely supported by recent studies. However, most studies, especially those on East Asian populations, have overlooked the complexity of 5-HTTLPR, which involves multiple different alleles with distinct functional properties. To address this issue, distinguishing multiple 5-HTTLPR alleles is essential. Here, using the 5-HTTLPR genotypes previously determined by exhaustive Sanger sequencing of approximately 1,500 Japanese subjects and their comprehensive SNP data, we constructed a method for 5-HTTLPR genotype imputation. We identified 28 tag SNPs for the imputation of four major 5-HTTLPR alleles, which collectively account for 97.6% of 5-HTTLPR alleles in the Japanese population. Our imputation method, achieved an accuracy of 0.872 in cross-validation, will contribute to association analysis of 5-HTTLPR in the Japanese subjects., Competing Interests: Competing interests: Some of the authors declared financial and non-financial relationships and activities, and conflicts of interest regarding this manuscript as indicated in the supplementary materials. The sponsor had no role in study design, data collection, data analysis, data interpretation or writing of the report., (© 2024. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Bone morphogenetic protein 3b (BMP3b), also known as growth differentiation factor 10 (GDF10), is a non-osteogenic BMP highly expressed in the skeleton. Although in vitro studies have shown that BMP3b suppresses osteoblast differentiation, the physiological role of BMP3b in regulating bone mass in vivo remains unknown. Here, we show that BMP3b deletion in mice leads to a high bone mass phenotype via an unexpected novel mechanism involving de-repression of canonical BMP/Smad signaling. BMP3b null mice were viable, and exhibited no significant difference in body size compared to wildtype control. Trabecular bone parameters assessed by histomorphometry and μCT, revealed a significant increase in bone volume and bone mineral density. Expression of osteoblast-differentiation genes were elevated in bone tissue of BMP3b null mice, whereas expression of osteoclast-related genes remained unchanged. Consistent with this, Bmp3b was highly expressed in osteoblasts relative to osteoclast cells. Ex-vivo culture of primary bone marrow mesenchymal stem cells (BMSCs) and primary bone marrow-derived osteoclasts revealed that inactivation of BMP3b enhances osteogenesis without affecting osteoclastogenesis. Mechanistically, we found that BMP3b suppressed BMP4-induced Smad1/5 phosphorylation and inhibited the activity of a BMP4-driven Id-1 luciferase reporter. Protein-protein interaction assays revealed that BMP3b competitively interfered with the association of BMP4 and BMP type I receptors. These findings suggest that BMP3b regulates bone mass by acting as a BMP receptor antagonist. Thus, maintenance of bone mass involves antagonism of canonical BMP/Smad signaling by a member of the BMP family., Competing Interests: Declaration of competing interest The authors declare that this article and related all data are original, is not under consideration by any other journals. The authors also declare that we will not submit this manuscript to any other journals during the review period of Bone. The authors also confirm that data from previously published papers have not been used in this manuscript and agree to provide information about any relevant publications., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cytochrome c oxidase (CcO) is the terminal enzyme in the electron transfer chain in mitochondria. It catalyzes the four-electron reduction of O 2 to H 2 O and harnesses the redox energy to drive unidirectional proton translocation against a proton electrochemical gradient. A great deal of research has been conducted to comprehend the molecular properties of CcO. However, the mechanism by which the oxygen reduction reaction is coupled to proton translocation remains poorly understood. Here, we review the chemical properties of a variety of key oxygen intermediates of bovine CcO (bCcO) revealed by time-resolved resonance Raman spectroscopy and the structural features of the enzyme uncovered by serial femtosecond crystallography, an innovative technique that allows structural determination at room temperature without radiation damage. The implications of these data on the proton translocation mechanism are discussed., 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 Elsevier Inc. All rights reserved.)

