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Infrared spectroscopy (IR) and quantum chemistry calculations that are based on the density functional theory (DFT) have been used to study the structure and molecular interactions of the nematic and twist-bend phases of thioether-linked dimers. Infrared absorbance measurements were conducted in a polarized beam for a homogeneously aligned sample in order to obtain more details about the orientation of the vibrational transition dipole moments. The distributions to investigate the structure and conformation of the molecule dihedral angle were calculated. The calculated spectrum was compared with the experimental infrared spectra and as a result, detailed vibrational assignments are reported.

6-Mercaptopurine (6-MP) is widely used for the treatment of paediatric leukaemia and lymphoma. Recently, germline variants in the NUDT15 gene have been identified as one of the major genetic causes for 6-MP-associated adverse effects such as myelosuppression. Patients with hypomorphic NUDT15 variants accumulate excessive levels of DNA-incorporated thioguanine in white blood cells, resulting in severe myelosuppression. Although preclinical studies suggest that these variants may influence the protein stability of NUDT15, this has not been directly characterised in patients. In this study, we report the development of a series of novel monoclonal antibodies against NUDT15, using which we quantitatively assessed NUDT15 protein levels in 37 patients with acute lymphoblastic leukaemia treated with 6-MP, using sandwich enzyme-linked immunosorbent assay (ELISA). The NUDT15 genotype was highly correlated with its protein levels (p 0.0001), with homozygous and compound heterozygous patients showing exceedingly low NUDT15 expression. There was a positive correlation between NUDT15 protein level and 6-MP tolerance (r = 0.631, p 0.0001). In conclusion, our results point to low NUDT15 protein abundance as the biochemical basis for NUDT15-mediated 6-MP intolerance, thus providing a phenotypic readout of inherited NUDT15 deficiency.

The MLL-10 trial (UMIN000004801) modified a Children's Oncology Group (COG) AALL0631 therapy for infants with KMT2A-rearranged acute lymphoblastic leukemia (ALL). In 2016, one registered case developed secondary immunodeficiency during maintenance therapy and eventually died due to cytomegalovirus infection. Around the same time, fatal secondary immunodeficiencies were reported in five infants with ALL in North America who had received COG-based chemotherapy between 1996 and 2015. Given these cases, we decided to conduct a retrospective study on the postchemotherapy immune status of infants with ALL. A questionnaire collected data on posttreatment immune function, frequency of infections, and supportive care for the 34 infants in the MLL-10 trial. Patients receiving allogeneic hematopoietic stem cell transplantation in first remission were excluded. Responses to the survey were obtained in 28 cases (85%). Most patients were immunocompetent after the completion of chemotherapy (median follow-up duration from the day of chemotherapy completion was 431 days), except for the aforementioned case. There were seven patients with nonsevere viral infection, all of whom recovered. In conclusion, severe chemotherapy-induced immunodeficiency in infants with ALL appears to be rare, but prospective data collection of immune function is necessary to clarify this finding.

Background Right ventricular (RV) pacing causes left ventricular (LV) dyssynchrony sometimes resulting in pacing‐induced cardiomyopathy. However, RV pacing for hypertrophic obstructive cardiomyopathy is one of the treatment options. LV flow energy loss (EL) using vector flow mapping (VFM) is a novel hemodynamic index for assessing cardiac function. Our study aimed to elucidate the impact of RV pacing on EL in normal LV function and hypertrophic cardiomyopathy (HCM) patients. Methods A total of 36 patients with dual‐chamber pacemakers for sick sinus syndrome or implantable cardioverter defibrillators for fatal ventricular tachyarrhythmias were enrolled. All patients were divided into two groups: 16 patients with HCM (HCM group) and others (non‐HCM group). The absolute changes in EL under AAI (without RV pacing) and DDD (with RV pacing) modes were assessed using VFM on color Doppler echocardiography. Results In the non‐HCM group, the mean systolic EL significantly increased from the AAI to DDD modes (14.0 ± 7.7 to 17.0 ± 8.6 mW/m, P = .003), whereas the mean diastolic EL did not change (19.0 ± 12.3 to 17.0 ± 14.8 mW/m, P = .231). In the HCM group, the mean systolic EL significantly decreased from the AAI to DDD modes (26.7 ± 14.2 to 21.6 ± 11.9 mW/m, P, In non‐HCM patients, the RV pacing decreased the vortex area and the circulation and in HCM patients, it increased the vortex area and the circulation. The RV pacing significantly increased systolic energy loss in the non‐HCM group (P = .003), but it significantly decreased in the HCM group (P

The twist-bend nematic phase (NTB) is a new spontaneous symmetry-breaking phenomenon observed in fluidic liquid crystal (LC) phases, which possesses a heliconical structure with a pitch ranging from several to tens of nanometers. Herein we demonstrate the distinct nano-to-macroscopic NTB phase behaviors associated with the ester-bond direction in two homologous series of sulfur-containing cyanobiphenyl-based LC dimers, viz. CBCOOnSCB and CBOCOnSCB (n = 2, 4, 6, 8, and 10). Both the series (excluding n = 2) formed NTB phases in which the homologues (n = 4 and 6) exhibited the NTB phases across a broad temperature range, which were observed to be stable even at room temperature and eventually formed NTB glasses. We found that both homologues (n = 4 and 6) displayed distinct phase-transition properties and optical textures with respect to the NTB phases. By performing tender resonant X-ray scattering measurements at the sulfur K-edge, we discovered their distinctly different nanoscopic helical pitch lengths. Within a similar shifted temperature, the pitches for CBOCOnSCB showed strong temperature dependence and were approximately double those of CBCOOnSCB, which exhibited significantly weaker temperature dependence. Compared to those of the representative twist-bend nematogenic dimers, the pitches of CBOCOnSCB and CBCOOnSCB are longer and shorter, respectively. It is assumed that the molecular bend (or the molecular biaxiality) of LC dimers strongly influences the precession angle of the heliconical helix, and hence the resulting pitch. These findings provide new insights into the molecular designs to modulate the nanoscale helical pitches of the NTB phases.

