Severe hemolysis, elevated liver enzymes, and low platelet syndrome requiring differentiation of thrombotic microangiopathy: Four cases from a nationwide survey in Japan.

Severe cases of hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome requiring plasma exchange or dialysis should be differentiated from other thrombotic microangiopathy (TMA) and treated appropriately. To evaluate the prevalence and clinical characteristics of such cases in Japan, a questionnaire-based survey was conducted among obstetricians who are members of the Perinatal Research Network Group in Japan. There were a total of 335 cases of HELLP syndrome over a 3-year period in the 48 facilities that responded to the survey. Four patients required plasma exchange or dialysis, of which two were diagnosed with atypical hemolytic uremic syndrome and two with TMA secondary to systemic lupus erythematosus. Although such severe HELLP syndrome is rare, identifying the clinical features and making accurate differential diagnosis are critical for optimal clinical outcomes for mothers and neonates.

Travel burdens to access care among children with cancer between 2016 and 2019: Analysis of a national population-based cancer registry in Japan.

BACKGROUND: Centralization of cancer care increases survival but increases the travel burden (i.e., travel durations, distances, and expenditures) in visiting hospitals. This study investigated the travel burdens to access cancer care for children aged 18 years and younger in Japan. METHODS: The study population comprised 10,709 patients diagnosed between 2016 and 2019 obtained from a national population-based cancer registry in Japan. Their residences were classified as urban or rural. We counted the number of patients treated at specialized hospitals and investigated the treatment centralization across diagnostic groups by Pareto plot. Travel burdens to access care were estimated using a route-planner web service and summarized using median values. A multivariable logistic model was performed to investigate factors associated with the events of car travel duration exceeding 1 h. RESULTS: Of the patients, 76.7% lived in urban areas, and 82.5% received treatment in designated hospitals for childhood cancer. The Pareto plot suggested that the top five hospitals treated 63.5% of patients with retinoblastoma. The estimated travel burdens for all patients were 0.62 h (0.57 h in urban areas and 1.00 h in rural areas), 16.9 km, and 0.0 dollars of toll charges. Regarding travel duration, 21.7% of patients had travel exceeding 1 h, and rural areas, retinoblastoma, malignant bone tumors, and childhood cancer-hub hospitals were associated with travel duration exceeding 1 h (adjusted odds ratios of 6.93, 3.59, 1.94, and 1.91, respectively). CONCLUSIONS: Most patients were treated in specialized hospitals and the treatments for specific diseases were centralized. However, most patients were estimated to travel less than 1 h, and the travel burden tended to increase for patients in rural areas, those with specific diseases, and those going to specialized hospitals. Cancer control measures in Japan have steadily improved centralized treatment while keeping the travel burden relatively manageable.

Explainable Machine Learning Classification to Identify Vulnerable Groups Among Parenting Mothers: Web-Based Cross-Sectional Questionnaire Study.

BACKGROUND: One life event that requires extensive resilience and adaptation is parenting. However, resilience and perceived support in child-rearing vary, making the real-world situation unclear, even with postpartum checkups. OBJECTIVE: This study aimed to explore the psychosocial status of mothers during the child-rearing period from newborn to toddler, with a classifier based on data on the resilience and adaptation characteristics of mothers with newborns. METHODS: A web-based cross-sectional survey was conducted. Mothers with newborns aged approximately 1 month (newborn cohort) were analyzed to construct an explainable machine learning classifier to stratify parenting-related resilience and adaptation characteristics and identify vulnerable populations. Explainable k-means clustering was used because of its high explanatory power and applicability. The classifier was applied to mothers with infants aged 2 months to 1 year (infant cohort) and mothers with toddlers aged >1 year to 2 years (toddler cohort). Psychosocial status, including depressed mood assessed by the Edinburgh Postnatal Depression Scale (EPDS), bonding assessed by the Postpartum Bonding Questionnaire (PBQ), and sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI) between the classified groups, was compared. RESULTS: A total of 1559 participants completed the survey. They were split into 3 cohorts, comprising populations of various characteristics, including parenting difficulties and psychosocial measures. The classifier, which stratified participants into 5 groups, was generated from the self-reported scores of resilience and adaptation in the newborn cohort (n=310). The classifier identified that the group with the greatest difficulties in resilience and adaptation to a child's temperament and perceived support had higher incidences of problems with depressed mood (relative prevalence [RP] 5.87, 95% CI 2.77-12.45), bonding (RP 5.38, 95% CI 2.53-11.45), and sleep quality (RP 1.70, 95% CI 1.20-2.40) compared to the group with no difficulties in perceived support. In the infant cohort (n=619) and toddler cohort (n=461), the stratified group with the greatest difficulties had higher incidences of problems with depressed mood (RP 9.05, 95% CI 4.36-18.80 and RP 4.63, 95% CI 2.38-9.02, respectively), bonding (RP 1.63, 95% CI 1.29-2.06 and RP 3.19, 95% CI 2.03-5.01, respectively), and sleep quality (RP 8.09, 95% CI 4.62-16.37 and RP 1.72, 95% CI 1.23-2.42, respectively) compared to the group with no difficulties. CONCLUSIONS: The classifier, based on a combination of resilience and adaptation to the child's temperament and perceived support, was able identify psychosocial vulnerable groups in the newborn cohort, the start-up stage of childcare. Psychosocially vulnerable groups were also identified in qualitatively different infant and toddler cohorts, depending on their classifier. The vulnerable group identified in the infant cohort showed particularly high RP for depressed mood and poor sleep quality.

