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OBJECTIVE: To examine the association between cerebral artery stenosis and depressive symptoms in elderly patients. METHODS: The study participants were 365 patients aged ≥65 years who visited the psychiatric outpatient clinic, Samsung Medical Center between January 1, 2000, and December 31, 2019, and were diagnosed with depressive disorder. They had brain imaging tests including magnetic resonance angiography (MRA), psychological evaluations including the 15-item Geriatric Depression Scale (GDS-15), and lab tests. Individuals' cerebral artery stenosis was identified and the association with significant depressive symptoms was examined. RESULTS: Of the 365 subjects, 108 had at least one location of cerebral artery stenosis (29.6 %). The mean score of GDS-15 in the stenosis group was 8.1 (SD, 3.8), higher than the mean GDS-15 score of 6.5 (SD, 4.0) for the group without stenosis (p < 0.001). Compared to no middle cerebral artery (MCA) stenosis, having MCA stenosis was associated with significant depressive symptoms (p = 0.005). Compared to no posterior cerebral artery (PCA) stenosis, having left PCA stenosis was associated with significant depressive symptoms (p = 0.022). In the multivariable linear regression analysis, only bilateral MCA stenosis had a positive association with the score of GDS-15 (p = 0.013). CONCLUSION: Bilateral MCA stenosis and left PCA stenosis are associated with significant depressive symptoms among elderly patients, with bilateral MCA stenosis positively associated with the severity of depression.
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Depressão , Angiografia por Ressonância Magnética , Humanos , Idoso , Masculino , Feminino , Depressão/epidemiologia , Constrição Patológica , Idoso de 80 Anos ou mais , Doenças Arteriais Cerebrais/diagnóstico por imagem , Doenças Arteriais Cerebrais/epidemiologia , Doenças Arteriais Cerebrais/complicações , Transtorno Depressivo/epidemiologia , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Posterior/diagnóstico por imagem , Escalas de Graduação PsiquiátricaRESUMO
BACKGROUND: The risk-benefit relationship of immunosuppressive therapies (ISTs) for elderly patients with neuromyelitis optica spectrum disorder (NMOSD) is not well established. This study aimed to investigate the safety and efficacy of IST in elderly patients with NMOSD. METHODS: This retrospective study analysed IST efficacy and safety in 101 patients with aquaporin-4 antibody-positive NMOSD aged over 65 years, treated for at least 6 months at five Korean referral centres, focusing on relapse rates, infection events and discontinuation due to adverse outcomes. RESULTS: The mean age at disease onset was 59.8 years, and female-to-male ratio was 4:1. Concomitant comorbidities at NMOSD diagnosis were found in 87 patients (86%). The median Expanded Disability Status Scale score at the initiation of IST was 3.5. The administered ISTs included azathioprine (n=61, 60%), mycophenolate mofetil (MMF) (n=48, 48%) and rituximab (n=41, 41%). Over a median of 5.8 years of IST, 58% of patients were relapse-free. The median annualised relapse rate decreased from 0.76 to 0 (p<0.001), and 81% experienced improved or stabilised disability. Patients treated with rituximab had a higher relapse-free rate than those treated with azathioprine or MMF (p=0.022). During IST, 21 patients experienced 25 severe infection events (SIEs) over the age of 65 years, and 3 died from pneumonia. 14 patients (14%) experienced 17 adverse events that led to switching or discontinuation of IST. When comparing the incidence rates of SIEs and adverse events, no differences were observed among patients receiving azathioprine, MMF and rituximab. CONCLUSION: In elderly patients with NMOSD, IST offers potential benefits in reducing relapse rates alongside a tolerable risk of adverse events.
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BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea. METHODS: This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients. RESULTS: Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients. CONCLUSION: This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.