The understanding of correlations between molecular details and macroscopic material behavior is a fundamental question of molecular chemistry/physics and offers practical interest in materials design with fine-property-tunability. Herein, we demonstrate extreme modulation of liquid crystal (LC) viscoelasticity triggered by a reversion of the ester bond direction in two series of sulfur-containing cyanobiphenyl-based LC dimers. They possess two oppositely directed ester linkages (i.e., COO or OCO), namely COOn and OCOn, respectively, and different carbon atom numbers of the short alkylene spacers (n = 4 and 6). Unexpectedly, it has been proven that the COOn homologs exhibit extraordinarily enhanced viscoelastic properties in the fluidic nematic (N) phase (up to about 1000 times) compared with their OCOn counterparts. Besides, dielectric spectroscopy revealed that the degree of the collective orientational fluctuation is significantly affected by reversing the ester bond direction, suggesting the existence of heliconical clusters embedded in the N state. Finally, we have proposed a novel eco-driving LC memory device based on a pulse-electric-field driving method using COO4 with an extremely high rotational viscosity.

Being a link between a uniaxial nematic and a chiral nematic, the twist bend nematic (NTB) has been an intriguing topic for research over the last decade as a key to understanding chirality generation. Accurate description and understanding of resonance effects in helical structures provide crucial knowledge on the phase behavior beyond positional ordering. We examined the manifestation of resonance effects in NTBvia tender resonant X-ray scattering (TReXS) at the sulfur K-edge. For the first time we demonstrate quantitatively that the energy dependence of the scattering peak in the NTB phase follows the energy dependence of the complex refractive indices measured by X-ray absorption. Taking advantage of molecular energy calculation, we decipher the distinct helical pitch variation trend for symmetric/asymmetric dimers from the perspective of hybridization and reveal the strong effect of substituting oxygen for sulfur atoms on the helical pitch and the thermal helix extension.

The prognosis for infants with acute lymphoblastic leukemia (ALL), particularly those with KMT2A gene rearrangement (KMT2A-r), is dismal. Continuous efforts have been made in Japan to investigate the role of hematopoietic stem cell transplantation (HSCT) for infants with KMT2A-r ALL, but improvement in outcome was modest. In the Japanese Pediatric Leukemia/Lymphoma Study Group MLL-10 trial, infants with ALL were stratified into 3 risk groups (low risk [LR], intermediate risk [IR], and high risk [HR]) according to KMT2A status, age, and presence of central nervous system leukemia. Children’s Oncology Group AALL0631 modified chemotherapy with the addition of high-dose cytarabine in early intensification was introduced to KMT2A-r patients, and the option of HSCT was restricted to HR patients only. The role of minimal residual disease (MRD) was also evaluated. Ninety eligible infants were stratified into LR (n = 15), IR (n = 19), or HR (n = 56) risk groups. The 3-year event-free survival (EFS) rate for patients with KMT2A-r ALL (IR + HR) was 66.2% (standard error [SE], 5.6%), and for those with germline KMT2A (KMT2A-g) ALL (LR), the 3-year EFS rate was 93.3% (SE, 6.4%). The 3-year EFS rate was 94.4% (SE, 5.4%) for IR patients and 56.6% (SE, 6.8%) for HR patients. In multivariable analysis, female sex and MRD ≥0.01% at the end of early consolidation were significant factors for poor prognosis. Risk stratification and introduction of intensive chemotherapy in this study were effective and were able to eliminate HSCT for a subset of infants with KMT2A-r ALL. Early clearance of MRD seems to have translated into favorable outcomes and should be incorporated into risk stratifications in future trials. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as #UMIN000004801.

We prospectively collected device and heart rate data through remote monitoring (RM) of patients with an implantable cardioverter defibrillator (ICD). The objective was to identify the predictors of lethal arrhythmic events (VT/VF).Thirty-three patients (mean age: 50 years) with ICDs [with functionality of heart rate variability (HRV) analysis] were divided into two groups [VT/VF (+), VT/VF (-) ]. Clinical, device (ventricular lead impedance; amplitude of ventricular electrogram), and HRV data were compared between the two groups. The NN interval-index (SDNNi) was calculated for every 5 minutes, and the mean, maximum, minimum, and standard deviation of SDNNi during the 24-hour period were used.During the observation period of 13 ± 10 months, 10 patients experienced VT/VF events. Total mean, max, and min SDNNi were higher in the VT/VF (+) than the VT/VF (-) group (132.9 ± 9.3 versus 93.5 ± 6.1, P = 0.0013; 214.6 ± 10.6 versus 167.0 ± 7.0, P = 0.0007; 71.2 ± 7.5 versus 43.9 ± 4.9, P = 0.0047). On logistic regression analysis, a total mean SDNNi of 100.1, max SDNNi of 185.0 and min SDNNi of 52.0 as cut-off values for prediction of a VT/VF event demonstrated significant receiver operating characteristic (ROC) curves (AUC = 0.86, P = 0.0007; AUC = 0.84, P = 0.0005; AUC = 0.78, P = 0.0030). The max ΔSDNNi, i.e., difference from baseline SDNNi, and min ΔSDNNi in 7 and 28 days preceding VT/VF events were significant predictors of VT/VF events.Time-domain HRV analysis through a RM system may help identify patients at high risk of lethal arrhythmic events; in addition, it may help predict the occurrence of lethal arrhythmic events in specific cases.

