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Abstract The nitrogen-vacancy (NV) centre in diamond is a promising candidate for quantum computing applications and magnetic sensing applications, because it is an atomic-scale defect with stable coherence time (T 2) and reliable accessibility at room temperature. We demonstrated a method for improving the NV spin properties (the full width half maximum (FWHM) value of the magnetic resonance spectrum and T 2) through a near-field (NF) etching method under ambient conditions. The NF etching method, based on a He-Cd ultraviolet laser (325 nm), which is longer than the absorption edge of the oxygen molecule, enabled selective removal of defects on the nanodiamond surface. We observed a decrease in the FWHM value close to 15% and an increase in T 2 close to 25%. Since our technique can be easily reproduced, a wide range of NV centre applications could be improved, especially magnetic sensing applications. Our results are especially attractive, because they have been obtained under ambient conditions and only require a light source with wavelength slightly above the O2 absorption edge.

Carotenoid-carrying lipoprotein (CCL) was rapidly isolated from the high density lipoprotein (HDL) fraction of the upstream migrating male chum salmon (Oncorhynchus keta) by a single-step density gradient ultracentrifugation. The two apolipoproteins (Mr = 24,000 and 12,000; designated apo-I and apo-II, respectively) were readily dissociated and separated in 0.1% SDS by gel filtration chromatography. Prominent features of the amino acid composition in the CCL included the relative high levels of glutamic acid, alanine, leucine, and lysine, and the low cysteine content. Apo-I, as well as the CCL, was rich in glutamic acid, alanine, leucine, and lysine. Compared to the amino acid composition of apo-I, apo-II included relatively high levels of glycine and tyrosine, and low threonine, serine, and arginine contents. When the intact CCL particle was treated with trypsin, apo-I was rapidly proteolyzed, while apo-II was resistant. However, both apo-I and apo-II isolated from the CCL particle were readily digested with trypsin. This suggested that a different structural arrangement rather than the amino acid compositions of the apolipoproteins was associated with the limited trypsin digestion of the CCL particle. Apo-II may be sheltered from the aqueous environment and lie partly within the CCL particle. The properties of both the HDL fraction and apolipoproteins from pink salmon (Oncorhynchus gorbuscha) were similar to those of the CCL from chum salmon.

Background: The management of chronic thromboembolic pulmonary hypertension (CTEPH) has advanced significantly in recent years, thereby improving patient prognosis. However, the impact of cancer on the outcomes of patients with CTEPH under current treatment remains unclear. This study aimed to investigate the prevalence of cancer in patients with CTEPH and determine how comorbid cancer affects their prognosis and clinical course., Methods: Data from an ongoing Japanese prospective cohort study were analyzed. Prevalence and primary cancer sites were evaluated. The association of a history of cancer with a composite endpoint, including all-cause death, lung transplantation, and worsening of CTEPH, as well as venous thromboembolism and bleeding events, was assessed., Results: Of the 1,270 patients in the cohort, 134 (10.6%) had a history of cancer, with the most common primary sites being the breast in women and the prostate in men. The incidence of composite outcome and all-cause death was higher in those with a history of cancer (p<0.001, log-rank test). In the Cox proportional hazard model, age- and sex-adjusted hazard ratios for the composite outcome and all-cause death were 2.69 (95% confidence interval, 1.48-4.89, p=0.001) and 4.25 (95% confidence interval, 1.98-9.10, p<0.001), respectively, for patients with a history of cancer. No significant differences in venous thromboembolism and bleeding events were observed between patients with and those without a history of cancer., Conclusions: A history of cancer, with a prevalence of 10.6%, is an independent risk factor for mortality in patients with CTEPH undergoing the currently recommended treatment., Competing Interests: Disclosure of interest Tsujino I. reports personal fees from Janssen Pharmaceutical and Nippon Shinyaku and affiliation with the division supported by endowments from Nippon Shinyaku, Nippon Boehringer Ingelheim, Mochida Pharmaceutical, Kaneka, Takeyama, and the Medical System Network outside the submitted work. Hosokawa K. reports personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, and Pfizer outside the submitted work. Taniguchi Y. reported grants from Janssen Pharmaceutical and Nippon Shinyaku and personal fees from Janssen Pharmaceutical and Nippon Shinyaku outside the submitted work. Inami T. reports personal fees from Janssen Pharmaceutical and Bayer Yakuhin outside the submitted work. Yamashita J. reports a grant from Abbott Vascular Japan and personal fees from Kaneka Medix, Boston Scientific Japan, Nihon Kohden, Philips Japan, Janssen Pharmaceutical, and Bayer Yakuhin outside the submitted work. Ogino H. reports consulting fees from Terumo, Japan Lifeline, and Century Medical, outside the submitted work. Ikeda N. reports personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, Daiichi Sankyo, and Bristol-Myers Squibb outside the submitted work. Yaoita N. reports personal fees from Bayer Yakuhin and Konica Minolta outside the submitted work. Shimokawahara H. reports a grant from Bayer Yakuhin and personal fees from Actelion Pharmaceuticals Japan, Bayer Yakuhin, and Nippon Shinyaku, outside the submitted work. Tanabe N. reports personal fees from Janssen Pharmaceutical, Bayer Yakuhin, and Nippon Shinyaku outside the submitted work. Kubota K. reports personal fees from Janssen Pharmaceutical and Nippon Shinyaku outside the submitted work. Ogihara Y. reports personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, and Daiichi Sankyo and grants from Bayer Yakuhin and Daiichi Sankyo outside the submitted work. Kawakami T. reports personal fees from Kaneka Medix, Abbott Medical Japan., and ACIST Japan outside the submitted work. Tamura Y. reports grants from Bayer Yakuhin, Nippon Shinyaku, and Mochida Pharmaceutical and personal fees from Bayer Yakuhin, Nippon Shinyaku, Daiichi Sankyo, and Janssen Pharmaceutical outside the submitted work. Abe K. reports a grant from Konica Minolta and Daiichi Sankyo outside the submitted work. Nakamura J., Masaki K., Funakoshi K., Adachi S., Hatano M, Shigeta A., Horimoto K., Dohi Y., and Tatsumi K. report no conflicts of interest., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

A new bioactive substance was identified from a leaf-litter actinomycete strain by screening for antibacterial activity against Neisseria gonorrhoeae. The thiazolyl peptide antibiotic, named thiazoplanomicin, was isolated from the secondary metabolites of the leaf-litter actinomycetes Actinoplanes sp. MM794L-181F6 by extraction with n-butanol, silica gel column chromatography, Sephadex LH-20 column chromatography, and preparative HPLC. Thiazoplanomicin was characterized by LC-HR-ESI-MS, NMR, and X-ray analyses, along with analysis of the degradation products and chemical derivatives, and determined to be a nocathiacin-like multiple macrocyclic thiazolyl peptide. Thiazoplanomicin showed potent antimicrobial activity against gonococcal strains, including those resistant to known anti-gonococcal compounds such as telithromycin, azithromycin, and ceftriaxone, with MIC values ranging from 0.0312 to 0.125 µg ml -1 . Such anti-gonococcal activity has not been reported on nocathiacin-like thiazolyl peptide antibiotic so far. Similar to other thiazolyl peptide antibiotics, thiazoplanomicin also showed potent antibacterial activity against Gram-positive bacteria with MIC values ranging from 0.0005 to 0.0156 µg ml -1 but showed no antibacterial activity against Escherichia coli., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Synaptic phenotypes in living patients with psychiatric disorders are poorly characterized. Excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is a fundamental component for neurotransmission. We recently developed a positron emission tomography (PET) tracer for AMPAR, [ 11 C]K-2, the first technology to visualize and quantify AMPARs density in living human brain. In this study, we characterized patients with major psychiatric disorders with [ 11 C]K-2. One hundred forty-nine patients with psychiatric disorders (schizophrenia, n = 42; bipolar disorder, n = 37; depression, n = 35; and autism spectrum disorder, n = 35) and 70 healthy participants underwent a PET scan with [ 11 C]K-2 for measurement of AMPAR density. We detected brain regions that showed correlation between AMPAR density and symptomatology scores in each of four disorders. We also found brain areas with significant differences in AMPAR density between patients with each psychiatric disorder and healthy participants. Some of these areas were observed across diseases, indicating that these are commonly affected areas throughout psychiatric disorders. Schizophrenia, bipolar disorder, depression, and autism spectrum disorder are uniquely characterized by AMPAR distribution patterns. Our approach to psychiatric disorders using [ 11 C]K-2 can elucidate the biological mechanisms across diseases and pave the way to develop novel diagnostics and therapeutics based on the synapse physiology., (© 2024. The Author(s).)

