[Text-mining of children's answers to national web-survey questions on parental status during COVID-19].

Objectives　Behavior at school has been restricted due to infection control during the COVID-19 pandemic. This study aimed to clarify children's opinions by examining the structure of their text responses to open-ended web survey questions, as well as how they differed to the psychological and socio-economic status of their parents.Method　From September to October 2020, approximately six months after the temporary closure of schools in Japan due to COVID-19, 2,111 respondents (elementary, junior high, and high school students) answered a questionnaire on "The third wave of CORONA-CODOMO project" website. The text data of 1,140 students who provided free-text answers to open-ended questions such as, "what are you concerned about and what do you want to say?" (comments) and "how should I get them to understand?" (proposals) were analyzed. Results were stratified by parental demographics such as age, employment status, the Kessler Psychological Distress Scale (K6), and financial status. The text mining assessed the frequency of word appearances, analyzed characteristic words, and showed a term network (word-relationship diagram).Results　The total number of lines (number of respondents) of comments and proposal texts were 531 and 1,017, respectively, and the average line length (number of characters) was 21.5 and 31.5, respectively. In the dependency relations frequency analysis, the actions of proposals and comments such as "speaking-listening", "event-disappearing", and "mask-removing" appeared. In the word network, words such as "moving" and "speaking" formed a strong co-occurrence network to "I", which had the largest node in proposals, while "COVID-19" in the comments strongly co-occurred with "end+?" (predicate attribute: question) and "I+want to disappear" (predicate attribute: aspirations). According to the parent attributes, in the proposals, the characteristic words (complementary similarity measure) were "talk" (35.9) in the employed group, "talk" (26.6) in the K6 lower score group, and "understand+not" (23.5/17.3, predicate attribute: negation) in the K6 higher score group/bad economic status. In the comments, it was "COVID-19" (28.1, 27.5) in the employed group and the high mental health group.Conclusions　While children displayed discomfort and fear of COVID-19 when asked about proposals, the children were willing to talk directly, also, they wanted someone to listen to them. The characteristics of the proposals in their answers were "I don't know" in both the high mental burden group and the bad economic status group of the parents.

Prominence of NUDT15 genetic variation associated with 6-mercaptopurine tolerance in a genome-wide association study of Japanese children with acute lymphoblastic leukaemia.

Inherited genetic variation is associated with 6-mercaptopurine (6-MP) dose reduction and frequent toxicities induced by 6-MP. However, the tolerable dose for 6-MP is not fully predicted by the known variation in NUDT15 and TPMT among Asian children with acute lymphoblastic leukaemia (ALL). We performed a genome-wide association study (GWAS) related to 6-MP dose among Japanese children with ALL. This GWAS comprised 224 patients previously enrolled in Tokyo Children's Cancer Study Group clinical studies with replication attempted in 55 patients. Genome-wide single nucleotide polymorphism (SNP) genotypes were evaluated for association with average 6-MP dose during the initial 168 days of maintenance therapy. Possible associations were observed across five gene-coding regions, among which only variants at 13q14.2 were significant and replicated genome-wide (rs116855232, NUDT15, ß = -10.99, p = 3.7 × 10-13 ). Notable findings were observed for variants in AFF3 (rs75364948, p = 2.05 × 10-6 ) and CHST11 (rs1148407, p = 2.09 × 10-6 ), but were not replicated possibly due to small numbers. A previously reported candidate SNP in MTHFR was associated with higher average 6-MP dose (rs1801133, p = 0.045), and FOLH1 (rs12574928) was associated in an evaluation of candidate regions (padjust  = 0.013). This study provides strong evidence that rs116855232 in NUDT15 is the genetic factor predominantly associated with 6-MP tolerable dose in children in Japan.

Children's daily lives and well-being: Findings from the CORONA-CODOMO survey 1st wave.

