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Aims: Safety of aspirin-free strategy immediately after percutaneous coronary intervention (PCI) for cardiovascular events in patients with diabetes was unknown., Methods and Results: We conducted the prespecified subgroup analysis on diabetes in the STOPDAPT-3 trial, which randomly compared prasugrel (3.75 mg/day) monotherapy (2984 patients) to dual antiplatelet therapy (DAPT) with prasugrel and aspirin (2982 patients) in patients with acute coronary syndrome or high bleeding risk. The co-primary endpoints were major bleeding events (Bleeding Academic Research Consortium 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) at 1 month. Of 5966 study patients, there were 2715 patients (45.5%) with diabetes. Patients with diabetes more often had chronic coronary syndrome, heart failure or cardiogenic shock, and comorbidities than those without. Patients with diabetes compared to those without had higher incidences of major bleeding and cardiovascular events. Regardless of diabetes, the effect of no-aspirin relative to DAPT was not different for the co-primary bleeding (diabetes: 5.05% versus 5.47%; HR, 0.92; 95%CI, 0.66-1.28 and non-diabetes: 3.99% versus 4.07%; HR, 0.98; 95%CI, 0.69-1.38; P for interaction = 0.81) and cardiovascular (diabetes: 5.54% versus 5.15%; HR, 1.08; 95%CI, 0.78-1.49 and non-diabetes: 2.95% versus 2.47%; HR, 1.20; 95%CI, 0.79-1.82; P for interaction = 0.70) endpoints. The incidences of subacute definite or probable stent thrombosis and any coronary revascularization were higher in the no-aspirin group than in the DAPT group regardless of diabetes., Conclusions: The effects of an aspirin-free prasugrel monotherapy (3.75 mg/day) relative to DAPT for major bleeding and cardiovascular events were not different regardless of diabetes. Clinical trial registration: ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Deep sea water (DSW) contains many trace minerals, and its applications, which include its use as drinking water, have gradually been expanding. Generally, humans tend to be lacking in mineral intake and deficiencies of trace minerals may increase the risk of several health problems. In recent years, the lack of exercise among the elderly has become an issue, leading to the onset of frailty and sarcopenia, which in turn increases the risk of dementia. Therefore, we investigated whether the daily intake of DSW-extract-added water (DSW; hardness 300 mg/L) impacted the training effect in aged mice. Treatment with DSW significantly induced a training effect in aged mice subjected to treadmill exercise. Locomotor function and metabolic capacity were also significantly increased in aged mice after DSW treatment. The results indicate that daily intake of DSW may enhance the training effect of exercise and affect locomotor performance., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Barium disilicide (BaSi 2 ) is a thin-film solar cell material composed of abundant elements, and its application potential is further enhanced by its formation on inexpensive substrates, such as glass. The effect of the substrate temperature on the co-sputtering of BaSi 2 and Ba targets to form BaSi 2 films on Si(111) and TiN/glass substrates was investigated. Contrary to expectations, the photoresponsivity reached maximum values exceeding 5 and 2 A W -1 , respectively, the highest value ever reported for as-deposited samples formed at 750 °C, more than 100 °C higher than those reported previously. Because the photoresponsivity is proportional to carrier lifetime, this result indicates that high-temperature growth can bring out the high performance of BaSi 2 as a light-absorbing layer. Because amorphous SiC (a-SiC) has a larger forbidden band gap and electron affinity than BaSi 2 , it is considered suitable as an electron transport layer (ETL) material for BaSi 2 solar cells. On the basis of this, the formation of BaSi 2 (absorption layer)/a-SiC (ETL)/TiN (electrode)/glass heterojunctions was also attempted, and the layered structure was examined by cross-sectional transmission electron microscopy (TEM). Polycrystalline BaSi 2 films were found to be even on the amorphous layer by TEM. A high photoresponsivity of over 2 A W -1 was obtained. Therefore, the BaSi 2 /a-SiC/TiN structure provides a guideline for the structural design of BaSi 2 -based thin-film solar cells on glass.

This study aimed to investigate the wear and microhardness of luting agents and computer-aided design-computer-aided manufacturing (CAD-CAM) resin blocks, and to compare the wear characteristics of resin-based luting agents used in bonded specimens of CAD-CAM resin blocks. After three-body wear test, the amount of wear and Vickers hardness were measured and Pearson's correlation coefficient was calculated. The lowest amount of wear and the highest Vickers hardness values were obtained for Estecem II. Filler loss was observed in five composite resin cements. A strong negative correlation was observed in the luting agents between the amount of wear and Vickers hardness value (r=-0.874, p<0.0001). Additionally, a strong positive correlation was observed between the amount of wear of the bonded specimen and amount of luting agent used alone (r=0.943, p<0.0001). To conclude, the wear resistance of the luting agent used in the bonded specimen was significantly influenced by the bonding between the filler and matrix resin.

The current guidelines for acute coronary syndrome (ACS) discourage the use of anticoagulation after percutaneous coronary intervention (PCI) without specific indications, although the recommendation is not well supported by evidence. In this post hoc analysis of the ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-3 (STOPDAPT-3) trial, 30-day outcomes were compared between the 2 groups with and without post-PCI heparin administration among patients with ACS who did not receive mechanical support devices. The co-primary end points were the bleeding end point, defined as the Bleeding Academic Research Consortium type 3 or 5 bleeding, and the cardiovascular end point, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke. Among 4,088 patients with ACS, 2,339 patients (57.2%) received post-PCI heparin. The proportion of patients receiving post-PCI heparin was higher among those with ST-elevation myocardial infarction compared with others (72.3% and 38.8%, p <0.001), and among patients with intraprocedural adverse angiographic findings compared with those without (67.6% and 47.5%, p <0.001). Post-PCI heparin compared with no post-PCI heparin was associated with a significantly increased risk of the bleeding end point (4.75% and 2.52%, adjusted hazard ratio 1.69, 95% confidence interval 1.15 to 2.46, p = 0.007) and a numerically increased risk of the cardiovascular end point (3.16% and 1.72%, adjusted hazard ratio 1.56, 95% confidence interval 0.98 to 2.46, p = 0.06). Higher hourly dose or total doses of heparin were also associated with higher incidence of both bleeding and cardiovascular events within 30 days. In conclusion, post-PCI anticoagulation with unfractionated heparin was frequently implemented in patients with ACS. Post-PCI heparin use was associated with harm in terms of increased bleeding without the benefit of reducing cardiovascular events. Trial identifier: STOPDAPT-3 ClinicalTrials.gov number, NCT04609111., Competing Interests: Declaration of competing interest Dr. Watanabe reports lecturer's fees from Abbott Medical Japan during the conduct of the study and from Daiichi Sankyo, Pfizer, Amgen, and Astellas outside the submitted work. Dr. Natsuaki reports honoraria from Abbott Medical Japan, Daiichi Sankyo, Medtronic, Terumo, Japan Lifeline, Asahi Intecc, Bristol-Myers Squibb, Otsuka, Amgen, Sanofi, Takeda, and Bayer. Dr. Morimoto reports lecturer's fees from Abbott, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Pfizer (New York, New York, United States), Tsumura, and UCB; manuscript fee from Pfizer; and advisory board membership for GlaxoSmithKline, Novartis, and Teijin. Dr. Obayashi reports lecturer's fee from Abbott Medical Japan. Dr. Suwa reports personal fees from Abbott Medical Japan and Daiichi Sankyo outside the submitted work. Dr. Ogita reports personal fees from Daiichi Sankyo, Abbott Medical Japan, and Japan Lifeline outside the submitted work. Dr. Suzuki reports grants from Abbott Medical Japan during the conduct of the study. Dr. Morishima reports honoraria from Abbott Medical Japan and Daiichi Sankyo. Dr. Kimura reports grants from Abbott Medical Japan and Boston Scientific and being an advisory board member for Abbott Medical Japan and Terumo Japan. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: There was no previous trial comparing aspirin monotherapy with a P2Y12 inhibitor monotherapy following short dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents (DES)., Methods: In the STOPDAPT-3, patients with acute coronary syndrome (ACS) or high bleeding risk (HBR) were randomly assigned to either 1-month DAPT with aspirin and prasugrel followed by aspirin monotherapy (aspirin group) or 1-month prasugrel monotherapy followed by clopidogrel monotherapy (clopidogrel group). This secondary analysis compared aspirin monotherapy with clopidogrel monotherapy by the 30-day landmark analysis. The co-primary endpoints were the cardiovascular endpoint defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischaemic stroke, and the bleeding endpoint defined as Bleeding Academic Research Consortium 3 or 5., Results: Of 6002 assigned patients, 5833 patients (aspirin group: N = 2920 and clopidogrel group: N = 2913) were included in the 30-day landmark analysis. Median age was 73 (interquartile range 64-80) years, women 23.4%, ACS 74.6%, and HBR 54.1%. The assigned monotherapy was continued at 1 year in 87.5% and 87.2% in the aspirin and clopidogrel groups, respectively. The incidence rates beyond 30 days and up to 1 year were similar between the aspirin and clopidogrel groups for both cardiovascular endpoint (4.5 and 4.5 per 100 person-year, hazard ratio [HR] 1.00 [95% confidence interval (CI) 0.77-1.30], P = .97), and bleeding endpoint (2.0 and 1.9, HR 1.02 [95% CI 0.69-1.52], P = .92)., Conclusions: Aspirin monotherapy compared to clopidogrel monotherapy was associated with similar cardiovascular and bleeding outcomes beyond 1 month and up to 1 year after PCI with DES., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. 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.)

