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The Chinese artichoke (Stachys affinis syn. S. sieboldii) is a widely cultivated crop, and its rhizome is used as a medicinal vegetable. To investigate the causes of viral diseases in Chinese artichokes, the infection rates of four virus species infecting Chinese artichoke were investigated. Since the Chinese artichoke propagates through its tuber, this study aimed to determine whether viral transmission to the progeny is possible through the tuber, by identifying the virus present in the tuber and investigating its accumulation. First, reverse transcription polymerase chain reaction analysis was performed to detect viruses using total RNA extracted from the flowers, leaves, and tubers of Chinese artichoke plants. Alfalfa mosaic virus (AMV) and Chinese artichoke mosaic virus (ChAMV) had high infectivity in Chinese artichoke and most plants were simultaneously infected with AMV and ChAMV. These viruses were present in all tissues, but their detection frequency and accumulation rates varied across different tissues of the Chinese artichoke. Also, we sequenced the coat protein (CP) genes of AMV and ChAMV to investigate genetic variations of virus between the leaf and tuber. It provides information on CP gene sequences and genetic diversity of isolates identified from new hosts of AMV and ChAMV. This study offers valuable insights into the distribution and spread of the ChAMV and AMV within Chinese artichoke plants, which have implications for the management and control of viral infections in crops.
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Background: Consensus has not yet been reached regarding combined anterior cruciate ligament reconstruction (ALLR) with revisional anterior cruciate ligament reconstruction (RACLR). We aimed to compare the clinical outcomes between patients who underwent isolated RACLR and those who underwent RACLR combined with ALLR. Methods: Between June 2010 and June 2021, 49 patients who underwent RACLR were retrospectively reviewed over a 24-month follow-up. Patients were categorized into the isolated RACLR (n = 37, group 1) or combined ALLR group (n = 12, group 2). Clinical outcomes were evaluated with several patient-reported outcome measures (PROMs) and minimal clinically important differences (MCIDs) for each PROM. The side-to-side difference (SSD) of the anterior instability was measured. The pivot-shift test was performed. Results: Baseline characteristics showed no differences between the groups. PROMs showed no significant differences between the groups at the 2-year follow-up. Group 2 was superior to group 1 in the MCID achievement rate for Lysholm knee and International Knee Documentation Committee (IKDC) subjective scores at 24 months postoperatively. At the final follow-up, the proportion of IKDC grade A in SSD for anterior laxity was higher in group 2 than in group 1 (58.3% versus [vs.] 18.3%, p = 0.009), and the proportion of pivot-shift grade 0 was also higher in group 2 (66.7% vs. 27.0%, p = 0.013). The "near return to activity" rate was also higher in group 2 than in group 1 (83.3% vs. 45.9%, p = 0.043). Conclusions: Combining ALLR with RACLR in non-athletes results in a higher proportion of patients with less mechanical graft failure and satisfactory clinical outcomes.
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Stimulator of interferon gene (STING)-associated vasculopathy with onset in infancy (SAVI) is an extremely rare autoinflammatory disease. We present the case of a female Korean patient with early-onset interstitial lung disease who was initially suspected to have systemic lupus erythematosus (SLE) but was ultimately diagnosed with SAVI. The patient exhibited signs of interstitial lung disease and cutaneous manifestations before the age of 1 year and continued to have recurrent fever accompanied by pulmonary infiltrates. Based on positive findings for antibodies associated with SLE, such as antinuclear antibodies and anti-double-stranded DNA, the pulmonary involvement was considered a manifestation of SLE. Another significant symptom was recurrent skin ulceration, which led to partial spontaneous amputation of most of the toes due to inflammation. Given the early onset of interstitial lung disease, severe skin ulcers, and symptoms resembling SLE, autoinflammatory syndrome, especially SAVI was suspected. Following confirmation by genetic testing at age 29 years, the patient was started on tofacitinib, a Janus kinase inhibitor. Despite the prolonged use of multiple immunosuppressive therapies, the patient's lung condition continued to worsen, ultimately requiring lung transplantation. This observational report highlights the importance of considering SAVI as a potential diagnosis when manifestations of interstitial lung disease are observed during infancy. Early proactive treatment is crucial for lung involvement, as this can have long-term effects on patient's prognosis.
