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Background: A nationwide survey conducted by the Japanese Society of Chemotherapy and the Japanese Association for Infectious Diseases in 2020 provided insights into antimicrobial prescription practices among clinic doctors. This study aimed to investigate factors influencing changes in antimicrobial prescriptions post-implementation of the National Action Plan on Antimicrobial Resistance (NAPAR) and doctors' inclination to prescribe antimicrobials for common cold cases., Methods: In September 2020, randomly selected questionnaires were distributed to 3000 community-based medical clinics in Japan. The primary objective was to assess the reduction in antimicrobial prescriptions post-NAPAR implementation. Multivariate linear regression analysis was employed to identify associated factors., Results: Analysis of 632 responses (response rate: 21.1 %) revealed determinants of decreased antimicrobial prescriptions, including familiarity with the Guide to Antimicrobial Stewardship (β = .482, t = 3.177, p = 0.002) and awareness of NAPAR (β = .270, t = 2.301, p = 0.022)., Conclusion: Interventions such as the Guide to Antimicrobial Stewardship may have contributed to the reduction in antimicrobial prescriptions among Japanese physicians. However, targeted strategies are needed to address high-prescription groups. Enhancing awareness and education on appropriate antimicrobial use should be integral components of future initiatives to combat antimicrobial resistance effectively., Competing Interests: Declaration of competing interest Shigefumi Maezaki has received lecture fees from Pfizer Japan Inc., Astellas Pharma Inc., Sumitomo Dainippon Pharma Co. Ltd., Shionogi & Co. Ltd., MSD K.K., KYORIN Pharmaceutical Co. Ltd., and Taisho Toyama Pharmaceutical Co. Ltd. Tetsuya Matsumoto has received lecture fees from MSD K.K., Pfizer Japan Inc., Taisho Toyama Pharmaceutical Co., Ltd., and Meiji Seika Pharma Co., Ltd., as well as research funding from Kewpie Corp. Norio Ohmagari, Yoshiaki Gu, Shinichiro Morioka, Shinya Tsuzuki, Hiroshi Soeda, Chikara Nakahama, Naoki Hasegawa, Yumiko Fujitomo, Masayuki Maeda, and Isao Miyairi have declared no conflicts of interest associated with this manuscript., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Context: Patients should be optimally informed about their illness for patients' autonomy and shared decision-making. However, diagnosis nondisclosure to patients is traditionally widespread in Japanese culture with family-oriented autonomy. There is insufficient research on quality of death (QOD) and quality of care (QOC) among patients who are not told their diagnosis., Objectives: This study aimed to examine the impact of diagnosis nondisclosure on QOD and QOC in cancer patients., Methods: We performed a secondary analysis of a cross-sectional, nationwide mortality follow-back survey. The bereaved families responded to the questionnaire. Measurements included decedents' QOC, QOD, and bereaved families' outcomes. After using the propensity score matching method based on the covariates which can affect nondisclosure actions to compare the "disclosure" group and "nondisclosure" group, we compared differences in QOC, QOD, and bereaved families' outcomes between the two groups., Results: Of the 110,990 family members who were sent the questionnaires, we finally analyzed 46,672 responses. The disclosure group and nondisclosure group included 42,300 (90.6%) and 4,372 (9.4%) decedents, respectively. Most of the QOD domains (14/18) showed significantly higher scores in the disclosure group compared with the nondisclosure group. In terms of QOC domains, all domains showed higher scores in the disclosure group. Respondents in the disclosure group reported higher overall care satisfaction., Conclusion: We demonstrated that overall QOD and QOC in decedents with cancer were significantly higher in decedents with explicit cancer diagnoses. Furthermore, bereaved family members' outcomes were better among the family members of decedents with an explicit cancer diagnosis., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

The scarcity of seed sludge poses a significant barrier to the advancement of anaerobic ammonia oxidation (anammox) process. In this investigation, two alternative sludge (anaerobic granular sludge (AGS) and activated flocculent sludge (AFS)) were employed to start up the anammox process in internal circulation (IC) reactors with the hydroxyapatite (HAP) strategy. Both reactors achieved rapid start-up on days 83 and 53, respectively. Subsequently, a nitrogen removal rate (NRR) of 1.34 gN/L/d was attained at a nitrogen loading rate (NLR) of 1.39 gN/L/d on days 107 and 81 correspondingly. The analysis of granular properties revealed that the anammox granular sludge (AMXGS) transformed from AGS exhibited superior granular size distribution and settling performance. Furthermore, the assessment of microbial community structure demonstrated that inoculating AFS was capable of enriching anammox bacteria (AnAOB) in a shorter time. Last but most importantly, this study provides a comprehensive analysis of the distinct granulation routes of AGS and AFS. AGS predominantly underwent a "broken-adsorption-granulation" process, whereas AFS exhibited not only a typical "adsorption-granulation" process but also a "biofilm growth-granulation" cycle process. The findings of this study offer a novel approach for quickly initiating anammox process when inoculating alternative sludge., 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.)

