Insight into the symbiotic lifestyle of DPANN archaea revealed by cultivation and genome analyses.

Decades of culture-independent analyses have resulted in proposals of many tentative archaeal phyla with no cultivable representative. Members of DPANN (an acronym of the names of the first included phyla Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanohaloarchaeota, and Nanoarchaeota), an archaeal superphylum composed of at least 10 of these tentative phyla, are generally considered obligate symbionts dependent on other microorganisms. While many draft/complete genome sequences of DPANN archaea are available and their biological functions have been considerably predicted, only a few examples of their successful laboratory cultivation have been reported, limiting our knowledge of their symbiotic lifestyles. Here, we investigated physiology, morphology, and host specificity of an archaeon of the phylum "Candidatus Micrarchaeota" (ARM-1) belonging to the DPANN superphylum by cultivation. We constructed a stable coculture system composed of ARM-1 and its original host Metallosphaera sp. AS-7 belonging to the order Sulfolobales Further host-switching experiments confirmed that ARM-1 grew on five different archaeal species from three genera-Metallosphaera, Acidianus, and Saccharolobus-originating from geologically distinct hot, acidic environments. The results suggested the existence of DPANN archaea that can grow by relying on a range of hosts. Genomic analyses showed inferred metabolic capabilities, common/unique genetic contents of ARM-1 among cultivated micrarchaeal representatives, and the possibility of horizontal gene transfer between ARM-1 and members of the order Sulfolobales Our report sheds light on the symbiotic lifestyles of DPANN archaea and will contribute to the elucidation of their biological/ecological functions.

Cell surface architecture of the cultivated DPANN archaeon Nanobdella aerobiophila.

The DPANN archaeal clade includes obligately ectosymbiotic species. Their cell surfaces potentially play an important role in the symbiotic interaction between the ectosymbionts and their hosts. However, little is known about the mechanism of ectosymbiosis. Here, we show cell surface structures of the cultivated DPANN archaeon Nanobdella aerobiophila strain MJ1T and its host Metallosphaera sedula strain MJ1HA, using a variety of electron microscopy techniques, i.e., negative-staining transmission electron microscopy, quick-freeze deep-etch TEM, and 3D electron tomography. The thickness, unit size, and lattice symmetry of the S-layer of strain MJ1T were different from those of the host archaeon strain MJ1HA. Genomic and transcriptomic analyses highlighted the most highly expressed MJ1T gene for a putative S-layer protein with multiple glycosylation sites and immunoglobulin-like folds, which has no sequence homology to known S-layer proteins. In addition, genes for putative pectin lyase- or lectin-like extracellular proteins, which are potentially involved in symbiotic interaction, were found in the MJ1T genome based on in silico 3D protein structure prediction. Live cell imaging at the optimum growth temperature of 65°C indicated that cell complexes of strains MJ1T and MJ1HA were motile, but sole MJ1T cells were not. Taken together, we propose a model of the symbiotic interaction and cell cycle of Nanobdella aerobiophila.IMPORTANCEDPANN archaea are widely distributed in a variety of natural and artificial environments and may play a considerable role in the microbial ecosystem. All of the cultivated DPANN archaea so far need host organisms for their growth, i.e., obligately ectosymbiotic. However, the mechanism of the ectosymbiosis by DPANN archaea is largely unknown. To this end, we performed a comprehensive analysis of the cultivated DPANN archaeon, Nanobdella aerobiophila, using electron microscopy, live cell imaging, transcriptomics, and genomics, including 3D protein structure prediction. Based on the results, we propose a reasonable model of the symbiotic interaction and cell cycle of Nanobdella aerobiophila, which will enhance our understanding of the enigmatic physiology and ecological significance of DPANN archaea.

Rhodoferax lithotrophicus sp. nov., a neutrophilic iron-oxidizing and -reducing bacterium isolated from iron-rich freshwater sediments.

