bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and In Vitro Functional Verification of Two Novel Mutations of GHR Gene in the Chinese Children with Laron Syndrome
Authors: Li Ran , Gong Fengying , Pan Hui , Liang Hanting , Miao Hui , Zhao Yuxing , Duan Lian , Yang Hongbo , Wang Linjie , Chen Shi , Zhu Huijuan 
Published: April 2021

PurposeLaron syndrome (LS) is a severe growth disorder caused byGHRgene mutation or post-receptor pathways defect. The clinical features of these patients collected in our present study were summarized,GHRgene variants were investigated and furtherin vitrofunctional verification was carried out.MethodsFour patients with LS were collected, their clinical characteristics were summarized, genomic DNA was extracted, andGHRgene was amplified and sequenced. GHR wild type (GHR-WT) and mutant GHR expression plasmids were constructed, and transiently transfected into HepG2 cells and HEK293T cells to observe the subcellular distribution of the GHR protein by immunofluorescence and to determine the expression of GHR and its post-receptor signaling pathway changes by Western blotting.ResultsAll of the four patients were male, and the median height was -4.72 SDS. FourGHRgene variants including c.587A&gt;C (p.Y196S), c.766C&gt;T (p.Q256*), c.808A&gt;G (p.I270V) and c.1707-1710del (p.E570Afs*30) were identified, and the latter two were novel mutations. The results of mutant GHR plasmids transfection experiments and immunofluorescence assay showed that the subcellular distribution of GHR-Q256* and GHR-E570Afs*30 mutant proteins in HepG2 and HEK293T cells presented with a unique ring-like pattern, gathering around the nucleus, while GHR-Y196S mutant protein was evenly distributed on HepG2 cell membrane similar to GHR-WT. The GHR protein levels of HepG2 cells transiently transfected with GHR-Y196S, GHR-Q256* and GHR-E570Afs*30 were all significantly lower when compared with cells transfected with GHR-WT (P&lt;0.05). Further mutant GHR post-receptor signal transduction investigation demonstrated that GH induced phosphorylated STAT5 levels of HepG2 cells transfected with three mutant plasmids were all significantly decreased in comparison with that of GHR-WT (P&lt;0.05).ConclusionsTwo novelGHRgene mutations (I270V and E570Afs*30) were found in our patients with LS. GHR mutations influenced the subcellular distribution and GHR protein levels, then led to the impaired post-receptor signal transduction, suggesting that theGHRmutations contributed to the pathological condition of LS patients.
Glycated Hemoglobin (HbA1c) Concentrations Among Children and Adolescents With Diabetes in Middle- and Low-Income Countries, 2010–2019: A Retrospective Chart Review and Systematic Review of Literature
Authors: Chen Xiuli , Pei Zhou , Zhang Miaoying , Xu Zhenran , Zhao Zhuhui , Lu Wei , Chen Linqi , Luo Feihong , Chen Ting , Sun Chengjun 
Published: April 2021