Ablation index (AI) is a useful tool of the CARTO® system to make effective lesions during pulmonary vein isolation (PVI) for atrial fibrillation (AF). However, the optimal distance between neighboring ablation points (interlesion distance (ILD)) is still unclear. Here, we evaluated the optimal ILDs in the AI-guided PVI. Forty-nine AF patients who underwent AI-guided PVI in our institute from July 2018 to March 2019 were retrospectively enrolled in this study. Target AI was set at 500 and 400 for anterior and posterior walls, respectively, and we compared the ILDs with and without electrical gaps after a first encircling PVI. In both PV, the ILDs with electrical gaps were longer than those without electrical gaps. The best cutoff values of ILD to detect the electrical gaps using the ROC curve were 5.4 mm for the RPV anterior wall (AUC, 0.67; sensitivity, 0.42; specificity, 0.84, P < 0.01) and 4.4 mm for the RPV posterior wall (AUC, 0.68; sensitivity, 0.91; specificity, 0.39, P < 0.01). Similarly, the best cutoff values of ILD were 5.5 mm for the LPV anterior wall (AUC, 0.74; sensitivity, 0.65; specificity, 0.82, P < 0.01) and 5.1 mm for the LPV posterior wall (AUC, 0.67; sensitivity, 0.79; specificity, 0.53, P =0.03). The optimal interlesion distances for PVI were different in each PV segment. To achieve the first-pass isolation, less than 5.4/4.4 mm for the RPV anterior/posterior and 5.5/5.1 mm for the LPV anterior/posterior walls of interlesion distances were the best cutoff values in the patients with AF.

Monosomy 7 (-7) occurs in various types of paediatric myeloid disorders and has a poor prognosis. Recent studies have demonstrated that patients with germline gain-of-function SAMD9/9L variants and loss-of-function GATA2 variants are prone to developing myelodysplastic syndrome (MDS) associated with -7. However, the prevalence of the genetic variants among paediatric haematologic disorders with -7 is unknown. The present study screened germline variants of GATA2 and SAMD9/9L in 25 patients with various types of paediatric haematological disorders associated with -7. The diagnoses of the 25 patients included MDS (n = 10), acute myeloid leukaemia (AML) and myeloid sarcomas (n = 9), juvenile myelomonocytic leukaemia (n = 3) and other disorders (n = 3). Seven patients with a germline pathogenic GATA2 variant were found. For SAMD9/9L screening, next-generation sequencing was used to detect low-abundance variants and found four novel germline variants. Functional analysis revealed that three out of the four variants showed growth-restricting capacity in vitro and thus, were judged to be pathogenic. Cases with GATA2 mutation tended to be older, compared to those with SAMD9/9L mutations. In conclusion, GATA2 and SAMD9/9L were sequenced in 25 patients with paediatric haematologic disorders associated with -7, and 40% of them were found to have some pathogenic germline variants in the three genes.

Complex atrial tachycardias (ATs) after catheter ablation or a MAZE procedure is sometimes difficult to determine the circuits of the tachycardia. A high-density, grid-shapes mapping catheter has been launched, which can be useful for detecting the detail circuits of tachycardias on three-dimensional mapping systems. The signal quality is also important for performing electrophysiological studies (EPSs), such as entrainment mapping, to identify the circuit. This unique mapping catheter has 1 mm electrodes on 2.5 Fr shafts, which improve the signal quality. The high-quality intracardiac electrograms facilitate differentiating small critical potentials, which allows us to perform detailed entrainment mapping in targeted narrow areas. Here, we describe a patient with a perimetral AT with epi-endocardium breakthrough after a MAZE surgery and catheter ablation, which was treated successfully along with detailed entrainment mapping using the HD Grid. This catheter with high-quality signals could be a significant diagnostic tool for a classic EPS as well as for the construction of 3D mapping.

The twist-bend nematic (NTB ) phase with a heliconical nanostructure of the local director generating symmetry breaking by achiral bent-shaped molecules is a hot topic of current liquid-crystal science. As opposed to the most common methylene-linked dimers, this study demonstrates chalcogen ether- and/or thioether-linked 6-(4-cyanophenyl)-2-naphthyl-based liquid-crystal dimers with symmetric and asymmetric π-conjugated mesogenic-arm structures that exhibit the NTB phase. Although the symmetric bis(ether)-linked dimer exhibits only the conventional nematic (N) phase, the asymmetric bis(ether)-linked dimer can form the NTB phase. All thioether-linked dimers form the NTB phase, wherein the dimers with asymmetric arms vitrify in the NTB phase on cooling to room temperature. The phase transitions are discussed in terms of the chalcogen linkage combination, mesogenic-arm symmetry, and spacer length. It is revealed that thioether-linked dimers based on asymmetric π-conjugated mesogenic arms with terminal cyano groups are highly beneficial for the realization of materials that form a wide range of NTB phases and glassy NTB states at room temperature.

Background: The wearable cardioverter defibrillator (WCD) has been available since 2014 in Japan, and its benefit in the in-hospital acute phase at high risk of ventricular tachyarrhythmia (VTA) has been established, but its clinical use in the outpatient setting remains unclear, especially in Japan. Methods and Results: The subjects consisted of 43 consecutive patients with WCD use in the outpatient setting from April 2014 to October 2019 at the present institute. Event alerts and wearing compliance were checked via the remote monitoring system, and a dedicated WCD training team contacted the patients if necessary. The median observation period was 51 days (IQR, 37–68 days) and the median daily wearing time was 23.1 h/day (IQR, 22.0–23.6 h/day). WCD was prescribed for primary prevention of VTA in 7 patients (16%), and for secondary prevention in 36 (84%). The common reason for WCD use was preventive therapy and/or clinical observation. Two appropriate and one inappropriate shock were observed. Eleven patients were not indicated for ICD because of successful catheter ablation optimal medical therapy, VTA in early onset of heart disease and refusal. The remaining 32 patients, however, underwent ICD implantation. Conclusions: In the present real-world study, the WCD wearing compliance was well-maintained in the outpatient setting. WCD is useful for patients at high risk of VTA.

