bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gonadal tumor risk in pediatric and adolescent phenotypic females with disorders of sex development and Y chromosomal constitution with different genetic etiologies
Authors: Lu Liangsheng , Luo Feihong , Wang Xiang 
Published: July 2022

ObjectivesThis retrospective study sought to investigate the risk and proportion of gonadal neoplasms in phenotypic female pediatric patients with DSD and the presence of the Y chromosome and different genetic backgrounds in a single Chinese center.Materials and MethodsFrom January 2012 to December 2020, pediatric and adolescent patients with DSD and the presence of the Y chromosome who had unambiguous female genitalia and underwent bilateral gonadectomy or gonadal biopsy were included in this study. Patients’ demographics, karyotype, laboratory test results, gross pathology, and histology of gonadal tissue were all collected. The patients were divided into three groups based on their different genetic backgrounds, and the percentage of gonadal tumors was calculated to assess the risk of gonadal tumor and malignancy by etiology.ResultsA total of 22 patients with DSD and an unambiguous female phenotype with a Y chromosome were recruited. The mean age was 10.91 ± 4.99 years (9 months to 19 years). Gonadal neoplasia was confirmed in six (27.3%) cases by pathological examination of surgical gonadal tissue samples. Among 44 gonadal samples from these 22 patients, the following were identified: five gonadoblastomas, three dysgerminomas, and two Leydig cell tumors. The youngest patient with a tumor was a 2-year-old girl with 46,XY complete gonadal dysgenesis (46,XY CGD or Swyer syndrome) and bilateral gonadoblastoma. Patients with 46,XY complete gonadal dysgenesis (4/6; 66.7%) had the highest tumor occurrence rate. Among 10 patients with Turner syndrome with the presence of the Y chromosome, only one patient was diagnosed with a gonadal tumor. Leydig cell tumor was diagnosed in only one of six patients with 46,XY androgen synthesis/action disorders.ConclusionPediatric patients with 46,XY complete gonadal dysgenesis had a significantly increased risk of developing gonadal tumors and underwent prophylactic gonadectomy as soon as the diagnosis was confirmed, whereas those with Turner syndrome with Y chromosome and 46,XY androgen synthesis/action disorders had a relatively low risk. In view of the limited number of patients, a large multicenter study with close follow-ups is needed to support these conclusions.
Separation Practices in Children and Adolescents Admitted for Suicidal Behavior: A National Survey of French Psychiatrists
Authors: Payet Maymouna Mourouvaye , Bonfils Nicolas A. , Ouss Lisa , Fourcade Lola J. , Touati-Pellegrin Marie , Golse Bernard , Cohen Jérémie F. , Woestelandt Laure 
Published: July 2022

ObjectivesTo assess practices of French psychiatrists regarding their management of children and adolescents with suicidal behaviors, focusing on the use of a separation protocol in which the youths are separated from their relatives.MethodsIn 2017, we conducted an online cross-sectional survey of French psychiatrists caring for children and adolescents. Participants were asked to describe their practice of a separation protocol in children and adolescents admitted for suicidal behavior. Our main analysis followed a descriptive approach. We also explored whether participant characteristics were associated with the use of a separation protocol.ResultsThe response rate was 218/2403 (9,1%); 57.9 % of respondents worked in a University hospital, and 60% of respondents reported routinely hospitalizing children. A separation protocol was set up by 91.1% of survey participants (systematically 39.6%, on a case-by-case basis 51.5%). The mean age from which a separation protocol was indicated was above 11 years; 64% of participants reported a separation period of ≤ 48 h. The most common (87%) criterion cited for establishing a separation period was family relationship difficulties. The most common (80.9%) reason to justify the use of a separation protocol was to allow a better clinical assessment. Exploratory analyses did not identify any participant characteristics associated with the use of a separation protocol (p &gt; 0.2 for all).ConclusionThe use of a separation protocol in children and adolescents admitted for suicidal behavior is a widespread practice in France, despite the deprivation of liberty it implies. This raises the question of the relevance and usefulness of such a practice.
The second-tier status of fragile X syndrome testing for unexplained intellectual disability/global developmental delay in the era of next-generation sequencing
Authors: Zhang Wen , Li Dong , Pang Nan , Jiang Li , Li Baomin , Ye Fanghua , He Fang , Chen Shimeng , Liu Fangyun , Peng Jing , Yin Jinghua , Yin Fei 
Published: July 2022

