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Abstract Radiotherapy with deep inspiration breath hold (DIBH) reduces doses to the lungs and organs at risk. The stability of breath holding and reproducibility of tumor location are higher during expiration than during inspiration; therefore, we developed an irradiation method combining DIBH and real-time tumor-tracking radiotherapy (RTRT) (DBRT). Nine patients were enrolled in this study. Fiducial markers were placed near tumors using bronchoscopy. Treatment planning computed tomography (CT) was performed thrice during DIBH, assisted by spirometer-based device. Each CT scan was fused using fiducial markers. Gross tumor volume (GTV) was contoured for each dataset and summed to create GTVsum; adding a 5-mm margin around GTVsum generated the planning target volume. The prescribed dose was mainly 42 Gy in four fractions. The treatment plan was created using DIBH CT (DBRT-plan), with a similar treatment plan created for expiratory CT for cases for which DBRT could not be performed (conv-plan). Vx defined as the volume of the lung received x Gy, and the mean lung dose, V20, V10, and V5 were evaluated. DBRT was completed in all patients. Mean dose, V20, and V10 were significantly lower in the DBRT-plan than in the conv-plan (all p = 0.003). Mean rates of decrease for mean dose, V20, and V10 were 14.0%, 27.6%, and 19.1%, respectively. No significant difference was observed in V5. We developed DBRT, a stereotactic body radiation therapy performed with the DIBH technique; it combines a spirometer-based breath-hold support system with an RTRT system. All patients who underwent DBRT completed the procedure without any technical or mechanical complications. This is a promising methodology that may significantly reduce lung doses.

Objective Whether the use of a balloon or stent in vertebroplasty for vertebral fractures, such as balloon kyphoplasty (BKP) or vertebral body stenting (VBS), actually contributes to the restoration of postoperative vertebral height is unclear. The aim of the current study was to compare the effectiveness of percutaneous vertebroplasty (PVP), BKP, and VBS in the correction of collapsed vertebrae in patients with painful vertebral fractures. Methods The cases studied involved 34 vertebrae in 28 patients treated with PVP, 43 vertebrae in 38 patients treated with BKP, and 20 vertebrae in 20 patients treated with VBS at Izinkai Takeda General Hospital. Changes in the vertebral height and local kyphosis angle were measured based on standing lumbar radiographs before and after surgery and were compared among the treatment groups. Results There were no differences in changes in the height of the anterior wall, middle body, or posterior wall of the treated vertebrae among the 3 treatment groups. The same was true for changes in the local kyphosis angle. The effectiveness of vertebral height restoration depended heavily upon preoperative vertebral instability in all the treatment groups. Correction loss due to balloon deflation effect or balloon sinking was noted with VBS or BKP. Conclusion BKP and VBS have the advantage of reducing the risk of extravertebral leakage of injected bone cement, but they have a disadvantage in that they are no more effective than PVP in restoring collapsed vertebrae despite the use of a balloon or metal stent.

The management of osteoporotic vertebral fractures (OVFs) in the elderly includes nonoperative treatment and vertebroplasty, but has not been established due to the diversity of patient backgrounds. The purpose of this study was to compare the impact of 3 treatment modalities for the management of OVF: orthotic treatment, percutaneous vertebroplasty (PVP), and balloon kyphoplasty (BKP). The method was based on an analysis of the latest RCTs, meta-analyses, and systematic reviews on these topics. No study showed a benefit of bracing with high level of evidence. Trials were found that showed comparable outcomes without orthotic treatment. Only 1 randomized controlled trial (RCT) showed an improvement in pain relief up to 6 months compared with no orthosis. Rigid and nonrigid orthoses were equally effective. Four of 5 RCTs comparing vertebroplasty and sham surgery were equally effective, and one RCT showed superior pain relief with vertebroplasty within 3 weeks of onset. In open trials comparing vertebroplasty with nonoperative management, vertebroplasty was superior. PVP and BKP were comparable in terms of pain relief, improvement in quality of life, and adjacent vertebral fractures. BKP does not affect global sagittal alignment, although BKP may restore vertebral body height. An RCT was published showing that PVP was effective in chronic cases without pain relief. Vertebroplasty improved life expectancy by 22% at 10 years. The superiority of orthotic therapy for OVF was seen only in short-term pain relief. Soft orthoses proved to be a viable alternative to rigid orthoses. Vertebroplasty within 3 weeks may be useful. There is no significant difference in clinical efficacy between PVP and BKP. Vertebroplasty improves life expectancy.

Background: Ventricular arrhythmia (VA) is a life-threatening condition associated with cardiac sarcoidosis (CS). Right bundle branch block (RBBB) is a common conduction disorder in CS; however, its association with VA remains unknown. Objectives: This study aimed to investigate the relationship between RBBB and VA in patients with CS. Methods: This was a post hoc analysis of ILLUMINATE-CS (Illustration of the Management and Prognosis of Japanese Patients with Cardiac Sarcoidosis), a multicenter, retrospective, and observational study that evaluated the clinical characteristics and prognosis of CS. Eligible patients were divided into two groups based on the presence or absence of RBBB at the time of diagnosis. The primary outcome was serious ventricular arrhythmia events (SVAEs), defined as a combination of sudden cardiac death and documented ventricular fibrillation, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator therapy. Results: Overall, 312 patients were studied, with 155 (49.7%) patients presenting with RBBB (RBBB group). Patients in the RBBB group had a higher prevalence of basal interventricular septum (IVS) thinning and prominent late gadolinium enhancement in the basal IVS on cardiac magnetic resonance imaging than those in the non-RBBB group. During a median follow-up of 3.0 years (IQR: 1.6-6.0 years), 66 patients experienced SVAE. In multivariable Cox regression analysis, the RBBB group was independently associated with a higher incidence of SVAEs (HR: 1.93 [95% CI: 1.14-3.28]; P = 0.015). Conclusions: In patients with CS, RBBB was an independent predictor of SVAEs, which might reflect the specific scar distribution that is predominant in the IVS.

Background Current guidelines recommend placing an implantable cardiac defibrillator for patients with cardiac sarcoidosis and a severely impaired left ventricular ejection fraction (LVEF) of ≤35%. In this study, we determined the association between mild or moderate LVEF impairment and fatal ventricular arrhythmic event (FVAE). Methods and Results We retrospectively analyzed 401 patients with cardiac sarcoidosis without sustained ventricular arrhythmia at diagnosis. The primary end point was an FVAE, defined as the combined endpoint of documented ventricular tachycardia or ventricular fibrillation and sudden cardiac death. Two cutoff points for LVEF were used: a sex‐specific lower threshold of normal range of LVEF (52% for men and 54% for women) and an LVEF of 35%, which is used in the current guidelines. During a median follow‐up of 3.2 years, 58 FVAEs were observed, and the 5‐ and 10‐year estimated incidences of FVAEs were 16.8% and 23.0%, respectively. All patients were classified into 3 groups according to LVEF: impaired LVEF group, mild to moderate impairment of LVEF group, and maintained LVEF group. Multivariable competing risk analysis showed that both the impaired LVEF group (hazard ratio [HR], 3.24 [95% CI, 1.49–7.04]) and the mild to moderate impairment of LVEF group (HR, 2.16 [95% CI, 1.04–4.46]) were associated with a higher incidence of FVAEs than the maintained LVEF group after adjustment for covariates. Conclusions Patients with cardiac sarcoidosis are at a high risk of FVAEs, regardless of documented ventricular arrhythmia at the time of diagnosis. In patients with cardiac sarcoidosis, mild to moderate impairment of LVEF is associated with FVAEs.

