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BACKGROUND: Atezolizumab-bevacizumab is a standard first-line treatment for unresectable hepatocellular carcinoma (uHCC). Given the diversity in HCC etiology and its potential impact on the tumor microenvironment, understanding how different liver disease etiologies affect treatment efficacy is important. OBJECTIVE: We assessed the influence of liver disease etiology on the efficacy of atezolizumab-bevacizumab and evaluated changes in liver function during treatment with atezolizumab-bevacizumab. PATIENTS AND METHODS: This study included 390 patients with uHCC treated with first-line atezolizumab-bevacizumab from Asan Medical Center, South Korea, and National Cancer Centre Singapore, Singapore from July 2016 to March 2023. Patients were classified to viral, metabolic dysfunction-associated liver disease (MASLD) and nonviral/non-MASLD groups. Albumin-bilirubin (ALBI) scores were recorded at baseline and every two cycles up to cycle six and at the time of disease progression. RESULTS: The majority of patients presented with viral etiologies (74.1%), and 17.2% had MASLD. Across etiological groups (viral versus MASLD versus nonviral/non-MASLD) no significant differences in objective response rate (23.2% versus 29.9% versus 23.5%, respectively; p = 0.515), progression-free survival (median 5.4 versus 7.7 versus 6.0 months; p = 0.320), and overall survival (18.1 versus 18.9 versus 14.4 months; p = 0.400) were observed. Among the patients with disease progression, ALBI scores at the time of progression were significantly higher than at baseline. Subsequent therapy was administered significantly less often to patients with ALBI grade 3 at disease progression compared with those with ALBI grades 1 or 2 (48.4% versus 78.8%, p = 0.002) CONCLUSIONS: Atezolizumab-bevacizumab demonstrates consistent efficacy regardless of HCC etiology, supporting its use as a first-line treatment across diverse patient populations. Liver function assessments remain crucial for managing therapy and predicting outcomes.
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Liposomes are applied to various anticancer treatments as representative drug delivery carriers. However, liposomes do not have their own targeting properties; therefore, there are limitations in drug delivery to specific tissues or cells. High targetability in drug delivery is an important factor in improving bioavailability and drug efficacy and reducing side effects; recent research has been actively investigated to modify the surface of liposomes to give them specific functions. In this study, we studied a drug delivery system for anticancer treatment that enhances targeting ability through fusion with exosomes on the surface of liposomes. We designed exosome-liposome hybrid nanoparticles loaded with a gemcitabine prodrug as a treatment for pancreatic ductal adenocarcinoma (PDAC). Membrane fusion with exosomes shows excellent targeting ability to pancreatic cancer cells due to intrinsic targeting ability and expansion of the macropinocytosis pathway.
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Carcinoma Ductal Pancreático , Desoxicitidina , Ensaios de Seleção de Medicamentos Antitumorais , Vesículas Extracelulares , Gencitabina , Lipossomos , Nanopartículas , Neoplasias Pancreáticas , Tamanho da Partícula , Pró-Fármacos , Desoxicitidina/análogos & derivados , Desoxicitidina/química , Desoxicitidina/farmacologia , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Humanos , Lipossomos/química , Nanopartículas/química , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Proliferação de Células/efeitos dos fármacos , Teste de Materiais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Antineoplásicos/química , Antineoplásicos/farmacologiaRESUMO
OBJECTIVE: Estimating children's target height (TH) plays an important role in diagnosing, evaluating and treating many paediatric endocrinological diseases. However, in many countries, employing Tanner's formula to predict children's final adult height (FAH) is considered misleading. Therefore, this study aimed to re-evaluate the validity of Tanner's formula for predicting the TH of Korean adolescents and young adults and develop a new formula suitable for Korean children. DESIGN/SETTING: Data were derived from the Korean National Health and Nutrition Examination Survey 2010-2019. PATIENTS: A total of 2586 participants (1266 men, 1320 women) were included, excluding participants for whom Tanner's formula could not be calculated because of missing parental height data. MAIN OUTCOME MEASURES: Tanner-based TH was compared with the FAH. RESULTS: The difference between Tanner-based TH and FAH was 4.86±0.178 cm for men and 4.81±0.150 cm for women. Sex-specific univariable and multivariable analyses were conducted to determine variables influencing positive height gap (greater than estimated TH). Both men and women with higher education levels were more likely to exhibit a positive height gap. Those with a history of chronic illness were less likely to exhibit a positive height gap, particularly in women. Using a new formula derived using linear regression analysis, the sum of parental heights explained 27.6% and 30.6% of the variance in sons' and daughters' heights, respectively. CONCLUSIONS: Tanner's formula for calculating TH tended to underestimate FAH; hence, our new formula may offer a better alternative for estimating TH and evaluating growth in Korean children and adolescents.
