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1.
J Pers Med ; 14(6)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38929818

RESUMO

Chronic kidney disease (CKD) is strongly associated with dementia. However, its independent association with Alzheimer's or Parkinson's disease remains unclear. This study investigated the prospective association of patients with CKD aged ≥55 years with an increased risk of Alzheimer's or Parkinson's disease. We conducted a retrospective cohort analysis using a national cohort sample of approximately one million patients. Primary outcome indicators measured included incidence of all-cause dementia, Alzheimer's disease, and Parkinson's disease events using person-years at risk. The hazard ratio was adjusted using the Cox proportional hazards model. We included 952 patients without CKD and 476 with CKD over 55 years using propensity score matching. The CKD group exhibited higher incidences of all-cause dementia, Parkinson's disease, and Alzheimer's disease than the non-CKD group. Furthermore, the CKD group had an elevated risk of all-cause dementia and a significantly increased risk of Parkinson's disease, especially among older women. Notably, the risk of Parkinson's disease was higher within the first 3 years of CKD diagnosis. These findings emphasize the link between CKD in mid- and late-life individuals and a higher incidence of all-cause dementia and Parkinson's disease rather than Alzheimer's disease.

2.
Materials (Basel) ; 17(10)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38793426

RESUMO

In this study, we investigated the micromechanical deformation and damage behavior of commercially extruded and additively manufactured 316L stainless steels (AMed SS316L) by combining experimental examinations and crystal plasticity modeling. The AMed alloy was fabricated using the laser powder bed fusion (LPBF) technique with an orthogonal scanning strategy to control the directionality of the as-fabricated material. Optical microscopy and electron backscatter diffraction measurements revealed distinct grain morphologies and crystallographic textures in the two alloys. Uniaxial tensile test results suggested that the LPBFed alloy exhibited an increased yield strength, reduced elongation, and comparable ultimate tensile strength in comparison to those of the extruded alloy. A microstructure-based crystal plasticity model was developed to simulate the micromechanical deformation behavior of the alloys using representative volume elements based on realistic microstructures. A ductile fracture criterion based on the microscopically dissipated plastic energy on a slip system was adopted to predict the microscopic damage accumulation of the alloys during plastic deformation. The developed model could accurately predict the stress-strain behavior and evolution of the crystallographic textures in both the alloys. We reveal that the increased yield strength in the LPBFed alloy, compared to that in the extruded alloy, is attributed to the higher as-manufactured dislocation density and the cellular subgrain structure, resulting in a reduced elongation. The presence of annealing twins and favorable texture in the extruded alloy contributed to its excellent elongation, along with a higher hardening rate owing to twin-dislocation interactions during plastic deformation. Moreover, the grain morphology and defect state (e.g., dislocations and twins) in the initial state can significantly affect strain localization and damage accumulation in alloys.

3.
Healthcare (Basel) ; 12(10)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38786374

RESUMO

Exergaming, a new type of sport, combined with virtual reality, has provided new opportunities for the aging population. This study analyzed the differences in leisure constraints, participation benefits, and continuous participation intention in virtual golf (represented as an exergame) depending on the participants' ages. Data collection was conducted from August 2023 to November 2023. A quantitative research design and a convenience sampling method were employed, targeting 310 regular virtual golf participants aged 20 years or older in the Republic of Korea. For comparative analysis, the survey participants were segmented into three groups: Group 1, young adults (18-35 years); Group 2, middle-aged adults (36-55 years); and Group 3, older adults (56-69 years). To compare and analyze participation behaviors in virtual golf, the dependent variables were identified: (a) leisure constraints (four factors) to limit formation and participation in leisure; (b) participation benefits (four factors) to encourage participation in leisure; and (c) continuous participation intention (single factor) to show likelihood to participate in leisure in the future. The results revealed that the young adult group showed statistically high results for costs under leisure constraints (F = 14.949, p < 0.001, ηp2 = 0.089), and the older adult group reported statistically high results in physical (F = 9.346, p < 0.001, ηp2 = 0.057) and mental (F = 7.249, p < 0.001, ηp2 = 0.045) participation benefits and continuous participation intention (F = 6.486, p < 0.01, ηp2 = 0.041). This study confirmed that virtual golf using advanced technology brings physical and mental benefits to older people based on reasonable cost and enables continuous participation in physical activity.

