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Microplastics (MPs) are recognized as environmental pollutants with potential implications for human health. Considering the rapid increase in obesity rates despite stable caloric intake, there is a growing concern about the link between obesity and exposure to environmental pollutants, including MPs. In this study, we conducted a comprehensive investigation utilizing in silico, in vitro, and in vivo approaches to explore the brain distribution and physiological effects of MPs. Molecular docking simulations were performed to assess the binding affinity of three plastic polymers (ethylene, propylene, and styrene) to immune cells (macrophages, CD4+, and CD8+ lymphocytes). The results revealed that styrene exhibited the highest binding affinity for macrophages. Furthermore, in vitro experiments employing fluorescence-labeled PS-MPs (fPS-MPs) of 1 µm at various concentrations demonstrated a dose-dependent binding of fPS-MPs to BV2 murine microglial cells. Subsequent oral administration of fPS-MPs to high-fat diet-induced obese mice led to the co-existence of fPS-MPs with immune cells in the blood, exacerbating impaired glucose metabolism and insulin resistance and promoting systemic inflammation. Additionally, fPS-MPs were detected throughout the brain, with increased activation of microglia in the hypothalamus. These findings suggest that PS-MPs significantly contribute to the exacerbation of systemic inflammation in high-fat diet-induced obesity by activating peripheral and central inflammatory immune cells.
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Parkinson's disease (PD) is a complex neurodegenerative disease in which neuroinflammation and oxidative stress interact to contribute to pathogenesis. This study investigates the in vivo neuroprotective effects of a patented yeast extract lysate in a lipopolysaccharide (LPS)-induced neuroinflammation model. The yeast extract lysate, named aldehyde-reducing composition (ARC), exhibited potent antioxidant and anti-aldehyde activities in vitro. Oral administration of ARC at 10 or 20 units/kg/day for 3 days prior to intraperitoneal injection of LPS (10 mg/kg) effectively preserved dopaminergic neurons in the substantia nigra (SN) and striatum by preventing LPS-induced cell death. ARC also normalized the activation of microglia and astrocytes in the SN, providing further evidence for its neuroprotective properties. In the liver, ARC downregulated the LPS-induced increase in inflammatory cytokines and reversed the LPS-induced decrease in antioxidant-related genes. These findings indicate that ARC exerts potent antioxidant, anti-aldehyde, and anti-inflammatory effects in vivo, suggesting its potential as a disease-modifying agent for the prevention and treatment of neuroinflammation-related diseases, including Parkinson's disease.
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Doenças Neurodegenerativas , Fármacos Neuroprotetores , Doença de Parkinson , Humanos , Doença de Parkinson/metabolismo , Lipopolissacarídeos/farmacologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/metabolismo , Doenças Neuroinflamatórias , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Doenças Neurodegenerativas/metabolismo , MicrogliaRESUMO
Obesity is a chronic peripheral inflammation condition that is strongly correlated with neurodegenerative diseases and associated with exposure to environmental chemicals. The aryl hydrocarbon receptor (AhR) is a ligand-activated nuclear receptor activated by environmental chemical, such as dioxins, and also is a regulator of inflammation through interacting with nuclear factor (NF)-κB. In this study, we evaluated the anti-obesity and anti-inflammatory activity of HBU651, a novel AhR antagonist. In BV2 microglia cells, HBU651 successfully inhibited lipopolysaccharide (LPS)-mediated nuclear localization of NF-κB and production of NF-κB-dependent proinflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6. It also restored LPS-induced mitochondrial dysfunction. While mice being fed a high-fat diet (HFD) induced peripheral and central inflammation and obesity, HBU651 alleviated HFD-induced obesity, insulin resistance, glucose intolerance, dyslipidemia, and liver enzyme activity, without hepatic and renal damage. HBU651 ameliorated the production of inflammatory cytokines and chemokines, proinflammatory Ly6chigh monocytes, and macrophage infiltration in the blood, liver, and adipose tissue. HBU651 also decreased microglial activation in the arcuate nucleus in the hypothalamus. These findings suggest that HBU651 may be a potential candidate for the treatment of obesity-related metabolic diseases.