Objectives: A quality indicator (QI) for the treatment of systemic lupus erythematosus (SLE) during pregnancy and childbirth that is useful for sharing standard treatment policies has not yet been developed. This study aimed to develop a QI for SLE associated with pregnancy and childbirth., Methods: To identify candidate QIs, we conducted a systematic literature review on the development of QIs for SLE related to pregnancy and childbirth and on clinical practice guidelines. Candidate QI items were extracted from the final selected articles, and a first evaluation, panel meeting, and second evaluation were conducted to determine whether the candidate items were appropriate as QIs. Items for which all panel members reached a consensus were designated pregnancy and childbirth-related SLE QIs., Results: Four articles on SLE QI development and 28 practice guidelines were listed through abstract/text screening. Based on these studies, 52 candidate QIs were extracted that were limited to items related to pregnancy and childbirth and 41 items were selected on which all panel members agreed., Conclusion: We developed pregnancy-related SLE QIs using the RAND/UCLA method and selected 41 items, which could be used clinically., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Importance: To date, several theta burst stimulation (TBS) protocols, such as intermittent TBS (iTBS), have been proposed; however, previous systematic reviews have revealed inconsistent efficacy findings in individual TBS studies for schizophrenia., Objective: To examine which TBS protocols are associated with the most favorable and acceptable outcomes in adults with schizophrenia., Data Sources: The Cochrane Library, PubMed, and Embase databases were searched for studies published before May 22, 2024., Study Selection: The inclusion criteria were as follows: (1) published and unpublished randomized clinical trials (RCTs) of any TBS treatment and (2) RCTs including individuals with schizophrenia spectrum disorders, other psychotic disorders, or both., Data Extraction and Synthesis: This study followed the Cochrane standards for data extraction and data quality assessment and used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline for reporting. The risk of bias of individual studies was assessed using the second version of the Cochrane risk of bias tool, and the Confidence in Network Meta-Analysis application was used to rate the certainty of evidence for meta-analysis results. At least 2 authors double-checked the literature search, data transfer accuracy, and calculations., Main Outcomes and Measures: The primary outcome of this study was improvement in scores related to negative symptoms. Our frequentist network meta-analysis used a random-effects model. The standardized mean difference (SMD) or odds ratio for continuous or dichotomous variables, respectively, was calculated with 95% CIs., Results: A total of 30 RCTs of 9 TBS protocols, with 1424 participants, were included. Only iTBS over the left dorsolateral prefrontal cortex (L-DLPFC) was associated with reduced negative symptom scores (SMD, -0.89; 95% CI, -1.24 to -0.55), overall symptom scores (SMD, -0.81; 95% CI, -1.15 to -0.48), Positive and Negative Syndrome Scale general subscale scores (SMD, -0.57; 95% CI, -0.89 to -0.25), depressive symptom scores (SMD, -0.70; 95% CI, -1.04 to -0.37), and anxiety symptom scores (SMD, -0.58; 95% CI, -0.92 to -0.24) and improved overall cognitive impairment scores (SMD, -0.52; 95% CI, -0.89 to -0.15) compared with a sham. However, positive symptom score changes, all-cause discontinuation rate, discontinuation rate due to adverse events, headache incidence, and dizziness incidence did not significantly differ between any TBS protocols and sham., Conclusions and Relevance: In this network meta-analysis, iTBS over the L-DLPFC was associated with improved scores for negative, depressive, anxiety, and cognitive symptoms in individuals with schizophrenia and was well tolerated by the participants. Other forms of TBS were not associated with benefit. Further research is needed to assess the potential role of TBS in the treatment of schizophrenia.

Lymphocytic myocarditis (LM) is primarily triggered by various factors including viral infections and subsequent immune responses. While rare, some patients with LM experience recurrence with a life-threatening fulminant form. Although combining steroids and immunosuppressants, such as azathioprine and mycophenolate mofetil, has demonstrated favourable outcomes in patients with LM, their efficacy is limited to the chronic phase. Indeed, various immunosuppressants have been used for LM with fulminant manifestation; however, their evidence remains lacking. In our case series, two patients with LM experienced fulminant relapses during steroid tapering, and another presented persistent cardiac enzymes elevation despite steroid therapies. Consequently, we initiated calcineurin inhibitors alongside steroids, resulting in well-controlled clinical courses without further recurrence of LM and significant adverse effects. Our cases suggest calcineurin inhibitors as therapeutic options for managing steroid-resistant LM with fulminant relapse., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Whether comprehensive risk assessment predicts post-referral outcome in patients with pulmonary arterial hypertension (PAH) referred for lung transplantation (LT) in Japan is unknown., Methods and Results: We retrospectively analyzed 52 PAH patients referred for LT. Risk status at referral was assessed using 3- and 4-strata models from the 2022 European Society of Cardiology and European Respiratory Society guidelines. The 3-strata model intermediate-risk group was further divided into 2 groups based on the median proportion of low-risk variables (modified risk assessment [MRA]). The primary outcome was post-referral mortality. During follow-up, 9 patients died and 13 patients underwent LT. There was no survival difference among 3-strata model groups. The 4-strata model classified 33, 16, and 3 patients as low intermediate, high intermediate, and high risk, respectively. The 4-strata model identified high-risk patients with a 1-year survival rate of 33%, but did not discriminate survival between the intermediate-risk groups. The MRA classified 15, 28, 8, and 1 patients as low, low intermediate, high intermediate, and high risk, respectively. High intermediate- or high-risk patients had worse survival (P<0.001), with 1- and 3-year survival rates of 64% and 34%, respectively. MRA high intermediate- or high-risk classification was associated with mortality (hazard ratio 12.780; 95% confidence interval 2.583-63.221; P=0.002)., Conclusions: Patients classified as high intermediate or high risk by the MRA after treatment should be referred for LT.