4.
Cancers (Basel) ; 16(10)2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38792008

RESUMO

Enhanced screening protocols for cancer detection have increased survival in patients with head and neck cancer (HNC), which highlights the need to address the sequelae of therapy-induced cardiovascular complications. This study was conducted to assess the incidence and risk of acute myocardial infarction (AMI) in patients with HNC who have not undergone radiation or chemotherapy using a comprehensive, population-based cohort dataset. A total of 2976 individuals without cancer and 744 individuals with HNC were matched using the propensity score method. The findings indicated that the occurrence rates of AMI were comparable between the HNC (2.19) and non-cancer groups (2.39). Cox regression analysis did not demonstrate a significant increase in the risk of AMI in patients with HNC (hazard ratio: 0.93, 95% confidence interval: 0.50-1.73). No increased risk of AMI was observed in the HNC group compared to the non-cancer group, regardless of the time since the HNC diagnosis. Subgroup analyses showed no notable differences in the AMI risk between the groups when considering sex, age, comorbidities, and cancer type. This study showed that patients with HNC who have not been treated with radiation or chemotherapy did not exhibit an increased incidence or risk of AMI compared to individuals without cancer.

5.
Cancers (Basel) ; 16(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38611030

RESUMO

Although cancer and ischemic heart disease (IHD) frequently manifest in the same individual, the risk of IHD events in cancer, especially head and neck cancer (HNC), remains unclear. We aimed to examine the incidence and risk of IHD events in patients with HNC using a population-based cohort dataset in South Korea (2002-2013). Through rigorous propensity score matching, we compared data from 2816 individuals without HNC and 704 individuals with HNC. Key independent variables were matched between groups, and the Charlson Comorbidity Index was used to match comorbidities. The Kaplan-Meier method depicted the cumulative probability of IHD throughout the follow-up period for both the study and control groups. The overall IHD incidence was significantly higher (19.93) in patients with HNC than in those without HNC (14.81), signifying an augmented IHD risk in the HNC cohort. Subsequent temporal analysis revealed a significant surge in IHD risk commencing 4 years after HNC diagnosis and persisting throughout the follow-up period. Subgroup analysis revealed an increased IHD risk in men with HNC and patients with cancers affecting the oral and sinonasal regions. This retrospective cohort study provides valuable scientific insights into the nuanced relationship between HNC and IHD, underscoring the need for tailored monitoring protocols and specialized care for susceptible individuals.

6.
Int J Mol Sci ; 25(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38612663

RESUMO

Some studies have demonstrated the effects of particulate matter (PM) on chronic rhinosinusitis with nasal polyps (CRSwNP) development, as well as the therapeutic role of retinoic acid (RA) in nasal polypogenesis. However, the immunologic effect of PM in innate lymphoid cells (ILCs) and the exact mechanism of the therapeutic effect of RA remain unclear. Therefore, the present study investigated the effects of fine-dust-induced inflammation in CRSwNP and the mechanisms of the therapeutic effect of RA. PM2.5 exposure exacerbated pathological damage in the nasal mucosa of mice with nasal polyps (NP) via upregulation of type 2 inflammation. Additionally, PM2.5 exposure increased the expression of type 2 cytokines and epithelial-cell-derived cytokines (IL-33 and IL-25) significantly, as well as the ILC populations in human-NP-derived epithelial cells (HNECs). Moreover, RA supplementation significantly increased the expression of ILCreg in Lin-CD45+CD127+ cells, which in turn increased the levels of the anti-inflammatory cytokine IL-10. The findings suggest that PM2.5 exposures could aggravate the CRSwNP type 2 inflammation, and RA treatment may ameliorate fine-dust-induced inflammation by modulating the innate immune response.