A neutrophilic iron-oxidizing and -reducing bacterium, strain MIZ03T, was previously isolated from a wetland in Ibaraki, Japan. Here, we report the detailed characteristics of this strain. It was motile with a single polar flagellum, and Gram-stain-negative. It could grow not only chemolithoautotrophically but also chemoorganotrophically by aerobic respiration and fermentation. Major cellular fatty acids were C16 : 1 ω7c/C16 : 1 ω6c, and C16 : 0. Phylogenetic analyses indicated that strain MIZ03T belonged to the genus Rhodoferax. This strain was closely related to Rhodoferax ferrireducens with 98.5 % of 16S rRNA gene sequence similarity. Based on its phenotypic and genomic based characteristics, we conclude that strain MIZ03T represents a new species in the genus Rhodoferax. We propose the name Rhodoferax lithotrophicus sp. nov. to accommodate this strain. The type strain is MIZ03T (=JCM 34246T=DSM 113266T). We also propose the name Rhodoferax koreensis sp. nov., of which the type strain is DCY110T (=KCTC 52288T=JCM 31441T), for the effectively, but not yet validly, published name 'Rhodoferax koreense'.

Promethearchaeum syntrophicum gen. nov., sp. nov., an anaerobic, obligately syntrophic archaeon, the first isolate of the lineage 'Asgard' archaea, and proposal of the new archaeal phylum Promethearchaeota phyl. nov. and kingdom Promethearchaeati regn. nov.

An anaerobic, mesophilic, syntrophic, archaeon strain MK-D1T, was isolated as a pure co-culture with Methanogenium sp. strain MK-MG from deep-sea methane seep sediment. This organism is, to our knowledge, the first cultured representative of 'Asgard' archaea, an archaeal group closely related to eukaryotes. Here, we describe the detailed physiology and phylogeny of MK-D1T and propose Promethearchaeum syntrophicum gen. nov., sp. nov. to accommodate this strain. Cells were non-motile, small cocci, approximately 300-750 nm in diameter and produced membrane vesicles, chains of blebs and membrane-based protrusions. MK-D1T grew at 4-30 °C with optimum growth at 20 °C. The strain grew chemoorganotrophically with amino acids, peptides and yeast extract with obligate dependence on syntrophy with H2-/formate-utilizing organisms. MK-D1T showed the fastest growth and highest maximum cell yield when grown with yeast extract as the substrate: approximately 3 months to full growth, reaching up to 6.7×106 16S rRNA gene copies ml-1. MK-D1T had a circular 4.32 Mb chromosome with a DNA G+C content of 31.1 mol%. The results of phylogenetic analyses of the 16S rRNA gene and conserved marker proteins indicated that the strain is affiliated with 'Asgard' archaea and more specifically DHVC1/DSAG/MBG-B and 'Lokiarchaeota'/'Lokiarchaeia'. On the basis of the results of 16S rRNA gene sequence analysis, the most closely related isolated relatives were Infirmifilum lucidum 3507LTT (76.09 %) and Methanothermobacter tenebrarum RMAST (77.45 %) and the closest relative in enrichment culture was Candidatus 'Lokiarchaeum ossiferum' (95.39 %). The type strain of the type species is MK-D1T (JCM 39240T and JAMSTEC no. 115508). We propose the associated family, order, class, phylum, and kingdom as Promethearchaeaceae fam. nov., Promethearchaeales ord. nov., Promethearchaeia class. nov., Promethearchaeota phyl. nov., and Promethearchaeati regn. nov., respectively. These are in accordance with ICNP Rules 8 and 22 for nomenclature, Rule 30(3)(b) for validation and maintenance of the type strain, and Rule 31a for description as a member of an unambiguous syntrophic association.

Safety and Effectiveness of Endovascular Treatment of Complications Associated with Persistent Sciatic Artery: A Qualitative Systematic Review.

PURPOSE: To evaluate the safety and effectiveness of endovascular therapy with stent grafts (SGs) to treat complications associated with persistent sciatic artery (PSA) by conducting a systematic review. MATERIALS AND METHODS: The MEDLINE, Web of Science, Scopus, and Ichushi Web databases were searched to identify articles focusing on endovascular treatment with SGs for complications associated with PSA published from inception to September 15, 2023. The review included 31 case reports, 2 case series, and 7 conference proceedings. Forty patients (median age, 67 years [range, 22-88 years]; 25 women) with 41 limbs underwent endovascular treatment with 65 SGs for ischemia (n = 26), aneurysm (n = 13), and trauma (n = 2). Prior treatments were systemic anticoagulation (n = 7), thrombolysis (n = 5), thrombectomy (n = 3), and amputation (n = 1), whereas concurrent treatments were thrombolysis (n = 6) and thrombectomy (n = 2). The median number of SGs implanted was 2 (range, 1-4). Early outcomes were technical success and adverse events (AEs). Late outcomes were primary patency, secondary patency, freedom from reintervention, and clinical success. RESULTS: The technical success rate was 100%. Intervention-specific AEs were reported in 4 cases; however, there were no severe AEs. The clinical success rates at 1 and 2 years were 100% and 95.7%, respectively. The primary patency rates at 1 and 2 years were 81.5% and 67.6%, respectively, and the secondary patency rates at 1 and 2 years were 94.5% and 81.6%, respectively. CONCLUSIONS: Endovascular treatment with SGs for complications associated with PSA is safe and effective with acceptable midterm patency and durability, and is supportable as the first-choice treatment.

