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Background: Attitudes toward suicide are essential in suicide prevention, as suicide is socio-culturally nuanced. Although the relationship between individual attitudes and suicidal behavior has been extensively studied, the effect of community attitudes-aggregated by region-on suicide mortality remains ambiguous. This study explored the association between community attitudes and real-world suicide mortality. Methods: Data on attitudes toward suicide from the 2018 Korea National Suicide Survey (N = 1500) and individual mortality data from the MicroData Integrated System were obtained. Confirmatory factor analysis supported a factor structure with three factors: "Permissiveness," "Unjustified behavior," and "Readiness to help/Preventability." Thirty regional units in South Korea aggregated the data for ecological analysis. We used negative binomial models to examine the association at the regional level, and stratified analysis by gender and age group was conducted. Results: "Permissiveness" was associated with reduced suicide rates in a univariate model (P < 0.001). Adjusting for gender, age, and additional sociodemographics did not alter the association. Additionally, this relationship was observed in males and individuals under 60 years of age after stratification. However, "Unjustified Behavior" and "Readiness to help/Preventability" exhibited no significant association with suicide in any model or stratum. Conclusion: The observed inverse association between permissive community attitudes and suicide contradicts the findings of previous research that links permissive individual attitudes to increased suicidal behavior. Our findings suggest that attitudes may operate differently at the individual and group levels. Although the cross-sectional design and single-country focus of this study warrant further investigation, our findings indicate that attitudes are significant contextual factors in the process of suicide, which could lead to novel approaches in suicide prevention.

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Gastric cancer (GC) is recognized as the fifth most prevalent malignant tumor worldwide. It is characterized by diverse clinical symptoms, treatment responses, and prognoses. In GC prognosis, the promotion of epithelial-mesenchymal transition (EMT) fosters cancer cell invasion and metastasis, thereby triggering the dissemination of tumor cells. This study proposes a nucleic acid amplification circuit-based hydrogel (NACH) assay for identifying exosomal miRNA derived from metastatic GC. The NACH assay employs the rolling circle amplification method and targets miRNA-21, a tumor-related oncogene, and miRNA-99a, which promotes EMT. Specific amplification probes for each target are immobilized within the hydrogel, enabling a streamlined, one-step amplification reaction. The NACH assay exhibits a detection limit of 1 fm for miRNA-21 and miRNA-99a, thereby enabling rapid and highly sensitive on-site detection. Performance evaluation using exosomal miRNA extracted from cell culture media, mouse plasma, and human plasma revealed fluorescence intensity patterns similar to those obtained in qRT-PCR. Furthermore, deploying a custom-developed portable fluorometer for the NACH assay allows for diagnostic performance assessment and point-of-care testing using clinical samples from GC patients. These findings emphasize the potential of the NACH assay to be used as a robust tool for the genetic diagnosis of GC based on exosome detection.

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Multicomponent radical tandem reactions have emerged as a crucial technique for synthesizing complex molecules in organic chemistry. In this study, we report a palladium-catalyzed four-component difluoroalkylative carbonylation of enynes and ethyl difluoroiodoacetate. This transformation proceeds through a multistep sequential reaction that introduces reactive difluoro and carbonyl groups while constructing the benzofuran skeleton. Moreover, a variety of valuable 2,3-disubstituted benzofuran derivatives were obtained in respectable yields with excellent functional group compatibility.

