Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/ped.14625

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Variants in the type IV collagen gene (COL4A1/2) cause early-onset cerebrovascular diseases. Most individuals are diagnosed postnatally, and the prenatal features of individuals with COL4A1/2 variants remain unclear. METHODS: We examined COL4A1/2 in 218 individuals with suspected COL4A1/2-related brain defects. Among those arising from COL4A1/2 variants, we focused on individuals showing prenatal abnormal ultrasound findings and validated their prenatal and postnatal clinical features in detail. RESULTS: Pathogenic COL4A1/2 variants were detected in 56 individuals (n=56/218, 25.7%) showing porencephaly (n=29), schizencephaly (n=12) and others (n=15). Thirty-four variants occurred de novo (n=34/56, 60.7%). Foetal information was available in 47 of 56 individuals, 32 of whom (n=32/47, 68.1%) had one or more foetal abnormalities. The median gestational age at the detection of initial prenatal abnormal features was 31 weeks of gestation. Only 14 individuals had specific prenatal findings that were strongly suggestive of features associated with COL4A1/2 variants. Foetal ventriculomegaly was the most common initial feature (n=20/32, 62.5%). Posterior fossa abnormalities, including Dandy-Walker malformation, were observed prenatally in four individuals. Regarding extrabrain features, foetal growth restriction was present in 16 individuals, including eight individuals with comorbid ventriculomegaly. CONCLUSIONS: Prenatal observation of ventriculomegaly with comorbid foetal growth restriction should prompt a thorough ultrasound examination and COL4A1/2 gene testing should be considered when pathogenic variants are strongly suspected.

DOI： 10.1136/jmedgenet-2020-106896

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Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Although imatinib is the first-line of therapy for Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML), in Japan, it is recommended by the manufacturer that lactating women treated with imatinib mesylate for CML should discontinue breastfeeding their infants. CASE: A 32-year-old pregnant patient was diagnosed with Ph-positive CML at 13 weeks of gestation. She received imatinib (400 mg/day) after 28 weeks of gestation. A female infant was delivered at a gestational age of 35 weeks and 3/7 days after preterm premature rupture of membranes. It was decided to feed only colostrum to the infant and formula feeding was done subsequently because of the risk of the transfer of imatinib to breast milk. The milk/plasma (M/P) ratio and the relative infant dose (RID) for imatinib were calculated to be 0.35 and 1.4%, respectively at 5 days of life. Moreover, the serum level of imatinib in the child of age 5 days was 27 ng/mL, which was much lower than the target trough value for CML (1000 ng/mL). CONCLUSION: The M/P ratio and RID values for maternally administered imatinib were within the safe range for breastfeeding, as reported in previous studies. In addition, it was found that the serum concentration of imatinib in the child was relatively low during short-term breastfeeding.

DOI： 10.1177/1078155220948942

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(財)小児愛育協会  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(財)小児愛育協会  

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Language：Japanese   Publisher：(株)メディカ出版  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2020&ichushi_jid=J07193&link_issn=&doc_id=20201110130009&doc_link_id=%2Fao7withi%2F2020%2F003306%2F014%2F0890-0892%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fao7withi%2F2020%2F003306%2F014%2F0890-0892%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：日本小児臨床薬理学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Basal meningoceles are rare congenital defects and often clinically occult until they result in life-threatening complications. Therefore, it is important to know the diagnostic clues to early diagnosis. CASE PRESENTATION: We describe three cases of congenital basal meningocele in a 3-year-old Japanese boy, a 1-month-old Japanese baby boy, and a 10-month-old Japanese baby girl. One of our patients died of sepsis due to traumatic rupture of the meningocele during nasal suction. His meningocele remained undiagnosed until it resulted in the fatal complication. The other patients underwent surgical repair without any complications. Their meningoceles were complicated by midfacial anomalies including cleft palate and hypertelorism, or a sign of nasal obstruction such as snoring. CONCLUSIONS: These clinical features may be a clue to the early diagnosis of congenital basal meningocele, which enables its safe preoperative management and provides an opportunity for surgical repair before the condition results in serious complications.