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Triple-negative breast cancer (TNBC) accounts for approximately 15-20% of all breast cancer types, indicating a poor survival prognosis with a more aggressive biology of metastasis to the lung and a short response duration to available therapies. Ibulocydine (IB) is a novel (cyclin-dependent kinase) CDK7/9 inhibitor prodrug displaying potent anti-cancer effects against various cancer cell types. We performed in vitro and in vivo experiments to determine whether IB inhibits metastasis and eventually overcomes the poor drug response in TNBC. The result showed that IB inhibited the growth of TNBC cells by inducing caspase-mediated apoptosis and blocking metastasis by reducing MMP-9 expression in vitro. Concurrently, in vivo experiments using the metastasis model showed that IB inhibited metastasis of MDA-MB-231-Luc cells to the lung. Collectively, these results demonstrate that IB inhibited the growth of TNBC cells and blocked metastasis by regulating MMP-9 expression, suggesting a novel therapeutic agent for metastatic TNBC.
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Movimento Celular , Metaloproteinase 9 da Matriz , Neoplasias de Mama Triplo Negativas , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Movimento Celular/efeitos dos fármacos , Feminino , Linhagem Celular Tumoral , Animais , Camundongos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Invasividade Neoplásica , Ensaios Antitumorais Modelo de Xenoenxerto , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Antineoplásicos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Camundongos NusRESUMO
Xelaglifam, developed as a GPR40/FFAR1 agonist, induces glucose-dependent insulin secretion and reduces circulating glucose levels for Type 2 diabetes treatment. This study investigated the effects of Xelaglifam in comparison with Fasiglifam on the in vitro/in vivo anti-diabetic efficacy and selectivity, and the mechanistic basis. In vitro studies on downstream targets of Xelaglifam were performed in GPR40-expressing cells. Xelaglifam treatment exhibited dose-dependent effects, increasing inositol phosphate-1, Ca2+ mobilization, and ß-arrestin recruitment (EC50: 0.76â¯nM, 20â¯nM, 68â¯nM), supporting its role in Gq protein-dependent and G-protein-independent mechanisms. Despite a lack of change in the cAMP pathway, the Xelaglifam-treated group demonstrated increased insulin secretion compared to Fasiglifam in HIT-T15 ß cells under high glucose conditions. High doses of Xelaglifam (<30â¯mg/kg) did not induce hypoglycemia in Sprague-Dawley rats. In addition, Xelaglifam lowered glucose and increased insulin levels in diabetic rat models (GK, ZDF, OLETF). In GK rats, 1â¯mg/kg of Xelaglifam improved glucose tolerance (33.4â¯% and 15.6â¯% for the 1 and 5â¯h) after consecutive glucose challenges. Moreover, repeated dosing in ZDF and OLETF rats resulted in superior glucose tolerance (34â¯% and 35.1â¯% in ZDF and OLETF), reducing fasting hyperglycemia (18.3â¯% and 30â¯% in ZDF and OLETF) at lower doses; Xelaglifam demonstrated a longer-lasting effect with a greater effect on ß-cells including 3.8-fold enhanced insulin secretion. Co-treatment of Xelaglifam with SGLT-2 inhibitors showed additive or synergistic effects. Collectively, these results demonstrate the therapeutic efficacy and selectivity of Xelaglifam on GPR40, supportive of its potential for the treatment of Type 2 diabetes.