Assuntos
Imunidade Inata , Pólipos Nasais , Humanos , Animais , Camundongos , Linfócitos , Inflamação/tratamento farmacológico , Citocinas , Poeira , Mucosa Nasal , Material Particulado/toxicidade
8.
Biomed Pharmacother ; 174: 116442, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38513596

RESUMO

Parkinson's disease (PD) is a complex neurodegenerative disorder with an unclear etiology. Despite significant research efforts, developing disease-modifying treatments for PD remains a major unmet medical need. Notably, drug repositioning is becoming an increasingly attractive direction in drug discovery, and computational approaches offer a relatively quick and resource-saving method for identifying testable hypotheses that promote drug repositioning. We used an artificial intelligence (AI)-based drug repositioning strategy to screen an extensive compound library and identify potential therapeutic agents for PD. Our AI-driven analysis revealed that efavirenz and nevirapine, approved for treating human immunodeficiency virus infection, had distinct profiles, suggesting their potential effects on PD pathophysiology. Among these, efavirenz attenuated α-synuclein (α-syn) propagation and associated neuroinflammation in the brain of preformed α-syn fibrils-injected A53T α-syn Tg mice and α-syn propagation and associated behavioral changes in the C. elegans BiFC model. Through in-depth molecular investigations, we found that efavirenz can modulate cholesterol metabolism and mitigate α-syn propagation, a key pathological feature implicated in PD progression by regulating CYP46A1. This study opens new avenues for further investigation into the mechanisms underlying PD pathology and the exploration of additional drug candidates using advanced computational methodologies.


Assuntos
Alcinos , Inteligência Artificial , Benzoxazinas , Ciclopropanos , Reposicionamento de Medicamentos , Doença de Parkinson , alfa-Sinucleína , Ciclopropanos/farmacologia , Ciclopropanos/uso terapêutico , Alcinos/farmacologia , Benzoxazinas/farmacologia , Reposicionamento de Medicamentos/métodos , Animais , alfa-Sinucleína/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Camundongos , Caenorhabditis elegans/efeitos dos fármacos , Camundongos Transgênicos , Humanos , Nevirapina/farmacologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
9.
Cancers (Basel) ; 16(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38539417

RESUMO

An increased risk of cancer among patients with rheumatoid arthritis (RA) has been reported. However, the risk of RA events among patients with head and neck cancer (HNC) is unknown. Therefore, we investigated the incidence and risk of RA among patients with HNC. This study was based on a cohort dataset. Overall, 2824 individuals without HNC and 706 patients with HNC were selected using propensity score matching. The overall RA event rate was 12.19 for patients with HNC and 7.60 for those without HNC. A significantly increased risk of developing RA was also observed among patients with HNC. The risk of developing RA over time was relatively high within the first year after HNC diagnosis; further, it increased significantly during the follow-up period. Moreover, middle-aged male patients with HNC exhibited an increased risk of developing RA compared with the controls; however, no significant difference was noted among female patients or other age groups. Notably, subgroup analysis according to cancer subtype revealed that only oral cancer survivors had an increased risk of developing RA. These results underscore the importance of vigilant monitoring by clinicians to promptly identify the onset of RA in patients with HNC.

10.
J Neuroinflammation ; 21(1): 53, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383441

RESUMO

BACKGROUND: Parkinson's disease (PD) is a common and costly progressive neurodegenerative disease of unclear etiology. A disease-modifying approach that can directly stop or slow its progression remains a major unmet need in the treatment of PD. A clinical pharmacology-based drug repositioning strategy is a useful approach for identifying new drugs for PD. METHODS: We analyzed claims data obtained from the National Health Insurance Service (NHIS), which covers a significant portion of the South Korean population, to investigate the association between antihistamines, a class of drugs commonly used to treat allergic symptoms by blocking H1 receptor, and PD in a real-world setting. Additionally, we validated this model using various animal models of PD such as the 6-hydroxydopmaine (6-OHDA), α-synuclein preformed fibrils (PFF) injection, and Caenorhabditis elegans (C. elegans) models. Finally, whole transcriptome data and Ingenuity Pathway Analysis (IPA) were used to elucidate drug mechanism pathways. RESULTS: We identified fexofenadine as the most promising candidate using National Health Insurance claims data in the real world. In several animal models, including the 6-OHDA, PFF injection, and C. elegans models, fexofenadine ameliorated PD-related pathologies. RNA-seq analysis and the subsequent experiments suggested that fexofenadine is effective in PD via inhibition of peripheral immune cell infiltration into the brain. CONCLUSION: Fexofenadine shows promise for the treatment of PD, identified through clinical data and validated in diverse animal models. This combined clinical and preclinical approach offers valuable insights for developing novel PD therapeutics.