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Although large-scale genome-wide association studies (GWASs) have revealed the genetic architecture of schizophrenia, these studies have mainly focused on populations of European ancestry. This study aimed to identify common genetic variants associated with schizophrenia in the Korean population and evaluate the performance of polygenic risk scores (PRSs) derived from large-scale GWASs across ancestries. In the Korean psychiatric GWAS project (KPGP), seven academic institutes and their affiliated hospitals across South Korea recruited a cohort of 1670 patients with DSM-IV-defined schizophrenia and 2271 healthy controls. A total of 6690,822 SNPs were tested for association with schizophrenia. We identified one previously unreported genome-wide significant locus rs2423464 (P = 2.83 × 10-11; odds ratio = 1.65; 95 % confidence interval = 1.43-1.91, minor allele frequency = 0.126). This variant was also associated with increased lysosomal-associated membrane protein family member 5 (LAMP5) gene expression. The PRS derived from the meta-analysis results of East Asian and European GWASs explained a larger proportion of the phenotypic variance in the Korean schizophrenia sample than the PRS of an East Asian or European GWAS. (R2 = 0.073 for meta-analysis; 0.028 for East Asian GWAS; 0.037 for European GWAS). GWASs involving diverse ethnic groups will expand our understanding of the genetic architecture of schizophrenia.

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Background Basal cell carcinoma (BCC) is the most common type of nonmelanoma skin cancer. Typically, resection requires a safety margin of ≥4 mm. When removing tumor cells, achieving complete excision with minimal safety margins and reconstructing the defect to preserve the original appearance are important. In this study, we used a 3-mm resection margin to confirm recurrence and re-resection rates. Methods Electronic medical records and photographic data were obtained for patients with primary BCC lesions less than 2 cm in diameter who underwent wide excision with a 3-mm surgical margin from January 2015 to November 2021. We analyzed factors determining recurrence and re-resection rates, such as tumor size, location, age, sex, underlying diseases (including immunosuppression state), ethnicity, subtypes, tumor borders, etc. Results This study included 205 patients. The mean age and follow-up period were 73.0 ± 11.5 years and 10.2 ± 8.0 months, respectively. The recurrence and re-resection rates were 1.95% and 25.85%, respectively. A statistically significant correlation was found between recurrence rate and tumor border ( p = 0.013) and the re-resection rate was correlated statistically with location ( p = 0.022) and immunosuppressed patients ( p = 0.006). Conclusion We found that a 3-mm excision margin provided sufficient safety in small facial BCC, resulting in ease of surgery and better aesthetic outcomes. However, surgical margins must be determined case by case by integrating various patient factors. In particular, a surgical margin of ≥4 mm is required for BCC in high-risk areas, immunosuppressed patients, or poorly defined border.

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A chlorotrimethylsilane (TMSCl)-mediated cascade phosphorylation and cycloisomerization of enynones with diphenylphosphine oxides is presented. This methodology enables the highly selective synthesis of monophosphorylated 2H-pyrans and bisphosphorylated dihydropyrans through precise solvent-reagent stoichiometry control. The strategy demonstrated excellent functional group compatibility and high yields (up to 96%), providing facile access to structurally diverse phosphorylated heterocycles with potential applications in medicinal chemistry and materials science.

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BACKGROUND/AIM: This study compared the initial outcomes of gas-insufflation one-step single-port transaxillary (GOSTA) robotic thyroidectomy with traditional open thyroidectomy for thyroid cancer at a single institution. PATIENTS AND METHODS: A retrospective analysis was conducted on 77 patients who underwent thyroidectomy for differentiated thyroid cancer from January to June 2024. Exclusion criteria included benign nodules, Graves' disease, and previous thyroid surgeries. Two surgeons performed the procedures, with one having no prior robotic surgery experience. RESULTS: Of the 77 patients, 48 underwent open thyroidectomy and 29 underwent GOSTA thyroidectomy. The GOSTA group had a significantly lower mean age (40.1 vs. 47.6 years, p=0.002) and a higher proportion of female patients (p=0.040). The open group patients had more harvested lymph nodes than the GOSTA group patients (7.9 vs. 2.4, p<0.001). The GOSTA group patients had longer operation time (156.4 vs. 80.6 min, p<0.001), and had extended hospital stay than the open group patients (5.9 vs. 3.4 days, p<0.001). Complication rates were similar between the groups. CONCLUSION: GOSTA robotic thyroidectomy provides comparable safety and effectiveness to open thyroidectomy, with improved cosmetic outcomes despite longer operation times and hospital stays. This technique is feasible for surgeons without prior robotic experience, offering a viable alternative for patients prioritizing cosmetic results.