BACKGROUND: The coronavirus disease 2019 pandemic has changed people's lives dramatically. Few data on the acute effects of the pandemic on children's daily lives and well-being have been published to date. This study aimed to capture its effects on Japanese children during the first peak of the outbreak. METHODS: We conducted a web-based, anonymous cross-sectional survey targeting Japanese children aged 7-17 years and parents/guardians of children aged 0-17 years. Eligible individuals were invited to participate in the survey from April 30 to May 31, 2020. This self-report questionnaire examined daily life and behaviors, psychological symptoms, well-being, quality of life, and positive parenting or abusive behaviors at the very beginning of the outbreak. RESULTS: A total of 2,591 children and 6,116 parents/guardians participated in our survey. Sixty-two percent of children reported screen time exceeding 2 h. Twenty percent of children reported abusive behaviors by family members. Nine in ten parents/guardians of school-aged children reported that their child had at least one acute stress symptom in the past month. Average mental health subscale scores from KINDLR questionnaire on quality of life were lower than the national average for all grades. Nearly half of parents/guardians refrained from seeking medical care for the child's symptoms. CONCLUSIONS: The COVID-19 pandemic had serious acute impacts on Japanese children's daily lives, well-being, family relationships, and health-care utilization, including some impacts that are potentially long-lasting; thus, proactive interventions and services are needed, as well as longitudinal surveys.

The coronavirus disease 2019 pandemic and the rights of the child in Japan.

BACKGROUND: Few studies have used direct reports by children to assess how the rights documented in the United Nations Convention on the Rights of the Child (CRC) have been affected during the pandemic of coronavirus disease 2019 (COVID-19). METHODS: Data were obtained from the CORONA-CODOMO Survey, a web-based survey conducted from April to May 2020 in Japan, targeting children aged 7-17 and parents/guardians of children aged 0-17. We focused on self-reports from children, including two open-ended questions asking their needs and opinions. The results were analyzed according to the five categories of rights defined by the CRC: education, health, safety, play, and participation. RESULTS: Among the 2,591 children who participated in the survey, 1,292 children (49.9%) answered at least one of the two open-ended questions. The most frequent concern was COVID-19 infecting members of their families (78.2%), followed by the inability to see their friends (74.3%). There were 1,523 direct comments from children. The comments covered a wide range of the rights in the CRC, including reopening of schools, disparities in education, access to health information, alternatives for playing and seeing friends, and needs for participation and being heard. Few comments were related to safety whereas a certain proportion of children were victimized within households. CONCLUSIONS: Our results suggest that the rights outlined in the CRC have been restricted during the COVID-19 pandemic. Health and educational professionals working with children and policymakers should introduce the rights-based approach to protect the best interests of children during and after the pandemic.

Allogeneic Stem Cell Transplantation for Acute Lymphoblastic Leukemia in Adolescents and Young Adults.

Hematologic stem cell transplantation (HSCT) is the most potent consolidation therapy for high-risk acute lymphoblastic leukemia (ALL), but their outcomes and complications in adolescent and young adult (AYA) patients remain unclear. We compared outcomes after HSCT for ALL among children (age 1 to 9 years; n = 607), adolescents (age 10 to 19 years; n = 783), and young adults (age 20 to 29 years old, n = 603), based on Japanese nationwide registry data. The 5-year overall survival (OS) rate among AYA patients was worse than that of children, at 64% (95% confidence interval [CI], 60% to 68%). In the AYA, the 5-year treatment-related mortality (TRM) after HSCT was 19% (95% CI, 16% to 22%), significantly higher than that in younger patients. The most common cause of TRM in the AYA was infection. The relapse rate was not different across the 3 age groups. When focusing on older adolescents (age 15 to 19 years), there was no difference in outcomes between those treated in pediatric centers and those treated in adult centers. In conclusion, the AYA had a greater risk of nonrelapse death than younger patients, and infection was the most common cause. Further optimization is required for HSCT in AYAs with ALL.

Neonatal Kawasaki disease: case report and data from nationwide survey in Japan.

