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Competing Interests: The authors have no conflicts of interest relevant to this article.

Competing Interests: The authors have no conflicts of interest relevant to this article.

Background and objectives Patients often experience significant quadriceps muscle weakness immediately after total knee arthroplasty (TKA), which can persist and lead to reduced physical function, increased risk of falls, and reduced patient satisfaction. Immediate postoperative quadriceps weakness is commonly caused by several factors, such as preoperative quadriceps weakness related to knee osteoarthritis (OA) and TKA-induced quadriceps weakness. Although many interventions have focused on addressing knee OA-related quadriceps weakness, there may be fewer studies specifically investigating TKA-induced quadriceps weakness. This study aimed to clarify whether TKA-induced quadriceps weakness is a significant predictor of quadriceps strength at three months postoperatively, highlighting the clinical importance of preoperative interventions targeting this specific weakness. Methods This secondary analysis of a randomized controlled trial included patients aged 60-79 years with advanced knee OA who underwent unilateral TKA. The study used pooled data from two groups of 11 participants each: those receiving preoperative low-intensity resistance training with blood flow restriction and those performing low-intensity resistance training with slow movement and tonic force generation. Quadriceps strength was assessed using a pull-type handheld dynamometer preoperatively at six weeks and one week as well as postoperatively at four days, one month, and three months. TKA-induced quadriceps weakness was defined as a change in strength from one week preoperatively to four days postoperatively. Postoperative quadriceps strength gain, reflecting postoperative recovery, was defined as the strength change from four days to three months postoperatively. Correlation and multiple regression analyses were used to identify the predictors of postoperative quadriceps strength at three months. Statistical significance was set at p < 0.05. Results The analysis included 22 participants. The median preoperative quadriceps strength was 1.1 Nm/kg (IQR: 0.9-1.4) at six weeks and 1.3 Nm/kg (IQR: 1.1-1.4) at one week. Quadriceps strength significantly decreased immediately after TKA (median quadriceps strength dropped to 0.4 Nm/kg (IQR: 0.3-0.4) at four days postoperatively) and gradually improved over three months (median three-month postoperative quadriceps strength was 0.9 Nm/kg (IQR: 0.8-1.0)). TKA-induced quadriceps weakness was -72% (SD: 11%), and postoperative quadriceps strength gain was 210% (IQR: 98-324%). TKA-induced quadriceps weakness was strongly correlated with quadriceps strength at four days (r = 0.84, p < 0.01). The postoperative quadriceps strength at four days was significantly correlated with the quadriceps strength at three months (r = 0.51, p = 0.02). Regression analysis showed that one-week preoperative quadriceps strength, TKA-induced quadriceps weakness, and postoperative quadriceps strength gain significantly predicted quadriceps strength at three months (R² = 0.77, p < 0.001). Conclusions This study highlights TKA-induced quadriceps weakness as a key predictor of postoperative quadriceps strength at three months. Preoperative interventions targeting TKA-induced weakness may improve postoperative recovery of quadriceps strength and functional outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Ethics Committee of Seirei Christopher University issued approval 19019. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This research was funded by the JSPS KAKENHI (grant number: JP19K19809). The authors declare no conflict of interest. The funding agency had no role in the design, execution, interpretation, or writing of the study. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kubo et al.)

Objectives: We evaluated the efficacy and safety of cyanoacrylate closure (CAC) for endovascular treatment of varicose veins with cyanoacrylate adhesive (VenaSeal® closure system) in Japan., Methods: A multicenter prospective consecutive registry study was conducted at 12 centers in Japan on 125 patients with primary varicose veins who underwent CAC. The patients were evaluated on target vein occlusion, postoperative complications, Visual Analogue Scale (VAS) for pain, revised Venous Clinical Severity Score (rVCSS), Aberdeen Varicose Vein Questionnaire (AVVQ), and EuroQol 5 dimensions 5-level (EQ-5D-5L) for 1-year after the surgery., Results: The closure rate was 92.6% at 1 year postoperatively, and 95.0% and 90.2% for GSV and SSV respectively with little difference ( p = .491). The mean VAS in the immediate postoperative period was 18.9 ± 23.4. Postoperative complications were observed in 20 patients (16%). Hypersensitivity-type phlebitis occurred in 7 patients (5.6%). Infection of the treated vein resulted in resection of GSV. The rVCSS and AVVQ improved significantly after 90 days and 1 year postoperatively ( p < .001), while the EQ-5D-5L have not changed., Conclusion: Cyanoacrylate Closure was considered generally a safe and minimally invasive treatment with good mid-term outcomes including SSV. However further study is required for some CAC specific complications., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: HM is consultant of Integral Co. Tokyo Japan. The other authors have no conflict of interest in relation to the contents of this manuscript.