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Dieta Hiperlipídica , Receptores de Hidrocarboneto Arílico , Animais , Camundongos , Citocinas , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Camundongos Obesos , NF-kappa B/metabolismo , Obesidade/tratamento farmacológico , Obesidade/etiologia , Obesidade/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Fator de Necrose Tumoral alfaRESUMO
This study aimed to investigate the effects of a violence-prevention education program using empathy (VPEP-E) on elementary school students. This quasi-experimental design examined fifth-grade students' (a) empathy level, (b) perception of violence, and (c) permissive and negligent attitudes toward violence, using a pre- and post-test design. A total of 101 students participated: the experimental group (n = 48) received eight sessions of VPEP-E, whereas the control group (n = 53) received violence prevention education through classroom lectures. Significant differences were observed between the groups' empathy level (t = 6.81, p < .001), perception of violence (t = 2.79, p = .006), and permissive and negligent attitudes toward violence (t = -2.21, p = .030; t = -2.02, p = .046). Thus, a school-based VPEP-E may help elementary school students. Long-term studies evaluating behavioral changes from VPEP-E implementation are needed for establishing the effects on violent behavior.
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The standard of treatment for completely resected limited-stage diffuse large B cell lymphoma (DLBCL) in patients without residual lesions has not yet been established. Previously, we designed a phase II trial to evaluate the safety and efficacy of three cycles of abbreviated R-CHOP in patients with completely resected limited-stage DLBCL and reported favorable survival outcomes. We present the long-term follow-up results to taking into account the importance of delayed relapse in patients with limited-stage DLBCL. With a median follow-up duration of 62.7 months (range, 60.2-75.5 months), the 5-year OS and DFS rates were both 95.0% (95% confidence interval, 85.59-104.11%). Only one patient experienced disease progression which was confirmed at 12.3 months, and one patient with primary intestinal DLBCL developed non-small cell lung cancer 6 years after treatment. The long-term results of our data support the use of three cycles of abbreviated R-CHOP for patients with completely resected limited-stage DLBCL. The study was reviewed and approved by the review boards of the participating institutes and registered at ClinicalTrials.gov , number NCT01279902, in August 3, 2010.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Imunoterapia/métodos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/terapia , Adulto , Idoso , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Prednisona/administração & dosagem , Estudos Prospectivos , Rituximab/administração & dosagem , Vincristina/administração & dosagemRESUMO
INTRODUCTION: Bisphenol F (BPF) and bisphenol S (BPS) are chemical substitutes for, and may have similar physiological effects to, bisphenol A (BPA). Bisphenols provoke endocrine disorders and are cytotoxic, oxidize hemoglobin, and induce morphological changes in human red blood cells (RBC). It is more sensitive to changes in the RBC number and hemoglobin (Hb) level during pregnancy. Therefore, we investigated the effects of bisphenols (BPs) and their substitute compounds on hemopoiesis and the serum biochemical parameters of pregnant women. METHODS: The study population comprised 196 pregnant women from the MAKE cohort study, recruitment for which occurred from 2017 to 2019. We measured the levels of BPA, BPF and BPS in urine samples and collected data on socioeconomic, lifestyle, and environmental factors at visits to the hospital. The associations between the levels of the three BPs and biochemical parameters were analyzed by multiple linear regression. RESULTS: The geometric mean urinary concentrations of specific gravity adjusted BPA, BPF, and BPS were 2.1, 0.2, and 0.1 µg/L, respectively. There was a significant negative association between the urinary concentration of BPA and the Hb level (ß = -0.5, p = 0.02). After stratifying by the median concentrations of the three BPs, the maternal urinary BPA level had a significantly negative effect on the RBC count, HB level, and hematocrit in the high BPA concentration group (RBC, ß = - 0.5, p = 0.001; Hb, ß = -1.4, p = 0.002; Hct, ß = -5.0, p = 0.001). CONCLUSIONS: BPA has a harmful effect on hemato-biochemical changes that occur during pregnancy. Further studies should investigate the relation between widespread exposure to bisphenols and effects on human health.