UNLABELLED: Kawasaki disease (KD) is a systemic vasculitis that develops during childhood, with a peak incidence from 6 to 23 months of age. KD also affects younger children, including neonates. We herein describe the case of a 22-day-old patient with incomplete KD. Some characteristics of neonatal KD are also presented with a review of nationwide surveys of KD in Japan involving approximately 130,000 patients during a 12-year period. The surveys identified 23 neonatal cases, accounting for 1/5,500 of patients of all ages with KD. We found that the characteristics of neonatal KD are likely to be incompatible with the classic criteria for KD and that the incidence of coronary disorders in neonatal patients was not statistically higher than that in older patients. These findings are very similar to those of previous reports of neonatal KD. CONCLUSION: Neonatal KD is rare and often presents with only a few features of KD. In addition, both neonatal and older patients with KD are at risk of coronary disorders. These characteristics present a challenge to pediatricians in the diagnosis and treatment of febrile neonates.

Computed tomography findings of ongoing subgaleal hemorrhage.

Neonatal subgaleal hemorrhage (SGH) is a serious adverse event that is often underestimated and sometimes goes unrecognized. It can cause bleeding complications and jeopardize the patient's life. Early diagnosis and prompt treatment are important in optimizing the outcome in neonates with SGH. Herein we describe the case of a newborn who developed severe SGH and died. We report unenhanced computed tomography (CT) of ongoing SGH, which showed a low-density region in the surrounding area of the head. The density could be explained by unclotted active bleeding and low hematocrit. Even if a patient with clinically suspected SGH has a low-density region on CT, the presence of SGH should not be excluded.

Cephalhematoma and petechial rashes associated with acute parvovirus B19 infection: a case report.

BACKGROUND: Parvovirus B19 can cause petechial rashes in the acute phase of illness as well as erythema infectiosum (fifth disease) during convalescence. This petechial rash is often called "gloves and socks" syndrome because of the typical distribution of the eruption. However, involvement of other sites (e.g., intertriginous area) and generalized involvement have been recently recognized. We report here a patient with parvovirus-associated petechiae and cephalhematoma. CASE PRESENTATION: The patient was a previously healthy 10-year-old boy. There was a family history of fatal bleeding; his sister died of intracranial bleeding with an uncertain cause at the age of 5 months. The patient was admitted to our hospital because of sudden onset of cephalhematoma associated with fever. He reported that he had no recent head trauma but that he massaged his scalp on the day before admission. On admission, his temperature was 38.8°C; otherwise, he was in a stable condition. Besides cephalhematoma, petechial rashes were present on his trunk and limbs. The initial laboratory tests were essentially normal, including platelet count and coagulation tests. Expanded laboratory tests were repeated to explore the etiology of his skin hemorrhage, all of which indicated that hematological disorders were unlikely. His symptoms subsided spontaneously over the next few days and he was discharged uneventfully. Anti-parvovirus IgM titer was elevated during hospitalization and typical erythema infectiosum was seen approximately 1 week after discharge. During 6 months follow-up, he remained stable without recurrence of a hemorrhagic episode. Finally, we concluded that his cephalhematoma was responsible for acute parvoviral infection. CONCLUSIONS: This is believed to be the first report describing a possible association between parvovirus B19 infection and cephalhematoma. Parvovirus B19 infection should be considered in the differential diagnosis of children who present with unexplained hemorrhage such as cephalhematoma or petechiae.

Reduced-intensity conditioning is effective for allogeneic hematopoietic stem cell transplantation in infants with MECOM-associated syndrome.

