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Abstract Although the causes of neurodevelopmental disorders remain unknown, several environmental risk factors have attracted considerable attention. We conducted a retrospective, longitudinal, population-based cohort study using data from infant health examinations of children born to mothers with pregnancies between April 1, 2014 and March 31, 2016 in Kobe City to identify the perinatal factors associated with neurodevelopmental referrals in 3-year-old children. There were 15,223 and 1283 children in the normal and referral groups, respectively. Neurodevelopmental referrals at the health checkup for 3-year-old children were significantly associated with the lack of social support during pregnancy (adjusted odds ratio [aOR] 1.99, 99% CI 1.14–3.45, p = 0.001), history of psychiatric consultation (aOR 1.56, 99% CI 1.10–2.22, p = 0.001), no social assistance post-delivery (aOR 1.49, 99% CI 1.03–2.16, p = 0.006), Edinburgh Post-natal Depression Scale (EPDS) score ≥ 9 (aOR 1.36, 99% CI 1.01–1.84, p = 0.008), infant gender (male) (aOR 2.51, 99% CI 2.05–3.06, p

Abstract Background This study aimed to establish a systematic method for diagnosing atrioventricular nodal reentrant tachycardia (AVNRT) with a bystander concealed nodoventricular pathway (cNVP). Methods We analyzed 13 cases of AVNRT with a bystander cNVP, 11 connected to the slow pathway (cNVP‐SP) and two to the fast pathway (cNVP‐FP), along with two cases of cNVP‐related orthodromic reciprocating tachycardia (ORT). Results The diagnostic process was summarized in three steps. Step 1 was identification of the presence of an accessory pathway by resetting the tachycardia with delay (n = 9) and termination without atrial capture (n = 4) immediately after delivery of a His‐refractory premature ventricular contraction (PVC). Step 2 was exclusion of ORT by atrio‐His block during the tachycardia (n = 4), disappearance of the reset phenomenon after the early PVC (n = 7), or dissociation of His from the tachycardia during ventricular overdrive pacing (n = 1). Moreover, tachycardia reset/termination without the atrial capture (n = 2/2) 1 cycle after the His‐refractory PVC was specifically diagnostic. Exceptionally, the disappearance of the reset phenomenon was also observed in the two cNVP‐ORTs. Step 3 was verification of the AVN as the cNVP insertion site, evidenced by an atrial reset/block preceding the His reset/block in fast–slow AVNRT with a cNVP‐SP and slow–fast AVNRT with a cNVP‐FP or His reset preceding the atrial reset in slow–fast AVNRT with a cNVP‐SP. Conclusion AVNRT with a bystander cNVP can be diagnosed in the three steps with few exceptions. Notably, tachycardia reset/termination without atrial capture one cycle after delivery of a His‐refractory PVC is specifically diagnostic.

Abstract Autosomal dominant polycystic kidney disease (ADPKD) is commonly caused by PKD1, and mosaic PKD1 variants result in milder phenotypes. We present the case of a 32 year-old male with chronic active Epstein–Barr virus who underwent bone marrow transplantation with chemoradiotherapy at age 9. Despite a low-frequency mosaic splicing PKD1 variant, he developed severe renal cysts and end-stage renal disease in his 30 s. This case highlights how environmental factors may contribute to the genetic predisposition to ADPKD.

Abstract Quantum tunneling is the phenomenon that makes superconducting circuits “quantum”. Recently, there has been a renewed interest in using quantum tunneling in phase space of a Kerr parametric oscillator as a resource for quantum information processing. Here, we report a direct observation of quantum interference induced by such tunneling and its dynamics in a planar superconducting circuit through Wigner tomography. We experimentally elucidate all essential properties of this quantum interference, such as mapping from Fock states to cat states, a temporal oscillation due to the pump detuning, as well as its characteristic Rabi oscillations and Ramsey fringes. Finally, we perform gate operations as manipulations of the observed quantum interference. Our findings lay the groundwork for further studies on quantum properties of superconducting Kerr parametric oscillators and their use in quantum information technologies.

