Cystic fibrosis (CF) is an autosomal recessive disease caused by the inheritance of two mutant cystic fibrosis transmembrane conductance regulator (CFTR) alleles, one from each parent. Autosomal recessive disorders are rarely associated with germline mutations or mosaicism. Here, we propose a case of paternal germline mutation causing CF. The subject also had an identifiable maternal mutant allele. We identified the compound heterozygous variants in the proband through Sanger sequencing, and in silico studies predicted functional effects on the protein. Also, short tandem repeat markers revealed the de novo nature of the mutation. The maternal mutation in the CFTR gene was c.1000C > T. The de novo mutation was c.178G > A, p.Glu60Lys. This mutation is located in the lasso motif of the CFTR protein and, according to in silico structural analysis, disrupts the interaction of the lasso motif and R-domain, thus influencing protein function. This first reported case of de novo mutation in Asia has notable implications for molecular diagnostics, genetic counseling, and understanding the genetic etiology of recessive disorders in the Iranian population.
Identifying the first de novo mutation in the cystic fibrosis transmembrane conductance regulator protein in Iran: a case report with insights from microsatellite markersA child can develop Cystic Fibrosis (CF) if both parents pass on mutated genes. In some rare cases, new genetic mutations occur spontaneously, causing CF. This report discusses a unique case where a child has one gene with a spontaneous mutation and inherits another gene mutation from the mother. We used a method called Sanger sequencing to find the two different gene changes in the affected person. We also used computer analysis to predict how these changes might affect the protein responsible for this genetic disease. To confirm that the child\'s new change is not inherited, we used a type of genetic marker called microsatellite markers. The mutation inherited from the mother and the new spontaneous mutation resulted in a unique change in the responsible protein. This mutation is located in a specific part of the protein called the lasso motif. Our computer simulations show that this mutation disrupts the interaction between the lasso motif and another part of the protein called the R-domain, which ultimately affects the protein\'s function. This case is significant because it is the first reported instance of a de novo mutation causing CF in Asia. It has important implications for genetic testing, counseling, and understanding how recessive genetic disorders like CF occur within the Iranian population.

(1) Background: Lyme borreliosis (LB) is a tick-borne disease known for its diagnostic challenges. Conventional two-tiered testing (CTTT) for antibodies is time-consuming, has low sensitivity in the early stages of disease, and sometimes generates false-positive IgM immunoblots. To tackle this issue, modified two-tiered testing (MTTT) was introduced, incorporating recombinant VlsE and C6 antigens to enhance diagnostic accuracy. (2) Methods: In this prospective study, we enrolled children exhibiting symptoms indicative of LB. We collected serum samples at various intervals and subjected them to analysis using standard enzyme immunoassays. We then compared these results with the outcomes from the VlsE and C6 assays. (3) Results: In our study, all 33 patients displaying erythema migrans (EM), a characteristic symptom of LB, exhibited positive responses to the C6 antigen. This finding underscores the potential utility of the C6 antigen as a reliable diagnostic tool for LB. Additionally, we observed a significant reduction in anti-VlsE antibody levels following antibiotic treatment in EM patients. (4) Conclusions: The utilization of recombinant VlsE and C6 antigens in LB diagnostics and monitoring has yielded promising results. Nonetheless, it is imperative for clinicians to exercise caution and interpret results in conjunction with clinical findings, considering the dynamic nature of medical guidelines. Even with recombinant antigen tests, some children with EM tested negative, highlighting the importance of clinical diagnosis for treatment decisions. Furthermore, clinicians should be mindful of the possibility of persistently positive VlsE/C6 test results during LB treatment monitoring.

The use of expanded carrier screening (ECS) to assess reproductive risk for autosomal recessive (AR) or X-linked recessive (XLR) conditions has been increasingly integrated into obstetrical care. The aim of this study was to determine what proportion of pediatric patients seen by a medical genetics practice could have had their diagnosis predicted if the parent(s) had undergone currently available ECS at the time of data collection in 2021. A retrospective chart review of patients seen for a medical genetic evaluation at a large academic institution was performed from June 1, 2017, through June 1, 2020. At this institution, 8% of patients were diagnosed with an AR or XLR condition. Of these patients, 61% of the diagnoses could have been predicted in advance if the parent(s) had undergone ECS via the panel referenced in this study. The results of this study highlight the broad range of conditions currently seen in a clinical setting that could be identified as a risk prior to or during pregnancy via ECS. In the prenatal setting, ascertainment of reproductive risk via ECS enables prospective parents to undertake interventions such as prenatal and preimplantation genetic diagnosis. For parents who decline reproductive risk-reducing measures, knowledge about neonatal risk allows for prompt confirmatory testing. In the pediatric setting, the option of early and focused testing can benefit affected individuals and their families.

