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Triangulenes as neutral radicals are becoming promising candidates for future applications such as spintronics and quantum technologies. To extend the potential of the advanced materials, it is of importance to control their electronic and magnetic properties by multiple graphitic nitrogen doping. Here, we synthesize triaza[5]triangulene on Au(111) by cyclodehydrogenation, and its derivatives by cleaving C-N bonds. Bond-resolved scanning tunneling microscopy and scanning tunneling spectroscopy provided detailed structural information and evidence for open-shell singlet ground state. The antiferromagnetic arrangement of the spins in positively doped triaza[5]triangulene was further confirmed by density function theory calculations. The key aspect of triangulenes with multiple graphitic nitrogen is the extra p z electrons composing the π orbitals, favoring charge transfer to the substrate and changing their low-energy excitations. Our findings pave the way for the exploration of exotic low-dimensional quantum phases of matter in heteroatom doped organic systems., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Scorpion venom contains linear peptides without disulfide bonds in addition to peptides with disulfide bonds. Many such linear peptides have an amphiphilic α-helical structure, often with antimicrobial activity and can be classified into three groups based on their molecular size. Among them, long-chain antimicrobial peptides consisting of more than 40 residues have not been thoroughly studied due to the difficulty of synthesizing them. We have previously reported a transcriptome analysis of the venom gland of Liocheles australasiae that revealed precursor sequences of long-chain antimicrobial peptides. In the study reported here, we identified the mature structure of one such long-chain antimicrobial peptide, LaCT1, which we synthesized using chemical ligation to confirm its structure and evaluate its biological activities. The result showed that LaCT1 exhibited significant antimicrobial activity. In addition, we identified its partial peptides consisting of an N- or C-terminal region, which may be generated by enzymatic cleavage in the venom. Among them, only the peptide containing the N-terminal half region was active. LaCT1 also not only showed insecticidal activity but also synergistically enhanced the effects of another insecticidal peptide identified in L. australasiae venom as well. These results provide insights into the role of antimicrobial peptides in scorpion venom., (© 2024 European Peptide Society and John Wiley & Sons Ltd.)

Camurati-Engelmann disease (CED) is an autosomal dominant bone dysplasia characterized by progressive hyperostosis of the skull base and diaphyses of the long bones. CED is further divided into two subtypes, CED1 and CED2, according to the presence or absence of TGFB1 mutations, respectively. In this study, we used exome sequencing to investigate the genetic cause of CED2 in three pedigrees and identified two de novo heterozygous mutations in TGFB2 among the three patients. Both mutations were located in the region of the gene encoding the straitjacket subdomain of the latency-associated peptide (LAP) of pro-TGF-β2. Structural simulations of the mutant LAPs suggested that the mutations could cause significant conformational changes and lead to a reduction in TGF-β2 inactivation. An activity assay confirmed a significant increase in TGF-β2/SMAD signaling. In vitro osteogenic differentiation experiment using iPS cells from one of the CED2 patients showed significantly enhanced ossification, suggesting that the pathogenic mechanism of CED2 is increased activation of TGF-β2 by loss-of-function of the LAP. These results, in combination with the difference in hyperostosis patterns between CED1 and CED2, suggest distinct functions between TGFB1 and TGFB2 in human skeletal development and homeostasis., (© 2024. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

The diazo group is an important functional group in organic synthesis because it confers high reactivity to the compounds and has been applied in various chemical reactions, such as the Sandmeyer reaction, Wolff rearrangement, cyclopropanation, and C-N bond formation with active methylene compounds. Previously, we revealed that 3-diazoavenalumic acid (3-DAA), which is potentially produced by several actinomycete species and contains an aromatic diazo group, is a biosynthetic intermediate of avenalumic acid. In this study, we aimed to construct a production system for phenyldiazene derivatives by adding several active methylene compounds to the culture of a 3-DAA-producing recombinant actinomycete. First, acetoacetanilide and its derivatives, which have an active methylene and are raw materials for arylide yellow dyes, were individually added to the culture of a 3-DAA-producing actinomycete. When their metabolites were analyzed, each expected compound with a phenyldiazenyl moiety was detected in the culture extract. Moreover, we established a one-pot in vitro enzymatic production system for the same phenyldiazene derivatives using a highly reactive diazotase, CmaA6. These results showed that the diazo group of natural products is an attractive tool for expanding the structural diversity of natural products both in vivo and in vitro., (© 2024 Wiley‐VCH GmbH.)

Objective The current standard treatment for locally advanced, unresectable stage III non-small-cell lung cancer (NSCLC) is concurrent chemoradiation therapy (CCRT) and durvalumab administration. Although reports have indicated that the prognosis of squamous cell carcinoma is poorer than that of adenocarcinoma, real-world data are currently inadequate. Methods The present study analyzed patients with stage III NSCLC who received CCRT at the study center between April 2018 and February 2022. These patients were retrospectively classified into adenocarcinoma and squamous cell carcinoma groups for an analysis of the progression-free survival (PFS), overall survival (OS), and patient background factors, including the age, performance status, smoking history, and pre-CCRT laboratory data. Results A total of 109 patients were included for the analysis; 25 were excluded, and 44 and 40 patients were classified into the adenocarcinoma and squamous cell carcinoma groups, respectively. The median PFS was significantly longer in the adenocarcinoma group than in the squamous cell carcinoma group [27.9 (95% confidence interval (CI): 15.2-not achieved) vs. 9.63 (95% CI: 5.88-13.9) months; p<0.01]. Similarly, the median OS was significantly longer in the adenocarcinoma group than in the squamous cell carcinoma group [not achieved (95% CI: 48.1-not achieved) vs. 23.8 (95% CI; 14.6-not achieved) months; p<0.01]. In the multivariate Cox proportional hazard analysis, the histological type was the only prognostic factor for the PFS (p<0.05) and OS (p<0.05). Conclusion The median PFS and OS were poorer in patients with squamous cell carcinoma than in those with stage III NSCLC treated with CCRT and durvalumab. The histological type was an independent factor affecting the PFS and OS.