The 40-Hz auditory steady-state response (ASSR) is influenced not only by parameters such as attention, stimulus type, and analysis level but also by stimulus duration and inter-stimulus interval (ISI). In this meta-analysis, we examined these parameters in 33 studies that investigated 40-Hz ASSRs in patients with schizophrenia. The average Hedges' g random effect sizes were - 0.47 and - 0.43 for spectral power and phase-locking, respectively. We also found differences in ASSR measures based on stimulus duration and ISI. In particular, ISI was shown to significantly influence differences in the 40-Hz ASSR between healthy controls and patients with schizophrenia. We proposed a novel hypothesis focusing on the role of novelty detection, dependent on stimulus duration and ISI, as a critical factor in determining these differences. Specifically, longer stimulus durations and shorter ISIs under random presentation, or shorter stimulus durations and longer ISIs under repetitive presentation, decrease the 40-Hz ASSR in healthy controls. Patients with schizophrenia show minimal changes in response to stimulus duration and ISI, thus reducing the difference between controls and patients. This hypothesis can consistently explain most of the studies that have failed to show a reduction in 40-Hz ASSR in patients with schizophrenia. Increased novelty-related activity, reflected as an increase in auditory evoked potential components at stimulus onset, such as the N1, could suppress the 40-Hz ASSR, potentially reducing the peak measures of spectral power and phase-locking. To establish the 40-Hz ASSR as a truly valuable biomarker for schizophrenia, further systematic research using paradigms with various stimulus durations and ISIs is needed., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Subglacial discharge from marine-terminating glaciers in Greenland injects large volumes of freshwater and suspended sediment into adjacent fjord environments. Although the discharge itself is nutrient poor, the formation of meltwater plumes can enhance marine biological production by stimulating upwelling of nutrient-rich fjord water. Despite the importance of meltwater discharge to marine ecosystems, little is known of the quantitative impact of discharge processes on phytoplankton growth, including the effects of local plumes, fjord-wide stirring and mixing, and suspended sediments on net primary production (NPP). Here, we report simulations of Bowdoin Fjord in northwestern Greenland using coupled non-hydrostatic ocean circulation and lower-trophic level ecosystem models, developed using field data. Our findings demonstrate that subglacial discharge plays a crucial role in NPP by stirring and mixing the entire fjord water system, which has a greater effect on NPP than local plume upwelling. Sensitivity tests suggest a 20% increase in NPP under conditions of enhanced discharge anticipated in the future. However, if glacier discharge and retreat exceed critical levels, NPP is predicted to decline by 88% relative to present values. This pattern reflects the negative impact of increased sediment flux on photosynthesis and weakened fjord stirring and mixing resulting from shallower outlet depths., (© 2024. The Author(s).)

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare disease associated with the presence of anti-glycine receptor (GlyR) antibodies. We herein report an autopsy case of an 80-year-old man diagnosed with anti-GlyR antibody-positive PERM who presented with symptoms of oculomotor dysfunction and autonomic failure. Despite intensive immunotherapy, the neurological symptoms showed almost no improvement, and the patient succumbed to aspiration pneumonia and bacterial translocation. Postmortem pathology revealed mild inflammatory changes and neuronal loss that were disproportionate to a severe clinical presentation. These results suggest that the clinical symptoms of PERM may result from antibody-mediated GlyR internalization, leading to neuronal disinhibition, rather than a neuroinflammatory signature.

Major depressive disorder (MDD) is a clinically and genetically heterogeneous disorder. To reduce heterogeneity, large-scale genome-wide association studies have recently identified genome-wide significant loci associated with seven MDD subtypes. However, it was unclear in which tissues the genes near those loci are specifically expressed. We investigated whether genes related to specific MDD subtypes would be preferably expressed in a specific tissue. At 14 novel subtype-specific loci related to seven MDD subtypes-(1) non-atypical-like features MDD, (2) early-onset MDD, (3) recurrent MDD, (4) MDD with suicidal thoughts, (5) MDD without suicidal thoughts, (6) MDD with moderate impairment, and (7) postpartum depression, we investigated whether 22 genome-wide significant genetic variant-mapped genes were tissue-specifically expressed in brain, female reproductive, male specific, cardiovascular, gastrointestinal, or urinary tissues in the Genotype-Tissue Expression (GTEx) subjects (n ≤ 948). To confirm the tissue-specific expression in the GTEx, we used independent Human Protein Atlas (HPA) RNA-seq subjects (n ≤ 95). Of 22 genes, nine and five genes were tissue-specifically expressed in brain and female reproductive tissues, respectively (p < 2.27 × 10 -3 ). RTN1, ERBB4, and AMIGO1 related to early-onset MDD, recurrent MDD, or MDD with suicidal thoughts were highly expressed in brain tissues (d = 1.19-2.71), while OAS1, LRRC9, DHRS7, PSMA5, SYPL2, and GULP1 related to non-atypical-like features MDD, early-onset MDD, MDD with suicidal thoughts, or postpartum depression were expressed at low levels in brain tissues (d = -0.17--1.48). DFNA5, CTBP2, PCNX4, SDCCAG8, and GULP1, which are related to early-onset MDD, MDD with moderate impairment, or postpartum depression, were highly expressed in female reproductive tissues (d = 0.80-2.08). Brain and female reproductive tissue-specific expression was confirmed in the HPA RNA-seq subjects. Our findings suggest that brain and female reproductive tissue-specific expression might contribute to the pathogenesis of MDD subtypes., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background/Objectives Enhancing preoperative quadriceps strength and mitigating quadriceps strength loss due to total knee arthroplasty (TKA) is crucial for post-TKA recovery. This study compared the safety and effect of a four-week preoperative regimen of low-load resistance training with blood flow restriction (LLRT-BFR) with those of low-intensity resistance training with slow movement and tonic force generation (LST) on the pre- and postoperative quadriceps strength in patients undergoing TKA. Methods In this randomized controlled trial, 22 patients were assigned to either the LLRT-BFR (n=11) or LST (n=11) group. Primary outcomes included changes in quadriceps strength before and after the intervention and surgery. To assess safety, we monitored D-dimer and high-sensitivity C-reactive protein levels pre- and post-intervention. Statistical analysis involved independent samples t -tests and Mann-Whitney U tests for group comparisons of quadriceps strength changes. Additionally, a two-way repeated-measures analysis of variance was used to assess safety parameters. Results No significant differences were observed between the BFR and LST groups in terms of the rate of increase in quadriceps strength pre- and post-intervention (BFR: median 12.1%, interquartile range -0.8% to 19.5%; LST: median 6.2%, interquartile range 2.7% to 14.7%; p>0.99) or in the rate of reduction in quadriceps strength pre- and post-surgery (BFR: mean -72.4%, standard deviation ±11.2%; LST: mean -75.3%, standard deviation ±12.2%; p=0.57). Safety assessments showed no significant main effects of time, group, or interaction on the safety parameters (all p>0.05). Conclusions LLRT-BFR and LST demonstrated comparable effects on quadriceps strength before and after intervention and surgery in patients undergoing TKA. The lack of significant changes in the safety parameters supports the safety profile of both interventions, indicating their suitability for preoperative conditioning in patients scheduled for TKA., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Ethics Committee of Seirei Christopher University issued approval 19019. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This research was funded by the JSPS KAKENHI (grant number: JP19K19809). The authors declare no conflict of interest. The funding agency had no role in the design, execution, interpretation, or writing of the study. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kubo et al.)