Background and Aims: High bleeding risk (HBR) and acute coronary syndrome (ACS) subtypes are critical in determining bleeding and cardiovascular event risk after percutaneous coronary intervention (PCI)., Methods and Results: In 4476 ACS patients enrolled in the STOPDAPT-3, where the no-aspirin and dual antiplatelet therapy (DAPT) strategies after PCI were randomly compared, the pre-specified subgroup analyses were conducted based on HBR/non-HBR and ST-segment elevation myocardial infarction (STEMI)/non-ST-segment elevation ACS (NSTE-ACS). The co-primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5, and the co-primary cardiovascular endpoint was a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischaemic stroke at 1 month. Irrespective of the subgroups, the effect of no-aspirin compared with DAPT was not significant for the bleeding endpoint (HBR [N = 1803]: 7.27 and 7.91%, hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.65-1.28; non-HBR [N = 2673]: 3.40 and 3.65%, HR 0.93, 95% CI 0.62-1.39; Pinteraction = 0.94; STEMI [N = 2553]: 6.58 and 6.56%, HR 1.00, 95% CI 0.74-1.35; NSTE-ACS [N = 1923]: 2.94 and 3.64%, HR 0.80, 95% CI 0.49-1.32; Pinteraction = 0.45), and for the cardiovascular endpoint (HBR: 7.87 and 5.75%, HR 1.39, 95% CI 0.97-1.99; non-HBR: 2.56 and 2.67%, HR 0.96, 95% CI 0.60-1.53; Pinteraction = 0.22; STEMI: 6.07 and 5.46%, HR 1.11, 95% CI 0.81-1.54; NSTE-ACS: 3.03 and 1.71%, HR 1.78, 95% CI 0.97-3.27; Pinteraction = 0.18)., Conclusion: In patients with ACS undergoing PCI, the no-aspirin strategy compared with the DAPT strategy failed to reduce major bleeding events irrespective of HBR and ACS subtypes. The numerical excess risk of the no-aspirin strategy relative to the DAPT strategy for cardiovascular events was observed in patients with HBR and in patients with NSTE-ACS., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The effects of aspirin-free strategy on bleeding and cardiovascular events in patients undergoing percutaneous coronary intervention with oral anticoagulation (OAC) have not been fully elucidated., Methods and Results: We conducted the prespecified subgroup analysis based on the use of OAC, including vitamin K antagonist and direct oral anticoagulants, within 7 days before percutaneous coronary intervention in the STOPDAPT-3 (Short and Optimal Duration of Dual Antiplatelet Therapy-3) trial, which randomly compared prasugrel monotherapy (2984 patients) to dual antiplatelet therapy (DAPT) with prasugrel and aspirin (2982 patients) in patients with acute coronary syndrome or high bleeding risk. The coprimary end points were major bleeding events (Bleeding Academic Research Consortium types 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month. Among 5966 study patients, there were 530 patients (8.9%) with OAC (no aspirin: N=248, and DAPT: N=282) and 5436 patients (91.1%) without OAC (no aspirin: N=2736, and DAPT: N=2700). Regardless of the use of OAC, the effects of no aspirin compared with DAPT were not significant for the bleeding end point (OAC: 4.45% and 4.27%, hazard ratio [HR], 1.04 [95% CI, 0.46-2.35]; no-OAC: 4.47% and 4.75%, HR, 0.94 [95% CI, 0.73-1.20]; P for interaction=0.82), and for the cardiovascular end point (OAC: 4.84% and 3.20%, HR, 1.53 [95% CI, 0.64-3.62]; no-OAC: 4.06% and 3.74%, HR, 1.09 [95% CI 0.83-1.42]; P for interaction =0.46)., Conclusions: The no-aspirin strategy compared with the DAPT strategy failed to reduce major bleeding events irrespective of the use of OAC. There was a numerical excess risk of the no-aspirin strategy relative to the DAPT strategy for cardiovascular events in patients with OAC.

Purpose: We investigated the recovery of the Japanese orthopedic association back pain evaluation questionnaire (JOABPEQ) scores and 6 min walk distance (6MWD) in patients after surgery for lumbar spinal stenosis and identified the items among 25 questions of JOABPEQ that showed recovery., Methods: A total of 227 patients (average age 71.5 years; SD: 7.5; 121 men) were included from a single center. The outcome measures were JOABPEQ, visual analog scale (VAS), and 6MWD and obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. Mixed-model repeated measures were used to compare the variables at each time point between the surgery groups., Results: The JOABPEQ, VAS, and 6MWD scores generally improved at 1 month postoperatively compared with those obtained preoperatively, and some parameters further improved at 3 months. However, improvement in the lumbar spine dysfunction item of JOABPEQ was delayed, showing improvement at 3 months postoperatively for decompression surgery (average score: pre, 64.6; 3 months, 78.5) and 6 months postoperatively for fusion surgery (average score: Pre, 64.3; 6 months, 77.1). Responses to the individual JOABPEQ questions generally improved after surgery. No significant changes in lumbar spine dysfunction occurred in the fusion group., Conclusion: Our results demonstrated the early postoperative recovery course of JOABPEQ and 6MWD. In the fusion group, significant changes in lumbar spine dysfunction started at 6 months postoperatively. These findings could help medical staff explain postoperative recovery to patients after lumbar spinal stenosis surgery and in their decision making regarding surgery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Side branch (SB) occlusion during bifurcation stenting is a serious complication. This study aimed to predict SB compromise (SBC) using optical coherence tomography (OCT)., Methods and results: Among the 168 patients who enrolled in the 3D-OCT Bifurcation Registry, 111 bifurcation lesions were analyzed to develop an OCT risk score for predicting SBC. SBC was defined as worsening of angiographic SB ostial stenosis (≥90%) immediately after stenting. On the basis of OCT before stenting, geometric parameters (SB diameter [SBd], length from proximal branching point to carina tip [BP-CT length], and distance of the polygon of confluence [dPOC]) and 3-dimensional bifurcation types (parallel or perpendicular) were evaluated. SBC occurred in 36 (32%) lesions. The parallel-type bifurcation was significantly more frequent in lesions with SBC. The receiver operating characteristic curve indicated SBd ≤1.77 mm (area under the curve [AUC]=0.73, sensitivity 64%, specificity 75%), BP-CT length ≤1.8 mm (AUC=0.83, sensitivity 86%, specificity 68%), and dPOC ≤3.96 mm (AUC=0.68, sensitivity 63%, specificity 69%) as the best cut-off values for predicting SBC. To create the OCT risk score, we assigned 1 point to each of these factors. As the score increased, the frequency of SBC increased significantly (Score 0, 0%; Score 1, 8.7%; Score 2, 28%; Score 3, 58%; Score 4, 85%; P<0.0001)., Conclusions: Prediction of SBC using OCT is feasible with high probability.