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Estatura , Inquéritos Nutricionais , Humanos , Masculino , Feminino , República da Coreia , Adolescente , Adulto JovemRESUMO
Methylcyclohexane (MCH) dehydrogenation is an equilibrium-limited reaction that requires high temperatures (>300 °C) for complete conversion. However, high-temperature operation can degrade catalytic activity and produce unwanted side products. Thus, a hybrid zeolite membrane (Z) is prepared on the inner surface of a tubular support and used it as a wall in a membrane reactor (MR) configuration. Pt/C catalysts is packed diluted with quartz sand inside the Z-coated tube and applied the MR for MCH dehydrogenation at low temperatures (190-250 °C). Z showed a remarkable H2-permselectivity in the presence of both toluene and MCH, yielding separation factors over 350. The Z-based MR achieved higher MCH conversion (75.3% ± 0.8% at 220 °C) than the conventional packed-bed reactor (56.4% ± 0.3%) and the equilibrium state (53.2%), owing to the selective removal of H2 through Z. In summary, the hybrid zeolite MR enhances MCH dehydrogenation at low temperatures by overcoming thermodynamic limitations and improves the catalytic performance and product selectivity of the reaction.
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Endothelial-to-mesenchymal transition (EndMT) is a complex biological process of cellular transdifferentiation by which endothelial cells (ECs) lose their characteristics and acquire mesenchymal properties, leading to cardiovascular remodeling and complications in the adult cardiovascular diseases environment. Melatonin is involved in numerous physiological and pathological processes, including aging, and has anti-inflammatory and antioxidant activities. This molecule is an effective therapeutic candidate for preventing oxidative stress, regulating endothelial function, and maintaining the EndMT balance to provide cardiovascular protection. Although recent studies have documented improved cardiac function by melatonin, the mechanism of action of melatonin on EndMT remains unclear. The present study investigated the effects of melatonin on induced EndMT by transforming growth factor-ß2/interleukin-1ß in both in vivo and in vitro models. The results revealed that melatonin reduced the migratory ability and reactive oxygen species levels of the cells and ameliorated mitochondrial dysfunction in vitro. Our findings indicate that melatonin prevents endothelial dysfunction and inhibits EndMT by activating related pathways, including nuclear factor kappa B and Smad. We also demonstrated that this molecule plays a crucial role in restoring cardiac function by regulating the EndMT process in the ischemic myocardial condition, both in vessel organoids and myocardial infarction (MI) animal models. In conclusion, melatonin is a promising agent that attenuates EC dysfunction and ameliorates cardiac damage compromising the EndMT process after MI.
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Melatonina , NF-kappa B , Melatonina/farmacologia , Animais , NF-kappa B/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Transdução de Sinais/efeitos dos fármacos , Camundongos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: The speech reception threshold (SRT), synonymous with the speech recognition threshold, denotes the minimum hearing level required for an individual to discern 50% of presented speech material. This threshold is measured independently in each ear with a repetitive up-down adjustment of stimulus level starting from the initial SRT value derived from pure tone thresholds (PTTs), measured via pure-tone audiometry (PTA). However, repetitive adjustments in the test contributes to increased fatigue for both patients and audiologists, compromising the reliability of the hearing tests. OBJECTIVE: Determining the first (initial) sound level closer to the finally determined SRT value, is important to reduce the number of repetitions. The existing method to determine the initial sound level is to average the PTTs called pure tone average (PTAv). METHODS: We propose a novel method using a machine learning approach to estimate a more optimal initial sound level for the SRT test. Specifically, a convolutional neural network with 1-dimensional filters (1D CNN) was implemented to predict a superior initial level than the conventional methods. RESULTS: Our approach produced a reduction of 37.92% in the difference between the initial stimulus level and the final SRT value. CONCLUSIONS: This outcome substantiates that our approach can reduce the repetitions for finding the final SRT, and, as the result, the hearing test time can be reduced.