Objective: Hepatic steatosis, the early stage of nonalcoholic fatty liver disease (NAFLD), currently lacks targeted pharmacological treatments. G protein-coupled receptors (GPCRs) in hepatocytes differentially regulate lipid metabolism depending on their coupling profile of G protein subtypes. Unlike G s , G i , and G q signaling, the role of G 12 signaling in hepatic steatosis remains elusive. The objective of this study was to investigate the effect of G 12 signaling on hepatic steatosis and obesity and its mechanisms., Methods: We generated mice expressing a G 12 -coupled designer GPCR in a liver-specific manner. We performed phenotypic analysis in the mice under the condition of fasting (acute hepatic steatosis model) or high-fat diet feeding (chronic hepatic steatosis model)., Results: In acute and chronic hepatic steatosis models, chemogenetic activation of hepatic G 12 signaling suppressed the progression of hepatic steatosis. The treatment led to an increased triglyceride secretion with little effect on mitochondrial respiratory activity, fatty acid oxidation, de novo lipogenesis, and fatty acid uptake. Furthermore, in a high-fat-diet-induced obesity model, activation of the G 12 -coupled designer GPCR exerted anti-obesity effects with increased whole-body energy expenditure and fat oxidation. Anti-FGF21 antibody treatment showed that the anti-obesity effects of the hepatic G 12 D activation relied in part on the hepatokine FGF21., Conclusions: Our findings indicate that the activation of G 12 signaling in the liver has the potential to prevent hepatic steatosis and obesity. This discovery provides a strong rationale for the development of drugs targeting G 12 -coupled GPCRs expressed in the liver., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Context: The Bereaved Family Survey is an important method for evaluating the quality of palliative care., Objectives: To examine the distress and benefits of bereaved families of patients with or without cancer, who participated in a Bereaved Family Survey, and identify factors associated with distress and benefits., Methods: We conducted a nationwide cross-sectional, self-reported questionnaire mail survey among the bereaved families of patients who died of cancer, heart disease, cerebrovascular disease, pneumonia, or kidney failure. Participants answered questions on a four-point Likert scale measuring the distress and benefit associated with participating in the Bereaved Family Survey. We conducted a qualitative analysis of responses to open-ended questions about the distress and benefits of participating in the survey to comprehensively examine the distress and benefits of participating in the survey., Results: Questionnaires were distributed to 115,816 eligible bereaved family members between February 2019 and February 2020; 62,576 (54.0%) family members returned valid responses. Distress and benefits accounted for 51.4% and 49.3%, respectively. The results of the binomial logistic analysis for distress were significantly higher among cancer patients (P < 0.001-0.003), 20-39-year-old patients (P < 0.001), female bereaved family members (P < 0.001), and bereaved family members with poor mental health statuses (P < 0.001). Factors related to "benefit" were significantly higher among over-80-year-old bereaved family members (P < 0.001), higher care evaluation scale (CES) scores (P < 0.001), and higher good death inventory (GDI) scores (P < 0.001)., Conclusion: Bereaved family members experience both distress and benefits. There is need to devise ways to reduce distress and increase its benefits to continue assessing the quality of palliative care., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

SpinX, an AI-guided spindle tracking software, allows the 3-dimensional (3D) tracking of metaphase spindle movements in mammalian cells. Using over 900 images of dividing cells, we create the Multi-SpinX framework to significantly expand SpinX's applications: a) to track spindles and cell cortex in multicellular environments, b) to combine two object tracking (spindle with kinetochores marked by centromeric probes) and c) to extend spindle tracking beyond metaphase to prometaphase and anaphase stages where spindle morphology is different. We have used a human-in-the-loop approach to assess our optimisation steps, to manually identify challenges and to build a robust computational pipeline for segmenting kinetochore pairs and spindles. Spindles of both H1299 and RPE1 cells have been assessed and validated for use through Multi-SpinX, and we expect the tool to be versatile in enabling quantitative studies of mitotic subcellular dynamics., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Binghao Chai reports financial support was provided by Carl Zeiss AG. Muntaqa Choudhry reports financial support was provided by Carl Zeiss AG. Viji M Draviam reports a relationship with Carl Zeiss AG that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Large or giant paraclinoid aneurysms have been treated with various strategies, including clipping, coiling, and parent artery occlusion (PAO). In addition, flow diverters (FDs) have been introduced for the management of these aneurysms. The aim of this study was to examine the management of unruptured large/giant paraclinoid aneurysms in Japan when FDs were being introduced by a nationwide survey., Methods: A total of 576 unruptured large/giant paraclinoid aneurysms treated in Japan between January 2012 and December 2016 were retrospectively studied., Results: Half of the large paraclinoid aneurysms were treated by coiling (50.3%), whereas giant aneurysms were occluded mainly by PAO (51.4%). A high nearly complete occlusion rate was achieved with clipping (94.1%), coiling (85.9%), PAO (82.4%), and FDs (77.6%). Coiling had higher risks of recurrence (28.3%) and retreatment (20.3%). Major