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Vacinas contra COVID-19 , COVID-19 , Hospitalização , Miastenia Gravis , SARS-CoV-2 , Vacinação , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/complicações , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Idoso , SARS-CoV-2/isolamento & purificação , Adulto , Prognóstico , Unidades de Terapia Intensiva , Respiração ArtificialRESUMO
B cell receptors (BCRs) denote antigen specificity, while corresponding cell subsets indicate B cell functionality. Since each B cell uniquely encodes this combination, physical isolation and subsequent processing of individual B cells become indispensable to identify both attributes. However, this approach accompanies high costs and inevitable information loss, hindering high-throughput investigation of B cell populations. Here, we present BCR-SORT, a deep learning model that predicts cell subsets from their corresponding BCR sequences by leveraging B cell activation and maturation signatures encoded within BCR sequences. Subsequently, BCR-SORT is demonstrated to improve reconstruction of BCR phylogenetic trees, and reproduce results consistent with those verified using physical isolation-based methods or prior knowledge. Notably, when applied to BCR sequences from COVID-19 vaccine recipients, it revealed inter-individual heterogeneity of evolutionary trajectories towards Omicron-binding memory B cells. Overall, BCR-SORT offers great potential to improve our understanding of B cell responses.
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Subpopulações de Linfócitos B , Aprendizado Profundo , Humanos , Filogenia , Vacinas contra COVID-19 , Receptores de Antígenos de Linfócitos B/genéticaRESUMO
The tumor microenvironment comprises both tumor and non-tumor stromal cells, including tumor-associated macrophages (TAMs), endothelial cells, and carcinoma-associated fibroblasts. TAMs, major components of non-tumor stromal cells, play a crucial role in creating an immunosuppressive environment by releasing cytokines, chemokines, growth factors, and immune checkpoint proteins that inhibit T cell activity. During tumors develop, cancer cells release various mediators, including chemokines and metabolites, that recruit monocytes to infiltrate tumor tissues and subsequently induce an M2-like phenotype and tumor-promoting properties. Metabolites are often overlooked as metabolic waste or detoxification products but may contribute to TAM polarization. Furthermore, macrophages display a high degree of plasticity among immune cells in the tumor microenvironment, enabling them to either inhibit or facilitate cancer progression. Therefore, TAM-targeting has emerged as a promising strategy in tumor immunotherapy. This review provides an overview of multiple representative metabolites involved in TAM phenotypes, focusing on their role in pro-tumoral polarization of M2.
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PURPOSE: Nerve conduction study (NCS) is essential for subclassifying Guillain-Barré syndrome (GBS). It is well known that the GBS subclassification can change through serial NCSs. However, the usefulness of serial NCSs is debatable, especially in patients with early stage GBS. METHODS: Follow-up NCS data within 3 weeks (early followed NCS, EFN) and within 3 to 10 weeks (late-followed NCS, LFN) were collected from 60 patients with GBS who underwent their first NCS (FN) within 10 days after symptom onset. Each NCS was classified into five subtypes (normal, demyelinating, axonal, inexcitable, and equivocal), according to Hadden's and Rajabally's criteria. We analyzed the frequency of significant changes in classification (SCCs) comprising electrodiagnostic aggravation and subtype shifts between demyelinating and axonal types according to follow-up timing. RESULTS: Between FN and EFN, 33.3% of patients with Hadden's criteria and 18.3% with Rajabally's criteria showed SCCs. Between FN and LFN, 23.3% of patients with Hadden's criteria and 21.7% with Rajabally's criteria showed SCCs, of which 71.4% (Hadden's criteria) and 46.2% (Rajabally's criteria) already showed SCCs from the EFN. The conditions of delayed SCCs between EFN and LFN were very early FN, mild symptoms at the FN, or persistent electrophysiological deterioration 3 weeks after symptom onset. CONCLUSIONS: A substantial proportion of patients with GBS showed significant changes in neurophysiological classification at the early stage. Serial NCS may be helpful for precise neurophysiological classification. This study suggests that follow-up NCSs should be performed within 3 weeks of symptom onset in patients with GBS in whom FN was performed within 10 days of symptom onset.