ObjectivesTo explore the glycemic control [represented by glycated hemoglobin (HbA1c) concentrations] in children with diabetes mellitus (DM) in east China and middle- and low-income countries, from 2010 to 2019.MethodsRetrospective data of children with DM from two hospital-based health records were reviewed. Data on HbA1c concentrations, hospitalization due to diabetic ketoacidosis, and patient demographics were collected and analyzed. A systematic review was subsequently performed to analyze publications that report HbA1c concentrations in patients aged &lt;18 years. Patients’ characteristics extracted from each publication were used to generate simulated individual data for pooled analysis. HbA1c estimates were derived from steady-state iterations.ResultsData of 843 diabetic children (aged 11.2 ± 3.9 years) with 2,658 HbA1c measures were retrieved from the two hospitals during the period 2010–2020. The duration of diabetes in the patients was 4.4 ± 2.8 years, and their HbA1c was 8.1 ± 2.2%. Patients who were internal migrants had significantly higher HbA1c concentration than resident patients (8.4 vs. 7.9%). The literature review yielded 1,164 publications, and the majority (74.1%) of patient data were published in high-income countries. The patient data extracted from these publications generated 486,416 HbA1c concentration estimates between 2005 and 2019. The average HbA1c concentration during the 15 years was 9.07 ± 2.15%. The mean HbA1c concentrations among children were 8.23, 8.73, 9.20, and 10.11% in high-income country (HIC), upper-middle income country (UMIC), lower-middle income country (LMIC), and low-income country (LIC) respectively. The mean rate of optimized glycemic control (HbA1c &lt;7.5%) among children was 32.4, 27.5, 21.7, and 12.7% in HIC, UMIC, LMIC, and LIC, respectively.ConclusionsThe current study indicated that there is substantial room for improvement in glycemic control in children with DM worldwide, especially in middle- and low-income countries.
Case Report: Resetting the Humoral Immune Response by Targeting Plasma Cells With Daratumumab in Anti-Phospholipid Syndrome
Authors: Pleguezuelo Daniel E. , Díaz-Simón Raquel , Cabrera-Marante Oscar , Lalueza Antonio , Paz-Artal Estela , Lumbreras Carlos , Serrano Hernández Antonio 
Published: April 2021

IntroductionMonoclonal antibodies (mAb) targeting plasma cells are malignant gammopathy designed and approved therapies. In recent years, these antibodies have also been increasingly introduced for non-malignant conditions such as autoimmune-mediated diseases. The Anti-Phospholipid Syndrome (APS) is an immune-mediated disorder in which autoantibodies against phospholipid associated proteins could elicit the activation of the coagulation cascade in specific situations. Therefore, the mainstream treatment for APS patients is the use of anticoagulant therapy. However, there are refractory patients who would benefit from targeting the antibodies rather than their effects. Rituximab, a B-cell depleting mAb, and intravenous immunoglobulins (IVIG) have been used in APS patients without showing a clear beneficial effect or a significant drop in anti-phospholipid antibody (aPL) levels.Clinical caseWe present our first APS case treated with daratumumab, an anti-CD38 mAb, in a 21-year-old patient with APS who presented with recurrent venous thromboembolic events despite adequate anticoagulant therapy. She tested positive for lupus anticoagulant, anti-cardiolipin IgG, anti-beta-2-glycoprotein-I IgG and anti-phosphatidylserine/prothrombin IgG and IgM. She was administered one dose weekly of daratumumab for 4 weeks. The treatment showed an adequate safety profile and was well tolerated. The patient was discharged after undergoing a clinically significant improvement. After the therapy, her levels of positive aPL declined significantly and most continued to decrease during the next three months. The patient experienced a new thrombotic episode two years after the therapy associated with poor adherence to antithrombotic therapy.ConclusionsThe treatment with daratumumab showed an adequate safety profile, was well tolerated and led to a significant clinical improvement. Levels of aPL lowered on therapy and the next three months and then rose again during follow-up. Further investigation is needed to better elucidate the role and optimal timing and doses of daratumumab in treatment of refractory APS.
Prevalence and Therapy Rates for Stuttering, Cluttering, and Developmental Disorders of Speech and Language: Evaluation of German Health Insurance Data
Authors: Sommer Martin , Waltersbacher Andrea , Schlotmann Andreas , Schröder Helmut , Strzelczyk Adam 
Published: April 2021