procedure-related complications were observed in 9.7%. Ischemic complications were common in PAO (9.5%), with cranial nerve symptoms common in clipping (10.9%). All treatment modalities achieved good clinical outcomes (93.5%-96.6%). Although not significant, pre-existing visual disturbance improved most frequently by clipping (53.7%), but also worsened most frequently by clipping (24.4%). Consequently, FD achieved a high occlusion rate with minimal complication and retreatment rates., Conclusions: All treatment modalities offer high rates of complete occlusion and good clinical outcomes. Coiling has the disadvantage of high rates of recurrence and retreatment. Clipping and PAO have the disadvantage of a high rate of major procedure-related complications; however, PAO can provide comparable treatment outcomes even in cases with refractory giant aneurysms. FDs are the optimal choice for the management for large/giant paraclinoid aneurysms due to its safety and efficacy., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study examines the neural mechanisms behind integrating syntactic and information structures during sentence comprehension using functional Magnetic Resonance Imaging. Focusing on Japanese sentences with canonical (SOV) and non-canonical (OSV) word orders, the study revealed distinct neural networks responsible for processing these linguistic structures. The left opercular part of the inferior frontal gyrus, left premotor area, and left posterior superior/middle temporal gyrus were primarily involved in syntactic processing. In contrast, the right inferior frontal sulcus, bilateral intraparietal sulci, and the left triangular part of the inferior frontal gyrus were linked to information structure processing. Importantly, the left opercular part of the inferior frontal gyrus (BA44) played a crucial role in integrating these structures during the later stages of comprehension, particularly when processing the second noun phrase. These findings enhance our understanding of the complex interplay between syntactic and information structures in language comprehension., 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 © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with cardiac sarcoidosis (CS) are at an increased risk of fatal ventricular arrhythmic events (FVAE). However, the predictive value of 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) in assessing the risk of FVAE in patients with CS remains uncertain., Methods: We included data from 121 patients with CS (39 men and 82 women; mean age: 59.5 years) who underwent FDG-PET imaging between March 2008 and November 2020, with follow-ups completed in July 2023. Of these, 82 patients had available cardiac magnetic resonance imaging data, including late gadolinium enhancement (LGE). FDG-PET images were analysed using a polar-map model to determine the regional mean percentage uptake relative to the maximal cardiac 18 F-FDG uptake in each of the 17 segments defined by the American Heart Association., Results: Patients experiencing FVAE after FDG-PET (n = 43) showed lower percent uptake in the basal inferoseptal segment compared to those who did not (n = 78) (41.8 ± 15.2 % vs. 54.4 ± 13.8 %, P < 0.001). Patients with a basal inferoseptal percent uptake below the median had a lower FVAE-free survival rate than those with a higher percent uptake (58.1 % vs. 78 % at 5 years, P = 0.007), which was consistent in patients with LGE in the same regions with reduced 18 F-FDG uptake. A Cox hazard model indicated that the FVAE risk decreased with a hazard ratio of 0.862 (95 % CI 0.770-0.964) for every 5 % increase in basal inferoseptal percent uptake (P = 0.009)., Conclusion: Reduced 18 F-FDG uptake in the basal interventricular septum, including the inferoseptal segment, may be a valuable predictor of future FVAE in patients with CS., Competing Interests: Declaration of competing interest S. Yasuda has received grant support from Takeda Pharmaceutical, Abbott, and Boston Scientific and lecture fees from Daiichi Sankyo and Bristol Myers Squibb. The other authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery., Background: Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC., Methods: International multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). Primary endpoint is OS from diagnosis. Time-dependent Cox regression analysis was performed to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at time of diagnosis. Adjusted OS probabilities were calculated., Results: Overall, 2,282 patients after left-sided pancreatic resection for RPC were included of whom 290 patients (13%) received neoadjuvant therapy. The most common neoadjuvant regimens were (m)FOLFIRINOX (38%) and gemcitabine-nab-paclitaxel (22%). After upfront surgery, 72% of patients received adjuvant chemotherapy, mostly a single-agent regimen (74%). Neoadjuvant therapy was associated with prolonged OS compared to upfront surgery (adjusted HR=0.69 [95%CI 0.58-0.83]) with an adjusted median OS of 53 vs. 37 months (P=0.0003) and adjusted 5-year OS rates of 47% vs. 35% (P=0.0001) compared to upfront surgery. Interaction analysis demonstrated a stronger effect of neoadjuvant therapy in patients with a larger tumor (P interaction =0.003) and higher serum CA19-9 (P interaction =0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (P interaction =0.43), splenic vein (P interaction =0.30), retroperitoneal (P interaction =0.84), and multivisceral (P interaction =0.96) involvement., Conclusions: Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared to upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Proteasome-dependent protein degradation and the digestion of peptides by aminopeptidases are essential for myogenesis. Methionine aminopeptidases (MetAPs) are uniquely involved in, both, the proteasomal degradation of proteins and in the regulation of