Despite recent advances in porous organic molecular crystals, the engineering of dual-pore systems within the intermolecular voids remains a significant challenge. In this study, we have achieved the crystallization-induced social self-sorting of "quasi-racemic" dialdehydes into a macrocyclic imine. X-ray crystallographic analysis unambiguously characterizes the resulting structure as incorporating two quasi-racemate pairs with four diamine molecules. Notably, different alkyl substituents on the quasi-racemates afford two types of one-dimensional pores within the macrocyclic imine crystal. The different adsorption properties of these pores were substantiated through adsorption experiments. An intriguing helical arrangement of guest molecules was observed within one of the pores. This study provides pioneering evidence that the social self-sorting of quasi-racemates offers a new methodology for creating dual-functional supramolecular materials.

Social anxiety disorder (SAD) and panic disorder (PD) are prevalent anxiety disorders characterized by a complex interplay of genetic and environmental factors. Both disorders share overlapping features and often coexist, despite displaying distinct characteristics. Childhood life adversity, overall stressful life events, and genetic factors contribute to the development of these disorders. DNA methylation, an epigenetic modification, has been implicated in the pathogenesis of these diseases. In this study, we investigated whether whole-genome DNA methylation risk scores (MRSs) for SAD risk, severity of social anxiety, childhood life adversity, PD risk, and overall stressful life events were associated with SAD or PD case‒control status. Preliminary epigenome-wide association studies (EWASs) for SAD risk, severity of social anxiety, and childhood life adversity were conducted in 66 SAD individuals and 77 healthy controls (HCs). Similarly, EWASs for PD risk and overall stressful life events were performed in 182 PD individuals and 81 HCs. MRSs were calculated from these EWASs. MRSs derived from the EWASs of SAD risk and severity of social anxiety were greater in PD patients than in HCs. Additionally, MRSs derived from the EWASs of overall stressful life events, particularly in PD individuals, were lower in SAD individuals than in HCs. In contrast, MRSs for childhood life adversity or PD risk were not significantly associated with PD or SAD case‒control status. These findings highlight the epigenetic features shared in both disorders and the distinctive epigenetic features related to social avoidance in SAD patients, helping to elucidate the epigenetic basis of these disorders., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Functional decline occurs during dialysis initiation, particularly in unplanned cases. To prevent unplanned hemodialysis, we aimed to identify associated factors from the first referral to the nephrology department to hemodialysis initiation and assess patient prognosis post-unplanned hemodialysis initiation., Methods: This retrospective study involved 257 Japanese patients initiating hemodialysis and compared patient characteristics based on whether hemodialysis was planned or unplanned at a single center. Patient outcomes were evaluated in collaboration with maintenance hemodialysis centers., Results: Unplanned hemodialysis initiation correlated with heart failure history (p < 0.05) and infections like pneumonia (p < 0.001). Patients with unplanned hemodialysis initiation had a worse prognosis than those with planned initiation (p < 0.001), and multivariable Cox regression showed it as an independent risk factor for death (p < 0.05)., Conclusions: Hygiene and careful attention to heart failure may reduce unplanned hemodialysis and improve patient well-being and healthcare efficiency. This retrospective analysis highlights crucial considerations for optimizing the initiation of hemodialysis., (© 2024 International Society for Apheresis and Japanese Society for Apheresis.)

Urothelial carcinoma of the bladder with osteoclast-like giant cells (UCOGCs) is rare among the subtypes of poorly differentiated urothelial carcinoma. Its clinical significance and optimal treatment are unknown, and few reports on genomic analysis of UCOGCs have been reported. Detailed analysis including genetic analysis for rare type variants of cancer could be a foothold for further research. The present case describes the case of a 75-year-old man who presented with a non-papillary bladder tumor 56 mm in diameter showing gross hematuria and pain on voiding. Following transurethral resection of the bladder tumor, the pathological diagnosis was invasive UCOGCs. Neoadjuvant chemotherapy and radical cystectomy were performed with the resected tumor pathologically diagnosed as invasive UCOGCs, high grade, pT3b, pN1. The present study also analyzed the genomic features using a cancer panel test. The panel test noted six gene alterations ( PIK3CA p.E542K, HRAS p.G13R, ARAF copy number amplification, CDKN2A copy number loss, TP53 p.E285V, ARID1A p.S90Pfs*11) and telomerase reverse transcriptase ( TERT ) promoter variant. Accumulation of knowledge from molecular-based testing is anticipated to determine precise treatment for rare cancer., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Kameyama et al.)