PurposeTo evaluate the prevalence and treatment patterns of speech and language disorders in Germany.MethodsA retrospective analysis of data collected from 32% of the German population, insured by the statutory German health insurance (AOK, Local Health Care Funds). We used The International Statistical Classification of Diseases and Related Health Problems, 10th revision, German Modification (ICD-10 GM) codes for stuttering (F98.5), cluttering (F98.6), and developmental disorders of speech and language (F80) to identify prevalent and newly diagnosed cases each year. Prescription and speech therapy reimbursement data were used to evaluate treatment patterns.ResultsIn 2017, 27,977 patients of all ages were diagnosed with stuttering (21,045 males, 75% and 6,932 females, 25%). Stuttering prevalence peaks at age 5 years (boys, 0.89% and girls, 0.40%). Cluttering was diagnosed in 1,800 patients of all ages (1,287 males, 71.5% and 513 females, 28.5%). Developmental disorders of speech and language were identified in 555,774 AOK-insurants (61.2% males and 38.8% females). Treatment data indicate a substantial proportion newly diagnosed stuttering individuals receive treatment (up to 45% of 6-year-old patients), with slightly fewer than 20 sessions per year, on average. We confirmed a previous study showing increased rates of atopic disorders and neurological and psychiatric comorbidities in individuals with stuttering, cluttering, and developmental disorders of speech and language.ConclusionThis is the first nationwide study using health insurance data to analyze the prevalence and newly diagnosed cases of a speech and language disorder. Prevalence and gender ratio data were consistent with the international literature. The crude prevalence of developmental disorders of speech and language increased from 2015 to 2018, whereas the crude prevalence for stuttering remained stable. For cluttering, the numbers were too low to draw reliable conclusions. Proportional treatment allocation for stuttering peaked at 6 years of age, which is the school entrance year, and is later than the prevalence peak of stuttering.
Prognostic and Clinicopathological Significance of E-Cadherin in Pancreatic Cancer Patients: A Meta-Analysis
Authors: Wang Pengbo , Zhu Zengkuan 
Published: April 2021

BackgroundSeveral recent studies have investigated the prognostic and clinicopathological significance of epithelial cadherin (E-cadherin) in pancreatic cancer; however, conclusions from these studies remain inconsistent. Therefore, we performed a meta-analysis to evaluate the effects of E-cadherin expression on the prognosis and clinicopathological characteristics of pancreatic cancer.MethodsEmbase, PubMed, and Web of Science were searched to identify articles associated with E-cadherin and pancreatic cancer. Hazard ratios (HRs) and odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated and summarized. All eligible studies were searched until May 20, 2020. Heterogeneity among studies was assessed using the Chi-square test and I2 statistic.ResultsOverall, 25 studies were identified, of which 12 reports with 1,032 cases concerned the prognosis of pancreatic cancer, and 22 involved the risk and clinical characteristics of pancreatic cancer. The overall results revealed that E-cadherin expression was significantly related to overall survival, gender, tumor grade, lymph node metastasis, tumor differentiation, and risk of pancreatic cancer. In the subgroup analysis, no significant heterogeneity or publication bias was observed.ConclusionsE-cadherin expression is strongly associated with the risk, clinical features, and prognosis of pancreatic cancer, suggesting that E-cadherin may be an effective biomarker for the clinical assessments and predicting prognosis of pancreatic cancer.
Risk Factors of Prolonged Mechanical Ventilation in Infants With Pierre Robin Sequence After Mandibular Distraction Osteogenesis: A Retrospective Cohort Study
Authors: Zhang Na , Mao Zhe , Cui Yingqiu , Xu Yingyi , Tan Yonghong 
Published: April 2021

Background: After mandibular distraction osteogenesis (MDO), most infants with Pierre Robin sequence (PRS) require mechanical ventilation to assist their breathing. However, the optimal duration of intubation during early mandibular distraction osteogenesis activation is poorly understood. This retrospective study was carried out to identify perioperative risk factors of prolonged mechanical ventilation in infants undergoing MDO.Methods: A total of 95 infants with PRS underwent MDO at Guangzhou Women and Children's Medical Center between 2016 and 2018, and the clinical records of 74 infants who met the selection criteria were analyzed. Of the 74 infants, 26 (35.1%) underwent prolonged mechanical ventilation, 48 (64.9%) did not. t-test, Wilcoxon Sum Rank test or chi-squared test were performed to compare variables that might associate with prolonged mechanical ventilation between the two groups, and then, significant variables identified were included in the multivariate logistic regression model to identify independent variables.Results: Univariate logistic regression analysis revealed that age, preoperative gonial angle, and postoperative pulmonary infection were associated with prolonged mechanical ventilation (all P &lt; 0.05). Multivariate logistic regression analysis confirmed that the preoperative gonial angle and postoperative pulmonary infection were independent risk factors of prolonged mechanical ventilation (both P &lt; 0.05).Conclusions: Infants with PRS and smaller preoperative gonial angle or postoperative pulmonary infection may be more likely to undergo prolonged mechanical ventilation after MDO. For others, extubation may be attempted within 6 days after MDO.
Case Report: Kaposiform Hemangioendothelioma With Spinal Involvement
Authors: Qiu Tong , Yang Kaiying , Dai Shiyi , Chen Siyuan , Ji Yi 
Published: April 2021