Myocardial Injury by COVID-19 Infection Assessed by Cardiovascular Magnetic Resonance Imaging　- A Prospective Multicenter Study.

BACKGROUND: This prospective multicenter study assessed the prevalence of myocardial injury in patients with COVID-19 using cardiac magnetic resonance imaging (CMR).Methods and Results: We prospectively screened 505 patients with moderate to severe COVID-19 disease from 7 hospitals in Japan. Of these patients, 31 (mean [±SD] age 63.5±10.4 years, 23 [74%] male) suspected of myocardial injury, based on elevated serum troponin or B-type natriuretic peptide concentrations either upon admission or 3 months after discharge, underwent CMR 3 months after discharge. The primary endpoint was the presence of myocardial injury, defined by any of the following: (1) contrast enhancement in the left or right ventricle myocardium on late gadolinium enhancement CMR; (2) left or right ventricular dysfunction (defined as <50% and <45%, respectively); and (3) pericardial thickening on contrast enhancement. The mean (±SD) duration between diagnosis and CMR was 117±16 days. The primary endpoint was observed in 13 of 31 individuals (42%), with 8 (26%) satisfying the modified Lake Louise Criteria for the diagnosis of acute myocarditis. CONCLUSIONS: This study revealed a high incidence of myocardial injury identified by CMR in patients with moderate to severe COVID-19 and abnormal findings for cardiac biomarkers.

Nationwide multicenter study on adverse events associated with a patency capsule: Additional survey of appropriate use of patency capsule study.

BACKGROUND AND AIM: The PillCam patency capsule (PC) without a radio frequency identification tag was released to preclude retention of the small bowel capsule endoscope (CE) in Japan in 2012. We conducted a multicenter study to determine tag-less PC-related adverse events (AEs). METHODS: We first conducted a retrospective survey using a standardized data collection sheet for the clinical characteristics of PC-related AEs among 1096 patients collected in a prospective survey conducted between January 2013 and May 2014 (Cohort 1). Next, we retrospectively investigated additional AEs that occurred before and after Cohort 1 within the period June 2012 and December 2014 among 1482 patients (Cohort 2). RESULTS: Of the 2578 patients who underwent PC examinations from both cohorts, 74 AEs occurred among 61 patients (2.37%). The main AEs were residual parylene coating in 25 events (0.97%), PC-induced small bowel obstruction, suspicious of impaction, in 23 events (0.89%), and CE retention even after patency confirmation in 10 events (0.39%). Residual parylene coating was significantly associated with Crohn's disease (P < 0.01). Small bowel obstruction was significantly associated with physicians with less than 1 year of experience handling the PC and previous history of postprandial abdominal pain (P < 0.01 and P < 0.03, respectively). CE retention was ascribed to erroneous judgment of PC localization in all cases. CONCLUSIONS: This large-scale multicenter study provides evidence supporting the safety and efficiency of a PC to preclude CE retention. Accurate PC localization in patients without excretion and confirmation of previous history of postprandial abdominal pain before PC examinations is warranted (UMIN000010513).

Right ventricular myocardial fibrosis evaluated by extracellular volume fraction by magnetic resonance imaging in patients with repaired tetralogy of Fallot: a meta-analysis.