The Response Time Concealed Information Test can reveal that a person recognizes a relevant item (probe, e.g., a murder weapon) among other, irrelevant items (controls), based on slower responses to the probe compared to the controls. A previous study (Lukács, 2022, JARMAC) analyzed the data of 14 experiments and demonstrated that classification accuracy is increased by increased test length (i.e., increased number of trials included in the analysis). However, that study left the important question open whether prior practice (whose trials are not included in the analysis) influences the classification accuracy of subsequent testing (i.e., subsequent trials included in the analysis). Reanalyzing the same data from the 14 experiments (comprising 2223 individual tests), we show that different sections of the test (each with the same number of trials), such as the first and second half of each examined test, do not differ substantially in their classification accuracy. The main implications for real-life application are that, at least up to about 600 trials, prior practice does not affect subsequent tests' results, and the number of examined relevant items or their order of presentation may be freely chosen without compromising the method's validity., (© 2024 American Academy of Forensic Sciences.)

Child malnutrition is a major health problem in Sub-Saharan Africa. Complementary foods made from African indigenous and locally available raw materials are often low in protein and nutrients. It is, therefore, important to supply complementary foods that are nutritious and affordable, and with an acceptable consistency and taste. The objective of this study was to develop, on a pilot scale, food-to-food fortified, convenient, canned complementary porridges based on blends of African indigenous crops, i.e., orange fleshed sweet potato (OFSP) flour, and leguminous (i.e., cowpea, and Bambara groundnut) and cereal flours (i.e., teff, finger millet, maize, and amaranth), and milk powder. Plant-based, African complementary foods are often lacking in vitamin A, zinc, iron, and energy. Porridge with OFSP on a 32% dry weight (dw) basis achieved recommended levels of vitamin A (530 µg per 100 g dw). Satisfactory energy (431 Kcal per 100 g dw) was obtained by supplementation of vegetable oil. A nutritious, low-cost porridge (costing 0.15 € per 100 g can) that fulfills consistency constraints was obtained by including supplements of zinc and iron salts as ingredients. The solids content and thus protein/energy could be significantly increased using protein fractionated or germinated cowpea flours without compromising on viscosity. The sensory profile was characterised by more intense vegetable, leguminous, and malty flavours as compared to traditional reference porridges., (© 2024 The Author(s). Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Background & Aims: The xenobiotic efflux pump P-glycoprotein is highly expressed on the apical membrane of the gastrointestinal tract, where it regulates the levels of intracellular substrates. P-glycoprotein is altered in disease, but the mechanisms that regulate the levels of P-glycoprotein are still being explored. The molecular motor myosin Vb (Myo5b) traffics diverse cargo to the apical membrane of intestinal epithelial cells. We hypothesized that Myo5b was responsible for the delivery of P-glycoprotein to the apical membrane of enterocytes., Methods: We used multiple murine models that lack functional Myo5b or the myosin binding partner Rab11a to analyze P-glycoprotein localization. Pig and human tissue were analyzed to determine P-glycoprotein localization in the setting of MYO5B mutations. Intestinal organoids were used to examine P-glycoprotein trafficking and to assay P-glycoprotein function when MYO5 is inhibited., Results: In mice lacking Myo5b or the binding partner Rab11a, P-glycoprotein was improperly trafficked and had decreased presence in the brush border of enterocytes. Immunostaining of a pig model lacking functional Myo5b and human biopsies from a patient with an inactivating mutation in Myo5b also showed altered localization of intestinal P-glycoprotein. Human intestinal organoids expressing the motorless MYO5B tail domain had colocalization with P-glycoprotein, confirming that P-glycoprotein was trafficked by MYO5B in human enterocytes. Inhibition of MYO5 in human intestinal cell lines and organoids resulted in decreased P-glycoprotein capacity. Additionally, inhibition of MYO5 in human colon cancer cells diminished P-glycoprotein activity and increased cell death in response to a chemotherapeutic drug., Conclusions: Collectively, these data demonstrate that Myo5b is necessary for the apical delivery of P-glycoprotein., (Copyright © 2025 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Mainland Japanese have been recognized as having dual ancestry, originating from indigenous Jomon people and immigrants from continental East Eurasia. Although migration from the continent to the Japanese Archipelago continued from the Yayoi to the Kofun period, our understanding of these immigrants, particularly their origins, remains insufficient due to the lack of high-quality genome samples from the Yayoi period, complicating predictions about the admixture process. To address this, we sequenced the whole nuclear genome of a Yayoi individual from the Doigahama site in Yamaguchi prefecture, Japan. A comprehensive population genetic analysis of the Doigahama Yayoi individual, along with ancient and modern populations in East Asia and Northeastern Eurasia, revealed that the Doigahama Yayoi individual, similar to Kofun individuals and modern Mainland Japanese, had three distinct genetic ancestries: Jomon-related, East Asian-related, and Northeastern Siberian-related. Among non-Japanese populations, the Korean population, possessing both East Asian-related and Northeastern Siberian-related ancestries, exhibited the highest degree of genetic similarity to the Doigahama Yayoi individual. The analysis of admixture modeling for Yayoi individuals, Kofun individuals, and modern Japanese respectively supported a two-way admixture model assuming Jomon-related and Korean-related ancestries. These results suggest that between the Yayoi and Kofun periods, the majority of immigrants to the Japanese Archipelago originated primarily from the Korean Peninsula., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Ménière's disease (MD) is characterized by loss of balance and hearing disorders. Although there is known to be endolymphatic hydrops involved in the pathological process, the pathogenesis of the disease is still largely unclear. Approximately half of patients with MD suffer from depressive symptoms and high levels of several stress hormones were observed in MD and depression, simultaneously. Recently, gut microbes have been shown to influence the function of the central nervous system in humans through their metabolites. We studied the intestinal microbiota of 10 patients with MD and 11 healthy donors (HD). Significant negative correlations were found between disease duration and alpha diversity indexes of gut microbes in patients with MD. The relative abundance of the species Butyricicoccus ambiguous taxa was increased in patients with MD compared with that of HD. In contrast, Oscillospiraceae UCG-002/UCG-005 ambiguous taxa and Anaerovoracaceae (Eubacterium) brachy group uncultured bacterium were increased in the relative abundance of HD than that of patients with MD. The relative abundance of the Butyricicoccus species was positively correlated with disease duration. Thus, these compositional alterations of gut microbes in patients with MD are associated with inner ear pathologies, such as endolymphatic hydrops, by changing the metabolite profiles in the intestine., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Altered gut microbiota is linked to systemic lupus erythematosus (SLE), but its association with disease development, disease activity, and post-intervention changes remains unclear. We compared new-onset SLE (NOSLE, n = 25), SLE in remission (RemSLE, n = 30), and healthy controls (HC, n = 30) cross-sectionally and conducted the first longitudinal analysis of NOSLE patients (n = 22) from pre-intervention to remission over 12 months. Significant β-diversity differences were observed in both NOSLE and RemSLE compared to HC, but not between NOSLE and RemSLE. Only four operational taxonomic units (OTUs) were enriched in NOSLE versus HC. However, 26 OTUs, including butyrate-producing bacteria (BPB), were depleted, and seven (including five BPBs) remained depleted in RemSLE compared to HC. OTUs positively and negatively correlated with disease activity were also identified. Longitudinal analysis revealed a reversal of several OTUs altered at onset and an increase in Streptococci, unrelated to the disease. Significant β-diversity differences were observed in patients with anti-SSA or anti-RNP antibodies and those with complement reduction compared to their counterparts. Our study identified gut microbiota alterations, including BPB depletion, in SLE regardless of onset or remission status, bacteria linked to disease activity, and a reversal of disease-associated bacteria along with the enrichment of Streptococci through intervention., Competing Interests: Declarations. Competing interests: EW received a grant from GSK plc. All other authors declare no competing interests., (© 2024. The Author(s).)