Objective: This study aimed to investigate the relationship between plasma glucose profiles and periodontal disease (PD) severity in men and women., Methods: We conducted a cross-sectional cohort study, enrolling all eligible patients with type 2 diabetes mellitus (T2DM) who regularly visited the outpatient department., Results: Patients were divided into severe and non-severe PD groups. The severe PD group showed a male predominance and significantly higher hemoglobin A1c (HbA1c) levels than the non-severe PD group. The optimal HbA1c cutoff value on the receiver operating characteristic curve for predicting severe PD was 7.3% [56 mmol/mol] (sensitivity, 52%; specificity, 73%; P = 0.01). Multivariate logistic regression revealed that male sex (odds ratio [OR], 2.75; 95% confidence interval [CI], 1.19-6.34; P = 0.01) and higher HbA1c levels (OR, 3.09; 95% CI, 1.42-6.70; P < 0 .01) were independently and significantly associated with the presence of severe PD. The prevalence rates of severe PD in patients with HbA1c levels < 7.3% [56 mmol/mol] and HbA1c levels ≥ 7.3% [56 mmol/mol] were 17.4% and 53.3% in women, and 50.0% and 66.7% in men, respectively., Conclusions: Men with T2DM had a high risk of severe PD independent of HbA1c levels. Plasma glucose management may be crucial for maintaining periodontal health in T2DM patients, particularly in women., Competing Interests: Conflict of interestHJ has received honoraria from Novo Nordisk, Sanofi, AstraZeneca Pharmaceuticals, Astellas Pharma, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Takeda, and Novartis Pharmaceuticals. SS has received honoraria from AstraZeneca Pharmaceuticals and Ono Pharmaceutical. The authors declare no other potential conflicts of interest relevant to this study., (© The Japan Diabetes Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose: To investigate the difference between the segmented axial length (AL) and the composite AL on a swept-source optical coherence tomography biometer and to evaluate the subsequent effects on artificial intelligence intraocular lens (IOL) power calculations: the Kane and Hill-RBF 3.0 formulas compared with established vergence formulas., Setting: National Hospital Organization, Tokyo Medical Center, Japan., Design: Retrospective case series., Methods: Consecutive patients undergoing cataract surgery with a single-piece IOL were reviewed. The prediction accuracy of the Barrett Universal II, Haigis, Hill-RBF 3.0, Hoffer Q, Holladay 1, Kane, and SRK/T formulas based on 2 ALs were compared for each formula. The heteroscedastic test was used with the SD of prediction errors as the endpoint for formula performance., Results: The study included 145 eyes of 145 patients. The segmented AL (24.83 ± 1.89) was significantly shorter than the composite AL (24.88 ± 1.96, P < .001). Bland-Altman analysis revealed a negative proportional bias for the differences between the segmented AL and the composite AL. The SD values obtained by Hoffer Q, Holladay 1, and SRK/T formulas based on the segmented AL (0.52 diopters [D], 0.54 D, and 0.50 D, respectively) were significantly lower than those based on the composite AL (0.57 D, 0.60 D, and 0.52 D, respectively, P < .01)., Conclusions: The segmented ALs were longer in short eyes and shorter in long eyes than the composite ALs. The refractive accuracy can be improved in the Hoffer Q, Holladay 1, and SRK/T formulas by changing the composite ALs to the segmented ALs., (Copyright © 2024 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Background: Osteochondromas of the mandibular condyle show facial asymmetry and malocclusion. Because condylar osteochondromas are generally resected in a preauricular approach with risks of facial nerve injury and visible scar, the authors report endoscopically assisted intraoral resection of osteochondroma of the mandibular condyle with a piezoelectric surgical device. Case presentation: A 38-year-old woman presented with malocclusion and facial asymmetry caused by deviation of the chin to the left. Computed tomography showed a hyperdense, well-circumscribed mass arising from the medial aspect of the right mandibular condyle with resorption of the skull base. The patient underwent an endoscopically-assisted intraoral condylectomy with a piezoelectric surgical device. The postoperative course was uneventful without trismus, malocclusion, or facial asymmetry, and there was no recurrence 4 years after surgery. Conclusion: Endoscopically assisted intraoral resection of osteochondroma of the mandibular condyle with a piezoelectric surgical device is a minimally invasive and safe surgery.

Responses to a sensory stimulus are inhibited by a preceding stimulus; if the two stimuli are identical, paired-pulse suppression (PPS) occurs; if the preceding stimulus is too weak to reliably elicit the target response, prepulse inhibition (PPI) occurs. PPS and PPI represent excitability changes in neural circuits induced by the first stimulus, but involve different mechanisms and are impaired in different diseases, e.g., impaired PPS in schizophrenia and Alzheimer's disease and impaired PPI in schizophrenia and movement disorders. Therefore, these measures provide information on several inhibitory mechanisms that may have roles in clinical conditions. In the present study, PPS and PPI of the auditory change-related cortical response were examined to establish normative data on healthy subjects (35 females and 32 males, aged 19-70 years). We also investigated the effects of age and sex on PPS and PPI to clarify whether these variables need to be considered as biases. The test response was elicited by an abrupt increase in sound pressure in a continuous sound and was recorded by electroencephalography. In the PPS experiment, the two change stimuli to elicit the cortical response were a 15-dB increase from the background of 65 dB separated by 600 ms. In the PPI experiment, the prepulse and test stimuli were 2- and 10-dB increases, respectively, with an interval of 50 ms. The results obtained showed that sex exerted similar effects on the two measures, with females having stronger test responses and weaker inhibition. On the other hand, age exerted different effects: aging correlated with stronger test responses and weaker inhibition in the PPS experiment, but had no effects in the PPI experiment. The present results suggest age and sex biases in addition to normative data on PPS and PPI of auditory change-related potentials. PPS and PPI, as well as other similar paradigms, such as P50 gating, may have different and common mechanisms. Collectively, they may provide insights into the pathophysiologies of diseases with impaired inhibitory function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Inui, Takeuchi, Borgil, Shingaki, Sugiyama, Taniguchi, Nishihara, Watanabe, Suzuki, Motomura and Kida.)

