{"title":"Does COVID-19 predispose patients to type 1 diabetes mellitus?","authors":"Aysun Ata, Arzu Jalilova, Tarık Kırkgöz, Hafize Işıklar, Günay Demir, Yasemin Atik Altınok, Behzat Özkan, Ayşin Zeytinlioğlu, Şükran Darcan, Samim Özen, Damla Gökşen","doi":"10.1297/cpe.2021-0050","DOIUrl":"https://doi.org/10.1297/cpe.2021-0050","url":null,"abstract":"<p><p>The novel coronavirus disease (COVID-19) has emerged as a global pandemic. This was a prospective, case-control study conducted in Izmir, Turkey. The aim of this study was to assess the relationship between COVID-19 and new-onset T1DM. We included pediatric patients (aged 6 mo-18 yr) with new-onset type-1 diabetes mellitus (T1DM) diagnosed during the COVID-19 pandemic, between April 2020 and January 2021. Polymerase chain reaction was used to diagnose COVID-19 after hospital admission. An enzyme-linked immunoassay for IgM and IgG against SARS-CoV-2 was performed after the diagnosis was confirmed. In the control group, the blood antibody test was conducted as close as possible to the time of the T1DM patient referral. A total of 118 participants were included in the study, comprising 57 (48%) patients with new-onset T1DM and 61 (52%) healthy controls. Of the 57 patients, 36 (63.2%) presented with DKA, 17 (29.7%) with diabetic ketosis, and four (7%) incidentally. The SARS-CoV-2 antibody test was positive in five (8.7%) patients with T1DM and six (10%) controls. The rate of positivity did not differ between the two groups (p = 0.901). It was not possible to demonstrate a clear association between SARS-CoV-2 infection and new-onset T1DM. Whether SARS-CoV-2 increases susceptibility to diabetes by triggering islet cell autoimmunity and affects the timing of overt diabetes in patients with existing autoimmunity should be studied in large cohorts.</p>","PeriodicalId":10678,"journal":{"name":"Clinical Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/07/14/cpe-31-033.PMC8713063.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39660862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yukiko Ueta, Keiko Aso, Youichi Haga, Hiroyuki Takahashi, Mari Satoh
{"title":"Congenital hypogonadotropic hypogonadism complicated by neuroblastoma.","authors":"Yukiko Ueta, Keiko Aso, Youichi Haga, Hiroyuki Takahashi, Mari Satoh","doi":"10.1297/cpe.2021-0070","DOIUrl":"https://doi.org/10.1297/cpe.2021-0070","url":null,"abstract":"<p><p>A 3-mo-old male infant was referred to our hospital with micropenis. Since his serum LH, FSH, and testosterone levels were low (< 0.3 mIU/mL, 0.08 mIU/mL, and < 0.03 ng/mL, respectively), Kallmann syndrome/normosmic hypogonadotropic hypogonadism was suspected. In the process of searching for complications of Kallmann syndrome/normosmic hypogonadotropic hypogonadism, a right adrenal gland tumor was incidentally discovered. The patient was diagnosed with stage 1 neuroblastoma. A homozygous p.P147L (c.C440T) mutation in the <i>KISS1R</i> gene was detected as a cause of the congenital hypogonadotropic hypogonadism. KISS1-KISS1R signaling, which is essential for GnRH secretion, exhibits anti-metastatic and/or anti-tumoral roles in numerous cancers. High <i>KISS1</i> expression levels reportedly predict better survival outcomes than low <i>KISS1</i> expression levels in neuroblastoma. Therefore, decreased KISS1-KISS1R signaling may have played a role in the neuroblastoma in this patient.</p>","PeriodicalId":10678,"journal":{"name":"Clinical Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/87/2e/cpe-31-159.PMC9297168.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40694815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Irine-Ikbale Sakou, Alexandra Soldatou, Aristeidis Seretis, Evangelos Karanasios, George Paltoglou, Kyriaki Karavanaki
{"title":"Markedly elevated troponin and NT-proBNP and myocardial dysfunction in an adolescent with severe diabetic ketoacidosis: A case report.","authors":"Irine-Ikbale Sakou, Alexandra Soldatou, Aristeidis Seretis, Evangelos Karanasios, George Paltoglou, Kyriaki Karavanaki","doi":"10.1297/cpe.2022-0017","DOIUrl":"https://doi.org/10.1297/cpe.2022-0017","url":null,"abstract":"<p><p>Severe diabetic ketoacidosis (DKA), rarely, may be associated with elevated troponin and proBNP levels in adults with a history of diabetes. However, few cases have reported this association in children with severe and complicated DKA. We describe a case of severe DKA (pH: 6.89, HCO3: 6.5) in a 14-yr-old female adolescent in which the symptoms of DKA were presented days before the diagnosis. The patient was under the effect of acidosis (Kussmaul respiration) for 12 h before admission to our hospital, where she was admitted in a critical clinical condition. After successful treatment with DKA with intensive intravenous fluid and regular insulin, the patient presented with abnormal cardiac rhythm, disturbance of interventricular septum motility, a mild decrease in left ventricular systolic function, negative T waves in leads III and aVF, and a marked increase in troponin and brain natriuretic peptide (NT-proBNP) levels. All abnormal findings completely resolved within 8 days after the initiation of DKA treatment. The phenomenon in our case was transient, and the patient had a good long-term outcome. However, it represents a challenge for clinicians; therefore, emphasis should be given to cardiac monitoring during the course of severe and prolonged DKA in children and adolescents.