Background: Approximately 10% of hypertrophic cardiomyopathy (HCM) patients have left ventricular systolic dysfunction (end-stage HCM) leading to severe heart-failure; however, risk stratification to identify patients at risk of progressing to end-stage HCM remains insufficient., Objectives: In this study, the authors sought to elucidate whether the coexistence of other cardiovascular disease (CVD)-related variants is associated with progression to end-stage HCM in patients with HCM harboring pathogenic or likely pathogenic (P/LP) sarcomeric variants., Methods: The authors performed genetic analysis of 83 CVD-related genes in HCM patients from a Japanese multicenter cohort. P/LP variants in 8 major sarcomeric genes (MYBPC3, MYH7, TNNT2, TNNI3, TPM1, MYL2, MYL3, and ACTC1) definitive for HCM were defined as "sarcomeric variants." In addition, P/LP variants associated with other CVDs, such as dilated cardiomyopathy and arrhythmogenic cardiomyopathy, were referred to as "other CVD-related variants.", Results: Among 394 HCM patients, 139 carried P/LP sarcomeric variants: 11 (7.9%) carried other CVD-related variants, 6 (4.3%) multiple sarcomeric variants, and 122 (87.8%) single sarcomeric variants. In a multivariable Cox regression analysis, presence of multiple sarcomeric variants (adjusted HR [aHR]: 3.35 [95% CI: 1.25-8.95]; P = 0.016) and coexistence of other CVD-related variants (aHR: 2.80 [95% CI: 1.16-6.78]; P = 0.022) were independently associated with progression to end-stage HCM. Coexisting other CVD-related variants were also associated with heart failure events (aHR: 2.75 [95% CI: 1.27-5.94]; P = 0.010)., Conclusions: Approximately 8% of sarcomeric HCM patients carried other CVD-related variants, which were associated with progression to end-stage HCM and heart failure events. Comprehensive surveillance of CVD-related variants within sarcomeric HCM patients contributes to risk stratification and understanding of mechanisms underlying end-stage HCM., Competing Interests: Funding Support and Author Disclosures This work was supported by grants from SENSHIN Medical Research Foundation (to Dr Ko and Dr Nomura), Japan Foundation for Applied Enzymology (to Dr Ko and Dr Nomura), Kanae Foundation for the Promotion of Medical Science (to Dr Nomura), Merck Sharp & Dohme Life Science Foundation (to Dr Ko and Dr Nomura), Sakakibara Heart Foundation Cardiovascular Research Program 2023 (to Dr Ko), Tokyo Biomedical Research Foundation (to Dr Nomura), Astellas Foundation for Research on Metabolic Disorders (to Dr Nomura), Novartis Foundation (Japan) for the Promotion of Science (to Dr Nomura), Japanese Circulation Society (to Dr Ko and Dr Nomura), Takeda Science Foundation (to Dr Ko and Dr Nomura), Cell Science Research Foundation (to Dr Nomura), Mochida Memorial Foundation for Medical and Pharmaceutical Research (to Dr Nomura), Japan Heart Foundation (to Dr Ko), Daiichi Sankyo Foundation of Life Science (to Dr Nomura), a Grant-in-Aid for Scientific Research (A) (to Dr Nomura), a Grant-in-Aid for Scientific Research (S) (to Dr Komuro), UTEC-UTokyo FSI Research Grant Program (to Dr Nomura), JST FOREST Program (grant number JPMJFR210U) (to Dr Nomura), Japan Agency for Medical Research and Development (AMED) (JP18km0405209, JP21ek0109543, JP21ek0109569, JP22ama121016, JP22ek0210172, JP22ek0210167, JP22bm1123011, JP23tm0724607, JP23gm4010020, JP223fa627011, JP23tm0524009, JP23tm0524004, JP23jf0126003, JP24ek0109755, and JP24ek0210205) (to Dr Nomura and Dr Komuro), and JP23ek0109600h0002 (to Dr Ko). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: The aim of this study was to compare the early postoperative mortality and morbidity in older patients with a fracture of the femoral neck, between those who underwent total hip arthroplasty (THA) and those who underwent hemiarthroplasty., Methods: This nationwide, retrospective cohort study used data from the Japanese Diagnosis Procedure Combination database. We included older patients (aged ≥ 60 years) who underwent THA or hemiarthroplasty after a femoral neck fracture, between July 2010 and March 2022. A total of 165,123 patients were included. The THA group was younger (mean age 72.6 (SD 8.0) vs 80.7 years (SD 8.1)) and had fewer comorbidities than the hemiarthroplasty group. Patients with dementia or malignancy were excluded because they seldom undergo THA. The primary outcome measures were mortality and complications while in hospital, and secondary outcomes were readmission and reoperation within one and two years after discharge, and the costs of hospitalization. We conducted an instrumental variable analysis (IVA) using differential distance as a variable., Results: The IVA analysis showed that the THA group had a significantly higher rate of complications while in hospital (risk difference 6.3% (95% CI 2.0 to 10.6); p = 0.004) than the hemiarthroplasty group, but there was no significant difference in the rate of mortality while in hospital (risk difference 0.3% (95% CI -1.7 to 2.2); p = 0.774). There was no significant difference in the rate of readmission (within one year: risk difference 1.3% (95% CI -1.9 to 4.5); p = 0.443; within two years: risk difference 0.1% (95% CI -3.2 to 3.4); p = 0.950) and reoperation (within one year: risk difference 0.3% (95% CI -0.6 to 1.1); p = 0.557; within two years: risk difference 0.1% (95% CI -0.4 to 0.7); p = 0.632) after discharge. The costs of hospitalization were significantly higher in the THA group than in the hemiarthroplasty group (difference $2,634 (95% CI $2,496 to $2,772); p < 0.001)., Conclusion: Among older patients undergoing surgery for a femoral neck fracture, the risk of early complications was higher after THA than after hemiarthroplasty. Our findings should aid in clinical decision-making in these patients., Competing Interests: H. Yasunaga reports an institutional grant (paid to The University of Tokyo) from The Ministry of Health, Labour and Welfare, Japan (23AA2003 and 22AA2003), not related to this study., (© 2024 The British Editorial Society of Bone & Joint Surgery.)

Objective: Several medications are associated with delirium; however, studies with adequate statistical power are limited, and it is difficult to determine the effects of the various concomitant medications used in clinical practice. Therefore, in this study, we aimed to comprehensively evaluate the safety signals of delirium-associated drugs using a spontaneous adverse event reporting system., Method: The JAPIC AERS (Food and Drug Administration Adverse Event Reporting System pre-processed by the Japan Pharmaceutical Information Center) was used for the analysis in this pharmacovigilance study. The reporting odds ratio (ROR) for delirium was adjusted for using multivariate logistic regression analysis with sex, age, indication, and melatonin receptor agonist use, and 22 drug categories were targeted as covariates., Results: After excluding patients with missing information, 7,527,568 patients were included in the study. Delirium signals were detected even after adjusting for covariates in 17 drug categories, including benzodiazepines (adjusted ROR, 1.76; 95% confidence interval [CI], 1.64-1.89), opioids (adjusted ROR, 4.42; 95% CI, 4.21-4.64), and tricyclic antidepressants (adjusted ROR, 2.44; 95% CI, 2.20-2.71)., Conclusions: These findings suggest that many drug classes, such as benzodiazepines, are independent risk factors for delirium and strengthen the evidence of an association between delirium and medications., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. The interests over the past three years are as follows: MH received honoraria from Ishiyaku Publishers, Inc., Meiji Seika Pharma Co., Ltd., Medical Friend. Co., Ltd., Nanzando Co., Ltd., Sumitomo Pharma Co., Ltd., and WELCIA Holdings Co., Ltd. RS received honoraria from Eisai Co., Ltd., Meiji Seika Pharma Co., Ltd., Merck & Co., Inc., Nippon Kayaku Co.,Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Factory, and Sumitomo Pharma Co., Ltd. KS received honoraria from Eisai Co., Ltd. SE received honoraria from Eisai Co., Ltd. AI received honoraria from Sumitomo Pharma Co., Ltd. and UCB Japan Co. Ltd. RM received honoraria from Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., and UCB Japan Co. Ltd. HA received honoraria from Sumitomo Pharma Co., Ltd. SY received honoraria from AstraZeneca K.K., Daiichi Sankyo Co., Ltd., EA Pharma Co., Ltd., Eisai Co., Ltd., Meiji Seika Pharma Co., Ltd., Nippon Shinyaku Co., Ltd., Nipro Corporation, Otsuka Pharmaceutical Factory, Pfizer Japan Inc., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Toa Eiyo Ltd., and Towa Pharmaceutical Co., Ltd. Funding was received from EA Pharma Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., SUGI Holdings Co., Ltd., and Otsuka Pharmaceutical Factory., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Proton therapy is highly effective for liver malignancies, and to increase its accuracy, placement of fiducial markers in the liver is preferred. We retrospectively evaluated the safety and feasibility of CT-guided fiducial marker implantation using ultra-fine 25-gauge needles before proton therapy for liver malignancies., Materials and Methods: Between May 2016 and April 2021, 334 cases were investigated. All of procedures were performed without anesthesia. Technical success was defined as the completion of implantation at the intended site. Tumor-marker distance and possibility of synchronization between tumors and markers were evaluated and compared with Mann-Whitney U test. Complications were evaluated using the Common Terminology Criteria for Adverse Events, version 4.0., Results: Technical success rate was 97.3%. Tumor-marker distance was 19.1 mm (median, range 0-96) in the group in which the implanted marker was synchronized with tumor (n = 315), while it was 34.5 mm (median, range 6-94) in the group in which the implanted marker was not synchronized (n = 13) (p value = 0.011 < 0.05). The complication rate was 2.4%, 2 were classified as grade 4 and 5 as grade 1, and 1 as grade 2. There were no grade 3 or higher complications that seemed to be related to the procedure., Conclusion: CT-guided marker implantation using a 25-gauge needle achieved a satisfactory success rate with few complications and was useful for the image-guided and respiratory-synchronized proton therapy. LEVEL OF EVIDENCE 3: Local non-random sample., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Background: A left ventricular assist device (LVAD) is an effective therapeutic option for advanced heart failure. Late right heart failure (LRHF) is a complication after LVAD implantation that is associated with increasing morbidity and mortality; however, the assessment of right heart function, including right heart reserve function after LVAD implantation, has not been established. We focused on a fluid-loading test with right heart catheterization to evaluate right heart preload reserve function and investigate its impact on LRHF., Methods: Patients aged > 18 years who received a continuous-flow LVAD between November 2007 and December 2022 at our institution, and underwent right heart catheterization with saline loading (10 mL/kg for 15 minutes) 1 month after LVAD implantation, were included., Results: Overall, 31 cases of LRHF or death (right heart failure [RHF] group) occurred in 149 patients. In the RHF vs the non-RHF groups, the pulmonary artery pulsatility index (PAPi) at rest (1.8 ± 0.89 vs 2.5 ± 1.4, P = 0.02) and the right ventricular stroke work index (RVSWi) change ratio with saline loading (0.96 ± 0.32 vs 1.1 ± 0.20, P = 0.03) were significantly different. The PAPi at rest and the RVSWi change ratio with saline loading were identified as postoperative risks for LRHF and death. The cohort was divided into 3 groups based on whether the PAPi at rest and the RVSWi change ratio were low. The event-free curve differed significantly among the 3 groups (P < 0.001)., Conclusions: Hemodynamic assessment with saline loading can evaluate the right ventricular preload reserve function of patients with an LVAD. A low RVSWi change with saline loading was a risk factor for LRHF following LVAD implantation., (Copyright © 2024 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Histiocytic necrotizing lymphadenitis (HNL) is an inflammatory disease of unknown etiology clinically characterized by painful lymphadenopathy. This study aimed to investigate the role of interferon (IFN)-α in the pathogenesis of HNL and the clinical significance of serum IFN-α levels for the diagnosis and monitoring of HNL disease activity., Methods: This study enrolled 47 patients with HNL and 43 patients with other inflammatory diseases that require HNL differentiation including malignant lymphoma (ML), bacterial lymphadenitis, and Kawasaki disease. Expression of IFN-stimulated genes (ISGs) and MX1 in the lymph nodes was measured by real-time quantitative reverse transcription polymerase chain reaction and immunofluorescence staining, respectively. Enzyme-linked immunosorbent assay was used to quantify serum cytokine levels. The results were compared with the clinical features and disease course of HNL., Results: Patients with HNL had a significantly elevated ISG expression in the lymph nodes compared with those with ML. MX1 and CD123, a specific marker of plasmacytoid dendritic cells (pDCs), were colocalized. In patients with HNL, serum IFN-α levels were significantly elevated and positively correlated with disease activity. The serum IFN-α level cutoff value for differentiating HNL from other diseases was 11.5 pg/mL., Conclusion: IFN-α overproduction from pDCs may play a critical role in HNL pathogenesis. The serum IFN-α level may be a valuable biomarker for the diagnosis and monitoring of disease activity in patients with HNL., Competing Interests: Declaration of competing interest All the authors declare that they have no relevant conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objective: This pharmacovigilance study evaluated the profile of clozapine-related adverse events by region using the Food and Drug Administration Adverse Event Reporting System (FAERS)., Methods: We categorized each case into five regions (America, Europe/West Asia, Oceania, Asia, and Africa) based on the reporting country information in the FAERS database. The number of clozapine-related adverse events reported in each region was aggregated according to the preferred term (PT) and the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ)., Results: A total of 101,872 clozapine-related adverse events were registered in the FAERS database. In America and Europe, leukocyte or neutrophil count abnormalities accounted for half of the top 10 PTs by relative reporting rate. However, Asia had higher relative reporting rates of pyrexia and salivary hypersecretion (13.91% and 10.85%, respectively). Regarding the SMQ, the relative reporting rates of infective pneumonia, convulsions, extrapyramidal syndrome, gastrointestinal obstruction, and hyperglycaemia/new onset diabetes mellitus were higher in Asia than in other regions (5.26%, 9.72%, 12.65%, 5.13%, and 8.26%, respectively), with significant differences even after adjusting for confounding factors using multivariate logistic regression analysis., Conclusion: Spontaneous reports of adverse events associated with clozapine show regional disparities, particularly in Asia, where concentration-dependent adverse events are more frequently reported. However, the spontaneous reporting system has several limitations, requiring further research for validation.