OBJECTIVE: The objective of this meta-analysis was to assess the clinical utility of anomalous discoveries on cardiac magnetic resonance, particularly the right ventricular extracellular volume (RV-ECV), among individuals who underwent surgical repair for Tetralogy of Fallot (rTOF). METHODS: We conducted a systematic search of electronic databases including PubMed, Web of Science Core Collection, Cochrane advanced search, and EMBASE. Our analysis involved a comparison of ECV levels between rTOF patients and controls, as well as an evaluation of the predictive value of ECV for future adverse events. RESULTS: We identified 16 eligible studies that encompassed 856 rTOF patients and 283 controls. Our meta-analysis showed a significant increase in LV-ECV among rTOF patients compared to control subjects (MD = 2.63, 95%CI: 1.35 to 3.90, p < 0.0001, I2 = 86%, p for heterogeneity < 0.00001). Moreover, RV-ECV was found to be substantially higher in patients compared to LV-ECV. Our meta-analysis also revealed a significant association between RV-ECV and adverse events (HR = 1.15, 95% CI: 1.04 to 1.27, p = 0.005, I2 = 0%, p for heterogeneity = 0.62), while LV-ECV did not show any significant association with adverse events (HR = 1.12, 95% CI: 0.92 to 1.36, p = 0.16, I2 = 0%, p for heterogeneity = 0.46). CONCLUSION: The results of this meta-analysis on RV-ECV confirmed the presence of RV fibrosis as one of the prognostic factors in rTOF patients.

3-Fr steerable microcatheter system via the upper limb artery in RADPLAT for right maxillary cancer.

BACKGROUND: To evaluate the efficacy of a catheter system using a 3-Fr sheath with a steerable microcatheter through right upper limb artery access for superselective intra-arterial cisplatin infusion and concomitant radiotherapy (RADPLAT) to treat right maxillary sinus squamous cell carcinoma (MS-SCC). MATERIAL AND METHODS: We retrospectively studied 46 sessions in eight patients treated between November 2020 and February 2023 using the catheter system briefly described below. A 3-Fr sheath was inserted into the distal radial, conventional radial, or brachial arteries. A coaxial catheter system with a 2.9-Fr steerable microcatheter and a 1.9-Fr microcatheter was advanced into the brachiocephalic artery. The right common carotid artery was selected by bending the tip of the steerable microcatheter. Coil embolization and intra-arterial cisplatin infusion after selecting each external carotid artery branch were achieved using this catheter system. RESULTS: Cisplatin infusion and coil embolization were successful in all sessions. Arterial occlusion at the sheath insertion sites was found in 29.4% (5/17) of the distal radial arteries and 33.3% (3/9) of the conventional radial arteries. No other major complications were observed during the procedure. CONCLUSION: Using a 3-Fr catheter system with a steerable microcatheter through right upper limb artery access is a feasible method for RADPLAT in treating right MS-SCC.

Clinical utility of Todai OncoPanel in the setting of approved comprehensive cancer genomic profiling tests in Japan.

Comprehensive cancer genome profiling (CGP) has been nationally reimbursed in Japan since June 2019. Less than 10% of the patients have been reported to undergo recommended treatment. Todai OncoPanel (TOP) is a dual DNA-RNA panel as well as a paired tumor-normal matched test. Two hundred patients underwent TOP as part of Advanced Medical Care B with approval from the Ministry of Health, Labour and Welfare between September 2018 and December 2019. Tests were carried out in patients with cancers without standard treatment or when patients had already undergone standard treatment. Data from DNA and RNA panels were analyzed in 198 and 191 patients, respectively. The percentage of patients who were given therapeutic or diagnostic recommendations was 61% (120/198). One hundred and four samples (53%) harbored gene alterations that were detected with the DNA panel and had potential treatment implications, and 14 samples (7%) had a high tumor mutational burden. Twenty-two samples (11.1%) harbored 30 fusion transcripts or MET exon 14 skipping that were detected by the RNA panel. Of those 30 transcripts, 6 had treatment implications and 4 had diagnostic implications. Thirteen patients (7%) were found to have pathogenic or likely pathogenic germline variants and genetic counseling was recommended. Overall, 12 patients (6%) received recommended treatment. In summary, patients benefited from both TOP DNA and RNA panels while following the same indication as the approved CGP tests. (UMIN000033647).

Microvascular dysfunction in patients with heart failure with preserved ejection fraction: A meta-analysis.

