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1.
Front Psychiatry ; 15: 1423609, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39351329

RESUMO

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.

2.
Mol Syst Biol ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39322849

RESUMO

The 3D genome prediction in cancer is crucial for uncovering the impact of structural variations (SVs) on tumorigenesis, especially when they are present in noncoding regions. We present InfoHiC, a systemic framework for predicting the 3D cancer genome directly from whole-genome sequencing (WGS). InfoHiC utilizes contig-specific copy number encoding on the SV contig assembly, and performs a contig-to-total Hi-C conversion for the cancer Hi-C prediction from multiple SV contigs. We showed that InfoHiC can predict 3D genome folding from all types of SVs using breast cancer cell line data. We applied it to WGS data of patients with breast cancer and pediatric patients with medulloblastoma, and identified neo topologically associating domains. For breast cancer, we discovered super-enhancer hijacking events associated with oncogenic overexpression and poor survival outcomes. For medulloblastoma, we found SVs in noncoding regions that caused super-enhancer hijacking events of medulloblastoma driver genes (GFI1, GFI1B, and PRDM6). In addition, we provide trained models for cancer Hi-C prediction from WGS at https://github.com/dmcb-gist/InfoHiC , uncovering the impacts of SVs in cancer patients and revealing novel therapeutic targets.

3.
Mol Brain ; 17(1): 62, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223564

RESUMO

We previously demonstrated that felodipine, an L-type calcium channel blocker, inhibits LPS-mediated neuroinflammatory responses in BV2 microglial cells and wild-type mice. However, the effects of felodipine on tau pathology, a hallmark of Alzheimer's disease (AD), have not been explored yet. Therefore, in the present study, we determined whether felodipine affects neuroinflammation and tau hyperphosphorylation in 3-month-old P301S transgenic mice (PS19), an early phase AD mice model for tauopathy. Felodipine administration decreased tauopathy-mediated microglial activation and NLRP3 expression in PS19 mice but had no effect on tauopathy-associated astrogliosis. In addition, felodipine treatment significantly reduced tau hyperphosphorylation at S202/Thr205 and Thr212/Ser214 residues via inhibiting JNK/P38 signaling in PS19 mice. Collectively, our results suggest that felodipine significantly ameliorates tau hyper-phosphorylation and tauopathy-associated neuroinflammatory responses in AD mice model for tauopathy and could be a novel therapeutic agent for AD.


Assuntos
Doença de Alzheimer , Felodipino , Camundongos Transgênicos , Microglia , Doenças Neuroinflamatórias , Proteínas Quinases p38 Ativadas por Mitógeno , Proteínas tau , Animais , Proteínas tau/metabolismo , Fosforilação/efeitos dos fármacos , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Felodipino/farmacologia , Felodipino/uso terapêutico , Doença de Alzheimer/patologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Camundongos , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
4.
ACS Appl Mater Interfaces ; 16(37): 49520-49532, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39238174

RESUMO

Recent trends in two-dimensional (2D) graphene have demonstrated significant potential for gas-sensing applications with significantly enhanced sensitivity even at room temperature. Herein, this study presents fabrication of distinctive gas sensor based on one-dimensional (1D) W18O49 nanofibers decorated 2D graphene, specifically coated on copper (Cu)-based interdigitated electrodes formed by DC sputtering, which can selectively detect NO2 gas at room temperature. The sensor device fabricated using W18O49/Gr1.5% (i.e., W18O49 nanofibers hybrid nanocomposite with 1.5 wt % graphene) displays excellent overall sensing performance at 27 °C (room temperature) with high response (∼150-160 times) to NO2 gas. The W18O49/Gr1.5%-based sensor device reflects the highly selective detection toward NO2 gas among various gases with quick response time of 3 s and speedy recovery in 6 s. The limit of detection of ∼0.3 ppm with excellent reproducibility and stability for 3 months in all weather conditions (tested in humidity conditions 20-97%) are superior features of the device under test. However, W18O49/Gr3% displayed higher selectivity for NO2 but resulted with comparatively reduced sensitivity than W18O49/Gr1.5% sensor. The enhanced sensing performance could be attributed to the graphene content to decorate the nanofibers on it, oxygen vacancies/defects, and the contacts between the sensing material and Cu. This favorable synthesis and properties of self-assembled hybrid composite materials provide a potential utilization for detecting NO2 gas in environmental safety inspection.