Background: There was no study evaluating the effects of an aspirin-free strategy in patients undergoing complex percutaneous coronary intervention (PCI)., Objectives: The authors aimed to evaluate the efficacy and safety of an aspirin-free strategy in patients undergoing complex PCI., Methods: We conducted the prespecified subgroup analysis based on complex PCI in the STOPDAPT-3 (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3), which randomly compared low-dose prasugrel (3.75 mg/d) monotherapy to dual antiplatelet therapy (DAPT) with low-dose prasugrel and aspirin in patients with acute coronary syndrome or high bleeding risk. Complex PCI was defined as any of the following 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or a target of chronic total occlusion. The coprimary endpoints were major bleeding events (Bleeding Academic Research Consortium 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month., Results: Of the 5,966 study patients, there were 1,230 patients (20.6%) with complex PCI. Regardless of complex PCI, the effects of no aspirin relative to DAPT were not significant for the coprimary bleeding (complex PCI: 5.30% vs 3.70%; HR: 1.44; 95% CI: 0.84-2.47; P = 0.18 and noncomplex PCI: 4.26% vs 4.97%; HR: 0.85; 95% CI: 0.65-1.11; P = 0.24; P for interaction = 0.08) and cardiovascular (complex PCI: 5.78% vs 5.93%; HR: 0.98; 95% CI: 0.62-1.55; P = 0.92 and noncomplex PCI: 3.70% vs 3.10%; HR: 1.20; 95% CI: 0.88-1.63; P = 0.25; P for interaction = 0.48) endpoints without significant interactions., Conclusions: The effects of the aspirin-free strategy relative to standard DAPT for the cardiovascular and major bleeding events were not different regardless of complex PCI. (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111)., Competing Interests: Funding Support and Author Disclosures This study was funded by Abbott Medical Japan. Dr Natsuaki has received honoraria from Abbott Medical Japan, Daiichi-Sankyo, Medtronic, Terumo, Japan Lifeline, Asahi Intecc, Bristol Myers Squibb, Otsuka, Amgen, Sanofi, Takeda, and Bayer. Dr Watanabe has received personal fees from Abbott Medical Japan during the conduct of the study as well as personal fees from Daiichi-Sankyo, Kowa, Abiomed, Bayer, Pfizer, Bristol Myers Squibb, and Otsuka outside the submitted work. Dr Morimoto has received lecturer fees from AstraZeneca, Bristol Myers Squibb, Daiichi-Sankyo, Japan Lifeline, Kowa, Pfizer, and Tsumura; has received manuscript fees from Bristol Myers Squibb and Pfizer; and has served on the Advisory Boards for Novartis and Teijin. Dr Suwa has received personal fees from Abbott Medical Japan and Daiichi-Sankyo outside the submitted work. Dr Kimura has received grants from Abbott Medical Japan and Boston Scientific; and has served on the Advisory Boards of Abbott Medical Japan and Terumo Japan. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The rapid and precise creation of complex molecules while controlling multiple selectivities is the principal objective in synthetic chemistry. Combining data science and organic synthesis to achieve this goal is an emerging trend, but few examples of successful reaction designs are reported. We develop an artificial neural network regression model using bond orbital data to predict chemical reactivities. Actual experimental verification confirms cycloheptatriene-selective [6 + 2]-cycloaddition utilizing nitroso compounds and norcaradiene-selective [4 + 2]-cycloaddition reactions employing benzynes. Additionally, a one-pot asymmetric synthesis is achieved by telescoping the enantioselective dearomatization of non-activated benzenes and cycloadditions. Computational studies provide a rational explanation for the seemingly anomalous occurrence of thermally prohibited suprafacial [6 + 2]-cycloaddition without photoirradiation., (© 2024. The Author(s).)

Background: Bleeding rates on dual antiplatelet therapy (DAPT) within 1 month after percutaneous coronary intervention (PCI) remain high in clinical practice, particularly in patients with acute coronary syndrome or high bleeding risk. Aspirin-free strategy might result in lower bleeding early after PCI without increasing cardiovascular events, but its efficacy and safety have not yet been proven in randomized trials., Methods: We randomly assigned 6002 patients with acute coronary syndrome or high bleeding risk just before PCI either to prasugrel (3.75 mg/day) monotherapy or to DAPT with aspirin (81-100 mg/day) and prasugrel (3.75 mg/day) after loading of 20 mg of prasugrel in both groups. The coprimary end points were major bleeding (Bleeding Academic Research Consortium 3 or 5) for superiority and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) for noninferiority with a relative 50% margin., Results: The full analysis set population consisted of 5966 patients (no-aspirin group, 2984 patients; DAPT group, 2982 patients; age, 71.6±11.7 years; men, 76.6%; acute coronary syndrome, 75.0%). Within 7 days before randomization, aspirin alone, aspirin with P2Y12 inhibitor, oral anticoagulants, and intravenous heparin infusion were given in 21.3%, 6.4%, 8.9%, and 24.5%, respectively. Adherence to the protocol-specified antiplatelet therapy was 88% in both groups at 1 month. At 1 month, the no-aspirin group was not superior to the DAPT group for the coprimary bleeding end point (4.47% and 4.71%; hazard ratio, 0.95 [95% CI, 0.75-1.20]; P superiority =0.66). The no-aspirin group was noninferior to the DAPT group for the coprimary cardiovascular end point (4.12% and 3.69%; hazard ratio, 1.12 [95% CI, 0.87-1.45]; P non inferiority =0.01). There was no difference in net adverse clinical outcomes and each component of coprimary cardiovascular end point. There was an excess of any unplanned coronary revascularization (1.05% and 0.57%; hazard ratio, 1.83 [95%CI, 1.01-3.30]) and subacute definite or probable stent thrombosis (0.58% and 0.17%; hazard ratio, 3.40 [95% CI, 1.26-9.23]) in the no-aspirin group compared with the DAPT group., Conclusions: The aspirin-free strategy using low-dose prasugrel compared with the DAPT strategy failed to attest superiority for major bleeding within 1 month after PCI but was noninferior for cardiovascular events within 1 month after PCI. However, the aspirin-free strategy was associated with a signal suggesting an excess of coronary events., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04609111., Competing Interests: Disclosures Dr Natsuaki reports honoraria from Abbott Medical Japan, Daiichi Sankyo, Medtronic, Terumo, Japan Lifeline, Asahi Intecc, Bristol-Myers Squibb, Otsuka, Amgen, Sanofi, Takeda and Bayer. Dr Watanabe reports personal fees from Abbott Medical Japan during the conduct of the study, and personal fees from Daiichi Sankyo, Kowa, Abiomed, Bayer, Pfizer, Bristol-Myers Squibb, and Otsuka, as well, outside the submitted work. Dr Morimoto reports lecturer’s fees from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Pfizer and Tsumura; manuscript fees from Bristol-Myers Squibb and Pfizer; advisory board for Novartis and Teijin. Dr Suwa reports personal fees from Abbott Medical Japan and Daiichi Sankyo outside the submitted work. Dr Ogita reports personal fees from Daiichi Sankyo, Abbott Medical Japan, and Japan Lifeline outside the submitted work. Dr Suzuki reports grants from Abbott Medical Japan during the conduct of the study. Dr Morishima reports honoraria from Abbott Medical Japan and Daiichi Sankyo. Dr Kimura reports grants from Abbott Medical Japan and Boston Scientific and being an advisory board member of Abbott Medical Japan and Terumo Japan. The remaining authors reported no conflicts.

We previously demonstrated that dietary supplementation with Dunaliella tertiolecta (DT) increases uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT) and improves diet-induced obesity (DIO) in C57BL/6 J mice at thermoneutrality (30 °C). Here, we investigated whether DT improves DIO in a thermoneutral UCP1-deficient (KO) animal. KO mice were fed a high-fat diet supplemented with DT for 12 weeks. Compared to control group without DT, body weight was significantly reduced in DT group with no difference in food intake. Dunaliella tertiolecta-supplemented mice exhibited lower adiposity and well-maintained multilocular morphology in BAT, in which a significant increase in gene expression of PR domain containing 16 was detected in DT group compared to control group. Moreover, increase in UCP2 level and/or decrease in ribosomal protein S6 phosphorylation were detected in adipose tissues of DT group relative to control group. These results suggest that DT supplementation improves DIO by stimulating UCP1-independent energy dissipation at thermoneutrality., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

This study was conducted to evaluate the effects of ceramic microbeads on the bond strength between resin and zirconia. Microbeads made of zirconia (TZ) and zircon (ZS) were treated with and without hydrofluoric acid (HF). The microbeads were sintered to zirconia disks using intermediate feldspathic porcelains. Two control groups, NB (without microbeads) and AS (without porcelain and microbeads), were also prepared. All specimens were treated with a phosphate primer and veneered with a light-curing resin composite. The 24-h shear bond strengths were determined and analyzed by the Tukey-Kramer test (α=0.05, n=10). The TZ-HF specimen exhibited the highest bond strength, followed by TZ, ZS-HF, ZS, AS, and NB. Scanning electron microscopy observations revealed that the TZ-HF specimen had a complicated debonded surface, and it included microconcavities where the microbeads were detached. Sintering etched zirconia beads onto a zirconia framework with feldspathic porcelains is useful for bonding layered resin composite materials.