DOI： 10.1186/s13256-017-1497-7

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Language：English   Publishing type：Research paper (scientific journal)  

Short-rib polydactyly syndrome type III is an autosomal recessive lethal skeletal ciliopathy, which is phenotypically similar to nonlethal asphyxiating thoracic dystrophy. Mutations in DYNC2H1 have been identified in both of these disorders, indicating that they are variants of a single disorder. However, short-rib polydactyly syndrome type III is the more severe variant. Here, we report novel compound heterozygous mutations in DYNC2H1 (p.E1894fsX10 and p.R3004C) in a patient with typical short-rib polydactyly syndrome type III phenotype. R3004 is located within the microtubule-binding domain of DYNC2H1, and its substitution is predicted to disrupt the interaction with microtubules. Considering the severe phenotype of our patient, our findings suggest that R3004 may be a key residue for the microtubule-binding affinity of dynein.

DOI： 10.1111/cga.12098

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: There is little available data on airway humidity during high-frequency ventilation (HFV). The purpose of this study is to evaluate the temperature drop in an endotracheal tube (ETT) during HFV. METHODS: We examined the airway temperature in a neonatal HFV system using Babylog® 8000 plus. We measured the temperature change of inspired gases in the ETT under various oscillatory frequencies and oscillatory volumes with a fixed base flow. The temperatures in the ETT during HFV were compared with the temperatures during conventional intermittent positive pressure ventilation (IPPV). RESULTS: As the oscillatory frequency was increased and the oscillatory volume (VThf) decreased, the difference in temperature between the Y piece and the inlet of an artificial lung in the ETT (ETT outside of body) increased. However, as the oscillatory frequency increased, there was no difference in the ETT temperature under constant oscillatory volume. In contrast, as the oscillatory volume was decreased, the difference in temperature in the ETT was greater under constant oscillatory frequency. Moreover, the temperature drop in the ETT with HFV was lower than that in the IPPV temperature with a similar respiratory volume. CONCLUSIONS: The temperature change in the ETT was not dependent on the oscillatory frequency when the oscillatory volume was fixed; however, the temperature was dependent on the oscillatory volume when the oscillatory frequency was fixed.

DOI： 10.1002/ppul.22973

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(公社)日本小児科学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND AND PURPOSE: A thrombosed dural sinus malformation (DSM) is a rare condition, the clinical features of which have not yet been completely characterized. Here, we describe the clinical course of a patient with a thrombosed DSM and discuss the outcomes in live birth cases from a review of the literature. CASE DESCRIPTION: An ultrasonography examination of a 32-year-old woman at 25 weeks' gestation indicated a fetal posterior fossa mass. The size of the intracranial mass remained constant during the second trimester and was observed to decrease from 33 weeks of gestation. A postnatal diagnosis of thrombosis in the dural sinus was established by magnetic resonance imaging and venography. No brain damage or hydrocephalus was noted. Although the circumference of the infant's head was enlarged at birth, her neurological outcome was normal at 1 year of age. CONCLUSIONS: Although normal cranial circumference is reportedly an essential factor for a favorable prognosis, the patient in this report with a cranial circumference at + 2.0 SD (35.6 cm) had a favorable prognosis. Further studies focused on improving clinical diagnostic accuracy in this rare entity will facilitate appropriate counseling.

DOI： 10.1111/jon.12099

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Since the mid-1980s, there have been increasing reports of severe invasive group A streptococcal (GAS) disease in children and adults. There are few reports, however, of neonatal invasive disease, particularly neonatal pleural empyema caused by GAS. Although many mechanisms have been reported for the pathophysiology of invasive GAS infections, similar reports for neonates were unable to be located. Reported herein is the case of a 3-day-old girl with pleural empyema caused by GAS that demonstrated a high invasive capacity for human epithelial cells.

DOI： 10.1111/ped.12061

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Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)   Publisher：名寄市立総合病院  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J03201&link_issn=&doc_id=20130822210008&doc_link_id=https%3A%2F%2Fsapmed.repo.nii.ac.jp%2Frecords%2F13684&url=https%3A%2F%2Fsapmed.repo.nii.ac.jp%2Frecords%2F13684&type=%E6%9C%AD%E5%B9%8C%E5%8C%BB%E7%A7%91%E5%A4%A7%E5%AD%A6%EF%BC%9A%E6%9C%AD%E5%B9%8C%E5%8C%BB%E7%A7%91%E5%A4%A7%E5%AD%A6%E5%AD%A6%E8%A1%93%E6%A9%9F%E9%96%A2%E3%83%AA%E3%83%9D%E3%82%B8%E3%83%88%E3%83%AA_ikor&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80183_3.gif

