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Boron-based multiple-resonance (MR) emitters exhibit the advantages of narrowband emission, high absolute photoluminescence quantum yield, thermally activated delayed fluorescence (TADF), and sufficient stability during the operation of organic light-emitting diodes (OLEDs). Thus, such MR emitters have been widely applied as blue emitters in triplet–triplet-annihilation-driven fluorescent devices used in smartphones and televisions. Moreover, they hold great promise as TADF or terminal emitters in TADF-assisted fluorescence or phosphor-sensitised fluorescent OLEDs. Herein we comprehensively review organoboron-based MR emitters based on their synthetic strategies, clarify structure–photophysical property correlations, and provide design guidelines and future development prospects. [ABSTRACT FROM AUTHOR]

Indenone azines, in which the exocyclic C=C bond in dibenzopentafulvalene is replaced by an azine moiety (C=N−N=C), have been synthesized as novel electron‐accepting π‐conjugated scaffolds. Structural modulation at the 7,7′‐positions of indenone azines enabled stereoselective syntheses of diastereomers in which the configurations of the two C=N bonds are E,E or Z,Z. X‐ray crystallographic analyses revealed that all the indenone azines exhibit high coplanarity in contrast to the twisted frameworks of dibenzopentafulvalene derivatives, resulting in the formation of densely π‐stacked structures. Electrochemical measurements and quantum chemical calculations revealed the electron‐accepting character of indenone azines comparable to isoindigo dyes. In particular, the intramolecular hydrogen bonds of 7,7′‐dihydroxy‐substituted derivatives impart enhanced electron‐accepting character and significantly red‐shifted photoabsorption. This study demonstrates that indenone azines represent a promising candidate as electron‐accepting building blocks for optoelectronic materials. [ABSTRACT FROM AUTHOR]

Organic light‐emitting diodes (OLEDs) receive considerable attention because of their commercial use in flat panel displays. Herein, highly efficient spiroborate‐based host materials are reported for use in blue OLEDs. Our designed spiroborates (SBOX) were simple to synthesize and exhibited high triplet excitation energies, narrow S‐T gaps, and balanced charge carrier mobilities. A blue OLED containing one of the designed spiroborates, SBON, as a host exhibited a high external quantum efficiency (27.6 %) and low turn‐on voltage (3.7 V) compared to those observed using 3,3′‐di(9H‐carbazol‐9‐yl)‐1,1′‐biphenyl (17.6 % and 4.5 V, respectively), indicating their potential as host materials in OLEDs. [ABSTRACT FROM AUTHOR]

Organic light‐emitting diodes (OLEDs) receive considerable attention because of their commercial use in flat panel displays. Herein, highly efficient spiroborate‐based host materials are reported for use in blue OLEDs. Our designed spiroborates (SBOX) were simple to synthesize and exhibited high triplet excitation energies, narrow S‐T gaps, and balanced charge carrier mobilities. A blue OLED containing one of the designed spiroborates, SBON, as a host exhibited a high external quantum efficiency (27.6 %) and low turn‐on voltage (3.7 V) compared to those observed using 3,3′‐di(9H‐carbazol‐9‐yl)‐1,1′‐biphenyl (17.6 % and 4.5 V, respectively), indicating their potential as host materials in OLEDs. [ABSTRACT FROM AUTHOR]

Background: This nationwide survey aimed to determine the status of jaundice management in Japan. Methods: A questionnaire about bilirubin level measurements and neonatal jaundice treatment was sent to 330 institutions providing neonatal care. The responses were analyzed according to institution level. Results: Of 330 institutions, 172 responded (52.1% response rate). Total bilirubin levels were measured in the central laboratory using spectrophotometry at 134 institutions and a blood gas analyzer at 81 institutions. Unbound bilirubin (UB) levels were measured by 79 institutions, while transcutaneous bilirubin measurements were taken at 63 institutions. There was no association between institution level and UB or transcutaneous bilirubin measurement. For phototherapy criteria, the Murata‐Imura criteria were adopted by 67 institutions, Nakamura criteria by 36, and Morioka criteria by 39. Light‐emitting diodes (LED) were used by 160 institutions versus fluorescent lights by 31. When a blue LED was used, 119 institutions used the high mode. There is no standard for increasing light intensity. No association was found between institution level and phototherapy criteria. UB was measured in 14 of 63 institutions using the Murata‐Imura criteria. Conclusions: There is a large variation in the management and treatment of neonatal jaundice among institutes in Japan. [ABSTRACT FROM AUTHOR]

The asymmetric oxidation of a sulfur-containing nine-membered heterocycle was achieved for the late-stage introduction of chirality to the substituents of π-electron systems. The oxidation of the sulfur atom considerably influenced the phase-transition behaviour and crystallinity of the resulting π-electron systems. [ABSTRACT FROM AUTHOR]

Invited for the cover of this issue is the group of Aiko Fukazawa at Kyoto University. The image depicts a N−N component replacing the one originally located between the exocyclic C=C bond of a cross‐conjugated dibenzofulvalene. Read the full text of the article at 10.1002/chem.202300181.“Inserting an azine moiety between the cross‐conjugated system of five‐membered rings has produced a new molecular skeleton… that combines the high planarity of the molecular skeleton with excellent electron‐accepting character.” This and more about the story behind the front cover can be found in the article at 10.1002/chem.202300181). [ABSTRACT FROM AUTHOR]