Background: Decreased diffusing capacity of the lungs for carbon monoxide (DLco) is associated with microvascular damage in chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) is an effective treatment for CTEPH, but the efficacy of BPA in patients with CTEPH with low DLco remains unclear because BPA does not directly address microvascular damage. This study investigates the influence of microvasculopathy on BPA in CTEPH according to DLco., Methods: We retrospectively analysed data from patients with inoperable CTEPH who underwent BPA at the University of Tokyo Hospital from July 2011 to August 2023. The patients were classified into two groups based on their preprocedural DLco (normal DLco (ND) and low DLco (LD) groups), with a DLco cut-off value of 80%. We compared the patient characteristics and effectiveness of BPA between the groups., Results: Among the 75 patients, 36 were in the LD group. The LD group had a shorter 6-minute walking distance (324±91 vs 427±114 m) than the ND group but the mean pulmonary artery pressure (mPAP) was similar (38.9±7.3 vs 41.1±9.2 mm Hg) before BPA. BPA improved the haemodynamic status and exercise tolerance in both groups. The LD group exhibited a higher mPAP (25.1±7.4 vs 21.5±5.6 mm Hg) and required more sessions of BPA (median 6 vs 4). Based on the analysis of covariance adjusted for baseline values, low DLco significantly correlated with mPAP (sβ=-0.304, 95% CI -7.015 to -1.132, p=0.007) and pulmonary vascular resistance (sβ=-0.324, 95% CI -141.0 to -29.81, p=0.003)., Conclusions: BPA was associated with an improvement in the haemodynamic status and exercise tolerance in patients with CTEPH even with low DLco. However, low DLco may attenuate the effect of BPA on mPAP and pulmonary vascular resistance and require more treatment sessions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Context: Domino osteoporotic vertebral fractures (OVFs) involve multiple OVFs occurring simultaneously or sequentially, before healing of the initial OVFs. However, the risk factors and long-term clinical outcomes of domino OVFs are unclear., Purpose: To identify the risk factors associated with domino OVFs and to assess their impact on patients' quality of life (QOL)., Study Design/setting: Multicenter prospective observational cohort study., Patient Sample: Patients (n = 190) treated conservatively for acute OVFs in 8 hospitals with 12-month follow-up., Outcome Measures: Clinical outcomes were assessed using the visual analog scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ). Multivariate analyses were performed to identify risk factors for domino OVFs., Methods: All patients underwent magnetic resonance imaging (MRI) at 3 months to detect subsequent domino OVFs. Domino OVF group included initial domino OVFs (multiple acute OVFs at baseline) and subsequent domino OVFs at 3 months. Paraspinal muscle assessment was performed using the lumbar indentation value and Goutallier classification. Patient characteristics, bone quality, paravertebral muscle degeneration, nutritional status, radiographic parameters, and QOL scores were compared between the nondomino and domino OVF groups., Results: We evaluated 50 (26.3%) patients with domino OVFs (34 with initial domino OVFs; 20 with subsequent domino OVFs). Walking ability was poorer in the domino than in the nondomino OVF group, from baseline to the 12 months follow-up. Groups with 3 or more adjacent domino OVFs showed worse VAS and ODI scores. Multivariate logistic regression analysis revealed that severe fatty degeneration of the paraspinal muscle was an independent risk factor for domino OVFs., Conclusions: Severe paraspinal muscle fatty degeneration is an independent risk factor for domino OVFs. Our study showed that the quality, rather than the quantity, of paraspinal muscles had an impact on domino OVFs. Early assessment of fatty degeneration in the paraspinal muscles is essential for predicting the development of domino OVFs., 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.)

Aims: The use of multimodal non-opioid analgesia in hip fractures, specifically acetaminophen combined with non-steroidal anti-inflammatory drugs (NSAIDs), has been increasing. However, the effectiveness and safety of this approach remain unclear. This study aimed to compare postoperative outcomes among patients with hip fractures who preoperatively received either acetaminophen combined with NSAIDs, NSAIDs alone, or acetaminophen alone., Methods: This nationwide retrospective cohort study used data from the Diagnosis Procedure Combination database. We included patients aged ≥ 18 years who underwent surgery for hip fractures and received acetaminophen combined with NSAIDs (combination group), NSAIDs alone (NSAIDs group), or acetaminophen alone (acetaminophen group) preoperatively, between April 2010 and March 2022. Primary outcomes were in-hospital mortality and complications. Secondary outcomes were opioid use postoperatively; readmission within 90 days, one year, and two years; and total hospitalization costs. We used propensity score overlap weighting models, with the acetaminophen group as the reference group., Results: We identified 93,018 eligible patients, including 13,068 in the combination group, 29,203 in the NSAIDs group, and 50,474 in the acetaminophen group. Propensity score overlap weighting successfully balanced patient characteristics among the three groups, with no significant difference in in-hospital mortality rates observed among the groups (combination group risk difference 0.0% (95% CI -0.5 to 0.4%); NSAIDs group risk difference -0.2% (95% CI -0.5 to 0.2%)). However, the combination group exhibited a significantly lower risk of in-hospital complications than the acetaminophen group (risk difference -1.9% (95% CI -3.2 to -0.6%)) as well as a significantly lower risk of deep vein thrombosis (risk difference -1.4% (95% CI -2.2 to -0.7%)). Furthermore, total hospitalization costs were higher in the NSAIDs group than in the acetaminophen group (difference USD $438 (95% CI 249 to 630); p < 0.001). No significant differences in other secondary outcomes were observed among the three groups., Conclusion: The combination of acetaminophen with NSAIDs appears to be safe and advantageous in terms of reducing in-hospital complications., Competing Interests: H. Yasanaga reports an institutional grant from The Ministry of Health, Labour and Welfare, Japan (23AA2003 and 22AA2003)., (© 2024 The British Editorial Society of Bone & Joint Surgery.)

