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Deficiency in mevalonate kinase (MVK) causes systemic inflammation. However, the molecular mechanisms linking the mevalonate pathway to inflammation remain obscure. Geranylgeranyl pyrophosphate, a non-sterol intermediate of the mevalonate pathway, is the substrate for protein geranylgeranylation, a protein post-translational modification that is catalyzed by protein geranylgeranyl transferase I (GGTase I). Pyrin is an innate immune sensor that forms an active inflammasome in response to bacterial toxins. Mutations in MEFV (encoding human PYRIN) result in autoinflammatory familial Mediterranean fever syndrome. We found that protein geranylgeranylation enabled Toll-like receptor (TLR)-induced activation of phosphatidylinositol-3-OH kinase (PI(3)K) by promoting the interaction between the small GTPase Kras and the PI(3)K catalytic subunit p110δ. Macrophages that were deficient in GGTase I or p110δ exhibited constitutive release of interleukin 1ß that was dependent on MEFV but independent of the NLRP3, AIM2 and NLRC4 inflammasomes. In the absence of protein geranylgeranylation, compromised PI(3)K activity allows an unchecked TLR-induced inflammatory responses and constitutive activation of the Pyrin inflammasome.
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Alquil e Aril Transferases/metabolismo , Febre Familiar do Mediterrâneo/metabolismo , Inflamassomos/metabolismo , Macrófagos/fisiologia , Mutação/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Pirina/genética , Alquil e Aril Transferases/genética , Animais , Células Cultivadas , Febre Familiar do Mediterrâneo/genética , Humanos , Imunidade Inata , Interleucina-1beta/metabolismo , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfatos de Poli-Isoprenil/metabolismo , Processamento de Proteína Pós-Traducional , Transdução de Sinais , Receptores Toll-Like/metabolismoRESUMO
CAPZA2 encodes the α2 subunit of CAPZA, which is vital for actin polymerization and depolymerization in humans. However, understanding of diseases associated with CAPZA2 remains limited. To date, only three cases have been documented with neurodevelopmental abnormalities such as delayed motor development, speech delay, intellectual disability, hypotonia, and a history of seizures. In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in the CAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on human CAPZA2 defects, documenting the fourth unambiguously diagnosed case. Furthermore, this splicing mutation type is reported here for the first time. Our research offers additional support for the existence of a CAPZA2-related non-syndromic neurodevelopmental disorder. Our findings augment our understanding of the phenotypic range associated with CAPZA2 deficiency and enrich the knowledge of the mutational spectrum of the CAPZA2 gene.
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Proteína de Capeamento de Actina CapZ , Deficiências do Desenvolvimento , Epilepsia , Heterozigoto , Hipotonia Muscular , Mutação , Pré-Escolar , Feminino , Humanos , Masculino , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/patologia , Epilepsia/genética , Sequenciamento do Exoma , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Hipotonia Muscular/genética , Hipotonia Muscular/patologia , Fenótipo , Splicing de RNA/genética , Proteína de Capeamento de Actina CapZ/genéticaRESUMO
AIM: Health-related quality of life(HRQoL) is essential for high-risk pregnant women and their spouses. This study aimed to explore the dyadic associations (including actor and partner effects) among self-efficacy, dyadic coping, and HRQoL of high-risk pregnant women and their spouses and examine the mediating effect of dyadic coping. METHODS: This cross-sectional study recruited participants from two Grade A tertiary hospitals in China from October 2022 to September 2023. A questionnaire including the Chinese version of the General Self-Efficacy Scale, Dyadic Coping Inventory, and 12 Short Form Health Survey Scales was used for the survey. The actor-partner interdependence mediation model was constructed to test dyadic associations and mediating effects. RESULTS: In the actor effects, self-efficacy was positively associated with dyadic coping and HRQoL (P < 0.05). Regarding partner effects, pregnant women's self-efficacy was positively associated with spouses' dyadic coping and physical health (P < 0.05). Dyadic coping partially mediated the relationship between self-efficacy and HRQoL for both groups(P < 0.05). CONCLUSION: The HRQoL of high-risk pregnant women and their spouses requires urgent attention. Enhancing self-efficacy and dyadic coping in these couples is related to their improved physical and mental health. Healthcare professionals should consider interactions between couples and include them together in perinatal care. Intervention programs for couples or families based on existing positive psychology and dyadic interventions may work together to improve the HRQoL of couples.