Introduction: Kaposiform hemangioendothelioma (KHE) is a rare, locally invasive vascular tumor that mostly appears in infants and adolescents. KHE with spinal involvement is extremely rare. The aim of this study was to review the imaging features, clinical manifestations and treatment of KHE patients with spinal involvement.Materials and Methods: We reviewed patients with KHE who were admitted to Pediatric Surgery of West China Hospital of Sichuan University from April 2014 to August 2020, and the cases were evaluated.Results: Seven patients with spinal involvement were enrolled in the study, including four (57.1%) males and three (42.9%) females. The age at onset ranged from 1.0 day to 4.0 years, with an average of 1.6 years. Five (71.4%) had pain due to bone destruction, three patients (42.9%) had decreased range of motion (ROM), four (57.1%) patients had scoliosis, two (28.6%) patients developed claudication, and three patients (42.9%) presented with a soft tissue mass in the neck of the back. Five patients (71.4%) had the Kasabach-Merritt phenomenon (KMP), with a minimum platelet value of 8 × 109/L. All patients were treated with sirolimus, and showed regression of the lesion and/or normalization of the hematologic parameters.Conclusion: KHE with spinal involvement is difficult to diagnose due to its rarity and variable symptoms, which need to be recognized to start early treatment. The management of KHE with spinal involvement should be performed by a multidisciplinary team. Sirolimus can improve outcomes in patients with KHE with spinal involvement.
An Overview of Tools to Score Severity in Pediatric Inflammatory Bowel Disease
Authors: Shaoul Ron , Day Andrew S. 
Published: April 2021

Background and Aims: The management of IBD entails the use of various treatments (nutrition, medications, and surgery) in order to induce and maintain remission. The assessment of IBD disease activity is based on a combination of symptoms, clinical findings, imaging, and endoscopic procedures. As in any disease, reliable assessment of disease activity or severity is required in order to plan relevant follow-up, decide on appropriate investigations, determine the best treatment option and subsequently assess response to treatment. It is important for proper documentation, follow-up, assessment of response to treatment and communication, especially in patients with IBD, to talk the same language by using validated and widely used scores for disease activity, endoscopic and radiologic activity, and patient reported outcomes both for clinical practice and research. This review aims to highlight key tools available for the assessment of disease activity or severity in individuals (especially children) with IBD.Methods: A literature search was performed using MEDLINE, Pubmed, and the Cochrane Library with the last search date of August 2020. Tools evaluating disease severity across various aspects (clinical, endoscopic, and radiological) were identified and discussed. Those tools validated and specific for children with IBD were included were available.Results: Over time a number of scoring systems have been developed to quantify clinical, endoscopic and imaging assessments in individuals with IBD. While some are exclusively for children or adults, others appear to have relevance to all age groups. In addition, some tools developed in adult populations are utilized in children, but have not expressly been validated in this age group.Conclusions: Although some available scoring tools are appropriate for children with IBD, others require consideration. The development and use of pediatric-specific tools is relevant and appropriate to optimal care of children and adolescents with IBD.
Case Report: Multiple Seizures After a Diphenoxylate-Atropine Overdose in a Small Child
Authors: Wang Chun-Hui , Song Li-Jia , Yang Yang , Qu Xiao-Peng , Lan Li , Liu Bei 
Published: April 2021