Background/aim: The lung-specific soluble lectins, SP-A and SP-D have been clinically used to diagnose interstitial lung disease, but their clinical significance in COVID-19 remains controversial. This study was undertaken to determine their association with other lectins (MBL and FCN1), disease severity, and radiographs in COVID-19 patients., Patients and Methods: A total of 131 patients with COVID-19 admitted in the Sapporo Medical University Hospital between May 22 and September 19, 2021, were enrolled in the study. Data including demographics, medical history, symptoms, signs, laboratory findings, and radiological images were collected from the patients' medical records. Chest computed tomography (CT) scanning was performed at admission. Serum levels of surfactant protein A and D (SP-A and SP-D), mannose-binding lectin (MBL) and ficolin1 (FCN1) were measured using enzyme-linked immunosorbent assay (ELISA) kits., Results: Compared to the control group, the COVID-19 group had significantly higher serum SP-A and FCN1 levels on admission (SP-A: 59.60±38.89 vs. 35.61±11.22 ng/ml; p<0.01, FCN1: 542.45±506.04 vs. 250.6±161.1 ng/ml; p<0.01). The severe group in COVID-19 had significantly higher serum SP-D and lower MBL levels than the non-severe group (SP-D: 141.7±155.7 vs. 61.41±54.54 ng/ml; p<0.01, MBL: 1,670±1,240 vs. 2,170±1,140 ng/ml; p<0.05). SP-D strongly reflected the degree of imaging findings, whereas SP-A showed a significant correlation, albeit slightly weaker than SP-D. Conversely, MBL and FNC1 were not significantly correlated with imaging findings., Conclusion: Among soluble serum lectins, SP-A and SP-D may be more sensitive to CT findings than reported disease biomarkers such as IL-6, LDH, and CRP due to their lung-specific characteristics., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Study Design: Retrospective review of prospectively collected data., Objective: We evaluated the responsiveness of the 6-minute walk distance (6MWD) and determined the threshold of the minimal clinically important difference (MCID) in patients who underwent lumbar spinal stenosis (LSS) surgery., Summary of Background Data: Little evidence exists on the MCID of 6MWD after LSS surgery. The 6MWD is an objective gait assessment that can be measured quickly., Materials and Methods: In total, 126 patients (74 men; average age, 72.2 ± 6.5 yr) were included and assessed preoperatively and at 12 months postoperatively. We used the Oswestry Disability Index (ODI), as an anchor to calculate the MCID for the 6MWD and measured internal and external responsiveness of the 6MWD. The external responsiveness was assessed in 2 ways: (1) One based on the anchoring questionnaire and (2) another based on the scale distribution. The anchor-based approach was evaluated using the Spearman rank correlation coefficient and receiver-operating characteristic curve. The distribution-based approach was evaluated using the minimal detectable change., Results: The ODI scores and 6MWD for each anchor significantly improved postoperatively. The change in the 6MWD was significantly correlated with change in the ODI (6 mo, r = -0.45; 12 mo, r = -0.49). The receiver-operating characteristic analysis demonstrated good discriminative properties for the 6MWD using the ODI anchor (6 mo, 0.72; 12 mo, 0.78). The cutoff values for 6MWD were 102.3 and 57.5 at 6 and 12 months, respectively. In the distribution-based approach, the minimal detectable change for the 6MWD was 95.7 m., Conclusions: We validated both the internal and external responsiveness of the 6MWD using the ODI and estimated the MCID in the 6MWD for patients undergoing LSS surgery. However, there was lower validity for the MCID among those participants with the high walking ability and low disability at baseline., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The success of the lead halide perovskites in diverse optoelectronics has motivated considerable interest in their fundamental photocarrier dynamics. Here we report the discovery of photocarrier-induced persistent structural polarization and local ferroelectricity in lead halide perovskites. Photoconductance studies of thin-film single-crystal CsPbBr 3 at 10 K reveal long-lasting persistent photoconductance with an ultralong photocarrier lifetime beyond 10 6  s. X-ray diffraction studies reveal that photocarrier-induced structural polarization is present up to a critical freezing temperature. Photocapacitance studies at cryogenic temperatures further demonstrate a systematic local phase transition from linear dielectric to paraelectric and relaxor ferroelectric under increasing illumination. Our theoretical investigations highlight the critical role of photocarrier-phonon coupling and large polaron formation in driving the local relaxor ferroelectric phase transition. Our findings show that this photocarrier-induced persistent structural polarization enables the formation of ferroelectric nanodomains at low temperature, which suppress carrier recombination and offer the possibility of exploring intriguing carrier-phonon interplay and the rich polaron photophysics., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

A new antibacterial 3-monoacyl- sn -glycerol, nostochopcerol ( 1 ), was isolated from a cultured algal mass of the edible cyanobacterium Nostochopsis lobatus MAC0804NAN. The structure of compound 1 was established by the analysis of NMR and MS data while its chirality was established by comparison of optical rotation values with synthetically prepared authentics. Compound 1 inhibited the growth of Bacillus subtilis and Staphylococcus aureus at MIC of 50 μg/mL and 100 μg/mL, respectively., (Copyright © 2023, Oku et al.)

A compact and simple 355-nm direct-detection Doppler wind lidar (DDDWL) was developed to measure the line-of-sight (LOS) wind speed of the background atmosphere from atmospheric molecule return signals with and without aerosols and clouds. A receiver design with a Fabry-Perot etalon interferometer (FPEI) without an inside deposited step coating or fiber coupling is considered for the DDDWL using the double-edge technique. The receiver with the double-edge technique uses a FPEI and wedge prism to form a double-edge filter. The development of the double-edge filter in this combination is, to the best of our knowledge, an improvement at 355-nm wavelength. Considerations for the DDDWL receiver with a FPEI revealed that a full-angle light beam divergence into the FPEI and a working FPEI aperture are significant factors for the receiver design. Preliminary experimental evaluation demonstrated that the DDDWL had the potential of LOS wind speed measurements with a random error of less than 1 m/s when the signal-to-noise ratio was approximately 300. The DDDWL-measured vertical LOS wind speed profile was consistent with that of a 2-µm coherent Doppler wind lidar within the measurement error range. The preliminary experimental LOS wind measurement results demonstrated the capability of the DDDWL to measure low LOS wind speeds.

Although decompression surgery for lumbar spinal canal stenosis (LSS) improves leg symptoms, low back pain (LBP), and disability, the factors related to the improvement of subjective disability have not been studied sufficiently. The purpose of the study was to clarify the relationship between subjective disability and objective physical function parameters. A total of 51 patients who underwent decompression were included and evaluated preoperatively and 6 and 12 months postoperatively. Patient-reported outcomes related to activity limitation due to LBP were evaluated using Roland-Morris disability questionnaire (RDQ) and VAS (Visual Analog Scale). Physical function was assessed using 6-min walk distance (6MWD) and trunk muscle strength. Univariate analysis and multivariable linear regression analysis were performed to identify significant factors for RDQ score change. The 6- and 12-month postoperative RDQ scores, VAS scores, and trunk extensor strength significantly improved relative to the preoperative values. In the univariate analysis, age, changes in VAS (LBP, leg pain, and numbness) scores, and change in 6MWD were associated with the RDQ score change ( p < 0.05). Multivariable linear regression showed that 6MWD changes were significantly associated with RDQ score changes, explaining 41% of the variance in the RDQ score change. This study showed the change in 6MWD was significantly associated with the RDQ score change. Our results suggest that improving 6MWD may reduce disability in activities of daily living., Competing Interests: The authors have no conflicts of interest to declare.