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Glicemia , Diabetes Mellitus Tipo 2 , Receptores Acoplados a Proteínas G , beta-Arrestinas , Animais , Humanos , Masculino , Ratos , beta-Arrestinas/metabolismo , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Cricetulus , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/sangue , Controle Glicêmico/métodos , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Secreção de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/metabolismoRESUMO
Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder characterized by hypoventilation due to impaired breathing control by the central nervous system and other symptoms of autonomic dysfunction. Mutations in paired-like homeobox 2 B (PHOX2B) are responsible for most cases of CCHS. Patients with CCHS have various phenotypes and severities, making the diagnosis difficult. This study aimed to present a comprehensive single-center experience of patients with CCHS, including key clinical features, treatment strategies, and outcomes. A retrospective chart review was performed for patients diagnosed with CCHS between January 2001 and July 2023 at Seoul National University Children's Hospital. Finally, we selected 24 patients and collected their demographic data, genotypes, ventilation methods, and clinical features related to autonomic dysfunction. The relationship between the clinical manifestations and genotypes was also examined. All patients used home ventilators, and tracheostomy was performed in 87.5% of patients. Fifteen (62.5%) patients had constipation and nine (37.5%) were diagnosed with Hirschsprung disease. Arrhythmia, endocrine dysfunction, and subclinical hypothyroidism were present in nine (37.5%), six patients (25.0%), and two patients (16.7%), respectively. A significant number of patients exhibited neurodevelopmental delays (19 patients, 79.2%). There was a correlation between the phenotype and genotype of PHOX2B in patients with CCHS. (r = 0.71, p < 0.001). Conclusion: There was a positive correlation between paired-like homeobox 2 B mutations (especially the number of GCN repeats in the polyalanine repeat mutations sequence) and clinical manifestations. This study also demonstrated how initial treatment for hypoventilation affects neurodevelopmental outcomes in patients with CCHS. What is Known: ⢠Congenital central hypoventilation syndrome is a rare genetic disorder characterized by hypoventilation and dysfunction of autonomic nervous system. ⢠The disease-defining gene of CCHS is PHOX2B gene - most of the cases have heterozygous PARMs and the number of GCN triplets varies among the patients(20/24 - 20/33). What is New: ⢠We have noted in the Korean patients with CCHS that there is a correlation between genotype (number of GCN repeats) and severity of phenotype. ⢠National support for rare diseases allowed for a prompter diagnosis of patients with CCHS in Korean population.
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Proteínas de Homeodomínio , Hipoventilação , Apneia do Sono Tipo Central , Humanos , Feminino , Masculino , Apneia do Sono Tipo Central/genética , Apneia do Sono Tipo Central/terapia , Apneia do Sono Tipo Central/diagnóstico , Estudos Retrospectivos , Hipoventilação/congênito , Hipoventilação/terapia , Hipoventilação/genética , Hipoventilação/diagnóstico , Lactente , República da Coreia/epidemiologia , Pré-Escolar , Proteínas de Homeodomínio/genética , Fatores de Transcrição/genética , Respiração Artificial/estatística & dados numéricos , Recém-Nascido , Criança , Fenótipo , Genótipo , Mutação , TraqueostomiaRESUMO
BACKGROUND: Several PD-1 antibodies approved as anti-cancer therapies work by blocking the interaction of PD-1 with its ligand PD-L1, thus restoring anti-cancer T cell activities. These PD-1 antibodies lack inter-species cross-reactivity, necessitating surrogate antibodies for preclinical studies, which may limit the predictability and translatability of the studies. RESULTS: To overcome this limitation, we have developed an inter-species cross-reactive PD-1 antibody, GNUV201, by utilizing an enhanced diversity mouse platform (SHINE MOUSE™). GNUV201 equally binds to human PD-1 and mouse PD-1, equally inhibits the binding of human PD-1/PD-L1 and mouse PD-1/PD-L1, and effectively suppresses tumor growth in syngeneic mouse models. The epitope of GNUV201 mapped to the "FG loop" of hPD-1, distinct from those of Keytruda® ("C'D loop") and Opdivo® (N-term). Notably, the structural feature where the protruding epitope loop fits into GNUV201's binding pocket supports the enhanced binding affinity due to slower dissociation (8.7 times slower than Keytruda®). Furthermore, GNUV201 shows a stronger binding affinity at pH 6.0 (5.6 times strong than at pH 7.4), which mimics the hypoxic and acidic tumor microenvironment (TME). This phenomenon is not observed with marketed antibodies (Keytruda®, Opdivo®), implying that GNUV201 achieves more selective binding to and better occupancy on PD-1 in the TME. CONCLUSIONS: In summary, GNUV201 exhibited enhanced affinity for PD-1 with slow dissociation and preferential binding in TME-mimicking low pH. Human/monkey/mouse inter-species cross-reactivity of GNUV201 could enable more predictable and translatable efficacy and toxicity preclinical studies. These results suggest that GNUV201 could be an ideal antibody candidate for anti-cancer drug development.