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Audiometria de Tons Puros , Teste do Limiar de Recepção da Fala , Humanos , Teste do Limiar de Recepção da Fala/métodos , Audiometria de Tons Puros/métodos , Adulto , Masculino , Feminino , Aprendizado de Máquina , Reprodutibilidade dos Testes , Limiar Auditivo/fisiologia , Redes Neurais de Computação , Percepção da Fala/fisiologiaRESUMO
INTRODUCTION: This study examined the association between sugar-sweetened beverage consumption before the first 24 months of life and attention-deficit/hyperactivity disorder (ADHD). METHODS: A population administrative cohort study was conducted in Korea (2008-2019) using linked national insurance data and a health screening survey. The cohort included 25,305 children in the exposed group with high sugar-sweetened beverage drinks (≥200 mL) and 339,931 in the reference groups (<200 mL) at 24 months of age. The primary outcome was the development of ADHD based on the International Classification of Disease (ICD) codes. Cox proportional model was used to identify the association between sugar-sweetened beverage consumption during early childhood and the later development of ADHD while controlling for multiple risk factors. RESULTS: Over a mean follow-up period of 9.2 years, the incidence rates of ADHD were 29.6 and 23.8 per 10,000 person-years in the exposed and reference groups, respectively. Compared with the reference group, children consuming high-sugar drinks were at an increased risk of ADHD (adjusted hazard ratio 1.17, 95% confidence interval [CI] 1.08-1.27). These associations remained significant even after applying alternative ADHD definitions or adjusting for confounding variables. CONCLUSION: Children who consume sweetened beverages during early childhood are at increased risk of developing ADHD later in life.
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Transtorno do Deficit de Atenção com Hiperatividade , Bebidas Adoçadas com Açúcar , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Bebidas Adoçadas com Açúcar/efeitos adversos , Bebidas Adoçadas com Açúcar/estatística & dados numéricos , Feminino , Masculino , República da Coreia/epidemiologia , Lactente , Pré-Escolar , Estudos de Coortes , Fatores de Risco , Modelos de Riscos Proporcionais , Incidência , Criança , SeguimentosRESUMO
Various X-ray techniques are employed to investigate specimens in diverse fields. Generally, scattering and absorption/emission processes occur due to the interaction of X-rays with matter. The output signals from these processes contain structural information and the electronic structure of specimens, respectively. The combination of complementary X-ray techniques improves the understanding of complex systems holistically. In this context, we introduce a multiplex imaging instrument that can collect small-/wide-angle X-ray diffraction and X-ray emission spectra simultaneously to investigate morphological information with nanoscale resolution, crystal arrangement at the atomic scale and the electronic structure of specimens.
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The Senior Meaning in Life Evaluation scale encompasses not only older adults' personal motivation and growth but also the meaning for them in society and in their relationships: With this scale, we aimed to present their voices. A three-phase process was followed: The scale's items were developed empirically from interviews of older adults; exploratory factor analysis (EFA) was conducted to test convergent and concurrent validity; and finally, confirmatory factor analysis (CFA) was performed. EFA resulted in 18 items grouped into 4 factors (i.e., proactive on life, overcoming emptiness, acceptance in life, and social contribution), which was supported by the CFA.