Mutations in the MECOM encoding EVI1 are observed in infants who have radioulnar synostosis with amegakaryocytic thrombocytopenia. MECOM-associated syndrome was proposed based on clinical heterogeneity. Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for progressive bone marrow failure. However, data regarding allogeneic HSCT for this rare disease are limited. We retrospectively assessed overall survival, conditioning regimen, regimen-related toxicities and long-term sequelae in six patients treated with allogeneic HSCT. All patients received a reduced-intensity conditioning (RIC) regimen consisting of fludarabine, cyclophosphamide or melphalan, and rabbit anti-thymocyte globulin and/or low-dose total body/thoracic-abdominal/total lymphoid irradiation, followed by allogeneic bone marrow or cord blood transplantation from unrelated donors between 4 and 18 months of age. All patients survived and achieved stable engraftment and complete chimerization with the donor type. Moreover, no patient experienced severe regimen-related toxicities, and only lower grades of acute graft-versus-host disease were observed. Three patients treated with low-dose irradiation had relatively short stature compared to three patients not treated with irradiation. Therefore, allogeneic HSCT with RIC is an effective and feasible treatment for infants with MECOM-associated syndrome. Future studies are needed to evaluate the use of low-dose irradiation to avoid risks of other long-term sequelae.

Time trends in emotional well-being and self-esteem in children and adolescents during the COVID-19 pandemic.

OBJECTIVE: Given their unique COVID-19 pandemic experience, it is necessary to evaluate the mental health of youth beyond the initial stages of the pandemic, in relation to the stringency of the social distancing measures. We aimed to describe long-term trends in emotional well-being and self-esteem among youth in Japan during the pandemic. METHOD: Using serial cross-sectional data from April 2020 to December 2021, we evaluated the trends in emotional well-being and self-esteem of youth aged 6-17 years using the self-report KINDL questionnaire, weighted to represent the age and gender distributions in the Japanese population. We then tested the associations between emotional well-being and self-esteem and stringency of social distancing policies, measured using the Oxford COVID-19 Stringency Index. Analyses were also stratified by gender and age group. RESULTS: The emotional well-being and self-esteem of youth improved transiently in 2020, followed by a slight worsening trend into 2021. While emotional well-being stayed lower compared to initial levels nearly 2 years into the pandemic, self-esteem began to improve by late 2021. 12-17 year-olds had lower emotional well-being and self-esteem compared to 6-11 year-olds throughout the study period. Females had lower emotional well-being than males in May 2020 and lower self-esteem than males in May and September/October 2020. More stringent social distancing measures were associated with lower emotional well-being and self-esteem, especially 6-11 year-olds' self-esteem and females' emotional well-being. CONCLUSION: During the COVID-19 pandemic, older youth tended to have lower emotional well-being and self-esteem than younger youth. Younger and female youth were especially vulnerable to stringent social distancing measures.

Collection of 2429 constrained headshots of 277 volunteers for deep learning.

Deep learning has rapidly been filtrating many aspects of human lives. In particular, image recognition by convolutional neural networks has inspired numerous studies in this area. Hardware and software technologies as well as large quantities of data have contributed to the drastic development of the field. However, the application of deep learning is often hindered by the need for big data and the laborious manual annotation thereof. To experience deep learning using the data compiled by us, we collected 2429 constrained headshot images of 277 volunteers. The collection of face photographs is challenging in terms of protecting personal information; we therefore established an online procedure in which both the informed consent and image data could be obtained. We did not collect personal information, but issued agreement numbers to deal with withdrawal requests. Gender and smile labels were manually and subjectively annotated only from the appearances, and final labels were determined by majority among our team members. Rotated, trimmed, resolution-reduced, decolorized, and matrix-formed data were allowed to be publicly released. Moreover, simplified feature vectors for data sciences were released. We performed gender and smile recognition by building convolutional neural networks based on the Inception V3 model with pre-trained ImageNet data to demonstrate the usefulness of our dataset.