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Reações Cruzadas , Imunoterapia , Receptor de Morte Celular Programada 1 , Animais , Humanos , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Camundongos , Reações Cruzadas/imunologia , Imunoterapia/métodos , Concentração de Íons de Hidrogênio , Neoplasias/imunologia , Neoplasias/terapia , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Linhagem Celular Tumoral , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Epitopos/imunologia , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Camundongos Endogâmicos C57BL , FemininoRESUMO
Brassica juncea belongs to the Brassicaceae family and is used as both an oilseed and vegetable crop. As only a few studies have reported on the cucumber mosaic virus (CMV) in B. juncea, we conducted this study to provide a basic understanding of the B. juncea and CMV interactions. B. juncea-infecting CMV (CMV-Co6) and non-infecting CMV (CMV-Rs1) were used. To identify the determinants of systemic infection in B. juncea, we first constructed infectious clones of CMV-Co6 and CMV-Rs1 and used them as pseudo-recombinants. RNA2 of CMV was identified as an important determinant in B. juncea because B. juncea were systemically infected with RNA2-containing pseudo-recombinants; CMV-Co6, R/6/R, and R/6/6 were systemically infected B. juncea. Subsequently, the amino acids of the 2a and 2b proteins were compared, and a chimeric clone was constructed. The chimeric virus R/6Rns/R6cp, containing the C-terminal region of the 2a protein of CMV-Rs1, still infects B. juncea. It is the 2a protein that determines the systemic CMV infection in B. juncea, suggesting that conserved 160G and 214A may play a role in systemic CMV infection in B. juncea.
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Despite increased awareness and availability of genetic testing for hereditary breast and ovarian cancer (HBOC) syndrome for over 20 years, there is still significant underuse of cascade genetic testing among at-risk relatives. This scoping review synthesized evidence regarding psychosocial barriers and facilitators of family communication and/or uptake of cascade genetic testing in relatives from HBOC families. Search terms included 'hereditary breast and ovarian cancer' and 'cascade genetic testing' for studies published from 2012-2022. Through searching common databases, and manual search of references, 480 studies were identified after excluding duplications. Each article was reviewed by two researchers independently and 20 studies were included in the final analysis. CASP, RoBANS 2.0, RoB 2.0, and MMAT were used to assess the quality of included studies. A convergent data synthesis method was used to integrate evidence from quantitative and narrative data into categories and subcategories. Evidence points to 3 categories and 12 subcategories of psychosocial barriers and facilitators for cascade testing: (1) facilitators (belief in health protection and prevention; family closeness; decisional empowerment; family support, sense of responsibility; self-efficacy; supportive health professionals); (2) bidirectional concepts (information; perception of genetic/cancer consequences; negative emotions and attitude); and (3) barriers (negative reactions from family and negative family dynamics). Healthcare providers need to systematically evaluate these psychosocial factors, strengthen facilitators and alleviate barriers to promote informed decision-making for communication of genetic test results and uptake of genetic testing. Bidirectional factors merit special consideration and tailored approaches, as they can potentially have a positive or negative influence on family communication and uptake of genetic testing.