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Inquéritos e Questionários , Humanos , Idoso , Análise Fatorial , Psicometria/métodos , Reprodutibilidade dos TestesRESUMO
PURPOSE: This manuscript presents RADCURE, one of the most extensive head and neck cancer (HNC) imaging datasets accessible to the public. Initially collected for clinical radiation therapy (RT) treatment planning, this dataset has been retrospectively reconstructed for use in imaging research. ACQUISITION AND VALIDATION METHODS: RADCURE encompasses data from 3346 patients, featuring computed tomography (CT) RT simulation images with corresponding target and organ-at-risk contours. These CT scans were collected using systems from three different manufacturers. Standard clinical imaging protocols were followed, and contours were manually generated and reviewed at weekly RT quality assurance rounds. RADCURE imaging and structure set data was extracted from our institution's radiation treatment planning and oncology information systems using a custom-built data mining and processing system. Furthermore, images were linked to our clinical anthology of outcomes data for each patient and includes demographic, clinical and treatment information based on the 7th edition TNM staging system (Tumor-Node-Metastasis Classification System of Malignant Tumors). The median patient age is 63, with the final dataset including 80% males. Half of the cohort is diagnosed with oropharyngeal cancer, while laryngeal, nasopharyngeal, and hypopharyngeal cancers account for 25%, 12%, and 5% of cases, respectively. The median duration of follow-up is five years, with 60% of the cohort surviving until the last follow-up point. DATA FORMAT AND USAGE NOTES: The dataset provides images and contours in DICOM CT and RT-STRUCT formats, respectively. We have standardized the nomenclature for individual contours-such as the gross primary tumor, gross nodal volumes, and 19 organs-at-risk-to enhance the RT-STRUCT files' utility. Accompanying demographic, clinical, and treatment data are supplied in a comma-separated values (CSV) file format. This comprehensive dataset is publicly accessible via The Cancer Imaging Archive. POTENTIAL APPLICATIONS: RADCURE's amalgamation of imaging, clinical, demographic, and treatment data renders it an invaluable resource for a broad spectrum of radiomics image analysis research endeavors. Researchers can utilize this dataset to advance routine clinical procedures using machine learning or artificial intelligence, to identify new non-invasive biomarkers, or to forge prognostic models.
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Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Masculino , Humanos , Feminino , Estudos Retrospectivos , Inteligência Artificial , Tomografia Computadorizada por Raios X/métodos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapiaRESUMO
BACKGROUND: Immune checkpoint inhibitor (ICI)-based treatments have become the mainstay of first-line treatment for unresectable hepatocellular carcinoma (HCC), but there has been a concern that intrahepatic HCC lesions may be less responsive to ICI monotherapy. We aimed to investigate the organ-specific response patterns among unresectable HCC patients treated with first-line atezolizumab-bevacizumab or lenvatinib. METHODS: This retrospective study included 386 patients with Child-Pugh A unresectable HCC who were treated with first-line atezolizumab-bevacizumab (n = 217) or lenvatinib (n = 169). The organ-specific response was separately evaluated according to the site of the lesions: liver, lung, lymph node (LN), and intraabdomen based on a radiological evaluation adopted from RECIST v 1.1. RESULTS: The median age was 60 years. Hepatitis B infection was the most common etiology (n = 270, 69.9%), and 291 (75.4%) patients had a viral etiology. The proportion of patients achieving a ≥ 30% reduction in the tumor burden for each organ category was overall higher in the atezolizumab-bevacizumab group than that in the lenvatinib group: 20.2% vs. 11.8%, 23.0% vs. 12.2%, 27.9% vs. 17.9% and 33.3% vs. 15.0% for intrahepatic, lung, LN, and intraabdominal lesions, respectively. The corresponding values for the subgroup with a viral etiology were 17.3% vs. 8.1%, 18.8% vs. 13.3%, 28.9% vs. 3.6%, and 36.0% vs. 12.5%, respectively. CONCLUSION: Compared to lenvatinib, atezolizumab-bevacizumab was associated with a favorable organ-specific response regardless of the site of the tumor lesions. Unlike anti-PD-1 monotherapy, atezolizumab-bevacizumab had a comparable organ-specific response between intrahepatic and extrahepatic lesions, especially for those with viral etiology HCCs.