Abstract A multistate platform model was developed to describe time‐to‐event (TTE) endpoints in an oncology trial through the following states: initial, tumor response (TR), progressive disease (PD), overall survival (OS) event (death), censor to the last evaluable tumor assessment (progression‐free survival [PFS] censor), and censor to study end (OS censor), using an ordinary differential equation framework. Two types of piecewise functions were used to describe the hazards for different events. Piecewise surge functions were used for events that require tumor assessments at the scheduled study visit times (TR, PD, and PFS censor). Piecewise constant functions were used to describe hazards for events that occur evenly throughout the study (OS event and OS censor). The multistate TTE model was applied to describe TTE endpoints from a published phase III study. The piecewise surge functions well‐described the observed surges of hazards/events for TR, PD, PFS, and OS occurring near scheduled tumor assessments and showed good agreement with all Kaplan‐Meier curves. With the flexibility of piecewise hazard functions, the model was able to evaluate covariate effects in a time‐variant fashion to better understand the temporal patterns of disease prognosis through different disease states. This model can be applied to advance the field of oncology trial design and optimization by: (1) enabling robust estimations of baseline hazards and covariate effects for multiple TTE endpoints, (2) providing a platform model for understanding the composition and correlations between different TTE endpoints, and (3) facilitating oncology trial design optimization through clinical trial simulations.

Abstract Protein induced by vitamin K absence or antagonist-II (PIVKA-II) is avitamin K (VK) deficiency indicator in neonates. However, PIVKA-II detection frequency in neonatal blood at birth and the correlation between PIVKA-II and gestational age are unclear. We retrospectively analyzed infants admitted to our institution between June 1, 2018, and March 31, 2022, whose clinical and PIVKA-II data were available, and classified them into preterm and term infant groups. Overall incidence of PIVKA-II-positive cases (≥ 50 mAU/mL) was 42.8%, including 0.6% apparent VK deficiency (≥ 5000 mAU/mL), 3.1% experimental VK deficiency (1000–4999 mAU/mL), and 10.7% latent VK deficiency (200–999 mAU/mL) cases. Incidence of PIVKA-II-positive cases was significantly higher in the term group than in the preterm group (49.4% vs. 29.7%, p

Endohedral metallofullerenes have excellent redox properties, which can be used to vary their reactivity to certain classes of molecules, such as alkyl halides. In this study, the thermal reaction of the La@C2v-C82 anion with benzyl bromide derivatives 1 at 110 °C afforded single-bonded adducts 2–5 with high regioselectivity. The products were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and visible–near infrared spectroscopy. The reaction of La@C2v-C82 with alkyl halides using the same conditions showed no consumption of La@C2v-C82, indicating that the reactivity of La@C2v-C82 toward alkyl halides was effectively increased by one-electron reduction. Single-crystal X-ray diffraction analysis of the single-bonded adduct 3a revealed the addition site of the p-methoxybenzyl group on La@C2v-C82. Theoretical calculations indicated that the addition site carbons in neutral La@C2v-C82 have high spin density, whereas those in the La@C2v-C82 anion do not have high charge densities. Thus, the reaction is believed to occur via electron transfer, followed by the radical coupling of La@C2v-C82 and benzyl radicals, rather than by bimolecular nucleophilic substitution reaction of La@C2v-C82 anion with 1.