Background: Clinical characteristics and the risk of cardiovascular events in patients with cardiac sarcoidosis (CS) according to the age of initial diagnosis are unclear. Methods: This study is a sub-analysis of the ILLUMINATE-CS registry, which is a retrospective, multicenter registry that enrolled patients with CS between 2001 and 2017. Patients were divided into three groups according to the tertile of age at the time of initial diagnosis of CS. The study compared the clinical background at the time of CS diagnosis and the incidence rate of cardiac events across age categories. Results: A total of 511 patients were analyzed in this study. In baseline, older patients were more likely to be female. History of hypertension, heart failure admission, and atrioventricular block were more common in patients with older age. There was no significant difference in the history of ventricular arrhythmias and left ventricular ejection fraction among all age groups. During a median follow-up period of 3.2 [IQR: 1.7–4.2] years, 35 deaths, 56 heart failure hospitalization, and 98 fatal ventricular arrhythmias was observed. The incidence rate of all-cause death and heart failure hospitalization was significantly higher in patients with older age (p

Abstract Pursuing the exotic quantum spin liquid (QSL) state in the Kitaev material α-RuCl3 has intrigued great research interest recently. A fascinating question is on the possible existence of a field-induced QSL phase in this compound. Here we perform high-field magnetization measurements of α-RuCl3 up to 102 T employing the non-destructive and destructive pulsed magnets. Under the out-of-plane field along the c* axis (i.e., perpendicular to the honeycomb plane), two quantum phase transitions are uncovered at respectively 35 T and about 83 T, between which lies an intermediate phase as the predicted QSL. This is in sharp contrast to the case with in-plane fields, where a single transition is found at around 7 T and the intermediate QSL phase is absent instead. By measuring the magnetization data with fields tilted from the c* axis up to 90° (i.e., in-plane direction), we obtain the field-angle phase diagram that contains the zigzag, paramagnetic, and QSL phases. Based on the K-J-Γ- $${{{\Gamma }}}^{{\prime} }$$ Γ ′ model for α-RuCl3 with a large Kitaev term we perform density matrix renormalization group simulations and reproduce the quantum phase diagram in excellent agreement with experiments.

Abstract Background Optimised antithrombotic therapy requires clinical experience and an understanding of the current guidelines. This retrospective study aimed to evaluate whether pharmacist interviews and interventions with patients taking oral antithrombotic drugs in the pharmaceutical outpatient cardiology clinic had favourable clinical outcomes including decreased bleeding. Methods The participants included patients visiting the outpatient clinic of cardiovascular internal medicine at the Kobe University Hospital from January–December 2017, and were taking oral antithrombotic medication. The observation period was from the first visit to the outpatient clinic to October 2021 or death. Patients who received pharmacist intervention more than twice were defined as the pharmacist intervention group. Two control patients per one pharmacist intervention group individual were selected from the non-intervention pool matched for age, gender and antithrombotic medication type. Results Of the 895 eligible patients, 132 were in the pharmacist intervention group and 264 were selected for the matched non-intervention group. Bleeding events according to the Bleeding Academic Research Consortium criteria over type 2 were significantly lower in the pharmacist intervention group compared with the non-intervention group (17.4% versus 28.4%, P = 0.019). There were no significant differences in mortality and heart failure hospitalisation frequency, stroke, or cardiovascular events between the groups. Multivariate analysis identified age (≥ 65 years) and pharmacist intervention as factors associated with bleeding (odds ratio = 2.29 and 0.51, respectively). Conclusion Pharmacist intervention in the outpatient clinic of cardiovascular internal medicine was effective in reducing the risk of bleeding in patients undergoing antithrombotic therapy.

Background and purposeMean pulmonary artery pressure (mPAP) is a key index for chronic thromboembolic pulmonary hypertension (CTEPH). Using machine learning, we attempted to construct an accurate prediction model for mPAP in patients with CTEPH.MethodsA total of 136 patients diagnosed with CTEPH were included, for whom mPAP was measured. The following patient data were used as explanatory variables in the model: basic patient information (age and sex), blood tests (brain natriuretic peptide (BNP)), echocardiography (tricuspid valve pressure gradient (TRPG)), and chest radiography (cardiothoracic ratio (CTR), right second arc ratio, and presence of avascular area). Seven machine learning methods including linear regression were used for the multivariable prediction models. Additionally, prediction models were constructed using the AutoML software. Among the 136 patients, 2/3 and 1/3 were used as training and validation sets, respectively. The average of R squared was obtained from 10 different data splittings of the training and validation sets.ResultsThe optimal machine learning model was linear regression (averaged R squared, 0.360). The optimal combination of explanatory variables with linear regression was age, BNP level, TRPG level, and CTR (averaged R squared, 0.388). The R squared of the optimal multivariable linear regression model was higher than that of the univariable linear regression model with only TRPG.ConclusionWe constructed a more accurate prediction model for mPAP in patients with CTEPH than a model of TRPG only. The prediction performance of our model was improved by selecting the optimal machine learning method and combination of explanatory variables.

Rehabilitative exercise following a brain stroke has beneficial effects on the morphological plasticity of neurons. Particularly, voluntary running exercise after focal cerebral ischemia promotes functional recovery and ameliorates ischemia-induced dendritic spine loss in the peri-infarct motor cortex layer 5. Moreover, neuronal morphology is affected by changes in the perineuronal environment. Glial cells, whose phenotypes may be altered by exercise, are known to play a pivotal role in the formation of this perineuronal environment. Herein, we investigated the effects of voluntary running exercise on glial cells after middle cerebral artery occlusion. Voluntary running exercise increased the population of glial fibrillary acidic protein-positive astrocytes born between post-operative days (POD) 0 and 3 on POD15 in the peri-infarct cortex. After exercise, transcriptomic analysis of post-ischemic astrocytes revealed 10 upregulated and 70 downregulated genes. Furthermore, gene ontology analysis showed that the 70 downregulated genes were significantly associated with neuronal morphology. In addition, exercise reduced the number of astrocytes expressing lipocalin 2, a regulator of dendritic spine density, on POD15. Our results suggest that exercise modifies the composition of astrocytic population and their phenotype.

Abstract Martensitic crystal structures are usually obtained by rapid thermal quenching of certain alloys, which induces stress and subsequent shear deformation. Here, we demonstrate that it is also possible to intentionally excite a suitable transverse acoustic phonon mode to induce a local shear deformation. We irradiate the surface of a partially stabilized zirconia plate with intense terahertz pulses and verify martensitic transformation from the tetragonal to the monoclinic phases by Raman spectroscopy and the observed destructive spallation of the zirconia microcrystals. We calculate the phonon modes in tetragonal zirconia and determine the decay channel that triggers the transformation. The phonon mode required for the martensitic transformation can be excited via the Klemens process. Since terahertz pulses can induce a specific local shear deformation beyond thermal equilibrium, they can be used to elucidate phase transformation mechanisms with approaches based on nonlinear phononics.