Association of the Japanese herbal kampo medicine kakkonto with antibiotic use and surgical drainage for noninfectious mastitis: A nationwide database study.

AIM: Kakkonto, a Japanese herbal kampo medicine, is empirically prescribed to improve milk stasis and ameliorate breast inflammation in patients with noninfectious mastitis. We investigated whether early use of kakkonto is associated with a reduction in antibiotic use and surgical drainage in patients with noninfectious mastitis. METHODS: We identified 34 074 patients with an initial diagnosis of noninfectious mastitis within 1 year of childbirth between April 2012 and December 2022 using the nationwide administrative JMDC Claims Database. Patients were divided into the kakkonto (n = 9593) and control (n = 9648) groups if they received and did not receive kakkonto on the day of the initial diagnosis of noninfectious mastitis, respectively. Antibiotic administration and surgical drainage within 30 days after the initial diagnosis of noninfectious mastitis in the two groups were compared using propensity score-stabilized inverse probability of treatment weighting analysis. RESULTS: The frequency of antibiotic administration within 30 days after the initial diagnosis of noninfectious mastitis was significantly lower in the kakkonto group than in the control group (10% vs. 12%; odds ratio, 0.88 [95% confidence interval, 0.80-0.96]). The frequency of antibiotic administration during 1-3 and 4-7 days after the initial diagnosis were also significantly lower in the kakkonto group than in the control group. The frequency of surgical drainage did not differ significantly between the two groups. CONCLUSIONS: Kakkonto was associated with reduced administration of antibiotics for noninfectious mastitis, making it a potential treatment option for relieving breast inflammation and promoting antimicrobial stewardship.

Association between the Timing of Urinary Antigen Testing and Outcomes in Legionella Pneumonia Patients: A Nationwide Database Study.

Objective Recommendations on the timing of Legionella urinary antigen tests for community-acquired pneumonia patients differ among guidelines in Japan, the United States, and European nations. We therefore evaluated the association between the timing of urinary antigen tests and in-hospital mortality in patients with Legionella pneumonia. Methods We conducted a retrospective cohort study using the Diagnosis Procedure Combination database, a nationwide database of acute care inpatients in Japan. Patients who underwent Legionella urinary antigen tests on the day of admission formed the tested group. Patients who were tested on day 2 of admission or later or were unexamined formed the control group. We performed a propensity score matching analysis to compare in-hospital mortality, length of hospital stay and duration of antibiotics use between the two groups. Results Of the 9,254 eligible patients, 6,933 were included in the tested group. One-to-one propensity score matching generated 1,945 pairs. The tested group had a significantly lower 30-day in-hospital mortality than the control group (5.7 vs. 7.7%; odds ratio, 0.72; 95% confidence intervals, 0.55-0.95; p=0.020). The tested group also showed a significantly shorter length of stay and duration of antibiotics use than the control group. Conclusion Urine antigen testing upon admission was associated with better outcomes in patients with Legionella pneumonia. Urine antigen tests upon admission may be recommended for all patients with severe community-acquired pneumonia.

Autism symptoms, functional impairments, and gaze fixation measured using an eye-tracker in 6-year-old children.