Background/aim: Patients with triple-negative breast cancer (TNBC) who obtain a pathological complete response (pCR) after neoadjuvant chemotherapy have an improved prognosis. Lymphocyte-predominant breast cancer is more likely to respond to neoadjuvant chemotherapy. Here, we investigated the correlation between tumor-infiltrating lymphocytes (TILs) in pre-treatment biopsy specimens from patients with TNBC in relation to response to NAC., Patients and Methods: The level of infiltration by immune cells expressing immune cell lineage surface markers (CD8, CD4, CD19, CD14, CD11c, and CD11b) in biopsy specimens from 52 patients with TNBC was examined using multispectral immunofluorescent labelling., Results: The level of CD8-positive TILs was significantly higher in patients with a pCR (p=0.045). The Cox proportional hazard model confirmed that lymph node involvement was associated with poorer disease-free survival (p=0.008). A high level of CD8-positive TILs was related to significantly prolonged disease-free survival in patients with node-positive TNBC (p=0.018)., Conclusion: Assessing infiltration by CD8-positive TILs in the primary tumor is a useful biomarker to predict pCR and improved outcome in patients with node-positive TNBC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Understanding how carbon dioxide (CO 2 ) behaves and interacts with surfaces is paramount for the development of sensors and materials to attempt CO 2 mitigation and catalysis. Here, we combine simultaneous atomic force microscopy (AFM) and scanning tunneling microscopy (STM) using CO-functionalized probes with density functional theory (DFT)-based simulations to gain fundamental insight into the behavior of physisorbed CO 2 molecules on a gold(111) surface that also contains one-dimensional metal-organic chains formed by 1,4-phenylene diisocyanide (PDI) bridged by gold (Au) adatoms. We resolve the structure of self-assembled CO 2 islands, both confined between the PDI-Au chains as well as free-standing on the surface and reveal a chiral arrangement of CO 2 molecules in a windmill-like structure that encloses a standing-up CO 2 molecule and other foreign species existing at the surface. We identify these species by the comparison of height-dependent AFM and STM imaging with DFT-calculated images and clarify the origin of the kagome tiling exhibited by this surface system. Our results show the complementarity of AFM and STM using functionalized probes and their potential, when combined with DFT, to explore greenhouse gas molecules at surface-supported model systems.

Background: Sarcopenia, characterized by muscle mass decline due to aging or other causes, is exacerbated by decreased estrogen levels after menopause in women. Isoflavones, a class of flavonoids acting on estrogen receptors, may have beneficial effects on metabolic disorders. We examined these effects in ovariectomized mice fed a high-fat, high-sucrose diet (HFHSD)., Methods: At 7 weeks old, female C57BL6/J mice (18-20 g, n = 12) underwent bilateral ovariectomy (OVX), and were then fed a high-fat, high-sucrose diet starting at 8 weeks of age. Half of the mice received isoflavone water (0.1%). Metabolic analyses, including glucose and insulin tolerance tests, were conducted. Muscle analysis involved grip strength assays, next-generation sequencing, quantitative RT-PCR, and western blotting of skeletal muscle after euthanizing the mice at 14 weeks old. Additionally, 16S rRNA gene sequence analysis of the gut microbiota was performed., Results: The results demonstrated that isoflavone administration did not affect body weight, glucose tolerance, or lipid metabolism. In contrast, isoflavone-treated mice had higher grip strength. Gene expression analysis of the soleus muscle revealed decreased Trim63 expression, and western blotting showed inactivation of muscle-specific RING finger protein 1 in isoflavone-treated mice. Gut microbiota analysis indicated higher Bacteroidetes and lower Firmicutes abundance in the isoflavone group, along with increased microbiota diversity. Gene sets related to TNF-α signaling via NF-κB and unfolded protein response were negatively associated with isoflavones., Conclusions: Isoflavone intake alters gut microbiota and increases muscle strength, suggesting a potential role in improving sarcopenia in menopausal women., Competing Interests: Nakajima, H. received individual compensation from Kowa Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd. Nakanishi, N. received individual compensation from Kowa Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., Nippon Boehringer Ingelheim Co., Ltd., and TERUMO CORPORATION. Hamaguchi, M. received grants from AstraZeneca K.K., Ono Pharma Co., Ltd., and Kowa Pharmaceutical Co., Ltd.; and also received individual compensation from AstraZeneca K.K., Ono Pharma Co., Ltd., Eli Lilly Japan K.K., Sumitomo Dainippon Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Corp., Sanofi K.K., and Kowa Pharmaceutical Co., Ltd. outside of the submitted work. Fukui, M. received grants from Ono Pharma Co., Ltd., Oishi Kenko Inc., Yamada Bee Farm, Nippon Boehringer Ingelheim Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Co., Ltd., Astellas Pharma Inc., MSD K.K., Kyowa Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Kowa Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Eli Lilly Japan K.K., Taisho Pharmaceutical Co., Ltd., Terumo Corp., Teijin Pharma Ltd., Nippon Chemiphar Co., Ltd., Abbott Japan Co., Ltd., and Johnson & Johnson K.K. Medical Co., TERUMO CORPORATION, and also received individual compensation from Nippon Boehringer Ingelheim Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Co., Ltd., Astellas Pharma Inc., MSD K.K., Kyowa Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Kowa Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., Ono Pharma Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Eli Lilly Japan K.K., Taisho Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., AstraZeneca K.K., Mochida Pharmaceutical Co., Ltd., Abbott Japan Co., Ltd., Teijin Pharma Ltd., Arkray Inc., Medtronic Japan Co., Ltd., and Nipro Corp., TERUMO CORPORATION, outside of the submitted work. Sasano, R. was employed by the company AiSTI SCIENCE Co., Ltd. The remaining 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.