</p>","PeriodicalId":10678,"journal":{"name":"Clinical Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f9/34/cpe-31-192.PMC9297169.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40694818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah Wing-Yiu Poon, Brian Hon-Yin Chung, Mandy Ho-Yin Tsang, Joanna Yuet-Ling Tung
{"title":"Successful transition from insulin to sulphonylurea in a child with neonatal diabetes mellitus diagnosed beyond six months of age due to C42R mutation in the <i>KCNJ11</i> gene.","authors":"Sarah Wing-Yiu Poon, Brian Hon-Yin Chung, Mandy Ho-Yin Tsang, Joanna Yuet-Ling Tung","doi":"10.1297/cpe.2022-0013","DOIUrl":"https://doi.org/10.1297/cpe.2022-0013","url":null,"abstract":"<p><p>Neonatal diabetes mellitus is a rare monogenic condition affecting 1 in 100,000-300,000 live births. Mutations in the subunits of ATP-sensitive potassium (K<sub>ATP</sub>) channels, which are the central gatekeepers of electrical activity, are the common cause of this condition, thereby reducing insulin secretion in the pancreatic beta cells. Most cases are diagnosed before 6 mo of age. The development of this condition in the latter half of the first year of life is rare; hence, testing in older infants is not routinely performed. Here, we describe the case of a patient who presented with neonatal diabetes mellitus and diabetic ketoacidosis at 10 mo of age. All the pancreatic autoantibodies were undetectable, prompting us to pursue genetic testing. At 13 yr of age, a heterozygous missense variant, C42R, was identified in the <i>KCNJ11</i> gene by exome sequencing. Subsequently, sulfonylurea was initiated, and insulin therapy was discontinued that resulted in improved blood glucose control and increased C-peptide levels. Given the potential benefit of switching to oral medication, genetic testing should be extended to all infants diagnosed with antibody-negative diabetes before 1 yr of age.</p>","PeriodicalId":10678,"journal":{"name":"Clinical Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f2/a7/cpe-31-168.PMC9297163.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40671781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genetic causes of central precocious puberty.","authors":"Toshihiro Tajima","doi":"10.1297/cpe.2022-0021","DOIUrl":"https://doi.org/10.1297/cpe.2022-0021","url":null,"abstract":"<p><p>Central precocious puberty (CPP) is a condition in which the hypothalamus-pituitary-gonadal system is activated earlier than the normal developmental stage. The etiology includes organic lesions in the brain; however, in the case of idiopathic diseases, environmental and/or genetic factors are involved in the development of CPP. A genetic abnormality in <i>KISS1R</i>, that encodes the kisspeptin receptor, was first reported in 2008 as a cause of idiopathic CPP. Furthermore, genetic alterations in <i>KISS1</i>, <i>MKRN3</i>, <i>DLK1</i>, and <i>PROKR2</i> have been reported in idiopathic and/or familial CPP. Of these, <i>MKRN3</i> has the highest frequency of pathological variants associated with CPP worldwide; but, abnormalities in <i>MKRN3</i> are rare in patients in East Asia, including Japan. <i>MKRN3</i> and <i>DLK1</i> are maternal imprinting genes; thus, CPP develops when a pathological variant is inherited from the father. The mechanism of CPP due to defects in <i>MKRN3</i> and <i>DLK1</i> has not been completely clarified, but it is suggested that both may negatively control the progression of puberty. CPP due to such a single gene abnormality is extremely rare, but it is important to understand the mechanisms of puberty and reproduction. A further development in the genetics of CPP is expected in the future.</p>","PeriodicalId":10678,"journal":{"name":"Clinical Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/74/4c/cpe-31-101.PMC9297165.