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Adaptação Psicológica , Gestantes , Qualidade de Vida , Autoeficácia , Cônjuges , Humanos , Feminino , Estudos Transversais , Qualidade de Vida/psicologia , Cônjuges/psicologia , Adulto , Gravidez , Gestantes/psicologia , China , Inquéritos e Questionários , Masculino , Adulto Jovem , Gravidez de Alto Risco/psicologiaRESUMO
PURPOSE: This study aimed to explore the pathways between family functioning and mental health in people with neuropathic pain, as well as to discuss the mediating role of pain intensity, self-perceived burden, pain catastrophizing, and functional status. DESIGN: Cross-sectional design reported using the STROBE guidelines. METHODS: A total of 277 people with neuropathic pain completed face-to-face questionnaires to evaluate family functioning, pain intensity, pain catastrophizing, self-perceived burden, functional status, and mental health. Structural equation modeling (SEM) was constructed to analyze the pathways between these variables. RESULTS: The positive total effect between family functioning and mental health was significant and partially mediated by self-perceived burden, pain catastrophizing, and functional status. In addition, better family functioning was associated with higher pain intensity, which worsens self-perceived burden, pain catastrophizing, and functional status, masking 23.68% of the positive effects between family functioning and mental health. CONCLUSIONS: Better family functioning was associated with better mental health, as explained by reduced self-perceived burden, reduced pain catastrophizing, and improved functional status. However, this benefit may be partially masked by the relationship that better family functioning explains higher pain intensity. CLINICAL IMPLICATIONS: Nurses' comprehensive assessment and management of neuropathic pain from both the family and individual levels, such as family functioning, pain intensity, self-perceived burden, pain catastrophizing, and functional status, may be beneficial in promoting patients' mental health. In addition, it is necessary to identify why good family functioning is associated with higher pain intensity and intervene in this regard.
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Catastrofização , Neuralgia , Humanos , Masculino , Feminino , Neuralgia/psicologia , Estudos Transversais , Pessoa de Meia-Idade , Adulto , Catastrofização/psicologia , Inquéritos e Questionários , Medição da Dor/métodos , Idoso , Estado Funcional , Saúde Mental , Família/psicologiaRESUMO
In this study, an internal fingerprint-guided epidermal thickness of fingertip skin is proposed for optical image encryption based on optical coherence tomography (OCT) combined with U-Net architecture of a convolutional neural network (CNN). The epidermal thickness of fingertip skin is calculated by the distance between the upper and lower boundaries of the epidermal layer in cross-sectional optical coherence tomography (OCT) images, which is segmented using CNN, and the internal fingerprint at the epidermis-dermis junction (DEJ) is extracted based on the maximum intensity projection (MIP) algorithm. The experimental results indicate that the internal fingerprint-guided epidermal thickness is insensitive to pressure due to normal correlation coefficients and the encryption process between epidermal thickness maps of fingertip skin under different pressures. In addition, the result of the numerical simulation demonstrates the feasibility and security of the encryption scheme by structural similarity index matrix (SSIM) analysis between the original image and the recovered image with the correct and error keys decryption, respectively. The robustness is analyzed based on the SSIM value in three aspects: different pressures, noise attacks, and data loss. Key randomness is valid by the gray histograms, and the average correlation coefficients of adjacent pixelated values in three directions and the average entropy were calculated. This study suggests that the epidermal thickness of fingertip skin could be seen as important biometric information for information encryption.