Invited for the cover of this issue is the group of Aiko Fukazawa at Kyoto University. The image depicts a N−N component replacing the one originally located between the exocyclic C=C bond of a cross‐conjugated dibenzofulvalene. Read the full text of the article at 10.1002/chem.202300181. [ABSTRACT FROM AUTHOR]

Keywords: azine; cross conjugation; electron acceptors; hydrogen bonds; pi conjugation EN azine cross conjugation electron acceptors hydrogen bonds pi conjugation 1 1 1 05/18/23 20230516 NES 230516 B The molecular design b in our manuscript is metaphorically represented by curling, a winter sport played on ice. Front Cover: Stereoselective Synthesis and Characterization of Indenone Azine-Based Electron-Accepting -Conjugated Systems (Chem. Eur. J. 28/2023) Azine, cross conjugation, electron acceptors, hydrogen bonds, pi conjugation. [Extracted from the article]

Ambipolar Charge Transport, High Triplet Energy, Host, Organic Light-Emitting Diodes, Spiroborate Keywords: Ambipolar Charge Transport; High Triplet Energy; Host; Organic Light-Emitting Diodes; Spiroborate EN Ambipolar Charge Transport High Triplet Energy Host Organic Light-Emitting Diodes Spiroborate 1 1 1 03/23/23 20230327 NES 230327 B Organic Electronics b . Spiroborate-based host materials with high triplet energies and ambipolar charge-transport properties are reported by Takuji Hatakeyama et al. in their Communication (e202217512). [Extracted from the article]

Spiroborate-based host materials with high triplet energies and ambipolar charge-transport properties are reported by Takuji Hatakeyama et al. in their Communication (e202217512). Keywords: Ambipolar Charge Transport; High Triplet Energy; Host; Organic Light-Emitting Diodes; Spiroborate EN Ambipolar Charge Transport High Triplet Energy Host Organic Light-Emitting Diodes Spiroborate 1 1 1 03/23/23 20230327 NES 230327 B Organic Electronics b . Ambipolar Charge Transport, High Triplet Energy, Host, Organic Light-Emitting Diodes, Spiroborate. [Extracted from the article]

The aim of this study is to investigate whether it is possible to detect future behavioral and emotional problems in extremely low-birth-weight infants by evaluating the neonatal head magnetic resonance imaging (MRI) using a scoring system. This study included 62 extremely low-birth-weight infants born between April 2015 and March 2017 and those who had undergone MRI at 36 to 42 weeks of gestation. These subjects were administered with the Strength and Difficulties Questionnaire (SDQ) at age 4–5, and the patients who responded to the questionnaire were included in the study. A positive correlation was observed between the Global Brain Abnormality Score and Total Difficulties Score of the SDQ (r = 0.26, p = 0.038). However, no significant difference was observed between the median Global Brain Abnormality Score of the normal and borderline-range group and the Total Difficulties Score of the clinical-range group (p = 0.51). This study demonstrated the relationship between the MRI findings in the newborn period and the emotional and behavioral problems in early childhood, but it is not clinically useful as a predictive marker. [ABSTRACT FROM AUTHOR]

Purpose: Infants born to mothers with chorioamnionitis (CAM) are at increased risk of developing adverse neurodevelopmental disorders in later life. However, clinical magnetic resonance imaging (MRI) studies examining brain injuries and neuroanatomical alterations attributed to CAM have yielded inconsistent results. We aimed to determine whether exposure to histological CAM in utero leads to brain injuries and alterations in the neuroanatomy of preterm infants using 3.0- Tesla MRI at term-equivalent age. Methods: A total of 58 preterm infants born before 34 weeks of gestation at Nagoya University Hospital between 2010 and 2018 were eligible for this study (CAM group, n = 21; non-CAM group, n = 37). Brain injuries and abnormalities were assessed using the Kidokoro Global Brain Abnormality Scoring system. Gray matter, white matter, and subcortical gray matter (thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens) volumes were evaluated using segmentation tools (SPM12 and Infant FreeSurfer). Results: The Kidokoro scores for each category and severity in the CAM group were comparable to those observed in the non-CAM group. White matter volume was significantly smaller in the CAM group after adjusting for covariates (postmenstrual age at MRI, infant sex, and gestational age) (p = 0.007), whereas gray matter volume was not significantly different. Multiple linear regression analyses revealed significantly smaller volumes in the bilateral pallidums (right, p = 0.045; left, p = 0.038) and nucleus accumbens (right, p = 0.030; left, p = 0.004) after adjusting for covariates. Conclusions: Preterm infants born to mothers with histological CAM showed smaller volumes in white matter, pallidum, and nucleus accumbens at term-equivalent age. [ABSTRACT FROM AUTHOR]

To determine the clinical features of bilirubin encephalopathy in preterm infants (pBE) in Japan. We performed a retrospective, nationwide questionnaire-based survey. The initial survey determined the number of children with pBE who were born after 2000. Using a structured questionnaire, the second survey clarified the clinical manifestations and characteristics of children with pBE, including demographic data, neurological symptoms, and MRI and auditory brainstem response (ABR) findings. The initial survey identified 41 pBE infants from 18 institutions. After exclusion of patients included in previous studies, clinical information was collected from 30 patients (21 boys and 9 girls) during the secondary survey. The median gestational age was 26 weeks and the median birthweight was 846 g. Chronic lung disease and symptomatic patent ductus arteriosus were common neonatal complications. Head control was observed in 63% and functional gait in 17% of patients. Purposeful hand use was seen in 57% and verbal communication in 50% of patients. MRI showed T2 hyperintensities in the globus pallidus of 29 of 30 patients. ABR abnormalities were present in 11 of 15 patients. None of the variables were significantly different between the 2017 and 2021 surveys. The pBE infants had severely impaired gross motor function and relatively preserved manual function and verbal communication. MRI and ABR findings aid in the diagnosis of pBE. [ABSTRACT FROM AUTHOR]