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder clinically characterized by abnormalities in eye contact during social exchanges. We aimed to clarify whether the amount of gaze fixation, measured at the age of 6 years using Gazefinder, which is an established eye-tracking device, is associated with ASD symptoms and functioning. Methods: The current study included 742 participants from the Hamamatsu Birth Cohort Study. Autistic symptoms were evaluated according to the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), and the functioning of the participating children in real life was assessed using the Japanese version of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II). The Gazefinder system was used for gaze fixation rates; two areas of interest (eyes and mouth) were defined in a talking movie clip, and eye gaze positions were calculated through corneal reflection techniques. Results: The participants had an average age of 6.06 ± 0.14 years (males: 384; 52%). According to ADOS, 617 (83%) children were assessed as having none/mild ASD and 51 (7%) as severe. The average VABS-II scores were approximately 100 (standard deviation = 12). A higher gaze fixation rate on the eyes was associated with a significantly lower likelihood of the child being assigned to the severe ADOS group after controlling for covariates (odds ratio [OR], 0.02; 95% confidence interval [CI], 0.002-0.38). The gaze fixation rate on the mouth was not associated with ASD symptoms. A higher gaze fixation rate on the mouth was associated with a significantly lower likelihood of the child being assigned to the low score group in VABS-II socialization after controlling for covariates (OR, 0.18; 95% CI, 0.04-0.85). The gaze fixation rate on the eyes was not associated with functioning. Conclusion: We found that children with low gaze fixation rates on the eyes were likely to have more ASD symptoms, and children with low gaze fixation rates on the mouth were likely to demonstrate poorer functioning in socialization. Hence, preschool children could be independently assessed in the general population for clinically relevant endophenotypes predictive of ASD symptoms and functional impairments.

Association between Legionella urinary antigen tests on admission and inhospital mortality in patients with atypical pneumonia: A nationwide database study.

Background: The guidelines for the requirement of Legionella urinary antigen tests on admission for patients hospitalized with community-acquired pneumonia differ in Japan, the United States, and Europe. We aimed to evaluate the association between the timing of Legionella urinary antigen testing and inhospital mortality in patients with atypical pneumonia. Methods: We identified 654,708 patients with atypical pneumonia from July 2010 to March 2021 using the Japanese national inpatient database. The patients were divided into groups that underwent Legionella urinary antigen tests on the day of admission (test group, n = 229,649) and those that underwent testing after the day of admission or were untested (control group, n = 425,059). A propensity score-stabilized inverse probability of treatment weighting analysis was performed to compare inhospital mortality, length of hospital stay, and total hospitalization costs between the two groups. Odds ratios (ORs) or differences and their 95% confidence intervals (CIs) were calculated using generalized linear models. Results: The tested group had a significantly lower 30-day inhospital mortality than that of the control group (7.7% vs. 9.0%; OR: 0.83 [95% CIs, 0.81-0.86]). The tested group also had a significantly shorter length of stay (difference, -2.3 [-2.6 to - 2.0] days and total hospitalization costs (-396 [-508 to - 285] US dollars) than that of the control group. Conclusions: Legionella urinary antigen testing upon admission is associated with better outcomes in patients with atypical pneumonia. Legionella urinary antigen testing performed on the day of admission is recommended for hospitalized patients with atypical pneumonia.

Depression and diet-related distress among Japanese women with gestational diabetes mellitus.

Although the association between gestational diabetes mellitus (GDM) and maternal postpartum depression has been reported, the association between these two factors during pregnancy has not been sufficiently examined. We compared pregnant women with and without GDM to clarify the association and examined factors related to depression in pregnant women with GDM. Questionnaires were administered longitudinally to pregnant Japanese women in the third trimester and at 2 and 4 weeks postpartum. One hundred and five and 108 pregnant women with and without GDM, respectively, were included in the study. Of the 105 women with GDM, 20 (19.0%) reported being depressed during pregnancy, which was significantly higher than that among those without GDM (9.3%). Binomial logistic regression analysis revealed that depression was significantly positively associated with diet-related distress and negatively associated with social support among women with GDM. Diet-related distress and social support are important factors in managing depression in pregnant women with GDM.

Structural Expansion of Catalytic RNA Nanostructures through Oligomerization of a Cyclic Trimer of Engineered Ribozymes.

The multimolecular assembly of three-dimensionally structured proteins forms their quaternary structures, some of which have high geometric symmetry. The size and complexity of protein quaternary structures often increase in a hierarchical manner, with simpler, smaller structures serving as units for larger quaternary structures. In this study, we exploited oligomerization of a ribozyme cyclic trimer to achieve larger ribozyme-based RNA assembly. By installing kissing loop (KL) interacting units to one-, two-, or three-unit RNA molecules in the ribozyme trimer, we constructed dimers, open-chain oligomers, and branched oligomers of ribozyme trimer units. One type of open-chain oligomer preferentially formed a closed tetramer containing 12 component RNAs to provide 12 ribozyme units. We also observed large assembly of ribozyme trimers, which reached 1000 nm in size.

Percutaneous ethanolamine oleate sclerotherapy for aggressive vertebral hemangioma: A case report.

