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This is the first study presenting the overall descriptive epidemiology of multiple myeloma (MM), including incidence, mortality rate, and prevalence, in South Korea between 2010 and 2018 based on nationwide medical insurance coverage and mortality statistics data. The incidence of MM between 2010 and 2018 was obtained from nationwide medical claims data, and mortality data were obtained from the Korea National Statistical Office. The age-standardized incidence rate (ASIR) and mortality rate (ASMR) and one- and five-year survival rates of patients with MM each year were estimated. There were 10,835 patients with MM aged ≥ 20 years in South Korea between 2010 and 2018. The ASIR was 2.42/100,000 in 2010 and increased to 2.71/100,000 in 2018, with an annual percent change (APC) of 1.86% (95% CI = 0.74-2.99%, P = 0.005). While this trend was significant in women, it was not statistically significant in men. The ASMR did not significantly change over time. Furthermore, the median survival time of patients with MM diagnosed between 2010 and 2018 was 3.36 years. Notably, the one-year survival rate of patients was increased from 65.3% in 2010 to 76.2% in 2017. Finally, the proportion of patients with MM who received novel therapeutic agents, such as proteasome inhibitors or immunomodulatory drugs, as first-line treatment increased from 37.7% in 2010 to 97.8% in 2018. The ASIR and prevalence of MM in South Korea increased between 2010 and 2018, especially in women and the survival rate of patients with MM has increased.
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BACKGROUND: Taking facial and intraoral clinical photos is one of the essential parts of orthodontic diagnosis and treatment planning. Among the diagnostic procedures, classification of the shuffled clinical photos with their orientations will be the initial step while it was not easy for a machine to classify photos with a variety of facial and dental situations. This article presents a convolutional neural networks (CNNs) deep learning technique to classify orthodontic clinical photos according to their orientations. METHODS: To build an automated classification system, CNNs models of facial and intraoral categories were constructed, and the clinical photos that are routinely taken for orthodontic diagnosis were used to train the models with data augmentation. Prediction procedures were evaluated with separate photos whose purpose was only for prediction. RESULTS: Overall, a 98.0% valid prediction rate resulted for both facial and intraoral photo classification. The highest prediction rate was 100% for facial lateral profile, intraoral upper, and lower photos. CONCLUSION: An artificial intelligence system that utilizes deep learning with proper training models can successfully classify orthodontic facial and intraoral photos automatically. This technique can be used for the first step of a fully automated orthodontic diagnostic system in the future.
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Inteligência Artificial , Aprendizado Profundo , Humanos , Redes Neurais de Computação , FaceRESUMO
Cancer stem cells (CSCs) have tumor initiation, self-renewal, metastasis and chemo-resistance properties in various tumors including colorectal cancer. Targeting of CSCs may be essential to prevent relapse of tumors after chemotherapy. Phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) signals are central regulators of cell growth, proliferation, differentiation, and apoptosis. These pathways are related to colorectal tumorigenesis. This study focused on PI3K and mTOR pathways by inhibition which initiate differentiation of SW620 derived CSCs and investigated its effect on tumor progression. By using rapamycin, LY294002, and NVP-BEZ235, respectively, PI3K and mTOR signals were blocked independently or dually in colorectal CSCs. Colorectal CSCs gained their differentiation property and lost their stemness properties most significantly in dual-blocked CSCs. After treated with anti-cancer drug (paclitaxel) on the differentiated CSCs cell viability, self-renewal ability and differentiation status were analyzed. As a result dual-blocking group has most enhanced sensitivity for anti-cancer drug. Xenograft tumorigenesis assay by using immunodeficiency mice also shows that dual-inhibited group more effectively increased drug sensitivity and suppressed tumor growth compared to single-inhibited groups. Therefore it could have potent anti-cancer effects that dual-blocking of PI3K and mTOR induces differentiation and improves chemotherapeutic effects on SW620 human colorectal CSCs.
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Diferenciação Celular/efeitos dos fármacos , Inibidores de Fosfoinositídeo-3 Quinase , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Antígeno AC133/genética , Antígeno AC133/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromonas/farmacologia , Cromonas/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Humanos , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Morfolinas/farmacologia , Morfolinas/uso terapêutico , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Quinolinas/farmacologia , Quinolinas/uso terapêutico , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
We investigated the role of profilin 2 in the stemness, migration, and invasion of HT29 cancer stem cells (CSCs). Increased and decreased levels of profilin 2 significantly enhanced and suppressed the self-renewal, migration, and invasion ability of HT29 CSCs, respectively. Moreover, profilin 2 directly regulated the expression of stemness markers (CD133, SOX2, and ß-catenin) and epithelial mesenchymal transition (EMT) markers (E-cadherin and snail). CD133 and ß-catenin were up-regulated by overexpression of profilin 2 and down-regulated by depletion of profilin 2. SOX2 was decreased by profilin 2 depletion. E-cadherin was not influenced by profilin 2- overexpression but increased by profilin 2- knockdown. The expression of snail was suppressed by profilin 2- knockdown. We speculated that stemness and the EMT are closely linked through profilin 2-related pathways. Therefore, this study indicates that profilin 2 affects the metastatic potential and stemness of colorectal CSCs by regulating EMT- and stemness-related proteins.