Introduction The incidence of new-onset atrial high-rate episode (AHRE) is higher among patients with cardiac implantable electronic devices (CIEDs) than in the general population. We sought to elucidate the clinical factors including P-wave dispersion (PWD) in sinus rhythm associated with AHRE in CIED patients. Methods and results One hundred one patients with newly implanted CIEDs from 2010 to 2014 at our institute were included. PWD was measured at the time of device implantation via a body-surface electrocardiogram. AHRE was defined as any episode of sustained atrial tachyarrhythmia (>170 bpm) recorded in the device’s memory. Patients were divided into an AHRE group (n=34) and non-AHRE group (n=67) in accordance with the presence or absence of AHRE within one year of device implantation and compared. The mean age was 75 ± 11 years old. A greater incidence of sick sinus syndrome (p=0.05) and longer PWD (62.6 ± 13.1 vs. 38.2 ± 13.9 ms; p

Objectives The Commission on Social Determinants of Health (CSDH) of the World Health Organization (WHO) recommends that national and municipal governments take adequate steps to "improve daily living conditions," "(create governance to) tackle the inequitable distribution of power, money, and resources," and "measure and understand the problem and assess the impact of" government actions. This study provides an analysis of the health promotion policies of Japan and other countries and examines their conformance to these recommendations, and offers suggestions for developing a conducive social environment for Japan's health promotion policies.Methods We reviewed grey literature on health promotion policies in Japan, the USA, England, Sweden, and Thailand, extracting the definitions of health inequalities and their characterization in each policy, and analyzing each document vis-á-vis the CSDH's three recommendations and "comprehensive national health equity surveillance framework."Results The health promotion policies of Japan, England, Sweden, and the USA had similar definitions of health inequality, emphasizing fairness and prioritizing the reduction of health inequality as the key strategy for health promotion. However, their primary approaches to improve daily living conditions varied: In Japan, the primary approach is to create opportunities for participation and ensure access to social resources. Meanwhile, the USA relies largely on objective assessments and scientific evidence-based actions. England focused on enhancing support for socially disadvantaged individuals and areas. In Sweden, a universal intervention based on life-course perspectives was stressed, while Thailand attached much value to a multi-sectoral collaboration. All these countries, however, had a health policy implementation plan in quest of the elimination of unfair distributions of power, money, and resources. The USA planned to monitor a total of 187 social factors, the largest number among the 6 subject countries. It also had a wide range of perspectives on health inequalities, including income and disability, as well as conducting assessments using information from outside the health sector, with items assessed at various levels, including individual, regional, and national policies.Conclusion With reference to these approaches in other countries, for Japan's health promotion policies, we recommend: (1) grasping of health inequalities from more diversified perspectives and adopting measures to address them, (2) setting targets based on multi-level social determinants of individual behavior and health status, including individual socioeconomic status, and (3) promoting collaborative initiatives and use of indicators with entities outside the health sector.

We report the synthesis, phase-transition behavior, and mesophase structures of the first homologous series of thioether-linked liquid crystal (LC) trimers, 4,4′-bis[ω-(4-cyanobiphenyl-4′-ylthio)alkoxy]biphenyls (CBSnOBOnSCB with a wide range of spacer carbon numbers, n = 3–11). All CBSnOBOnSCB homologs exhibited LC phases. Interestingly, even-n and odd-n homologs showed monotropic layered smectic A (SmA) and pseudo-layered twist-bend nematic (NTB) phases, respectively, below a nematic (N) phase. This alternate formation, which depends on spacer chain parity, is attributed to different average molecular shapes, which are associated with the relative orientations of the biphenyl moieties: linear and bent shapes for even-n and odd-n homologs, respectively. In addition, X-ray diffraction analysis indicated a strong cybotactic N phase tendency, with a triply intercalated structure. The phase-transition behavior and LC phase structures of thioether-linked CBSnOBOnSCB were compared with those of the all-ether-linked classic LC trimers CBOnOBOnOCB. Overall, thioether linkages endowed CBSnOBOnSCB with a monotropic LC tendency and lowered phase-transition temperatures, compared to those of CBOnOBOnOCB, for the same n. This is attributed to enhanced flexibility and bending (less molecular anisotropy) of the molecules, caused by the greater bond flexibility and smaller inner bond angles of the C–S–C bonds, compared to those of the C–O–C bonds.

An analysis of the IR absorbance for the segmented functional groups of liquid crystal dimers mesogen and linker enabled the orientation order to be determined and information about the dipole interactions in the nematic and twist-bend nematic phases to be obtained. The long axis orientational order increases as the temperature decreases in the nematic phase, although much more slowly than for the classical nematics, and then reverses this trend in the twist-bend nematic phase due to the tilt of the molecules. In the nematic phase, the short axis of the molecule performs an isotropic uniform rotation and has a uniaxial alignment. In the twist-bend nematic phase, however, biaxial ordering occurs and grows significantly in accordance with the helical deformation of the director. Changes in the mean absorbance in the twist-bend nematic phase were observed: a decrease for the longitudinal dipole at the nematic-twist-bend nematic phase transition, thus emphasizing the antiparallel axial interaction of the dipoles, while the absorbance of the transverse dipoles remains unchanged up to 340 K, and then the latter become parallelly correlated.