Background: Home-based rehabilitation involves professional rehabilitation care and guidance offered by physical, occupational, and speech therapists to patients in their homes to help them recuperate in a familiar living environment. The effects on the patient's motor function and activities of daily living (ADLs), and caregiver burden for community-dwelling patients are well-documented; however, little is known about the immediate benefits in patients discharged from the hospital. Therefore, we examined the effects of continuous home-based rehabilitation immediately after discharge to patients who received intensive rehabilitation during hospitalization., Methods: We retrospectively reviewed 150 patients [mean (standard deviation, SD) = 81 (9) years] discharged from the convalescent rehabilitation and community-based integrated care wards undergoing tailored home-based rehabilitation for 6 months (provided by physical or occupational therapists: 1-2 sessions of 40-60 min each per week). The outcome measures at baseline and after 3 and 6 months were compared., Results: The participants included in this study had orthopedic (n = 76), cerebrovascular (n = 50), neuromuscular (n = 11), cardiovascular (n = 5), respiratory (n = 3), cancer (n = 3) and other diseases (n = 2). The mean (SD) time from discharge to the start of rehabilitation was 4 (4) days. One-way analysis of variance and post-hoc comparisons showed significant improvements at 3 months from baseline in grip strength (p = 0.002), 5-repetition sit-to-stand test (p < 0.001), Standing test for Imbalance and Disequilibrium test (p = 0.025), Functional Independence Measure (p < 0.001), modified Frenchay Activities Index (p < 0.001). Additionally, a statistically significant improvement was observed in the Japanese Zarit Caregiver Burden Interview score at 6 months from baseline (p < 0.001)., Conclusions: Home-based rehabilitation improves motor function, ADLs, and instrumental ADLs even after intensive inpatient rehabilitation and decreases the burden of the caregiver in the long term. Hence, tailored home-based rehabilitation should be continuously implemented after the completion of intensive inpatient rehabilitation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sato et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Socially assistive robots introduced in nursing care settings have multidimensional psychological impacts on care recipients and caregivers. This study aims to explore the longitudinal changes induced by socially assistive robots, focusing on a chain of human behaviors., Methods: In this qualitative study, nine participants from two nursing homes who had experience in manipulating socially assistive robots were interviewed in a semi-structured focus group using a topic guide to explore the changes in care recipients and caregivers. Following the framework analysis method, the transcripts were coded using the International Classification of Functioning, Disability, and Health (ICF). The identified codes were charted for each side-care recipients and caregivers sides- using a causal loop diagram, a tool used to visualize nonlinear dynamics in complex systems., Results: Three and seven kinds of codes in the domains of "body functions" and "activities and participation", respectively, were identified on the care recipients' side; whereas on the caregivers' side, one and five kinds of codes in the domains of "body functions" and "activities and participation", respectively, were found. The codes obtained from the facility with longer experience were represented graphically as a reinforcing feedback loop, in which favorable changes were amplified in a chain of events. Robot use directly changed the mental functions of care recipients, and the caregivers' perceptions of these positive changes led to their own emotional and behavioral changes, which would reduce the burden of care. Moreover, the findings suggest that sharing information regarding these changes and objectively recognizing the effectiveness of robots among staff members can be the key to continuous robot use in nursing care settings. Conversely, the figure obtained from the novice facility shows fragmented chain relationships of the codes, indicating that all the effects of robot use are recognizable and form a chain reaction after continuous robot use for more than several months., Conclusions: This study revealed important aspects regarding the longitudinal effects of socially assistive robots in nursing care settings. These implications should be broadly implemented for effective robot use and reduction of the burden of care in nursing care settings., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol was approved by the Ethics Committees of the Kanagawa Prefectural Institute of Industrial Science and Technology and the Ethics Committee of the National Center for Geriatrics and Gerontology (approval number 22TB20). All participants provided written informed consent before participation. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