Assuntos

Procedimentos Cirúrgicos Robóticos , Neoplasias da Glândula Tireoide , Tireoidectomia , Humanos , Tireoidectomia/métodos , Tireoidectomia/efeitos adversos , Feminino , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Masculino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Resultado do Tratamento , Duração da Cirurgia , Axila , Tempo de Internação

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Virus-specific nasal resident T cells are important for protection against subsequent infection with a similar virus. Here we examine the phenotypes and functions of SARS-CoV-2-specific T cells in the nasal mucosa of vaccinated individuals with breakthrough infection (BTI) or without infection. Nasal tissues are obtained from participants during sinus surgery. Analysis of activation-induced markers implicates that a considerable proportion of spike (S)-reactive nasal CD8+ T cells express CD103, a tissue-resident marker. MHC-I multimer staining is performed to analyze the ex vivo phenotype and function of SARS-CoV-2 S-specific CD8+ T cells. We detect multimer+CD8+ T cells with tissue-resident phenotypes in nasal tissue samples from vaccinees without infection as well as vaccinees with BTI. Multimer+CD8+ T cells remain present in nasal tissues over one year after the last exposure to S antigen, although the frequency decreases. Upon direct ex vivo stimulation with epitope peptides, nasal multimer+CD8+ T cells-particularly the CD49a+ subset-exhibit immediate effector functions, including IFN-γ production. CITE-seq analysis of S-reactive AIM+CD8+ T cells confirms the enhanced effector function of the CD49a+ subset. These findings indicate that among individuals previously exposed to S antigen by vaccination or BTI, S-specific nasal-resident CD49a+CD8+ memory T cells can rapidly respond to SARS-CoV-2 during infection or reinfection.

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Linfócitos T CD8-Positivos , COVID-19 , Interferon gama , Células T de Memória , Mucosa Nasal , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T CD8-Positivos/imunologia , Interferon gama/imunologia , Interferon gama/metabolismo , SARS-CoV-2/imunologia , Mucosa Nasal/imunologia , Mucosa Nasal/virologia , COVID-19/imunologia , COVID-19/virologia , Células T de Memória/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Integrina alfa1/imunologia , Integrina alfa1/metabolismo , Vacinas contra COVID-19/imunologia , Antígenos CD/metabolismo , Antígenos CD/imunologia , Memória Imunológica/imunologia , Cadeias alfa de Integrinas

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BACKGROUND: NUP98 rearrangements (NUP98-r) are rare but overrepresented mutations in pediatric acute myeloid leukemia (AML) patients. NUP98-r is often associated with chemotherapy resistance and a particularly poor prognosis. Therefore, characterizing pediatric AML with NUP98-r to identify aberrations is critically important. METHODS: Here, we retrospectively analyzed the clinicopathological features, genomic and transcriptomic landscapes, treatments, and outcomes of pediatric patients with AML. RESULTS: Nine patients with NUP98-r mutations were identified in our cohort of 142 patients. Ten mutated genes were detected in patients with NUP98-r. The frequency of FLT3-ITD mutations differed significantly between the groups harboring NUP98-r and those without NUP98-r (P = 0.035). Unsupervised hierarchical clustering via RNA sequencing data from 21 AML patients revealed that NUP98-r samples clustered together, strongly suggesting a distinct subtype. Compared with that in the non-NUP98-r fusion and no fusion groups, CMAHP expression was significantly upregulated in the NUP98-r samples (P < 0.001 and P = 0.001, respectively). Multivariate Cox regression analyses demonstrated that patients harboring NUP98-r (P < 0.001) and WT1 mutations (P = 0.030) had worse relapse-free survival, and patients harboring NUP98-r (P < 0.008) presented lower overall survival. CONCLUSIONS: These investigations contribute to the understanding of the molecular characteristics, risk stratification, and prognostic evaluation of pediatric AML patients.