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Síndrome de Guillain-Barré , Zinostatina , Humanos , Síndrome de Guillain-Barré/diagnóstico , Estudos de Condução Nervosa , NeurofisiologiaRESUMO
Myasthenia gravis (MG) is an autoimmune disorder that affects the neuromuscular junctions, resulting in muscle weakness and fatigue. Muscle weakness, restricted mobility, and frequent use of corticosteroids in patients with MG may predispose them to a higher risk of fractures. However, studies on the impact of MG on bone health and the associated fracture risk are scarce. Utilizing claim database of the Korean National Health Insurance Service collected between 2002 and 2020, we compared the risk of major osteoporotic fracture between 23 118 patients with MG and 115 590 individuals as an age- and sex-matched control group using multivariable Cox proportional hazard models. Over a median follow-up duration of 5.58 years, the MG group (mean age 53.7 years; 55% women) had higher risk of major osteoporotic fracture compared with controls (incidence rate 13.59 versus 9.74 per 10 000 person-years), which remained independent of age, sex, comorbidities, drug use including anti-osteoporotic agents, and previous fracture history (adjusted hazard ratio [aHR] 1.19, P < 0.001; subdistributed HR 1.14, P < 0.001 adjusted for mortality as competing risk). Subgroup analyses showed a greater association between MG and major osteoporotic fracture risk in younger (age 50 or younger) than older individuals (aHR 1.34 vs. 1.17) and in men compared with women (aHR 1.32 vs. 1.15; P for interaction < 0.05 for all). An imminent divergence of the fracture risk curve between MG and controls was observed for vertebral fracture, while there was time delay for non-vertebral sites, showing site-specific association. Factors associated with higher fracture risk in patients with MG were older age, female gender, high dose glucocorticoid use (>7.5 mg/day), immunosuppressant use, and previous history of fracture. In summary, patients with MG had higher risk of major osteoporotic fracture compared with controls, which calls further preventive actions in this patient group.
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Miastenia Gravis , Humanos , Feminino , Masculino , Miastenia Gravis/epidemiologia , Miastenia Gravis/complicações , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Fatores de Risco , Adulto , Idoso , Fraturas por Osteoporose/epidemiologia , Estudos de Coortes , Modelos de Riscos ProporcionaisRESUMO
STUDY DESIGN: This was a single-institutional retrospective cohort study. OBJECTIVE: Wound infections are common following spine metastasis surgery and can result in unplanned reoperations. A recent study published an online wound complication risk calculator but has not yet undergone external validation. Our aim was to evaluate the accuracy of this risk calculator in predicting 30-day wound infections and 30-day wound reoperations using our operative spine metastasis population. METHODS: An internal operative database was used to identify patients between 2012 and 2022. The primary outcomes were 1) any surgical site infection and 2) wound-related revision surgery within 30 days following surgery. Patient details were manually collected from electronic medical records and entered into the calculator to determine predicted complication risk percentages. Predicted risks were compared to observed outcomes using receiver operator characteristic (ROC) curves with areas under the curve (AUC). RESULTS: A total of 153 patients were included. The observed 30-day postoperative wound infection incidence was 5% while the predicted wound infection incidence was 6%. In ROC analysis, good discrimination was found for the wound infection model (AUC = 0.737; P = 0.024). The observed wound reoperation rate was 5% and the predicted wound reoperation rate was 6%. ROC analysis demonstrated poor discrimination for wound reoperations (AUC = 0.559; P = 0.597). CONCLUSIONS: The online wound-related risk calculator was found to accurately predict wound infections but not wound reoperations within our metastatic spine surgery cohort. We suggest that the model may be clinically useful despite underlying population differences, but further work must be done to generate and validate accurate prediction tools.
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Reoperação , Neoplasias da Coluna Vertebral , Infecção da Ferida Cirúrgica , Humanos , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/secundário , Masculino , Infecção da Ferida Cirúrgica/epidemiologia , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Medição de Risco , Adulto , Estudos de Coortes , Fatores de Risco , Curva ROCRESUMO
Genetic neuromuscular diseases are clinically and genetically heterogeneous genetic disorders that primarily affect the peripheral nerves, muscles, and neuromuscular junctions. This study aimed to identify pathogenic variants, calculate carrier frequency, and predict the genetic prevalence of autosomal recessive neuromuscular diseases (AR-NMDs). We selected 268 AR-NMD genes and analyzed their genetic variants sourced from the gnomAD database. After identifying the pathogenic variants using an algorithm, we calculated the carrier frequency and predicted the genetic prevalence of AR-NMDs. In total, 10,887 pathogenic variants were identified, including 3848 literature verified and 7039 manually verified variants. In the global population, the carrier frequency of AR-NMDs is 32.9%, with variations across subpopulations ranging from 22.4% in the Finnish population to 36.2% in the non-Finnish European population. The predicted genetic prevalence of AR-NMDs was estimated to be 24.3 cases per 100,000 individuals worldwide, with variations across subpopulations ranging from 26.5 to 41.4 cases per 100,000 individuals in the Latino/Admixed American and the Ashkenazi Jewish populations, respectively. The AR-NMD gene with the highest carrier frequency was GAA (1.3%) and the variant with the highest allele frequency was c.-32-13 T>G in GAA with 0.0033 in the global population. Our study revealed a higher-than-expected frequency of AR-NMD carriers, constituting approximately one-third of the global population, highlighting ethnic heterogeneity in genetic susceptibility.