BACKGROUND: Although microvascular dysfunction (MVD) is considered an essential pathophysiology in patients with heart failure with preserved ejection fraction (HFpEF), the frequency and prognostic impact of MVD are not fully understood. This meta-analysis evaluated the frequency of MVD in patients with HFpEF and its utility in risk stratification. MATERIALS AND METHODS: On May 26, 2022, a literature search was performed on PubMed, Web of Science, the Cochrane library, and Embase using the search terms such as "Heart failure with preserved ejection fraction," "HFpEF," "microvascular dysfunction," and "MVD." The prevalence of MVD in patients with HFpEF was calculated using the general inverse variance method. A comprehensive literature review was conducted to examine the association between MVD and prognosis in patients with HFpEF. RESULTS: Data pertaining to a total of 941 patients diagnosed with HFpEF were extracted from the collective pool of 9 studies. The results of the meta-analysis revealed that the frequency of MVD among patients with HFpEF was found to be 55.5% (95% CI: 34.8%-76.2%), with a substantial degree of heterogeneity (I2 = 98%, p for heterogeneity <.001). Among the five studies that provided data on the association between MVD and prognosis, a significant statistical association was observed in four of them. CONCLUSIONS: This meta-analysis revealed that approximately 50% of patients diagnosed with HFpEF exhibited MVD. Moreover, the presence of MVD demonstrated significant prognostic implications in multiple studies conducted on patients with HFpEF. These findings strongly suggest that MVD plays a crucial role in the underlying pathophysiology of patients with HFpEF.

Virological outcomes of various first-line ART regimens in patients harbouring HIV-1 E157Q integrase polymorphism: a multicentre retrospective study.

BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are recommended as first-line ART for people living with HIV (PLWH) in most guidelines. The INSTI-resistance-associated mutation E157Q, a highly prevalent (2%-5%) polymorphism of the HIV-1 (human immunodeficiency virus type 1) integrase gene, has limited data on optimal first-line ART regimens. We assessed the virological outcomes of various first-line ART regimens in PLWH with E157Q in real-world settings. METHODS: A multicentre retrospective observational study was conducted on PLWH who underwent integrase genotypic drug-resistance testing before ART initiation between 2008 and 2019 and were found to have E157Q. Viral suppression (<50 copies/mL) rate at 24 and 48 weeks, time to viral suppression and time to viral rebound (≥100 copies/mL) were compared among the first-line ART regimens. RESULTS: E157Q was detected in 167 (4.1%) of 4043 ART-naïve PLWH. Among them, 144 had available clinical data after ART initiation with a median follow-up of 1888 days. Forty-five started protease inhibitors + 2 NRTIs (PI group), 33 started first-generation INSTI (raltegravir or elvitegravir/cobicistat) + 2 NRTIs (INSTI-1 group), 58 started once-daily second-generation INSTI (dolutegravir or bictegravir) + 2 NRTIs (INSTI-2 group) and eight started other regimens. In the multivariate analysis, the INSTI-2 group showed similar or favourable outcomes compared with the PI group for viral suppression rates, time to viral suppression and time to viral rebound. Two cases in the INSTI-1 group experienced virological failure. CONCLUSIONS: The general guideline recommendation of second-generation INSTI-based first-line ART for most PLWH is also applicable to PLWH harbouring E157Q.

Coronary flow reserve evaluated by phase-contrast cine cardiovascular magnetic resonance imaging of coronary sinus: a meta-analysis.

BACKGROUND: Phase-contrast cine cardiovascular magnetic resonance (CMR) of the coronary sinus has emerged as a non-invasive method for measuring coronary sinus blood flow and coronary flow reserve (CFR). However, its clinical utility has not yet been established. Here we performed a meta-analysis to clarify the clinical value of CMR-derived CFR in various cardiovascular diseases. METHODS: An electronic database search was performed of PubMed, Web of Science Core Collection, Cochrane Advanced Search, and EMBASE. We compared the CMR-derived CFR of various cardiovascular diseases (stable coronary artery disease [CAD], hypertrophic cardiomyopathy [HCM], dilated cardiomyopathy [DCM]) and control subjects. We assessed the prognostic value of CMR-derived CFR for predicting major adverse cardiac events (MACE) in patients with stable CAD. RESULTS: A total of 47 eligible studies were identified. The pooled CFR from our meta-analysis was 3.48 (95% confidence interval [CI], 2.98-3.98) in control subjects, 2.50 (95% CI, 2.38-2.61) in stable CAD, 2.01 (95% CI, 1.70-2.32) in cardiomyopathies (HCM and DCM). The meta-analysis showed that CFR was significantly reduced in stable CAD (mean difference [MD] = -1.48; 95% CI, -1.78 to -1.17; p < 0.001; I2 = 0%; p for heterogeneity = 0.33), HCM (MD = -1.20; 95% CI, -1.63 to -0.77; p < 0.001; I2 = 0%; p for heterogeneity = 0.49), and DCM (MD = -1.53; 95% CI, -1.93 to -1.13; p < 0.001; I2 = 0%; p for heterogeneity = 0.45). CMR-derived CFR was an independent predictor of MACE for patients with stable CAD (hazard ratio = 0.52 per unit increase; 95% CI, 0.37-0.73; p < 0.001; I2 = 84%, p for heterogeneity < 0.001). CONCLUSIONS: CMR-derived CFR was significantly decreased in cardiovascular diseases, and a decreased CFR was associated with a higher occurrence of MACE in patients with stable CAD. These results suggest that CMR-derived CFR has potential for the pathological evaluation of stable CAD, cardiomyopathy, and risk stratification in CAD.