Purpose: Predicting individual risks for adverse outcomes in preterm infants is necessary for perinatal management and antenatal counseling for their parents. To evaluate whether a machine learning approach can improve the prediction of severe infant outcomes beyond the performance of conventional logistic models, and to identify maternal and fetal factors that largely contribute to these outcomes. Methods: A population-based retrospective study was performed using clinical data of 31,157 infants born at < 32 weeks of gestation and weighing ≤ 1500 g, registered in the Neonatal Research Network of Japan between 2006 and 2015. We developed a conventional logistic model and 6 types of machine learning models based on 12 maternal and fetal factors. Discriminative ability was evaluated using the area under the receiver operating characteristic curves (AUROCs), and the importance of each factor in terms of its contribution to outcomes was evaluated using the SHAP (SHapley Additive exPlanations) value. Results: The AUROCs of the most discriminative machine learning models were better than those of the conventional models for all outcomes. The AUROCs for in-hospital death and short-term adverse outcomes in the gradient boosting decision tree were significantly higher than those in the conventional model (p = 0.015 and p = 0.002, respectively). The SHAP value analyses showed that gestational age, birth weight, and antenatal corticosteroid treatment were the three most important factors associated with severe infant outcomes. Conclusion: Machine learning models improve the prediction of severe infant outcomes. Moreover, the machine learning approach provides insight into the potential risk factors for severe infant outcomes. [ABSTRACT FROM AUTHOR]

Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative pluripotent stem cells present in the bone marrow, peripheral blood, and organ connective tissues. We assessed the homing and therapeutic effects of systemically administered nafimestrocel, a clinical-grade human Muse cell-based product, without immunosuppressants in a neonatal hypoxic–ischemic (HI) rat model. HI injury was induced on postnatal day 7 (P7) and was confirmed by T2-weighted magnetic resonance imaging on P10. HI rats received a single dose nafimestrocel (1 × 106 cells/body) or Hank's balanced salt solution (vehicle group) intravenously at either three days (on P10; M3 group) or seven days (on P14; M7 group) after HI insult. Radioisotope experiment demonstrated the homing of chromium-51-labeled nafimestrocel to the both cerebral hemispheres. The cylinder test (M3 and M7 groups) and open-field test (M7 group) showed significant amelioration of paralysis and hyperactivity at five weeks of age compared with those in the vehicle group. Nafimestrocel did not cause adverse events such as death or pathological changes in the lung at ten weeks in the both groups. Nafimestrocel attenuated the production of tumor necrosis factor-α and inducible nitric oxide synthase from activated cultured microglia in vitro. These results demonstrate the potential therapeutic benefits and safety of nafimestrocel. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of antenatal corticosteroid (ACS) treatment on neonatal outcomes in small for gestational age (SGA) infants born at 24–31 gestational weeks compared with non-SGA infants. Methods: A population-based retrospective study was conducted that analyzed clinical data from the Neonatal Research Network of Japan database, which enrolls neonates born at < 32 gestational weeks and weighing 1500 g or less (n = 22,414). Propensity score matching (with the ratio of ACS to no-ACS groups of 1:1) was performed in SGA (n = 7028) and non-SGA (n = 15,386) infants, respectively. Univariate logistic and interaction analyses were performed to compare the short-term neonatal outcomes of infants with and without ACS treatment in utero. Results: In the SGA and non-SGA infants, ACS treatment significantly reduced in-hospital mortality (odds ratio 0.67 95% confidence interval [0.50–0.88] and 0.62 [0.50–0.78], respectively), respiratory distress syndrome (0.77 [0.69–0.87] and 0.63 [0.58–0.68], respectively), and composite adverse outcomes (0.73 [0.58–0.91] and 0.57 [0.50–0.65], respectively). ACS treatment also significantly reduced intraventricular hemorrhage (grade III/IV), periventricular leukomalacia, and sepsis in the non-SGA infants, but not in the SGA infants. However, interaction analyses revealed no significant differences between the SGA and non-SGA infants in the efficacy of ACS treatment on short-term outcomes except for respiratory distress syndrome. Conclusions: ACS treatment was associated with beneficial effects on mortality, respiratory distress syndrome, and adverse composite outcomes in extremely and very preterm SGA infants, with similar efficacy on all neonatal outcomes except for respiratory distress syndrome observed in the non-SGA infants. [ABSTRACT FROM AUTHOR]

Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative pluripotent stem cells present in the bone marrow, peripheral blood, and organ connective tissues. We assessed the homing and therapeutic effects of systemically administered nafimestrocel, a clinical-grade human Muse cell-based product, without immunosuppressants in a neonatal hypoxic–ischemic (HI) rat model. HI injury was induced on postnatal day 7 (P7) and was confirmed by T2-weighted magnetic resonance imaging on P10. HI rats received a single dose nafimestrocel (1 × 106 cells/body) or Hank's balanced salt solution (vehicle group) intravenously at either three days (on P10; M3 group) or seven days (on P14; M7 group) after HI insult. Radioisotope experiment demonstrated the homing of chromium-51-labeled nafimestrocel to the both cerebral hemispheres. The cylinder test (M3 and M7 groups) and open-field test (M7 group) showed significant amelioration of paralysis and hyperactivity at five weeks of age compared with those in the vehicle group. Nafimestrocel did not cause adverse events such as death or pathological changes in the lung at ten weeks in the both groups. Nafimestrocel attenuated the production of tumor necrosis factor-α and inducible nitric oxide synthase from activated cultured microglia in vitro. These results demonstrate the potential therapeutic benefits and safety of nafimestrocel. [ABSTRACT FROM AUTHOR]