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Predisposição Genética para Doença , Doenças Neuromusculares , Humanos , Frequência do Gene , Doenças Neuromusculares/epidemiologia , Doenças Neuromusculares/genética , Prevalência , Saúde GlobalRESUMO
Myasthenia Gravis (MG) patients with anti-acetylcholine receptor (AChR) antibodies frequently show hyperplastic thymi with ectopic germinal centers, where autoreactive B cells proliferate with the aid of T cells. In this study, thymus and peripheral blood (PB) samples were collected from ten AChR antibody-positive MG patients. T cell receptor (TCR) repertoires were analyzed using next-generation sequencing (NGS), and compared with that of an age and sex matched control group generated from a public database. Certain V genes and VJ gene recombination pairs were significantly upregulated in the TCR chains of αß-T cells in the PB of MG patients compared to the control group. Furthermore, the TCR chains found in the thymi of MG patients had a weighted distribution to longer CDR3 lengths when compared to the PB of MG patients, and the TCR beta chains (TRB) in the MG group's PB showed increased clonality encoded by one upregulated V gene. When TRB sequences were sub-divided into groups based on their CDR3 lengths, certain groups showed decreased clonality in the MG group's PB compared to the control group's PB. Finally, we demonstrated that stereotypic MG patient-specific TCR clonotypes co-exist in both the PB and thymi at a much higher frequency than that of the clonotypes confined to the PB. These results strongly suggest the existence of a biased T cell-mediated immune response in MG patients, as observed in other autoimmune diseases.
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Breast cancer is a frequently occurring malignant tumor that is one of the leading causes of cancer-related deaths in women worldwide. Monoclonal antibodies that block programed cell death 1 (PD-1)/programed cell death ligand 1 (PD-L1) - a typical immune checkpoint - are currently the recommended standard therapies for many advanced and metastatic tumors such as triple-negative breast cancer. However, some patients develop drug resistance, leading to unfavorable treatment outcomes. Therefore, other approaches are required for anticancer treatments, such as downregulation of PD-L1 expression and promotion of degradation of PD-L1. Scoparone (SCO) is a bioactive compound isolated from Artemisia capillaris that exhibits antitumor activity. However, the effect of SCO on PD-L1 expression in cancer has not been confirmed yet. This study aimed to evaluate the role of SCO in PD-L1 expression in breast cancer cells in vitro. Our results show that SCO downregulated PD-L1 expression in a dose-dependent manner, via AKT inhibition. Interestingly, SCO treatment did not alter PTEN expression, but increased the expression of mitogen-activated protein kinase phosphatase-3 (MKP-3). In addition, the SCO-induced decrease in PD-L1 expression was reversed by siRNA-mediated MKP-3 knockdown. Collectively, these findings suggest that SCO inhibited the expression of PD-L1 in breast cancer cells by upregulating MKP-3 expression. Therefore, SCO may serve as an innovative combinatorial agent for cancer immunotherapy.