Study Design: Prospective cohort study., Purpose: This study aimed to identify the optimal preoperative bone health assessment for adult spinal deformity (ASD) surgery through correlation analysis between intraoperative pedicle screw (PS) insertion torque and various bone quality measures, including bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DEXA), Hounsfield unit (HU) by computed tomography (CT), and vertebral bone quality (VBQ) score by magnetic resonance imaging., Overview of Literature: Existing data on optimal assessment tools for ASD surgery are limited., Methods: The study included patients with ASD aged >60 years who underwent spinal corrective fusion surgery from the lower thoracic spine to the pelvis. The intraoperative PS insertion torque was measured using a torque meter. Pearson correlation coefficients were calculated between the PS insertion torque and the BMD, HU, and VBQ score. Preoperative bone quality was compared between the proximal junctional failure (PJF) and non-PJF groups., Results: Thirty-one patients with 177 PS at T10, T11, and T12 were analyzed. The PS insertion torque showed a moderate positive correlation with lumbar spine BMD (r=0.59-0.69, p<0.01), total hip BMD (0.58-0.62, p<0.01), and HU value (r=0.58-0.66, p<0.01). However, the VBQ score did not show significant correlation (r=-0.28 to -0.23, p >0.05). Notably, a strong correlation was found between the PS insertion torque and the HU value for screws of the same size (r=0.71 and 0.74, p<0.01). The HU value at T12 and the PS insertion torque at T10 were significantly lower in the PJF group than in the non-PJF group., Conclusions: This study demonstrates a positive correlation between the PS insertion torque and HU value in the lower thoracic spine and a moderate correlation with BMD but not the VBQ score. Preoperative assessment using DEXA and CT is crucial for optimizing bone health management in ASD surgery.

Background: The contemporary outcome of balloon pulmonary angioplasty (BPA) and pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) are unclear., Objectives: This study aimed to clarify the characteristics and outcomes of CTEPH patients treated with BPA and PEA in Japan., Methods: Among 1,270 participants enrolled between 2018 and 2023 in the CTEPH AC (Chronic Thromboembolic Pulmonary Hypertension Anticoagulant) registry, a Japanese nationwide CTEPH registry, 369 treatment-naive patients (BPA strategy: n = 313; PEA strategy: n = 56) and 690 on-treatment patients (BPA strategy: n = 561; PEA strategy: n = 129) were classified according to the presence of prior reperfusion therapy. Morbidity and mortality events (all-cause death, rescue mechanical reperfusion therapy, and/or initiation of parenteral pulmonary vasodilators), pulmonary hemodynamics, exercise tolerance, and relevant laboratory test results were evaluated., Results: The BPA strategy was chosen in older patients than the PEA strategy (mean age, BPA vs PEA: 66.5 ± 12.6 years vs 62.5 ± 11.8 years; P  = 0.028). Median follow-up period was 615 (Q1-Q3: 311-997) days in treatment-naive patients and 1,136 (Q1-Q3: 684-1,300) days in on-treatment patients. BPA strategy had as acceptable morbidity and mortality as PEA strategy (5-year morbidity and mortality event rate, BPA vs PEA: 10.2% [95% CI: 5.2%-19.5%] vs 16.1% [95% CI: 4.3%-50.6%] in treatment-naive patients; 9.7% [95% CI: 6.7%-13.8%] vs 6.9% [95% CI: 2.7%-17.3%] in on-treatment patients), with greater improvement of renal function; glomerular filtration rate in propensity score-matched population (difference between change: 4.9 [95% CI: 0.5-9.3] mL/min/1.73 m 2 ; P  = 0.030)., Conclusions: BPA strategy was more frequently chosen in older patients compared with PEA strategy and showed acceptable outcomes for efficacy with greater advantage for improvement in renal function. (Multicenter registry of chronic thromboembolic pulmonary hypertension in Japan; UMIN000033784)., Competing Interests: This study is supported by the Japan Agency for Medical Research and Development (grant numbers JP20ek0109371, JP19lk0201102, JP22lk0201125, and JP19lk1601003), JSPS KAKENHI (grant number JP20286266), and grant from Konica Minolta based on a contract. The funding body had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Dr Hosokawa has received grants from Konica Minolta; and personal fees from Bayer Yakuhin, Nippon Shinyaku, Janssen Pharmaceutical, Pfizer, and Konica Minolta, outside the submitted work. Dr Taniguchi has received grants from Nippon Shinyaku and Janssen Pharmaceutical; and personal fees from Nippon Shinyaku, Janssen Pharmaceutical, and Bayer Yakuhin, outside the submitted work. Dr Inami has received personal fees from Janssen Pharmaceutical and Bayer Yakuhin, outside the submitted work. Dr Yamashita has received a grant from Abbott Vascular Japan; and personal fees from Kaneka Medix, Boston Scientific Japan, Nihon Kohden, Philips Japan, Janssen Pharmaceutical, and Bayer Yakuhin, outside the submitted work. Dr Ogino has received consulting fees from Terumo, Japan Lifeline, and Century Medical; and personal fees from Bayer Yakuhin, Daiichi-Sankyo, Pfizer, and Nippon Shinyaku, outside the submitted work. Dr Tsujino has received personal fees from Nippon Shinyaku and Janssen Pharmaceutical; and affiliation with the division supported by endowments from Nippon Shinyaku, Nippon Boehringer Ingelheim, Mochida Pharmaceutical, Kaneka Medix, Takeyama, and Medical System Network, outside the submitted work. Dr Hatano has received personal fees from Bayer Yakuhin and Janssen Pharmaceutical, outside the submitted work. Dr Yaoita has received personal fees from Bayer Yakuhin and Konica Minolta, outside the submitted work. Dr Ikeda has received personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, Daiichi -Sankyo, and Bristol Myers Squibb, outside the submitted work. Dr Shimokawahara has received a grant from Bayer Yakuhin; and personal fees from Bayer Yakuhin and Nippon Shinyaku, outside the submitted work. Dr Tanabe has received personal fees from Janssen Pharmaceutical, Bayer Yakuhin, and Nippon Shinyaku, outside the submitted work. Dr Kubota has received personal fees from Janssen Pharmaceutical and Nippon Shinyaku, outside the submitted work. Dr Ogihara has received grants from Bayer Yakuhin; and personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, Daiichi-Sankyo, and Bristol Myers Squibb, outside the submitted work. Dr Kawakami has received personal fees from Kaneka Medix and Abbott Medical Japan, and consulting fees from ACIST Japan, outside the submitted work. Dr Tamura has received grants from Bayer Yakuhin, Nippon Shinyaku, and Mochida Pharmaceutical; and personal fees from Bayer Yakuhin, Nippon Shinyaku, Daiichi-Sankyo, and Janssen Pharmaceutical, outside the submitted work. Dr Abe has received a grant from Konica Minolta and Daiichi-Sankyo, outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Group 2 innate lymphoid cells (ILC2s) are a subset of innate lymphocytes that produce type 2 cytokines, including IL-4, IL-5, and IL-13. GATA3 is a critical transcription factor for ILC2 development at multiple stages. However, when and how GATA3 is induced to the levels required for ILC2 development remains unclear. Herein, we identify ILC2-specific GATA3-related tandem super-enhancers (G3SE) that induce high GATA3 in ILC2-committed precursors. G3SE-deficient mice exhibit ILC2 deficiency in the bone marrow, lung, liver, and small intestine with minimal impact on other ILC lineages or Th2 cells. Single-cell RNA-sequencing and subsequent flow cytometry analysis show that GATA3 induction mechanism, which is required for entering the ILC2 stage, is lost in IL-17RB + PD-1 - late ILC2-committed precursor stage in G3SE-deficient mice. Cnot6l, part of the CCR4-NOT deadenylase complex, is a possible GATA3 target during ILC2 development. Our findings implicate a stage-specific regulatory mechanism for GATA3 expression during ILC2 development., (© 2024. The Author(s).)