Neonatal necrotizing enterocolitis (NEC) is a serious disease of premature infants that necessitates intensive care and frequently results in life-threatening complications and high mortality. Dedifferentiated fat cells (DFATs) are mesenchymal stem cell-like cells derived from mature adipocytes. DFATs were intraperitoneally administrated to a rat NEC model, and the treatment effect and its mechanism were evaluated. The NEC model was created using rat pups hand fed with artificial milk, exposed to asphyxia and cold stress, and given oral lipopolysaccharides after cesarean section. The pups were sacrificed 96 h after birth for macroscopic histological examination and proteomics analysis. DFATs administration significantly improved the survival rate from 25.0 (vehicle group) to 60.6% (DFAT group) and revealed a significant reduction in macroscopical, histological, and apoptosis evaluation compared with the vehicle group. Additionally, the expression of C–C motif ligand 2 was significantly decreased, and that of interleukin-6 decreased in the DFAT group. DFAT administration ameliorated 93 proteins mainly related to proteins of fatty acid metabolism of the 436 proteins up-/down-regulated by NEC. DFATs improved mortality and restored damaged intestinal tissues in NEC, possibly by improving the abnormal expression of fatty acid-related proteins and reducing inflammation. [ABSTRACT FROM AUTHOR]

Aim: Antenatal corticosteroids (ACS) are recommended for women at risk of preterm birth before 34 weeks' gestation. However, adverse effects of ACS on the fetal brain have also been reported. The time interval from ACS administration to delivery (ACS‐to‐delivery interval) might alter the effect of ACS on the fetal brain. This study aimed to evaluate the effect of ACS‐to‐delivery interval on cord blood S100 calcium‐binding protein B (S100B) levels as a biomarker of brain damage. Methods: Women who delivered between 2012 and 2020 at a tertiary medical center were divided into three groups according to ACS use and ACS‐to‐delivery interval, retrospectively: non‐ACS, ACS ≤7 days, and ACS >7 days. Patients who did not complete the ACS regimen were excluded. The primary outcome was cord blood S100B levels. Results: Cord blood S100B levels were significantly lower in the ACS ≤7 days group than in the non‐ACS and ACS >7 days groups. In the multiple regression analysis, birth ≤7 days after ACS showed a significant negative association with S100B level (p < 0.001). Conclusions: Reduced S100B levels were observed in infants born ≤7 days after ACS but not in infants born >7 days after ACS. These findings suggest the importance of ACS timing to optimize its effects on the fetal brain, although further studies are required to identify these mechanisms. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR), followed by postnatal early catch-up growth, is associated with an increased risk of metabolic dysfunction, including type 2 diabetes in humans. This study aims to determine the effects of FGR and early catch-up growth after birth on the pathogenesis of type 2 diabetes, with particular attention to glucose tolerance, pancreatic islet morphology, and fibrosis, and to elucidate its mechanism using proteomics analysis. The FGR rat model was made by inducing mild intrauterine hypoperfusion using ameroid constrictors (ACs). On day 17 of pregnancy, ACs were affixed to the uterine and ovarian arteries bilaterally, causing a 20.9% reduction in birth weight compared to sham pups. On postnatal day 4 (P4), the pups were assigned to either the good nutrition (GN) groups with 5 pups per dam to ensure postnatal catch-up growth or poor nutrition groups with 15 pups per dam to maintain lower body weight. After weaning, all pups were fed regular chow food ad libitum (P21). Rats in both FGR groups developed glucose intolerance; however, male rats in the FGR good nutrition (FGR-GN) group also developed hypertriglyceridemia and dysmorphic pancreatic islets with fibrosis. A comprehensive and functional analysis of proteins expressed in the pancreas showed that FGR, followed by early catch-up growth, severely aggravated cell adhesion-related protein expression in male offspring. Thus, FGR and early catch-up growth caused pancreatic islet morphological abnormalities and fibrosis associated with the disturbance of cell adhesion-related protein expressions. These changes likely induce glucose intolerance and dyslipidemia in male rats. [ABSTRACT FROM AUTHOR]