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HMGB1 is a prototypical danger-associated molecular pattern (DAMP) molecule that co-localizes with amyloid beta (Aß) in the brains of patients with Alzheimer's disease. HMGB1 levels are significantly higher in the cerebrospinal fluid of patients. However, the cellular and subcellular distribution of HMGB1 in relation to the pathology of Alzheimer's disease has not yet been studied in detail. Here, we investigated whether HMGB1 protein levels in brain tissue homogenates (frontal cortex and striatum) and sera from Tg-APP/PS1 mice, along with its cellular and subcellular localization in those regions, differed. Total HMGB1 levels were increased in the frontal cortices of aged wildtype (7.5 M) mice compared to young (3.5 M) mice, whereas total HMGB1 levels in the frontal cortices of Tg-APP/PS1 mice (7.5 M) were significantly lower than those in age-matched wildtype mice. In contrast, total serum HMGB1 levels were enhanced in aged wildtype (7.5 M) mice and Tg-APP/PS1 mice (7.5 M). Further analysis indicated that nuclear HMGB1 levels in the frontal cortices of Tg-APP/PS1 mice were significantly reduced compared to those in age-matched wildtype controls, and cytosolic HMGB1 levels were also significantly decreased. Triple-fluorescence immunohistochemical analysis indicated that HMGB1 appeared as a ring shape in the cytoplasm of most neurons and microglia in the frontal cortices of 9.5 M Tg-APP/PS1 mice, indicating that nuclear HMGB1 is reduced by aging and in Tg-APP/PS1 mice. Consistent with these observations, Aß treatment of both primary cortical neuron and primary microglial cultures increased HMGB1 secretion in the media, in an Aß-dose-dependent manner. Our results indicate that nuclear HMGB1 might be translocated from the nucleus to the cytoplasm in both neurons and microglia in the brains of Tg-APP/PS1 mice, and that it may subsequently be secreted extracellularly.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Proteína HMGB1 , Idoso , Animais , Humanos , Camundongos , Alarminas , Encéfalo , Microglia , Neurônios , Modelos Animais de DoençasRESUMO
BACKGROUND AND PURPOSE: Anti-neurofascin-155 (NF155) antibody is one of the autoantibodies associated with autoimmune nodopathy. We aimed to determine the clinical features of South Korean patients with anti-NF155-antibody-positive autoimmune nodopathy. METHODS: The sera of 68 patients who fulfilled the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) were tested for anti-NF155 antibodies using a cell-based assay (CBA) and enzyme-linked immunosorbent assay (ELISA). The anti-NF155-positive sera were also assayed for NF155 immunoglobulin G (IgG) subclasses, and for anti-NF186 and NF140 antibodies. The clinical features of the patients were reviewed retrospectively. RESULTS: Among the 68 patients, 6 (8.8%) were positive for anti-NF155 antibodies in both the CBA and ELISA. One of those six patients was also positive for anti-NF186 and anti-NF140 antibodies. IgG4 was the predominant subclass in four patients. The mean age at onset was 32.2 years. All six positive patients presented with progressive sensory ataxia. Five patients treated using corticosteroids presented a partial or no response. All six patients were treated using intravenous immunoglobulin (IVIg). Among them, five exhibited a partial or poor response and the other exhibited a good response. All three patients treated using rituximab showed a good response. CONCLUSIONS: The clinical characteristics of the patients were consistent with those in previous studies. Anti-NF155 antibody assay is necessary for diagnosing autoimmune nodopathy and its appropriate treatment, especially in young patients with CIDP who present with sensory ataxia and poor therapeutic responses to corticosteroids and IVIg.
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BACKGROUND AND PURPOSE: Germinal centers (GCs) can be observed in the thymic tissues of patients with thymoma-associated myasthenia gravis (MG). Although an association between thymic GCs and MG has been suggested, it is unknown whether the presence of GCs could predict the development of MG after the resection of thymoma, known as postthymectomy MG. METHODS: We conducted a retrospective analysis of previously nonmyasthenic patients who underwent surgical removal of the thymoma. All available thymic tissue slides were rereviewed by a pathologist to assess for GCs. Patients were classified into GC-positive and GC-negative groups based on the presence of GCs. The incidence of postthymectomy MG was compared between the two groups, and the risk factors for postthymectomy MG were assessed. RESULTS: Of the 196 previously nonmyasthenic patients who underwent thymoma resection, 21 were GC-positive, whereas 175 were GC-negative. Postthymectomy MG developed in 11 (5.6%) patients and showed a higher incidence in the GC-positive group than in the GC-negative group (33.3% vs. 2.3%, p < 0.001). No postoperative radiotherapy and the presence of GCs were risk factors for postthymectomy MG in the univariate analysis. In multivariate analysis, invasive thymoma (hazard ratio [HR] = 9.835, 95% confidence interval [CI] = 1.358-105.372), postoperative radiotherapy (HR = 0.160, 95% CI = 0.029-0.893), and presence of GCs (HR = 15.834, 95% CI = 3.742-67.000) were significantly associated with postthymectomy MG. CONCLUSIONS: Thymic GCs may be a significant risk factor for postthymectomy MG. Even in patients with thymoma who do not show clinical symptoms of MG, postthymectomy MG should be considered, especially if thymic GCs are observed.