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Anticorpos Monoclonais Humanizados , Bevacizumab , Carcinoma Hepatocelular , Neoplasias Hepáticas , Compostos de Fenilureia , Quinolinas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Quinolinas/uso terapêutico , Quinolinas/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Estudos Retrospectivos , Compostos de Fenilureia/uso terapêutico , Compostos de Fenilureia/administração & dosagem , Idoso , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: The relationship between epilepsy and depression is bidirectional. One condition exacerbates the other. However, there are no current guidelines for treating depression in epilepsy patients. In some cases, seizures worsen when antidepressants (AD) are prescribed or when they are discontinued due to adverse events. The Shugan Jieyu capsule, composed of Acanthopanax senticosus and Hypericum perforatum, is a widely used herbal medicine for treating depression. This study aimed to explore the effectiveness and safety of Shugan Jieyu capsules (SJC) in relieving depression in patients with epilepsy. METHODS: We searched English, Korean, Japanese, and Chinese databases in October 2023 to collect all relevant randomized clinical trials (RCTs). The primary outcomes were the depression scale scores and seizure frequency. The secondary outcomes were quality of life (QoL) and adverse events. RESULTS: Nine RCTs were included in this meta-analysis. Compared with AD, SJC showed significant differences in the improvement of depression (SMD: 3.82, 95% CI: 3.25, 4.39) and reduction in seizure frequency (MD: 0.39 times/month, 95% CI: 0.28, 0.50). SJC showed more beneficial results than antiepileptic drugs (AED) in terms of antidepressant effects (SMD: 1.10, 95% CI: 0.69, 1.51) and QoL (MD: 11.75, 95% CI: 10.55, 12.95). When patients were prescribed AED, the additional administration of SJC improved depression symptoms (SMD: 0.96, 95% CI: 0.28, 1.63). The SJC treatment group had a lower incidence of side effects than the control group. However, the difference was not statistically significant. CONCLUSIONS: Our results suggest that SJC may be effective in treating depression in patients with epilepsy. Additionally, SJC has the potential to help reduce seizure frequency in epilepsy patients with depression.
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Epilepsia , Humanos , Epilepsia/tratamento farmacológico , Antidepressivos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Convulsões/tratamento farmacológico , Convulsões/induzido quimicamenteRESUMO
BACKGROUND: Vitamin D deficiency is relatively common among patients with multiple myeloma. The prognostic significance of vitamin D deficiency in Asian patients with multiple myeloma remains unevaluated. This study aimed to assess the prognostic value of vitamin D levels in this Korean patient population. METHODS: From September 2017 to May 2020, 98 patients were enrolled in the study. Vitamin D deficiency was defined as 25-hydroxyvitamin D level of less than 10 ng/mL. RESULTS: Thirty-six patients (36.7%) had vitamin D deficiency. These patients had significantly lower 2-year progression-free survival rates (44.8% vs. 66.9%, P = .008) and overall survival (OS) rates (2-year OS 47.2% vs. 74.2%, P = .024) compared with those without deficiency. Furthermore, patients who received vitamin D supplementation showed a trend towards improved OS compared with those who did not, with a 2-year OS rate of 51.9% vs. 33.3% (P = .14). CONCLUSION: These findings suggest that vitamin D levels are a significant prognostic factor in patients with multiple myeloma.
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Mieloma Múltiplo , Deficiência de Vitamina D , Humanos , Prognóstico , Mieloma Múltiplo/complicações , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Vitamina D , República da Coreia/epidemiologiaRESUMO
BACKGROUND: Ever since the start of the coronavirus disease 2019 (COVID-19) pandemic, students have been spending an increasingly longer time staring at electrical devices to take online courses. OBJECTIVE: This study aimed to investigate the effect of the virtual class environment on eye and musculoskeletal problems in university students during the COVID-19 pandemic. METHODS: A total of 365 university students were enrolled in this study. They completed an online survey to examine the effects of online learning on eye and musculoskeletal health during the COVID-19 pandemic. The questionnaires consisted of four sections: demographic and general information, environmental and work factors, device-related factors, and visual display terminal syndrome (VDTS). RESULTS: Participants have been taking online classes of 14.5 hours per week during the COVID-19 pandemic. They reported the mean daily usage of digital devices of 4.8±2.2 hours before the pandemic but this increased to 8.1±2.9 during the pandemic. Eye fatigue and neck, shoulder, and back pain have also been reported. The mean VDTS score was significantly influenced by gender, obesity, daily exercise, regular breaks, wear of blue light-blocking glasses, daily hours of electronic device use, and illumination of room. CONCLUSION: The results of this study showed that university students taking online classes suffered more from VDTS, especially in eye fatigue and neck, lower back, and shoulder pain during COVID-19 pandemic than prior. This study suggests that it is necessary to take breaks in online classes and regularly provide appropriate eye exercise and physical activity to prevent VDTS.