Assuntos
Doenças Neurodegenerativas , Doença de Parkinson , Terfenadina/análogos & derivados , Animais , Doença de Parkinson/patologia , Caenorhabditis elegans/metabolismo , Doenças Neurodegenerativas/metabolismo , Oxidopamina , Modelos Animais de Doenças , alfa-Sinucleína/metabolismo , Neurônios Dopaminérgicos
11.
JAMA Netw Open ; 7(2): e2355331, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38334998

RESUMO

Importance: Valuable evidence regarding clinical characteristics, treatments, and outcomes for non-small cell lung cancer (NSCLC) is limited to individual hospital databases or national-level registries. The common data and federated analysis framework developed through the Extensible Platform for Observational Research in Lung Cancer (EXPLORE-LC) initiative allows for research across multiple high-quality data sources, which may provide a deeper understanding of the NSCLC landscape and identification of unmet needs of subpopulations. Objective: To describe clinical characteristics, initial treatment patterns, subsequent treatment, and overall survival (OS) of patients with NSCLC in South Korea. Design, Setting, and Participants: This multicenter cohort study included patients aged 18 years and older who were diagnosed with NSCLC between 2014 and 2019 and followed up until March 2020 at 3 tertiary hospitals in South Korea. Clinical data were collected using a common data model and clinical data warehouse. Patients who had an initial diagnosis of nonsquamous (NSQ) or squamous (SQ) NSCLC and who had received at least 1 treatment for NSCLC were included in the study. Data were analyzed from June through November 2022. Main Outcomes and Measures: The primary outcome was clinical OS for patients with NSCLC. Secondary outcomes were clinical characteristics and treatment patterns subsequent to the diagnosis of NSCLC. Results: Among 22 101 patients with NSCLC who received anticancer treatment analyzed in this study, 17 350 patients (78.5%) had NSQ and 4751 patients (21.5%) had SQ NSCLC. Clinical characteristics and outcomes and treatment patterns were assessed for 13 084 patients with NSQ cancer who had known EGFR and ALK status (75.4%; mean [SD] 62.2 [10.5] years; 6552 males [50.1%]) and all 4751 patients with SQ cancer (mean [SD] age, 67.1 [8.6] years; 4427 males [93.2%]). More than half of patients with NSQ cancer were never smokers (7399 patients [56.6%]). Patients with SQ cancer were mostly males and former or current smokers (4235 patients [89.1%]) and were diagnosed at a later clinical stage than patients with NSQ cancer (eg, stage I: 1165 patients [24.5%] vs 5388 patients [41.2%]). Patients with EGFR-positive and ALK-positive NSQ cancer diagnosed between 2017 and 2019 had better median OS than similar patients diagnosed between 2014 and 2016 (EGFR-positive: not reached [95% CI, 35.9 months to not reached] vs 28.4 months [95% CI, 25.8 to 30.0 months]; P < .001; ALK-positive: not reached [95% CI, not reached] vs 49.5 months [95% CI, 35.1 months to not reached]; P < .001). No significant difference was observed in OS from first-line treatment for patients with SQ cancer. Conclusions and Relevance: This study, which pooled medical data from multiple clinical data warehouses to produce a large study cohort, may provide meaningful insights into the clinical practice of NSCLC and underscores the value of a common data model approach. The analyzable dataset may hold great promise for future comprehensive identification of subpopulations and unmet needs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Masculino , Humanos , Idoso , Feminino , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/diagnóstico , Estudos de Coortes , Estudos Retrospectivos , Receptores Proteína Tirosina Quinases/uso terapêutico , Receptores ErbB
12.
bioRxiv ; 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38260557