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Leucemia Mieloide Aguda , Complexo de Proteínas Formadoras de Poros Nucleares , Humanos , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Criança , Feminino , Masculino , Pré-Escolar , Adolescente , Lactente , Mutação , Estudos Retrospectivos , Transcriptoma/genética , Rearranjo Gênico , Prognóstico

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Controllable ß-carbon elimination to extrude norbornene remains a long-standing challenge in palladium and norbornene chemistry. Herein, this manuscript describes a switchable synthesis of biologically active C4-ethylaminoindole and C7-aminoindoline scaffolds by controlling ß-carbon elimination, utilizing aziridine as a C-H ethylamination reagent through a C-N bond cleavage reaction. Furthermore, the protecting groups of the product can be easily removed, offering an unusual method for the synthesis of dopamine receptor agonists.

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BACKGROUND: The ultimate goal of successful schizophrenia treatment is not just to alleviate psychotic symptoms, but also to reduce distress and achieve subjective well-being (SWB). We aimed to identify the determinants of SWB and their interrelationships in schizophrenia. METHODS: Data were obtained from 637 patients with schizophrenia enrolled in multicenter, open-label, non-comparative clinical trials. The SWB under the Neuroleptic Treatment Scale (SWN) was utilized; a cut-off score of 80 indicated a high level of SWB at baseline and 6 months. Various machine learning (ML) algorithms were employed to identify the determinants of SWB. Furthermore, network analysis and structural equation modeling (SEM) were conducted to explore detailed relationship patterns. RESULTS: The random forest (RF) model had the highest area under the curve (AUC) of 0.794 at baseline. Obsessive-compulsive symptoms (OCS) had the most significant impact on high levels of SWB, followed by somatization, cognitive deficits, and depression. The network analysis demonstrated robust connections among the SWB, OCS, and somatization. SEM analysis revealed that OCS exerted the strongest direct effect on SWB, and also an indirect effect via the mediation of depression. Furthermore, the contribution of OCS at baseline to SWB was maintained 6 months later. CONCLUSIONS: OCS, somatization, cognition, and depression, rather than psychotic symptoms, exerted significant impacts on SWB in schizophrenia. Notably, OCS exhibited the most significant contribution not only to the current state of well-being but also to follow-up SWB, implying that OCS was predictive of SWB. The findings demonstrated that OCS management is critical for the treatment of schizophrenia.

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BACKGROUND AND AIMS: CircRNAs and autophagy are closely involved in the physiological and pathological processes of ovarian cancer; however, their exact mechanisms are still undetermined. This investigation aimed to elucidate the function and associated pathways of circFAM188A, which modulates proliferation, autophagy, and invasion in ovarian cancer (EOC). METHODS: The expression of circFAM188A in the tissues of EOC patients was assessed via RT-PCR. To elucidate proliferation, invasion, and autophagy in the tumor cells, Transwell, 5-ethynyl-2'-deoxyuridine (EdU), and mRFP-GFP-LC3 reporter assays were conducted. The binding sites between circ-FAM188A and the miR-670-3p, miR-670-3p and YY1 were predicted using bioinformatics and verified by dual-luciferase reporter assays. Pulldown assays demonstrated binding between ULK1 and circ-FAM188A. ULK1 was found to be crucial in the initial stage of autophagy. Moreover, an in vivo xenograft model was established by subcutaneous injection of nude mice with EOC cells. RESULT: Expression of circ-FAM188A was increased in EOC tissues relative to normal ovarian tissues and circ-FAM188A overexpression promoted proliferation, invasion, and autophagy; these effects were reversed by circ-FAM188A silencing. miR-670-3p and circ-FAM188A co-localized in the cytoplasm. circ-FAM188A enhanced YY1 expression by sponging miR-670-3p and was also shown to interact with ULK1. CONCLUSION: It is thus suggested that circ-FAM188A modulates autophagy by sponging miR-670-3p as well as interacting with ULK1.