Diagnostic accuracy of whole heart coronary magnetic resonance angiography: a systematic review and meta-analysis.

BACKGROUND: The purpose of this meta-analysis was to comprehensively investigate the diagnostic ability of 1.5 T and 3.0 T whole heart coronary angiography (WHCA) to detect significant coronary artery disease (CAD) on X-ray coronary angiography. METHODS: A literature search of electronic databases, including PubMed, Web of Science Core Collection, Cochrane advanced search, and EMBASE, was performed to retrieve and integrate articles showing significant CAD detectability of 1.5 and 3.0 T WHCA. RESULTS: Data from 1899 patients from 34 studies were included in the meta-analysis. 1.5 T WHCA had a summary area under ROC of 0.88 in the patient-based analysis, 0.90 in the vessel-based analysis, and 0.92 in the segment-based analysis. These values for 3.0 T WHCA were 0.94, 0.95, 0.96, respectively. Contrast-enhanced 3.0 T WHCA had significantly higher specificity than non-contrast-enhanced 1.5 T WHCA on a patient-based analysis (0.87, 95% CI 0.80-0.92 vs. 0.74, 95% CI 0.64-0.82, P = 0.02). There were no differences in diagnostic performance on a patient-based analysis by use of vasodilators, beta-blockers or between Asian and Western countries. CONCLUSIONS: The diagnostic performance of WHCA was deemed satisfactory, with contrast-enhanced 3.0 T WHCA exhibiting higher specificity compared to non-contrast-enhanced 1.5 T WHCA in a patient-based analysis. There were no significant differences in diagnostic performance on a patient-based analysis in terms of vasodilator or beta-blocker use, nor between Asian and Western countries. However, further large-scale multicentre studies are crucial for the widespread global adoption of WHCA.

Machine learning to predict left ventricular reverse remodeling by guideline-directed medical therapy by utilizing texture feature of extracellular volume fraction in patients with non-ischemic dilated cardiomyopathy.

Extracellular volume fraction (ECV) by cardiac magnetic resonance (CMR) allows for the non-invasive quantification of diffuse myocardial fibrosis. Texture analysis and machine learning are now gathering attention in the medical field to exploit the ability of diagnostic imaging for various diseases. This study aimed to investigate the predictive value of texture analysis of ECV and machine learning for predicting response to guideline-directed medical therapy (GDMT) for patients with non-ischemic dilated cardiomyopathy (NIDCM). A total of one-hundred and fourteen NIDCM patients [age: 63 ± 12 years, 91 (81%) males] were retrospectively analyzed. We performed texture analysis of ECV mapping of LV myocardium using dedicated software. We calculated nine histogram-based features (mean, standard deviation, maximum, minimum, etc.) and five gray-level co-occurrence matrices. Five machine learning techniques and the fivefold cross-validation method were used to develop prediction models for LVRR by GDMT based on 14 texture parameters on ECV mapping. We defined the LVRR as follows: LVEF increased ≥ 10% points and decreased LVEDV ≥ 10% on echocardiography after GDMT > 12 months. Fifty (44%) patients were classified as non-responders. The area under the receiver operating characteristics curve for predicting non-responder was 0.82 for eXtreme Gradient Boosting, 0.85 for support vector machine, 0.76 for multi-layer perception, 0.81 for Naïve Bayes, 0.77 for logistic regression, respectively. Mean ECV value was the most critical factor among texture features for differentiating NIDCM patients with LVRR and those without (0.28 ± 0.03 vs. 0.36 ± 0.06, p < 0.001). Machine learning analysis using the support vector machine may be helpful in detecting high-risk NIDCM patients resistant to GDMT. Mean ECV is the most crucial feature among texture features.