RESUMO

The tectorial membrane (TM) is an apical extracellular matrix (ECM) in the cochlea essential for auditory transduction. The TM exhibits highly ordered domain-specific architecture. Alpha-tectorin/TECTA is a glycosylphosphatidylinositol (GPI)-anchored ECM protein essential for TM organization. Here, we identified that TECTA is released by distinct modes: proteolytic shedding by TMPRSS2 and GPI-anchor-dependent release from the microvillus tip. In the medial/limbal domain, proteolytically shed TECTA forms dense fibers. In the lateral/body domain produced by the supporting cells displaying dense microvilli, the proteolytic shedding restricts TECTA to the microvillus tip and compartmentalizes the collagen-binding site. The tip-localized TECTA, in turn, is released in a GPI-anchor-dependent manner to form collagen-crosslinking fibers, required for maintaining the spacing and parallel organization of collagen fibrils. Overall, we showed that distinct release modes of TECTA determine the domain-specific organization pattern, and the microvillus coordinates the release modes along its membrane to organize the higher-order ECM architecture.

13.
Cancers (Basel) ; 15(23)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38067220

RESUMO

Patients with head and neck cancer (HNC) often experience cognitive impairment. However, the relationship between cancer and Alzheimer's disease (AD) remains unclear. We aimed to elucidate the relationship between patients with HNC and their subsequent AD development. This retrospective study used data from a nationwide representative cohort sample, the Korean National Health Insurance Service Cohort. The cancer group was defined based on the presence of diagnostic codes for HNC (C00-C14 and C30-C32). After matching the independent variables with a propensity score of 4:1, a total of 2304 people without HNC and 576 with HNC were enrolled in this study. Hazard ratios (HRs) of AD incidence (per 1000 person-years) and 95% confidence intervals (CIs) in HNC patients were calculated. The incidence of AD was 14.92 in HNC patients and 9.77 in non-cancer patients. Additionally, the HNC group was found to have a higher risk of developing AD compared with the non-cancer group. Female and middle-aged HNC patients had a higher risk of developing AD events compared with other subgroups. Surprisingly, during the observation period, the risk of developing AD was relatively high within the first year after HNC diagnosis. In conclusion, our study suggests that HNC and AD are positively correlated.

14.
Opt Express ; 31(24): 39981-39994, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38041309

RESUMO

In practical applications to free-space quantum communications, the utilization of active beam coupling and stabilization techniques offers notable advantages, particularly when dealing with limited detecting areas or coupling into single-mode fibers(SMFs) to mitigate background noise. In this work, we introduce highly-enhanced active beam-wander-correction technique, specifically tailored to efficiently couple and stabilize beams into SMFs, particularly in scenarios where initial optical alignment with the SMF is misaligned. To achieve this objective, we implement a SMF auto-coupling algorithm and a decoupled stabilization method, effectively and reliably correcting beam wander caused by atmospheric turbulence effects. The performance of the proposed technique is thoroughly validated through quantitative measurements of the temporal variation in coupling efficiency(coincidence counts) of a laser beam(entangled photons). The results show significant improvements in both mean values and standard deviations of the coupling efficiency, even in the presence of 2.6 km atmospheric turbulence effects. When utilizing a laser source, the coupling efficiency demonstrates a remarkable mean value increase of over 50 %, accompanied by a substantial 4.4-fold improvement in the standard deviation. For the entangled photon source, a fine mean value increase of 14 % and an approximate 2-fold improvement in the standard deviation are observed. Furthermore,the proposed technique successfully restores the fidelity of the polarization-entangled state, which has been compromised by atmospheric effects in the free-space channel, to a level close to the fidelity measured directly from the source. Our work will be helpful in designing spatial light-fiber coupling system not only for free-space quantum communications but also for high-speed laser communications.