Poisoning is a type of accidental injury and it is considered a major public health problem worldwide. Oral drug poisoning in children is an important cause of accidental injury and even death. It is a common critical emergency in the field of pediatrics. Once a child unintentionally takes an overdose, regardless of whether it caused poisoning or not, they should be admitted to the hospital for emergency treatment. Acute poisoning in children most frequently occurs through the digestive tract. Drug poisoning can happen in children of all ages. In children younger than 1 year, drug poisoning is mostly caused by the parents during feeding, while in children aged 1–3 years, it predominantly occurs as a result of an accident. A case of diagnosis and treatment of a child with diphenoxylate-atropine poisoning is reported herein. The early manifestation of this child was acute toxic encephalopathy with clinical manifestations of a coma, convulsions, and respiratory depression. A brain MRI showed extensive damage to the bilateral caudate nucleus, lenticular nucleus, parietal lobe, precuneus lobe, and occipital lobe. Accidental administration of a large dose of diphenoxylate results in severe clinical symptoms and can cause obvious diffuse brain damage.
Biosensing the Presence of Metal Nanoparticles by Spectrally- and Time-Resolved Endogenous Fluorescence in Water Moss Fontinalis antipyretica
Authors: Marcek Chorvatova Alzbeta , Uherek Martin , Chorvat Dusan 
Published: April 2021

Pollution by heavy metals represents a significant environmental burden. We employed confocal microscopy with spectral detection and fluorescence lifetime imaging (FLIM) to evaluate the effect of nanoparticles (NPs) from various metals (Zinc, Nickel, Cobalt, Copper) on endogenous fluorescence of Fontinalis antipyretica moss. Short term (3–5 day) exposure to NPs, designed and fabricated by direct synthesis using femtosecond laser ablation in water, was studied. The green flavonoid and/or lignin endogenous fluorescence peaking between 500 and 560 nm was found to be increased by Zn and significantly reduced by Cu. The overall red chlorophyll fluorescence intensity with a maximum of 680 nm remained largely unchanged after exposure to Ni and Zn, but was decreased in the presence of Co and completely abolished by Cu. All NPs but Zn induced changes in the fluorescence lifetimes, demonstrating increased sensitivity of this parameter to environmental pollution. Gathered data indicate fast responsiveness of the endogenous fluorescence in the Fontinalis antipyretica moss to the presence of heavy metals that can thus potentially serve as a biosensing tool for monitoring environmental pollution in the moss natural environment.
Humor in Dark Personalities: An Empirical Study on the Link Between Four Humor Styles and the Distinct Subfactors of Psychopathy and Narcissism
Authors: Lobbestael Jill , Freund Vanessa Lea 
Published: April 2021

BackgroundHumor is a main ingredient of interpersonal relationships. Two sets of psychopathological traits known for their devastating impact on interpersonal relationships are psychopathy and narcissism. The current study was developed to provide a fine-grained analysis of the relationship between four humor styles (affiliative, self-enhancing, self-defeating, and aggressive) and both psychopathic and narcissistic traits. Specifically, it addresses how humor styles relate to the three psychopathy subfactors (following the triarchic model) and four subfactors of grandiose narcissism.MethodSelf-report measures in a non-clinical male sample N = 177.ResultsMultiple regression analyses revealed psychopathic and narcissistic traits’ relation to using both benign and injurious humor. Subfactor analyses showed that aggressive and self-defeating humor were mostly associated with impulsivity and entitlement, while dominance levels actuated the use of humor to cope with stress. The cold-heartedness component of psychopathy proved to be particularly humorless, setting it aside as a distinctively disturbing psychopathic subfactor.Conclusions and implicationsHumor strongly colors the interpersonal style of both psychopathic and narcissistic personalities. Differential components of both personality types inform on the possible underlying motivations that drive the use of distinct styles of humor. This implies that psychopathic and narcissistic traits could potentially be lowered through the alternation of humor styles.