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Astenopia , COVID-19 , Humanos , Astenopia/epidemiologia , Astenopia/etiologia , COVID-19/epidemiologia , Pandemias , Universidades , EstudantesRESUMO
Thyroid hormone resistance (RTH) is characterized by a decreased sensitivity of target tissues to thyroid hormones due to a defect in the THRα- and THRß-encoded thyroid hormone receptors (THRs). The clinical manifestations range from no symptoms to simple goiter and hypo- or hyperthyroidism, depending on the receptor subtype distribution in the tissues. Here, we report the case of a thyroid hormone-resistant 12-month-old boy carrying a novel THRß variant who was initially diagnosed with congenital hypothyroidism. An extensive evaluation revealed increased free T4 level and inappropriately increased thyroid-stimulating hormone (TSH) level; a normal lipid profile, sex hormone-binding globulin, and free alpha subunit of TSH; exaggerated TSH response to THR; and no radiological evidence of pituitary adenoma. A targeted next-generation sequencing panel identified a heterozygote c.993T>G (p.Asn331Lys) mutation in the THRß gene. During the first year of life, a higher dose of levothyroxine was administered to the patient due to uncompensated RTH. Levothyroxine treatment was continued after 3 years to maintain TSH level <5 mIU/mL, but the observed weight gain was poor, height increase was insufficient, and bone development was delayed. However, neither hyperactivity nor developmental delay was observed. Patients with RTH exhibit various clinical features. Due to its heterogeneous nature, genetic test for accurate diagnosis is important to provide proper management.
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MR1 is a ubiquitously expressed MHC-Ib molecule that presents microbial metabolites to MR1-restricted T cells, but there are differences in the antigen presentation pathway of an intracellular microbe compared to exogenous antigen. We have shown the importance of endosomal trafficking proteins in MR1-dependent presentation of Mycobacterium tuberculosis (Mtb). Two pore channels (TPCs) are endosomal calcium channels that regulate endosomal trafficking. Due to their location on endosomes, we hypothesized that TPCs could be required for MR1-dependent presentation of antigens derived from the intracellular microbe Mtb. We found that TPCs are critical for the presentation of Mtb by MR1; inhibition of TPCs had no effect on MR1 presentation of extracellular (exogenous) antigens, HLA-B presentation, or HLA-II presentation. Finally, we found that the calcium sensitive trafficking protein Synaptotagmin 7 was also key in the presentation of Mtb by MR1. This calcium-dependent endosomal pathway is a novel mechanism by which the immune system can sample intracellular antigens.
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Artificial intelligence (AI) and machine learning (ML) are becoming critical in developing and deploying personalized medicine and targeted clinical trials. Recent advances in ML have enabled the integration of wider ranges of data including both medical records and imaging (radiomics). However, the development of prognostic models is complex as no modeling strategy is universally superior to others and validation of developed models requires large and diverse datasets to demonstrate that prognostic models developed (regardless of method) from one dataset are applicable to other datasets both internally and externally. Using a retrospective dataset of 2,552 patients from a single institution and a strict evaluation framework that included external validation on three external patient cohorts (873 patients), we crowdsourced the development of ML models to predict overall survival in head and neck cancer (HNC) using electronic medical records (EMR) and pretreatment radiological images. To assess the relative contributions of radiomics in predicting HNC prognosis, we compared 12 different models using imaging and/or EMR data. The model with the highest accuracy used multitask learning on clinical data and tumor volume, achieving high prognostic accuracy for 2-year and lifetime survival prediction, outperforming models relying on clinical data only, engineered radiomics, or complex deep neural network architecture. However, when we attempted to extend the best performing models from this large training dataset to other institutions, we observed significant reductions in the performance of the model in those datasets, highlighting the importance of detailed population-based reporting for AI/ML model utility and stronger validation frameworks. We have developed highly prognostic models for overall survival in HNC using EMRs and pretreatment radiological images based on a large, retrospective dataset of 2,552 patients from our institution.Diverse ML approaches were used by independent investigators. The model with the highest accuracy used multitask learning on clinical data and tumor volume.External validation of the top three performing models on three datasets (873 patients) with significant differences in the distributions of clinical and demographic variables demonstrated significant decreases in model performance. Significance: ML combined with simple prognostic factors outperformed multiple advanced CT radiomics and deep learning methods. ML models provided diverse solutions for prognosis of patients with HNC but their prognostic value is affected by differences in patient populations and require extensive validation.