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Compostos Benzidrílicos , Eritrócitos , Fenóis , Complicações na Gravidez , Compostos Benzidrílicos/toxicidade , Compostos Benzidrílicos/urina , Estudos de Coortes , Feminino , Hemoglobinas , Humanos , Oxirredução , Fenóis/toxicidade , Fenóis/urina , Gravidez , Complicações na Gravidez/induzido quimicamente , República da CoreiaRESUMO
BACKGROUND: Persistent organic pollutants (POPs) may cause diabetes, in part through aryl hydrocarbon receptor (AhR) binding. Ensuing mitochondrial dysfunction is postulated to mediate this effect. We aim to investigate the association of POPs with incident diabetes indirectly by bio-assaying AhR ligand bioactivity and intracellular ATP level induced by participant serum samples. METHODS: In incident case-cohort analyses of one ELSA-Brasil center, 1605 eligible subjects without diabetes at baseline had incident diabetes ascertained by self-report, medication use, OGTT or HbA1c at follow-up 4 years later. We assayed AhR ligand bioactivity (AhRL) and intracellular ATP content, the latter reflecting the presence of mitochondria-inhibiting substances (MIS), following incubation of recombinant mouse Hepa1c1c7 cells with participant sera for 71 incident diabetes cases and 472 randomly selected controls. RESULTS: In multiply-adjusted proportional hazards regression analyses, those with above-median AhRL and below-median MIS-ATP had 69 and 226% greater risk of developing diabetes (HR = 1.69; 95%CI 1.01-2.83 and 3.26; 1.84-5.78), respectively. A strong interaction was seen between the two exposures (HRhigh AhRL/low MIS-ATP vs. low AhRL/high MIS-ATP = 8.15; 2.86-23.2). CONCLUSION: The markedly increased incidence of diabetes seen in those with both higher AhR ligand bioactivity and increased mitochondrial inhibition supports the hypothesis that widespread POPs exposure contributes to the diabetes epidemic.
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Diabetes Mellitus Tipo 2/epidemiologia , Receptores de Hidrocarboneto Arílico/metabolismo , Trifosfato de Adenosina/metabolismo , Adulto , Animais , Linhagem Celular , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Poluentes Ambientais/efeitos adversos , Feminino , Hemoglobinas Glicadas/análise , Humanos , Incidência , Ligantes , Estudos Longitudinais , Masculino , Camundongos , Pessoa de Meia-Idade , AutorrelatoRESUMO
Various types of skin substitutes composed of fibroblasts and/or keratinocytes have been used for the treatment of diabetic ulcers. However, the effects have generally not been very dramatic. Recently, human umbilical cord blood-derived mesenchymal stromal cells (hUCB-MSCs) have been commercialised for cartilage repair as a first cell therapy product using allogeneic stem cells. In a previous pilot study, we reported that hUCB-MSCs have a superior wound-healing capability compared with fibroblasts. The present study was designed to compare the treatment effect of hUCB-MSCs with that of fibroblasts on the diabetic wound healing in vitro. Diabetic fibroblasts were cocultured with healthy fibroblasts or hUCB-MSCs. Five groups were evaluated: group I, diabetic fibroblasts without coculture; groups II and III, diabetic fibroblasts cocultured with healthy fibroblasts or hUCB-MSCs; and groups IV and V, no cell cocultured with healthy fibroblasts or hUCB-MSCs. After a 3-day incubation, cell proliferation, collagen synthesis levels and glycosaminoglycan levels, which are the major contributing factors in wound healing, were measured. As a result, a hUCB-MSC-treated group showed higher cell proliferation, collagen synthesis and glycosaminoglycan level than a fibroblast-treated group. In particular, there were significant statistical differences in collagen synthesis and glycosaminoglycan levels (P = 0·029 and P = 0·019, respectively). In conclusion, these results demonstrate that hUCB-MSCs may have a superior effect to fibroblasts in stimulating diabetic wound healing.
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Células Cultivadas/fisiologia , Pé Diabético/terapia , Sangue Fetal , Fibroblastos/fisiologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Cicatrização/fisiologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Feminino , Humanos , Masculino , Projetos Piloto , República da CoreiaRESUMO
The purpose of this study was to examine the effect of coping knowledge for emergency preparedness in Korean elementary school students. A school-based coping education program was provided seven times to 271 fourth- and fifth-grade students in two urban schools by researchers with the school nurses. The Process Model of Stress and Coping and Self-Care Deficit Theory were the theoretical frameworks used to guide this research. The Coping Knowledge for Emergency Situations Questionnaire, developed by the authors, was used to gather data. In the coping education group, there was statistically significant improvement in the coping knowledge (t = 4.589, p < .001) from that of the control group (n = 270). The results highlight the importance of emergency preparedness for elementary school students and the need to develop educational programs for various emergency situations.