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: The authors have no conflicts of interest relevant to this article.

Competing Interests: The authors have no conflicts of interest relevant to this article.

Endoplasmic reticulum (ER)-plasma membrane (PM) tethering is crucial for the non-vesicular lipid transport between the ER membrane and the PM. However, the PM-associated ER can impede the PM binding of cytoskeletons and other organelles. It is poorly understood how the competition between the ER and cytoskeletons/organelles on the PM is resolved. Here, we show that, upon septin collar assembly, ER-PM tethering proteins are excluded from the yeast bud sites, and the PM-associated ER is locally detached from the PM. Our results suggest that PM flows by polarized exocytosis extrude PM proteins, including ER-PM tethering proteins, from the bud sites. When the reorganization of the ER-PM tethering was inhibited by exocytosis repression, septin localization was restricted to the PM sites poor in ER-PM tethering proteins. This study proposes machinery reconciling ER-septin competition on the PM, providing mechanistic insights into the spatial organization of PM-associated organelles and cytoskeletons.

Aim: To assess physician-reported treatment of metastatic bladder cancer in Japan. Methods: 76 physicians completed the CancerMPact ® survey in July 2020, considering patients treated within 6 months. Results: Physicians treated a mean of 38.1 patients per month. Of cisplatin-eligible and -ineligible patients, 97.6 and 89.3%, respectively, received first-line platinum-based therapy, most commonly cisplatin plus gemcitabine (72.9%) and carboplatin plus gemcitabine (59.7%). 1.6 and 5.6% received first-line immune checkpoint inhibitors, respectively. 48.4 and 45.0%, respectively, progressed and received second-line therapy, most commonly with pembrolizumab (61.7%). Conclusion: In 2020, most patients with metastatic bladder cancer in Japan received first-line platinum-based chemotherapy; however, >50% received no subsequent treatment, highlighting the need for new treatment regimens to improve outcomes and maximize first-line treatment benefits.

Background/aim: A genomic analysis based on next-generation sequencing is important for deciding cancer treatment strategies. Cancer tissue sometimes displays intratumor heterogeneity and a pathologic specimen may contain more than two tumor grades. Although tumor grades are very important for the cancer prognosis, the impact of higher tumor grade distribution in a specimen used for a genomic analysis is unknown., Patients and Methods: We retrospectively analyzed the data of 61 clear cell carcinoma and 46 prostate cancer patients that were diagnosed between December 2018 and August 2022 using the GeneRead Human Comprehensive Cancer Panel or SureSelect PrePool custom Tier2. Genome annotation and curation were performed using the GenomeJack software., Results: Tumor mutation burden (TMB) was increased in proportion to the higher tumor grade distribution in grade 2 clear cell renal cell carcinoma (ccRCC). In PC, Grade Group 3/4 specimens that included an increased distribution of Gleason pattern 4 had more frequent gene mutations., Conclusion: Our results suggest the importance of selecting the maximum distribution of higher tumor grade areas to obtain results on the precise gene alterations for genomics-focused treatments., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Plasma membrane damage (PMD) occurs in all cell types due to environmental perturbation and cell-autonomous activities. However, cellular outcomes of PMD remain largely unknown except for recovery or death. In this study, using budding yeast and normal human fibroblasts, we found that cellular senescence-stable cell cycle arrest contributing to organismal aging-is the long-term outcome of PMD. Our genetic screening using budding yeast unexpectedly identified a close genetic association between PMD response and replicative lifespan regulations. Furthermore, PMD limits replicative lifespan in budding yeast; upregulation of membrane repair factors ESCRT-III (SNF7) and AAA-ATPase (VPS4) extends it. In normal human fibroblasts, PMD induces premature senescence via the Ca 2+ -p53 axis but not the major senescence pathway, DNA damage response pathway. Transient upregulation of ESCRT-III (CHMP4B) suppressed PMD-dependent senescence. Together with mRNA sequencing results, our study highlights an underappreciated but ubiquitous senescent cell subtype: PMD-dependent senescent cells., (© 2024. The Author(s).)

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Biological membranes, including plasma membrane (PM) and organelle membranes, restrict the flux of ions, molecules and organelles. However, the barrier function of biological membranes is frequently compromised by various perturbations, including physical membrane damage and protein- or chemical-induced pore formation. Recent evidence suggests that, upon PM damage, protein gelation and solid condensation are utilized to restrict ion/molecule/organelle flux across the damaged membranes by zoning the cytoplasm. In addition, membrane permeabilization dramatically alters intramembrane and extramembrane ion/molecule concentrations via the flux across the permeabilized membrane. The changes in ion/molecule concentration and their downstream pathways induce protein phase transition to form zones for biological processes or protein sequestration. Here, we review the mechanisms and functions of protein phase transition after biological membrane permeabilization., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Japanese Biochemical Society.)

C-C chemokine receptor type 2 (CCR2) is the receptor for C-C motif chemokine 2 (CCL2) and is associated with various inflammatory diseases and cancer metastasis. Although many inhibitors for CCR2 have been developed, it remains unresolved which inhibitors are the most effective in the clinical setting. In the present study, we compared 10 existing human CCR2 antagonists in a calcium influx assay using human monocytic leukemia cells. Among them, MK0812 was found to be the most potent inhibitor of human CCR2. Furthermore, we generated a human CCR2B knock-in mouse model to test the efficacy of MK0812 against a lung metastasis model of breast cancer. Oral administration of MK0812 to humanized mice did indeed reduce the number of monocytic myeloid-derived suppressor cells and the rate of lung metastasis. These results suggest that MK0812 is the most promising candidate among the commercially available CCR2 inhibitors. We propose that combining these two screening methods may provide an excellent experimental method for identifying effective drugs that inhibit human CCR2., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.)