Background: Absolute lymphocyte count (ALC) is a predictive and prognostic factor for various tumor types, including breast cancer. Palbociclib is a CDK4/6 inhibitor widely used for the treatment of metastatic estrogen receptor (ER)-positive, HER2-negative breast cancer. However, predictive biomarkers of the efficacy of palbociclib remain unelucidated. We conducted a retrospective study to examine the predictive value of the baseline ALC in patients treated with palbociclib., Methods: The medical records of patients with ER-positive, HER2-negative breast cancer treated with palbociclib plus hormonal therapy between December 2017 and December 2021 were analyzed retrospectively. The cutoff value of ALC was set at 1800 cells/μL at the initiation of palbociclib treatment. The clinical benefit rate (CBR) was defined as the rate of complete or partial response or stable disease for at least 6 months. Progression-free survival (PFS) rates were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses were performed using Cox proportional hazards regression., Results: All of the 202 patients were women, with a median age of 59 years and a performance status (PS) of ≤ 2. The median numbers of lines of chemotherapy and endocrine therapy before palbociclib treatment were 0 (range, 0-9) and 1 (range, 0-7), respectively. Fifty-one patients had liver metastases. Forty-six patients tested negative for progesterone receptor (PgR) expression. The median follow-up time was 9.1 months. The CBR was significantly higher in the ALC-high group than in the ALC-low group (79% vs. 60%; P = 0.018). The median PFS was significantly longer in the ALC-high group than in the ALC-low group (26.8 months vs. 8.4 moths, respectively; P = 0.000013). ALC, age, PS, PgR status, prior chemotherapy, prior endocrine therapy, and liver metastasis were entered into the multivariate analysis. ALC was identified as an independent factor for PFS (P = 0.00085), along with liver metastasis (P = 0.0020), PS (P = 0.026), and prior endocrine therapy (P = 0.019)., Conclusion: ALC can serve as a predictor of palbociclib efficacy in patients with metastatic ER-positive, HER2-negative breast cancer., (© 2024. The Author(s).)

Background: Sarcopenic obesity, which is associated with a poorer prognosis than that of sarcopenia alone, may be positively affected by soy isoflavones, known inhibitors of muscle atrophy. Herein, we hypothesize that these compounds may prevent sarcopenic obesity by upregulating the gut metabolites with anti-inflammatory effects., Methods: To explore the effects of soy isoflavones on sarcopenic obesity and its mechanisms, we employed both in vivo and in vitro experiments. Mice were fed a high-fat, high-sucrose diet with or without soy isoflavone supplementation. Additionally, the mouse C2C12 myotube cells were treated with palmitic acid and daidzein in vitro., Results: The isoflavone considerably reduced muscle atrophy and the expression of the muscle atrophy genes in the treated group compared to the control group ( Fbxo32 , p = 0.0012; Trim63 , p < 0.0001; Foxo1 , p < 0.0001; Tnfa , p = 0.1343). Elevated levels of daidzein were found in the muscles and feces of the experimental group compared to the control group (feces, p = 0.0122; muscle, p = 0.0020). The real-time PCR results demonstrated that the daidzein decreased the expression of the palmitate-induced inflammation and muscle atrophy genes in the C2C12 myotube cells ( Tnfa , p = 0.0201; Il6 , p = 0.0008; Fbxo32 , p < 0.0001; Hdac4 , p = 0.0002; Trim63 , p = 0.0114; Foxo1 , p < 0.0001). Additionally, it reduced the palmitate-induced protein expression related to the muscle atrophy in the C2C12 myotube cells ( Foxo1 , p = 0.0078; MuRF1, p = 0.0119)., Conclusions: The daidzein suppressed inflammatory cytokine- and muscle atrophy-related gene expression in the C2C12 myotubes, thereby inhibiting muscle atrophy.

Brown algae are one of the most abundant biomasses on Earth. To recycle them as blue carbon sources, an effective decomposition system is necessary. This study focused on microorganisms present in seawater that decompose brown algae which contain laminarin and alginate. Where Undaria and Sargassum spp. were present, genera Psychromonas, Psychrobacter, and Pseudoalteromonas were predominant in seawater, while genera Arcobacter and Fusobacterium increased in abundance during the process of decomposition. The inoculation of Undaria samples into laminarin-minimal media led to a predominance of Pseudoalteromonas species. A Pseudoalteromonas isolate, identified as Pseudoalteromonas distincta, possesses genes encoding a putative laminarinase, polysaccharide lyase family 6 (PL6) alginate lyases, and a PL7 alginate lyase. The culture media of P. distincta contained no monosaccharides, suggesting the rapid conversion of polysaccharides to metabolites. These findings indicated that Pseudoalteromonas species play a major role in the decomposition of brown algae and affect the microbiota associated with them., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Fibroblast growth factor (FGF) 21, a hormone produced by the liver, improves glucose and lipid metabolism. We recently demonstrated that the FGF21 gene (Fgf21) underwent DNA demethylation in the mouse liver via peroxisome proliferator-activated receptor (PPAR) α during the fetal to lactation periods. Furthermore, we found that the DNA methylation state of Fgf21 was involved in obesity in adult animals. In the present study, we analyzed the DNA methylation state of the FGF21 gene (FGF21) in obese patients using genomic DNA extracted from human monocytes and macrophages and investigated the pathophysiological significance of the FGF21 expression response to pemafibrate (PM), a PPARα ligand. We examined 67 patients with obesity stratified into in- and outpatient cohorts. A positive correlation was observed between serum FGF21 levels and triglyceride (TG) levels before PM administration. However, changes in serum FGF21 levels following PM administration did not correlate with the FGF21 DNA methylation rate, except at one CpG site. The body mass index (BMI) and serum TG levels positively correlated with the FGF21 DNA methylation rate, particularly at different CpG positions. A negative correlation was observed between absolute changes in serum FGF21 levels and the ratio of change in serum TG levels after PM administration. Collectively, these results indicate the potential of FGF21 DNA methylation as a surrogate indicator of BMI and serum TG levels, while absolute changes in serum FGF21 levels after PM administration may offer prognostic insights into the efficacy of reducing serum TG levels through PM administration.