translation (via involvement in post-translational modification). Suppressing MetAP1 and MetAP2 expression inhibits the myogenic differentiation of C2C12 myoblasts. However, the molecular mechanism by which inhibiting MetAPs impairs cellular function remains to be elucidated. Here, we provide evidence for our hypothesis that MetAPs regulate proteostasis and that their inhibition increases ER stress by disrupting the post-translational modification, and thereby compromises cell integrity. Thus, using C2C12 myoblasts, we investigate the effect of inhibiting MetAPs on cell proliferation and the molecular mechanisms underpinning its effects. We found that exposure to bengamide B (a MetAP inhibitor) caused C2C12 myoblasts to lose their proliferative abilities via cell cycle arrest. The underlying mechanism involved the accumulation of abnormal proteins (due to the decrease in the N-terminal methionine removal function) which led to increased endoplasmic reticulum stress, decreased protein synthesis, and a protective activation of the autophagy pathway. To identify the MetAP involved in these effects, we use siRNAs to specifically knockdown MetAP1 and MetAP2 expressions. We found that only MetAP2 knockdown mimicked the effects seen with bengamide B treatment. Thus, we suggest that MetAP2, rather than MetAP1, is involved in maintaining the integrity of C2C12 myoblasts. Our results are useful in understanding muscle regeneration, obesity, and overeating disorders. It will help guide new treatment strategies for these disorders., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Study Objective: This study aimed to examine extent, fraction, and trends of general payments to anesthesiologists and non-physician anesthesia providers (NPAPs) in the United States., Design: This is a cross-sectional analysis of general payments by pharmaceutical and medical device industry to all anesthesiologists (2014-2023) and NPAPs (2021-2023) for non-research purposes using the Open Payments Database, a federal transparency database under the Physician Payments Sunshine Act between 2014 and 2023., Setting: The United States., Participants: All active practicing anesthesiologists and NPAPs, including certified registered nurse anesthetists and anesthesiologist assistants, in the United States., Measurements: Fraction of providers receiving non-research payments; total payment amounts; median payment amounts per provider; relative annual average percentage change from 2014 to 2023., Main Results: A total of $297.8 million general payments were made by industry to 75.4 % of all active anesthesiologists from 2014 to 2023, while $7.2 million was made to 46.8 % of NPAPs from 2021 to 2023. Median annual payments ranged from $59-$120 for anesthesiologists and $37-$38 for NPAPs. The proportion of anesthesiologists receiving payments declined at a relative annual average percentage change (RAAPC) of -2.9 % from 2014 to 2019, followed by a substantial decrease in 2020. Subsequently, the number of payment recipients increased at an RAAPC of 15.4 % (2020-2023) for anesthesiologists and 9.0 % (2021-2023) for NPAPs. Payment distribution was highly concentrated, with the top 1 % of anesthesiologists and NPAPs receiving 78.2 % and 52.5 % of total payments in 2023, respectively. Among anesthesiology subspecialties, pain medicine physicians consistently received the highest median payments ($332-$767) throughout the study period., Conclusions: This study demonstrated large financial relationships between industry and anesthesia providers, with a disproportionate concentration of payments among a minority of providers., Competing Interests: Declaration of competing interest The author received an internal grant from Tohoku University School of Medicine outside this study., (Copyright © 2024. Published by Elsevier Inc.)

Importin α is a crucial player in the nucleocytoplasmic transport of nuclear localization signal (NLS)-containing cargo proteins and is suggested to bind to DNA directly. We hypothesized that importin α, after binding to DNA, may move along DNA via sliding or hopping. We investigated the movement dynamics of importin αs fused to AcGFP along DNA using single-molecule fluorescence microscopy and single-tethered DNA arrays. Single-molecule data demonstrated importin α diffuses along DNA in fast and slow mobility modes. The diffusion by importin α in the fast mobility mode did not depend on salt concentration, suggesting sliding motion with continuous contact with DNA. The sliding was supported by restricted diffusion of importin α in Cas9 obstacles bound to DNA. Next, we tested whether importin α can transport a cargo molecule along DNA. Two-color imaging data established that importin α co-slides along DNA with SV40 TAg-NLS as a model cargo. We found that importin β1 together with RanGTP significantly enhanced the DNA binding of importin α and the recruitment of a model cargo TRIM28 to DNA, suggesting that importin β1/RanGTP are involved in the switching of importin α/cargo from the nuclear transport pathway to DNA sliding. Single-molecule and in vivo immunofluorescence assay demonstrates importin α assists in accumulating TRIM28 within nuclear chromatin regions. Thus, we present novel findings on the sliding dynamics and the cargo transport of importin α along DNA. The relatively faster sliding by importin α allows efficient delivery of cargo proteins to their target sites, even on long genomic DNA., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Background: The FOxTROT trial has reported advantages of neoadjuvant chemotherapy (NAC) in locally advanced colon cancer (LACC). Here we present results of the embedded randomized phase II trial testing the addition of panitumumab to neoadjuvant FOLFOX compared with FOLFOX alone in RAS and BRAF-wild-type patients and with biomarker hyperselction., Patients and Methods: Patients had operable, CT-predicted stage T3-4, N0-2, M0 colon adenocarcinoma. KRAS-wt pts allocated to NAC could optionally be sub-randomized 1:1 to FOLFOX ± panitumumab during the pre-operative phase. RAS/BRAF were tested by NGS; EREG/AREG by RNAseq. Primary endpoint is time to recurrence (TTR) in RAS/BRAF-wt patients; secondary endpoints include safety, histological downstaging, disease-free survival (DFS), colon cancer-specific survival (CCSS), overall survival (OS), and impact of primary tumor location and EREG/AREG., Results: In total 269 KRAS-wt patients were enrolled into the embedded phase II trial. Extended RAS/BRAF data were available for 232 (83%) patients; 22/232(9.5%) were RAS-mutant; 41/210(20%) were BRAF-mutant. Median follow up was 42 months. In 169 RAS/BRAF-wt patients there was a trend towards reduced recurrences with FOLFOX plus panitumumab compared with FOLFOX (12% vs 21%, HR=0.51, p=0.09); significant improvements were seen for DFS, CCSS and OS. Within the hyperselected EREG/AREG high group, there was significant reduction in recurrences with panitumumab. Panitumumab was not associated with increased pathological regression of the primary tumor (TRG 1-3 16% vs 22%,p=0.27). FOLFOX plus panitumumab was associated with higher rates of grade 3 diarrhoea (8% vs 3%,) and rash (22% vs 2%)., Conclusion: This exploratory analysis from a randomized phase II study shows a non-significant improvement in TTR from the addition of neoadjuvant panitumumab to peri-operative FOLFOX in RAS/BRAF-wt LACC. Hyperselection with EREG/AREG status was associated with increased efficacy. A dedicated prospective trial within a biomarker selected population is under development., Clinical Trials Registration: ISRCTN87163246., Competing Interests: Conflict of Interest: JS - advisory/steering committee: Astra-Zeneca, Boehinger-Ellison, BMS, GSK, Johnson & Johnson, Merck Serono, Sanofi, Servier Takeda. Speaker Fees - GSK, Merck Serono, Pierre Fabre Medicament, Servier, Takeda; Research Funding - Pierre Fabre Medicament, Merck Serono, GSK DM - no disclosures FE - no disclosures KH - no disclosures RG - no disclosures MS - no disclosures BG - no disclosures LM - no disclosures CW - speaker fees - Servier PQ - advisory and research funding Roche Diagnostics DB - no disclosures HW - no disclosures KM - no disclosures AB - no disclosures NW - Amgen, Astellas, Bristol Myers Squibb, GSK and Pfizer, and research funding to institution from Adlai Nortyem GSK and Pierre Fabre, (Copyright © 2025. Published by Elsevier Ltd.)

An agrivoltaic system (AVS), wherein crops and electricity are simultaneously produced on the same agricultural land, contributes to renewable energy production and food security. AVS is expected to expand energy production in rural areas; however, its energy balance has not been comprehensively investigated. In this study, the energy balance of an AVS established in 2021 in the paddy fields on Shonai Plain was determined. The factors affecting rice growth and yield and the amount of electricity generated were monitored for 3 years (2021-2023). The photosynthetic photon flux density (PPFD) in the AVS field decreased by 26-39 %. Rice growth and yield decreased by >20 % due to insufficient light, as the photovoltaic (PV) panels intercepted most of the solar radiation. The energy balance of the AVS was -3102.47 GJ·ha -1 because energy input was required for installing the AVS. However, since 2083.46 GJ· ha -1 of energy was generated by the AVS, it is expected that the energy balance will become positive after >2 years of operation. To improve rice production, it is necessary to model PPFD and rice growth; additionally, PV panels should be movable so that the amount of PPFD can be adjusted depending on the model., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yoshiki Kuwabara reports financial support was provided by Nippon Life Insurance Foundation. Yoshiki Kuwabara reports financial support was provided by Mechanic Co., Ltd. Yoshiki Kuwabara reports financial support was provided by Japanese Society of Irrigation, Drainage, and Rural Engineering. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Glioblastomas contacting the subventricular zone (SVZ) are associated with poor prognosis and the impact of ventricular entry (VE) during resection remains controversial. Since glioblastomas with SVZ involvement often require VE, both SVZ involvement and VE are confounding factors. This study aimed to evaluate the effect of VE during glioblastoma resection by comparing patients with and without SVZ involvement., Methods: This multi-institutional retrospective study reviewed newly diagnosed isocitrate dehydrogenase (IDH)-wildtype glioblastoma who underwent resection. The focus was on VE, complications, and recurrence patterns based on SVZ status., Results: A total of 418 patients were included. with 278 (66.5%) undergoing VE and 140 (33.5 %) without. Patients with VE had significantly shorter overall survival (OS) than those without VE (18.6 vs. 25.6 months, p = 0.008). VE was more common in patients with SVZ tumors (94.2%) compared to non-SVZ tumors (26.3%, p < 0.0001). Notably, 44 patients with non-SVZ tumors experienced VE, whereas 15 patients with SVZ tumors did not. Regardless of SVZ status, VE did not affect the rates of complications, such as symptomatic subdural effusion, hydrocephalus, infection, or nonlocal recurrence. OS was similar with each group: for SVZ tumors, OS was 17.7 months with VE vs. 19.9 months without VE (p = 0.34), and for non-SVZ tumors, OS was 30.8 months with VE vs. 25.6 months without VE (p = 0.63)., Conclusions: VE during glioblastoma resection does not impact complications or nonlocal recurrence. Surgeons may safely perform VE during resection of both SVZ and non-SVZ glioblastomas without adverse effects., (Copyright © 2024. Published by Elsevier Inc.)