Contrast defect of left atrial appendage on computed tomography is associated with higher risk of recurrence after catheter ablation in patients with paroxysmal atrial fibrillation.

The previous study has shown that the contrast defect of the left atrial appendage (LAA) on contrast-enhanced cardiac computed tomography (CT) is associated with a higher rate of stroke in patients with atrial fibrillation (AF). This study aimed to investigate the association between LAA CT contrast defect and the risk of arrhythmia recurrence after catheter ablation (CA) in patients with paroxysmal AF. A total of 283 paroxysmal AF patients [age: 67 ± 10 years, 185 (65%) males] who underwent cardiac CT before CA were retrospectively analyzed. The presence or absence of LAA CT contrast defect was visually assessed using early phase CT images. Recurrence was an episode of atrial arrhythmia beyond the first 90 days post-ablation. LAA flow velocity was measured using transesophageal echocardiography in 246 paroxysmal AF patients. Sixty-eight (24%) patients had an LAA CT contrast defect. LAA flow velocity was significantly reduced in patients with LAA CT defect compared to those without (56.8 ± 28.7 cm/s vs. 41.1 ± 19.1 cm/s, p < 0.001). During a median follow-up period of 858 days, arrhythmia recurrence was identified in 85 (30%) patients. On a Kaplan Meier curve, patients with LAA CT contrast defect had significantly higher recurrence rates than those without (p = 0.043). On a multivariable Cox regression analysis, LAA CT contrast defect was a significant and independent predictor after adjustment of age, sex and left atrial volume index (hazard ratio: 1.79, 95% confidence interval: 1.03-3.07, p = 0.036). LAA CT contrast defect was associated with decreased LAA flow velocity and a higher rate of arrhythmia recurrence after CA, suggesting its usefulness as a non-invasive predictor for high-risk AF patients resistant to CA therapy.

Sideroxyarcus emersonii gen. nov. sp. nov., a neutrophilic, microaerobic iron- and thiosulfate-oxidizing bacterium isolated from iron-rich wetland sediment.

A neutrophilic iron-oxidizing bacterium, strain MIZ01T, which was previously isolated from a wetland in Ibaraki, Japan, was taxonomically characterized in detail. Strain MIZ01T was a motile, curved-rod shaped, Gram-stain-negative bacterium. It was able to grow at 10-40 °C (optimally at 30-35 °C) and at pH 5.5-7.0 (optimally at pH 6.0). It grew microaerobically and chemolithoautotrophically using thiosulfate, in addition to ferrous iron, as the sole electron donor. Major cellular fatty acids of strain MIZ01T were C16 : 1 ω7c/C16 : 1 ω6c and C16 : 0. The complete genome sequence (2.74 Mbp) was determined, showing that its DNA G+C content was 60.0 mol%. Phylogenetic analyses indicated that strain MIZ01T belonged to the family Gallionellaceae, class Betaproteobacteria, and was closely related to an isolate tentatively named 'Sideroxydans lithotrophicus' ES-1 (98.2 % of 16S rRNA gene sequence similarity). Based on its phenotypic and phylogenetic characteristics, we conclude that strain MIZ01T represents a new genus and species in the family Gallionellaceae for which we propose the name Sideroxyarcus emersonii gen. nov., sp. nov. The type strain is strain MIZ01T (=JCM 39089T=DSM 111897T).

Nanobdella aerobiophila gen. nov., sp. nov., a thermoacidophilic, obligate ectosymbiotic archaeon, and proposal of Nanobdellaceae fam. nov., Nanobdellales ord. nov. and Nanobdellia class. nov.