Abusive and positive parenting behavior in Japan during the COVID-19 pandemic under the state of emergency.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic has changed the lives of children and parents, raising concerns about child maltreatment. OBJECTIVE: We examined the prevalence of abusive parenting behavior during the pandemic of the COVID-19 and its relations with physical, psychological, and social factors and positive parenting behavior. PARTICIPANTS AND SETTING: An online survey was performed during the COVID-19 state of emergency in Japan. Participants were 5344 parents of children aged 0-17 years. METHODS: We conducted an anonymous online survey using multiple platforms, including websites of child-related organizations and social networking services (SNS). Multiple logistic regression analyses were performed to identify factors associated with abusive behavior. RESULTS: One-fifth of parents reported abusive behaviors, whereas over 80% of parents reported positive parenting behaviors (e.g., empathizing with a child). Abusive parenting behaviors were associated with longer screen time (6+ hours per day: OR, 1.44; 95%CI, 1.05-1.98), poor maternal mental health (K6 = 13+: OR, 2.23; 95%CI, 1.71-2.89), and the occurrence of domestic violence (OR, 4.54; 95%CI, 3.47-5.95). Positive parenting behaviors, especially showing empathy, were associated with lower risks of abusive behaviors (OR, 0.51: 95%CI, 0.39-0.66). CONCLUSIONS: Positive parenting behavior is essential to the prevention of child maltreatment during the COVID-19 pandemic.

Successful treatment of acute myeloid leukemia co-expressing NUP98/NSD1 and FLT3/ITD with preemptive donor lymphocyte infusions.

Patients with acute myeloid leukemia (AML) co-expressing NUP98/NSD1 and FLT3/ITD have a dismal prognosis despite undergoing hematopoietic stem cell transplantation (HSCT). There are a few studies on successful treatment of relapsed AML co-expressing NUP98/NSD1 and FLT3/ITD. We report a refractory case of molecular relapse of AML co-expressing NUP98/NSD1 and FLT3/ITD post-matched sibling HSCT. Donor lymphocyte infusion (DLI) at an early stage of post-transplantation resulted in complete molecular remission for 29 months with durable chronic graft-versus-host disease. Our case suggests the clinical efficacy of preemptive DLI following minimal residual disease analysis for the treatment of refractory AML.

Recent trends in practice patterns and comparisons between immunoglobulin and corticosteroid in pediatric immune thrombocytopenia.

The clinical benefits and practice patterns of different pharmacologic regimes in acute pediatric immune thrombocytopenia (ITP) remain unclear in Japan. Using a national inpatient database, we analyzed recent trends in practice patterns for acute pediatric ITP, and compared risks of 6-month readmission, total hospitalization costs, and lengths of hospital stay between ITP children treated with intravenous immunoglobulin (IVIG) and corticosteroid, using inverse probability weighting analyses. From 2010 to 2014, the proportions of IVIG use increased from 43.4 to 66.0% (P trend < 0.001), while the proportions of corticosteroid use and watchful waiting decreased from 16.4 to 10% and from 28.6 to 14.3%, respectively (P trend < 0.001). No significant difference in 6-month readmission risk was observed between IVIG and corticosteroid (p = 0.28). Total length of hospital stay in the corticosteroid group was 3.5 days longer than that in IVIG (95% confidence interval, 2.1-4.6 days), whereas total hospitalization cost was greater in IVIG than in corticosteroid (difference, ¥ 207,994; 95% confidence interval, ¥ 149586-¥ 280728). A trend toward increased IVIG use was observed during the study period. Total hospitalization cost was considerably greater in the IVIG than in the corticosteroid group, whereas readmission risks were similar in both groups.

Relapsed acute lymphoblastic leukemia with unusual multiple bone invasions: A case report.

The present study describes a unique pediatric case with multiple bone invasions of acute lymphoblastic leukemia (ALL) during remission. An eight-year-old male with a history of ALL was admitted complaining of intermittent and migrating pain in the limb 2 years following complete remission. Magnetic resonance imaging and whole-body positron emission tomography with 18F-fluorodeoxyglucose revealed abnormal multifocal involvement in the bones and corresponding soft tissues. Repeated bone marrow (BM) aspiration indicated normal cellular marrow without leukemic cells, and marked leukemic cell infiltration in different sections of the ilium, respectively. These findings suggested isolated bone relapse, and it is probable that systematic BM relapse occurred as a consequence.