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Epiderme , Dedos , Estudos Transversais , Epiderme/diagnóstico por imagem , Dedos/diagnóstico por imagem , Algoritmos , BiometriaRESUMO
This cross-sectional study aimed to investigate the relationship between family functioning, pain intensity, self-perceived burden, and pain catastrophizing. Moreover, we also wanted to explore the multiple mediating roles of pain intensity and self-perceived burden. From October 2022 to March 2023, 252 Chinese people with neuropathic pain completed face-to-face questionnaires to assess family functioning, pain intensity, self-perceived burden, and pain catastrophizing. Data analysis was done using descriptive statistics and a structural equation model. The results showed better family functioning was significantly associated with more intense pain, less self-perceived burden, and less pain catastrophizing. Mediation analysis showed that family functioning could indirectly affect pain catastrophizing through pain intensity and self-perceived burden in addition to a direct effect on pain catastrophizing. Moreover, the mediating variable of pain intensity played a masking role. These findings suggest that good family functioning can effectively reduce the self-perceived burden and pain catastrophizing in patients with neuropathic pain. However, family functioning cannot show its maximum effectiveness, and it may be necessary to construct a model of family functioning suitable for patients with neuropathic pain in the future.
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Catastrofização , Dor Crônica , População do Leste Asiático , Relações Familiares , Neuralgia , Humanos , Dor Crônica/complicações , Dor Crônica/psicologia , Estudos Transversais , Depressão , População do Leste Asiático/psicologia , Neuralgia/complicações , Neuralgia/psicologia , Medição da Dor/métodos , Inquéritos e Questionários , Relações Familiares/psicologia , Carga de SintomasRESUMO
OBJECTIVE: To explore the clinical features and genetic etiology of a child with Char syndrome. METHODS: A child who was presented at the Department of Child Health, Henan Children's Hospital in February 2022 was selected as the study subject. Clinical data of the child was collected, and peripheral blood samples of the child and her parents were collected for the extraction of genomic DNA. Whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child had mainly manifested facial dysmorphism, patent ductus arteriosus, growth retardation, curving of fifth fingers and middle toes. Whole exome sequencing revealed that she has harbored a heterozygous c.944A>C (p.Glu315Ala) variant of the TFAP2B gene, which was verified to be de novo by Sanger sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated to be likely pathogenic (PM1+PM2_Supporting+PM6+PP3). CONCLUSION: The heterozygous c.944A>C (p.Glu315Ala) variant of the TFAP2B gene probably underlay the Char syndrome in this child. Above finding has expanded the mutational and phenotypic spectra of the TFAP2B gene, which has facilitated early identification and diagnosis of Char syndrome.
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Fator de Transcrição AP-2 , Humanos , Fator de Transcrição AP-2/genética , Feminino , Sequenciamento do Exoma , Criança , Mutação , Permeabilidade do Canal Arterial/genética , Pré-Escolar , Heterozigoto , Anormalidades Múltiplas , Face/anormalidades , Dedos/anormalidadesRESUMO
Zinc metal batteries are strongly hindered by water corrosion, as solvated zinc ions would bring the active water molecules to the electrode/electrolyte interface constantly. Herein, we report a sacrificial solvation shell to repel active water molecules from the electrode/electrolyte interface and assist in forming a fluoride-rich, organic-inorganic gradient solid electrolyte interface (SEI) layer. The simultaneous sacrificial process of methanol and Zn(CF3SO3)2 results in the gradient SEI layer with an organic-rich surface (CH2OC- and C5 product) and an inorganic-rich (ZnF2) bottom, which combines the merits of fast ion diffusion and high flexibility. As a result, the methanol additive enables corrosion-free zinc stripping/plating on copper foils for 300 cycles with an average coulombic efficiency of 99.5%, a record high cumulative plating capacity of 10 A h/cm2 at 40 mA/cm2 in Zn/Zn symmetrical batteries. More importantly, at an ultralow N/P ratio of 2, the practical VO2//20 µm thick Zn plate full batteries with a high areal capacity of 4.7 mAh/cm2 stably operate for over 250 cycles, establishing their promising application for grid-scale energy storage devices. Furthermore, directly utilizing the 20 µm thick Zn for the commercial-level areal capacity (4.7 mAh/cm2) full zinc battery in our work would simplify the manufacturing process and boost the development of the commercial zinc battery for stationary storage.