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Aprendizado Profundo , Neoplasias de Cabeça e Pescoço , Humanos , Prognóstico , Estudos Retrospectivos , Inteligência Artificial , Neoplasias de Cabeça e Pescoço/diagnóstico por imagemRESUMO
This study evaluates the efficacy and safety of fractional CO2 lasers for treating genitourinary syndrome of menopause (GSM) in Korean women. The patients received three laser applications at an interval of 4 weeks each. The severity of GSM symptoms was assessed using a visual analog scale (VAS) at baseline and at every visit. The objective scale was measured using the vaginal health index score (VHIS) and Vaginal Maturation Index (VMI) after completion of the laser procedure. During each procedure, the patients' pain in the VAS score was recorded. In the last visit, patients evaluated their satisfaction with the laser therapy using a 5-point Likert scale. Thirty women completed all the study protocols. After two sessions of laser therapy, some GSM symptoms (vaginal dryness and urgency) and VHIS improved significantly. After completion of the treatment, all GSM symptoms improved (p < 0.05), and the VHIS further increased significantly (VHIS at baseline, 8.86 ± 3.2 vs. V3, 16.83 ± 3.15, p < 0.001). The average satisfaction was 4.3. This study shows that fractional CO2 laser treatment is effective and safe for Korean women with GSM. Further studies are needed to confirm these results and assess the long-term effects of laser therapy.
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Cardiac tissue damage following ischemia leads to cardiomyocyte apoptosis and myocardial fibrosis. Epigallocatechin-3-gallate (EGCG), an active polyphenol flavonoid or catechin, exerts bioactivity in tissues with various diseases and protects ischemic myocardium; however, its association with the endothelial-to-mesenchymal transition (EndMT) is unknown. Human umbilical vein endothelial cells (HUVECs) pretreated with transforming growth factor ß2 (TGF-ß2) and interleukin 1ß (IL-1ß) were treated with EGCG to verify cellular function. In addition, EGCG is involved in RhoA GTPase transmission, resulting in reduced cell mobility, oxidative stress, and inflammation-related factors. A mouse myocardial infarction (MI) model was used to confirm the association between EGCG and EndMT in vivo. In the EGCG-treated group, ischemic tissue was regenerated by regulating proteins involved in the EndMT process, and cardioprotection was induced by positively regulating apoptosis and fibrosis of cardiomyocytes. Furthermore, EGCG can reactivate myocardial function due to EndMT inhibition. In summary, our findings confirm that EGCG is an impact activator controlling the cardiac EndMT process derived from ischemic conditions and suggest that supplementation with EGCG may be beneficial in the prevention of cardiovascular disease.
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BACKGROUND: The importance of extracurricular activities (EAs) has been emphasized in medical education. These activities could enhance medical students' emotional and physical health and afford them developmental opportunities. Despite the growing amount of research related to this theme, few studies review and synthesize the existing literature. This study aims to provide an understanding of the educational implications of EAs in medical colleges and constructs an integrated conceptual framework concerning their types and learning outcomes by literature review. METHODS: An integrative literature review was conducted following Torraco's method, with the aim to generate a new framework for the given topic. The authors utilized Scopus and PubMed as databases, using search terms "extracurricular," "medical," and "students." Initially, titles and abstracts were screened to include relevant studies, and the researchers verified the eligibility of the articles by following the inclusion and exclusion criteria. Of the 263 articles identified, 64 empirical studies were selected for further review. RESULTS: EAs in undergraduate medical education can be classified into direct extracurricular activities and indirect extracurricular activities, the latter of which is sorted into nine sub-categories. We identified seven main categories regarding the learning outcomes of EAs. In addition to general activities (e.g., pro-social activities, team sports), some distinctive activities such as research have been largely addressed in previous studies. The results of EAs were discussed in relation to academic growth, career development, and psychological experiences. CONCLUSIONS: This review identified the types and learning outcomes of EAs in the context of medical education, thereby suggesting ways to improve the quality of EAs and maximize their educational effects.