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Miastenia Gravis , Timoma , Neoplasias do Timo , Humanos , Timoma/complicações , Timoma/cirurgia , Estudos Retrospectivos , Timectomia/efeitos adversos , Neoplasias do Timo/complicações , Neoplasias do Timo/cirurgia , Miastenia Gravis/complicaçõesRESUMO
OBJECTIVE: Inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) have shown promise in predicting mortality in various types of cancer. The purpose of this study was to assess NLR, PLR, and SII in predicting 30-day mortality and overall survival (OS) among surgically treated patients with spinal metastasis. METHODS: This was a retrospective study including 153 patients who underwent surgery for spinal metastasis between 2012 and 2022. Electronic medical records were manually reviewed, and NLR, PLR, and SII were calculated from preoperative neutrophil, platelet, and lymphocyte counts. Receiver operating characteristic curves with areas under the curve were generated to determine cutoff values. Logistic regression was used to determine the odds ratios (ORs) for 30-day mortality. The Kaplan-Meier method and Cox regression were used to determine the hazard ratio (HR) for OS limited to 5 years postoperatively. RESULTS: Preoperative cutoff values were as follows: NLR > 10.2, PLR > 260, and SII > 2900. Overall, 35.9% (55/153) of patients had elevated NLR, 45.7% (70/153) had elevated PLR, and 30.7% (47/153) had elevated SII. The overall 30-day mortality was 8.5% (13/153). After controlling for confounders such as performance status and primary tumor type, high NLR (OR 5.20, 95% CI 1.21-22.28; p = 0.026) and SII (OR 4.92, 95% CI 1.17-20.63; p = 0.029) were associated with increased odds of 30-day postoperative mortality. The median OS time in the study population was 26 months (95% CI 12-40 months). After controlling for confounders such as Eastern Cooperative Oncology Group status, primary tumor, and hypoalbuminemia, high NLR was associated with shorter OS (HR 2.23, 95% CI 1.48-3.97; p = 0.003). CONCLUSIONS: High preoperative NLR and SII were independently associated with 30-day postoperative mortality in this study. Elevated NLR was also found to be associated with shorter OS. The prognostic role of these metrics warrants further investigation.
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Neoplasias da Coluna Vertebral , Humanos , Prognóstico , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/patologia , Neutrófilos/patologia , Estudos Retrospectivos , Linfócitos/patologia , InflamaçãoRESUMO
Dysregulation of brain iron levels causes functional disturbances and damages neurons. Hepcidin (a peptide hormone) plays a principal role in regulating intracellular iron levels by modulating ferroportin (FPN, the only known iron exporter) through triggering its internalization and lysosomal degradation. We observed a significant and rapid iron surge in the cortices of ischemic hemispheres at 3 h after cerebral ischemia (middle cerebral artery occlusion, MCAO) that was maintained until 4 d post-MCAO. We showed upregulation of hepcidin expression in the brain as early as 3 h post-MCAO, mainly in astrocytes, and significant hepcidin accumulation in serum from 6 h post-MCAO, and these inductions were maintained for 1 day and 7 days, respectively. High mobility group box 1 (HMGB1), a prototypic danger-associated molecular pattern, accumulates markedly after transient MCAO and plays critical roles in damage aggravation via its proinflammatory effects. Here, we demonstrated that treatment with recombinant HMGB1 stimulated astrocytes to induce hepcidin expression in a TLR4- and CXCR4-dependent manner. Furthermore, hepcidin-mediated intracellular iron accumulation in neurons was confirmed by an experiment using N-methyl-D-aspartate (NMDA)-conditioned medium-treated primary astrocytes and fresh primary cortical neurons treated with hepcidin-containing astrocyte-conditioned medium. Moreover, HMGB1-mediated local hepcidin upregulation and subsequent local iron surge were found to cause ferroptosis in the postischemic brain, which was suppressed by the functional blocking of HMGB1 using intranasally administered HMGB1 A box or anti-HMGB1 antibody. These findings show that HMGB1 serves as a ferroptosis inducer by upregulating hepcidin in astrocytes and thus aggravates acute damage in the postischemic brain.