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40694814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Goiter in a 6-year-old patient with novel thyroglobulin gene variant (Gly145Glu) causing intracellular thyroglobulin transport disorder: Correlation between goiter size and the free T3 to free T4 ratio.","authors":"Misayo Matsuyama, Hirotake Sawada, Shinobu Inoue, Akira Hishinuma, Ryo Sekiya, Yuichiro Sato, Hiroshi Moritake","doi":"10.1297/cpe.2022-0006","DOIUrl":"https://doi.org/10.1297/cpe.2022-0006","url":null,"abstract":"<p><p>Thyroglobulin gene abnormalities cause thyroid dyshormonogenesis. A 6-yr-old boy of consanguineous parents presented with a large goiter and mild hypothyroidism (thyroid-stimulating hormone [TSH] 7.2 μIU/mL, free T3 [FT3] 3.4 pg/mL, free T4 [FT4] 0.6 ng/dL). Despite levothyroxine (LT4) administration and normal TSH levels, the goiter progressed slowly and increased rapidly in size at the onset of puberty. Thyroid scintigraphy revealed a remarkably high <sup>123</sup>I uptake of 75.2%, with a serum thyroglobulin level of 13 ng/ml, which was disproportionately low for the goiter size. DNA sequencing revealed a novel homozygous missense variant, c.434G>A [p.Gly145Glu], in the thyroglobulin gene. Goiter growth was suppressed by increasing the LT4 dose. Thyroidectomy was performed at 17-yr-of-age. Thyroglobulin analysis of the thyroid tissue detected mutant thyroglobulin present in the endoplasmic reticulum, demonstrating that thyroglobulin transport from the endoplasmic reticulum to the Golgi apparatus was impaired by the Gly145Glu variant. During the clinical course, an elevated FT3/FT4 ratio was observed along with thyroid enlargement. A high FT3/FT4 ratio and goiter seemed to be compensatory responses to impaired hormone synthesis. Thyroglobulin defects with goiter should be treated with LT4, even if TSH levels are normal.</p>","PeriodicalId":10678,"journal":{"name":"Clinical Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1d/21/cpe-31-185.PMC9297170.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40583170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I Wayan Eka Satriawibawa, I Made Arimbawa, Ketut Ariawati, Ida Bagus Gede Suparyatha, I Gusti Ngurah Sanjaya Putra, I Nyoman Budi Hartawan
{"title":"Serum iron is negatively correlated with the HbA1c level in children and adolescents with type 1 diabetes mellitus.","authors":"I Wayan Eka Satriawibawa, I Made Arimbawa, Ketut Ariawati, Ida Bagus Gede Suparyatha, I Gusti Ngurah Sanjaya Putra, I Nyoman Budi Hartawan","doi":"10.1297/cpe.2022-0012","DOIUrl":"https://doi.org/10.1297/cpe.2022-0012","url":null,"abstract":"<p><p>Although mainly affected by the blood glucose levels, the level of HbA1c could be influenced by other important factors, such as an iron deficiency, which is commonly found in children with type 1 diabetes mellitus (T1DM). However, a clinical judgment could not be established, as previous studies still reported conflicting results and lack of data regarding Indonesia. We aimed to evaluate the correlation between the serum iron and HbA1c levels in children with T1DM. This single-center cross-sectional study was conducted from February to October 2020 at Sanglah Hospital, Bali, Indonesia. Patients aged 1-18 yr were included in this study. The HbA1c and serum iron levels were evaluated in the blood samples. Spearman and partial correlation analyses were used to analyze the correlations between variables. The statistical significance was set at <i>P</i> < 0.05. Thirty-three subjects were analyzed, with a mean age of 11.24 ± 3.76 yr. Low serum iron and poor glycemic index were found in 54.5% and 69.7% of the subjects, respectively. Spearman correlation analysis revealed a low negative correlation between the serum iron and HbA1c levels (Spearman's rho = -0.376, <i>P</i> = 0.031). A partial correlation showed a moderate negative correlation (r = -0.473, <i>P</i> = 0.013) after adjusting for confounding variables. This study found a moderate negative correlation between the serum iron and HbA1c level in children and adolescents with T1DM.</p>","PeriodicalId":10678,"journal":{"name":"Clinical Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c3/0c/cpe-31-242.PMC9637419.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40714822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The clinical course of Rathke's cleft cysts in pediatric patients: impact on growth and pubertal development.","authors":"Yousuke Higuchi, Kosei Hasegawa, Toshihide Kubo, Hiroyuki Tanaka, Hirokazu Tsukahara","doi":"10.1297/cpe.2021-0034","DOIUrl":"https://doi.org/10.1297/cpe.2021-0034","url":null,"abstract":"<p><p>Rathke's cleft cysts (RCCs) are non-neoplastic epithelial lesions in the sellar or suprasellar regions. RCCs are usually asymptomatic; however, some patients experience headaches, visual disturbances, and endocrine disorders. The best treatment for associated endocrinopathy remains elusive. We aimed to investigate the clinical course, magnetic resonance imaging findings, and response to therapy in 10 pediatric patients with RCCs and endocrinopathy. Growth impairment and precocious puberty were observed to be prevalent. One patient with suprasellar extension of RCC underwent surgery, while the others were treated medically. Of the nine patients, seven patients showed stable cyst size, while two patients displayed reduction in cyst size. Hormone replacement and gonadotropin suppression therapy were found to be effective. Imaging and endocrine follow-ups are warranted because of the potential for changes in the cyst size and hormonal changes.