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: As the presence of fetal hemoglobin (HbF) affects the accuracy of hemoglobin A1c (HbA1c) analysis methods, HbA1c measurement may not be a good indicator for patients with neonatal diabetes mellitus, whereas glycated albumin (GA) may be a good indicator. OBJECTIVE: To investigate whether total glycated hemoglobin (GHb) or HbF-adjusted HbA1c (adj-HbA1c) can act as a glycemic control marker in infants. SUBJECTS AND METHODS: Plasma glucose (PG), GA, HbF, GHb measured using the affinity method, and HbA1c measured using the latex-immunoturbidimetry (LA) or the high-performance liquid chromatography (HPLC) methods were determined in 26 full-term newborn infants aged 4-234 d. Adj-HbA1c was calculated as HbA1c/(total Hb - HbF). RESULTS: GHb, adj-HbA1c measured using the LA and the HPLC methods were 4.8 ± 0.5%, 4.5 ± 0.5%, and 4.7 ± 0.6%, respectively. GA was most positively correlated with PG (r = 0.696, p < 0.0001). GHb was positively correlated with both PG (r = 0.479, p = 0.013) and GA (r = 0.727, p < 0.0001). Adj-HbA1c measured using the LA method was positively correlated with GA (r = 0.465, p = 0.017), but not PG (r = 0.304, p = 0.132). Adj-HbA1c measured using the HPLC method was correlated with neither PG (r = -0.077, p = 0.710) nor GA (r = 0.360, p = 0.071). CONCLUSIONS: GHb measured using the affinity method may be a useful glycemic control marker in infants. Although adj-HbA1c measured using the LA method was correlated with GA, it may not be a practical measure because it was not correlated with PG and determining HbF levels using HPLC method can be troublesome. Adj-HbA1c measured using the HPLC method should not be used as a glycemic marker in infants.

DOI： 10.1111/pedi.12013

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Glycated albumin (GA) reflects glycemic control in patients with neonatal diabetes mellitus (NDM). However, GA in NDM patients is apparently low in relation to glycemia. OBJECTIVE: To establish the reference intervals for GA in healthy infants. SUBJECTS AND METHODS: Fifty-eight healthy, full-term newborn infants were used to define the GA reference values and to investigate its relationship to plasma glucose (PG) and serum albumin. The infants were categorized into three groups according to age: group A, 5 (4-6) median (range) d: n = 18; group B, 33 (30-38) d: n = 19; and group C, 181 (50-352) d: n = 21. We also studied 212 non-diabetic adults [group D, 53 (28-78) yr old] and the 5 NDM patients previously reported for GA comparisons. RESULTS: In the infants, GA was strongly positively correlated with logarithmic transformation of age [log (age)] (p = 0.831, p < 0.0001). The GA in groups A, B, C, and D were 7.3 ± 1.0%, 8.6 ± 1.1%, 10.9 ± 0.8%, and 14.0 ± 1.1%, respectively. The GA was more strongly positively correlated with serum albumin (r = 0.768, p < 0.0001) than with PG (r = 0.596, p < 0.0001). When GA levels were compared with the age-dependent reference values, GA in the transient NDM patient was normalized although GA in the four permanent NDM patients decreased but remained high after insulin therapy. CONCLUSIONS: This study showed that the reference range for GA in infants is lower than that of adults and increases with age, with which we confirmed that GA in the NDM patients reflected the clinical course. Consequently, GA in NDM patients should be compared with the age-based reference values to assess the accurate glycemic status.

DOI： 10.1111/j.1399-5448.2012.00895.x

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Language：English   Publishing type：Research paper (scientific journal)  

Heterozygous COL2A1 mutations create a group of skeletal dysplasias collectively termed type II collagenopathies. Sporadic cases of type II collagenopathies are almost exclusively caused by de novo mutations. Very few cases with intrafamilial recurrence due to germinal mosaicism have been known. We report here on a family in which a severe form of skeletal dysplasia was recurrent in two sibs whose phenotype was most consistent with platyspondylic lethal skeletal dysplasia Torrance type (PLSD-T). A COL2A1 analysis showed that the two sibs had a heterozygous mutation in the encoded triple helical region of COL2A1, c.3545G>A (p.Gly1182Asp) in exon 50. The parents did not consent to a molecular analysis; however, the presence of the same mutation in the two sibs is proof of germinal mosaicism in one of the parents. PLSD-T has been shown to arise from a heterozygous dominant negative COL2A1 mutation in the encoded C-propeptide region. However, our observation suggests that the phenotype is also caused by a COL2A1 mutation in the encoded C-terminal triple helical region.