Respiratory distress is common in neonates admitted to neonatal intensive care units. Additionally, infectious diseases such as intrauterine infections or vertical transmission are important underlying causes of respiratory failure. However, pathogens often cannot be identified in neonates, and there are many cases in which antibacterial drugs are empirically administered. Next-generation sequencing (NGS) is advantageous in that it can detect trace amounts of bacteria that cannot be detected by culturing or bacteria that are difficult to cultivate. However, there are few reports on the diagnosis of infectious diseases using NGS in the neonatal field, especially those targeting respiratory distress. The purpose of our study was to investigate the microorganisms associated with neonatal respiratory distress and to determine whether less invasive collection specimens such as plasma and gastric fluid are useful. Neonates were prospectively recruited between January and August 2020 from Nagoya University Hospital. The inclusion criteria were as follows: 1) admission to the neonatal intensive care unit; 2) respiratory distress presentation within 48 h of birth; and 3) suspected infection, collection of blood culture, and administration of antibiotics. Plasma samples and blood cultures were simultaneously collected. Gastric fluid samples were also collected if the patient was not started on enteral nutrition. Information on the patients and their mothers were collected from the medical records. DNA was extracted from 140 µL of plasma and gastric fluid samples. DNA sequencing libraries were prepared, and their quality was analyzed. DNA libraries were sequenced using high-throughput NGS. The NGS data of plasma and gastric fluid samples were analyzed using the metagenomic pipeline PATHDET, which calculated the number of reads assigned to microorganisms and their relative abundance. Putative pathogens were listed. Overall, 30 plasma samples and 25 gastric fluid samples from 30 neonates were analyzed. Microorganism-derived reads of gastric fluid samples were significantly higher than those of plasma samples. Transient tachypnea of the newborn was the most common cause of respiratory distress with 13 cases (43%), followed by respiratory distress syndrome with 7 cases (23%). There were 8 cases (29%) of chorioamnionitis and 7 cases (25%) of funisitis pathologically diagnosed. All blood cultures were negative, and only two gastric fluid cultures were positive for group B Streptococcus (Patient 15) and Candida albicans (Patient 24). Putative pathogens that met the positive criteria for PATHET were detected in four gastric fluid samples, one of which was group B Streptococcus from Patient 15. In the gastric fluid sample of Patient 24, Candida albicans were detected by NGS but did not meet the positive criteria for PATHDET. Cluster analysis of the plasma samples divided them into two study groups, and the indicator genera of each cluster (Phormidium or Toxoplasma) are shown in Figure 1. Clinical findings did not show any significant differences between the two groups. Cluster analysis of the gastric fluid samples divided them into three study groups, and the indicator genera of each cluster (Ureaplasma, Nostoc, and Streptococcus) are shown in Figure 2. The incidence rate of chorioamnionitis was significantly higher in Ureaplasma group than in the other two groups. Gastric fluid may be useful for assessing neonatal patients with respiratory distress. To the best of our knowledge, this was the first study to reveal that the presence of Ureaplasma in the gastric fluid of neonates with respiratory distress was associated with chorioamnionitis. The early diagnosis of intra-amniotic infections using gastric fluid and its treatment may change the treatment strategy for neonatal respiratory distress. Screening for Ureaplasma in neonates with respiratory distress may reduce the need for empirical antibiotic administration. Further research is required to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: In Japan, the mortality rate of extremely low birth weight (ELBW) infants is notably low in comparison with other developed countries, but the prevalence of chronic lung disease (CLD) and retinopathy of prematurity (ROP) is relatively high. This study aimed to estimate the mortality and morbidity of ELBW infants born in 2015 who were admitted to neonatal intensive care units (NICUs) in Japan and to examine the factors that affected the short‐term outcomes of these infants. We also compared the mortality of ELBW infants born in 2005, 2010, and 2015. Methods: We analyzed the mortality, morbidity, and factors related to short‐term outcomes of ELBW infants, using data from 2782 infants born in 2015 and registered at NICUs in Japan. Results: The mortality rates during NICU stays were 17.0%, 12.0%, and 9.8% for ELBW infants born in 2005, 2010, and 2015, respectively. Among ELBW infants born in 2015, multiple logistic regression analysis showed that short gestational age and low birthweight Z‐score contributed to the increased risk of death. Births by cesarean section and antenatal corticosteroid administration were significantly associated with a reduced risk of death. Among infants who survived, CLD was observed in 53.1% and ROP requiring treatment was observed in 30.4%. Conclusions: Mortality in ELBW infants decreased significantly from 2005 to 2015. As CLD and ROP may affect quality of life and long‐term outcomes of infants who survived, prevention strategies and management for these complications are critical issues in neonatal care in Japan. [ABSTRACT FROM AUTHOR]

Background: Chromosome 13q deletion syndrome shows variable clinical features related to the different potential breakpoints in chromosome 13q. The severely malformed phenotype is known to be associated with the deletion of a critical region in 13q32. However, esophageal atresia is a rare symptom and the relevant region is unknown. Thus, determining the association between accurate breakpoints and new clinical features is essential. Case presentation: A 28-year-old Japanese primigravid woman was referred for fetal growth restriction, absence of a gastric bubble, cerebellar hypoplasia, overlapping fingers, and polyhydramnios at 31 weeks gestation. At 38 + 0 weeks, she delivered a 1774 g female infant. The infant presented with isolated esophageal atresia (Gross type A), Dandy–Walker malformation, right microphthalmia, left coloboma, overlapping fingers, pleurocentrum in the thoracic vertebrae, reduced anogenital distance, and hearing loss. Her karyotype was diagnosed as 46,XX,del(13)(q32.1–qter) by amniocentesis, but array comparative genomic hybridization after birth revealed the deletion of 13q31.3–qter. At 48 days after birth, the infant underwent surgery for esophageal atresia and was later discharged from the hospital at 7 months of age. Conclusion: This case report and the literature reviews supports the previous findings on the pathological roles of haploinsufficiency of the ZIC2/ZIC5 in Dandy–Walker malformation and the EFBN2 haploinsufficiency in eye malformation and hearing loss. Furthermore, the possible involvement of IRS2, COLA1, and COLA2 in eye malformation were identified. This is the first case of 13q deletion syndrome with esophageal atresia (Gross A), but it may be a symptom of VATER/VACTER association (vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects), as in the previous cases. These symptoms might also be associated with EFBN2 haploinsufficiency, although further research is required. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate prenatal predictors of mortality in fetuses with congenital diaphragmatic hernia (CDH). Methods: A systematic literature search was performed to identify relevant observational studies that evaluated the ability of lung-to-head ratio (LHR), observed-to-expected LHR (o/e-LHR), observed-to-expected total fetal lung volume (o/e-TFLV), lung-to-thorax transverse area ratio (L/T ratio), intrathoracic herniation of the liver and the stomach, and side of diaphragmatic hernia, using a threshold for the prediction of mortality in fetuses with CDH. Study quality was assessed using the QUADAS-2 tool. Hierarchical summary receiver operating characteristic curves were constructed. Results: A total of 50 articles were included in this meta-analysis. The QUADAS-2 tool identified a high risk of bias in more than one domain scored in all parameters. Among those parameters, the diagnostic odds ratio of mortality with o/e-LHR < 25%, o/e-TFLV < 25%, and L/T ratio < 0.08 were 11.98 [95% confidence interval (CI) 4.65–30.89], 11.14 (95% CI 5.19–23.89), and 10.28 (95% CI 3.38–31.31), respectively. The predictive values for mortality were similar between the presence of liver herniation and retrocardiac fetal stomach position. Conclusions: This systematic review suggests that o/e-LHR, o/e-TFLV, and L/T ratio are equally good predictors of neonatal mortality in fetuses with isolated CDH. [ABSTRACT FROM AUTHOR]