</p>","PeriodicalId":10678,"journal":{"name":"Clinical Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/42/1d/cpe-31-038.PMC8713062.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39660863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Partial nephrogenic diabetes insipidus with a novel arginine vasopressin receptor 2 gene variant.","authors":"Atsushi Ishida, Haruo Mizuno, Kohei Aoyama, Shiori Sasaki, Yutaka Negishi, Takeshi Arakawa, Takayasu Mori","doi":"10.1297/cpe.2021-0029","DOIUrl":"https://doi.org/10.1297/cpe.2021-0029","url":null,"abstract":"<p><p>X-linked nephrogenic diabetes insipidus (NDI) is caused by variations in arginine vasopressin receptor 2 (<i>AVPR2</i>). Some patients show partial resistance to arginine vasopressin (AVP). A 19-month-old Japanese boy presented with polydipsia since infancy. His mother had a history of polydipsia during pregnancy, and his maternal granduncle also had polydipsia. Intermediate urine osmolality and markedly high plasma AVP levels were observed in the water deprivation test. Subsequent pitressin administration caused no further elevation in urine osmolality. We diagnosed the patient with partial NDI, initiated therapy with hydrochlorothiazide, and placed him on a low-sodium diet. Although his urine volume decreased by 20-30% after the initiation of therapy, progressive hydronephrosis and growth retardation developed 2 years later. We investigated his genetic background by multiplex targeted sequencing of genes associated with inherited renal diseases, including <i>AVPR2</i> and aquaporin-2 (<i>AQP2</i>). We identified a hemizygous missense variant in <i>AVPR2</i> NM_000054:c.371A>G,p.(Tyr124Cys) in the boy and a heterozygous variant in the mother at the same locus. Distinguishing partial NDI from primary polydipsia is difficult because of its mild symptoms. Markedly elevated plasma AVP levels with intermediate urine osmolality may suggest partial NDI, and genetic analysis can be useful for such patients.</p>","PeriodicalId":10678,"journal":{"name":"Clinical Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/19/88/cpe-31-044.PMC8713061.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39660864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Urinary stone in a 12-year-old adolescent with new-onset type 1 diabetes and diabetic ketoacidosis.","authors":"Kikumi Ushijima-Fuchino, Yuko Koga, Satoko Umino, Junko Nishioka, Junichiro Araki, Shuichi Yatsuga, Yushiro Yamashita","doi":"10.1297/cpe.2021-0069","DOIUrl":"https://doi.org/10.1297/cpe.2021-0069","url":null,"abstract":"<p><p>Dehydration and acidosis increase the risk for urinary stone formation. Urinary stones have been reported in three pediatric cases of diabetic ketoacidosis (DKA). A 24-h urine collection was performed for two of the three children. One patient had high urine sodium levels, while the other had low urine citrate excretion. We report the case of a 12-yr-old adolescent boy with urinary stones, new-onset type 1 diabetes mellitus (T1D), and DKA, excluding other metabolic disorders. After DKA was diagnosed, the patient received a 0.9% saline bolus and continuous insulin infusion. Hyperglycemia and ketoacidosis were well-controlled on the third day after admission. However, the patient developed abdominal pain radiating to the back. Urinary stones were suspected, and a urinalysis was performed. The patient's urine revealed significant elevation in red blood cells and calcium oxalate crystals. Computed tomography revealed a high-density left ureteric mass, suggestive of a urinary stone. Although both the previously reported pediatric cases involved metabolic diseases, additional tests in this patient excluded metabolic diseases other than T1D. DKA may be related to the formation of calcium oxalate crystals owing to dehydration and acidosis. Therefore, physicians should consider urinary stone formation in DKA patients.</p>","PeriodicalId":10678,"journal":{"name":"Clinical Pediatric Endocrinology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d4/95/cpe-31-199.PMC9297177.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40694819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}