Doxepin is an antihistamine and tricyclic antidepressant that binds to the histamine H 1 receptor (H 1 R) with high affinity. Doxepin is an 85:15 mixture of the E- and Z-isomers. The Z-isomer is well known to be more effective than the E-isomer, whereas based on the crystal structure of the H 1 R/doxepin complex, the hydroxyl group of Thr112 3.37 is close enough to form a hydrogen bond with the oxygen atom of the E-isomer. The detailed binding characteristics and reasons for the differences remain unclear. In this study, we analyzed doxepin isomers bound to the receptor following extraction from a purified H 1 R protein complexed with doxepin. The ratio of the E- and Z-isomers bound to wild-type (WT) H 1 R was 55:45, indicating that the Z-isomer was bound to WT H 1 R with an approximately 5.2-fold higher affinity than the E-isomer. For the T112 3.37 V mutant, the E/Z ratio was 89:11, indicating that both isomers have similar affinities. Free energy calculations using molecular dynamics (MD) simulations also reproduced the experimental results of the relative binding free energy differences between the isomers for WT and T112 3.37 V. Furthermore, MD simulations revealed that the hydroxyl group of T112 3.37 did not form hydrogen bonds with the E-isomer, but with the adjacent residues in the binding pocket. Analysis of the receptor-bound doxepin and MD simulations suggested that the hydroxyl group of T112 3.37 contributes to the formation of a chemical environment in the binding pocket, which is slightly more favorable for the Z-isomer without hydrogen bonding with doxepin., (© 2024 The Author(s). Journal of Molecular Recognition published by John Wiley & Sons Ltd.)

Objectives: The objectives were to investigate the clinical characteristics and course of long COVID, defined as the persistence of symptoms at least one month after the onset of COVID-19, in outpatients and to clarify differences in symptoms between SARS CoV-2 mutant strains. Methods: Our observational study in a primary care institution in Japan included 1053 patients with long COVID who visited our outpatient clinic between April 2021 and March 2023. Symptom distribution, performance status, and patient background at the time of the first outpatient visit were compared between infectious strains (Delta and before group and Omicron group). Background factors and symptoms related to time to remission were also analyzed. Results: The severity of COVID-19 in the acute phase was mild, moderate, and severe in 82.2%, 14.9%, and 2.9% in the Delta and before group; and in 97.6%, 1.7%, and 0.4% in the Omicron group, respectively. Vaccination coverage was significantly different between the Delta and before (37.1%) and Omicron groups (73.1%) ( p < 0.001), probably due to the period of vaccine unavailability in the former group. Symptoms of fatigue and headache occurred most frequently, irrespective of infectious strain. The mean number of symptoms per patient was significantly higher in the Delta and before group than the Omicron group (3.4 vs. 2.7, p < 0.0001). The median time overall to remission of long COVID was 169 days. Cox hazard model analysis identified female sex, high body mass index, and dyspnea (but not infectious strain) as significant factors prolonging the time to remission ( p < 0.05). Conclusions: Differences in the number of symptoms between infectious strains may be related to differences in viral virulence and/or vaccination coverage. However, the clinical course was found to be minimally influenced by the infectious strain. The present results should improve the understanding of prognosis in patients with long COVID from both the clinical and social perspectives.

Background: We previously demonstrated that higher simple guideline-directed medical therapy (GDMT) scores (comprising renin-angiotensin system inhibitors, β-blockers, mineralocorticoid antagonists, and sodium-glucose cotransporter 2 inhibitors) at discharge were correlated with improved prognosis in heart failure (HF) patients. HF readmissions are linked to adverse outcomes, emphasizing the need for enhanced optimization of GDMT., Methods and Results: Using the simple GDMT score, we evaluated the effect of revising and modifying in-hospital GDMT on the prognosis of patients with HF readmissions. In this retrospective analysis of 2,100 HF patients, we concentrated on 1,222 patients with HF with reduced ejection/moderately reduced ejection fraction, excluding patients with HF with preserved ejection fraction, on dialysis, or who died in hospital. A higher current GDMT score was associated with better HF prognosis. Of the 1,222 patients in the study, we analyzed 372 cases of rehospitalization, calculating the simple GDMT scores at admission and discharge. Patients were divided into groups according to score improvement. Multivariate analysis showed a significant association between improved in-hospital simple GDMT score and the composite outcome (HF readmission+all-cause mortality; hazard ratio 0.459; 95% confidence interval 0.257-0.820; P=0.008). Even after propensity score matching to adjust for background, among rehospitalized patients, those with an improved in-hospital simple GDMT score had a better prognosis., Conclusions: Our results highlight the potential of robust interventions and score elevation during hospitalization leading to improved outcomes.

The interplay between the molecular shape and the intermolecular interaction plays a decisive role in self-assembled structures. Recently, inherent randomness of low ordered assemblies, resulting from lack of short- and long-range periodicities, has attracted significant attention due to the unique structural, electronic, and mechanical properties. Here, we present procrystalline self-assemblies of pentaphenyl cyclopentadienyl derivatives on Ag(111) and Au(111) with scanning tunneling microscopy, operating at 4.3 K under ultrahigh vacuum conditions. Two examples, using 5-fold symmetric molecules substituted with methyl or fluorine groups, show that weak interactions, such as π-π stacking, CH-π interactions, and CH···F hydrogen bonding, play a pivotal role in formation of the procrystalline assembly. Our results may give insights into the intricate relationship between the molecular shape and the intermolecular interaction in the formation of non-crystalline assemblies.