Aim: This study aimed to examine the usefulness of seed density as a predictor of seed migration in patients with prostate cancer who received brachytherapy using Iodine-125 loose seed. Methods: From May 2006 to April 2016, 320 patients with localized prostate cancer underwent transperineal brachytherapy using iodine-125 loose seeds. Among them, 202 (63.1%) patients received brachytherapy monotherapy and 118 (36.9%) received combined brachytherapy and external beam radiotherapy. Seed density was calculated using the following formula: seed density = implanted seed number/prostate volume. All patients underwent radiography of the chest, abdomen and pelvis, and computed tomography at 1 day, 1 month, and 1 year after brachytherapy to evaluate the presence of seed migration. Results: In total, the number of implanted seeds was 21,876. Seed migration was detected in 92 (28.8%) patients. Of a total of 21,876 seeds, 144 (0.66%) showed migration. The number of needles, number of seeds, and seed density were significantly higher in the group with migration than in the group without migration (p = 0.05). The ROC cutoff values for prostate volume, number of needles, number of seeds, and seed density were 20.9 cc, 21, 65, and 3.0, respectively. In the univariate analysis, prostate volume, number of needles, number of seeds, seed density, and treatment modality were all significant factors in predicting migration (p = 0.05). In the multivariate analysis, seed density and treatment modality were significant factors in predicting migration (p = 0.05). Conclusion: Seed density is useful for predicting seed migration. In cases with seed density > 3.0, it is necessary to take measures such as considering the use of stranded seeds.

Abstract Global longitudinal strain (GLS), a new cardiac parameter measured by the speckle‐tracking method, is reportedly more sensitive than ejection fraction (EF) in detecting slight cardiac dysfunction in heart failure patients. We validated the utility of GLS in allogeneic hematopoietic stem cell transplantation (HSCT) patients during a long‐term follow‐up. Medical records of patients who underwent allogeneic HSCT between 2013 and 2020 were reviewed retrospectively. We evaluated the last echocardiography performed before transplantation and those performed annually during the 5 years after transplantation. We also investigated newly diagnosed cardiac events, which developed after HSCT. Among 85 patients, 22 used cardioprotective drugs. The median follow‐up duration in surviving patients was 54.1 months (range, 2.9–92.6 months). GLS significantly decreased year by year, and patients taking cardioprotective agents tended to have a better GLS at 5 years than at 3 years, while EF did not change. Fifteen patients developed newly diagnosed cardiac events. Multivariate analysis revealed that low GLS and high serum ferritin levels at baseline were independently associated with the development of cardiac events. Therefore, we need a continuous follow‐up of cardiac function by GLS and prescription of cardioprotective drugs might be considered for HSCT patients with low GLS. Further research is warranted.

Abstract Aims With the rapidly increasing ageing population, heart failure is an urgent challenge, particularly in developed countries. The study aimed to investigate the main aetiologies of chronic heart failure in a super‐aged society. Methods and results The KUNIUMI registry chronic cohort is a community‐based, prospective, observational study of chronic heart failure in Awaji Island, Japan. Inhabitants of this island aged ≥65 years accounted for 36.3% of the population. In the present study, data from patients with symptomatic heart failure were extracted from the registry. A total of 1646 patients were enrolled from March 2019 to March 2021, accounting for ~1.3% of the inhabitants of Awaji Island. We analysed 852 patients with symptomatic heart failure. The mean age was high (78.7 ± 11.1 years), with 357 patients (41.9%) being female. The proportion of women increased significantly with advancing age and constituted more than half of the patients aged 85 years and older (P 75 years. Patients with atrial functional mitral regurgitation had a higher prevalence of atrial fibrillation (especially long‐standing persistent atrial fibrillation) and a larger left atrial volume index when compared with patients with other types of mitral regurgitation (P

Abstract Aims Acute decompensated heart failure (ADHF) is a frequent cause of hospitalization for patients with heart disease, and ADHF patients are at high risk of heart failure (HF) re‐hospitalization. Residual congestion at discharge is also a strong predictor of poor outcomes and re‐hospitalization for ADHF patients. However, the impact of residual congestion at discharge on worsening renal function (WRF) in both high‐aged and older patients remains uncertain because previous studies of WRF in ADHF patients were conducted for older patients. We therefore designed and conducted a retrospective, population‐based study using the Kobe University Heart Failure Registry in Awaji Medical Center (KUNIUMI) Registry to investigate the association of residual congestion at discharge with WRF in ADHF patients according to age. Methods and results We studied 966 hospitalized ADHF patients with a mean age of 80.2 ± 11.4 years from among 1971 listed in the KUNIUMI Registry. WRF was defined as an increase of ≥0.3 mg/dL in the serum creatinine level during the hospital stay compared with the value on admission. The primary endpoint was defined as cardiovascular death or HF re‐hospitalization after discharge over a mean follow‐up period of 2.0 ± 0.1 years. The primary endpoint was recorded for 369 patients (38.2%). As expected, patients with both WRF and residual congestion at discharge had significantly less favourable outcomes compared with those without one of them, and patients without either of these two characteristics had the most favourable outcomes, whereas those with residual congestion and with WRF had the least favourable outcomes. Moreover, WRF was significantly associated with worse outcomes for high‐aged patients ≥80 years old, but not for those

Background and purpose: To minimize cognitive decline without increasing brain tumor recurrence (BTR) by reduced-dose whole-brain radiotherapy (RD-WBRT) (25 Gy, 10 fractions) + stereotactic radiosurgery (SRS) in patients with ≤ 4 brain metastases. Materials and methods: Eligible patients with ≤ 4 brain metastases on contrast-enhanced MRI and Karnofsky Performance Status ≥ 70. The primary endpoint was the non-inferiority of BTR at distant sites in the brain (BTR-distant)-free survival at 6 months compared to that of the standard dose (SD)-WBRT (30 Gy, 10 fractions) + SRS arm in a randomized clinical trial (JROSG99-1) of SRS with/without SD-WBRT. Secondary endpoints included BTR at any brain sites (BTR-all) and neurocognitive function assessed by a six-test standardized battery. Results: Forty patients from seven institutions were enrolled (median age 69 years). The primary tumor site was a lung in 28 patients; 20 patients had a solitary brain metastasis. The median survival time was 19.0 months (95 %CI: 13.8 %–27.5 %). The BTR-distant-free survival at 6 months was 76.9 % (59.5 %–87.7 %), which is comparable to that of historical control although predetermined non-inferiority (>71 %) could not be confirmed (p = 0.16). The cumulative incidence of BTR-all at 6 months accounting for the competing risk of death was 23.0 % (11.4–37.1), which was not worse than that of historical control (p = 0.774). The frequency of the cumulative incidence of persistent cognitive decline at 6 months was 48.6 % under the [>2.0 SD in ≥ 1 test] definition. Conclusions: RD-WBRT may yield comparable intracranial tumor control when combined with SRS, and may reduce the risk of neurocognitive decline compared to that after SD-WBRT.