5.
Microorganisms ; 12(9)2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39338480

RESUMO

A resurgence of Mycoplasma pneumoniae (MP)-the leading cause of community-acquired bacterial pneumonia, particularly in children-occurred following the COVID-19 pandemic. We aimed to investigate the clinical manifestations, macrolide resistance patterns, and therapeutic approaches related to the MP pneumonia epidemic. Children and adolescents diagnosed with MP pneumonia in September-December 2023 were screened. Clinical data were retrospectively collected from 13 major hospitals using concordant microbiological criteria, including either a positive PCR result or four-fold increase in serological markers. Demographic characteristics, treatment modalities, and clinical outcomes were analyzed. Of the 474 screened patients, 374 (median age: 7.7 [IQR, 5.4-9.6] years; hospitalization rate: 88.6%) met the microbiological confirmation criteria. Most patients experienced fever (98.9%), and lobular/lobar consolidation (59.1%) was the dominant radiological finding. The macrolide resistance rate remained high at 87.0%; corticosteroids were widely used (55.6%) alongside macrolides, despite resistance. Patients with consolidation had prolonged fever (median 8 vs. 7 days, p = 0.020) and higher hospitalization rates (92.3% vs. 83.0%, p = 0.008). Macrolide resistance did not significantly influence radiological outcomes. This study highlights the ongoing challenge of macrolide resistance in MP pneumonia and need for tailored therapeutic approaches. Despite high resistance, macrolides remain commonly prescribed, often concurrently with corticosteroids.

6.
J Anim Sci Technol ; 66(4): 859-862, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39165743

RESUMO

It has been reported that the administration of Limosilactobacillus fermentum alleviates diseases such as osteoporosis and colitis. In this study, we report the complete genome sequence of Limosilactobacillus fermentum KUFM407, a probiotic strain of LAB isolated from Korean traditional fermented food, Kimchi. Whole genome sequencing of L. fermentum KUFM407 was performed on the Illumina MiSeq and Oxford Nanopore MinION platform. The genome consisted of one circular chromosome (2,077,616 base pair [bp]) with a guanine cytosine (GC) content of 51.5% and one circular plasmid sequence (13,931 bp). Genome annotation identified 1,932 protein-coding genes, 15 rRNAs, and 58 tRNAs in the assembly. The function annotation of the predicted proteins revealed genes involved in the biosynthesis of bacteriocin and fatty acids. The complete genome of L. fermentum KUFM407 could provide valuable information for the development of new probiotic food and health supplements.

7.
IEEE J Transl Eng Health Med ; 12: 550-557, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39155923

RESUMO

The objective of this study was to develop a sound recognition-based cardiopulmonary resuscitation (CPR) training system that is accessible, cost-effective, easy-to-maintain and provides accurate CPR feedback. Beep-CPR, a novel device with accordion squeakers that emit high-pitched sounds during compression, was developed. The sounds emitted by Beep-CPR were recorded using a smartphone, segmented into 2-second audio fragments, and then transformed into spectrograms. A total of 6,065 spectrograms were generated from approximately 40 minutes of audio data, which were then randomly split into training, validation, and test datasets. Each spectrogram was matched with the depth, rate, and release velocity of the compression measured at the same time interval by the ZOLL X Series monitor/defibrillator. Deep learning models utilizing spectrograms as input were trained using transfer learning based on EfficientNet to predict the depth (Depth model), rate (Rate model), and release velocity (Recoil model) of compressions. Results: The mean absolute error (MAE) for the Depth model was 0.30 cm (95% confidence interval [CI]: 0.27-0.33). The MAE of the Rate model was 3.6/min (95% CI: 3.2-3.9). For the Recoil model, the MAE was 2.3 cm/s (95% CI: 2.1-2.5). External validation of the models demonstrated acceptable performance across multiple conditions, including the utilization of a newly-manufactured device, a fatigued device, and evaluation in an environment with altered spatial dimensions. We have developed a novel sound recognition-based CPR training system, that accurately measures compression quality during training. Significance: Beep-CPR is a cost-effective and easy-to-maintain solution that can improve the efficacy of CPR training by facilitating decentralized at-home training with performance feedback.