15.
Life (Basel) ; 13(12)2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38137840

RESUMO

Several studies have investigated the association between chronic rhinosinusitis (CRS) and ophthalmological complications. However, it remains uncertain whether CRS is independently associated with the development of normal tension glaucoma (NTG). Therefore, this retrospective cohort study aimed to investigate the prospective association between CRS and the increased incidence and risk of NTG using a representative population-based dataset. The selection of both the CRS and comparison groups was meticulously conducted through the propensity scoring method. The incidence and risk ratios of NTG were measured using person-years at risk and a weighted Cox proportional hazards model. We enrolled 30,284 individuals without CRS (comparison group) and 15,142 individuals with CRS. The NTG incidence rates were 1.19 and 0.81 in the CRS and comparison groups, respectively. The CRS group showed a significantly increased risk of subsequent development for NTG (adjusted hazard ratio = 1.41, 95% confidence interval = 1.16-1.72), regardless of the CRS subtype. Additionally, the risk of developing NTG was relatively higher in the first 2 years after CRS diagnosis. Moreover, a subgroup analysis revealed a higher risk of NTG in elderly female individuals with CRS. The present findings underscore the importance of monitoring and managing NTG risk in individuals with CRS, especially in elderly female patients.

16.
Bioengineering (Basel) ; 10(11)2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-38002434

RESUMO

The complex process of bone regeneration is influenced by factors such as inflammatory responses, tissue interactions, and progenitor cells. Currently, multiple traumas can interfere with fracture healing, causing the prolonging or failure of healing. In these cases, bone grafting is the most effective treatment. However, there are several drawbacks, such as morbidity at the donor site and availability of suitable materials. Advantages have been provided in this field by a variety of stem cell types. Adipose-derived stem cells (ASCs) show promise. In the radiological examination of this study, it was confirmed that the C/S group showed faster regeneration than the other groups, and Micro-CT also showed that the degree of bone formation in the defect area was highest in the C/S group. Compared to the control group, the change in cortical bone area in the defect area decreased in the sham group (0.874), while it slightly increased in the C/S group (1.027). An increase in relative vascularity indicates a decrease in overall bone density, but a weak depression filled with fibrous tissue was observed outside the compact bone. It was confirmed that newly formed cortical bone showed a slight difference in bone density compared to surrounding normal bone tissue due to increased distribution of cortical bone. In this study, we investigated the effect of bone regeneration by ADMSCs measured by radiation and pathological effects. These data can ultimately be applied to humans with important clinical applications in various bone diseases, regenerative, and early stages of formative differentiation.

17.
Allergy Asthma Immunol Res ; 15(5): 647-658, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37827981

RESUMO

PURPOSE: Several studies have reported a possible link between chronic rhinosinusitis (CRS) and rheumatoid arthritis (RA). However, it remains unclear whether CRS could influence the risk of developing RA. Therefore, in this study, we focused on examining the association between CRS and RA. METHODS: A total of 14,867 individuals with CRS and 14,867 without CRS were enrolled after 1:1 propensity score match from a nationwide longitudinal cohort database in South Korea. RA incidence was assessed using person-years at risk, and the hazard ratio (HR) was examined using the Cox proportional hazards model. RESULTS: The incidence of RA (per 1,000 person-years) was 6.51 for those with CRS, 6.55 for those with CRS without nasal polyps (CRSsNP), and 5.96 for those with CRS with nasal polyps (CRSwNP). We found that CRS individuals had a significantly increased risk of subsequent RA development with an adjusted HR of 1.41, regardless of the phenotype (adjusted HR was 1.42 in CRSsNP and 1.37 in CRSwNP patients). Moreover, the risk of developing RA over time was relatively higher within the first 4 years after the diagnosis of CRS. CONCLUSIONS: Our nationwide population-based cohort study suggests that CRS may be associated with a subsequent increase in RA events, regardless of the phenotype. Therefore, physicians should consider RA risk when diagnosing and treating CRS patients.