ObjectiveAlthough many unexplained intellectual disability/global developmental delay (ID/GDD) individuals have benefited from the excellent detection yield of copy number variations and next-generation sequencing testing, many individuals still who suffer from ID/GDD of unexplained etiology. In this study, we investigated the applicability of fragile X syndrome (FXS) testing in unexplained ID/GDD individuals with negative or absent genetic testing.MethodsIn this study, we used the triplet repeat primed polymerase chain reaction to evaluate the value and application of fragile X testing in unexplained ID/GDD individuals with negative or absent genetic testing (n = 681) from three hospitals.ResultsOf the 681 ID/GDD individuals with negative or absent genetic testing results detected by FXS testing, 12 men and one woman were positive. This corresponded to a diagnostic yield of 1.9% for FXS testing in our cohort. All FXS individuals had either a family history of ID/GDD or suggestive clinical features. The detection yield of FXS testing in ID/GDD individuals who completed genetic testing (2.70%, 12/438) was significantly higher than in individuals without any genetic testing (0.40%, 1/243).ConclusionsThis is the first report of FXS testing in ID/GDD individuals who lacked previous genetic testing, which promotes standardization of the FXS diagnostic process. These results highlight the utility of FXS testing of unexplained ID/GDD individuals with negative results from standard genetic testing. In the era of next-generation sequencing, FXS testing is more suitable as a second-tier choice and provides clinicians and geneticists with auxiliary references for tracing the etiology of ID/GDD.
Rare cause of coronary artery ectasia in children: A case report of methylmalonic acidemia with hyperhomocysteinemia
Authors: Juan Tu , Chao-ying Chen , Hua-rong Li , Ling Wan 
Published: July 2022

BackgroundMethylmalonic acidemia (MMA) with hyperhomocysteinemia is caused by cobalamin deficiency, mainly due to disturbance of cobalamin C (cblC) metabolism. Its clinical manifestations involve many organs. However, cases of coronary artery ectasia have been rarely reported.Case presentationHere, we report the case of a 4-year-old girl who was hospitalized mainly because of pallor, brown urine, and fatigue, followed by hypertension, renal insufficiency, hemolytic anemia, cardiac enlargement, cardiac insufficiency, and coronary artery ectasia. Thrombotic microangiopathy (TMA) was confirmed by renal pathological examination. Metabolic examination showed hyperhomocysteinemia and methylmalonic aciduria. Furthermore, genetic assessment confirmed MMACHC gene variant, which confirmed the final diagnosis of a cblC defect. Intramuscular injection of hydroxy-cobalamin, oral medications of betaine, levocarnitine, folic acid, and aspirin were administered. Three months later, the patient’s condition was significantly improved. Anemia was corrected, and the renal function was normal. Heart size, cardiac function, and coronary artery structure completely returned to normal.ConclusionThe clinical manifestation of cblC deficiency is atypical. This critical condition may be associated with multiple organ involvement. A rare complication, coronary artery ectasia, can also occur. Early identification, careful evaluation, and appropriate treatment are crucially important for the improvement of this disease prognosis.
Using a route planner to optimize door-to-door visits for a pediatric home-hospitalization program: Feasibility study
Authors: Batlle Astrid , Boada Imma , Thió-Henestrosa Santiago , Sevilla Mariona Fernández de , García-García Juan José 
Published: July 2022

BackgroundHospital Sant Joan de Déu (Barcelona) initiated a pediatric acute home-hospitalization program. Due to high patient turnover and the health staff's lack of planning training, daily scheduling was a time-consuming task. Home-hospitalization planning is a vehicle routing problem that can be solved with a technological solution. It was therefore decided to evaluate the efficacy and necessity of the SmartMonkey.io planner.ObjectivesTo compare traditional manual route planning with a route optimizer, and to evaluate the technical feasibility of the implementation of a route planner into a homecare program.MethodsEight participants (experienced homecare staff and inexperienced hospital staff) were included. Personal interviews were performed to assess their eagerness to try a technological solution to the planning problem. Objective benefits including reduced travel time (time planning, distance traveled, and time traveled) were evaluated. Paired t-test, t-test, and Pearson's correlation were used to compare manual and route planner scheduling. Participants then answered a questionnaire to assess planning difficulty and the acceptance of the route planner.ResultsHomecare staff were initially reluctant to use the technology. Significant differences (P &lt; 0.0001) in three variables were found between manual planning and the route planner. A moderate correlation between time planning and plan difficulty (r = 0.59, P &lt; 0.0001) was found with manual planning but not with the route planner. All route planner schedules saved time and distance. No significant differences were found between expertise and planning method. It was noted that it was easy to create plans with the route planner, while difficulty with manual planning increased as more locations were added. All participants evaluated the route planning tool favorably.ConclusionsRoute-planning technology saved planning time and generated better plans than manual planning. The route planner's learning curve was fast and results were obtained in the same amount of time regardless of difficulty and expertise. SmartMonkey.io also has the potential to reduce internal and environmental costs and increase staff productivity.
The relationship of domestic pet ownership with the risk of childhood asthma: A systematic review and meta-analysis
Authors: Ji Xiaoyi , Yao Yuan , Zheng Ping , Hao Chuangli 
Published: July 2022