Malaria remains a significant global public health concern, with a recent increase in the number of zoonotic malaria cases in Southeast Asian countries. However, limited reports on the vector for zoonotic malaria exist owing to difficulties in detecting parasite DNA in Anopheles mosquito vectors. Herein, we demonstrate for the first time that several Anopheles mosquitoes contain simian malaria parasite DNA using droplet digital PCR (ddPCR), a highly sensitive PCR method. An entomological survey was conducted to identify simian malaria vector species at Phra Phothisat Temple (PPT), central Thailand, recognized for a high prevalence of simian malaria in wild cynomolgus macaques. A total of 152 mosquitoes from six anopheline species were collected and first analyzed by a standard 18S rRNA nested-PCR analysis for malaria parasite which yielded negative results in all collected mosquitoes. Later, ddPCR was used and could detect simian malaria parasite DNA, i.e. Plasmodium cynomolgi, in 25 collected mosquitoes. And this is the first report of simian malaria parasite DNA detection in Anopheles sawadwongporni. This finding proves that ddPCR is a powerful tool for detecting simian malarial parasite DNA in Anopheles mosquitoes and can expand our understanding of the zoonotic potential of malaria transmission between monkeys and humans., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Microvascular invasion (MVI) is a risk factor for postoperative recurrence of hepatocellular carcinoma (HCC), even in early-stage HCC. In small HCC ≤ 3 cm, treatment options include anatomical resection or non-anatomical resection, and MVI has a major effect on treatment decisions. We aimed to identify the predictors of MVI in small HCC ≤ 3 cm., Methods: We retrospectively studied 129 patients with very early or early-stage HCC ≤ 3 cm who had undergone 18 F-fluorodeoxyglucose positron emission tomography/computed tomography and subsequent hepatic resection from January 2016 to August 2023. These patients were divided into the derivation cohort (n = 86) and validation cohort (n = 43). We examined the risk factors for MVI using logistic regression analysis, and established a predictive scoring system in the derivation cohort. We evaluated the accuracy of our scoring system in the validation cohort., Results: In the derivation cohort, a Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), prothrombin induced by vitamin K deficiency or antagonist-II (PIVKA-II), and metabolic tumor volume (MTV) were independent predictors of MVI. We established the scoring system using these three factors. In the validation test, there were no MVI-positive cases with a score of 0 and 1, and all cases were MVI-positive with a score of 4. Moreover, with a score ≥ 2, the sensitivity, specificity, and accuracy of our scoring system were 100%, 71.4%, and 81.4%, respectively., Conclusions: Our scoring system can accurately predict MVI in small HCC ≤ 3 cm, and could contribute to establishing an appropriate treatment strategy., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Lipid mediators have been suggested to play important roles in the pathogenesis of rheumatoid arthritis (RA). Lipidomics has recently allowed for the comprehensive analysis of lipids and has revealed the potential of lipids as biomarkers for the early diagnosis of RA and prediction of therapeutic responses. However, the relationship between disease activity and the lipid profile in RA remains unclear. In the present study, we performed a plasma lipidomic analysis of 278 patients with RA during treatment and examined relationships with disease activity using the Disease Activity Score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR). In all patients, five lipids positively correlated and seven lipids negatively correlated with DAS28-ESR. Stearic acid [FA(18:0)] (r = -0.45) and palmitic acid [FA(16:0)] (r = -0.38) showed strong negative correlations. After adjustments for age, body mass index (BMI), and medications, stearic acid, palmitic acid, bilirubin, and lysophosphatidylcholines negatively correlated with disease activity. Stearic acid inhibited osteoclast differentiation from peripheral blood monocytes in in vitro experiments, suggesting its contribution to RA disease activity by affecting bone metabolism. These results indicate that the lipid profile correlates with the disease activity of RA and also that some lipids may be involved in the pathogenesis of RA., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Little is known about how to effectively increase bystander cardiopulmonary resuscitation (CPR), so we evaluated the 10-year trend of the proportion of bystander CPR in an area with wide dissemination of chest compression-only CPR (CCCPR) training combined with conventional CPR training., Methods and results: We conducted a descriptive study after a community intervention, using a prospective cohort from September 2010 to December 2019. The intervention consisted of disseminating CCCPR training combined with conventional CPR training in Toyonaka City since 2010. We analyzed all non-traumatic out-of-hospital cardiac arrest (OHCA) patients resuscitated by emergency medical service personnel. The primary outcome was the trend of the proportion of bystander CPR. We conducted multivariate logistic regression models and assessed the adjusted odds ratio (AOR) using a 95% confidence interval (CI) to determine bystander CPR trends. Since 2010, we have trained 168,053 inhabitants (41.9% of the total population of Toyonaka City). A total of 1,508 OHCA patients were included in the analysis. The proportion of bystander CPR did not change from 2010 (43.3%) to 2019 (40.0%; 1-year incremental AOR 1.02 [95% CI: 0.98-1.05])., Conclusions: The proportion of bystander CPR did not increase even after wider dissemination of CPR training. In addition to continuing wider dissemination of CPR training, other strategies such as the use of technology are necessary to increase bystander CPR.

Anoxygenic photosynthesis is diversified into two classes: chlorophototrophy based on a bacterial type-I or type-II reaction center (RC). Whereas the type-I RC contains both bacteriochlorophyll and chlorophyll, type-II RC-based phototrophy relies only on bacteriochlorophyll. However, type-II phototrophic bacteria theoretically have the potential to produce chlorophyll a by the addition of an enzyme, chlorophyll synthase, because the direct precursor for the enzyme, chlorophyllide a, is produced as an intermediate of BChl a biosynthesis. In this study, we attempted to modify the type-II proteobacterial phototroph Rhodovulum sulfidophilum to produce chlorophyll a by introducing chlorophyll synthase, which catalyzes the esterification of a diterpenoid group to chlorophyllide a thereby producing chlorophyll a. However, the resulting strain did not accumulate chlorophyll a, perhaps due to absence of endogenous chlorophyll a-binding proteins. We further heterologously incorporated genes encoding the type-I RC complex to provide a target for chlorophyll a. Heterologous expression of type-I RC subunits, chlorophyll synthase, and galactolipid synthase successfully afforded detectable accumulation of chlorophyll a in Rdv. sulfidophilum. This suggests that the type-I RC can work to accumulate chlorophyll a and that galactolipids are likely necessary for the type-I RC assembly. The evolutionary acquisition of type-I RCs could be related to prior or concomitant acquisition of galactolipids and chlorophylls., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