Assuntos
Reanimação Cardiopulmonar , Reanimação Cardiopulmonar/educação , Reanimação Cardiopulmonar/instrumentação , Humanos , Som , Espectrografia do Som , Processamento de Sinais Assistido por Computador/instrumentação , Aprendizado Profundo , Smartphone , Desenho de Equipamento
8.
J Neuroinflammation ; 21(1): 200, 2024 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-39129007

RESUMO

BACKGROUND: We recently reported that the dopamine (DA) analogue CA140 modulates neuroinflammatory responses in lipopolysaccharide-injected wild-type (WT) mice and in 3-month-old 5xFAD mice, a model of Alzheimer's disease (AD). However, the effects of CA140 on Aß/tau pathology and synaptic/cognitive function and its molecular mechanisms of action are unknown. METHODS: To investigate the effects of CA140 on cognitive and synaptic function and AD pathology, 3-month-old WT mice or 8-month-old (aged) 5xFAD mice were injected with vehicle (10% DMSO) or CA140 (30 mg/kg, i.p.) daily for 10, 14, or 17 days. Behavioral tests, ELISA, electrophysiology, RNA sequencing, real-time PCR, Golgi staining, immunofluorescence staining, and western blotting were conducted. RESULTS: In aged 5xFAD mice, a model of AD pathology, CA140 treatment significantly reduced Aß/tau fibrillation, Aß plaque number, tau hyperphosphorylation, and neuroinflammation by inhibiting NLRP3 activation. In addition, CA140 treatment downregulated the expression of cxcl10, a marker of AD-associated reactive astrocytes (RAs), and c1qa, a marker of the interaction of RAs with disease-associated microglia (DAMs) in 5xFAD mice. CA140 treatment also suppressed the mRNA levels of s100ß and cxcl10, markers of AD-associated RAs, in primary astrocytes from 5xFAD mice. In primary microglial cells from 5xFAD mice, CA140 treatment increased the mRNA levels of markers of homeostatic microglia (cx3cr1 and p2ry12) and decreased the mRNA levels of a marker of proliferative region-associated microglia (gpnmb) and a marker of lipid-droplet-accumulating microglia (cln3). Importantly, CA140 treatment rescued scopolamine (SCO)-mediated deficits in long-term memory, dendritic spine number, and LTP impairment. In aged 5xFAD mice, these effects of CA140 treatment on cognitive/synaptic function and AD pathology were regulated by dopamine D1 receptor (DRD1)/Elk1 signaling. In primary hippocampal neurons and WT mice, CA140 treatment promoted long-term memory and dendritic spine formation via effects on DRD1/CaMKIIα and/or ERK signaling. CONCLUSIONS: Our results indicate that CA140 improves neuronal/synaptic/cognitive function and ameliorates Aß/tau pathology and neuroinflammation by modulating DRD1 signaling in primary hippocampal neurons, primary astrocytes/microglia, WT mice, and aged 5xFAD mice.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Camundongos Transgênicos , Doenças Neuroinflamatórias , Receptores de Dopamina D1 , Transdução de Sinais , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Camundongos , Peptídeos beta-Amiloides/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Receptores de Dopamina D1/metabolismo , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Sinapses/patologia , Cognição/efeitos dos fármacos , Dopamina/metabolismo , Camundongos Endogâmicos C57BL , Masculino , Humanos
9.
Sci Rep ; 14(1): 15582, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971807