In addition to the well-known motor control, the cerebellum has recently been implicated in memory, cognition, addiction, and social behavior. Given that the cerebellum contains more neurons than the cerebral cortex and has tight connections to the thalamus and brainstem nuclei, it is possible that the cerebellum also regulates sleep/wakefulness. However, the role of the cerebellum in sleep was unclear, since cerebellar lesion studies inevitably involved massive inflammation in the adjacent brainstem, and sleep changes in lesion studies were not consistent with each other. Here, we examine the role of the cerebellum in sleep and wakefulness using mesencephalon- and rhombomere 1-specific Ptf1a conditional knockout ( Ptf1a cKO) mice, which lack the cerebellar cortex and its related structures, and exhibit ataxic gait. Ptf1a cKO mice had similar wake and non-rapid eye movement sleep (NREMS) time as control mice and showed reduced slow wave activity during wakefulness, NREMS and REMS. Ptf1a cKO mice showed a decrease in REMS time during the light phase and had increased NREMS delta power in response to 6 h of sleep deprivation, as did control mice. Ptf1a cKO mice also had similar numbers of sleep spindles and fear memories as control mice. Thus, the cerebellum does not appear to play a major role in sleep-wake control, but may be involved in the generation of slow waves., 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 © 2022 Fujiyama, Takenaka, Asano, Miyanishi, Hotta-Hirashima, Ishikawa, Kanno, Seoane-Collazo, Miwa, Hoshino, Yanagisawa and Funato.)

Deep-sea water (DSW) contains multiple minerals and is widely used as drinking water, for cosmetic purposes, and as seasoning. In this study, several types of extract-added water with different levels of hardness (200, 300, 500) were prepared from DSW collected off the coast of Muroto City, Kochi Prefecture. We administrated it to obese mice for two months and tested it for several effects. Although there was no anti-obesity effect for any hardness level in obese mice, the cognitive functions of each DSW-extract-added water-treated group were significantly improved compared to control obese mice in the water maze test. Time-to-fall by the rota-rod test was also dramatically improved in the DSW-extract-added water-treated groups. The levels of triglycerides and blood urea nitrogen were significantly decreased in DSW-extract-added water-treated obese mice. However, these results did not depend on the hardness. Hardness levels of 200 or 300 of DSW-extract-added water had greater effects on cognitive function and serum scores compared to a level of 500. We analyzed DSW using inductively coupled plasma atomic emission spectroscopy and inductively coupled plasma mass spectrometry. High concentrations of magnesium and potassium were detected, but sodium was not detected at very high concentrations. Although the detailed mechanisms of its effects are not yet understood, chronic intake of DSW-extract-added water may have a beneficial effect on health.

Study Design: This was a retrospective review of prospectively collected data., Objective: We aimed to evaluate the responsiveness of the 6-minute walk distance (6MWD) and determine the threshold of the minimal clinically important difference (MCID) in the 6MWD in patients who underwent surgery for lumbar spinal canal stenosis (LSS) surgery., Summary of Background Data: The 6MWD rapidly and objectively assesses the walking distance in patients with LSS. To date, no study has assessed the MCID in the 6MWD in patients who underwent LSS surgery., Materials and Methods: A total of 41 patients (16 women; average age: 69.4 y, SD: 7.8 y) were included and assessed preoperatively and at 6 months postoperatively. We evaluated the 6MWD and Oswestry Disability Index (ODI), which is a health-related patientrReported outcome, used as an anchor to calculate the MCID for in the 6MWD. We used 2 different approaches to examine the responsiveness of the 6MWD: internal and external responsiveness. The external responsiveness was assessed in 2 ways: one based on the anchoring questionnaire and the other based on the scale distribution of the scale. The anchor-based approach was evaluated using the Spearman rank correlation coefficient and the receiver operating characteristic curve. The distribution-based approach was evaluated using the minimal detectable change., Results: The ODI scores and 6MWD for each anchor significantly improved postoperatively. The correlation coefficient between changes in the 6MWD and ODI was r=-0.58. The area under the receiver operating characteristic curve for the ODI anchor was 0.70 (95% confidence interval: 0.52-0.89), and the cutoff value for the ODI anchor was 50 m (sensitivity=0.57, specificity=0.71). In the distribution-based approach, the minimal detectable change for the 6MWD was 105.9 m., Conclusions: Both the internal and the external responsiveness of the 6MWD were validated using the ODI. Therefore, the MCID in the 6MWD in patients undergoing LSS surgery ranges from 50 to 105.9 m., Level of Evidence: Level III., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Behçet's disease (BD) is a recurrent multisystem inflammatory disease. Anti-tumor necrosis factor (TNF) α agents have been used to treat patients with intestinal BD with severe disease activity or those who are resistant to conventional treatments; however, the long-term efficacy of anti-TNFα agents in intestinal BD remains unclear. In the present study, we investigated the clinical outcomes and predictors of discontinuation of anti-TNFα agents in patients with intestinal BD., Methods: We reviewed the medical records of patients with intestinal BD who received first-line anti-TNFα agents between January 2009 and June 2020. The primary outcome was the percentage of patients who continued anti-TNFα therapy for 48 weeks. Secondary outcomes included the percentage of patients who achieved marked improvement, complete remission, and mucosal healing, as well as predictors of discontinuation of anti-TNFα agents., Results: A total of 29 patients were included in the study. Twenty-two (75.9%) patients continued anti-TNFα therapy for 48 weeks. The percentage of patients who achieved marked improvement, complete remission, and mucosal healing at week 48 was 48.3%, 37.9%, and 48.3%, respectively. At week 96, 11 (37.9%) patients achieved marked improvement, complete remission, and mucosal healing. A higher C-reactive protein level (CRP; ≥ 1 mg/dL) at baseline was a predictor of discontinuation of anti-TNFα agents., Conclusions: The 48-week continuation rate of anti-TNFα agents was 75.9% in bio-naïve patients with intestinal BD. However, a higher baseline CRP level (≥ 1 mg/dL) was associated with discontinuation of anti-TNFα agents., (© 2022. The Author(s).)

A beneficial surrogate marker for evaluating the effect of medical therapy is warranted to avoid deferred lesion revascularization. Similar to coronary artery imaging for monitoring the effects of medical therapy by analyzing plaque regression and stabilization, we hypothesized that evaluation of serial changes in the quantitative flow ratio (QFR) would serve as a surrogate marker of the effects of medical therapy against deferred lesion revascularization. Here, we investigated serial changes in QFR over time after percutaneous coronary intervention in patients who underwent medical therapy as a secondary prevention. Patients with intermediate stenosis in an untreated vessel observed at the baseline (BL) coronary angiography and follow-up (FU) coronary angiography performed 6-18 months after BL angiography were screened in 2 centers. A total of 52 patients were able to analyze both BL and FU QFR. The median QFR was 0.83 (IQR, 0.69, 0.89) at BL and 0.80 (IQR, 0.70, 0.86) at FU. The number of positive ΔQFR and negative ΔQFR were 21 and 31, respectively. The median ΔQFR was 0.05 (IQR, 0.03, 0.09) in positive ΔQFR and  - 0.05 (IQR,  - 0.07,  - 0.03) in negative ΔQFR (p < 0.0001). Univariate and multivariate analyses revealed that LDL-C at FU predicted improvement in the QFR (OR 0.95, 95% confidence interval [0.91, 0.98], P = 0.001). Assessment of serial changes in the QFR may serve as a surrogate marker for the effects of medical therapy in patients with residual intermediate coronary stenosis., (© 2021. Springer Japan KK, part of Springer Nature.)