OBJECTIVE Embryonal tumor with multilayered rosettes (ETMR) is one of the childhood central nervous system tumors with the poorest prognosis; thus, establishing an optimal treatment strategy is essential, However, because of the low incidence and molecular heterogeneity of the tumor, the optimal treatment has not yet been determined. In this study the authors evaluated the prognostic impact of a multimodal treatment approach in patients with ETMR. METHODS The authors evaluated 4 patients with ETMR at their institution who showed varied clinical features and also conducted clinical characterization and prognostic analysis of previously reported cases of the ETMR-presenting locus 19q13.42 with a chromosome 19 microRNA cluster (C19MC) amplification, which is known to be a diagnostic hallmark of the tumor. RESULTS Of the 4 patients with ETMR in the authors’ institution, in 1 case the patient’s tumor showed a neuroblastoma-like appearance without multilayered rosettes; however, the diagnosis was confirmed by the presence of amplified C19MC. From a clinical standpoint, 2 patients who underwent gross-total resection (GTR) of the tumor and chemotherapy followed by high-dose chemotherapy (HDC) had long-term complete remission with or without local irradiation. In the multivariate analysis of 43 cases with C19MC-altered ETMR reported in the literature, HDC and local irradiation were significantly correlated with better event-free survival (HR 0.17, p = 0.0087; HR 0.17, p = 0.010) and overall survival (OS) (HR 0.29, p = 0.023; HR 0.28, p = 0.019), respectively. GTR was also correlated with better OS (HR 0.40, p = 0.039). CONCLUSIONS This case series demonstrated pathological and clinical heterogeneity among ETMR cases and the diagnostic importance of the molecular genetic approach among embryonal tumors, particularly during infancy. Based on the results of the analysis of molecularly uniformed ETMR cases, multimodal treatment may play a significant role in the prognosis of these tumors.

BackgroundThis study focuses on postpartum women, who are one of the most vulnerable populations during the COVID-19 pandemic, aiming to reveal mental health consequences of social restrictions, loss of social support, or loss of autonomy.MethodsA cross-sectional study for postpartum women was conducted in October 2020 (N = 600). The Edinburgh Postpartum Depression Scale (EPDS) was used to measure postpartum depression. The prevalence ratios were estimated by log-binomial regression models, adjusting for age, education, household income, residence area, parity, the timing of delivery, and a prior history of depression.ResultsThe prevalence of postpartum depression was 28.7% (EPDS ≥ 9), 18.6% (≥ 11), and 13.1% (≥ 13). Social restrictions including cancellation of home visits by health care professionals, or cancellation of infant checkups or vaccinations, loss of support during pregnancy or after delivery including loss of opportunities to consult with health care professionals or friends, or cancellation of parents or other family members’ visits to support, and loss of autonomy about delivery or breastfeeding, were associated with postnatal depression.ConclusionAbout 30% of women who delivered and raised a baby during the COVID-19 pandemic had postpartum depression, which is much higher than a pre-pandemic meta-analysis. COVID-19 related social restrictions or loss of social support from healthcare professionals, family, and friends were significantly associated with postpartum depression. Also, loss of maternal autonomy in delivery and breastfeeding is associated with postpartum depression. The results indicate that both formal and informal support should not be limited to prevent postpartum depression during the pandemic.

Various treatments have been used to treat chronic immune thrombocytopenic purpura in children; however, none of it has been established as the standard of care. The administration of thrombopoietin receptor agonists (TPO-RAs) has been approved as a new treatment option in Japan. In this case series, TPO-RAs were administered to 16 patients (eltrombopag, n=9; romiplostim, n=7). Excluding the data of two patients who underwent splenectomy immediately after starting treatment with these medicines, platelet counts increased to ≥50,000/µl in seven patients. The adverse events recorded were grade 2 liver dysfunction (n=1), according to the common terminology criteria for adverse events version 4, and myelofibrosis (classified as MF1 or mild reticulin fibrosis), as observed on bone marrow biopsy (n=2). We continued the administration of TPO-RAs at the same dose in these patients because the complications they experienced were mild. The risk of adverse events associated with long-term use of TPO-RAs in this pediatric population remains unclear, and a prospective evaluation is needed.

Background Local impedance (LI) at a distal tip of the ablation catheter can indirectly measure catheter contact and tissue temperature during radiofrequency catheter ablation (RFCA). LI decreases by RFCA, and a degree of LI drop is correlated with lesion size. However, data on the effects of catheter contact angle on lesion size and LI drop were scarce. This study aimed to evaluate the influence of catheter contact angle on lesion size and LI drop in a porcine experimental study. Methods Lesions were created on porcine myocardial left ventricles by the LI-sensing ablation catheter (IntellaNav MiFi OI®). Contact force (CF) was measured using pressure to current transducer (load cell). Radiofrequency ablation was performed with a power of 30 Watt and a duration of 30 seconds. CF (0g, 5g, 10g, 20g, and 30g) and catheter angle (30°, 45°, and 90°) were changed in each set (total 120 lesions, n=8 each). LI rise, LI drop by RF application, and lesion size (maximum lesion width, maximum surface width, and maximum lesion depth) were evaluated. Results There was no angular dependence in LI rise in all CF. The values of LI rise increased as CF increased. The LI drop also increased as CF increased in all contact angles. Regarding the difference of catheter angles, LI drop with 90° was lower than those with 30° and 45°in CF 10g, 20g, and 30g, respectively. Maximum lesion width and surface width were larger in 30° and 45° than those in 90°, whereas there were no differences in maximum lesion depth. Conclusion LI drop in 90° were significantly lower than those in 45° and 30°. Although lesion depths were not different among the three angles, the absolute values of LI drop were different. Caution should be exercised to comprehend the LI drop with catheter angles. Funding Acknowledgement Type of funding sources: None.