Purpose: The prenatal diagnosis of the stomach position in congenital diaphragmatic hernia (CDH) has been a reliable prognostic factor, but few studies have focused on the postnatal position. We therefore evaluated the significance of the nasogastric (NG) tube position just after birth. Methods: The Japanese CDH Study Group database enrolled 1037 CDH neonates over 15 years. In our multicenter retrospective study, 464 cases of left-sided isolated CDH with prenatal diagnoses were divided into two groups: NG tube below the diaphragm (BD; n = 190) or above the diaphragm (AD; n = 274). The primary outcome was the 90-day survival rate, and the secondary outcomes were mechanical ventilation duration, hospitalization duration, and recurrence rate. Results: The BD group had a significantly higher 90-day survival rate (98.4 vs. 89.4%, p < 0.001), shorter mechanical ventilation (11 vs. 19 days, p < 0.001), shorter hospitalization (38 vs. 59 days, p < 0.001), and lower recurrence rate (p = 0.002) than the AD group. A multivariate analysis showed that BD (adjusted odds ratio, 3.68; 95% confidence interval 1.02–13.30) was a favorable prognostic factor for the 90-day survival. Conclusion: The assessment of the NG tube position revealed it to be a reliable prognostic factor of left-sided isolated CDH. Therefore, it should be included as a routine assessment. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to determine global professional opinion and practice for the use of therapeutic hypothermia (TH) for treating infants with mild hypoxic-ischaemic encephalopathy (HIE). Methods: A web-based survey (REDCap) was distributed via emails, social networking sites, and professional groups from October 2020 to February 2021 to neonatal clinicians in 35 countries. Results: A total of 484 responses were obtained from 35 countries and categorized into low/middle-income (43%, LMIC) or high-income (57%, HIC) countries. Of the 484 respondents, 53% would provide TH in mild HIE on case-to-case basis and only 25% would never cool. Clinicians from LMIC were more likely to routinely offer TH in mild HIE (25% v HIC 16%, p < 0.05), have a unit protocol for providing TH (50% v HIC 26%, p < 0.05), use adjunctive tools, e.g., aEEG (49% v HIC 32%, p < 0.001), conduct an MRI post TH (48% v HIC 40%, p < 0.05) and less likely to use neurological examinations as a HIE severity grading tool (80% v HIC 95%, p < 0.001). The majority of respondents (91%) would support a randomized controlled trial that was sufficiently large to examine neurodevelopmental outcomes in mild HIE after TH. Conclusions: This is the first survey of global opinion for TH in mild HIE. The overwhelming majority of professionals would consider "cooling" an infant with mild HIE, but LMIC respondents were more likely to routinely cool infants with mild HIE and use adjunctive tools for diagnosis and follow-up. There is wide practice heterogeneity and a sufficiently large RCT designed to examine neurodevelopmental outcomes, is urgently needed and widely supported. [ABSTRACT FROM AUTHOR]

Purpose: Predicting lethal pulmonary hypoplasia in infants with congenital diaphragmatic hernia (CDH) before extracorporeal membrane oxygenation (ECMO) initiation is difficult. This study aimed to predict lethal pulmonary hypoplasia in patients with CDH prior to ECMO. Methods: This was a multicenter cohort study involving neonates prenatally diagnosed with isolated unilateral CDH (born 2006–2020). Patients who required ECMO due to respiratory insufficiency were included in this study. Patients who underwent ECMO due to transient disorders were excluded from analysis. Blood gas analysis data within 24 h of birth were compared between survivors and non-survivors. Predictive abilities were assessed for factors with significant differences. Results: Overall, 34 patients were included (18 survivors and 16 non-survivors). The best pre-ductal PaO2 was significantly lower in non-survivors than in survivors (50.4 [IQR 30.3–64.5] vs. 67.5 [IQR 52.4–103.2] mmHg, respectively; p = 0.047). A cutoff PaO2 of 42.9 mmHg had a sensitivity, specificity, and positive predictive value of 50.0%, 94.4%, and 88.9%, respectively, to predict mortality. Conclusion: The best PaO2 within 24 h after birth predicted mortality following ECMO initiation. This should be shared to families and caregivers to optimize the best interests of the infants with CDH. [ABSTRACT FROM AUTHOR]