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Neoplasias Colorretais/genética , Proteínas de Neoplasias/biossíntese , Células-Tronco Neoplásicas , Profilinas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Células HT29 , Humanos , Invasividade Neoplásica/genética , Profilinas/biossíntese , Via de Sinalização Wnt/genética , beta Catenina/biossínteseRESUMO
Background/Aims: To date, there is no prospective study that specifically investigated the efficacy of infliximab in intestinal Behçet's disease (BD). This study evaluated the efficacy of infliximab in patients with moderate-to-severe active intestinal BD that are refractory to conventional therapies. Methods: This phase 3, interventional, open-label, single-arm study evaluated clinical outcomes of infliximab treatment in patients with moderate-to-severe intestinal BD. The coprimary endpoints were clinical response, decrease in disease activity index for intestinal BD (DAIBD) score ≥20 from weeks 0 to 8 for the induction therapy and week 32 for the maintenance therapy. Results: A total of 33 patients entered the induction therapy and were treated with infliximab 5 mg/kg intravenously at weeks 0, 2, and 6. The mean DAIBD score changed from 90.8±40.1 at week 0 to 40.3±36.4 at week 8, with a significant mean change of 50.5±36.4 (95% confidence interval, 37.5 to 63.4; p<0.001). Thirty-one (93.9%) continued to receive 5 mg/kg infliximab every 8 weeks during the maintenance therapy. The mean change in the DAIBD score after the maintenance therapy was statistically significant (61.5±38.5; 95% confidence interval, 46.0 to 77.1; p<0.001, from weeks 0 to 32). The proportion of patients who maintained a clinical response was 92.3% at week 32. No severe adverse reactions occurred during the induction and maintenance therapies. Conclusions: This study provided evidence that infliximab 5 mg/kg induction and maintenance therapies are efficacious and well-tolerated in patients with moderate-to-severe active intestinal BD. (ClinicalTrials.gov identifier: NCT02505568).
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Síndrome de Behçet , Enteropatias , Humanos , Síndrome de Behçet/tratamento farmacológico , Infliximab/efeitos adversos , Enteropatias/tratamento farmacológico , Intestinos , Estudos Prospectivos , Resultado do TratamentoRESUMO
Objective: To investigate the effects of long-acting injectable 3-monthly paliperidone palmitate on the clinical and social functioning of patients with schizophrenia. Methods: This study enrolled patients with schizophrenia receiving long-acting injectable 1-monthly paliperidone palmitate for at least 4 months and who subsequently received 3-monthly paliperidone palmitate. Accordingly, 418 patients were followed up for 24 weeks. Their clinical symptoms and social functioning were measured using the Clinical Global Impression-Severity of Illness and Personal and Social Performance scales. Results: The Personal and Social Performance total score was significantly higher after 3-monthly paliperidone palmitate treatment than at baseline (baseline vs. week 24: 54.3 ± 18.0 vs. 61.0 ± 14.5 [mean ± standard deviation]; p < 0.001; Wilcoxon signed-rank test); the proportion of patients in the mildly ill group (scores 71-100) also increased significantly (baseline vs. week 24: 16.5% vs. 20.6%; p < 0.001; McNemar-Bowker test). The mean Clinical Global Impression-Severity of Illness score decreased significantly (baseline vs. week 24: 3.7 ± 1.0 vs. 3.4 ± 0.9; p < 0.001; Wilcoxon signed-rank test), as did the proportion of patients in the severely ill group (baseline vs. week 24: 4.1% vs. 2.1%; p < 0.001; McNemar-Bowker test). Conclusion: Continuous 3-monthly paliperidone palmitate treatment significantly enhances the personal and social performance of patients with schizophrenia and reduces the proportion of those with severe illness. These findings suggest that long-acting injectable antipsychotic administration at intervals longer than 1 month might improve the social functioning of and promote return to activities of daily living in patients with schizophrenia.
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The aim of this study was to evaluate the effects of the tongue and lip pressure on dentofacial morphology. The subjects comprised 194 patients with malocclusion. Anterior and posterior tongue elevation and lip pressures were evaluated using the Iowa Oral Performance Instrument (IOPI) device. The lateral cephalograms of each subject were traced and digitized to perform the analysis. Statistical analysis was used to investigate the relationship between perioral muscle force and the cephalometric variables. Anterior and posterior tongue pressure was both higher in males than in females. No sex difference in lip pressure was observed. The group with a low posterior tongue pressure showed a short ramus height, short posterior facial height, and clockwise-rotated mandible. On the other hand, lip pressure had a significant influence on maxillary incisor angulation. Skeletal pattern was not found to be significantly related with lip pressure. The anterior tongue pressure appeared as a mixed pattern of the two results. Tongue pressure was related to skeletal measurements, such as short posterior facial height, and lip pressure was related to the angulation of the anterior teeth. This study suggests that there may be differences in dentofacial morphology according to the differences in perioral muscle force.