Background Patients with acute aortic dissection (AAD) sometimes are complicated with atrial fibrillation (AF). However, the impact of AF and the use of oral anticoagulation (OAC) on the prognosis of AAD remains unclear. In this study, we evaluated the prognostic impact of AF and OAC therapy in patients with type B AAD. Methods Consecutive patients diagnosed with type B AAD between January 2010 and December 2020 in our university hospital were retrospectively analyzed. All patients were divided into 2 groups based on the concomitance with or without AF. The primary endpoint was set as major adverse cardiovascular events (MACEs), including all-cause death, enlargement of aortic diameter, aortic ruptures, and cerebral infarction. Kaplan-Meier survival curves were constructed, and Cox proportional hazards analysis was performed to identify independent predictors of clinical events at 1 year. Results A total of 146 patients diagnosed with type B AAD were enrolled, with a mean age of 66±12 years, and 81% of male. Thirty-two patients (22%) experienced MACEs during 272±142 days-observation. Concomitant AF was observed in 27 patients (18%). In the Kaplan-Meier curve analysis, the patients with AF showed significantly higher events than those without AF (log-lank p75 years (HR: 2.635, 95% CI: 1.268–5.388 p=0.011) were independent predictors of MACEs. Regarding OAC in patients with AF, Kaplan-Meier analysis showed that usage of OAC was associated with a higher incidence of MACEs than those without (log-rank, p=0.036) Conclusion Presence of AF, enlargement of descending aorta diameter, and age were independent predictors of future MACEs in patients with type B AAD. Additionally, usage of OAC is associated with MACEs in patients with type B AAD complicated with AF. Funding Acknowledgement Type of funding sources: None.

A 61-year-old male was referred to our hospital to receive catheter ablation of paroxysmal atrial fibrillation. Since no anatomical abnormalities were detected by preoperative computed tomography of left atrium and pulmonary veins (PVs), he underwent a cryoballoon ablation for a PV isolation. We performed single, 3-min freeze applications to all four PVs while monitoring the esophageal temperature. Immediately after the procedure, he complained of nausea, followed by a body weight loss of 9 kg over 2 months. Since no structural abnormalities were detected even through careful evaluation, he was diagnosed with hypoperistalsis caused by the cryoballoon ablation. Although his symptoms partially improved, they persisted over a year. The cryoballoon procedure is believed to be relatively safe, but even just a simple 3-min freeze application caused severe hypoperistalsis in the present case. Operators should recognize the risk of such complications.

Stereocomplex (SC) crystallization is first reported for enantiomeric blends of individually noncrystallizable chiral α-monosubstituted 2-hydroxyalkanoic acid (α-MS2HAA)-based random copolymers wit...

We investigated the crystallization behavior, structure, morphology, and thermal properties of stereo diblock poly(lactide) (PLA) copolymers of crystalline poly(L-lactide) (PLLA) and amorphous poly(DL-lactide) (PLLA-b-PDLLA) having different molecular weights of the PLLA block, as representative and typical examples of crystalline and amorphous block copolymers. PLLA-b-PDLLA polymers were crystallizable for PLLA fractions down to 25.4%. The transition temperature from the δ-form to the α-form decreased with a decrease in the PLLA fraction and finally only α-form crystallites were formed for PLLA-b-PDLLA with a PLLA fraction of 25.4%. The melting temperature (Tm), radial growth rate of spherulites, and total crystallization rate decreased with decreasing PLLA fraction. Surprisingly, the long period, the mean lamellar thickness (dc), and the mean thickness of the amorphous layer increased with decreasing PLLA fraction. The contradiction between the dependence of Tm and dc on the PLLA fraction can be explained by the fact that the degree of disorder in the crystalline lattice increased and the crystalline surface area along the direction perpendicular to the c-axis became small with decreasing PLLA fraction, and their synergy effect. Some fractions of PDLLA chains were confined in the amorphous regions between the crystalline regions, but the remaining parts of the PDLLA chains should have been excluded from the amorphous regions between the crystalline regions and, as a result, located outside of the alternately layered crystalline and amorphous regions. Confinement of PDLLA chains in the amorphous regions between the crystalline regions is in marked contrast with the result reported for PLLA/PDLLA blends, wherein PDLLA molecules were excluded from the amorphous regions between the crystalline regions.

The twist–bend nematic (NTB) phase is one of the new types of nematics found recently, which possesses local nematic order with a heliconical orientational modulation at the nanoscale. Herein, we quantitatively determined, for the first time, the temperature-dependent elastic and viscosity properties in both the nematic (N) and NTB phases using a thioether-linked cyanobiphenyl dimer CBS7SCB exhibiting a broad temperature range of the NTB phase which is stable down to room temperature. In the N phase, the fundamental elastic moduli: splay and bend elastic moduli (K11 and K33, respectively) are found to be in the order of 10−12 N, and the effective rotational viscosity (γ1) is determined to be in the range of 5–200 mPa s. Meanwhile, the NTB phase is found to exhibit a compressive elastic modulus B in the order of several tens of kilopascals, the effective K11 in the order of 10−10–10−8 N, and a considerably large γ1 value of ∼68.7 Pa s right below the N–NTB phase transition. The present study provides insights into the comprehensive viscoelastic properties based on comparison of the obtained experimental data with not only the existing theoretical prediction but also the preceding experimental works.

Background Although complications associated with pazopanib, a multitarget tyrosine kinase inhibitor, are known, periosteal reaction as a side effect has never been reported. Observation We present a case involving a male pediatric patient with desmoid tumors treated for 6 months with pazopanib who presented with pain and periosteal reaction in the ilium and scapula. Three months after termination of pazopanib therapy, the periosteal reaction in the scapula resolved and that in the ilium improved. Conclusion Children receiving pazopanib presenting with focal pain should be examined for the periosteal reaction; this knowledge may facilitate correct diagnosis of symptoms as a drug-associated finding.