RESUMO

Selecting relevant feature subsets is essential for machine learning applications. Among the feature selection techniques, the knockoff filter procedure proposes a unique framework that minimizes false discovery rates (FDR). However, employing a deep neural network architecture for a knockoff filter framework requires higher detection power. Using the knockoff filter framework, we present a Deep neural network with PaIrwise connected layers integrated with stochastic Gates (DeepPIG) for the feature selection model. DeepPIG exhibited better detection power in synthetic data than the baseline and recent models such as Deep feature selection using Paired-Input Nonlinear Knockoffs (DeepPINK), Stochastic Gates (STG), and SHapley Additive exPlanations (SHAP) while not violating the preselected FDR level, especially when the signal of the features were weak. The selected features determined by DeepPIG demonstrated superior classification performance compared with the baseline model in real-world data analyses, including the prediction of certain cancer prognosis and classification tasks using microbiome and single-cell datasets. In conclusion, DeepPIG is a robust feature selection approach even when the signals of features are weak. Source code is available at https://github.com/DMCB-GIST/DeepPIG .

10.
BMC Infect Dis ; 24(1): 740, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060964

RESUMO

BACKGROUND: Group B Streptococcus (GBS) causes invasive infections in newborns and elderly individuals, but is a noninvasive commensal bacterium in most immunocompetent people. Recently, the incidence of invasive GBS infections has increased worldwide, and there is growing interest in the molecular genetic characteristics of invasive GBS strains. Vaccines against GBS are expected in the near future. Here, we aimed to analyze the molecular epidemiology of GBS according to the invasiveness in South Korea. METHODS: We analyzed GBS isolates collected and stored in two hospitals in South Korea between January 2015 and December 2020. The invasiveness of these isolates was determined via a retrospective review of clinical episodes. Totally, 120 GBS isolates from 55 children and 65 adults were analyzed. Serotype and sequence type (ST) were determined using multiplex polymerase chain reaction (PCR) and multilocus sequence typing, respectively. Fourteen virulence factor-encoding genes of GBS were analyzed using multiplex PCR. RESULTS: Forty one (34.2%) were invasive infection-related GBS isolates (iGBS). The most frequently detected serotype was III (39/120, 32.5%), and it accounted for a high proportion of iGBS (21/41, 51.2%). The most frequent ST was ST19 (18/120, 15.0%), followed by ST2 (17/120, 14.2%). Serotype III/ST17 was predominant in iGBS (12/41, 29.3%), and all 17 ST2 strains were noninvasive. The distribution of most of the investigated virulence factors was not significantly related to invasiveness; noteworthily, most of the serotype III/ST17 iGBS carried pilus island (PI) 2b (10/12, 83.3%), and the prevalence of fbsB was significantly low compared with noninvasive GBS isolates (P = 0.004). Characteristically, the combination of bca(+)-cspA(+)-pavA(+)-fbsB(-)-rib(+)-bac(-) was predominant in iGBS (24.4%, 10/41). CONCLUSIONS: Serotype III/ST17 GBS carrying PI-2b was frequently detected in iGBS. There was no significant association between invasiveness and the pattern of virulence factors; however, a specific combination of virulence factors was predominant in iGBS.


Assuntos
Epidemiologia Molecular , Tipagem de Sequências Multilocus , Sorogrupo , Infecções Estreptocócicas , Streptococcus agalactiae , Fatores de Virulência , Humanos , República da Coreia/epidemiologia , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Fatores de Virulência/genética , Streptococcus agalactiae/genética , Streptococcus agalactiae/patogenicidade , Streptococcus agalactiae/classificação , Streptococcus agalactiae/isolamento & purificação , Adulto , Estudos Retrospectivos , Criança , Feminino , Masculino , Pré-Escolar , Pessoa de Meia-Idade , Idoso , Reação em Cadeia da Polimerase Multiplex , Lactente , Adulto Jovem , Adolescente , Recém-Nascido
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