Brush or delta brush is a well-known characteristic waveform in preterm electroencephalograms. However, the longitudinal trajectory of brushes and its association with neurodevelopment remain uncertain. We analyzed the longitudinal incidence of brushes in 36 extremely low birth weight infants without severe brain lesions and its association with neurodevelopment and white matter abnormality. Conventional eight-channel electroencephalograms were recorded at 30, 32, 36, and 40 postmenstrual weeks (PMW). Incidence of brushes was calculated as the sum of brushes from each channel separated by active sleep and quiet sleep. A developmental delay was defined as a developmental quotient of <85 assessed at corrected age of 18 months. White matter abnormalities were evaluated with term-equivalent magnetic resonance imaging. The median incidence of brushes (per minute) in 36 infants at PMW 30, 32, 36, and 40 was 16.4, 20.4, 22.5, and 1.8 during active sleep and 7.5, 10.3, 11.5, and 1.7 during quiet sleep, respectively. Among the 36 infants, 14 infants were diagnosed with developmental delay. Longitudinal trajectories of the incidence of brushes were different between the normal and the delayed development groups. Brushes were observed most frequently at 36 PMW in the delayed development group. The incidence of brushes at 36 PMW was significantly correlated with the severity of white matter abnormalities and negatively correlated with the developmental quotient. The incidence of brushes at 36 PMW can be a unique predictor of early neurodevelopment in extremely low birth weight infants without severe brain lesions. [ABSTRACT FROM AUTHOR]

Purpose: We compared the efficacy of thoracoscopic repair (TR) with that of open repair (OR) for neonatal congenital diaphragmatic hernia (CDH). Methods: The subjects of this multicenter retrospective cohort study were 524 infants with left-sided isolated CDH, diagnosed prenatally, and treated at one of 15 participating hospitals in Japan between 2006 and 2018. The outcomes of infants who underwent TR and those who underwent OR were compared, applying propensity score matching. Results: During the study period, 57 infants underwent TR and 467 underwent OR. Ten of the infants who underwent TR required conversion to OR for technical difficulties and these patients were excluded from the analysis. The survival rate at 180 days was similar in both groups (TR 98%; OR 93%). Recurrence developed after TR in 3 patients and after OR in 15 patients (TR 7%, OR 3%, p = 0.40). The propensity score was calculated using the following factors related to relevance of the surgical procedure: prematurity (p = 0.1), liver up (p < 0.01), stomach position (p < 0.01), and RL shunt (p = 0.045). After propensity score matching, the multivariate analysis adjusted for severity classification and age at surgical treatment revealed a significantly shorter hospital stay (odds ratio 0.50) and a lower incidence of chronic lung disease (odds ratio 0.39) in the TR group than in the OR group. Conclusions: TR can be performed safely for selected CDH neonates with potentially better outcomes than OR. [ABSTRACT FROM AUTHOR]

Perinatal hypoxic ischemic encephalopathy (HIE) results in serious neurological dysfunction and mortality. Clinical trials of multilineage-differentiating stress enduring cells (Muse cells) have commenced in stroke using intravenous delivery of donor-derived Muse cells. Here, we investigated the therapeutic effects of human Muse cells in an HIE model. Seven-day-old rats underwent ligation of the left carotid artery then were exposed to 8% oxygen for 60 min, and 72 hours later intravenously transplanted with 1 × 104 of human-Muse and -non-Muse cells, collected from bone marrow-mesenchymal stem cells as stage-specific embryonic antigen-3 (SSEA-3)+ and −, respectively, or saline (vehicle) without immunosuppression. Human-specific probe revealed Muse cells distributed mainly to the injured brain at 2 and 4 weeks, and expressed neuronal and glial markers until 6 months. In contrast, non-Muse cells lodged in the lung at 2 weeks, but undetectable by 4 weeks. Magnetic resonance spectroscopy and positron emission tomography demonstrated that Muse cells dampened excitotoxic brain glutamatergic metabolites and suppressed microglial activation. Muse cell-treated group exhibited significant improvements in motor and cognitive functions at 4 weeks and 5 months. Intravenously transplanted Muse cells afforded functional benefits in experimental HIE possibly via regulation of glutamate metabolism and reduction of microglial activation. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) abnormalities in preterm infants with bilirubin encephalopathy (BE) become less clear as the infants age. We assessed MRI findings in children with preterm BE older than 36 months corrected age (CA).Methods: In a previous questionnaire survey, hospitals were asked to provide head MRI data of patients older than 36 months CA. MRI findings were reviewed by three pediatric neurology specialists and classified as no abnormalities, partial globus pallidus (GP) lesions, or diffuse GP lesions.Results: In total, 33 MRI scans were available from 28 patients. The median gestational age and birth weight were 26 weeks and 824 g, respectively. The prevalence of MRI abnormalities was 100% in patients at 37 to 48 months CA, 71% in those at 49 to 60 months CA, 50% in those at 61 to 72 months CA, 67% in those at 73 to 84 months CA, and 38% in those at 85 months CA or older. Partial GP lesions were more common than diffuse GP lesions at all ages. No significant differences in sex, gestational age, birth weight, or gross motor function impairment were observed among lesion groups.Conclusions: GP lesions were detected on MRI in most children with preterm BE when studied after 36 months CA, although MRI abnormalities became less apparent along with age. Partial GP lesions may be a characteristic of older children with preterm BE. [ABSTRACT FROM AUTHOR]