A 66-year-old man presented to our institution with a positive fecal occult blood test and lower abdominal pain. Although a tumor was found in the sigmoid colon, biopsy and imaging studies failed to enable the diagnosis of the cancer, and the patient underwent surgery for treatment and diagnosis. The tumor had two distinct areas with differing features shown both histopathologically and on imaging; it was thus diagnosed as a leiomyosarcoma of the sigmoid colon with a pleomorphic component. Here, we describe a rare case of leiomyosarcoma of the sigmoid colon with a pleomorphic component. There are no reports of leiomyosarcoma with pleomorphic components arising in the colon in the literature; thus, the recurrence and metastatic characteristics are unknown. Therefore, accumulating cases in the literature may provide valuable insights into diagnosing and treating these rare tumors., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Introduction: Campylobacter spp. are a public health concern, yet there is still no effective vaccine or medicine available., Methods: Here, we developed a Campylobacter jejuni -specific antibody and found that it targeted a menaquinol cytochrome c reductase complex QcrC., Results: The antibody was specifically reactive to multiple C. jejuni strains including clinical isolates from patients with acute enteritis and was found to inhibit the energy metabolism and growth of C. jejuni . Different culture conditions produced different expression levels of QcrC in C. jejuni , and these levels were closely related not only to the energy metabolism of C. jejuni but also its pathogenicity. Furthermore, immunization of mice with recombinant QcrC induced protective immunity against C. jejuni infection., Discussion: Taken together, our present findings highlight a possible antibody- or vaccination-based strategy to prevent or control Campylobacter infection by targeting the QcrC-mediated metabolic pathway., 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 Hosomi, Hatanaka, Hinenoya, Adachi, Tojima, Furuta, Uchiyama, Morita, Nagatake, Saika, Kawai, Yoshii, Kondo, Yamasaki and Kunisawa.)

Pyrola japonica, a member of the family Ericaceae, is a mixotroph that grows on forest floors and obtains carbon (C) from both its photosynthesis and its mycorrhizal fungi. Its mycorrhizal community is dominated by Russulaceae. However, the mechanism of its C acquisition and its flexibility are not well understood. Our aim was to assess the impact of disturbance of the mycorrhizal fungal communities on C acquisition by P. japonica. We repeatedly applied a fungicide (Benomyl) to soils around P. japonica plants in a broad-leaved forest of central Japan, in order to disturb fungal associates near roots. After fungicide treatment, P. japonica roots were collected and subjected to barcoding by next-generation sequencing, focusing on the ITS2 region. The rate of mycorrhizal formation and α-diversity did not significantly change upon fungicide treatments. Irrespective of the treatments, Russulaceae represented more than 80% of the taxa. Leaves and seeds of the plants were analysed for 13 C stable isotope ratios that reflect fungal C gain. Leaf and seed δ 13 C values with the fungicide treatment were significantly lower than those with the other treatments. Thus the fungicide did not affect mycorrhizal communities in the roots, but disturbed mycorrhizal fungal pathways via extraradical hyphae, and resulted in a more photosynthetic behaviour of P. japonica for leaves and seeds., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Sarcopenia is a poor prognostic factor in cancer patients. In recent years, there have been reports that serum creatinine and cystatin C (Cr/CysC) ratio is associated with sarcopenia. However, the prognostic value of the Cr/CysC ratio in biliary tract cancer is unclear. We evaluated the impact of the Cr/CysC ratio on sarcopenia and prognosis in biliary tract cancer., Methods: We retrospectively reviewed the records of 190 patients with biliary tract cancer who had undergone surgical resection from January 2017 to March 2023. Frozen serum samples collected at the time of surgery were used to measure CysC. We calculated the Cr/CysC ratio and investigated the relationship with sarcopenia and the prognostic significance., Results: We calculated the cutoff value of the Cr/CysC ratio for low skeletal muscle index (SMI) (< 42 cm 2 /m 2 for males and < 38 cm 2 /m 2 for females). The optimal cutoff value of the Cr/CysC ratio was 0.848. The low Cr/CysC ratio group was significantly associated with higher preoperative CRP and lower albumin, lower SMI, lower handgrip strength, and higher intramuscular adipose tissue content. In multivariate analysis, patients with a low Cr/CysC ratio showed poorer overall survival (hazard ratio 2.60, 95% confidence interval 1.07-6.29, p = 0.033), which was significantly worse than in those with a high Cr/CysC ratio., Conclusions: In patients with biliary tract cancer, the Cr/CysC ratio showed weak correlation with sarcopenic indicators. However, the Cr/CysC ratio could be strong prognostic factor in biliary tract cancer., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Coronary artery spasms related to atrial fibrillation ablation procedures could cause lethal ventricular fibrillation or cardiopulmonary arrest. It may be useful to try intravenous atropine sulfate while preparing urgent coronary artery angiography in hemodynamically unstable coronary artery spasms cases to prevent development of the lethal arrhythmias., Competing Interests: The authors declare no conflict of interests for this article., (© 2024 The Author(s). Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

The Plasmodium life cycle involves differentiation into multiple morphologically distinct forms, a process regulated by developmental stage-specific gene expression. Histone proteins are involved in epigenetic regulation in eukaryotes, and the histone variant H3.3 plays a key role in the regulation of gene expression and maintenance of genomic integrity during embryonic development in mice. However, the function of H3.3 through multiple developmental stages in Plasmodium remains unknown. To examine the function of H3.3, h3.3-deficient mutants (Δh3.3) were generated in P. berghei. The deletion of h3.3 was not lethal in blood stage parasites, although it had a minor effect of the growth rate in blood stage; however, the in vitro ookinete conversion rate was significantly reduced, and the production of the degenerated form was increased. Regarding the mosquito stage development of Δh3.3, oocysts number was significantly reduced, and no sporozoite production was observed. The h3.3 gene complemented mutant have normal development in mosquito stage producing mature oocysts and salivary glands contained sporozoites, and interestingly, the majority of H3.3 protein was detected in female gametocytes. However, Δh3.3 male and female gametocyte production levels were comparable to the wild-type levels. Transcriptome analysis of Δh3.3 male and female gametocytes revealed the upregulation of several male-specific genes in female gametocytes, suggesting that H3.3 functions as a transcription repressor of male-specific genes to maintain sexual identity in female gametocytes. This study provides new insights into the molecular biology of histone variants H3.3 which plays a critical role on zygote-to-oocyst development in primitive unicellular eukaryotes., (Copyright © 2024. Published by Elsevier B.V.)