Aim: To investigate the characteristics of coronary artery bifurcation type (parallel or perpendicular type) using three-dimensional (3D) optical coherence tomography (OCT), and determine the feasibility, reproducibility, assessment time and correlation with bifurcation angles measured by 3D quantitative coronary angiography (QCA)., Methods and Results: We evaluated 60 lesions at the coronary bifurcation that were treated by main vessel (MV) stenting with kissing balloon inflation (KBI) under OCT/optical frequency domain imaging (OFDI) guidance. Inter- and intra-observer agreement regarding the assessment of 3D bifurcation types were 0.88 and 0.94, respectively. The assessment times of 3D-OCT bifurcation type with OCT and OFDI were within about 30 seconds. 3D-OCT bifurcation types showed the greatest correlation with the distal bifurcation angle assessed by 3D-QCA among the three bifurcation angles (distal bifurcation angle, proximal bifurcation angle and main vessel angle), and the optimal cut-off distal bifurcation angle to predict a perpendicular type bifurcation, as determined by ROC analysis, was 51.0° (AUC 0.773, sensitivity 0.80, specificity 0.67). Based on this cut-off value for the distal bifurcation angle (51°), the diagnostic accuracy for perpendicular type bifurcation in cases with a BA ≥ 51° (n = 34) was 70.6% (24/34) and that of the parallel type bifurcation in cases of BA < 51° (n = 26) was 76.9% (20/26)., Conclusion: Performing 3D-OCT for assessment of coronary artery bifurcation type is feasible and simple, and can be done in a short time with high reproducibility., Competing Interests: Dr. Okamura received honoraria from Terumo Corp. and Abbott Vascular. The other authors have no conflicts of interest to declare in relation to this investigation.

Global trends focus on a balanced intake of foods and beverages to maintain health. Drinking water (MIU; hardness = 88) produced from deep sea water (DSW) collected offshore of Muroto, Japan, is considered healthy. We previously reported that the DSW-based drinking water (RDSW; hardness = 1000) improved human gut health. The aim of this randomized double-blind controlled trial was to assess the effects of MIU on human health. Volunteers were assigned to MIU ( n = 41) or mineral water (control) groups ( n = 41). Participants consumed 1 L of either water type daily for 12 weeks. A self-administered questionnaire was administered, and stool and urine samples were collected throughout the intervention. We measured the fecal biomarkers of nine short-chain fatty acids (SCFAs) and secretory immunoglobulin A (sIgA), as well as urinary isoflavones. In the MIU group, concentrations of three major SCFAs and sIgA increased postintervention. MIU intake significantly affected one SCFA (butyric acid). The metabolic efficiency of daidzein-to-equol conversion was significantly higher in the MIU group than in the control group throughout the intervention. MIU intake reflected the intestinal environment through increased production of three major SCFAs and sIgA, and accelerated daidzein-to-equol metabolic conversion, suggesting the beneficial health effects of MIU.

Purpose: Zirconia cores and frameworks are widely used in restorative dentistry. Although these structures are veneered with porcelain for esthetic reasons, the use of indirect composite resins (ICRs) is expected to increase in the future. The purpose of this study was to investigate the effects of microslits of different dimensions formed by Nd:YVO 4 laser machining on the bond strength between two types of zirconia (3 mol% yttria-partially stabilized zirconia (Y-TZP) and ceria-partially stabilized zirconia/alumina nanocomposite (Ce-TZP/A)) and porcelain or an ICR., Methods: The zirconia disks were assigned as follows: 1) blasted with alumina particles (AB) and 2-4) surface machined with gridded microslits with a width, pitch, and depth of 50, 75, or 100 µm (MS50, MS75, and MS100, respectively). After the bonding of the veneering materials to the disks, half of the specimens veneered with the ICR were subjected to thermocycling (4-60°C, 20000 cycles). All the specimens were subsequently shear tested (n = 10/group)., Results: There was no significant difference between the groups of the disks bonded to porcelain. On the other hand, for the disks bonded to the ICR, the bond strengths of the MS groups after thermocycling were statistically higher than that of the AB group. However, there was no significant difference in the bond strengths of the disks with different microslits., Conclusion: Within the study limitations, it can be concluded that, for porcelain, the design of the mechanical retentive structure must be modified. However, for the investigated ICR, a simple gridded pattern can improve the bond strength with zirconia.

Aims: Clinical scores that consider physical and social factors to predict long-term observations in patients after acute heart failure are limited. This study aimed to develop and validate a prediction model for patients with acute heart failure at the time of discharge., Methods and Results: This study was retrospective analysis of the Kitakawachi Clinical Background and Outcome of Heart Failure Registry database. The registry is a prospective, multicentre cohort of patients with acute heart failure between April 2015 and August 2017. The primary outcome to be predicted was the incidence of all-cause mortality during the 3 years of follow-up period. The development cohort derived from April 2015 to July 2016 was used to build the prediction model, and the test cohort from August 2016 to August 2017 was used to evaluate the prediction model. The following potential predictors were selected by the least absolute shrinkage and selection operator method: age, sex, body mass index, activities of daily living at discharge, social background, comorbidities, biomarkers, and echocardiographic findings; a risk scoring system was developed using a logistic model to predict the outcome using a simple integer based on each variable's β coefficient. Out of 1253 patients registered, 1117 were included in the analysis and divided into the development (n = 679) and test (n = 438) cohorts. The outcomes were 246 (36.2%) in the development cohort and 143 (32.6%) in the test cohort. Eleven variables including physical and social factors were set into the logistic regression model, and the risk scoring system was created. The patients were divided into three groups: low risk (score 0-5), moderate risk (score 6-11), and high risk (score ≥12). The observed and predicted mortality rates were described by the Kaplan-Meier curve divided by risk group and independently increased (P < 0.001). In the test cohort, the C statistic of the prediction model was 0.778 (95% confidence interval: 0.732-0.824), and the mean predicted probabilities in the groups were low, 6.9% (95% confidence interval: 3.8-10%); moderate, 30.1% (95% confidence interval: 25.4%-34.8%); and high, 79.2% (95% confidence interval: 72.6%-85.8%). The predicted probability was well calibrated to the observed outcomes in both cohorts., Conclusions: The Kitakawachi Clinical Background and Outcome of Heart Failure score was helpful in predicting adverse events in patients with acute heart failure over a long-term period. We should evaluate the physical and social functions of such patients before discharge to prevent adverse outcomes., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

We developed novel closo -dodecaborate ([B 12 H 11 ] 2- ) anion-containing translocator protein (TSPO) ligand as a boron carrier for boron neutron capture therapy. This compound shows high water solubility and can deliver boron to TSPO highly expressed in breast cancer cells. We describe the synthesis and in vitro evaluation of a dodecaborate-based pyrazolopyrimidine., Competing Interests: The authors declare no competing financial interest., (© 2021 American Chemical Society.)

Through first-principles real-time density-matrix (FPDM) dynamics simulations, we investigated spin relaxation due to electron-phonon and electron-impurity scatterings with spin-orbit coupling (SOC) in two-dimensional Dirac materials silicene and germanene at finite temperatures. We discussed the applicability of conventional descriptions of spin relaxation mechanisms by Elliott-Yafet (EY) and D'yakonov-Perel' (DP) compared to the FPDM method, which is determined by a complex interplay of intrinsic SOC, external fields, and scattering strength. For example, the electric field dependence of the spin lifetime by FPDM is close to the DP mechanism for silicene at room temperature but similar to the EY mechanism for germanene. Because of its stronger SOC strength and buckled structure in contrast to graphene, germanene has a giant spin lifetime anisotropy and spin-valley locking effect under nonzero E z and low temperatures. More importantly, germanene has a long spin lifetime (∼100 ns at 50 K) and an ultrahigh carrier mobility, making it advantageous for spin-valleytronic applications.

Fundamental properties of alkali metal fluorides (MF, M = Cs, K) dissolved in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) or in 3,3,3-trifluoroethanol (TFE) are investigated, including solubility, conductivity, and viscosity. Solid-state structures of single crystals obtained from CsF/HFIP and CsF/TFE are described for the first time, giving insights into the multiple interactions between fluorinated alcohols and CsF. Applications in electrochemical fluorination reactions are successfully demonstrated.

Objective: Amphotericin B (AMPH-B) is used to prevent opportunistic infections associated with immunosuppressive therapy after heart transplantation (HTx), while the blood concentrations of tacrolimus (TAC) are carefully controlled. Although AMPH-B has the potential to inhibit TAC metabolism in in vitro studies, its interaction with clinically used AMPH-B oral suspension has not been investigated. In the present study, we examined whether oral AMPH-B therapy influences the pharmacokinetics of TAC in HTx patients., Materials and Methods: A retrospective study was performed at the National Cerebral and Cardiovascular Center in Japan. All patients with HTx enrolled in the study received standard triple-drug immunosuppression therapy including the regular release of TAC, mycophenolate mofetil, and prednisolone as well as prophylactic therapy with AMPH-B oral suspension. Patient characteristics and clinical laboratory data were collected from the electronic medical record system. Blood concentrations of TAC were used for pharmacokinetic analysis., Results: A total of 14 patients were enrolled in the study. There were no statistically significant differences in the variables except for serum creatinine levels and eGFR before and after discontinuation of oral AMPH-B therapy. The dose and trough concentrations of TAC and the area under the time-concentration curve and apparent oral clearance calculated from its concentrations were not influenced by discontinuation of AMPH-B treatment., Conclusion: The prophylactic treatment with AMPH-B oral suspension did not influence the pharmacokinetics of TAC and was demonstrated as a safe and easy method to prevent early post-HTx fungal infection.