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Predisposição Genética para Doença , Testes Genéticos , Humanos , Feminino , Predisposição Genética para Doença/psicologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/psicologia , Neoplasias Ovarianas/diagnóstico , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Síndrome Hereditária de Câncer de Mama e Ovário/psicologia , Síndrome Hereditária de Câncer de Mama e Ovário/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/psicologia , Neoplasias da Mama/diagnóstico , Família/psicologiaRESUMO
We aimed to evaluate the clinical features of respiratory syncytial virus (RSV) infection and risk factors for severe RSV disease among Korean children in 2022/2023. A total of 235 children were identified, and 84.3% were hospitalized. Patients under 3 months and 2 years of age accounted for 20.9% and 54.5%, respectively. Pneumonia was diagnosed in 40.9% of children and bronchiolitis in 23.8%. Respiratory support and intensive care were required in 43.4% and 7.7% of patients, respectively. Haemophilus influenzae nasopharyngeal colonization and the presence of underlying disease showed a significant correlation with severity indicators. The clinical impact of RSV infection was high on infants and toddlers, even those having no underlying disease or not being indicated for palivizumab.
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Toxic epidermal necrolysis (TEN) is a life-threatening mucocutaneous disorder commonly caused by drugs. TEN is often treated with corticosteroids, intravenous immunoglobulin (IVIG), or cyclosporine; however, the efficacy of these treatments is controversial. Etanercept (a TNF-α antagonist) was proven to decrease skin-healing time in a randomized clinical trial. Herein, we report the case of a 44-month-old boy who developed TEN due to deflazacort as the probable culprit drug and was successfully treated with etanercept. The patient presented to the emergency department complaining of erythematous maculopapular rashes and vesicles all over the face and body, with vesicles on the hands, feet, and trunk. Symptoms started 4 days before presentation, with edema of the upper lip, which progressed to erythematous macules over the body. He was started on deflazacort for nephrotic syndrome 21 days before the visit. Approximately 20% of the body surface area (BSA) was covered by vesicular lesions. Under the diagnosis of Steven Johnson syndrome/TEN, deflazacort was discontinued, and intravenous dexamethasone (1.5 mg/kg/day), a 5-day course of IVIG (0.4 mg/kg/day), and cyclosporine (3 mg/kg/day) were administered. The lesions seemed to be stationary for 3 days, but on the 6th day of hospitalization, when IVIG was discontinued, the vesicular lesions progressed to approximately 60% of the BSA. Etanercept 0.8 mg/kg was administered subcutaneously. Lesions stopped progressing, and bullous lesions started epithelialization. However, on the 15th day, around 30% of the BSA was still involved; thus, a second dose of etanercept was administered. No acute or sub-acute complications were observed. In conclusion, the use of etanercept in children with TEN that is not controlled with conventional therapy is both effective and safe.
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Etanercepte , Síndrome de Stevens-Johnson , Pré-Escolar , Humanos , Masculino , Etanercepte/uso terapêutico , Pregnenodionas/toxicidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/tratamento farmacológico , Síndrome de Stevens-Johnson/etiologiaRESUMO
INTRODUCTION: Children's rare lung diseases are a heterogeneous group of rare lung diseases with significant morbidity and mortality. There is very limited information on the incidence and prevalence of children's rare lung diseases in Asia. We investigated the nationwide incidence, prevalence, and pattern of medical service utilization of children's rare lung diseases in Korea. METHODS: We studied patients who were diagnosed with rare lung diseases coded per International Statistical Classification of Diseases and Related Health Problems, 10th Edition and registered in the national rare diseases database of confirmed patients. Data was extracted from the Korean National Health Insurance Service Claims database over 2019-2021. RESULTS: Average incidence rate was 12.9 new cases per million children per year, and average prevalence rate was 60.2 cases per million children during the study period of 2019-2021. We found that more than 65% of new cases were diagnosed before 2 years of age. ChILD, primary ciliary dyskinesia, and cystic fibrosis were usually diagnosed after 6 years of age. Congenital airway and lung anomalies were often diagnosed before 2 years of age. Busan and Gyeongsangnam-do residents tended to visit hospitals near their place of residence, while residents of other areas tended to visit hospitals in Seoul regardless of their area of residence. CONCLUSIONS: We examined the epidemiology of rare lung diseases in children in South Korea. Our estimation of the incidence and prevalence could be used for sustainable health care and equitable distribution of health care resources.