The maintenance of cellular redox balance is crucial for cell survival and homeostasis and is disrupted with aging. Selenoproteins, comprising essential antioxidant enzymes, raise intriguing questions about their involvement in hematopoietic aging and potential reversibility. Motivated by our observation of mRNA downregulation of key antioxidant selenoproteins in aged human hematopoietic stem cells (HSCs) and previous findings of increased lipid peroxidation in aged hematopoiesis, we employed tRNASec gene (Trsp) knockout (KO) mouse model to simulate disrupted selenoprotein synthesis. This revealed insights into the protective roles of selenoproteins in preserving HSC stemness and B-lineage maturation, despite negligible effects on myeloid cells. Notably, Trsp KO exhibited B lymphocytopenia and reduced HSCs' self-renewal capacity, recapitulating certain aspects of aged phenotypes, along with the upregulation of aging-related genes in both HSCs and pre-B cells. While Trsp KO activated an antioxidant response transcription factor NRF2, we delineated a lineage-dependent phenotype driven by lipid peroxidation, which was exacerbated with aging yet ameliorated by ferroptosis inhibitors such as vitamin E. Interestingly, the myeloid genes were ectopically expressed in pre-B cells of Trsp KO mice, and KO pro-B/pre-B cells displayed differentiation potential toward functional CD11b+ fraction in the transplant model, suggesting that disrupted selenoprotein synthesis induces the potential of B-to-myeloid switch. Given the similarities between the KO model and aged wild-type mice, including ferroptosis vulnerability, impaired HSC self-renewal and B-lineage maturation, and characteristic lineage switch, our findings underscore the critical role of selenoprotein-mediated redox regulation in maintaining balanced hematopoiesis and suggest the preventive potential of selenoproteins against aging-related alterations., (Copyright © 2025 American Society of Hematology.)

Background and Objectives: Skin microbiome dysbiosis can cause skin barrier dysfunction and stimulate scar property change. Skin barrier disruption post-burn injury leads to an imbalance in skin microbe diversity and distribution. We aimed to examine the changes in the skin microbiome of re-epithelialized burn scars., Material and Methods: Twenty three patients were enrolled between January 2020 and July 2022. Twenty-six (13 Scar 1, immediately after complete wound healing; and 13 Scar 2, 3 months after complete wound healing) of seventy-eight scar skin samples (39 Scar 1 and 39 scar 2) qualified for analysis. Microbial community analysis was performed. Biomechanical scar properties of each patient and their correlation with skin microbiome were investigated., Results: The α-diversity of the scarred skin microbiome increased with time (Shannon's index, p = 0.029; Simpson's index, p = 0.009). The linear discriminant analysis effect size results showed that Bacteroides abundance decreased in scars after 3 months, whereas Campylobacter and Cutibacterium abundance increased. Campylobacter and Cutibacterium negatively and positively correlated with the final distensibility gross and biological elasticity, respectively. These results were consistent with the changes in the biomechanical properties of scars., Conclusion: The scar skin microbial communities in patients with burns changed with biomechanical scar properties over time, and specific skin microorganisms correlated with biomechanical scar dynamics at the genus level., Competing Interests: Declaration of Competing Interest Our authors declare that we have no conflicts of interest relevant to this work. The funder had no role in the design of the study, collection, analyses, or interpretation of data, writing of the manuscript, or the decision to publish the results., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hepatitis B virus (HBV) can be transmitted within a family, but an interspousal transmission in elderly cases is rare and the change of viral quasispecies during the event is unclear. We experienced two acute hepatitis B males (AH1 and AH2, 67 and 71 years old, respectively) whose HBV was transmitted from their wives with chronic HBV infection (CH1 and CH2, 67 and 66 years old, respectively). To clarify the characteristics of HBV quasispecies in such cases, we performed long-read deep sequencing of HBV preS1/preS2/S domain using samples from the 2 couples. HBV full-genome sequences determined with direct sequencing showed that the HBV sequences belonged to subgenotype B1. AH1 was 98.0-99.2 % identical to CH1, and AH2 was 98.5-99.5 % identical to CH2, whereas the identity between AH1 and AH2 was 96.9 %. The long-read deep sequencing of amplicons including preS1/preS2/S domains with PacBio Sequel IIe showed the numbers of nucleotides with >5 % substitution frequencies in AH1, AH2, CH1 and CH2 were 0 (0 %), 4 (0.31 %), 39 (3.06 %) and 28 (2.20 %), respectively, indicating that CH1 and CH2 were more heterogeneous than AH1 and AH2. From a phylogenetic analysis based on the deep sequencing, minor CH1/CH2 clones that were close to AH1/AH2 clones were considered to be substantially distinct from the major populations in CH1/CH2. The major population formed during chronic infection under the immune pressure might not be suitable to establish new infection and this might be one of the reasons why the transmission had not occurred for a long time after marriage., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

The benthic pennate diatom Nitzschia navis-varingica, known for producing domoic acid (DA) and its isomers, is widely distributed in the Western Pacific (WP) region. To investigate the genetic differentiation and gene flow patterns among the populations in the WP, the genetic diversity of 354 strains of N. navis-varingica was analysed using two nuclear-encoded rDNA loci: the large subunit rDNA (LSU rDNA) and the internal transcribed spacer 2 (ITS2). Frustule morphology of each strain was examined by TEM. The LSU rDNA phylogeny revealed a monophyletic lineage encompassing all strains, with sequence divergences of <0.9 %. Phylogenetic and population genetic analyses of ITS2 identified eight distinct clades (designated as Groups A to H) with moderate to high genetic heterogeneity (0.5-19.7 %). The low genetic differentiations between the geographically separated populations (pairwise F ST of <0.03) suggested high gene flow and lack of spatial genetic structuring. Molecular clock analysis of the ITS2 phylogeny traced the evolutionary history of N. navis-varingica to the Eocene Epoch, and the split between clades likely occurred from the mid-Miocene to Pleistocene Epochs (10.8-1.2 Ma). The population dispersal in the WP were likely influenced by historical events like the Quarternary glacial cycles during the period, contributing to its homogenous distributions in the region., 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 B.V. All rights reserved.)