Background: Suicide attempts are a moderately heritable trait, and genetic correlations with psychiatric and related intermediate phenotypes have been reported. However, as several mental disorders as well as major depressive disorder (MDD) are strongly associated with suicide attempts, these genetic correlations could be mediated by psychiatric disorders. Here, we investigated genetic correlations of suicide attempts with psychiatric and related intermediate phenotypes, with and without adjusting for mental disorders., Methods: To investigate the genetic correlations, we utilized large-scale genome-wide association study summary statistics for suicide attempts (with and without adjusting for mental disorders), nine psychiatric disorders, and 15 intermediate phenotypes., Results: Without adjusting for mental disorders, suicide attempts had significant positive genetic correlations with risks of attention-deficit/hyperactivity disorder, schizophrenia, bipolar disorder, MDD, anxiety disorders and posttraumatic stress disorder; higher risk tolerance; earlier age at first sexual intercourse, at first birth and at menopause; higher parity; lower childhood IQ, educational attainment and cognitive ability; and lower smoking cessation. After adjusting for mental disorders, suicide attempts had significant positive genetic correlations with the risk of MDD; earlier age at first sexual intercourse, at first birth and at menopause; and lower educational attainment. After adjusting for mental disorders, most of the genetic correlations with psychiatric disorders were decreased, while several genetic correlations with intermediate phenotypes were increased., Conclusions: These findings highlight the importance of considering mental disorders in the analysis of genetic correlations related to suicide attempts and suggest that susceptibility to MDD, reproductive behaviors, and lower educational levels share a genetic basis with suicide attempts after adjusting for mental disorders.

Background: Genetic and environmental factors contribute to the pathogenesis of schizophrenia (SZ) and bipolar disorder (BD). Among genetic risk groups stratified by combinations of Polygenic Risk Score (PRS) deciles for SZ, BD and SZ versus BD, genetic SZ risk groups had high SZ risk and prominent cognitive impairments. Furthermore, epigenetic alterations are implicated in these disorders. However, it was unclear whether DNA Methylation Risk Scores (MRSs) for SZ risk derived from blood and brain tissues were associated with SZ risk, particularly the PRS-stratified genetic SZ risk group., Methods: Epigenome-wide association studies (EWASs) of SZ risk in whole blood were preliminarily conducted between 66 SZ patients and 30 healthy controls (HCs) and among genetic risk groups (individuals with low genetic risk for SZ and BD in HCs (n=30) and in SZ patients (n=11), genetic BD risk in SZ patients (n=25) and genetic SZ risk in SZ patients (n=30)) stratified by combinations of PRSs for SZ, BD and SZ versus BD. Next, differences in MRSs based on independent EWASs of SZ risk in whole blood, postmortem frontal cortex (FC) and superior temporal gyrus (STG) were investigated among our case‒control and PRS-stratified genetic risk status groups., Results: Among case‒control and genetic risk status groups, 33 and 351 genome-wide significant differentially methylated positions (DMPs) associated with SZ were identified, respectively, many of which were hypermethylated. Compared with the low genetic risk in HCs group, the genetic SZ risk in SZ group had 39 genome-wide significant DMPs, while the genetic BD risk in SZ group had only six genome-wide significant DMPs. The MRSs for SZ risk derived from whole blood, FC and STG were higher in our SZ patients than in HCs in whole blood and were particularly higher in the genetic SZ risk in SZ group than in the low genetic risk in HCs and genetic BD risk in SZ groups. Conversely, the MRSs for SZ risk based on our whole-blood EWASs among genetic risk groups were also associated with SZ in the FC and STG. There were no correlations between the MRSs and PRSs., Conclusions: These findings suggest that the MRS is a potential genetic marker in understanding SZ, particularly in patients with a genetic SZ risk., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. Published by BMJ.)

The concept of a domino-type reaction has been applied in a wide range of fields such as synthetic organic chemistry, material engineering, and life science. To extend the domino concept to redox chemistry, we designed and synthesized a dimeric quinodimethane (QD) with a nonplanar dithiin spacer. The domino-redox properties can be activated by raising the temperature, based on a thermally equilibrated twisted conformation of QD, which has a higher HOMO level that is more readily oxidized. After one QD unit is oxidized (trigger), steric repulsion and electronic interaction between electrophores make the neighboring QD unit adopt a twisted conformation (domino process), which facilitates the following oxidation. Thus, a domino-redox reaction was achieved for the first time by a change in the HOMO level due to a drastic change in the molecular conformation., (© 2023 Wiley-VCH GmbH.)

Competing Interests: The authors have no conflicts of interest relevant to this article.

Herein, we report the functionalization of polyhedral oligosilsesquioxanes (POSS) and related siloxanes with arynes. Using o-triazenylarylboronic acids as aryne precursors and silica gel as the activator, the transformation of siloxane bearing various arynophilic moieties on the side chains was achieved with high yields without touching the siloxane core. This method was applied to the conjugation of POSS and pharmaceutical cores using an aryne derived from the synthetic intermediate of cabozantinib. Furthermore, orthogonal dual functionalization of POSS was realized by combining the aryne reaction with Huisgen cyclization.

Competing Interests: The authors have no conflicts of interest relevant to this article.

Competing Interests: The authors have no conflicts of interest relevant to this article.

Competing Interests: The authors have no conflicts of interest relevant to this article.

Competing Interests: The authors have no conflicts of interest relevant to this article.

Competing Interests: The authors have no conflicts of interest relevant to this article.