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Cardiac fibrosis is a common pathological feature of cardiac remodelling process with disordered expression of multiple genes and eventually lead to heart failure. Emerging evidence suggests that long noncoding RNAs (lncRNAs) have emerged as critical regulators of various biological processes. However, the exact mechanisms of lncRNAs as mediators in cardiac fibrosis have not been fully elucidated. This study aimed to profile the lncRNA expression pattern in human cardiac fibroblasts (HCFs) with cardiac fibrosis. We treated HCFs with transforming growth factor-ß (TGF-ß) to induce their activation. Then, strand-specific RNA-seq was performed to profile and classify lncRNAs; and perform functional analysis in HCFs. We study the transformation of HCFs with molecular and cell biology methods. Among all identified lncRNA candidates, 176 and 526 lncRNAs were upregulated and downregulated respectively in TGF-ß-stimulated HCFs compared with controls. Functional analyses revealed that the target genes of differentially expressed lncRNAs were mainly related to focal adhesion, metabolic pathways, Hippo signaling pathway, PI3K-Akt signaling pathway, regulation of actin cytoskeleton, and hypertrophic cardiomyopathy. As a representative, novel lncRNAs NONHSAG005537 and NONHSAG017620 inhibited the proliferation, migration, invasion, and transformation of HCFs induced by TGF-ß. Collectively, our study established the expression signature of lncRNAs in cardiac fibrosis and demonstrated the cardioprotective role of NONHSAG005537 and NONHSAG017620 in cardiac fibrosis, providing a promising target for anti-fibrotic therapy.
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RNA Longo não Codificante , Humanos , RNA Longo não Codificante/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fibrose , Fibroblastos/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
MAIN CONCLUSION: This paper reviews the progress of research on the morphology, physiology and molecular biology of distyly in plants. It will help to elucidate the mysteries of distyly in plants. Distyly is a unique representative type of heterostyly in plants, primarily characterized by the presence of long style and short style within the flowers of the same species. This interesting trait has always fascinated researchers. With the rapid development of molecular biology, the molecular mechanism for the production of dimorphic styles in plants is also gaining ground. Researchers have been studying plant dimorphic styles from various perspectives. The researchers are gradually unravelling the mechanisms by which plants produce distyly traits. This paper reviews advances in the study of plant dimorphic style characteristics, mainly in terms of the morphology, physiology and molecular biology of plants with dimorphic styles. The aim is to provide a theoretical basis for the study of the mechanism of distyly formation in plants.
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Flores , Biologia Molecular , Flores/genética , FenótipoRESUMO
In our large-scale study, the correlation between obstructive sleep apnea (OSA) related to rapid eye movement (REM) sleep and cardiac autonomic dysfunction was assessed by standard polysomnography (PSG). Cardiac autonomic dysfunction was evaluated by the measurement of heart rate variability (HRV). The cardiovascular disease (CVD) risk was determined using the cross-sectional prevalence of CVD and its overall 10 year risk according to the Framingham risk score (FRS). 4152 individuals were included in the study. A higher apnea-hypopnea index during REM sleep (AHIREM ) was correlated with increased CVD risk. The adjusted odds ratios (95% CIs) for CVD prevalence and its high 10 year risk in participants having severe OSA during REM sleep (AHIREM ≥30 events/h) were 1.452 (1.012-2.084) and 1.904 (1.470-2.466) in the demographic adjusted model and 1.175 (0.810-1.704) and 1.716 (1.213-2.427) in the multivariate adjusted model, respectively, compared with the group with a AHIREM of <5 events/h. Fully adjusted multivariate linear regression models showed the independent association between AHIREM and a more elevated ratio of low-frequency and high-frequency (LF/HF) and LF in normalised units [LF (n.u.)] (P = 0.042, P = 0.027 in all participants and P = 0.033, P = 0.029 in participants with AHI during non-REM sleep <5 events/h, respectively). Mediation analysis demonstrated that OSA during REM sleep and CVD risk was significantly mediated by LF/HF and LF (n.u.). OSA during REM sleep may be a marker behind CVD risk because it promotes cardiac autonomic dysfunction.