DOI： 10.1002/ajmg.a.35509

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本小児感染症学会  

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BACKGROUND: Disseminated neonatal herpes simplex virus (HSV) infection causes a typical systemic inflammatory response syndrome and has a high mortality rate. However, the validity of anti-inflammatory intervention against this condition remains unknown. OBJECTIVES: We sought to demonstrate the sequential changes in the pathophysiology of disseminated neonatal HSV infections. STUDY DESIGN: The HSV serum copy number as well as high-mobility group box 1 (HMGB1) and cytochrome c concentrations, which predict the severity and mortality rate of sepsis, were sequentially evaluated in a patient with disseminated neonatal HSV infection caused by HSV-2. RESULTS: As the patient presented with evidence of hyper-inflammation and severe illness, we empirically undertook anti-inflammatory intervention that included the administration of prednisolone, high-dose immunoglobulin, and blood exchange therapy in addition to high-dose acyclovir (ACV) therapy. The patient survived without significant neurological sequela. We found that (1) the serum concentrations of both HMGB1 and cytochrome c were extremely high, (2) temporal increases in these biomarkers were observed after admission, and (3) interestingly, the increase in HMGB1 level preceded that of cytochrome c. These results suggested that the pathophysiology of this condition changed sequentially in a dramatic manner, and the timing of our anti-inflammatory intervention was prior to the transition of pathological status from hyper-inflammation to massive apoptosis. CONCLUSIONS: Anti-inflammatory intervention may only be effective if it is undertaken during the early phase of disseminated neonatal HSV infections.

DOI： 10.1016/j.jcv.2011.12.017

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)   Publisher：旭川医科大学  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2012&ichushi_jid=J03513&link_issn=&doc_id=20120315450025&doc_link_id=https%3A%2F%2Fasahikawa-med.repo.nii.ac.jp%2Frecords%2F3783&url=https%3A%2F%2Fasahikawa-med.repo.nii.ac.jp%2Frecords%2F3783&type=%E6%97%AD%E5%B7%9D%E5%8C%BB%E7%A7%91%E5%A4%A7%E5%AD%A6%EF%BC%9A%E6%97%AD%E5%B7%9D%E5%8C%BB%E7%A7%91%E5%A4%A7%E5%AD%A6%E5%AD%A6%E8%A1%93%E6%88%90%E6%9E%9C%E3%83%AA%E3%83%9D%E3%82%B8%E3%83%88%E3%83%AA_AMCoR&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80003_3.gif

Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(公社)日本小児科学会  

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)   Publisher：旭川厚生病院  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2010&ichushi_jid=J02713&link_issn=&doc_id=20101124290001&doc_link_id=%2Fer6asahi%2F2010%2F002001%2F002%2F0003-0008%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fer6asahi%2F2010%2F002001%2F002%2F0003-0008%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)   Publisher：旭川厚生病院  

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Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)   Publisher：旭川厚生病院  

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Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)   Publisher：旭川厚生病院  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(財)小児愛育協会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2007&ichushi_jid=J01547&link_issn=&doc_id=20070615450001&doc_link_id=%2Fda3risyo%2F2007%2F005501%2F001%2F0003-0009%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fda3risyo%2F2007%2F005501%2F001%2F0003-0009%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本周産期・新生児医学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2006&ichushi_jid=J04116&link_issn=&doc_id=20060515390001&doc_link_id=%2Fdy1jspnm%2F2006%2F004201%2F001%2F0001-0006%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdy1jspnm%2F2006%2F004201%2F001%2F0001-0006%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)   Publisher：旭川厚生病院  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2005&ichushi_jid=J02713&link_issn=&doc_id=20051108430001&doc_link_id=%2Fer6asahi%2F2005%2F001501%2F002%2F0003-0009%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fer6asahi%2F2005%2F001501%2F002%2F0003-0009%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(財)小児愛育協会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2005&ichushi_jid=J01547&link_issn=&doc_id=20050907040007&doc_link_id=%2Fda3risyo%2F2005%2F005301%2F007%2F0033-0038%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fda3risyo%2F2005%2F005301%2F007%2F0033-0038%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)   Publisher：旭川厚生病院  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(財)小児愛育協会  

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Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)   Publisher：旭川厚生病院  

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Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)   Publisher：旭川厚生病院  

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Event date： 2005.12

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Audience： Teachers,　General

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Type：Certification seminar

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Audience： Teachers,　Guardians,　General

Type：Lecture

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