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Pneumopatias , Doenças Raras , Humanos , República da Coreia/epidemiologia , Criança , Incidência , Prevalência , Pré-Escolar , Masculino , Feminino , Lactente , Pneumopatias/epidemiologia , Adolescente , Doenças Raras/epidemiologia , Recém-Nascido , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Bases de Dados FactuaisRESUMO
BACKGROUND: Asthma is a heterogeneous disease with different outcomes. For children with asthma at the age of 7 years, 67-75% are symptom-free as adults. Data on the important link between childhood and adult asthma are sparse. OBJECTIVE: We aimed to investigate factors associated with persistence of childhood asthma over three years of follow-up by linking data between Korea childhood Asthma Study (KAS) and their matched claims data from Health Insurance Review and Assessment Service (HIRA). METHODS: We analyzed data from 450 preadolescent children aged 7 to 10 years and classified them into remission or persistence groups. Baseline clinical characteristics and exposure to air pollution materials including PM2.5 and PM10 during three years of follow-up were compared. The main outcome was asthma persistence which was defined as the presence of asthma episodes with healthcare utilization and prescription of asthma medications within three years after KAS enrollment. RESULTS: At the third year of follow-up, after stepwise regression analysis, lower age at enrollment (adjusted odds ratio (aOR): 0.79; 95% confidence interval (CI): 0.64-0.96), male sex (aOR: 1.66; 95%CI: 1.05-2.63), proximity from an air-polluting facility (aOR: 2.4; 95%CI: 1.34-4.29), higher level outdoor PM2.5 (aOR: 1.1; 95%CI: 1.02-1.20), and higher rate of doctor-diagnosed food allergy (FA) (aOR: 2.33; 95%CI: 1.06-5.12) were significantly associated with persistence. CONCLUSION: We discovered various independent risk factors for the persistence of childhood asthma. By linking HIRA claims data, we could clarify risk factors for persistence in a well-defined study population.
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Asma , COVID-19 , Doenças Transmissíveis , Hipersensibilidade , Criança , Humanos , Incidência , Pandemias , COVID-19/epidemiologia , COVID-19/complicações , Asma/epidemiologia , Asma/terapia , Asma/etiologia , Hipersensibilidade/epidemiologia , Doenças Transmissíveis/complicações , Doenças Transmissíveis/epidemiologia , Aceitação pelo Paciente de Cuidados de SaúdeRESUMO
Dendritic cells (DCs) are readily generated from the culture of mouse bone marrow (BM) treated with either granulocyte macrophage-colony stimulating factor (GM-CSF) or FMS-like tyrosine kinase 3 ligand (FLT3L). CD11c+MHCII+ or CD11c+MHCIIhi cells are routinely isolated from those BM cultures and generally used as in vitro-generated DCs for a variety of experiments and therapies. Here, we examined CD11c+ cells in the BM culture with GM-CSF or FLT3L by staining with a monoclonal antibody 2A1 that is known to recognize mature or activated DCs. Most of the cells within the CD11c+MHCIIhi DC gate were 2A1+ in the BM culture with GM-CSF (GM-BM culture). In the BM culture with FLT3L (FL-BM culture), almost of all the CD11c+MHCIIhi cells were within the classical DC2 (cDC2) gate. The analysis of FL-BM culture revealed that a majority of cDC2-gated CD11c+MHCIIhi cells exhibited a 2A1-CD83-CD115+CX3CR1+ phenotype, and the others consisted of 2A1+CD83+CD115-CX3CR1- and 2A1-CD83-CD115-CX3CR1- cells. According to the antigen uptake and presentation, morphologies, and gene expression profiles, 2A1-CD83-CD115-CX3CR1- cells were immature cDC2s and 2A1+CD83+CD115-CX3CR1- cells were mature cDC2s. Unexpectedly, however, 2A1-CD83-CD115+CX3CR1+ cells, the most abundant cDC2-gated MHCIIhi cell subset in FL-BM culture, were non-DCs. Adoptive cell transfer experiments in the FL-BM culture confirmed that the cDC2-gated MHCIIhi non-DCs were precursors to cDC2s, i.e., MHCIIhi pre-cDC2s. MHCIIhi pre-cDC2s also expressed the higher level of DC-specific transcription factor Zbtb46 as similarly as immature cDC2s. Besides, MHCIIhi pre-cDC2s were generated only from pre-cDCs and common DC progenitor (CDP) cells but not from monocytes and common monocyte progenitor (cMoP) cells, verifying that MHCIIhi pre-cDC2s are close lineage to cDCs. All in all, our study identified and characterized a new cDC precursor, exhibiting a CD11c+MHCIIhiCD115+CX3CR1+ phenotype, in FL-BM culture.