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Proteína Homóloga à Proteína-1 Relacionada à Autofagia , Autofagia , Carcinoma Epitelial do Ovário , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos Nus , MicroRNAs , Neoplasias Ovarianas , RNA Circular , Humanos , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Feminino , MicroRNAs/genética , Autofagia/genética , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/metabolismo , Animais , Camundongos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Proliferação de Células/genética , RNA Circular/genética , RNA Circular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Linhagem Celular Tumoral , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Movimento Celular/genética , Pessoa de Meia-Idade

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This perspective focuses on functional models of photosynthesis to achieve molecular photocatalytic systems that mimic photosystems I and II (PSI and PSII). A long-lived and high-energy electron-transfer state of 9-mesityl-10-methylacridinium ion (Acr+-Mes) has been attained as a simple and useful model of the photosynthetic reaction center. Acr+-Mes has been used as an effective photoredox catalyst for photocatalytic hydrogen evolution and regioselective reduction of NAD(P)+ from plastoquinone analogs as a molecular functional model of PSI. A functional molecular model system to mimic the function of PSII has also been developed to oxidize water by plastoquinone analogs to produce O2 and plastoquinol analogs. The PSI molecular models have finally been integrated with the PSII molecular models to achieve production of a solar fuel (hydrogen) and NAD(P)H and its analogs from water by use of solar energy as a molecular artificial photosynthesis.

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This study assessed pretreatment breast MRI coupled with machine learning for predicting early clinical responses to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), focusing on identifying non-responders. A retrospective analysis of 135 TNBC patients (107 responders, 28 non-responders) treated with NAC from January 2015 to October 2022 was conducted. Non-responders were defined according to RECIST guidelines. Data included clinicopathologic factors and clinical MRI findings, with radiomics features from contrast-enhanced T1-weighted images, to train a stacking ensemble of 13 machine learning models. For subgroup analysis, propensity score matching was conducted to adjust for clinical disparities in NAC response. The efficacy of the models was evaluated using the area under the receiver-operating-characteristic curve (AUROC) before and after matching. The model combining clinicopathologic factors and clinical MRI findings achieved an AUROC of 0.752 (95% CI 0.644-0.860) for predicting non-responders, while radiomics-based models showed 0.749 (95% CI 0.614-0.884). An integrated model of radiomics, clinicopathologic factors, and clinical MRI findings reached an AUROC of 0.802 (95% CI 0.699-0.905). After propensity score matching, the hierarchical order of key radiomics features remained consistent. Our study demonstrated the potential of using machine learning models based on pretreatment MRI to non-invasively predict TNBC non-responders to NAC.

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Imageamento por Ressonância Magnética , Terapia Neoadjuvante , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/patologia , Feminino , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Aprendizado de Máquina , Resultado do Tratamento , Idoso , Curva ROC , Mama/diagnóstico por imagem , Mama/patologia , Radiômica

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The Narasaka-Heck reaction is one of the most straightforward methods for constructing pyrroline derivatives. Herein, we report a novel nickel-catalyzed three-component carbonylation reaction, which cleverly realizes the continuous construction of C(sp3)-N bonds and C(sp3)-C(sp2) bonds and effectively promotes the synthesis of acyl-substituted pyrroline derivatives. Furthermore, this strategy not only expands the conversion pathway of γ,δ-unsaturated oxime esters but also provides a new method for the synthesis of nitrogen-containing heterocyclic compounds.