UNASSIGNED: While there is some evidence in the literature demonstrating success in using a triage software application in ED, none of the solution was developed specifically to support a holistic decision of pediatricians in triage and diagnosis purposes to initiate the first treatment properly. To explore the usefulness and possibility of employing a digital-based solution to enhance clinician performance, the mobile application was developed and then assessed in different perspectives.
UNASSIGNED: The primary objective of this study is to contribute implementation practice of an application to support pediatric triage and diagnoses. The secondary objective is to present the results of the preliminary evaluation of the application.
UNASSIGNED: The application called Pedicmeter was developed. Formative tests with revisions were applied throughout the development phase. A number of summative extensive evaluations were also conducted to investigate the efficacy of the proposed method. The evaluation focused on measuring the ability of an application to support a pediatric staff\'s decision to determine an overall severity level and disease diagnosis. Finally, the user\'s (clinician\'s) satisfaction of using the application was measured.
UNASSIGNED: The application Pedicmeter enables clinicians to make more accurate decisions in determining emergency level of pediatric patients by 6.66%. The application accurately diagnosed a disease with 73.08% accuracy and 66.67% accuracy for respiratory and infectious diseases, respectively. The diagnostic information that the application suggested shows that it does have an influence on a clinician\'s diagnosis. Using the app showed improvements in diagnostic accuracy for asthma, croup, sepsis, but it showed a decrease in the accuracy of a clinician\'s decision for pneumonia. The benefit of the application that satisfies the pediatricians the most is the helpfulness of the features of the application (86%), while the least satisfying factor was the required number of inputs (63%).
UNASSIGNED: The developed application conceptually shows a promising opportunity to enhance clinicians\' decisions from the pilot study. However, the study also reveals further tweaks are required and unveils challenging issues and the concerns of clinician users when use the application. Further research will be conducted to investigate and determine the limiting factors and specific issues revealed by this study. Longitudinal data collection and analysis also need to be conducted to investigate the clinical implications.

Respiratory diseases, including asthma, bronchitis, pneumonia, and upper respiratory tract infection (RTI), are among the most common diseases in clinics. The similarities among the symptoms of these diseases precludes prompt diagnosis upon the patients\' arrival. In pediatrics, the patients\' limited ability in expressing their situation makes precise diagnosis even harder. This becomes worse in primary hospitals, where the lack of medical imaging devices and the doctors\' limited experience further increase the difficulty of distinguishing among similar diseases. In this paper, a pediatric fine-grained diagnosis-assistant system is proposed to provide prompt and precise diagnosis using solely clinical notes upon admission, which would assist clinicians without changing the diagnostic process. The proposed system consists of two stages: a test result structuralization stage and a disease identification stage. The first stage structuralizes test results by extracting relevant numerical values from clinical notes, and the disease identification stage provides a diagnosis based on text-form clinical notes and the structured data obtained from the first stage. A novel deep learning algorithm was developed for the disease identification stage, where techniques including adaptive feature infusion and multi-modal attentive fusion were introduced to fuse structured and text data together. Clinical notes from over 12000 patients with respiratory diseases were used to train a deep learning model, and clinical notes from a non-overlapping set of about 1800 patients were used to evaluate the performance of the trained model. The average precisions (AP) for pneumonia, RTI, bronchitis and asthma are 0.878, 0.857, 0.714, and 0.825, respectively, achieving a mean AP (mAP) of 0.819. These results demonstrate that our proposed fine-grained diagnosis-assistant system provides precise identification of the diseases.

BACKGROUND: Brain tumours are the most common solid tumour in children and are a cause of mortality in adults. Most cases of brain tumour-related death are attributed to glioblastoma (GBM), with an elevated rate for high-grade glioma (HGG). Showing strong heterogeneity, the lesion location, molecule expression and type of HGG differ between adults and children. However, with regard to pathogenesis, brain tumours are expected to have the same underlying molecular processes.
METHODS: In this study, we obtained data from the Gene Expression Omnibus (GEO) database to analyse molecular expression in HGG between adults and children. The same and different mutations were identified in these groups, and the genes involved were compared using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Molecular analysis revealed the same trend of differences between children and adults, which was verified in The Cancer Genome Atlas (TCGA).
RESULTS: A total of 12 microarrays including 455 HGG patients were screened. Through a rigorous intersecting process, we identified miR-10a, miR-10b, and miR-139 as having common differences, as well as 6 target genes, such as CDK6, SOX4 and VEGFA, etc. And 12 long noncoding RNAs (lncRNAs).
CONCLUSIONS: We identified that these key molecules are involved in development and progression of HGG between adults and children. The findings provide a comprehensive description of the similarities in advanced diseases between adults and children and molecular diagnostic directions for precision small-molecule medicine to treat HGG in different age populations.

Increased prenatal diagnoses of sex chromosome aneuploidies (SCAs) amid limited knowledge of their prognoses heighten the need to understand how families contend with the implications of an SCA. To explore the experiences of parents and individuals who received a genetic diagnosis of an SCA (excluding Turner syndrome), we conducted semistructured qualitative telephone interviews with 43 participants affected by these conditions. Parents (n = 35) and individuals (n = 8) expressed almost unanimous interest in more optimistic portrayals of their condition from their providers, even when the prognosis is uncertain. While some participants reported success in receiving accurate information from their provider and identifying supportive resources, numerous families received outdated or misleading information about their condition and lacked direction in accessing follow-up care and support. Parents desire greater coordination of their child\'s medical care and access to care that approaches an SCA holistically. Opportunities remain to improve the diagnosis and care of individuals with SCAs.