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Medula Óssea , Antígenos de Histocompatibilidade Classe II , Camundongos , Animais , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Receptor 1 de Quimiocina CX3C/metabolismo , Células da Medula Óssea , Células Dendríticas , Diferenciação Celular , Receptores Proteína Tirosina Quinases/metabolismoRESUMO
The study adapted the Family Gene Toolkit and developed a customized web application for Swiss and Korean families harboring BRCA1 or BRCA2 pathogenic variants to support family communication of genetic testing results and promote cascade genetic testing among at-risk relatives. In the first step, narrative data from 68 women with BRCA1/BRCA2 pathogenic variants and clinician feedback informed a culturally sensitive adaptation of the content consistent with current risk management guidelines. In the second step, the Information Technology team developed the functions and the interface of the web application that will host the intervention. In the third step, a new sample of 18 women from families harboring BRCA1/BRCA2 pathogenic variants tested the acceptability and usability of the intervention using "think-aloud" interviews and a questionnaire. Participants expressed high levels of satisfaction with the intervention. They provided positive feedback for the information regarding active coping, strategies to enhance family communication, interactive elements, and illustrative stories. They reported that the information was useful and the web application was easy to navigate. Findings suggest that the Family Gene Toolkit is well-designed and can increase rates of cascade testing among at-risk relatives. Its efficacy will be tested in a subsequent randomized trial.
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Ventilation should be assisted without asynchrony or cardiorespiratory instability during anesthesia emergence until sufficient spontaneous ventilation is recovered. In this multicenter cohort study, we develop and validate a reinforcement learning-based Artificial Intelligence model for Ventilation control during Emergence (AIVE) from general anesthesia. Ventilatory and hemodynamic parameters from 14,306 surgical cases at an academic hospital between 2016 and 2019 are used for training and internal testing of the model. The model's performance is also evaluated on the external validation cohort, which includes 406 cases from another academic hospital in 2022. The estimated reward of the model's policy is higher than that of the clinicians' policy in the internal (0.185, the 95% lower bound for best AIVE policy vs. -0.406, the 95% upper bound for clinicians' policy) and external validation (0.506, the 95% lower bound for best AIVE policy vs. 0.154, the 95% upper bound for clinicians' policy). Cardiorespiratory instability is minimized as the clinicians' ventilation matches the model's ventilation. Regarding feature importance, airway pressure is the most critical factor for ventilation control. In conclusion, the AIVE model achieves higher estimated rewards with fewer complications than clinicians' ventilation control policy during anesthesia emergence.