18.
BMB Rep ; 56(12): 657-662, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37817435

RESUMO

Neurodegenerative diseases are characterized by distinct protein aggregates, such as those of α-synuclein and tau. Lysosomal defect is a key contributor to the accumulation and propagation of aberrant protein aggregates in these diseases. The discoveries of common proteinopathies in multiple forms of lysosomal storage diseases (LSDs) and the identification of some LSD genes as susceptible genes for those proteinopathies suggest causative links between LSDs and the proteinopathies. The present study hypothesized that defects in lysosomal genes will differentially affect the propagation of α-synuclein and tau proteins, thereby determining the progression of a specific proteinopathy. We established an imaging-based high-contents screening (HCS) system in Caenorhabditis elegans (C. elegans) model, by which the propagation of α-synuclein or tau is measured by fluorescence intensity. Using this system, we performed RNA interference (RNAi) screening to induce a wide range of lysosomal malfunction through knock down of 79 LSD genes, and to obtain the candidate genes with significant change in protein propagation. While some LSD genes commonly affected both α-synuclein and tau propagation, our study identified the distinct sets of LSD genes that differentially regulate the propagation of either α-synuclein or tau. The specificity and efficacy of these LSD genes were retained in the disease-related phenotypes, such as pharyngeal pumping behavior and life span. This study suggests that distinct lysosomal genes differentially regulate the propagation of α-synuclein and tau, and offer a steppingstone to understanding disease specificity. [BMB Reports 2023; 56(12): 657-662].


Assuntos
Deficiências na Proteostase , Sinucleinopatias , Tauopatias , Animais , Humanos , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Agregados Proteicos , Tauopatias/genética , Proteínas tau/genética , Proteínas tau/metabolismo , Lisossomos/genética , Lisossomos/metabolismo
19.
Comput Biol Med ; 166: 107532, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37816272

RESUMO

Premature ventricular contraction (PVC) is a common and harmless cardiac arrhythmia that can be asymptomatic or cause palpitations and chest pain in rare instances. However, frequent PVCs can lead to more serious arrhythmias, such as atrial fibrillation. Several PVC detection models have been proposed to enable early diagnosis of arrhythmias; however, they lack reliability and generalizability due to the variability of electrocardiograms across different settings and noise levels. Such weaknesses are known to aggravate with new data. Therefore, we present a deep learning model with a novel attention mechanism that can detect PVC accurately, even on unseen electrocardiograms with various noise levels. Our method, called the Denoise and Contrast Attention Module (DCAM), is a two-step process that denoises signals with a convolutional neural network (CNN) in the frequency domain and attends to differences. It focuses on differences in the morphologies and intervals of the remaining beats, mimicking how trained clinicians identify PVCs. Using three different encoder types, we evaluated 1D U-Net with DCAM on six external test datasets. The results showed that DCAM significantly improved the F1-score of PVC detection performance on all six external datasets and enhanced the performance of balancing both the sensitivity and precision of the models, demonstrating its robustness and generalization ability regardless of the encoder type. This demonstrates the need for a trainable denoising process before applying the attention mechanism. Our DCAM could contribute to the development of a reliable algorithm for cardiac arrhythmia detection under real clinical electrocardiograms.

20.
J Appl Microbiol ; 134(9)2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37699790

RESUMO

AIMS: Diet and nutrition are important aspects of skin physiology and health. However, the influence of diet on the bacterial flora of different skin sites is not well understood. Therefore, we investigated the relationship between dietary patterns (DPs) and skin bacterial flora on the forearm (a dry site) and the neck (a sebaceous site) of healthy Korean adults. METHODS AND RESULTS: In metagenomics analysis, Shannon and Simpson indices were higher on the forearm than on the neck and were negatively correlated with the two dominant species, Cutibacterium acnes and Staphylococcus epidermidis, on two skin sites. In addition, the Simpson index of the forearm was positively associated with DP1 (characterized by a high intake of vegetables, mushrooms, meat, fish and shellfish, seaweed, and fat and oil), while that on the neck was negatively associated with DP2 (characterized by a high intake of fast food). A high intake of DP1 was associated with a lower abundance of dominant species, including C. acnes, and higher degrees of the co-occurrence network, whereas a high intake of DP2 was associated with the opposite pattern. CONCLUSIONS: Specific diets may impact both skin bacterial diversity and composition, as well as the co-occurrence of bacteria, which may vary across different skin sites.


Assuntos
Antebraço , Pele , Animais , Bactérias/genética , Verduras , República da Coreia
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