We performed linear calculations to determine the Type I planetary migration rate for 3D locally isothermal disks with radial temperature gradients. For 3D disks with radial temperature gradients, the linear wave equation has a divergent term of the third pole, which makes corotation a nonremoval singularity. We suppressed the divergence with the Landau prescription to obtain the wave solutions. Despite the singularity at corotation, we derived a definite torque on the planet because the divergent term amplifies the waves only in the neighborhood of corotation and has little effect on the planetary torque. Consequently, we derived the formulas for the total, Lindblad, and corotation torques for locally isothermal disks. The resulting torque term due to the disk temperature gradient agrees well with the results of previous 3D hydrodynamical simulations for locally isothermal disks. Our linear calculation also provides the 3D horseshoe torque, which is close to the results of previous 3D hydrodynamical simulations.

Unlike drug selection, radiation parameters (field, dose) are not based on driver gene mutations in patients with metastatic non-small cell lung cancer (NSCLC). This study aimed to compare radiosensitivity in NSCLC with and without EGFR driver gene mutations using clinical and in vitro data. The clinical study included 42 patients who underwent whole-brain radiotherapy for brain metastases from NSCLC; of these, 13 patients had EGFR mutation-positive tumors. The Kaplan–Meier method was used to calculate the cranial control rate without intracranial recurrence. In the in vitro study, colony formation and double-strand DNA breaks were examined in two EGFR mutation-negative and three EGFR mutation-positive NSCLC-derived cell lines. Colony formation was assessed 14 days after irradiation with 0 (control), 2, 4, or 8 Gy. DNA double-strand breaks were evaluated 0.5 and 24 h after irradiation. EGFR mutation-positive patients had a significantly better cranial control rates than EGFR mutation-negative patients (p = 0.021). EGFR mutation-positive cells formed significantly fewer colonies after irradiation with 2 or 4 Gy than EGFR mutation-negative cells (p = 0.002, respectively) and had significantly more DNA double-strand breaks at 24 h after irradiation (p < 0.001). Both clinical and in vitro data suggest that EGFR mutation-positive NSCLC is radiosensitive.

Background and purpose: The low tracking accuracy of lung stereotactic body radiotherapy (SBRT) risks reduced treatment efficacy. We used four-dimensional computed tomography (4DCT) images to determine the correlation between changes in fiducial marker positions and lung volume for lung tumors, and we evaluated the effectiveness of the combined use of these images in lung SBRT. Materials and methods: Data of 30 patients who underwent fiducial marker placement were retrospectively analyzed. We calculated the motion amplitudes of the center of gravity coordinates of the lung tumor and fiducial markers in each phase and the ipsilateral, contralateral, and bilateral lung volumes using 4DCT. Moreover, we calculated the cross-correlation coefficient between the fiducial marker position and the lung volume changes waveform for the motion amplitude waveform of the lung tumor over three gating windows (all phases, ≤2 mm3, and ≤3 mm3). Results: Compared with the lung volume, approximately 30 % of the fiducial markers demonstrated a low correlation with the lung tumor. In the ≤2 mm3 and ≤3 mm3 gating windows, the cross-correlation coefficients between the lung tumor and the optimal marker (r > 0.9: 83 % and 86 %) were significantly different for all fiducial markers (r > 0.9: 39 %, 53 %) and the ipsilateral (r > 0.9: 35 % and 40 %), contralateral (r > 0.9: 44 % and 41 %), and bilateral (r > 0.9: 39 % and 45 %) lung volumes. Conclusions: Some of the fiducial markers showed a low correlation with the lung tumor. This study indicated that the combined use of lung volume monitoring can improve tracking accuracy.

Background: For optimal treatment, it is important to maintain optimal multi-leaf collimator (MLC) transmission in intensity-modulated radiation therapy (IMRT). However, adjustment of transmissions has not been reported in veterinary medicine. Aim: This study aimed to demonstrate that appropriate MLC parameter adjustment for IMRT using 4- and 6-MV energy can reduce the need for quality assurance revalidation in real companion animal clinical cases. Methods: The MLC parameters (leaf transmission and leaf offset) of the treatment planning system were adjusted by evaluating seven plans (10 × 10 cm, 3ABUT, DMLC, 7segA, FOURL, HDMLC, and HIMRT) and 20 pre-clinical cases (10 cases each in 4 and 6 MV groups). Subsequently, 101 IMRT plans of 88 cases (77 dogs and 11 cats) were evaluated for absolute dose of plan target volume (PTV) and organs at risk (OAR) and were analyzed for the relative dose distribution by gamma analysis (3%/3 mm, >10%) using EBT3 film. Results: After adjustment of the MLC parameters (leaf transmission and leaf offset, 4 MV: 0.008 and 0, 6 MV: 0.005 and 0), the data from 101 plans (4MV: 64 plans and 6MV: 37 plans) treated with IMRT showed PTV

This exploratory and retrospective study aimed to evaluate whether there is a difference in the overall survival (OS) rates of patients with stage IV lung cancer who underwent radiation therapy (RT) depending on the presence or absence of immune checkpoint inhibitors (ICIs) and the timing of their use. Eighty patients with histologically confirmed stage IV lung cancer were enrolled, and ICIs were administered to thirty (37.5%). ICIs were administered before RT and after RT in 11 and 20 patients, respectively. The median follow-up period was 6 (range: 1–37) months. Patients treated with ICIs had significantly better OS rates than those not treated with ICIs (p < 0.001). The 6-month OS rates in patients treated with and without ICIs were 76.3% and 34.5%, respectively. The group that received ICI therapy after RT had a significantly better OS rate than the group that received ICI therapy prior to RT (6-month OS: 94.7% vs. 40.0%, p < 0.001). In the multivariate analysis, performance status (0–1 vs. 2–4) and ICI use after RT were significant factors for OS (p = 0.032 and p < 0.001, respectively). Our results suggest that ICI administration after RT may prolong the OS of patients with stage IV lung cancer.

Abstract Background Establishing fecal microbiota transplantation (FMT) to prevent multifactorial diarrhea in calves is challenging because of the differences in farm management practices, the lack of optimal donors, and recipient selection. In this study, the underlying factors of successful and unsuccessful FMT treatment cases are elucidated, and the potential markers for predicting successful FMT are identified using fecal metagenomics via 16S rRNA gene sequencing, fecal metabolomics via capillary electrophoresis time-of-flight mass spectrometry, and machine learning approaches. Results Specifically, 20 FMT treatment cases, in which feces from healthy donors were intrarectally transferred into recipient diarrheal calves, were conducted with a success rate of 70%. Selenomonas was identified as a microorganism genus that showed significant donor–recipient compatibility in successful FMT treatments. A strong positive correlation between the microbiome and metabolome data, which is a prerequisite factor for FMT success, was confirmed by Procrustes analysis in successful FMT (r = 0.7439, P = 0.0001). Additionally, weighted gene correlation network analysis confirmed the positively or negatively correlated pairs of bacterial taxa (family Veillonellaceae) and metabolomic features (i.e., amino acids and short-chain fatty acids) responsible for FMT success. Further analysis aimed at establishing criteria for donor selection identified the genus Sporobacter as a potential biomarker in successful donor selection. Low levels of metabolites, such as glycerol 3-phosphate, dihydroxyacetone phosphate, and isoamylamine, in the donor or recipients prior to FMT, are predicted to facilitate FMT. Conclusions Overall, we provide the first substantial evidence of the factors related to FMT success or failure; these findings could improve the design of future microbial therapeutics for treating diarrhea in calves. Video abstract

Understanding the collisional behavior of dust aggregates is essential in the context of planet formation. It is known that low-velocity collisions of dust aggregates result in bouncing rather than sticking when the filling factor of colliding dust aggregates is higher than a threshold value. However, a large discrepancy between numerical and experimental results on the threshold filling factor was reported so far. In this study, we perform numerical simulations using soft-sphere discrete element methods and demonstrate that the sticking probability decreases with increasing aggregate radius. Our results suggest that the large discrepancy in the threshold filling factor may reflect the difference in the size of dust aggregates in earlier numerical simulations and laboratory experiments.