Aims: To review the literature and identify factors that make sense of and influence nurses' career success. We sought to provide insights into achieving nurses' career success., Design: An integrative review conducted in May 2022 using Whittemore and Knafl's methodology of integrative review., Methods: The databases searched were PubMed, Web of Science, Scopus, and CINAHL. Search criteria included the keywords "nurs*" and "career success" in the title and abstract. The quality of the reviewed papers was assessed using the JBI Critical Appraisal Tool for cross-sectional studies and qualitative research. We extracted five types of information from quantitative studies: the definition of career success, factors of career success instruments, reliability or validity of career success instruments, and factors influencing nursing career success. Furthermore, we extracted two types of information from qualitative studies: themes that imply career success and factors that influence nurses' career success. Primary data were categorized into two perspectives: (1) what nurses' career success means and (2) what influences nurses' career success. Categorized data were unified into similar contents. Themes were developed from unified subgroups., Results: Fourteen studies were included in the analysis. Seven themes were integrated into the factors that make sense of nurses' career success: satisfaction, positive attitude towards work, quality work in nursing, continuation of career and professional development, positive interaction at work, person-organization fit, and enrichment of an individual's life. Three themes were integrated into the factors influencing nursing career success: personal resources, positive behavior toward nursing work and research, and job resources and environment., No Patient or Public Contribution: Patients or members of the public were not involved in this review., (© 2023 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Competing Interests: The authors have no conflicts of interest relevant to this article.

Herein, a novel aryne species, 3-triazenylaryne, was developed and its regioselectivity was revealed. Based on the regioselectivity, various alkyne moieties were introduced by iodoalkynylation, and further derivatization to o -triazenylarylboronic acids as 3-alkynylaryne precursors was enabled. Therefore, 3-triazenylaryne was developed as a divergent platform for the generation of various 3-alkynylarynes.

Use of anticoagulants is increasing with the aging of societies. The safe first-line drug is likely to be a direct oral anticoagulant (DOAC), but outcomes of treatment of traumatic brain injury (TBI) with anticoagulants are uncertain. Therefore, we examined the clinical effect of idarucizumab as reversal therapy in elderly patients with TBI who were treated with dabigatran. A retrospective multi-center observational study was performed in patients ≥65 years of age who developed acute traumatic subdural hematoma during treatment with dabigatran and underwent reversal therapy with idarucizumab. The items examined included patient background, neurological and imaging findings at arrival, course after admission, complications, and outcomes. A total of 23 patients were enrolled in the study. The patients had a mean age of 78.9 years. Cause of TBI was fall in 60.9% of the subjects. Mean Glasgow Coma Scale score at arrival was 8.7; anisocoria was present in 31.8% of cases. Exacerbation of consciousness was found in 30.4%, but only in 13.3% of subjects treated with idarucizumab before consciousness and imaging findings worsened. Dabigatran was discontinued in 81.8% of cases after hematoma development, with a mean withdrawal period of 12.1 days. The favorable outcome rate was 21.7%, and mortality was 39.1%. In multi-variate analysis, timing of idarucizumab administration was associated with a favorable outcome. There were ischemic complications in 3 cases (13.1%), and all three events occurred ≥7 days after administration of idarucizumab. These findings suggest that in cases that develop hematoma during treatment with dabigatran, it is important to administer idarucizumab early and restart dabigatran after conditions stabilize., Competing Interests: Dr. Suehiro received research funding from Boehringer Ingelheim., (© Eiichi Suehiro et al., 2023; Published by Mary Ann Liebert, Inc.)

Purpose: To evaluate the performance of traditional vergence formulas with segmented axial length (AL) compared to traditional composite AL in extremely long eyes, and to determine whether the segmented AL can be extended to the new-generation formulas, including the Barrett Universal II, Emmetropia Verifying Optical 2.0 (EVO2), Hill-RBF 3.0 (Hill3), Kane, and Ladas Super formula (LSF) formulas in extremely long eyes., Setting: National Hospital. Organization, Tokyo Medical Center, Japan., Design: Retrospective case series., Methods: Consecutive patients who underwent uncomplicated cataract surgery implanted with a three-piece intraocular lens between December 2015 and March 2021 were retrospectively reviewed. The composite AL was measured with a swept-source optical coherence tomography (SS-OCT) biometer using a mean refractive index. The segmented AL was calculated by summing the geometric lengths of the ocular segments (cornea, aqueous, lens, and vitreous) using multiple specific refractive indices based on the data obtained by the SS-OCT-based biometer. When refraction was measured at three months postoperatively, the median absolute errors (MedAEs) were calculated with two ALs for each formula., Results: The study included 31 eyes of 22 patients. The segmented AL (30.45 ± 1.23 mm) was significantly shorter than the composite AL (30.71 ± 1.28 mm, p < 0.001). The MedAEs were significantly reduced when using segmented AL for SRK/T, Haigis, Hill3, and LSF, compared to those obtained using composite AL (0.38 vs. 0.62, 0.48 vs. 0.79, 0.50 vs. 0.90, 0.34 vs. 0.61, p < 0.001 for all formulas, respectively). On the contrary, the MedAE obtained by Kane with segmented AL was significantly worse compared to the one with composite AL (0.35 vs. 0.27, p = 0.03)., Conclusion: In extremely high myopic eyes, the segmented AL improves the performance of SRK/T, Haigis, Hill3, and LSF formulas compared to the composite AL, while the segmented AL worsens the prediction accuracy of the Kane formula.