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Molecular-profiling-based cancer diagnosis has significant implications for predicting disease prognosis and selecting targeted therapeutic interventions. The analysis of cancer-derived extracellular vesicles (EVs) provides a noninvasive and sequential method to assess the molecular landscape of cancer. Here, we developed an all-in-one fusogenic nanoreactor (FNR) encapsulating DNA-fueled molecular machines (DMMs) for the rapid and direct detection of EV-associated microRNAs (EV miRNAs) in a single step. This platform was strategically designed to interact selectively with EVs and induce membrane fusion under a specific trigger. After fusion, the DMMs recognized the target miRNA and initiated nonenzymatic signal amplification within a well-defined reaction volume, thus producing an amplified fluorescent signal within 30 min. We used the FNRs to analyze the unique expression levels of three EV miRNAs in various biofluids, including cell culture, urine, and plasma, and obtained an accuracy of 86.7% in the classification of three major breast cancer (BC) cell lines and a diagnostic accuracy of 86.4% in the distinction between patients with cancer and healthy donors. Notably, a linear discriminant analysis revealed that increasing the number of miRNAs from one to three improved the accuracy of BC patient discrimination from 78.8 to 95.4%. Therefore, this all-in-one diagnostic platform performs nondestructive EV processing and signal amplification in one step, providing a straightforward, accurate, and effective individual EV miRNA analysis strategy for personalized BC treatment.

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OBJECTIVE: Suicide is a significant public health issue, with South Korea having the highest suicide rate among Organisation for Economic Cooperation and Development countries. This study aimed to develop clinical guidelines for suicide prevention in psychiatric patients in Korea using the ADAPTE methodology. METHODS: The development process involved a comprehensive review of literature, expert consultations, and consensus-building using the Nominal Group Technique and Delphi method. The guidelines focus on evidence-based psychiatric treatments, including both pharmacological and non-pharmacological approaches, tailored to the Korean context. Key findings underscoring the need for standardized treatment protocols for patients with major psychiatric disorders, including bipolar disorder, major depressive disorder, and schizophrenia. RESULTS: The guidelines incorporate treatments like lithium, clozapine, atypical antipsychotics, electroconvulsive therapy, and cognitive behavioral therapy, which have shown effectiveness in suicide prevention. Applicability and acceptability within Korea's healthcare system were addressed, ensuring feasibility given the country's medical insurance coverage and accessibility. The guidelines were validated through expert reviews and Delphi rounds, achieving consensus on the final recommendations. CONCLUSION: The developed guidelines provide a structured, evidence-based approach to reducing suicide rates among psychiatric patients in Korea. Future research will focus on expanding these guidelines to include screening protocols for high-risk groups.

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Contenções Ortodônticas , Impressão Tridimensional , Retratamento , Humanos , Feminino , Desenho de Aparelho Ortodôntico , Masculino

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BACKGROUND: Tetracyclines are a class of antibacterial drugs commonly used in clinical practice, but there is no systematic analysis of the adverse effects (AEs) of these drugs. We performed such pharmacovigilance analyses using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database to explore tetracycline-related AEs. RESEARCH DESIGN AND METHODS: We used the pharmacovigilance analysis tool Open Vigil 2.1 to access FAERS data and obtained AE reports from January 2004 to June 2023, including doxycycline, minocycline, tigecycline, omadacycline, sarecycline, and eravacycline as the top suspect drugs. The signal value of the AE of the analyzed drug was calculated by the reporting odds ratio (ROR). RESULTS: A total of 15,020 cases were identified by analyzing drugs. In terms of adverse signals, doxycycline caused gastrointestinal mucosal necrosis (ROR = 1699.652); minocycline was reported to cause bone hyperpigmentation (ROR = 30976.223); tigecycline is responsible for blood fibrinogen decreased (ROR = 1714.078). CONCLUSIONS: AE reports of tetracycline drugs varied significantly. We found some AEs not mentioned in the instruction, such as the ototoxicity of tetracyclines. Doxycycline was associated with psychiatric side effects; minocycline presented in thyroid and skin tissue-associated tumors; abnormal signals were detected with eravacycline in the blood system.