High defect tolerance has been considered a primary reason for the long charge carrier lifetime and high photoluminescence quantum yield in bulk lead halide perovskites (LHPs). On the other hand, surface defects play a critical role in determining charge carrier dynamics and optical properties, especially for LHP nanocrystals and quantum dots. Understanding the nature of surface defects and developing strategy for their effective passivation are thus of strong interest. Focusing on a prototypical LHP, CsPbBr 3 , our work uses first-principles calculations to reveal that interstitial sites and antisites can have lower formation energies when they form at the surface while simultaneously creating deep trap states within the bandgap. Meanwhile, the formation of halide vacancies is energetically less favorable. On the basis of a new surface defect model, we demonstrate the explicit role of molecular ligands in passivating these defects, which eliminate trap states in favor of shallow states and enhance photoluminescence.

Introduction: The objectives of the present study were to clarify the frequency and content of family issues for patients in Japanese clinics, and the concordance between physicians' and patients' views of family issues., Methods: In this study, we used a cross-sectional design with a questionnaire survey. Participants were outpatients and their physicians in charge (four family physicians) at four Japanese clinics. The main body of research was conducted between April 5 and May 15, 2004. After obtaining oral informed consent, the physician in charge distributed questionnaires to participating patients to complete at home. The questionnaire comprised three items: 1) Do you have any worries about your family? 2) Are you comfortable consulting a physician regarding your family issue?, and 3) If possible, could you tell us why you feel like that?Participants provided written informed consent and answered the questionnaire before sealing it in an envelope and posting it back to the research center. Physicians in charge completed their version of the questionnaire and independently sent the data to the center., Results: Of the 272 participating patients, 118 (45.6%) had family issues. "Health problems with family members" (28%) and "family life cycle issues" (19.5%) were the main content of these issues. Physicians indicated that 45.7% of patients had family issues. The rate of concordance between physicians' and patients' perspectives regarding family issues was 46.6%., Conclusions: Family issues can therefore be regarded as a common health problem due to the frequency. There was some inconsistency between physicians' and patients' views, but much of this discrepancy may be resolved by developing the specialty of family practice., Competing Interests: None, (Copyright © Japan Medical Association.)

Background: In Japan, both the prevalence of the elderly and super-elderly and those of acute heart failure (AHF) have been increasing rapidly., Methods: This registry was a prospective multicenter cohort, which enrolled a total of 1253 patients with AHF. In this study, 1117 patients' follow-up data were available and were categorized into three groups according to age: <75 years old (nonelderly), 75-84 years old (elderly), and ≥ 85 years old (super-elderly). The endpoint was defined as all-cause death and each mode of death after discharge during the 3-years follow-up period., Results: Based on the Kaplan-Meier analysis, a gradually increased risk of all-cause death according to age was found. Among the three groups, the proportion of HF death was of similar trend; however, the proportion of infection death was higher in elderly and super-elderly patients. After adjusting for potentially confounding effects using the Cox and Fine-Gray model, the hazard ratio (HR) of all-cause death increased significantly in elderly and super-elderly patients (HR, 2.60; 95% confidence interval [CI], 1.93-3.54 and HR, 5.04; 95% CI, 3.72-6.92, respectively), when compared with nonelderly patients. The highest sub-distribution HR in detailed mode of death was infection death in elderly and super-elderly patients (HR, 4.25; 95% CI, 1.75-10.33 and HR, 10.10; 95% CI, 3.78-27.03, respectively)., Conclusions: In this population, the risk of all-cause death was found to increase in elderly and super-elderly. Elderly patients and especially super-elderly patients with AHF were at a higher risk for noncardiovascular death, especially infection death., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: This study investigated whether combination therapy (CT) with renin-angiotensin system inhibitors and β-blockers improved endpoints in acute heart failure (AHF). Methods and Results: AHF patients were recruited to this prospective multicenter cohort study between April 2015 and August 2017. Patients were divided into 3 categories based on ejection fraction (EF), namely heart failure (HF) with reduced EF (HFrEF), HF with midrange EF (HFmrEF), and HF with preserved EF (HFpEF), and a further into 2 groups according to physical status (those who could walk independently outdoors and those who could not). The composite endpoint included all-cause mortality and hospitalization for HF. Data at the 1-year follow-up were available for 1,018 patients. The incidence of the composite endpoint was significantly lower in the CT than non-CT group for HFrEF patients, but not among HFmrEF and HFpEF patients. For patients who could walk independently outdoors, a significantly lower rate of the composite endpoint was recorded only in the HFrEF group. The differences were maintained even after adjustment for comorbidities and prescriptions, with hazard ratios (95% confidence intervals) of 0.39 (0.20-0.76) and 0.48 (0.22-0.99), respectively. Conclusions: In this study, CT was associated with the prevention of adverse outcomes in patients with HFrEF. Moreover, CT prevented adverse events only among patients without a physical disorder, not among those with a physical disorder., Competing Interests: The authors have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021, THE JAPANESE CIRCULATION SOCIETY.)

A 48-year-old male was transported to the emergency room with a dirty rusty nail stuck in his chest. Three-dimensional computed tomography (3D-CT) scan revealed that the nail had penetrated the sternum and its tip was close to the left innominate vein. Emergency surgery was performed to avoid severe infections and major vascular injury. The nail was easily removed. We cleansed and debrided the wound which remained open to prevent infection, and was closed on post-operative day 3.

Assessing the seasonal patterns of the Amazon rainforests has been difficult because of the paucity of ground observations and persistent cloud cover over these forests obscuring optical remote sensing observations. Here, we use data from a new generation of geostationary satellites that carry the Advanced Baseline Imager (ABI) to study the Amazon canopy. ABI is similar to the widely used polar orbiting sensor, the Moderate Resolution Imaging Spectroradiometer (MODIS), but provides observations every 10-15 min. Our analysis of NDVI data collected over the Amazon during 2018-19 shows that ABI provides 21-35 times more cloud-free observations in a month than MODIS. The analyses show statistically significant changes in seasonality over 85% of Amazon forest pixels, an area about three times greater than previously reported using MODIS data. Though additional work is needed in converting the observed changes in seasonality into meaningful changes in canopy dynamics, our results highlight the potential of the new generation geostationary satellites to help us better understand tropical ecosystems, which has been a challenge with only polar orbiting satellites.

Arene dearomatization is a straightforward method for converting an aromatic feedstock into functionalized carbocycles. Enantioselective dearomatizations of chemically inert arenes, however, are quite limited and underexplored relative to those of phenols and indoles. We developed a method for diazo-free generation of silver-carbene species from an ynamide and applied it to the dearomatization of nonactivated arenes. Transiently generated norcaradiene could be trapped by intermolecular [4 + 2] cycloaddition, synthesizing polycycles with five consecutive stereogenic centers. This protocol constitutes the first highly enantioselective reaction based on the diazo-free generation of silver-carbene species. Mechanistic investigations revealed a dearomatization followed by two different classes of pericyclic reactions, as well as the origin of the chemo- and enantioselectivity.

Daikenchuto (TU-100) is herbal medicine which predominantly contains ginger, Japanese pepper, and ginseng. We investigated whether TU-100 can affect the composition of gut flora and intestinal tumor development using Apc Min/+ mice, a murine model of intestinal tumor. Bacterial 16S rRNA sequencing and short-chain fatty acid analysis were performed on faecal samples. Tumor number and size were analysed. Any change in gene expression of the tumor tissues was assessed by real-time PCR. Principal coordinate analysis (PCoA) showed that the faecal microbiota cluster of TU-100-fed mice was different from the microbiota of control mice. However, no significant difference was observed in the concentration of short-chain fatty acids, tumor number, and gene expression levels between the two groups. Our data showed that TU-100 can affect the intestinal environment; however, it does not contribute in tumor progression or inhibition in our setting.