In oncology drug development, overall response rate (ORR) is commonly used as an early endpoint to assess the clinical benefits of new interventions; however, ORR benefit may not always translate into a long-term clinical benefit such as overall survival (OS). Most of the work on developing endpoints based on tumor growth dynamics relies on empirical validation, leading to a lack of generalizability of the endpoints across indications and therapeutic modalities. Additionally, many of these metrics are model-based and do not use data from all the patients. The objective of this work is to use longitudinal tumor size data and new lesion information (that is, the same information used by the ORR) to develop novel endpoints that can improve early clinical decision-making compared to the ORR. We investigate in this work multiple candidate novel endpoints based on tumor size ratio that utilize longitudinal tumor size data from all the patients regardless of their follow-up, rely only on tumor size and new lesion information, and are model-free. An extensive simulation study is conducted, exploring a wide spectrum of tumor size data and overall survival outcomes by modulating a variety of trial characteristics such as slow vs fast tumor growth, high vs low drug efficacy rates, variability in patients' responses, variations in the number of patients, follow-up periods, new lesion rates and survival curve shapes. The proposed novel endpoints based on tumor size ratio consistently outperform the ORR by having a comparable or higher correlation with the OS. Further, the novel endpoints exhibit superior accuracy compared to the ORR in predicting the long-term OS benefit. Retrospective empirical validation on BMS clinical trials confirms our simulation findings. These findings suggest that the tumor size ratio-based endpoints could replace ORR for early clinical decision-making in oncology drug development., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: This study aimed to develop and validate a Japanese version of the Public Attitudes Toward Epilepsy (PATE-J) Scale to measure attitudes towards epilepsy among the general Japanese population., Methods: The study employed a cross-sectional design using an online survey of 537 participants from the general public in Japan, with follow-up surveys at 2 weeks and 3 months. The PATE Scale was translated following standard guidelines and validated by conducting confirmatory factor analysis (CFA) on the complete data set to assess the original two-factor structure of the PATE Scale. Internal consistency assessment, and convergent validity testing with the Modified Epilepsy Stigma Scale (M-ESS), Perceived Devaluation Discrimination Scale (PDDS), and Epilepsy Knowledge Scale (EKS) were carried out., Results: CFA confirmed the two-factor structure of the PATE-J, comprising "Personal Domain" and "General Domain." The model showed acceptable fit indices ( χ ²(76) = 607.974, comparative fit index = 0.849, Tucker-Lewis index = 0.820, root-mean-square error of approximation = 0.114, standardized root-mean-square residual = 0.078) and high reliability (Cronbach's α  = 0.87 for Personal Domain and 0.75 for General Domain). Strong correlations with the M-ESS ( r  = 0.713, p  < 0.001), and weaker correlations with the PDDS, along with a negative correlation with the EKS ( r  = -0.306, p  < 0.001), highlighted the PATE-J's distinctiveness. No significant associations were found between demographic factors and PATE-J scores., Conclusion: The PATE-J demonstrates strong psychometric properties and cultural relevance for measuring public attitudes toward epilepsy in Japan. Its validated two-factor structure supports cross-cultural comparisons and provides a reliable tool for assessing public attitudes, informing interventions, and guiding education campaigns., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Granulomatous interstitial nephritis (GIN) has been reported in <0.5% of patients with inflammatory bowel disease, and most cases of GIN are drug-induced. A 13-year-old boy was referred for the evaluation of abdominal pain, diarrhea, and weight loss. The patient was diagnosed with non-drug-induced GIN and Crohn's disease based on total colonoscopy and a biopsy of the colon and kidney. Both tissues contained macrophages and increased epithelial expression of IκBζ, a protein involved in the NF-κB pathway. There may be more patients with GIN complicated by Crohn's disease than expected, and macrophages may be involved in the pathogenesis.