We report here a case of postoperative recurrent adenosquamous carcinoma (ASC) of the esophagogastric junction (EGJ) treated with S-1 therapy. A 79-year-old woman was diagnosed with carcinoma of the EGJ. Thoracoscopic subtotal esophagectomy was performed, and pathological examination revealed advanced ASC with lymph node metastasis. Five months after surgery, multiple lung metastases and multiple lymph node metastases were observed, and the patient was treated with S-1 monotherapy, which showed partial response and may be effective for advanced ASC of the EGJ. On the other hand, immunohistological analysis of the tumors showed a relatively wide range of areas that could differentiate into both adenocarcinoma and squamous cell carcinoma, suggesting that tumor cells with multidifferentiation potential, or at least the ability to differentiate into both adeno-epithelial and squamous epithelial cells, were the likely source of the tumors., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Asthma is a widespread airway disorder where GATA3-dependent Type-2 helper T (Th2) cells and group 2 innate lymphoid cells (ILC2s) play vital roles. Asthma-associated single nucleotide polymorphisms (SNPs) are enriched in a region located 926-970 kb downstream from GATA3 in the 10p14 (hG900). However, it is unknown how hG900 affects the pathogenesis of allergic airway inflammation. To investigate the roles of the asthma-associated GATA3 enhancer region in experimental allergic airway inflammation, we first examined the correlation between GATA3 expression and the activation of the hG900 region was analyzed by flow cytometry and ChIP-qPCR. We found that The activation of enhancers in the hG900 region was strongly correlated to the levels of GATA3 in human peripheral T cell subsets. We next generated mice lacking the mG900 region (mG900KO mice) were generated by the CRISPR-Cas9 system, and the development and function of helper T cells and ILCs in mG900KO mice were analyzed in steady-state conditions and allergic airway inflammation induced by papain or house dust mite (HDM). The deletion of the mG900 did not affect the development of lymphocytes in steady-state conditions or allergic airway inflammation induced by papain. However, mG900KO mice exhibited reduced allergic inflammation and Th2 differentiation in the HDM-induced allergic airway inflammation. The analysis of the chromatin conformation around Gata3 by circular chromosome conformation capture coupled to high-throughput sequencing (4C-seq) revealed that the mG900 region interacted with the transcription start site of Gata3 with an influencing chromatin conformation in Th2 cells. These findings indicate that the mG900 region plays a pivotal role in Th2 differentiation and thus enhances allergic airway inflammation., Competing Interests: Competing interests statement:The authors declare no competing interest.

Crystalglobulin-induced nephropathy is a rare disease that causes the deposition of crystallized monoclonal immunoglobulins into the glomerular capillary and arteriole spaces. Here, we report the case of a patient who presented with skin ulcers, urinary protein, and renal dysfunction. The patient underwent renal and skin biopsies, and the biopsy tissue samples were subjected to mass spectrometry. The patient was diagnosed with crystalglobulin-induced nephropathy. A literature review suggested that pathological examinations using electron microscopy, mass spectrometry, and immunofluorescent staining of paraffin-embedded biopsy samples treated with pronase may be useful for the diagnosis of this condition., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Although clonal hematopoiesis of indeterminate potential (CHIP) is an adverse prognostic factor for atherosclerotic disease, its impact on nonischemic dilated cardiomyopathy (DCM) is elusive. The authors performed whole-exome sequencing and deep target sequencing among 198 patients with DCM and detected germline mutations in cardiomyopathy-related genes and somatic mutations in CHIP driver genes. Twenty-five CHIP driver mutations were detected in 22 patients with DCM. Ninety-two patients had cardiomyopathy-related pathogenic mutations. Multivariable analysis revealed that CHIP was an independent risk factor of left ventricular reverse remodeling, irrespective of known prognostic factors. CHIP exacerbated cardiac systolic dysfunction and fibrosis in a DCM murine model. The identification of germline and somatic mutations in patients with DCM predicts clinical prognosis., Competing Interests: This work was supported by grants from the SENSHIN Medical Research Foundation (to Dr Nomura), the Japan Foundation for Applied Enzymology (to Drs Ko, Nomura, and Dai), the Kanae Foundation for the Promotion of Medical Science (to Dr Nomura), the MSD Life Science Foundation (to Dr Nomura), the Sakakibara Heart Foundation Cardiovascular Research Program 2023 (to Dr Ko), the Tokyo Biomedical Research Foundation (to Dr Nomura), the Astellas Foundation for Research on Metabolic Disorders (to Dr Nomura), the Novartis Foundation (Japan) for the Promotion of Science (to Dr Nomura), the Japanese Circulation Society (to Drs Ko and Nomura), the Takeda Science Foundation (to Drs Ko and Nomura), the Cell Science Research Foundation (to Dr Nomura), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (to Dr Nomura), the Japan Heart Foundation (to Dr Ko), and the Daiichi-Sankyo Foundation of Life Science (to Dr Nomura); a Grant-in-Aid for Scientific Research (A) (to Dr Nomura); a Grant-in-Aid for Scientific Research (S) (to Dr Komuro); the UTEC-UTokyo FSI Research Grant Program (to Dr Nomura); the JST FOREST Program (grant JPMJFR210U) (to Dr Nomura); a Japan Society for the Promotion of Science Grant-in-Aid for Japan Society for the Promotion of Science fellow (23KJ0434) (to Dr Dai) and AMED JP23ek0109600h0002 (to Dr Ko); and JP20ek0109487, JP18km0405209, JP21ek0109543, JP21tm0724601, JP22ama121016, JP22ek0210172, JP22ek0210167, JP22bm1123011, JP23tm0724607, JP23gm4010020, JP23tm0524009, JP23tm0524004, JP23jf0126003, and JP24ek0109755 (to Drs Nomura and Komuro). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

In clinical practice, theta burst stimulation (TBS) presents as a more efficient and potentially more effective therapeutic modality than conventional repetitive transcranial magnetic stimulation (rTMS), as it allows for the delivery of more stimuli in less time and at similar intensities. To date, accelerated treatment plans according to various continuous (cTBS) and intermittent TBS (iTBS) protocols for depression have been proposed. To investigate which of the TBS protocols provided a favorable risk-benefit balance for individuals with depression, this systematic review and random-effects model network meta-analysis was conducted. The study outcomes included response rate (primary), depression symptom improvement, remission rate, all-cause discontinuation rate, incidence of switch to mania, and incidence of headache/discomfort at treatment site. In this meta-analysis, a total of 23 randomized controlled trials (n = 960, mean age = 41.88 years, with 60.78% females) were included. Approximately 69.57% of the trials included individuals with an exclusive diagnosis of major depressive disorder. The following six TBS protocols (target) were evaluated: cTBS (right-dorsolateral prefrontal cortex [R-DLPFC]), cTBS (R-DLPFC) + iTBS (left-DLPFC [L-DLPFC]), iTBS (L-DLPFC), iTBS (L-DLPFC) + iTBS (R-DLPFC), iTBS (left-dorsomedial prefrontal cortex) + iTBS (right-dorsomedial prefrontal cortex), and iTBS (occipital lobe). Compared to sham, cTBS (R-DLPFC) + iTBS (L-DLPFC), iTBS (L-DLPFC), and iTBS (occipital lobe) had a higher response rate (k = 23); cTBS (R-DLPFC) + iTBS (L-DLPFC) and iTBS (L-DLPFC) dominated in the depression symptom improvement (k = 23); and iTBS (L-DLPFC) had a higher remission rate (k = 15). No significant differences were found for all-cause discontinuation rate (k = 17), incidence of switch to mania (k = 7), and incidence of headache/discomfort at treatment site (k = 10) between any TBS protocols and sham. Thus, cTBS (R-DLPFC) + iTBS (L-DLPFC) and iTBS (L-DLPFC) demonstrate favorable risk-benefit balance for the treatment of depression., (© 2024. The Author(s).)

Aim: Postmortem brain research is necessary for elucidating the pathology of schizophrenia; an increasing number of studies require a combination of suitable tissue samples preserved at multiple brain banks. In this study, we examined whether a comparative study of protein expression levels can be conducted using postmortem brain samples preserved in different facilities., Methods: We compared the demographic factors of postmortem brain samples preserved in two institutions and measured and compared the expression levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glial fibrillary acidic protein (GFAP) in the prefrontal cortex and superior temporal gyrus. GAPDH is generally used as a loading control for western blotting, and GFAP is considered as an astrocyte marker in the brain., Results: We found significant differences between the two institutions in postmortem interval, age at death, and preservation time. To reduce the effects of these differences on our measurements, the parameters were set as covariates in our analyses of covariance. Subsequently, no differences in GAPDH and GFAP expression were found between institutions., Conclusions: When studies are conducted using brain samples preserved in different brain banks, differences in demographic factors should be carefully considered and taken into account by statistical methods to minimize their impact as much as possible. Since there was no significant difference in the protein expression levels of GAPDH and GFAP in either region between the two institutions that preserved the postmortem brains, we concluded that it is possible to perform protein quantitative analysis assuming that there is no effect of difference between two institutions., (© 2024 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Retroperitoneal leiomyosarcoma (RPLMS) is rare and usually presents as a large abdominal mass with poor clinical symptoms. Radiological findings of an RPLMS arising in the pelvis of a woman resemble those of adnexal tumors. Herein, we present a case of RPLMS mimicking an adnexal tumor which was differentiated from having an ovarian origin as the right ovarian vein was passing through the tumor but there was no direct vascular connection with the tumor. Therefore, it is important to identify the ovarian vein to distinguish between these tumors., (© 2024 The Authors.)