Abstract Background Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) sheets have recently attracted attention as an alternative approach to injected cell suspensions for stem cell therapy. However, cell engraftment and cytokine expression levels between hUC-MSC sheets and their cell suspensions in vivo have not yet been compared. This study compares hUC-MSC in vivo engraftment efficacy and cytokine expression for both hUC-MSC sheets and cell suspensions. Methods hUC-MSC sheets were prepared using temperature-responsive cell culture; two types of hUC-MSC suspensions were prepared, either by enzymatic treatment (trypsin) or by enzyme-free temperature reduction using temperature-responsive cell cultureware. hUC-MSC sheets and suspensions were transplanted subcutaneously into ICR mice through subcutaneous surgical placement and intravenous injection, respectively. hUC-MSC sheet engraftment after subcutaneous surgical transplantation was investigated by in vivo imaging while intravenously injected cell suspensions were analyzing using in vitro organ imaging. Cytokine levels in both transplant site tissues and blood were quantified by enzyme-linked immunosorbent assay. Results After subcutaneous transplant, hUC-MSC sheets exhibited longer engraftment duration than hUC-MSC suspensions. This was attributed to extracellular matrix (ECM) and cell–cell junctions retained in sheets but enzymatically altered in suspensions. hUC-MSC suspensions harvested using enzyme-free temperature reduction exhibited relatively long engraftment duration after intravenous injection compared to suspensions prepared using trypsin, as enzyme-free harvest preserved cellular ECM. High HGF and TGF-β1 levels were observed in sheet-transplanted sites compared to hUC-MSC suspension sites. However, no differences in human cytokine levels in murine blood were detected, indicating that hUC-MSC sheets might exert local paracrine rather than endocrine effects. Conclusions hUC-MSC sheet transplantation could be a more effective cell therapeutic approach due to enhanced engraftment and secretion of therapeutic cytokines over injected hUC-MSC suspensions.

The planning fallacy refers to a cognitive bias wherein people underestimate the time it will take to complete tasks. Its degree is affected by unpacking. When a task is broken into com ponents, each component is visualized, and the planning fallacy is reduced. This study exam ined the effects of unpacking at a more macro level by comparing single and multiple plans. The participants were 122 university students. They were first instructed to plan their exam study approximately ten days before the final Management Psychology exam. Some partici pants only planned about Management Psychology, while the rest planned about multiple sub jects, including Management Psychology. During the exam, they answered a questionnaire about the actual time they spent studying and so on. Results showed no difference in exam scores between multiple-subject planners and single-subject planners. Planned study time and actual study time were shorter for multiple-subject planners. The plans as a whole were more detailed for multiple-subject planners, and the part of the plans concerning Management Psychology was simpler for multiple-subject planners. The multiple-subject planners may have studied more efficiently due to the unpacking effect. That implies that planning for mul tiple tasks simultaneously is more effective than planning for only one task.

Objective: to evaluate the efficacy and safety of human placenta hydrolysate (HPH) Laennec® in the treatment of nonalcoholic fatty liver disease (NAFLD) in a clinical trial.Material and methods. The study involved hospitalized NAFLD patients (with non-alcoholic steatohepatitis, cirrhosis) (n=34, mean age 53±14 years). In the therapy group (n=17), patients received Laennec® HPH (4 ml intravenous drip infusion in a solution of 5% glucose 5 times a week for 2 weeks). In the control group (n=17), patients hospitalized in other departments of the clinic did not receive any therapy for NAFLD. The effectiveness of therapy was assessed after 2 and 3 weeks by subjective NAFLD symptoms (fatigue, anorexia, bloating, constipation, nausea, and pain in hypochondrium) and biochemical indicators of liver function: levels of blood serum aspartate aminotrans-ferase (AST), alanine notransferase (ALT), gamma-glutamyltransferase (GGT).Results. At the start of the study, there were no significant differences between the groups in the values of the studied indicators of liver function: blood levels of AST, ALT, GGT, etc. By the end of Week 1, a significant decrease in AST levels was registered in the group receiving Laennec® (–35 U/l; control: –8 U/l; p