Background The prognostic role of BNP (B‐type natriuretic peptide) in patients with cardiac sarcoidosis without evident heart failure is unknown. Methods and Results This is a post hoc analysis of ILLUMINATE‐CS (Illustration of the Management and Prognosis of Japanese Patients With Cardiac Sarcoidosis), a multicenter, retrospective, and observational study that evaluated the clinical characteristics and prognosis of cardiac sarcoidosis. We analyzed patients with cardiac sarcoidosis without evident heart failure at the time of diagnosis. The association between baseline BNP levels and prognosis was investigated. The primary end point was the combined end point of all‐cause death, heart failure hospitalization, and fatal ventricular arrhythmia. In total, 238 patients (61.0±11.1 years, 37% men) were analyzed, and 61 primary end points were observed during a median follow‐up period of 3.0 (interquartile range, 1.7–5.8) years. Patients with high BNP (BNP above the median value of BNP) were older and had a lower renal function and left ventricular ejection fraction than those with low BNP values. Kaplan–Meier curve analysis indicated that high BNP levels were significantly associated with a high incidence of primary end points (log‐rank P=0.004), and this association was retained even in multivariable Cox regression (hazard ratio, 2.06 [95% CI, 1.19–3.55]; P=0.010). Log‐transformed BNP as a continuous variable was associated with the primary end point (hazard ratio, 2.12 [95% CI, 1.31–3.43]; P=0.002). Conclusions High baseline BNP level was an independent predictor of future adverse events in patients with cardiac sarcoidosis without heart failure at the time of diagnosis. Registration URL: https://www.umin.ac.jp/english/; Unique Identifier: UMIN‐CTR: UMIN000034974.

Abstract Background Left ventricular (LV) involvement in diabetic cardiomyopathy has been reported; however, only limited data exist on right ventricular (RV) involvement. Therefore, our purpose was to investigate RV systolic dysfunction and its association with LV longitudinal myocardial dysfunction in patients with type 2 diabetes mellitus (T2DM) and preserved LV ejection fraction (LVEF). Methods We studied 177 T2DM patients with preserved LVEF and 79 age-, sex-, and LVEF-matched healthy volunteers. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS), and RV systolic function was assessed as RV free-wall strain, and predefined cutoff values for subclinical dysfunction were set at GLS

Abstract Aims Haemodynamic assessment during stress testing is not commonly performed in patients with heart failure with reduced ejection fraction (HFrEF) because of its invasiveness, lower feasibility, and safety concerns. This study aimed to assess the haemodynamic characteristics of patients with HFrEF in response to non‐invasive preload stress during dynamic postural alterations achieved by combining both semi‐sitting position and passive leg‐lifting and to evaluate whether combined postural stress could be used for risk stratification in these patients. Methods and results For this study, 101 patients with HFrEF and 35 age‐matched and sex‐matched healthy controls were prospectively recruited. After all standard echocardiographic measurements were obtained in the left decubitus position, all subjects underwent postural stress testing, which consisted of changing from semi‐sitting position to passive leg‐lifting. During a median follow‐up period of 12.2 months, 21 (21%) patients developed adverse cardiovascular events. In patients without adverse cardiovascular events, the stroke volume index (SVi) significantly changed from 28 ± 8 to 35 ± 10 mL/m2 (P

In real materials, a spin quantum number assumes a fixed value, which makes it challenging to realize a crossover between quantum and classical spin regimes. Here the authors demonstrate such a crossover in a weakly coupled chain compound by controlling the amount of quantum correlations, in the form of the inverse spin quantum number, with external pressure.

BackgroundPancreatic neuroendocrine carcinoma (PanNEC) is a rare disease entity with rapid progression and poor prognosis. Here, we report a PanNEC case with unique morphological features mimicking intraductal papillary mucinous carcinoma.Case presentationA 69-year-old Japanese man was referred to our hospital for further evaluation of weight loss and deterioration of diabetes mellitus. Contrast-enhanced computed tomography showed a solid and cystic mass with hypo-enhancement at the tail of the pancreas. The main pancreatic duct (MPD) was diffusely dilated without obstruction, accompanied by marked parenchymal atrophy. Multiple peritoneal and omental nodules were observed, suggesting tumor dissemination. Endoscopic retrograde cholangiopancreatography revealed that the mass correlated with the dilated MPD. During pancreatography, a large amount of mucus was extruded from the pancreatic orifice of the ampulla. Based on these imaging findings, intraductal papillary mucinous carcinoma was suspected. Per-oral pancreatoscopy (POPS)-guided tumor biopsies were conducted for the lesion's solid components. Histopathological examination of the biopsied material confirmed small-cell-type PanNEC with a Ki-67 labeling index of 90%. Due to his condition's rapid decline, the patient was given the best supportive care and died 28 days after diagnosis.ConclusionAlthough rare, PanNEC, which correlates with the MPD and is accompanied by marked dilation of the MPD, does exist as one phenotype. In such cases, POPS-guided biopsy could be a useful diagnostic modality.

Abstract. Prospective case-control study This study aimed to investigate the effect of self-quarantine on the changes in low back symptoms and activities of daily living (ADL) due to low physical activity because of the COVID-19 pandemic in patients with lumbar spinal stenosis (LSS). The frequency and intensity of low back and leg pain have reportedly increased in healthy subjects because of self-quarantine. Patients with LSS who self-quarantined from baseline (SQ group) were matched to controls who did not self-quarantine (non-SQ group), based on age, sex, medication, ADL, and the numeric rating scale score for low back symptoms. The change in low back symptoms, ADL, and health-related quality of life between baseline and follow-up were compared between the groups. The SQ and non-SQ group included 80 and 60 patients, respectively. Compared with the baseline, the numeric rating scale score for low back pain at follow-up in the SQ group significantly improved (P = .004, median; 1 point), but not in the non-SQ group. No significant difference was found regarding changes in leg pain or numbness. Low back pain improvement did not lead to ADL improvement. The short form 12 evaluation revealed the role/social component score in the SQ group to be significantly lower than that in the non-SQ group; no difference was found for the physical or mental components at follow-up. Self-quarantine with conservative treatment effected short-term low back pain improvement in patients with LSS. However, no improvement in ADL was found. Self-quarantine had an unfavorable impact for health-related quality of life. The effect of self-quarantine can influence the treatment results of LSS.