Objectives: To examine the effect of social support on the risk of caregiver's functional disability due to spouse's functional disability., Design: Longitudinal study., Setting and Participants: In this cohort study using the Ohsaki Cohort 2006 Study data, the baseline survey was conducted from December 1, 2006, to December 15, 2006, and included 7598 older adults, including 3799 couples, ≥65 years of age., Methods: The incidence of spouse's functional disability was defined as certification for the Long-term Care Insurance, which uses a nationally uniform standard of functional disability. The primary outcome was the incidence of the caregiver's functional disability, and the follow-up period was between December 16, 2006, and November 30, 2019. Five social support questionnaires were used to assess the degree of emotional and instrumental social support available to each participant. The Cox proportional hazards model was used to evaluate the incidence of functional disability among caregivers after the occurrence of spouses' functional disability. Subgroup analyses were also conducted according to the status of emotional and instrumental social support., Results: The caregiver's functional disability increased significantly among those whose spouses had functional disability compared with those whose spouses had no disability [multivariate hazard ratio (HR), 1.86]. Emotional and instrumental social support showed significant positive interactions on this association (emotional and instrumental support: P for interaction < .01 and < .01, respectively), and the risk of caregiver's disability was higher among those without social support than among those with social support (with emotional support: HR, 1.84; without emotional support: HR, 2.51; with instrumental support: HR, 1.85; without instrumental support: HR, 2.31)., Conclusions and Implications: Social support may help to alleviate the increased risk for caregiver's functional disability due to the spouse's functional disability., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Salivary gland cancer is a rare disease composed of more than 20 histological types with different grades of malignancy. The aim of this multicenter, retrospective study was to identify the most important predictors affecting recurrence and survival after surgery., Material and Methods: A total of 543 patients with salivary gland cancers that underwent curative surgery between 2012 and 2022 in 13 institutions in northern Japan were evaluated in this study. Predictors affecting recurrence and survival were identified by univariate and multivariate Cox regression analyses. Age, sex, primary site, histological type, pathological T status, surgical margin, lymph node metastasis, extranodal extension, and postoperative radiotherapy were the variables evaluated., Results: Multivariate Cox regression analysis showed that increasing age, submandibular cancer, pathological T status 3 or 4, positive surgical margin, and lymph node metastasis, especially with extranodal extension, were independent risk factors for both recurrence and survival. Sublingual cancer was an independent risk factor for recurrence. Postoperative radiotherapy was associated with a lower risk of recurrence and a good prognosis, and adenoid cystic carcinoma was associated with a good prognosis., Conclusion: Lymph node metastasis with extranodal extension was the most important prognostic factor affecting both recurrence and survival after surgery, adenoid cystic carcinoma was associated with a good prognosis, and postoperative radiotherapy was associated with a lower risk of recurrence and a good prognosis., 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 Ltd.. All rights reserved.)

Serine hydroxymethyltransferase (SHMT) plays a critical role in the 1C metabolism pathway. This pathway is involved in the synthesis of many amino and nucleic acids, and SHMT is considered a target for drugs through folate metabolism, especially for cancer and malaria. A detailed analysis of the interactions between SHMTs and drugs will greatly contribute to the development of new drugs. An anthraquinone compound was found in a compound library screening against SHMT from Enterococcus faecium (efmSHMT), from which mangiferin was implied as a compound that binds to efmSHMT. The binding assay indicated that mangiferin could bind to efmSHMT, and crystal structure analysis revealed interactions between efmSHMT and mangiferin at the binding site. Mangiferin bound to the binding site, turning the glucose moiety inward, which was supported by the docking model study. Although mangiferin does not share its molecular structure with other known inhibitors, such as pyrazolopyran-based compounds, the complex structure of the binding site did not differ much from those of other structures. The ligand binding site of efmSHMT may possess a preferred conformation., 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.)