Background: Appropriate indications and protocols for induction therapy using basiliximab have not been fully established in heart transplant (HTx) recipients. This study elucidated the influence of induction therapy using basiliximab along with delayed tacrolimus (Tac) initiation on the outcomes of high-risk HTx recipients., Methods and results: A total of 86 HTx recipients treated with Tac-based immunosuppression were retrospectively reviewed. Induction therapy was administered to 46 recipients (53.5%) with impaired renal function, pre-transplant sensitization, and recipient- and donor-related risk factors (Induction group). Tac administration was delayed in the Induction group. Induction group subjects showed a lower cumulative incidence of acute cellular rejection grade ≥1R after propensity score adjustment, but this was not significantly different (hazard ratio [HR]: 0.63, 95% confidence interval [CI]: 0.37-1.08, P=0.093). Renal dysfunction in the Induction group significantly improved 6 months post-transplantation (P=0.029). The cumulative incidence of bacterial or fungal infections was significantly higher in the Induction group (HR: 10.6, 95% CI: 1.28-88.2, P=0.029)., Conclusions: These results suggest that basiliximab-based induction therapy with delayed Tac initiation may suppress mild acute cellular rejection and improve renal function in recipients with renal dysfunction, resulting in its non-inferior outcome, even in high-risk patients, when applied to the appropriate recipients. However, it should be carefully considered in recipients at a high risk of bacterial and fungal infections.

Background: Cigarette smoking is known to be a significant risk factor associated with non-alcoholic fatty liver disease (NAFLD). We aimed to examine the association between smoking status and the severity of fatty liver with regard to sex and smoking cessation., Methods: In total, 13,466 subjects (6,642 males and 6,824 females) who had undergone abdominal ultrasonography for health check-up, multivariable logistic regression analysis was retrospectively conducted to assess the association between smoking status and the prevalence of NAFLD stratified by sex after adjusting for other potential confounders., Results: Male sex (odds ratio [OR] 3.27, 95% confidence interval [CI] 3.00-3.57) and smoking history (former smoker: OR 1.23, 95% CI 1.10-1.38, current smoker: OR 1.31, 95% CI 1.17-1.47) were significantly associated with NAFLD. In males with a smoking history, an increased pack-year was strongly associated with the prevalence and severity of NAFLD (prevalence of moderate to severe fatty liver: Pack-year from 0.01 to 9.99, 21.3%; Pack-year from 10.00 to 19.99, 27.2%; Pack-year ≥20.00, 33.7%; P<0.0001), although the prevalence of moderate to severe fatty liver was inversely associated with the duration of smoking cessation (more than 10 years vs. within 5 years, OR 0.71, 95% CI 0.53-0.96). In female subjects, light current smoking was negatively associated with NAFLD (current smoker with a pack-year from 0.01 to 9.99 vs. never smoker, OR 0.41, 95% CI 0.19-0.76)., Conclusions: Smoking status and pack-year were strongly associated with the prevalence and severity of NAFLD, especially in Japanese males. However, smoking cessation improved NAFLD in this population.

The three-dimensional reconstruction of optical coherence tomography and optical frequency domain imaging (3D-OCT/OFDI) helps optimize bifurcation percutaneous coronary interventions (PCIs) with side branch (SB) dilatation by identifying the optimal rewiring position. 3D-OCT/OFDI's diagnostic performance for assessing the rewiring position into a jailed SB is unknown. We retrospectively evaluated the diagnostic performances of a conventional (ver. 1.1) and a new (ver. 1.2) online 3D-OFDI reconstruction system based on an offline 3D reconstruction system's performance. We analyzed 45 patients' 52 OFDI pullbacks with main vessel stenting followed by rewiring into a jailed SB for coronary bifurcation lesions. We counted the undetected stent struts in the polygon of confluence as the stent detection performance. We assessed the diagnostic agreement regarding the rewiring position into a jailed SB by the three 3D reconstruction systems. The percentage of undetected struts and the diagnostic agreement of ver.1.2 were significantly better than those of ver.1.1 [5.1 ± 5.1% vs. 30.2 ± 14.2%; p < 0.0001, and 94.2% (49/52) vs. 76.9% (40/52); p = 0.0120]. The new online 3D-OFDI reconstruction system provides better diagnostic performance than the conventional online system for assessing the rewiring position into a jailed SB.

Background: In Japan, the long-term care insurance (LTCI) system has an important role in helping elderly people, but there have been no clinical studies that have examined the relationship between the LTCI and prognosis for patients with acute heart failure (HF)., Methods and results: This registry was a prospective multicenter cohort, 1,253 patients were enrolled and 965 patients with acute HF aged ≥65 years were comprised the study group. The composite endpoint included all-cause death and hospitalization for HF after discharge. We divided the patients into 4 groups: (i) patients without LTCI, (ii) patients requiring support level 1 or 2, (iii) patients with care level 1 or 2, and (iv) patients with care levels 3-5. The Kaplan-Meier analysis identified a lower rate of the composite endpoint in group (i) than in the other groups. After adjusting for potentially confounding effects using a Cox proportional regression model, the hazard ratio (HR) of the composite endpoint increased significantly in groups (iii) and (iv) (adjusted HR, 1.62; 95% confidence interval [CI], 1.22-1.98 and adjusted HR, 1.62; 95% CI, 1.23-2.14, respectively) when compared with group (i). However, there was no significant difference between groups (i) and (ii)., Conclusions: The level of LTCI was associated with a higher risk of the composite endpoint after discharge in acute HF patients.

We investigated the effect of evodiamine-containing microalga Dunaliella tertiolecta (DT) on the prevention of diet-induced obesity in a thermoneutral C57BL/6J male (30 °C). It attenuates the activity of brown adipose tissue (BAT), which accelerates diet-induced obesity. Nine-week-old mice were fed a high-fat diet supplemented with 10 g (Low group) or 25 g (High group) DT powder per kg food for 12 weeks. Compared to control mice without DT supplementation, body weight gain was significantly reduced in the High group with no difference in food intake. Tissue analyses indicated maintenance of multilocular morphology in BAT and reduced fat deposition in liver in DT-supplemented mice. Molecular analysis showed a significant decrease in mammalian target of rapamycin-ribosomal S6 protein kinase signaling pathway in white adipose tissue and upregulation in mRNA expression of brown fat-associated genes including fibroblast growth factor-21 ( Fgf21 ) and uncoupling protein 1 ( Ucp1 ) in BAT in the High group compared to the control. In the experiments using C3H10T1/2 adipocytes, DT extract upregulated mRNA expression of brown fat-associated genes in dose-dependent and time-dependent manners, accompanied by a significant increase in secreted FGF21 levels. Our data show the ability of DT as a nutraceutical to prevent brown fat attenuation and diet-induced obesity in vivo., Competing Interests: The authors declare no conflict of interest regarding the publication of this article.

Background: During these 2 decades (1999-2019), many therapeutic strategies have been developed in the field of heart transplant (HTx) to improve post-HTx outcomes. In the present study, 116 consecutive HTx adults between 1999 and 2019 were retrospectively reviewed to evaluate the influences of a therapeutic modification on post HTx outcomes., Methods and results: Patient survival, functional status and hemodynamics after HTx and modification of therapeutic strategies were reviewed. The overall cumulative survival rate at 10 and 20 years post-HTx was 96.4 and 76.7%, respectively. There were no significant differences in survival rate or exercise tolerance after HTx between extracorporeal and implantable continuous flow-LVAD. Post-HTx patient survival in patients, irrespective of the donor risk factors such as donor age, low LVEF, history of cardiac arrest, was equivalent across cohorts, while longer TIT and higher inotrope dosage prior to procurement surgery were significant risk factors for survival. In 21 patients given everolimus (EVL) due to renal dysfunction, serum creatinine significantly decreased 1 year after initiation. In 22 patients given EVL due to transplant coronary vasculopathy (TCAV), maximum intimal thickness significantly decreased 3 years after initiation., Conclusions: The analysis of a 20-year single-center experience with HTx in Japan shows encouraging improved results when several therapeutic modifications were made; for example, proactive use of donor hearts declined by other centers and the use of EVL in patients with renal dysfunction and TCAV.