Abstract Background Left ventricular (LV) longitudinal myocardial dysfunction is considered a marker of preclinical LV dysfunction in patients with type 2 diabetes mellitus (T2DM). High heart rate (HR) is associated with cardiovascular outcomes, but the effect of HR on LV longitudinal myocardial function in T2DM patients is uncertain. Methods We studied 192 T2DM patients with preserved LV ejection fraction (LVEF), and 81 age-, sex-, and LVEF-matched healthy volunteers. HR was measured as the average HR during echocardiography, and high HR was defined as resting HR ≥ 70 beats/minute. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS). The predefined cutoff for subclinical LV dysfunction was set at GLS

Abstract Aims Guidelines for the diagnosis and treatment of acute and chronic heart failure (HF) provided by the European Society of Cardiology state that echocardiography is recommended for the assessment of the myocardial structure and function of subjects with suspected HF including HF with reduced (HFrEF), mid‐range (HFmrEF), and preserved ejection fraction (HFpEF) as class I of recommendation and level C of evidence. However, the impact of timing of echocardiography on survival for hospitalized HF patients or the prevalence of echocardiography during their stay has not yet been fully investigated. Therefore, we designed and conducted a prospective multicentre study, Optimal Timing of Echocardiography for Heart Failure Inpatients in Japanese Institutions (OPTIMAL) study, to investigate and evaluate the prevalence of echocardiography during the in‐hospital stay of HF patients, and the impact of timing of echocardiography on their survival. Methods and results OPTIMAL was based on a nationwide, prospective, multicentre registry at 10 institutions in Japan endorsed by the Japanese Society of Echocardiography. A total of 601 patients hospitalized with HF were enrolled between August 2016 and July 2018 at the participating centres. Their mean age was 73.9 ± 13.0 years, left ventricular ejection fraction was 37.0% (26.0–50.0), and 256 patients (42.6%) were female. Admission echocardiography (admission echo) was categorized as either standard or point‐of‐care echocardiography performed within 3 days of admission, as was pre‐discharge echocardiography (pre‐discharge echo) within 3 days of discharge. The primary endpoint was defined as cardiovascular death over a median follow‐up period of 18.9 months (9.3–26.5 months). Admission echo was performed for 476 patients (79.2%) and pre‐discharge echo for 216 patients (35.9%). The primary endpoint of cardiovascular death occurred in 65 patients (10.8%). Kaplan–Meier curve findings indicated that survival of patients with pre‐discharge echo was significantly better than that of patients without it (log‐rank P

Recently, various types of functionalized metal oxide nanoparticles have been used for many applications because of their unique chemical and physical properties. To synthesize metal oxide nanoparticles, liquid-phase synthesis techniques have been developed. The production process of metal oxide nanoparticles in aqueous media is extremely complex because the formation, crystal structure, crystallinity, chemical composition, and morphology of the particles are considerably dependent on the preparation conditions (e.g., anion and cation concentrations and species, additives, solution pH, reaction temperature, and reaction time). Accordingly, clarifying these effects is fundamental to accurately understand the formation mechanism of metal oxide nanoparticles to further develop new functionalized nanoparticles. In this review, the influence of anions (Cl−, SO42−, and NO3−) and cations (Ni2+, Cu2+, and Cr3+) on the formation and structure of iron oxide nanoparticles in aqueous media is described.

Streaming instability is considered to be one of the dominant processes in promoting planetesimal formation by the gravitational collapse of dust clumps. The development of streaming instability is expected to form dust clumps in which the local dust density is strongly enhanced and even greater than the Roche density. The resulting clumps can collapse to form planetesimals. Recent simulations showed that such strong clumping occurs in a wider parameter space than previously expected. However, the indicated timescale for strong clumping can be on the order of tens to hundreds of Keplerian periods. In this paper, we estimate the growth time of dust grains during the pre-clumping phase. We find that the dust growth proceeds considerably before the strong clumping because even the moderate clumping due to streaming instability increases the local dust-to-gas ratio to ≳10. Depending on the sound speed, the dust collision velocity can be kept below ∼1 m s ^−1 once sufficiently strong dust clumping occurs. Thus, even silicate grains might have the potential to grow safely toward the size whose Stokes number is unity during the clumping. Our results demonstrate the importance of local dust coagulation during dust clumping due to streaming instability.

Thanks to “dust-to-planet” simulations (DTPSs), which treat the collisional evolution directly from dust to giant-planet cores in a protoplanetary disk, we showed that giant-planet cores are formed in ≲10 au in several 10 ^5 yr, because porous pebbles grow into planetesimals via collisions prior to drift in 10 au. However, such porous pebbles are unlikely to reproduce the polarized millimeter wavelength light observed from protoplanetary disks. We thus investigate gas-giant core formation with nonporous pebbles via DTPSs. Even nonporous bodies can grow into planetesimals and massive cores that are possible to be gas giants are also formed in several 10 ^5 yr. The rapid core formation is mainly via the accretion of planetesimals produced by collisional coagulation of pebbles drifting from the outer disk. The formation mechanism is similar to the case with porous pebbles, while core formation occurs in a wider region (5–10 au) than that with porous pebbles. Although pebble growth and core formation depend on the disk temperature, core formation is likely to occur with disk temperatures in typical optical thick disks around protostars.

Characterizing the physical properties of dust grains in a protoplanetary disk is critical to comprehending the planet formation process. Our study presents Atacama Large Millimeter/submillimeter Array (ALMA) high-resolution observations of the young protoplanetary disk around DG Tau at a 1.3 mm dust continuum. The observations, with a spatial resolution of ≈0.″04, or ≈5 au, revealed a geometrically thin and smooth disk without substantial substructures, suggesting that the disk retains the initial conditions of the planet formation. To further analyze the distributions of dust surface density, temperature, and grain size, we conducted a multiband analysis with several dust models, incorporating ALMA archival data of the 0.87 and 3.1 mm dust polarization. The results showed that the Toomre Q parameter is ≲2 at a 20 au radius, assuming a dust-to-gas mass ratio of 0.01. This implies that a higher dust-to-gas mass ratio is necessary to stabilize the disk. The grain sizes depend on the dust models, and for the DSHARP compact dust, they were found to be smaller than ∼400 μ m in the inner region ( r ≲ 20 au) while exceeding larger than 3 mm in the outer part. Radiative transfer calculations show that the dust scale height is lower than at least one-third of the gas scale height. These distributions of dust enrichment, grain sizes, and weak turbulence strength may have significant implications for the formation of planetesimals through mechanisms such as streaming instability. We also discuss the CO snowline effect and collisional fragmentation in dust coagulation for the origin of the dust size distribution.