A co-culture of a novel thermoacidophilic, obligate symbiotic archaeon, designated as strain MJ1T, with its specific host archaeon Metallosphaera sedula strain MJ1HA was obtained from a terrestrial hot spring in Japan. Strain MJ1T grew in the co-culture under aerobic conditions. Coccoid cells of strain MJ1T were 200-500 nm in diameter, and attached to the MJ1HA cells in the co-culture. The ranges and optima of the growth temperature and pH of strain MJ1T in the co-culture were 60-75 °C (optimum, 65-70 °C) and pH 1.0-4.0 (optimum, pH 2.5), respectively. Core lipids of dialkyl glycerol tetraethers (GDGT)-3 and GDGT-4 were highly abundant in MJ1T cells concentrated from the co-culture. Strain MJ1T has a small genome (0.67 Mbp) lacking genes for biosynthesis of essential biomolecules, such as nucleotides, lipids and ATP. The genomic DNA G+C content was 24.9 mol%. The 16S rRNA gene sequence of strain MJ1T was most closely related to that of the cultivated species, 'Nanopusillus acidilobi' strain N7A (85.8 % similarity). Based on phylogenetic and physiological characteristics, we propose the name Nanobdella aerobiophila gen. nov., sp. nov. to accommodate the strain MJ1T (=JCM 33616T=DSM 111728T). In addition, we propose the names Nanobdellaceae fam. nov., Nanobdellales ord. nov., and Nanobdellia class. nov. to accommodate the novel genus.

Large volume was associated with increased risk of acute non-hematologic adverse events in the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer: preliminary results of prospective phase I/II clinical trial.

OBJECTIVE: This is the preliminary results of a multi-center prospective clinical trial evaluating the feasibility of the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer. METHODS: Patients with FIGO stage IB2, IIA2, IIB, IIIA, IIIB and IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by MRI were eligible. Protocol therapy consisted of 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of hybrid of intracavitary and interstitial and pelvic radiotherapy with central shield up to 50-50.4 Gy in 25-28 fractions. The primary endpoint of phase I part was that the rate of grade ≥ 3 acute non-hematologic adverse events related to hybrid of intracavitary and interstitial would be <10%. RESULTS: Between October 2015 and October 2019, 74 patients underwent primary registration, with 52 patients eventually proceeding to the secondary registration. The median pretreatment tumor width was 5.7 cm, and FIGO Stages were IB2 10, IIA2 2, IIB 20 and IIIB 20, respectively. The median high-risk clinical target volume D90 was 72.0 Gy (54.8-86.6 Gy, EQD2), rectum D2cc was 53.7 Gy (29.3-80.3 Gy) and bladder D2cc was 69.8 Gy (38.9-84.8 Gy). The rate of grade ≥ 3 non-hematologic adverse events related to hybrid of intracavitary and interstitial was 1.9% (1/52), and 17.3% (9/52) of patients experienced non-hematologic adverse events related to hybrid of intracavitary and interstitial of any grade. In multivariate analysis, high-risk clinical target volume ≥ 35 ml was associated with an increased risk of any grade of acute non-hematologic adverse events related to hybrid of intracavitary and interstitial (P = 0.036). CONCLUSION: The feasibility and reproducibility of hybrid of intracavitary and interstitial were demonstrated from a multi-center prospective clinical trial.

Learning Curve of Endoscopic Retrograde Cholangiopancreatography Using Single-Balloon Enteroscopy.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy is technically difficult. Extensive training is required to develop the ability to perform this procedure. AIMS: To investigate the learning curve of single-balloon-assisted enteroscopy ERCP (SBE-ERCP). METHODS: We conducted a retrospective, observational case series at a single center. We evaluated the SBE-ERCP procedures between April 2011 and February 2021. The main outcomes were the rate of reaching the target site and the success rate of the entire procedure. These parameters were additionally expressed as a learning curve. RESULTS: A total of 687 SBE-ERCP procedures were analyzed. The learning curve was analyzed in blocks of 10 cases. In this study, seven endoscopists, experts in conventional ERCP, were included. The overall SBE-ERCP procedural success rate was 92.2% (634/687 cases). Combining all data from individual endoscopists' evaluation periods, the insertion and success rates of the SBE-ERCP procedures gradually increased with increased experience performing SBE-ERCP. The insertion success rates for the number of SBE-ERCP cases (< 20, 21-30, > 30) were 82.9%, 92.9%, and 94.3%, respectively; the procedure success rates were 74.3%, 81.4%, and 92.9%, respectively. The endoscopists who had performed > 30 SBE-ERCP cases had a success rate of ≥ 90%. CONCLUSIONS: Our results suggest that performing > 30 cases is one of the targets for conventional ERCP experts to become competent in performing SBE-ERCP in patients with a surgically altered anatomy.