As a strategy for the primary Norwood operation, the right ventricular-pulmonary artery shunt is associated with satisfactory early outcome. However, use of this shunt after bilateral pulmonary artery banding remains controversial. This study compared the operative outcomes and late hemodynamics in patients who underwent the Norwood operation, preceded by bilateral pulmonary artery banding, with a right ventricular-pulmonary artery shunt or with bidirectional Glenn anastomosis (comprehensive stage II strategy). We retrospectively reviewed 38 patients who underwent the Norwood operation preceded by bilateral pulmonary artery banding between 2004 and 2017. Of these, 17 underwent the Norwood operation with a right ventricular-pulmonary artery shunt (Group S), whereas 21 underwent the comprehensive stage II strategy (Group G). 5 years after the Norwood operation, 10 (60%) and 17 (81%) patients in Group S and Group G, respectively, underwent the Fontan procedure. Group S showed significantly lower pressure in the superior vena cava after bidirectional Glenn anastomosis than Group G (13 ± 2 mmHg vs. 18 ± 3 mmHg; p < 0.01), but pressures were similar after the Fontan procedure. The right ventricular end-diastolic volume at 1 year post-Fontan procedure was significantly higher in Group S than in Group G (142 ± 41% vs. 91 ± 28%; p < 0.01). In terms of early outcomes, the Norwood operation with a right ventricular-pulmonary artery shunt enabled low pressure in the superior vena cava, but in the long term, this shunt adversely influenced the right ventricular volume., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

π-Conjugated molecules are viewed as fundamental components in forthcoming molecular nanoelectronics in which semiconducting functional units are linked to each other via metallic molecular wires. However, it is still challenging to construct such block cooligomers on the surface. Here, we present a synthesis of [18]-polyene-linked Zn-porphyrin cooligomers via a two-step reaction of the alkyl groups on Cu(111) and Cu(110). Nonyl groups (-C 9 H 19 ) substituted at the 5,15- meso positions of Zn-porphyrin were first transformed to alkenyl groups (-C 9 H 10 ) by dehydrogenation. Subsequently, homocoupling of the terminal -CH 2 groups resulted in the formation of extended [18]-polyene-linked porphyrin cooligomers. The structures of the products at each reaction step were investigated by bond-resolved scanning tunneling microscopy at low temperatures. A combination of angle-resolved photoemission spectroscopy and density functional theory calculations revealed the metallic property of the all trans [18]-polyene linker on Cu(110). This finding may provide an approach to fabricate complex nanocarbon structures on the surface.

We investigated the impact of the Coronavirus disease 2019 (COVID-19) pandemic on the management of endocrine and metabolic disorders in Japan. We conducted a cross-sectional nationwide questionnaire survey targeting board-certified endocrinologists under the auspices of the Japan Endocrine Society. The questionnaire consisted of multiple-choice questions and open-ended responses. Out of approximately 2,700 specialists, 528 (19.5%) opted to participate, suggesting a high level of interest in COVID-19 management among endocrinologists. The study found that almost half of participants had encountered cases of endocrine and metabolic disorders following COVID-19 infection or vaccination. Conditions related to thyroid diseases, glucose metabolism disorders/diabetes, and hypothalamic-pituitary disorders were particularly prevalent. Diabetes and obesity were identified as having high rates of severe cases or fatalities due to COVID-19. The study also highlighted challenges in routine diagnosis and treatment, emphasizing the potential benefits of combining remote consultations with in-person visits to optimize the frequency of examinations and check-ups during infectious disease outbreak which disrupts access to healthcare providers. The insights obtained from this survey are expected to contribute to ensuring appropriate healthcare provision for patients with endocrine and metabolic disorders by using flexible consultation formats, particularly even in the conditions where medical access may be limited due to future outbreaks of emerging or re-emerging infectious diseases.

Intestinal bacteria metabolize dietary substances to produce bioactive postbiotics, among which some are recognized for their role in promoting host health. We here explored the postbiotic potential of two omega-3 α-linolenic acid-derived metabolites: trans -10- cis -15-octadecadienoic acid (t10,c15-18:2) and cis -9- cis -15-octadecadienoic acid (c9,c15-18:2). Dietary intake of lipids rich in omega-3 α-linolenic acid elevated levels of t10,c15-18:2 and c9,c15-18:2 in the serum and feces of mice, an effect dependent on the presence of intestinal bacteria. Notably, t10,c15-18:2 mitigated skin inflammation in mice that became hypersensitive after exposure to 2,4-dinitrofluorobenzene, an experimental model for allergic contact dermatitis. In particular, t10,c15-18:2-but not c9,c15-18:2-attenuated ear swelling and edema, characteristic symptoms of contact hypersensitivity. The anti-inflammatory effects of t10,c15-18:2 were due to its ability to suppress the release of vascular endothelial growth factor A from keratinocytes, thereby mitigating the enhanced vascular permeability induced by hapten stimulation. Our study identified retinoid X receptor as a functional receptor that mediates the downregulation of skin inflammation upon treatment with t10,c15-18:2. Our results suggest that t10,c15-18:2 holds promise as an omega-3 fatty acid-derived postbiotic with potential therapeutic implications for alleviating the skin edema seen in allergic contact dermatitis-induced inflammation., 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 Saika, Nagatake, Kishino, Kitamura, Honda, Hosomi, Tiwari, Node, Kawai, Kondo, Ishida, Kabashima, Ogawa and Kunisawa.)