Background: 5p deletion syndrome is known as cri-du-chat syndrome, but there are no reports on congenital diaphragmatic hernia complications associated with it.Case Presentation: A 28-year-old primigravida Japanese woman was referred for 5 mm of nuchal translucency. Fetal growth restriction was found at 20 weeks, and a left-sided congenital diaphragmatic hernia was diagnosed at 24 weeks. The karyotype of the fetus was diagnosed as 46, XX, del(5)(p14) and referred to our hospital. At 36 + 6 weeks, a 1524 g female infant was delivered after premature membrane rupture, with Apgar scores of 4 and 6 at 1 and 5 minutes, respectively. The baby was intubated immediately with sedation and muscle relaxation, after birth for initial treatment for congenital diaphragmatic hernia. The peripheral blood karyotype was consistent with the prenatal result. The infant was discharged alive, without any respiratory support, after the defect of the diaphragm was repaired.Conclusion: The results of this study may be helpful for antenatal genetic counseling. [ABSTRACT FROM AUTHOR]

Background: Infants born to mothers with hypertensive disorders of pregnancy (HDP) have adverse neurodevelopmental consequences in later life. Magnetic resonance spectroscopy (MRS) is used to predict subsequent neurodevelopment in the field of perinatology.Aim: We aimed to determine whether exposure to HDP in utero leads to alterations in brain metabolites in preterm infants using multi-voxel proton MRS at term-equivalent age.Study Design: Retrospective cohort study.Subjects: A total of 103 preterm infants born before 34 weeks of gestation at Nagoya University Hospital between 2010 and 2018 were eligible. Twenty-seven infants were born to mothers with HDP (HDP group), and 76 were born to mothers without HDP (non-HDP group).Outcome Measures: The peak area ratios of N-acetylaspartate (NAA)/choline (Cho), NAA/creatine (Cr), and Cho/Cr were evaluated at 10 designated regions of interest (bilateral frontal lobes, basal ganglia, thalami, temporal lobes, and occipital lobes).Results: The peak area ratios of NAA/Cho and NAA/Cr in the bilateral thalami were significantly higher in the HDP group than in the non-HDP group after adjustment for covariates (postmenstrual age at MRS assessment and infant sex). No significant differences were observed in other regions. Preeclampsia, abnormal umbilical artery blood flow, and fetal growth restrictions were significantly associated with increased NAA/Cho and NAA/Cr ratios in the thalami.Conclusions: Based on the evidence that NAA/Cho and NAA/Cr ratios constantly increase with postmenstrual age in normal brain development, exposure to maternal HDP in utero may accelerate brain maturation and increase neuronal activity in preterm infants. [ABSTRACT FROM AUTHOR]

Recent asteroid missions have revealed that many sub-kilometer asteroids are rubble piles. Large parts of their surfaces are covered with boulders larger than tens of centimeters. An evaluation of the abundance and size distribution of boulders provides clues to understand surface processes on boulder-covered asteroids. Here we report a new method that automatically measures the abundance of small boulders (sub-pixel to a few pixels), whose boundaries cannot be recognized with visual inspection, by quantifying the surface radiance variation that occurs during the spinning of the asteroid. After validating our approach with previous boulder counting data, we apply this method to images of the asteroids Ryugu and Itokawa, which were visited by JAXA's Hayabusa and Hayabusa2, and obtain a global distribution of the boulders larger than 0.75–3 ​m, which corresponds to 1.5–6 pixels. We find that the boulder number density of this size range is smaller (1) on the western bulge than on the eastern hemisphere and (2) on the equatorial ridge than on the higher latitudes, both of which exceed the number density of boulders ​> ​5 ​m by an order of magnitude. The boulder size distribution at 1.25–20 ​m shows that the boulders smaller than 1 ​m are more abundant at the equator than at mid-latitudes, while those larger than 1 ​m in diameter are more abundant at mid-latitudes than at the equator. This contrast suggests size-dependent migration of boulders in the latitudinal direction. We also find that the typical boulder size (the size reaching the cumulative areal coverage of 50%) is 1.9 ​m at the equatorial region (10°S-10°N) while it is 2.6 ​m at mid-latitudes (40°S-50°S, 40°N-50°N). The typical boulder size is also smaller in the western bulge (2.0–2.2 ​m). We construct global maps of the power-law index of the size frequency distribution of boulders and find minor variations over the entire surface of Ryugu (−2.53 ​± ​0.03) for boulders larger than 1.25 ​m. This small variation suggests homogeneous size sorting processes on Ryugu. Surface roughness does not show a significant correlation with the v-band albedo but shows a high anti-correlation (R ​= ​−0.73) with the current geological slope on the eastern hemisphere. Our method is useful enhancement of smooth area detection and boulder distribution characterization that will be applicable to other planetary explorations in the future, including those of Phobos and other asteroids. • Automatic analysis of pixel-scale boulders based on pixel radiance variation as asteroid spins. • Distribution of sub-meter boulders on Ryugu indistinguishable from visual counting. • Method detects the east-west dichotomy in the distribution of small boulders (several meters in diameter). • Uniform power-law index of boulder size frequency distribution on Ryugu suggests homogeneous size sorting. • Boulder distribution is correlated with current geologic slope. [ABSTRACT FROM AUTHOR]