Background and ObjectiveThe relationship between pet ownership and childhood asthma remains controversial. In recent years, there have been increasing studies with large sample size. Therefore, we conducted this systematic review and meta-analysis to evaluate the relationship between pet ownership and childhood asthma.MethodRelevant research was retrieved from PubMed, Cochrane, EMBASE, and Web of science. The retrieval was as of October 1, 2021. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included studies. Stata 15.0 was used to conduct the meta-analysis.ResultsA total of 60 studies with large sample size published between 1995 and 2021 were included in this systematic review and meta-analysis, which included 18 cohort studies and 42 case-control studies covering 27 countries and 1,871,295 children. As shown by meta-analysis results, cat ownership (OR = 1.18, 95%CI: 1.05∼1.33) and dog ownership (OR = 1.12, 95%CI: 1.0 0∼1.24) have a significant bearing on the occurrence of childhood asthma. Pet ownership was also positively correlated with the occurrence of severe childhood asthma (OR = 1.15, 95%CI: 1.11∼1.20).ConclusionPet ownership, especially cats and dogs, is associated with the occurrence of asthma in children.
The extended clinical and genetic spectrum of CTNNB1-related neurodevelopmental disorder
Authors: Lee Seungbok , Jang Se Song , Park Soojin , Yoon Jihoon G. , Kim Soo Yeon , Lim Byung Chan , Chae Jong Hee 
Published: July 2022

PurposeLoss-of-function mutations ofCTNNB1have been established as the cause of neurodevelopmental disorder with spastic diplegia and visual defects. Although most patients share key phenotypes such as global developmental delay and intellectual disability, patients withCTNNB1-related neurodevelopmental disorder show a broad spectrum of clinical features.MethodsWe enrolled 13 Korean patients withCTNNB1-related neurodevelopmental disorder who visited Seoul National University Children’s Hospital (5 female and 8 male patients with ages ranging from 4 to 22 years). They were all genetically confirmed as having pathogenic loss-of-function variants inCTNNB1using trio or singleton whole exome sequencing. Variants called from singleton analyses were confirmed to bede novothrough parental Sanger sequencing.ResultsWe identified 11de novotruncating variants inCTNNB1in 13 patients, and two pathogenic variants, c.1867C &gt; T (p.Gln623Ter) and c.1420C &gt; T (p.Arg474Ter), found in two unrelated patients, respectively. Five of them were novel pathogenic variants not listed in the ClinVar database. While all patients showed varying degrees of intellectual disability, impaired motor performance, and ophthalmologic problems, none of them had structural brain abnormalities or seizure. In addition, there were three female patients who showed autistic features, such as hand stereotypy, bruxism, and abnormal breathing. A literature review revealed a female predominance of autistic features inCTNNB1-related neurodevelopmental disorder.ConclusionThis is one of the largest single-center cohorts ofCTNNB1-related neurodevelopmental disorder. This study investigated variable clinical features of patients and has expanded the clinical and genetic spectrum of the disease.
Population pharmacokinetics and initial dose optimization of tacrolimus in children with severe combined immunodeficiency undergoing hematopoietic stem cell transplantation
Authors: Chen Xiao , Wang Dongdong , Zheng Feng , Zhai Xiaowen , Xu Hong , Li Zhiping 
Published: July 2022