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PURPOSE: Cancer coping self-efficacy refers to an individual's confidence in dealing with challenges from cancer-related events, and a positive association with quality of life (QoL) has been demonstrated. Considering unresolved physical and psychological symptoms at the survivorship phase, which are known to worsen QoL, the association between cancer coping self-efficacy and QoL needs to be evaluated controlling for known contributing factors of QoL. This study aimed to describe cancer survivors' cancer coping self-efficacy, symptoms and their relationship with QoL. METHODS: A descriptive correlational study was conducted. Participants were cancer survivors who completed intended treatment except for hormone therapy (N = 240). Cancer coping self-efficacy, symptoms, and QoL were measured. To evaluate the association of cancer survivors' cancer coping self-efficacy with QoL, correlation and multiple regression analysis were conducted. RESULTS: Cancer coping self-efficacy demonstrated a significant positive association with QoL. Symptoms had a significant negative association with QoL. Fully active cancer survivors demonstrated significantly better QoL than those with functional deterioration. Self-efficacy for using spiritual coping had a significant positive association with QoL, along with symptoms and functional status, which explained 37.5% of QoL. CONCLUSIONS: Cancer survivors' QoL was related to spiritual coping self-efficacy, symptoms and functional status. Improving spiritual coping self-efficacy and managing symptoms reflecting survivors' functional status need to be integrated into survivorship care.
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BACKGROUND: To the best of our knowledge, there have been no investigations of longitudinal asthma trajectories based on asthma exacerbation frequency and medications required for asthma control in children. OBJECTIVE: To investigate longitudinal asthma trajectories based on the exacerbation frequency throughout childhood and asthma medication ranks. METHODS: A total of 531 children aged 7 to 10 years were enrolled from the Korean childhood Asthma Study. Required asthma medications for control of asthma from 6 to 12 years of age and asthma exacerbation frequency from birth to 12 years of age were obtained from the Korean National Health Insurance System database. Longitudinal asthma trajectories were identified on the basis of asthma exacerbation frequency and asthma medication ranks. RESULTS: Four asthma clusters were identified: lesser exacerbation with low-step treatment (8.1%), lesser exacerbations with middle-step treatment (30.7%), highly frequent exacerbations in early childhood with small-airway dysfunction (5.7%), and frequent exacerbations with high-step treatment (55.6%). The frequent exacerbations with high-step treatment cluster were characterized by a high prevalence of male sex, increased blood eosinophil (counts) with fractional exhaled nitric oxide, and high prevalence of comorbidities. The highly frequent exacerbation in early childhood with small-airway dysfunction cluster was characterized by recurrent wheeze in preschool age, with high prevalence of acute bronchiolitis in infancy and a greater number of family members with small-airway dysfunction at school age. CONCLUSION: The present study identified 4 longitudinal asthma trajectories on the basis of the frequency of asthma exacerbation and asthma medication ranks. These results would help clarify the heterogeneities and pathophysiologies of childhood asthma.
Assuntos
Asma , Eosinofilia , Criança , Humanos , Masculino , Pré-Escolar , Feminino , Asma/tratamento farmacológico , Asma/epidemiologia , Família , Teste da Fração de Óxido Nítrico ExaladoRESUMO
Various therapeutic approaches, including supplemental nutritional support, have been tried for the treatment of atopic dermatitis (AD). Previous studies have reported the role of vitamin D in the treatment of AD with inconsistent results. The aim of this study was to evaluate the effectiveness of vitamin D in the treatment of AD, with considerations on the heterogeneities of AD. Randomized controlled trials (RCTs) on the efficacy of vitamin D supplementation for AD treatment, published before June 30, 2021 were identified in the PubMed, EMBASE, MEDLINE, and Cochrane Library databases. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation system. This meta-analysis included 5 RCTs with 304 cases of AD. We found that vitamin D supplementation did not decrease AD severity, even when AD was classified as severe vs non-severe. However, vitamin D supplementation was found to be effective in the treatment of AD in RCTs that included both children and adults, but not in those that included only children. Geographic location was associated with a significant difference in the therapeutic effect of vitamin D supplementation. Moreover, vitamin D supplementation of > 2,000 IU/day decreased AD severity, but supplementation ≤ 2,000 IU/day did not. Vitamin D supplementation, in general, was not effective for the treatment of AD. However, vitamin D supplementation might provide a therapeutic effect depending on the geographic location and dose of supplementation. The results of the present meta-analysis suggest that vitamin D supplementation might be targeted for patients with AD who may benefit from vitamin D supplementation.