Adjustment disorder has three main subtypes: adjustment disorder with depressed mood, adjustment disorder with anxiety, and adjustment disorder with disturbance of conduct. The disorder is moderately heritable and has lifetime comorbidities with major depressive disorder (MDD), anxiety disorders, or risk-tolerant personality. However, it remains unclear whether the degrees of genetic correlations between adjustment disorder and other psychiatric disorders and intermediate phenotypes are similar or different to those between MDD, anxiety disorders or risk-tolerant personality and these other psychiatric disorders and intermediate phenotypes. To compare patterns of genetic correlations, we utilized large-scale genome-wide association study summary statistics for adjustment disorder-related disorders and personality trait, eleven other psychiatric disorders and fifteen intermediate phenotypes. Adjustment disorder had highly positive genetic correlations with MDD, anxiety disorders, and risk-tolerant personality. Among other psychiatric disorders, adjustment disorder, MDD, anxiety disorders and risk-tolerant personality were positively correlated with risks for schizophrenia (SCZ), bipolar disorder (BD), SCZ + BD, attention-deficit/hyperactivity disorder, and cross disorders. In contrast, adjustment disorder was not significantly correlated with risks for obsessive-compulsive disorder, Tourette syndrome, or posttraumatic stress disorder despite significant genetic correlations of MDD or anxiety disorders with these disorders. Among intermediate phenotypes, adjustment disorder, MDD, anxiety disorders, and risk-tolerant personality commonly had a younger age at first sexual intercourse, first birth, and menopause, lower cognitive ability, and higher rate of smoking initiation. Adjustment disorder was not genetically correlated with extraversion, although the related disorder and personality were correlated with extraversion. Only adjustment disorder was correlated with a higher smoking quantity. These findings suggest that adjustment disorder could share a genetic etiology with MDD, anxiety disorders and risk-tolerant personality trait, as well as have a disorder-specific genetic etiology., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Increased heart dose during postoperative radiotherapy (RT) for left-sided breast cancer (BC) can cause cardiac injury, which can decrease patient survival. The deep inspiration breath-hold technique (DIBH) is becoming increasingly common for reducing the mean heart dose (MHD) in patients with left-sided BC. However, treatment planning and DIBH for RT are laborious, time-consuming and costly for patients and RT staff. In addition, the proportion of patients with left BC with low MHD is considerably higher among Asian women, mainly due to their smaller breast volume compared with that in Western countries. The present study aimed to determine the optimal machine learning (ML) model for predicting the MHD after RT to pre-select patients with low MHD who will not require DIBH prior to RT planning. In total, 562 patients with BC who received postoperative RT were randomly divided into the trainval (n=449) and external (n=113) test datasets for ML using Python (version 3.8). Imbalanced data were corrected using synthetic minority oversampling with Gaussian noise. Specifically, right-left, tumor site, chest wall thickness, irradiation method, body mass index and separation were the six explanatory variables used for ML, with four supervised ML algorithms used. Using the optimal value of hyperparameter tuning with root mean squared error (RMSE) as an indicator for the internal test data, the model yielding the best F2 score evaluation was selected for final validation using the external test data. The predictive ability of MHD for true MHD after RT was the highest among all algorithms for the deep neural network, with a RMSE of 77.4, F2 score of 0.80 and area under the curve-receiver operating characteristic of 0.88, for a cut-off value of 300 cGy. The present study suggested that ML can be used to pre-select female Asian patients with low MHD who do not require DIBH for the postoperative RT of BC., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2023, Spandidos Publications.)

Objective: Olfactory impairments, including identification, have been reported in patients with schizophrenia, while few studies have examined the olfactory function of unaffected first-degree relatives of patients with schizophrenia, and the sample sizes of first-degree relatives were relatively small. Here, we investigated olfactory identification ability among patients with schizophrenia, first-degree relatives and healthy controls (HCs) using relatively large sample sizes at a single institute., Methods: To assess olfactory identification ability, the open essence odorant identification test was administered to 172 schizophrenia patients, 75 first-degree relatives and 158 healthy controls. Differences in olfactory identification and correlations between olfactory ability and clinical variables were examined among these participants., Results: We found a significant difference in olfactory identification ability among the diagnostic groups ( p  = 7.65 × 10 -16 ). Schizophrenia patients displayed lower olfactory identification ability than first-degree relatives (Cohen's d  = -0.57, p  = 3.13 × 10 -6 ) and healthy controls ( d  = -1.00, p  = 2.19 × 10 -16 ). Furthermore, first-degree relatives had lower olfactory identification ability than healthy controls ( d  = -0.29, p  = 0.039). Olfactory identification ability moderately and negatively correlated with the duration of illness ( r  = -0.41, p  = 1.88 × 10 -8 ) and negative symptoms ( r  = -0.28, p  = 1.99 × 10 -4 ) in schizophrenia patients, although the correlation with the duration of illness was affected by aging ( r  = -0.24)., Conclusions: Our results demonstrated that schizophrenia patients have impaired olfactory identification ability compared with first-degree relatives and healthy controls, and the impaired olfactory identification ability of first-degree relatives was intermediate between those in schizophrenia patients and healthy controls. Olfactory identification ability was relatively independent of clinical variables. Therefore, olfactory identification ability might be an intermediate phenotype for schizophrenia.

Aim: This study aimed to develop the nurses' Work Values Scale (WVS) to determine how important certain values are for nurses and to psychometrically test the scale., Design: Instrument development and validation study., Method: A two-phase scale development process comprising item generation, scale improvement and psychometric property evaluation was used. In the first phase, scale items were identified. In the second phase, item and exploratory factor analyses were performed in Study 1, and confirmatory factor analysis, validity verification and reliability verification of the nurses' WVS were performed in Study 2., Results: As a result of the analysis, a scale of 30 items with four subdomains was developed. In convergent validity and reliability verification, it was shown that the nurses' WVS has acceptable validity and reliability., No Patient or Public Contribution: Patients or members of the public were not involved in this study., (© 2023 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Competing Interests: The authors have no conflicts of interest relevant to this article.

Competing Interests: The authors have no conflicts of interest relevant to this article.