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Ferroptose , Proteína HMGB1 , Ratos , Animais , Astrócitos/metabolismo , Ratos Sprague-Dawley , Regulação para Cima , Hepcidinas/genética , Hepcidinas/metabolismo , Meios de Cultivo Condicionados/metabolismo , Encéfalo/metabolismoRESUMO
We configured a long-distance ranging apparatus to test the principle of dual-comb time-of-flight measurement using ultrashort lasers. Emphasis was given to the evaluation of open-air performance quantitatively in terms of the measurement resolution and stability. The test results revealed that our dual-comb asynchronous optical pulse sampling permits micrometer-resolved ranging with a repeatability of 2.05 µm over a 648 m distance in dry weather conditions. Further atmospheric effects were evaluated in three different weather conditions with corresponding Allan deviations. Finally, the capability of simultaneous determination of multiple targets was verified with the potential of advanced industrial applications, such as manufacturing, surveying, metrology, and geodesy.
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In multicellular organisms, including higher plants, asymmetric cell divisions (ACDs) play a crucial role in generating distinct cell types. The Arabidopsis root ground tissue initially has two layers: endodermis (inside) and cortex (outside). In the mature root, the endodermis undergoes additional ACDs to produce the endodermis itself and the middle cortex (MC), located between the endodermis and the pre-existing cortex. In the Arabidopsis root, gibberellic acid (GA) deficiency and hydrogen peroxide (H2O2) precociously induced more frequent ACDs in the endodermis for MC formation. Thus, these findings suggest that GA and H2O2 play roles in regulating the timing and extent of MC formation. However, details of the molecular interaction between GA signaling and H2O2 homeostasis remain elusive. In this study, we identified the PEROXIDASE 34 (PRX34) gene, which encodes a class III peroxidase, as a molecular link to elucidate the interconnected regulatory network involved in H2O2- and GA-mediated MC formation. Under normal conditions, prx34 showed a reduced frequency of MC formation, whereas the occurrence of MC in prx34 was restored to nearly WT levels in the presence of H2O2. Our results suggest that PRX34 plays a role in H2O2-mediated MC production. Furthermore, we provide evidence that SCARECROW-LIKE 3 (SCL3) regulates H2O2 homeostasis by controlling transcription of PRX34 during root ground tissue maturation. Taken together, our findings provide new insights into how H2O2 homeostasis is achieved by SCL3 to ensure correct radial tissue patterning in the Arabidopsis root.
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Personal wearable devices are considered important in advanced healthcare, military, and sports applications. Among them, e-textiles are the best candidates because of their intrinsic conformability without any additional device installation. However, e-textile manufacturing to date has a high process complexity and low design flexibility. Here, we report the direct laser writing of e-textiles by converting raw Kevlar textiles to electrically conductive laser-induced graphene (LIG) via femtosecond laser pulses in ambient air. The resulting LIG has high electrical conductivity and chemical reliability with a low sheet resistance of 2.86 Ω/â¡. Wearable multimodal e-textile sensors and supercapacitors are realized on different types of Kevlar textiles, including nonwoven, knit, and woven structures, by considering their structural textile characteristics. The nonwoven textile exhibits high mechanical stability, making it suitable for applications in temperature sensors and micro-supercapacitors. On the other hand, the knit textile possesses inherent spring-like stretchability, enabling its use in the fabrication of strain sensors for human motion detection. Additionally, the woven textile offers special sensitive pressure-sensing networks between the warp and weft parts, making it suitable for the fabrication of bending sensors used in detecting human voices. This direct laser synthesis of arbitrarily patterned LIGs from various textile structures could result in the facile realization of wearable electronic sensors and energy storage.