Orthopedic implants such as arthroplasty prostheses, fracture plates, and intramedullary nails often use materials like Ti6Al4V alloy and commercially pure titanium (CP-Ti), which have Young's modulus significantly higher than that of human cortical bone, potentially causing stress shielding and inhibiting effective fracture healing. TiNbSn alloy, a β-type titanium alloy with a lower Young's modulus (40-49 GPa), has shown promise in reducing stress shielding and enhancing bone healing by promoting effective load sharing with bone. This study used 5-hole plates made from TiNbSn alloy and CP-Ti to investigate their effects on bone healing in a rat femoral fracture model. Micro-CT analysis and mechanical testing were performed six weeks postoperatively to assess bone healing. Additionally, Finite element method (FEM) analysis was employed to evaluate stress shielding and interfragmentary movement (IFM) at the fracture site. Micro-CT analysis revealed significantly higher bone volume and mineral density in the TiNbSn group than in the CP-Ti group. Mechanical testing showed increased maximum load and stiffness in the TiNbSn group (77.2 ± 10.0 N for the TiNbSn alloy plate group versus 53.3 ± 8.5 N for the CP-Ti group (p = 0.002)). FEM analysis indicated that TiNbSn plates reduced stress shielding and allowed for greater displacement and strain, promoting IFM conducive to bone healing. The findings suggest that TiNbSn alloy plates are more effective than CP-Ti plates in promoting bone healing by reducing stress shielding and enhancing IFM. The lower Young's modulus of TiNbSn allows better load distribution, facilitating bone regeneration and strengthening at the fracture site., 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 Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an infectious disease that presents a formidable challenge due to the absence of established therapeutic strategies that are explicitly tailored to its management. This study aimed to assess the impact of routine antimicrobial therapy on patients diagnosed with SFTS in Japan. We conducted a comprehensive retrospective cohort analysis using extensive data from a national inpatient database., Methods: This study scrutinized data from adult patients with SFTS and categorized them based on whether they received antimicrobial treatment within the initial 2 days of hospital admission. A meticulous evaluation was carried out on a range of outcomes, such as in-hospital mortality rates, overall costs associated with hospitalization, and length of hospital stay. Overlap weighting was applied along with multivariate regression models to enhance the reliability of the findings through confounder adjustment. The outcomes showed no significant improvement in the prognosis of patients with SFTS who received routine antimicrobial therapy. The use of antimicrobials did not yield statistically significant improvements in in-hospital mortality rates or other secondary outcomes, suggesting that such therapeutic interventions may not be necessary during the early stages of hospital admission., Conclusion: In our study, administration of antimicrobials within 2 days of admission for SFTS did not affect prognosis. The standard use of antimicrobial treatments may be an issue that should be reconsidered., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: The prognosis of patients with coronavirus disease 2019 (COVID-19) was poor although its survival rate has been improved after the occurrence of the Omicron strain. Autoimmune pulmonary alveolar proteinosis (APAP), a lung disease caused by macrophage dysfunction induced by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF)-neutralizing autoantibodies, is characterized by the deposition of proteinaceous material in the alveolar spaces. The clinical course of COVID-19 in patients with APAP remains unclear and this study aimed to clarify it., Methods: The data of 23 patients with APAP, who were diagnosed with COVID-19 between January 2020 and May 2023 and collected through a nationwide questionnaire surveillance system, were retrospectively reviewed., Results: Based on the epidemiological frequency at disease onset, suspected strains of severe acute respiratory syndrome coronavirus 2 were Omicron (n = 18) and non-Omicron (n = 5). Fifteen patients were vaccinated. Six and three patients received anti-viral drugs and corticosteroids, respectively. One patient in the third trimester of pregnancy died despite treatment in the intensive care unit. Six patients were complicated by pneumonia and/or required supplemental oxygen. These patients were suspected to have non-Omicron strains (p = 0.087). Vaccination status showed a significant association with suspected Omicron strains. The radiological findings in four patients and shortness of breath improved in two of the four patients after COVID-19., Conclusions: The severity and prognosis of the patients were not worse than those predicted based on the results of a previous study. The transition from a non-Omicron strain to an Omicron strain and the vaccination status may have affected these results., Competing Interests: Declaration of competing interest Toru Arai received lecture fees from Boehringer Ingelheim and Shionogi for activities not connected to the submitted work; Yoshikazu Inoue is a consultant or steering/advisory committee member of Boehringer Ingelheim, Roche, SAVARA, and Taiho (not related to this study) and received lecture fees from Boehringer Ingelheim, Shionogi, Kyorin, Thermo Fisher, and GSK (not related to this study). Keiichi Akasaka has no conflict of interest; Aiko Masunaga has no conflict of interest; Masaki Fujita has no conflict of interest; Etsuo Yamaguchi has no conflict of interest; Mika Saigusa has no conflict of interest; Koji Murakami has no conflict of interest; Yu Kurahara has no conflict of interest; Kazunari Tsuyuguchi has no conflict of interest; Takuji Suzuki has no conflict of interest; Yasunari Miyazaki has no conflict of interest; Masashi Bando has no conflict of interest; Takafumi Suda has no conflict of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

This retrospective study aimed to kinematically classify mandibular movements collected during Temporomandibular Disorders (TMD) treatment, employing Fourier transformation (FT), Principal Component Analysis (PCA), and K-means clustering (k-means), and to investigate their correlation with symptoms of pain-related TMD. The study included five TMD participants diagnosed with myalgia (age: 39-86 years, with an SD of 18.96) and three healthy participants (age: 32-42 years, with an SD of 5.13) with no stomatognathic problems. TMD participants underwent tailored treatment for their symptoms, and their maximum unassisted mouth opening (MMO) was recorded randomly with a motion capture system (ARCUS digma II, Kavo, Biberach, Germany) at multiple time points. MMO for healthy participants served as a control. The dataset comprising 28 trials, was transferred to the AnyBody Modeling System (AnyBody Technology, Aalborg, Denmark) to extract joint angle time series, which were then transformed into Fourier series. Subsequently, PCA and k-means clustering were conducted. Two clusters were identified: Cluster 1, predominantly composed of symptomatic trials, and Cluster 2, mainly consisting of asymptomatic trials. Distinct transition pathways between the clusters were observed among participants, corresponding to the alleviation of pain-related symptoms during TMD treatment. These findings suggest that this approach has potential as an effective tool for diagnosing and assessing TMD by identifying symptomatic kinematic patterns and tracking temporal changes in mandibular movement. Despite the small dataset, these results suggest promise for a novel functional assessment method for TMD based on kinematic features., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the content of this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)