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Doenças Cardiovasculares , Apneia Obstrutiva do Sono , Humanos , Sono REM/fisiologia , Polissonografia , Estudos Transversais , China/epidemiologia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologiaRESUMO
PURPOSE OF REVIEW: Despite the growing scope of artificial intelligence (AI) and deep learning (DL) applications in the field of ophthalmology, most have yet to reach clinical adoption. Beyond model performance metrics, there has been an increasing emphasis on the need for explainability of proposed DL models. RECENT FINDINGS: Several explainable AI (XAI) methods have been proposed, and increasingly applied in ophthalmological DL applications, predominantly in medical imaging analysis tasks. SUMMARY: We summarize an overview of the key concepts, and categorize some examples of commonly employed XAI methods. Specific to ophthalmology, we explore XAI from a clinical perspective, in enhancing end-user trust, assisting clinical management, and uncovering new insights. We finally discuss its limitations and future directions to strengthen XAI for application to clinical practice.
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PURPOSE: Currently, the choice of contralateral prophylactic mastectomy (CPM) for breast cancer patients is variable and controversial. Breast cancer patients must make complex and rapid decisions based on the benefits and risks of CPM. Although there are many qualitative studies on the decision-making experiences of breast cancer patients, there is a lack of synthesis of these qualitative studies. Our study goals were to conduct a meta-synthesis of qualitative studies on the decision-making experiences, real-life experiences, psychological feelings and needs of breast cancer patients in CPM decision-making, with the aim of providing information to support the development of CPM practice decisions. METHODS: Using a meta-ethnographic approach, qualitative research studies were analysed and synthesised using the method of "reciprocal translational analysis", and themes related to the decision-making experiences of breast cancer patients with respect to CPM were identified. RESULTS: Five hundred ninety-three documents were retrieved. This meta-synthesis ultimately collected 8 studies. Four themes were identified: (1) decision motivations for survival and body intention; (2) negative and vacillating decision emotions; (3) diverse but weak decision support; (4) short-term satisfaction but long-term unknown and differentiated decision effects. CONCLUSIONS: We found that although patients had different feelings about the effects of CPM in detail, most patients were satisfied with the short-term effects of CPM, but the long-term effects of CPM were still unknown. The study protocol was registered with PROSPERO (International prospective register of systematic reviews) in May 2022 (Registration number: CRD42022334260).
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Neoplasias da Mama , Mastectomia Profilática , Feminino , Humanos , Neoplasias da Mama/cirurgia , Neoplasias da Mama/psicologia , Tomada de Decisões , Mastectomia/psicologia , Mastectomia Profilática/psicologia , Pesquisa QualitativaRESUMO
Rationale: Previous genetic studies of obstructive sleep apnea (OSA) have limitations in terms of precise case definition, integrated quantitative traits, and interpretation of genetic functions; thus, the heritability of OSA remains poorly explained. Objectives: To identify novel genetic variants associated with OSA and objective sleep-related traits and to explore their functional roles. Methods: A genome-wide association study was performed in 20,590 Han Chinese individuals (5,438 OSA and 15,152 control samples). Human samples and point mutation knockin mice were used for follow-up investigation of gene functions. Measurements and Main Results: Two characteristic study-wide significant loci (P < 2.63 × 10-9) for OSA were identified: the PACRG intronic variant rs6455893 on 6q26 (odds ratio [OR] = 1.62; 95% confidence interval [CI], 1.39-1.89; P = 6.98 × 10-10) and the missense variant rs3746804 (p.Pro267Leu) in the riboflavin transporter SLC52A3 on 20p13 (OR = 0.83; 95% CI, 0.79-0.88; P = 7.57 × 10-10). In addition, 18 genome-wide significant loci associated with quantitative OSA and objective sleep-related traits were identified, 5 of which exceeded the study-wide significance threshold. Rs3746804 was associated with elevated serum riboflavin concentrations, and the corresponding mutation in mice increased riboflavin concentrations, suggesting that this variant may facilitate riboflavin uptake and riboflavin-dependent physiological activity. Conclusions: We identified several novel genome-wide significant loci associated with OSA and objective sleep-related traits. Our findings provide insight into the genetic architecture of OSA and suggest that SLC52A3 might be a therapeutic target, whereas riboflavin might be a therapeutic agent.