The present study aimed to explore the population pharmacokinetics and initial dose optimization of tacrolimus in children with severe combined immunodeficiency (SCID) undergoing hematopoietic stem cell transplantation (HSCT). Children with SCID undergoing HSCT treated with tacrolimus were enrolled for analysis. Population pharmacokinetics of tacrolimus was built up by a nonlinear mixed-effects model (NONMEM), and initial dose optimization of tacrolimus was simulated with the Monte Carlo method in children weighing &lt;20 kg at different doses. A total of 18 children with SCID undergoing HSCT were included for analysis, with 130 tacrolimus concentrations. Body weight was included as a covariable in the final model. Tacrolimus CL/F was 0.36–0.26 L/h/kg from body weights of 5–20 kg. Meanwhile, we simulated the tacrolimus concentrations using different body weights (5–20 kg) and different dose regimens (0.1–0.8 mg/kg/day). Finally, the initial dose regimen of 0.6 mg/kg/day tacrolimus was recommended for children with SCID undergoing HSCT whose body weights were 5–20 kg. It was the first time to establish tacrolimus population pharmacokinetics in children with SCID undergoing HSCT; in addition, the initial dose optimization of tacrolimus was recommended.
Cost-Effectiveness Analysis of Capecitabine Plus Oxaliplatin Versus Gemcitabine Plus Oxaliplatin as First-Line Therapy for Advanced Biliary Tract Cancers
Authors: Chen Ruijia , Zhang Yalan , Lin Kongying , Huang Defu , You MaoJin , Lai Yanjin , Wang Jinye , Hu Yingying , Li Na 
Published: July 2022

Background: In the first-line treatment of biliary tract cancers (BTCs), XELOX (capecitabine plus oxaliplatin) showed comparable clinical efficacy and safety to gemcitabine and oxaliplatin (GEMOX), with fewer visits and better treatment management. Our study aims to investigate the cost-effectiveness of XELOX and GEMOX as the first-line therapy for BTCs from the perspective of the Chinese healthcare systems and to provide valuable suggestions for clinical decision-making.Methods: A Markov model was developed using the phase 3 randomized clinical trial (ClinicalTrials.gov number, NCT01470443) to evaluate the cost-effectiveness of XELOX and GEMOX. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were used as the primary outcomes of the model. Uncertainty was assessed using univariate and probabilistic sensitivity analysis.Results: The QALYs for the XELOX and GEMOX groups were 0.66 and 0.54, respectively. In China, the total cost of XELOX treatment is US $12,275.51, which is lower than that of the GEMOX regimen. In addition, XELOX is more effective than GEMOX, making it the preferred regimen. A sensitivity analysis determined that XELOX therapy has a stable economic advantage in China.Conclusion: Compared to GEMOX, XELOX is a more cost-effective treatment as a first-line treatment for advanced BTC from the perspective of the Chinese health service system.
Human Umbilical Cord Blood Mononuclear Cells Ameliorate CCl4-Induced Acute Liver Injury in Mice via Inhibiting Inflammatory Responses and Upregulating Peripheral Interleukin-22
Authors: Zhang Jinming , Zhai Hengben , Yu Pei , Shang Dabao , Mo Ruidong , Li Ziqiang , Wang Xiaolin , Lu Jie , Xie Qing , Xiang Xiaogang 
Published: July 2022

Background: Human umbilical cord blood mononuclear cells (hUCBMNCs) show therapeutic effects on many inflammatory diseases. The deterioration of acute liver injury is attributed to excessive inflammatory responses triggered by damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). Whether hUCBMNCs treatment is a promising strategy for acute liver injury/failure needs to be investigated.Methods: Liver injury mice induced by PAMPs, DAMPs, or DAMPs plus PAMPs were developed. DAMPs included CCl4 (carbon tetrachloride), APAP (acetaminophen), and ConA (Concanavalin A). PAMPs included Klebsiella pneumoniae (K.P.) and Salmonella typhimurium (S. Typhimurium). DAMP plus PAMP-induced liver injury was developed by sequential CCl4 and K.P. administration. hUCBMNCs were injected intravenously.Results: hUCBMNCs significantly prolonged mice survival time in DAMP plus PAMP-induced liver failure but had no benefit in bacteria-infected mice. hUCBMNCs significantly alleviated hepatic necrosis post CCl4/ConA insult. In CCl4-induced acute liver injury, peripheral levels of interleukin (IL)-22 were upregulated and liver regeneration was enhanced after treating with hUCBMNCs at 48h. The levels of p62 and LC3B-II, autophagy markers, were also upregulated in the hUCBMNC-treated group.Conclusion: hUCBMNCs as a kind of cell therapeutic strategy could attenuate acute liver injury in mice, which is executed by enhancing autophagy and regeneration in the liver via inhibiting inflammatory responses and upregulating peripheral IL-22.
Uncovering the Effect and Mechanism of Rhizoma Corydalis on Myocardial Infarction Through an Integrated Network Pharmacology Approach and Experimental Verification
Authors: Li Jingyan , Wu Junxuan , Huang Junying , Cheng Yuanyuan , Wang Dawei , Liu Zhongqiu 
Published: July 2022