Asymmetric diphenyldiacetylenes (DPDAs) bearing a fixed hexylthio group and different alkyl groups with carbon numbers (n) of 0–8 and 12 at each termini (or 4- and 4ʹ- positions), abbreviated as 6S–DPDA–n, were synthesised and their phase transition behaviour and birefringence were evaluated. It was found that alkyl-unsubstituted and methyl-substituted analogues (6S–DPDA–0 and 6S–DPDA–1, respectively) do not show any mesophases, whereas 6S–DPDA–n (n ≥ 2) form enantiotropic liquid crystal phases. Wherein, the nematic (N) phase for 6S–DPDA–4 is supercooled to room temperature, and 6S–DPDA–12 forms not only N phase but also highly ordered mesophase under room temperature. In light of the fact that symmetrically alkylthio-possessing 6S–DPDA–S6, 6S–DPDA–0 and 6S–DPDA–1 are not mesogenic, the present results strongly suggest that an alkyl group opposite to an alkylthio group plays a vital role to induce mesophases. Single-crystal X-ray analysis revealed anti-parallel packed molecules in the lattice. 6S–DPDA–7 have higher birefringence than 7–DPDA–7 being the symmetric alkyl counterpart, over the entire range of each N phase, which is supported by the enhanced polarisabilities based on density functional theory calculation.

This paper presents a method of reconstructing transient, three-dimensional axisymmetric temperature fields in water formed by laminar free convection from a small heating sphere. This method is based on the temperature dependence of the water absorption coefficient at a near-infrared wavelength of 1150 nm. The horizontal line profiles of the absorbance at this wavelength, obtained using a unidirectional transmission imaging technique, were approximated with multi-Gaussian functions to robustly and efficiently apply the inverse Abel transform. In the experiment, a 1-mm-diameter steel sphere in water was heated by electromagnetic induction. The reconstruction results show the formation of spherical temperature distributions within the thermal conduction regime, followed by the occurrence of upward free convection, leading to a laminar plume. The size and shape of the plume depended on the heat generation rate in the sphere. These results were analyzed and verified through a comparison with the results of a numerical simulation on the temperature and flow fields.

Individual busulfan (BU) dosing based on pharmacokinetic (PK) data is preferable for hematopoietic stem cell transplantation (HSCT) conditioning, but information on BU PK in infants is scarce. We report BU PK data on HSCT conditioning for infants with KMT2A-gene-rearrangement-positive acute lymphoblastic leukemia (MLL-r ALL). Infants showed wide variation in BU PK indices, such as clearance (CL) and volume of distribution (Vd) value, which are distributed more widely among those who received oral, rather than intravenous (IV), BU. Because the steady state concentration (Css) fluctuates readily in infants, dose re-adjustment based on PK at the initial administration was important even if the initial dose was determined by a PK test. HSCT can be performed safely within the Css range of 600–900 ng/mL per dose, although it was difficult to fit within the therapeutic index of BU. The clinical outcome of engraftment, graft-versus-host disease, adverse events, including sinusoidal obstruction syndrome, and survival did not correlate with the BU PK data, which paradoxically suggests that remaining within this Css range helped minimize transplant-related toxicities, while securing engraftment in infants with MLL-r ALL.

Enantiomeric alternating lactic acid-based copolymers, i.e., poly(l-lactic acid-alt-glycolic acid) [P(LLA-alt-GA)] and poly(d-lactic acid-alt-glycolic acid) [P(DLA-alt-GA)], with the number-average...

We designed hydrogen-bonded liquid crystals (HBLCs) between a 4-n-alkylthiobenzoic acid homologous series and a 4,4-bipyridine at each ratio of 2/1 (mol/mol), and investigated their mesomorphic behavior. They show a wide range of mesophases compared with those formed in each single component of 4-n-alkylthiobenzoic acids. With increasing alkyl chains, they represent the following gradual changing for thermally additional phase sequences; from nematic phase to smectic (Sm) A (SmA) phase, then to SmC phase and further to SmI phase. In addition, their phase transition behavior was comprehensively discussed together with those for two familiar counterparts based on 4-n-alkylbenzoic acids and 4-n-alkoxybenzoic acids. It was found that the melting points are the highest for 4-n-alkoxy complexes and the trends of those for the rest depend on the alkyl chain length, whereas the isotropic points and the resultant mesophase ranges are clearly in the order of 4-n-alkoxy >4-n-alkyl >4-n-alkylthio complexes.

Background The relationship between atrial high-rate episode (AHRE) burden (i.e., the frequency of atrial tachyarrhythmia) and heart failure (HF) risk is unclear. We hypothesized that new-onset and higher burden of AHRE are associated with HF. Methods and Results: We included 104 consecutive patients with cardiac implantable electronic devices (CIEDs) capable of continuous atrial rhythm monitoring. Patients with AF history were excluded. To stratify patients, AHREs were evaluated only during the initial 1 year after CIED implantation. The primary endpoint was all-cause death or new-onset or worsening HF that required unplanned hospitalization or readjustment of HF drug therapy. At 1 year after CIED implantation, 34/104 patients (33%) exhibited AHREs. No difference in basal clinical characteristics except for left ventricular ejection fraction between patients with and without new-onset AHREs was found. AHRE groups had more HF events than the non-AHRE group. All patients were divided into 3 groups based on AHRE burden: none, low, and high. Worsening HF was observed in 12 patients (12%). Cox hazard analysis revealed that AHRE and higher AHRE burden were independent predictive factors for worsening HF. The high group showed a higher risk for HF than the non-AHRE groups, but no significant difference was found between the low- and non-AHRE groups. Conclusions New-onset higher AHRE burden was associated with subsequent risk for HF in patients with CIEDs.

Polarized beam infrared (IR) spectroscopy provides valuable information on changes in the orientation of samples in nematic phases, especially on the role of intermolecular interactions in forming the periodically modulated twist–bent phase. Infrared absorbance measurements and quantum chemistry calculations based on the density functional theory (DFT) were performed to investigate the structure and how the molecules interact in the nematic (N) and twist–bend (NTB) phases of thioether dimers. The nematic twist–bend phase observed significant changes in the mean IR absorbance. On cooling, the transition from the N phase to the NTB phase was found to be accompanied by a marked decrease in absorbance for longitudinal dipoles. Then, with further cooling, the absorbance of the transverse dipoles increased, indicating that transverse dipoles became correlated in parallel. To investigate the influence of the closest neighbors, DFT calculations were performed. As a result of the optimization of the molecular cores system, we observed changes in the square of the transition dipoles, which well corresponds to absorbance changes observed in the IR spectra. Interactions of molecules dominated by pairing were observed, as well as the axial shift of the core to each other.