Background: Few prediction models for individuals with early-stage out-of-hospital cardiac arrest (OHCA) have undergone external validation. This study aimed to externally validate updated prediction models for OHCA outcomes using a large nationwide dataset., Methods and Results: We performed a secondary analysis of the JAAM-OHCA (Comprehensive Registry of In-Hospital Intensive Care for Out-of-Hospital Cardiac Arrest Survival and the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest) registry. Previously developed prediction models for patients with cardiac arrest who achieved the return of spontaneous circulation were updated. External validation was conducted using data from 56 institutions from the JAAM-OHCA registry. The primary outcome was a dichotomized 90-day cerebral performance category score. Two models were updated using the derivation set (n=3337). Model 1 included patient demographics, prehospital information, and the initial rhythm upon hospital admission; Model 2 included information obtained in the hospital immediately after the return of spontaneous circulation. In the validation set (n=4250), Models 1 and 2 exhibited a C-statistic of 0.945 (95% CI, 0.935-0.955) and 0.958 (95% CI, 0.951-0.960), respectively. Both models were well-calibrated to the observed outcomes. The decision curve analysis showed that Model 2 demonstrated higher net benefits at all risk thresholds than Model 1. A web-based calculator was developed to estimate the probability of poor outcomes (https://pcas-prediction.shinyapps.io/90d&#95;lasso/)., Conclusions: The updated models offer valuable information to medical professionals in the prediction of long-term neurological outcomes for patients with OHCA, potentially playing a vital role in clinical decision-making processes.

The fission yeast Schizosaccharomyces pombe ecl family genes respond to various starvation signals and induce appropriate intracellular responses, including the extension of chronological lifespan and induction of sexual differentiation. Herein, we propose that the colonization of hemocoel 1 (COH1) protein of Metarhizium robertsii, an insect-pathogenic fungus, is a functional homolog of S. pombe Ecl1 family proteins.

Background: 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) parameters are prognostic factors in multiple malignancies. However, the prognostic value in bile duct carcinoma is unclear. We evaluated the impact of metabolic parameters of 18 F-FDG-PET/CT in resectable extrahepatic bile duct carcinoma., Methods: We retrospectively reviewed the records of 100 patients with extrahepatic bile duct carcinoma who had undergone 18 F-FDG-PET/CT and subsequent surgical resection between January 2017 and January 2023. We calculated maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) and investigated their prognostic significance., Results: The optimal cutoff values of SUVmax, MTV, and TLG for predicting overall survival (OS) after surgery were 3.88, 3.55 and 7.55, respectively. In multivariate analysis, each metabolic parameter influenced both OS and recurrence-free survival (RFS). TLG showed the lowest Akaike information criteria statistic value, indicating that it had the best ability to predict OS and RFS. High TLG was significantly associated with the number of lymph node metastases and poorly differentiated type. Patients with high TLG showed poorer RFS and OS, which were significantly worse than in those with low TLG., Conclusions: Tumor TLG predicted tumor malignancy potential and could be a useful prognostic predictor for extrahepatic bile duct carcinoma., (© 2024 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Objectives: Lymphovascular invasion (LVI) is a critical risk factor for lymph node metastasis (LNM), which requires additional surgery after endoscopic resection of T1 colorectal cancer (CRC). However, the impact of additional staining on estimating LNM is unclear. This systematic review aimed to evaluate the impact of additional staining on determining LNM in T1 CRC., Methods: We searched five electronic databases. Outcomes were diagnostic odds ratio (DOR), assessed using hierarchical summary receiver operating characteristic curves, and interobserver agreement among pathologists for positive LVI, assessed using Kappa coefficients (κ). We performed a subgroup analysis of studies that simultaneously included a multivariable analysis for other risk factors (deep submucosal invasion, poor differentiation, and tumor budding)., Results: Among the 64 studies (18,097 patients) identified, hematoxylin-eosin (HE) and additional staining for LVI had pooled sensitivities of 0.45 (95% confidence interval [CI] 0.32-0.58) and 0.68 (95% CI 0.44-0.86), specificities of 0.88 (95% CI 0.78-0.94) and 0.76 (95% CI 0.62-0.86), and DORs of 6.26 (95% CI 3.73-10.53) and 6.47 (95% CI 3.40-12.32) for determining LNM, respectively. In multivariable analysis, the DOR of additional staining for LNM (DOR 5.95; 95% CI 2.87-12.33) was higher than that of HE staining (DOR 1.89; 95% CI 1.13-3.16) (P = 0.01). Pooled κ values were 0.37 (95% CI 0.22-0.52) and 0.62 (95% CI 0.04-0.99) for HE and additional staining for LVI, respectively., Conclusion: Additional staining for LVI may increase the DOR for LNM and interobserver agreement for positive LVI among pathologists., (© 2023 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: We sought to evaluate the influence of the rudimentary ventricle on long-term outcomes after the Fontan operation, focusing on exercise capacity and cardiac performance. Methods: Between 1995 and 2021, 290 patients underwent a total cavopulmonary connection. "Two-ventricle" Fontan circulation was defined as a rudimentary ventricle >30% of the dominant ventricle or >50% of its predicted normal value. This cohort was compared with patients with single-ventricle Fontan circulation. The primary endpoint was Fontan failure, and the secondary endpoints were VO 2 and cardiac catheterization data at ten years postoperatively. Results: The median follow-up after the Fontan operation was 7.9 years (interquartile range: 1.9-13.9). No significant difference was found in Fontan failure-free survival between the "two-ventricle" Fontan circulation group and the single-ventricle Fontan circulation group (83/91, 93% vs 156/199, 78%), respectively at 20 years; P  = .11). No significant difference was found in VO 2 or cardiac performance except cardiac index, with 2.9 (2.3-4.8) versus 2.5 (2.3-4.3) L/min/m 2 ( P  = .047). Fifty-one patients in the "two-ventricle" Fontan circulation group were followed up for over ten years after the Fontan operation. In the subgroup analysis of this cohort, the rudimentary ventricular end-diastolic volume/dominant ventricular end-diastolic volume ratio showed a significant positive correlation with dominant ventricular end-diastolic pressure (r = 0.58 [95% CI 0.35-0.74], P  = .002) and a significant negative correlation with VO 2 (r = -0.61 [95% CI -0.80 to -0.28], P  = .001). Conclusions: The rudimentary ventricle was not significantly associated with any clinical disadvantages regarding Fontan failure. However, a large rudimentary ventricle was significantly associated with higher end-diastolic pressure and lower exercise capacity., 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.