Compressive strength is a key to understanding the internal structure of dust aggregates in protoplanetary disks and their resultant bodies, such as comets and asteroids in the solar system. Previous work has modeled the compressive strength of highly porous dust aggregates with volume filling factors lower than 0.1. However, a comprehensive understanding of the compressive strength from low (0.1) volume filling factors is lacking. In this paper, we investigate the compressive strength of dust aggregates by using aggregate compression simulations resolving constituent grains based on Johnson-Kendall-Roberts theory to formulate the compressive strength comprehensively. We perform a series of numerical simulations with moving periodic boundaries mimicking the compression behavior. As a result, we find that the compressive strength becomes sharply harder when the volume filling factor exceeds 0.1. We succeed in formulating the compressive strength comprehensively by taking into account the rolling motion of aggregates for low volume filling factors and the closest packing of aggregates for high volume filling factors. We also find that the dominant compression mechanisms for high volume filling factors are sliding and twisting motions, while rolling motion dominates for low volume filling factors. We confirm that our results are in good agreement with previous numerical studies. We suggest that our analytical formula is consistent with the previous experimental results if we assume the surface energy of silicate is ≃210 ± 90 mJ m ^−2 . Now, we can apply our results to properties of small compact bodies, such as comets, asteroids, and pebbles.

By performing N -body simulations, we investigated the fundamental processes of collisions between dust aggregates composed of submicron-sized icy dust monomers. We examined the mass distribution of fragments in the collisional outcomes in a wide range of the mass ratio and the collision velocity between colliding dust aggregates. We derived analytic expressions of the mass distribution of large remnants and small fragments by numerical fitting to the simulation results. Our analytic formulae for masses of the large remnants can reproduce the contribution of mass transfer from a large target to a small projectile, which occurs for a mass ratio of ≳3 and is shown in a previous study. We found that the power-law index of the cumulative mass distribution of the small fragments is independent of the mass ratio and only weakly dependent on the collision velocity. On the other hand, the mass fraction of fragments of individual dust monomers decreases with an increasing total mass of colliding aggregates for a fixed mass ratio. This tendency implies that multiple hierarchical disruptive collisions (i.e., collisions between fragments, and collisions between fragments of fragments) are required for producing a large number of individual dust monomers via collisional fragmentation. Our fragment model suggests that the total geometric cross section integrated over the fragments is estimated to be about the same order as the geometric cross section of the target.

The structure of dust aggregates affects many aspects of planet formation, such as the dust collision outcome, opacity, and radiation field. The millimeter-wave scattering polarization in protoplanerary disks indicates that dust aggregates have relatively compact structures with a volume-filling factor ≳0.1. In this study, to explain such compact dust aggregates, we examined the compression of dust aggregates in sticking collisions with high mass ratios by performing a large number of N -body simulations of sequential dust collisions for a wide parameter range. Previous N -body simulations reported inefficient compression in equal-mass collisions between large dust aggregates. In contrast, we found that collisions with high mass ratios can compress the dust aggregate much more effectively. We also developed a new compression model that explains our results for sequential collisions with high mass ratios. Finally, we applied the new compression model to dust aggregates in protoplanetary disks and found a possible pathway to create relatively compact dust aggregates that explain the observed millimeter-wave scattering polarization.

Aims: Circulating amino acid (AA) abnormalities serve as predictors of adverse outcomes in patients with heart failure (HF). However, the role of the gut microbiota in AA disturbances remains unknown. Thus, we investigated gut microbial functions and their associations with AA metabolic alterations in patients with HF.Methods and Results: We performed whole-genome shotgun sequencing of fecal samples and mass spectrometry-based profiling of AAs in patients with compensated HF. Plasma levels of total essential AAs (EAAs) and histidine were significantly lower in patients with HF than in control subjects. HF patients also displayed increased and decreased abundance of gut microbial genes involved in the degradation and biosynthesis, respectively, of EAAs, including branched-chain AAs (BCAAs) and histidine. Importantly, a significant positive correlation was observed between the abundance of microbial genes involved in BCAA biosynthesis and plasma BCAA levels in patients with HF, but not in controls. Moreover, network analysis revealed that the depletion of Eubacterium and Prevotella, which harbor genes for BCAA and histidine biosynthesis, contributed to decreased abundance of microbial genes involved in the biosynthesis of those EAAs in patients with HF.Conclusions: The present study demonstrated the relationship between gut microbiota and AA metabolic disturbances in patients with HF.

Abstract Background Left ventricular (LV) longitudinal dysfunction has been identified in type 2 diabetes mellitus (T2DM) patients with preserved LV ejection fraction (LVEF). However, the impact of T2DM on LV longitudinal function or the association of LV longitudinal function with outcome for dilated cardiomyopathy (DCM) remains unclear. Methods We retrospectively studied 206 patients with non-ischemic DCM, mean age of 59 ± 17 years and LVEF of 31 ± 8% (all

Abstract Background Balloon aortic valvuloplasty (BAV) offers an alternative to conventional aortic valve replacement in elderly and frail patients with severe aortic stenosis (AS) for whom there are no other effective options. We aimed to investigate the mid-term effect of BAV on mitral regurgitation (MR) in patients with severe AS. Methods Our analysis was based on the data from 83 patients with severe AS (mean age, 86 ± 5 years; female, 68) treated using BAV. Echocardiography was performed before the procedure and at 1 and 3 months after. MR was quantified by measuring the MR jet area, with more-than-moderate MR being clinically significant. Results Forty patients were classified in this group (MR group). Significant reduction of MR was observed in the MR group at 1 month and 3 months after procedure, with no improvement in patients in the non-MR group. At 3 months, 15 of the 40 patients in the MR group still had significant MR, with the change at 1 month in the left ventricular end-systolic dimension (OR: 1.36; 95% CI: 1.05–1.76; P = 0.022) and MR jet area (OR: 1.95; 95% CI: 1.16–3.29; P = 0.012) being predictive of persisting significant MR at 3 months after BAV. The prevalence of New York Heart Association functional class III or IV decreased at 1 and 3 months after BAV in both groups. Conclusions BAV provides a useful therapeutic strategy for elderly patients with severe AS who are not candidates for surgical or transcatheter aortic valve replacement, especially in those with significant MR.

Qing Dai/Indigo Naturalis (QD) has been shown to ameliorate ulcerative colitis (UC) in clinical trials; however, its mechanism remains elusive. This study investigates the effects of QD on murine dextran sulfate sodium salt-induced colitis. Oral administration of QD protected the animals from colitis as manifested by weight loss, diarrhea, and rectal bleeding. QD was distinguishingly more effective than 5-aminosalicylate. Focused microarray analysis of genes expressed in the distal colon suggested that QD influences the inflammatory pathway. Anti-inflammatory activity of QD was confirmed by the suppression of nitric oxide (NO) production in response to interleukin-1β in cultured hepatocytes. Some of the constituents in QD, such as tryptanthrin (TRYP) and indigo, suppressed NO production. TRYP maintained body weight but did not inhibit bleeding. Indigo, on the other hand, partially ameliorated bleeding, but did not maintain body weight. The combination of TRYP and indigo did not show additive ameliorating activity. The methanol extract of QD showed an anti-colitis activity like that of TRYP. In contrast, the methanol-insoluble QD fraction moderately ameliorated diarrhea and bleeding. Combining these two fractions resulted in full anti-colitis activity. Further clarification of the active constituents will help in the discovery of a safe and potent prescription for UC. Keywords: Ulcerative colitis, Dextran sulfate sodium salt, Qing Dai/Indigo Naturalis, Tryptanthrin, NO