Background: Myocardial infarction (MI), characterized by reduced blood flow to the heart, is a coronary artery disorder with the highest morbidity and mortality among cardiovascular diseases. Consequently, there is an urgent need to identify effective drugs to treat MI. Rhizoma Corydalis (RC) is the dry tuber of Corydalis yanhusuo W.T. Wang, and is extensively applied in treating MI clinically in China. Its underlying pharmacological mechanism remains unknown. This study aims to clarify the molecular mechanism of RC on MI by utilizing network pharmacology and experimental verification.Methods: Based on network pharmacology, the potential targets of the RC ingredients and MI-related targets were collected from the databases. Furthermore, core targets of RC on MI were identified by the protein-protein interaction (PPI) network and analyzed with Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was used to validate the binding affinity between the core targets and the bioactive components. Oxygen-glucose deprivation (OGD) was performed on H9c2 cells to mimic MI in vitro. A Cell Counting Kit-8 assay was used to assess the cardioprotective effect of the active ingredient against OGD. Western blot analysis and RT-qPCR were used to measure the cell apoptosis and inflammation level of H9c2 cells.Results: The network pharmacology obtained 60 bioactive components of RC, 431 potential targets, and 1131 MI-related targets. In total, 126 core targets were screened according to topological analysis. KEGG results showed that RC was closely related to the phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (PKB, also called Akt) signaling pathway. The experimental validation data showed that tetrahydropalmatine (THP) pretreatment preserved cell viability after OGD exposure. THP suppressed cardiomyocyte apoptosis and inflammation induced by OGD, while LY294002 blocked the inhibition effect of THP on OGD-induced H9c2 cell injury. Moreover, the molecular docking results indicated that THP had the strongest binding affinity with Akt over berberine, coptisine, palmatine, and quercetin.Conclusion: THP, the active ingredient of RC, can suppress OGD-induced H9c2 cell injury by activating the PI3K/Akt pathway, which in turn provides a scientific basis for a novel strategy for MI therapy and RC application.
Nodosin Exerts an Anti-Colorectal Cancer Effect by Inhibiting Proliferation and Triggering Complex Cell Death in Vitro and in Vivo
Authors: Fan Huixia , Hao Xiaopeng , Gao Yuan , Yang Jian , Liu Aojun , Su Yarui , Xia Yong 
Published: July 2022

Colorectal cancer (CRC) is one of the most common digestive system cancer in the world. Its incidence and mortality are increasing annually. Presently, CRC lacks long-term effective treatment methods and drugs. Therefore, finding new treatment methods and drugs is of great significance for CRC treatment. Compounds derived from natural plants have been widely used in tumor research and treatment because of their good antitumor activity these years. This study found that nodosin, a diterpenoid extracted from the medicinal plant Rabdosia serra (Maxim.) Hara, inhibited the growth of CRC cells SW480, HT-29 and LoVo in a dose- and time-dependent manner, with inhibitory concentrations (IC50) of 7.4, 7.7, and 6.6 μM respectively. We selected highly metastatic and poorly differentiated SW480 cells for further studies. We found that nodosin could inhibit cell proliferation by inhibiting DNA synthesis and induce cell death by inducing oxidative stress, apoptosis and autophagy in cells. Through in vitro assays combined with transcriptomic analysis, it was found that nodosin could downregulate tribbles pseudokinase 3 and upregulate oxidative stress-induced growth inhibitor 1 to induce oxidative stress in cells; nodosin-induced reactive oxygen species were able to upregulate the expression of heme oxygenase 1 to induce apoptosis and the expression of cathepsin L. and light chain-3 to induce autophagy. In vivo, we found that nodosin inhibited tumor growth and induced cells to undergo apoptosis and autophagy without significant toxic effects. In conclusion, our findings suggest that nodosin exerts anti-CRC effects mainly through its ability to induce apoptosis and autophagy in vitro and in vivo. Therefore, our study contributes to the development of nodosin-based potential CRC therapeutic drugs.