In the alkyl addition reaction of aromatic nitriles using Grignard reagents, ketones are formed after hydrolysis. However, this addition reaction is often slow compared to that using reactive organolithium(i) reagents. In this study, we improved the reaction by using zinc(ii)ates, which are generated in situ using Grignard reagents and zinc chloride (ZnCl 2 ) as a catalyst. As a result, the corresponding ketones and amines were obtained via hydrolysis and reduction, respectively, in good yields under mild reaction conditions. Scale-up reactions are also demonstrated. Interestingly, using a catalytic amount of ZnCl 2 was more effective than using a stoichiometric amount of zinc(ii)ates. Possible transition states are proposed on the basis of the active zinc(ii)ate species, and DFT calculations were carried out to elucidate a plausible reaction mechanism., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The effect of the U-shaped cavity of conformationally flexible chiral Lewis acidic boron-based catalysts in multiselective Diels-Alder reactions was investigated. The U-shaped catalysts can recognize substituents at the terminal acetylene moiety of propynal based on steric factors and can also recognize alkyne and alkene substrates based on the match/mismatch between the catalysts and substrates. Moreover, even in a mixture of different catalysts and substrates, the desired competitive reactions can proceed multiselectively. This proof-of-concept study should contribute to the development of artificial enzyme-like catalysis in vitro.

Introduction: Domino osteoporotic vertebral fracture (OVF) is as a subsequent fracture that develops within 3 months before the initial OVF heals. There is limited evidence regarding the efficacy of osteoanabolic agents on its treatment. This study evaluated the effects of bisphosphonates and anabolic agents teriparatide and romosozumab on subsequent domino OVF., Methods: This was post hoc analysis of a prospective, multicenter, observational study conducted across 8 hospitals, enrolling 144 patients with conservatively treated OVF, grouped into patients receiving bisphosphonate (BP, n  = 55), teriparatide (TPTD, n  = 62), and romosozumab (Romo, n  = 27). The primary outcome was the incidence of subsequent OVF at 3 and 12 months, whereas the secondary outcomes included the incidence of pseudoarthrosis and progression of vertebral collapse (VC). Pseudoarthrosis was classified as stable or unstable based on vertebral instability., Results: The use of osteoanabolic agents did not reduce the incidence of subsequent OVF at 3 and 12 months. There were no significant differences in the background data or type of conservative treatment among the three groups. However, the TPTD and Romo groups had significantly lower rates of unstable pseudarthrosis ( p  = 0.03). Additionally, there were no significant differences in VC progression between groups, but it tended to be higher in the BP group than the TPTD and Romo group ( p  = 0.07)., Conclusion: Osteoanabolic agents were beneficial in reducing unstable pseudoarthrosis, but were not more effective than bisphosphonates in the development of subsequent domino OVF. A more comprehensive approach to the treatment of osteoporosis is needed to prevent domino OVFs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The specific expansion of T-cell receptor β chain variable region (TCR-Vβ21.3 + ) CD4 + and CD8 + T cells was observed in Japanese patients with multisystem inflammatory syndrome in children. In contrast, these findings were not observed in patients with toxic shock syndrome and Kawasaki disease. T-cell receptor β chain variable region repertoire analysis to detect specific expansion of Vβ21.3 + T cells might be useful for differentiating multisystem inflammatory syndrome in children from toxic shock syndrome and Kawasaki disease., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Reliable predictors of treatment efficacy in heart failure have been long awaited. DNA damage has been implicated as a cause of heart failure., Objectives: The purpose of this study was to investigate the association of DNA damage in myocardial tissue with treatment response and prognosis of heart failure., Methods: The authors performed immunostaining of DNA damage markers poly(ADP-ribose) (PAR) and γ-H2A.X in endomyocardial biopsy specimens from 175 patients with heart failure with reduced ejection fraction (HFrEF) of various underlying etiologies. They calculated the percentage of nuclei positive for each DNA damage marker (%PAR and %γ-H2A.X). The primary outcome was left ventricular reverse remodeling (LVRR) at 1 year, and the secondary outcome was a composite of cardiovascular death, heart transplantation, and ventricular assist device implantation., Results: Patients who did not achieve LVRR after the optimization of medical therapies presented with significantly higher %PAR and %γ-H2A.X. The ROC analysis demonstrated good performance of both %PAR and %γ-H2A.X for predicting LVRR (AUCs: 0.867 and 0.855, respectively). There was a negative correlation between the mean proportion of DNA damage marker-positive nuclei and the probability of LVRR across different underlying diseases. In addition, patients with higher %PAR or %γ-H2A.X had more long-term clinical events (PAR HR: 1.63 [95% CI: 1.31-2.01]; P < 0.001; γ-H2A.X HR: 1.48 [95% CI: 1.27-1.72]; P < 0.001)., Conclusions: DNA damage determines the consequences of human heart failure. Assessment of DNA damage is useful to predict treatment efficacy and prognosis of heart failure patients with various underlying etiologies., Competing Interests: Funding Support and Author Disclosures This work was supported by a Japan Society for the Promotion Science (JSPS) Grant-in-Aid for Scientific Research (A) (to Dr Nomura), a JSPS Grant-in-Aid for Scientific Research (S) (to Dr Komuro), a JSPS Grant-in-Aid for JSPS fellows (grant number 23KJ0434 to Dr Dai), the UTEC-UTokyo FSI Research Grant Program (to Dr Nomura), JST FOREST Program (grant number JPMJFR210U to Dr Nomura), Japan Foundation for Applied Enzymology (to Drs Ko and Dai), SENSHIN Medical Research Foundation (to Dr Ko), Merck Sharp & Dohme Life Science Foundation (to Dr Ko), Takeda Science Foundation (to Dr Ko), Japanese Circulation Society (to Dr Ko), Japan Heart Foundation (to Dr Ko), Sakakibara Heart Foundation Cardiovascular Research Program 2023 (to Dr Ko), and Japan Agency for Medical Research and Development (AMED) (grant nos. 22ek0109600h0002 to Dr Ko and JP20ek0210141, JP20ek0109487, JP17gm0810013, JP18km0405209, JP19ek0210118, JP21ek0109543, and JP21ek0109569 to Drs Nomura and Komuro). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A 58-year-old woman with rheumatoid arthritis was diagnosed with methotrexate-associated Hodgkin lymphoma. After receiving several chemotherapy regimens, she started nivolumab treatment. Two weeks later, she was hospitalized with worsening finger, wrist, and elbow joint pain. A synovial biopsy of the wrist joint showed villous synovial proliferation and linear infiltration of CD68-/CD3-positive T cells (with more CD8 than CD4 T cells) but no CD20-positive B cells or CD138-positive macrophages. These findings corresponded to synovitis associated with immune-related adverse events, which are induced mainly by T cells and are different from typical rheumatoid arthritis (RA), in which B cells play a central role.

A BF 3 -mediated domino dehydration/electrophilic cyclization of silylalkynols to form 2,3-fused tricyclic benzofulvenes was achieved. In the latter step, in situ generated BF 3 ·OH 2 enables the electrophilic activation of alkynes. The predominant Z -selectivity of the reaction is also discussed.