Vertebral hemangiomas are the most common benign lesion of the spine which are often an asymptomatic incidental finding. However, a few hemangiomas are aggressive and characterized by bone expansion and extraosseous extension into the paraspinal and epidural spaces. We report the case of a patient presenting an aggressive vertebral hemangioma causing back pain and bilateral numbness of the legs. Among various treatment modalities, a minimally invasive percutaneous sclerotherapy procedure using ethanolamine oleate under computed tomography and fluoroscopic guidance was safely and successfully performed with good clinical outcomes.

Isothermal self-assembly of multicomponent and evolutive DNA nanostructures.

Thermal annealing is usually needed to direct the assembly of multiple complementary DNA strands into desired entities. We show that, with a magnesium-free buffer containing NaCl, complex cocktails of DNA strands and proteins can self-assemble isothermally, at room or physiological temperature, into user-defined nanostructures, such as DNA origamis, single-stranded tile assemblies and nanogrids. In situ, time-resolved observation reveals that this self-assembly is thermodynamically controlled, proceeds through multiple folding pathways and leads to highly reconfigurable nanostructures. It allows a given system to self-select its most stable shape in a large pool of competitive DNA strands. Strikingly, upon the appearance of a new energy minimum, DNA origamis isothermally shift from one initially stable shape to a radically different one, by massive exchange of their constitutive staple strands. This method expands the repertoire of shapes and functions attainable by isothermal self-assembly and creates a basis for adaptive nanomachines and nanostructure discovery by evolution.

High-mobility group box-1 peptide ameliorates bronchopulmonary dysplasia by suppressing inflammation and fibrosis in a mouse model.

BACKGROUND: This study aimed to examine the effect of the HMGB1 peptide on Bronchopulmonary dysplasia (BPD)-related lung injury in a mouse model. RESULTS: HMGB1 peptide ameliorates lung injury by suppressing the release of inflammatory cytokines and decreasing soluble collagen levels in the lungs. Single-cell RNA sequencing showed that the peptide suppressed the hyperoxia-induced inflammatory signature in macrophages and the fibrotic signature in fibroblasts. These changes in the transcriptome were confirmed using protein assays. CONCLUSION: Systemic administration of HMGB1 peptide exerts anti-inflammatory and anti-fibrotic effects in a mouse model of BPD. This study provides a foundation for the development of new and effective therapies for BPD.

Two-Dimensional DNA Origami Lattices Assembled on Lipid Bilayer Membranes.

Molecular self-assembly has attracted much attention as a method to create novel supramolecular architectures. The scaffolded DNA origami method has enabled the construction of almost arbitrarily shaped DNA nanostructures, which can be further used as components of higher-order architectures. Here, we describe a method to construct and visualize two-dimensional (2D) lattices self-assembled from DNA origami tiles on lipid bilayer membranes. The weak adsorption of DNA origami tiles onto the mica-supported lipid bilayer allows their lateral diffusion along the surface, facilitating interactions among the tiles to assemble and form large 2D lattices. Depending on the design (i.e., shape, size, and interactions with each other) of DNA origami tiles, a variety of 2D lattices made of DNA are constructed.

Neonatal outcomes of congenital diaphragmatic hernia in full term versus early term deliveries: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to review the optimal timing of delivery at term for neonates with prenatally diagnosed congenital diaphragmatic hernia (CDH). We reviewed the literature up to December 19, 2022 using MEDLINE and the Cochrane Library databases. The inclusion criteria were original articles, comparative studies of CDH neonates delivered at an early term (37-38 weeks of gestation) and at full term (39 weeks of gestation or later), and comparative studies investigating outcomes of CDH neonates. Six studies met the inclusion criteria, including 985 neonates delivered at an early term and 629 delivered at full term. The cumulative rate of survival to discharge showed no significant difference between CDH neonates delivered at an early term (395/515; 76.7%) or at full term (345/467; 73.9%) (risk ratio [RR] 1.01; 95% confidence interval [CI], 0.89-1.16; p = 0.85). Furthermore, the number of neonates requiring oxygen therapy at discharge was not significantly different between CDH neonates delivered at an early term (32/370; 8.6%) and at full term (14/154; 9.1%) (RR, 0.99; 95% CI, 0.36-2.70; p = 0.99). Therefore, the optimal timing of delivery at term for neonates with CDH remains unclear.

Single-Molecule Visualization of B-Z Transition in DNA Origami Using High-Speed AFM.