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Estudo de Associação Genômica Ampla , Apneia Obstrutiva do Sono , Animais , Humanos , Camundongos , População do Leste Asiático , Proteínas de Membrana Transportadoras/genética , Proteínas dos Microfilamentos/genética , Chaperonas Moleculares/genética , Riboflavina , Sono , Apneia Obstrutiva do Sono/genéticaRESUMO
AIM: To compare the relationship between parent-child postoperative pain scores and explore the factors that led to the difference in the score. METHODS: Convenience sampling was used to select children and their parents who were 5-14 years old and scheduled for elective surgery as study subjects. When the child returned to the ward after surgery, the parent and child used the pain assessment tool to score the child's postoperative pain, respectively. RESULTS: A total of 214 children and their parents were included in the study. The results showed that the postoperative pain scores of parents and children were 3.69 ± 2.47 and 4.05 ± 2.90, respectively, and there were differences between the scores (P < 0.05). The results of multiple linear regression indicated that whether the child used Patient-Controlled Analgesia, different types of surgery and parents' pre-operative anxiety may be the reasons for the differences in parent-child scores. CONCLUSION: The parents' pain scores differed from their children's pain scores. If health-care professionals wanted to use the parents' pain score to replace the child's pain score, consideration should be given to whether children used patient-controlled analgesia, different types of surgery and the parents' pre-operative anxiety on the parents' pain score.
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Dor Pós-Operatória , Pais , Humanos , Pré-Escolar , Criança , Adolescente , Dor Pós-Operatória/diagnóstico , Modelos LinearesRESUMO
OBJECTIVE: To explore the clinical characteristics and genetic variants in two children with Tuberous sclerosis complex (TSC). METHODS: Two children who had presented at the Children's Hospital Affiliated to Zhengzhou University respectively in June 2020 and July 2021 were selected as the study subjects. Clinical data of the children were collected, and potential pathogenic variants were screened by whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of their family members. RESULTS: Child 1 was a 7-month-and-29-day-old male, and child 2 was a 2-year-and-6-month-old male. Both children had shown symptoms of epileptic seizures and multiple hypomelanotic macules. Genetic testing revealed that both children had harbored de novo variants of the TSC2 gene, namely c.3239_3240insA and c.3330delC, which were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION: This study has uncovered the genetic etiology for two children with TSC. Above findings have also enriched the phenotypic and mutational spectrum of TSC in the Chinese population.
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Esclerose Tuberosa , Humanos , Lactente , Masculino , Família , Testes Genéticos , Genômica , Mutação , Esclerose Tuberosa/genética , Pré-Escolar , População do Leste AsiáticoRESUMO
OBJECTIVE: To carry out Sanger sequencing for MMACHC gene variants among 65 Chinese pedigrees affected with combined methylmalonic aciduria and homocysteinemia, and summarize their genetic and clinical characteristics and prognosis. METHODS: Clinical characteristics of the 65 children identified with Methylmalonic acidemia and homocysteinemia at the Children's Hospital Affiliated to Zhengzhou University (Zhengzhou Children's Hospital) from April 2017 to April 2022 were selected as the study subjects. Potential variants of the MMACHC gene were detected by direct sequencing of the PCR products. RESULTS: The median age of the 65 children was 3 months (14 days to 17 years old). These included 28 cases (43.08%) from neonatal screening, 11 cases (16.92%) with a history of jaundice, and 9 cases (13.85%) with various degrees of anemia. The main clinical symptoms included development delay, slow growth, epilepsy, hydrocephalus, lethargy, feeding difficulty, regression or decline in motor ability, recurrent respiratory infections, anemia, jaundice, respiratory and heart failures, hydrocephalus, limb weakness, and hypertension. Blood and urine tandem mass spectrometry screening has revealed increase of methylmalonic acid, propionyl carnitine, propionyl carnitine/acetylcarnitine ratio, and propionyl carnitine/free carnitine ratio to various extents, and blood homocysteine was increased in all patients. The detection rate of genetic variants was 98.46% (128/130), and in total 22 types of MMACHC gene variants were detected. The most common ones have included c.609G>A (W203X) (58/128), c.658-660del (K220del) (19/128), and c.80A>G (Q27A) (16/128). Two novel variants have been identified, namely c.565C>T (p.R189C) and c.624_ 625delTG (p.A208Afs), which were respectively predicted as likely pathogenic (PM2_Supporting+PM3+PP2+PP3) and pathogenic (PVS1+PM2_Supporting+PM3+PP2) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Exon 4 had the highest frequency for the detection. CONCLUSION: Identification of MMACHC gene variants has confirmed the diagnosis in the children, among which the c.609G>A variant has the highest frequency. Discovery of the new variants has enriched the mutational spectrum of the MMACHC gene.