Aim: To update the major depressive disorder (MDD) treatment guidelines of the Japanese Society of Mood Disorders, we conducted a systematic review and pairwise meta-analysis of double-blind, randomized, placebo-controlled trials of available antidepressants in Japan for older adults with MDD., Methods: Outcome measures included response rate (primary), improvement in depressive symptom scale score, remission rate, all-cause discontinuation, discontinuation due to adverse events, and at least one adverse event. A random-effects model was used to calculate the risk ratio (RR) and standardized mean difference (SMD) with a 95% confidence interval (95% CI)., Results: Nine double-blind, randomized, placebo-controlled trials (n = 2145) were identified. No study has been conducted in Japan. Our meta-analysis included the following antidepressants: duloxetine, escitalopram, imipramine, sertraline, venlafaxine, and vortioxetine. Antidepressants have significantly higher response rates than placebo (RR [95% CI] = 1.38 [1.04, 1.83], p = 0.02). Antidepressants outperformed placebo in terms of improving depressive symptom scale score (SMD [95% CI] = -0.62 [-0.92, -0.33], p < 0.0001). However, antidepressants were associated with a higher discontinuation rate due to adverse events (RR [95% CI] = 1.94 [1.30, 2.88], p = 0.001) and a higher incidence of at least one adverse event (RR [95% CI] = 1.11 [1.02, 1.21], p = 0.02) compared to placebo. The groups did not differ significantly in terms of remission rate or all-cause discontinuation., Conclusions: Our meta-analysis concluded that treatment with antidepressants available in Japan is only weakly recommended for moderate to severe MDD in older adults., (© 2024 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Introduction: The question remains to be elucidated: "Is treatment with antidepressants at doses approved in Japan effective for Japanese patients with MDD?" It is crucial to confirm this in order to provide appropriate treatments for Japanese patients with major depressive disorder (MDD). Therefore, we conducted a systematic review and random-effects pairwise meta-analysis including these nine double-blind, randomized, placebo-controlled trials., Methods: We calculated the standardized mean difference (SMD) and risk ratio (RR) with a 95% confidence interval (95% CI)., Results: Pooled newer antidepressants outperformed placebo regarding improvement of depressive symptom scale scores [SMD (95% CI) = -0.20 (-0.27, -0.12), p < 0.00001], response to treatment [RR (95% CI) = 1.23 (1.13, 1.32), p < 0.00001], and remission rate [RR (95% CI) = 1.30 (1.16, 1.45), p < 0.00001]. Although all-cause discontinuation was not significantly different between the treatment groups, the pooled antidepressant group showed a higher discontinuation rate due to adverse event [RR (95% CI) = 1.60 (1.13, 2.26), p = 0.007] and a higher incidence of at least one adverse event than the placebo group [RR (95% CI) = 1.13 (1.08, 1.18), p < 0.00001]., Discussion: We concluded that newer antidepressants are effective for Japanese adults with MDD although the clinicians must monitor the health conditions of these individuals., (© 2023 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Transform-limited photon emission from quantum emitters is essential for high-fidelity entanglement generation. In this Letter, we report the coherent optical property of a single negatively charged lead-vacancy (PbV) center in diamond. Photoluminescence excitation measurements reveal stable fluorescence with a linewidth of 39 MHz at 6 K, close to the transform limit estimated from the lifetime measurement. We observe 4 orders of magnitude different linewidths of the two zero-phonon lines, and find that the phonon-induced relaxation in the ground state contributes to this huge difference in the linewidth. Because of the suppressed phonon absorption in the PbV center, we observe nearly transform-limited photon emission up to 16 K, demonstrating its high temperature robustness compared to other color centers in diamond.

Dearomative intramolecular Diels-Alder/sulfur extrusion reaction of thiophenes with alkynes successfully afforded fluoranthenes in moderate to excellent yields. The proximity of both reactive sites fixed at the peri-position of naphthalene would play an important role in the progress of this reaction. Tri(o-tolyl)phosphine effectively suppressed the side reactions as a sulfur scavenger., (© 2023 Wiley-VCH GmbH.)

Background: Periprosthetic bone loss following total hip arthroplasty (THA) threatens prosthesis stability. This systematic review and network meta-analysis aimed to compare the efficacy of anti-osteoporotic drugs for measures of hip function according to functional outcomes, periprosthetic femoral bone mineral density loss in each Gruen zone, and revision surgery after THA., Methods: The systematic search of six literature databases was conducted in December 2021 in accordance with PRISMA guidelines. Adult participants who underwent primary THA were included. A random-effects network meta-analysis was performed within a frequentist framework, and the confidence in the evidence for each outcome was evaluated using the CINeMA tool, which assessed the credibility of results from the network meta-analysis. We included 22 randomized controlled trials (1243 participants) comparing the efficacy and safety of bisphosphonates (including etidronate, clodronate, alendronate, risedronate, pamidronate, and zoledronate), denosumab, selective estrogen receptor modulator, teriparatide, calcium + vitamin D, calcium, and vitamin D. We defined the period for revision surgery as the final follow-up period., Results: Raloxifene, bisphosphonate, calcium + vitamin D, and denosumab for prosthetic hip function might have minimal differences when compared with placebos. The magnitude of the anti-osteoporotic drug effect on periprosthetic femoral bone loss varied across different Gruen zones. Bisphosphonate, denosumab, teriparatide might be more effective than placebo in Gruen zone 1 at 12 months after THA. Additionally, bisphosphonate might be more effective than placebo in Gruen zones 2, 5, 6, and 7 at 12 months after THA. Denosumab was efficacious in preventing bone loss in Gruen zones 6 and 7 at 12 months after THA. Teriparatide was likely to be efficacious in preventing bone loss in Gruen zone 7 at 12 months after THA. Raloxifene was slightly efficacious in preventing bone loss in Gruen zones 2 and 3 at 12 months after THA. Calcium was slightly efficacious in preventing bone loss in Gruen zone 5 at 12 months after THA. None of the studies reported revision surgery., Conclusions: Bisphosphonate and denosumab may be effective anti-osteoporotic drugs for preventing periprosthetic proximal femoral bone loss due to stress shielding after THA, particularly in cementless proximal fixation stems, which are the most commonly used prostheses worldwide., Competing Interests: Declaration of competing interest The first author would like to declare that they received financial support in the form of J&J Medical Research Grant. However, this financial assistance has not directly or indirectly influenced the work submitted for publication in Journal of Orthopaedic Science. The funding was utilized solely for the purpose of data collection and analysis of the manuscript. There are no other financial or non-financial competing interests that the author needs to disclose., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Disclosures Dr Hosokawa reports personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, and Pfizer, outside the submitted work. Dr Taniguchi reports grants from Janssen Pharmaceutical and Nippon Shinyaku; and personal fees from Janssen Pharmaceutical and Nippon Shinyaku, outside the submitted work. Dr Ikeda reports personal fees from Daiichi-Sankyo, Bayer Yakuhin, and Bristol-Myers Squibb, outside the submitted work. Dr Inami reports personal fees from Janssen Pharmaceutical and Bayer Yakuhin, outside the submitted work. Dr Murohara reports a grant and personal fees from Daiichi Sankyo, outside the submitted work. Dr Hatano reports a grant from Japan Agency for Medical Research and Development and personal fees from Janssen Pharmaceutical and Bayer Yakuhin, outside the submitted work. Dr Tamura reports grants from Bayer Yakuhin, Nippon Shinyaku, and Mochida Pharmaceutical; and personal fees from Bayer Yakuhin, Nippon Shinyaku, Daiichi Sankyo, and Janssen Pharmaceutical, outside the submitted work. Dr Yamashita reports a grant from Abbott Vascular Japan; and personal fees from Kaneka Medix, Boston Scientific Japan, Nihon Kohden, Philips Japan, Janssen Pharmaceutical, and Bayer Yakuhin, outside the submitted work. Dr Tsujino reports personal fees from Janssen Pharmaceutical and Nippon Shinyaku; and affiliation with the division supported by endowments from Nippon Shinyaku, Nippon Boehringer Ingelheim, and Mochida Pharmaceutical, outside the submitted work. Dr Yaoita reports personal fees from Bayer Yakuhin and Konica Minolta, outside the submitted work. Dr Minatsuki reports a grant from Fukuda Foundation for Medical Technology, outside the submitted work. Dr Todaka reports a grant from Mochida Pharmaceutical; and personal fee from Bayer Yakuhin, outside the submitted work. Dr Fukuda reports grants from Bayer Yakuhin, Daiichi Sankyo, Nippon Boehringer Ingelheim, Pfizer, Eisai, Janssen Pharmaceutical, Nippon Shinyaku, GlaxoSmithKline, and Mochida Pharmaceutical; and personal fees from Bayer Yakuhin, Daiichi Sankyo, Nippon Boehringer Ingelheim, Pfizer, Eisai, Janssen Pharmaceutical, Nippon Shinyaku, GlaxoSmithKline, and Mochida Pharmaceutical, outside the submitted work. Dr Tsutsui reports grants from Mitsubishi Tanabe Pharma, IQVIA Services Japan, MEDINET, Medical Innovation Kyushu, Kowa, Daiichi Sankyo, Johnson & Johnson, NEC, and Nippon Boehringer Ingelheim; personal fees from Novartis Pharma, Ono Pharmaceutical, Nippon Boehringer Ingelheim, Bayer Yakuhin, Kowa, Teijin Pharma, Mitsubishi Tanabe Pharma, Pfizer Japan, Daiichi Sankyo, Novartis Pharma, Janssen Pharmaceutical, Pfizer Japan, Bayer Yakuhin, Otsuka Pharmaceutical, AstraZeneca, and Nippon Rinsho; and is Chairman of Japan Heart Failure Society, outside the submitted work. Dr Abe reports a grant from Konica Minolta and Daiichi Sankyo, outside the submitted work. Drs Watanabe, Yasuda, Kobayakawa, Adachi, and Tatsumi report no conflicts of interest.