We performed cavotricuspid isthmus (CTI) linear ablation for atrial flutter; however, the tachycardia cycle length was not changed at all. In such cases, repeated or broad line ablation is usually performed. We presented that high-density three-dimensional mapping after the first CTI linear ablation, which revealed the complex tachycardia circuit with the epicardial and endocardial breakthrough.

The recurrence of atrial fibrillation (AF) after catheter ablation (CA) is still an unsolved issue. Although structural remodeling is relatively well defined, the method to assess electrical remodeling of the atrium is not well established. In this study, we evaluated the relationship between atrial conduction properties and recurrence after CA for AF. One hundred six consecutive patients (66 ± 11 years old, male: 68%) who underwent CA for AF with a CARTO system from July 2016 to July 2019 were enrolled in this study. An activation map of both atria was constructed to precisely evaluate the total conduction time, distance, and conduction velocity between the earliest and latest activation sites during sinus rhythm. All parameters were compared between the patients with or without AF recurrence. Of the patients, 27 had an AF recurrence (Rec group). The left atrial (LA) conduction velocity was significantly slower in the Rec group than in the non-Rec group (101.2 ± 17.9 vs. 116.9 ± 18.0 cm/s, P

The effect of genetic variation on second malignant neoplasms (SMNs) remains unclear. First, we identified the pathogenic germline variants in cancer-predisposing genes among 15 children with SMNs after childhood leukemia/lymphoma using whole-exome sequencing. Because the prevalence was low, we focused on the association between SMNs and NUDT15 in primary acute lymphoblastic leukemia (ALL) cases. NUDT15 is one of the 6-mercaptopurine (6-MP) metabolic genes, and its variants are common in East Asian individuals. The prevalence of NUDT15 hypomorphic variants was higher in patients with SMNs (n = 14; 42.9%) than in the general population in the gnomAD database (19.7%; P = .042). In the validation study with a cohort of 438 unselected patients with ALL, the cumulative incidence of SMNs was significantly higher among those with (3.0%; 95% confidence interval [CI], 0.6% to 9.4%) than among those without NUDT15 variants (0.3%; 95% CI, 0.0% to 1.5%; P = .045). The 6-MP dose administered to patients with ALL with a NUDT15 variant was higher than that given to those without SMNs (P = .045). The 6-MP–related mutational signature was observed in SMN specimens after 6-MP exposure. In cells exposed to 6-MP, a higher level of 6-MP induced DNA damage in NUDT15-knockdown induced pluripotent stem cells. Our study indicates that NUDT15 variants may confer a risk of SMNs after treatment with 6-MP in patients with ALL.

A 14-year-old male with autism was admitted to our hospital owing to altered consciousness and gait disturbance. Blood tests showed a white blood cell (WBC) count of 728,600/µl, and brain computed tomography revealed intracranial hemorrhage and a midline shift of the brain. The chronic phase of chronic myeloid leukemia (CML) was confirmed as per bone marrow aspiration findings. The patient underwent emergency craniotomy for hematoma removal, and he subsequently received hydroxyurea and rasburicase combination therapy. However, he developed tumor lysis syndrome (TLS) and died on the second day of hospitalization. Histopathological examination of autopsy specimens did not reveal any condition that could account for his death other than CML. Several reports have described intracranial hemorrhage during the accelerated phase or blast crisis of CML, but few have described this complication during the chronic phase. TLS concomitant with CML in the chronic phase or following hydroxyurea (an inhibitor of DNA synthesis) administration is rare. It is essential for clinicians to be aware that patients with chronic phase CML and high WBC counts may develop TLS, following the administration of hydroxyurea alone. In addition, extreme caution is warranted in severe cases accompanied by intracranial hemorrhage.

BACKGROUND: In patients with medulloblastoma, one of the most significant challenges is to reduce the dose of craniospinal irradiation (CSI) to minimize neurological sequelae in survivors. Molecular characterization of patients treated using lower-dose CSI rather than standard therapy is important for further reducing the treatment burden. METHODS: We conducted DNA methylation analysis using an Illumina Methylation EPIC array to investigate molecular prognostic markers in 38 patients with medulloblastoma who were registered in the Japan Pediatric Molecular Neuro-Oncology Group and were treated using lower-dose CSI rather than standard-dose radiation therapy. RESULTS: Among the patients, 23 were classified as having a “standard-risk” and 15 as having a “high-risk” according to the classic classification based on tumor resection rate and presence of metastasis, respectively. The median follow-up period was 71.5 months. The median CSI dose was 18 Gy in both groups, and 10 patients in the “high-risk” group received a CSI dose of 23.4 Gy or 24 Gy. Molecular subgrouping revealed the “standard-risk” cohort included 5 WNT, 2 SHH, and 16 Group 3/4 cases; all 15 patients in the “high-risk” cohort had Group 3/4 medulloblastoma. Among the patients with Group 3/4 medulloblastoma, 13 of the 16 “standard-risk” patients were subclassified as subtypes I, IV, VI, and VII, which were associated with a good prognosis according to the novel sub-subclassification among Group 3/4 medulloblastomas. However, only 6 of the 15 “high-risk” patients were included in the subtypes. The good prognostic subtype cases among “high-risk” cohort were all survived without recurrence, in contrast to a worse prognosis (5-year progression free survival=33.3%; p=0.01) of the other cases. CONCLUSION: Although these findings require validation in a larger cohort, the present findings suggest that the novel sub-subclassification of Group 3/4 medulloblastoma may be a promising prognostic biomarker for reducing the dose of CSI in patients with metastatic medulloblastoma.