To study the physical properties of molecules and their reaction processes, direct visualization of target molecules is one of the straightforward methods. Atomic force microscopy (AFM) enables the direct imaging of biomolecules under physiological conditions at nanometer-scale spatial resolution. In addition, using the DNA origami technology, the precise placement of target molecules in a designed nanostructure has been achieved, and the detection of the molecules at the single-molecule level has been realized. DNA origami is applied for visualizing the detailed movement of molecules combining with high-speed AFM (HS-AFM), which enables the analysis of the dynamic movement of biomolecules in a subsecond time resolution.Here, we describe the combination of the DNA origami system with HS-AFM for the imaging of rotation of dsDNA originated from B-Z transition. The rotation of dsDNA during B-Z transition is directly visualized in a DNA origami using the HS-AFM. These target-oriented observation systems serve to the detailed analysis of DNA structural changes in real time at molecular resolution.

FNAIT pathogenesis determined by serial analysis of three subsequent pregnancies of a woman with severe fetal and neonatal alloimmune thrombocytopenia (FNAIT) with anti-HPA-4b and anti-HPA-5b alloantibodies in the first sibling.

BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by anti-HPA alloantibody, and anti-HPA-4b is the most common cause in Japanese. Anti-HPA-5b is frequently detected in pregnant women, but it is still controversial whether anti-HPA-5b causes severe FNAIT. CASE PRESENTATION: A Japanese woman with anti-HPA-4b and anti-HPA-5b alloantibodies delivered a baby with severe FNAIT who was both HPA-4b and HPA-5b incompatible. We carefully monitored the patient's following three pregnancies (the second and the fourth siblings were HPA-4b incompatible and HPA-5b compatible; the third sibling was both HPA-4b and HPA-5b compatible). FNAIT was not observed in all three siblings, although a modest decrease in cord blood platelet count was observed in the HPA-4b incompatible siblings compared to the HPA-4b compatible sibling. Serial monitoring of anti-HPA titer showed that anti-HPA-4b markedly decreased in late pregnancy and recovered after delivery of the HPA-4b incompatible siblings, but these decreases were not observed during the mother's pregnancy with the HPA-4b compatible sibling. In contrast, anti-HPA-5b remained at a high titer during pregnancy with all three siblings. CONCLUSION: Our data indicate that dynamic changes of anti-HPA-4b occur during pregnancy and strongly suggest that anti-HPA-5b was mainly responsible for severe FNAIT in this case.

Photocontrolled DNA nanotubes as stiffness tunable matrices for controlling cellular behavior.

Cell behavior is determined by a variety of properties of the extracellular environment like ligand spacing, nanotopography, and matrix stiffness. Matrix stiffness changes occur during many biological processes like wound healing, tumorigenesis, and development. These spatio-temporal dynamic changes in stiffness can cause significant changes in cell morphology, cell signaling, migration, cytoskeleton etc. In this paper, we have created photocontrolled stiffness-tunable DNA nanotubes which can undergo reversible changes in their conformation upon UV and VIS irradiation. When used as a substrate for cell culture, the photocontrolled DNA nanotubes can tune the cell morphology of HeLa cells from a long spindle-shaped morphology with long filopodia protrusions to a round morphology with short filopodia-like extrusions. Such a photocontrolled nanosystem can give us deep insights into the cell-matrix interactions in the native extracellular matrix caused by nanoscopic changes in stiffness.

A longitudinal study of the psychological impact of child-rearing difficulty and COVID-19 on mothers in the postpartum period in Japan.

Background: Postpartum mothers may experience psychological stress due to the sudden changes in their bodies and situation. This study investigates the changes in depressive symptoms among nursing mothers and their child-rearing difficulties before and one month after the declared state of emergency due to COVID-19 pandemic in Japan. The study also assesses whether adding the stress induced by the pandemic to parenting difficulties affected women's depressive symptoms. Method: An online survey was conducted with 309 postpartum women. Participants completed questionnaires that included the Quick Inventory of Depressive Symptomatology (QIDS-SR-J), draft version of the Comprehensive Scale for Parenting Resilience and Adaptation (CPRA+α), and original questions about the COVID-19 stress. Results: A factor analysis was performed on CPRA+α, which found five main factors: difficulty in coping with child and oneself, dissatisfaction with husband, distrust in parents, being tired of the child, and distrust in physician. As a result of t-test of these five factors and the QIDS revealed that there was a significant difference in depressive symptoms before and after the COVID-19 outbreak. In addition to these five factors, the COVID-19 stress of impact on income and employment increased depressive symptoms, while the stress of refraining from going out decreased depressive symptoms. Limitation: Differences in the characteristics of children and mothers were not considered in the study. Longitudinal studies focusing on the period after the declaration of a state of emergency in 2020 are considered necessary. Conclusion: Childcare difficulties and the COVID-19 pandemic induced stress are associated with postpartum women's depressive symptoms.