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Erros Inatos do Metabolismo dos Aminoácidos , Hidrocefalia , Humanos , Erros Inatos do Metabolismo dos Aminoácidos/genética , OxirredutasesRESUMO
OBJECTIVE: To analyze the clinical phenotype and genetic variant in a child with Raynaud-Claes syndrome (RCS). METHODS: A child who was diagnosed with RCS at the Children's Hospital Affiliated to Zhengzhou University for delayed language and motor development in August 2022 was selected as the study subject. Clinical data of the child were collected, and potential genetic variant was detected by next-generation sequencing and Sanger sequencing. The pathogenicity of the candidate variant was analyzed. RESULTS: The child, a 4-year-and-4-month-old male, has manifested global developmental delay, speech disorders, special facial features and behavioral abnormalities. Genetic testing revealed that he has harbored a hemizygous c.1174C>T (p.Gln392Ter) variant of the CLCN4 gene, which was not detected in either of his parents. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION: The c.1174C>T (p.Gln392Ter) variant of the CLCN4 gene probably underlay the PCS in this child. Above finding has expanded the mutational spectrum of the CLCN4 gene and enabled genetic counseling and prenatal diagnosis for his family.
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Aconselhamento Genético , Testes Genéticos , Feminino , Humanos , Masculino , Gravidez , Canais de Cloreto/genética , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Mutação , Pré-EscolarRESUMO
OBJECTIVE: To analyze the clinical characteristics and pathogenic gene in a Chinese pedigree affected with mitochondrial DNA depletion syndrome 8A (MTDPS8A). METHODS: Whole exome sequencing was carried out for the patient. Sanger sequencing was used to verify the results, and PolyPhen-2 and PROVEAN software were used to predict the impact of amino acid changes on the function of the protein. RESULTS: The patient, a two-month-old female, was admitted to the hospital for poor milk intake and poor mental response. Her clinical manifestations included feeding difficulty, shortness of breath and low muscle tone. Auxiliary laboratory test indicated that the infant was underdeveloped with abnormal liver, kidney, and heart functions accompanied by hyperlacticacidemia. She responded poorly to treatment and eventually died. Sequencing revealed that the child has carried compound heterozygous missense variants of the RRM2B gene, namely c.16delA (p.R6Gfs*22) and c.175G>C (p.A59P), which were respectively inherited from her father and mother, and both were newly discovered pathologic variants. CONCLUSION: The c.16delA and c.175G>C compound heterozygous variants of the RRM2B gene probably underlay the pathogenesis of MTDPS8A. Above finding has strengthened the understanding of the clinical feature and genetic etiology of this disease and expanded the mutation spectrum of the RRM2B gene.
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Testes Genéticos , Ribonucleotídeo Redutases , Proteínas de Ciclo Celular , Criança , China , DNA Mitocondrial/genética , Feminino , Humanos , Lactente , Mutação , Linhagem , Sequenciamento do ExomaRESUMO
PURPOSE OF REVIEW: Artificial intelligence (AI) is the fourth industrial revolution in mankind's history. Natural language processing (NLP) is a type of AI that transforms human language, to one that computers can interpret and process. NLP is still in the formative stages of development in healthcare, with promising applications and potential challenges in its applications. This review provides an overview of AI-based NLP, its applications in healthcare and ophthalmology, next-generation use case, as well as potential challenges in deployment. RECENT FINDINGS: The integration of AI-based NLP systems into existing clinical care shows considerable promise in disease screening, risk stratification, and treatment monitoring, amongst others. Stakeholder collaboration, greater public acceptance, and advancing technologies will continue to shape the NLP landscape in healthcare and ophthalmology. SUMMARY: Healthcare has always endeavored to be patient centric and personalized. For AI-based NLP systems to become an eventual reality in larger-scale applications, it is pertinent for key stakeholders to collaborate and address potential challenges in application. Ultimately, these would enable more equitable and generalizable use of NLP systems for the betterment of healthcare and society.