Abstract This study investigated the relationship between sleep habits in early childhood and academic performance and non-cognitive skills in the first grade. We retrospectively analyzed a longitudinal population-based cohort from birth through early childhood, up to elementary school, in Amagasaki City, Japan. The primary outcome was academic performance in the first grade. Other outcomes were self-reported non-cognitive skills. Overall, 4395 children were enrolled. Mean national language scores for children with bedtimes at 18:00–20:00, 21:00, 22:00, and ≥ 23:00 were 71.2 ± 19.7, 69.3 ± 19.4, 68.3 ± 20.1, and 62.5 ± 21.3, respectively. Multiple regression analysis identified bedtime at 3 years as a significant factor associated with academic performance. However, sleep duration was not significantly associated with academic performance. Bedtime at 3 years also affected non-cognitive skills in the first grade. Diligence decreased with a later bedtime (21:00 vs. 18:00–20:00; odds ratio [OR]: 1.98, 95% confidence interval [CI] 1.27–3.09; 22:00 vs. 18:00–20:00; OR: 2.15, 95% CI 1.37–3.38; ≥ 23:00 vs. 18:00–20:00; OR: 2.33, 95% CI 1.29–4.20). Thus, early bedtime at 3 years may be associated with a higher academic performance and better non-cognitive skills in the first grade. Optimum early-childhood sleep habits may positively impact academic future.

Background: The utility of synthetic ECV, which does not require hematocrit values, has been reported; however, high-quality CT images are essential for accurate quantification. Second-generation Deep Learning Reconstruction (DLR) enables low-noise and high-resolution cardiac CT images. The aim of this study is to compare the differences among four reconstruction methods (hybrid iterative reconstruction (HIR), model-based iterative reconstruction (MBIR), DLR, and second-generation DLR) in the quantification of synthetic ECV. Methods: We retrospectively analyzed 80 patients who underwent cardiac CT scans, including late contrast-enhanced CT (derivation cohort: n = 40, age 71 ± 12 years, 24 males; validation cohort: n = 40, age 67 ± 11 years, 25 males). In the derivation cohort, a linear regression analysis was performed between the hematocrit values from blood tests and the CT values of the right atrial blood pool on non-contrast CT. In the validation cohort, synthetic hematocrit values were calculated using the linear regression equation and the right atrial CT values from non-contrast CT. The correlation and mean difference between synthetic ECV and laboratory ECV calculated from actual blood tests were assessed. Results: Synthetic ECV and laboratory ECV showed a high correlation across all four reconstruction methods (R ≥ 0.95, p < 0.001). The bias and limit of agreement (LOA) in the Bland–Altman plot were lowest with the second-generation DLR (hybrid IR: bias = −0.21, LOA: 3.16; MBIR: bias = −0.79, LOA: 2.81; DLR: bias = −1.87, LOA: 2.90; second-generation DLR: bias = −0.20, LOA: 2.35). Conclusions: Synthetic ECV using second-generation DLR demonstrated the lowest bias and LOA compared to laboratory ECV among the four reconstruction methods, suggesting that second-generation DLR enables more accurate quantification.

Objectives: Non-viral mediated plasmid DNA transfection by electroporation (EP) is an established method for gene transfection. In this study, the usefulness of direct EP at an intradermal (i.d.) site (DEP) with implanted electrodes to achieve a high protein expression level was investigated. In addition, DEP application with various intervals with a low application voltage was also evaluated to confirm its effect on protein expression. Methods: Green fluorescent protein (GFP)- and luciferase-encoding DNA were administrated, and GFP and luciferase were evaluated. Results: A higher protein expression level was observed after green fluorescent protein (GFP)- and luciferase-encoding DNA were delivered by i.d. injection followed by DEP application. When luciferase expression was observed with an in vivo imaging system, continuous expression was confirmed over 21 days after i.d. injection followed by DEP at 100 V. This approach provided increased gene expression levels compared with conventional EP methods via the stratum corneum layer. In addition, the effect of application voltage on luciferase expression was investigated; two-time applications (repeated DEP) at 20 V with 5 min intervals showed similar luciferase expression level to single DEP application with 100 V. Histological observations showed the skin became thicker after a single DEP at 100 V, whereas no apparent thickness changes were confirmed after repeated DEP at 20 V with 5 min intervals. Conclusions: This study revealed that direct i.d. voltage application achieved high protein expression levels even at low voltages. Skin is a promising administration site for DNA vaccines, so this approach may be effective for DNA vaccine delivery into skin tissue.