Abstract Background The effect of sodium glucose cotransporter type 2 (SGLT2) inhibitor on left ventricular (LV) longitudinal myocardial function in type 2 diabetes mellitus (T2DM) patients with heart failure (HF) has remained unclear. Methods We analyzed data from our previous prospective multicenter study, in which we investigated the effect of the SGLT2 inhibitor dapagliflozin on LV diastolic functional parameters of T2DM patients with stable HF at five institutions in Japan. Echocardiography was performed at baseline and 6 months after administration of dapagliflozin. LV diastolic function was defined as the ratio of mitral inflow E to mitral e′ annular velocities (E/e′). LV longitudinal myocardial function was assessed as global longitudinal strain (GLS), which in turn was determined as the averaged peak longitudinal strain from standard LV apical views. Results E/e′ significantly decreased from 9.3 to 8.5 cm/s 6 months after administration of dapagliflozin (p = 0.020) as previously described, while GLS showed significant improvement from 15.5 ± 3.5% to 16.9 ± 4.1% (p

Abstract Background Type 2 diabetes mellitus (T2DM) is a major cause of heart failure (HF) with preserved ejection fraction (HFpEF), usually presenting as left ventricular (LV) diastolic dysfunction. Thus, LV diastolic function should be considered a crucial marker of a preclinical form of DM-related cardiac dysfunction. However, the impact of glycemic variability (GV) on LV diastolic function in such patients remains unclear. Methods We studied 100 asymptomatic T2DM patients with preserved LV ejection fraction (LVEF) without coronary artery disease (age: 60 ± 14 years, female: 45%). GV was evaluated as standard deviation of blood glucose level using continuous glucose monitoring system for at least 72 consecutive hours. LV diastolic function was defined as mitral inflow E and mitral e’ annular velocities (E/e’), and > 14 was determined as abnormal. Results E/e’ in patients with high GV (≥ 35.9 mg/dL) was significantly higher than that in patients with low GV (11.3 ± 3.9 vs. 9.8 ± 2.8, p = 0.03) despite similar age, gender-distribution, and hemoglobin A1c (HbA1c). Multivariate logistic regression analysis showed that GV ≥ 35.9 mg/dL (odds ratio: 3.67; 95% confidence interval: 1.02–13.22; p 14. In sequential logistic models for the associations of LV diastolic dysfunction, one model based on clinical variables including age, gender and hypertension was not improved by addition of HbA1c (p = 0.67) but was improved by addition of high GV (p = 0.04). Conclusion Since HFpEF is a syndrome caused by diverse agents, reducing GV may represent a potential new therapeutic strategy for the prevention of the development of HFpEF in T2DM patients.

In esthetic dental care, porcelain-fused-to-metal crowns have long been used for dental restoration. Since a dental prosthesis is placed in the harsh environment of the oral cavity over long periods, metal allergy due to eluate from the metal frame has proved to be problem, prompting the development of new methods for tooth repair. Zirconia ceramics are used in dental prostheses for tooth restoration because of their excellent strength and high biocompatibility. They are widely used clinically for cosmetic dentistry. This study evaluates the suitability of yttria-based zirconia and ceria-based nano-zirconia for use in dentistry. The mechanical properties of zirconia powders with different compositions are evaluated in terms of sintering density, crystalline phases, structure, translucency, bending strength, fracture toughness, and impact toughness. In addition, a fracture strength test was carried out on sintered bodies that imitate a single crown coping assuming a molar tooth. Yttria-based zirconia was found to have a natural tooth tone and excellent light transmission. Ceria-based nano-zirconia was found to have more than double the fracture toughness (single-edge pre-cracked beam method) and bending strength compared to yttria-based zirconia and excellent strength for dental prostheses.

Background Myocardial extracellular volume fraction (ECV), measured by cardiac magnetic resonance imaging, is a useful prognostic marker for patients who have undergone aortic valve replacement (AVR) for aortic stenosis. However, the prognostic significance of ECV measurements based on computed tomography (CT) is unclear. This study evaluated the association between ECV measured with dual‐energy CT and clinical outcomes in patients with aortic stenosis who underwent transcatheter or surgical AVR. Methods and Results We retrospectively enrolled 95 consecutive patients (age, 84.0±5.0 years; 75% women) with severe aortic stenosis who underwent preprocedural CT for transcatheter AVR planning. ECV was measured using iodine density images obtained by delayed enhancement dual‐energy CT. The primary end point was a composite outcome of all‐cause death and hospitalization for heart failure after AVR. The mean ECV measured with CT was 28.1±3.8%. During a median follow‐up of 2.6 years, 22 composite outcomes were observed, including 15 all‐cause deaths and 11 hospitalizations for heart failure. In Kaplan‐Meier analysis, the high ECV group (≥27.8% [median value]) had significantly higher rates of composite outcomes than the low ECV group (

Heterometallic complexes of tetrakis(µ-carboxylato)diruthenium(II,III) with tetracyanidoaurate(III) [Ru2(RCOO)4Au(CN)4]n (R = CH3 (1), C2H5 (2), i-C3H7 (3), and t-C4H9 (4)) were synthesized and characterized by C,H,N-elemental analysis and infrared spectroscopy and diffuse reflectance spectroscopy. The molecular structures were determined by a single-crystal X-ray diffraction method. A polymeric arrangement with the Ru2(RCOO)4+ units alternately linked by Au(CN)4− units is formed in these complexes. The trans-bridging mode of the Au(CN)4− unit for connecting the two Ru2(RCOO)4+ units was observed for 1 and 4, while the cis-bridging mode of the Au(CN)4− unit was observed for 2 and 3. Magnetic susceptibility data with variable temperature were modeled with a zero-field splitting model (D = 75 cm−1) and the presence of weak antiferromagnetic coupling between the RuIIRuIII units (zJ = −0.15~−0.10 cm−1) was estimated. N2-adsorption isotherms showed Type II curves with SBET of 0.728–2.91 m2 g−1.

A vanadium dioxide VO2 film shows metal-insulator transition (MIT) induced by changing environmental temperature. We report the temperature dependence of electromotive force properties generated in VO2/Ni80Fe20 bilayer junctions under the ferromagnetic resonance (FMR) of the Ni80Fe20 layer. An electromotive force generated in a VO2/Ni80Fe20 bilayer junction under the FMR showed a small change across the MIT temperature of the VO2 film, while the VO2 film resistance drastically changed. This behavior was not only explained with the temperature dependence of the electromotive force property generated in the Ni80Fe20 film itself under the FMR, but also with the generated electromotive forces due to the inverse spin-Hall effect (ISHE) in the VO2 film under the FMR of the Ni80Fe20 film. That is, we successfully demonstrated the spin injection from a Ni80Fe20 film into a VO2 film across the MIT temperature of the VO2 film.

Topological edge states can emerge not only in a fermionic electron system but also in a bosonic system. Here, Nawa et al. report topologically nontrivial triplon bands in a two-dimensional dimerized quantum antiferromagnet Ba2CuSi2O6Cl2, suggesting a bosonic realization of the coupled Su-Schrieffer-Heeger model.