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Adaptação Psicológica , Defesa Civil/organização & administração , Emergências/psicologia , Educação em Saúde/organização & administração , Conhecimentos, Atitudes e Prática em Saúde , Estudantes/psicologia , Adolescente , Criança , Feminino , Humanos , Masculino , República da Coreia , Inquéritos e QuestionáriosRESUMO
Breast cancer is a heterogeneous disease, and its subtypes are characterized by hormone receptor and human epidermal growth factor receptor 2 (HER2) expression status. "HER2-low" tumors, which exhibit a low level of HER2 expression (immunohistochemistry 1+ or 2+ without gene amplification), were conventionally considered not amenable to anti-HER2 targeting agents based on the results of a phase III trial of trastuzumab. However, this perspective is being challenged by the emergence of novel anti-HER2 antibody-drug conjugates, such as trastuzumab-deruxtecan. These innovative therapies have demonstrated remarkable efficacy against HER2-low breast cancer, shedding new light on a previously overlooked category of breast cancer. Such promising results highlight the need for in-depth investigations of the biology and prognostic implications of HER2-low tumors. In this review, we comprehensively summarize the current evidence surrounding this topic and highlight areas that warrant further exploration and research in the future.
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Neoplasias da Mama , Receptor ErbB-2 , Feminino , Humanos , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Camptotecina/análogos & derivados , Imunoconjugados/uso terapêutico , Terapia de Alvo Molecular , Prognóstico , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Trastuzumab/uso terapêuticoRESUMO
Electrocardiogram (ECG) changes after primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) patients are associated with prognosis. This study investigated the feasibility of predicting left ventricular (LV) dysfunction in STEMI patients using an artificial intelligence (AI)-enabled ECG algorithm developed to diagnose STEMI. Serial ECGs from 637 STEMI patients were analyzed with the AI algorithm, which quantified the probability of STEMI at various time points. The time points included pre-PCI, immediately post-PCI, 6 h post-PCI, 24 h post-PCI, at discharge, and one-month post-PCI. The prevalence of LV dysfunction was significantly associated with the AI-derived probability index. A high probability index was an independent predictor of LV dysfunction, with higher cardiac death and heart failure hospitalization rates observed in patients with higher indices. The study demonstrates that the AI-enabled ECG index effectively quantifies ECG changes post-PCI and serves as a digital biomarker capable of predicting post-STEMI LV dysfunction, heart failure, and mortality. These findings suggest that AI-enabled ECG analysis can be a valuable tool in the early identification of high-risk patients, enabling timely and targeted interventions to improve clinical outcomes in STEMI patients.
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Inteligência Artificial , Eletrocardiografia , Infarto do Miocárdio com Supradesnível do Segmento ST , Disfunção Ventricular Esquerda , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Masculino , Feminino , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico , Pessoa de Meia-Idade , Idoso , Prognóstico , Intervenção Coronária Percutânea , AlgoritmosRESUMO
Numerous techniques, including double opposing Z-plasty, have been introduced to repair traumatic cleft earlobes and break the linear scar. Even with multiple operative methods available for repairing traumatic cleft earlobe, notable scar contractures and dimpling of the earlobe border remain in some cases. The authors noted patients with different sized components on either side of the traumatized earlobe. For these patients, the authors utilized epithelialized skin to elevate two small triangular flaps from the larger component of the cleft earlobe and transferred them to the smaller component to augment the volume and elongate the scar. There was minimal tissue loss and dissection. Five patients with an asymmetrical secondary cleft earlobe with different sized components underwent lobe repair via this method, and there was no scar contracture or dimpling after at least 6 months of follow-up. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Pavilhão Auricular/lesões , Pavilhão Auricular/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos/transplante , Adulto , Cicatriz/prevenção & controle , Estética , Feminino , Seguimentos , Humanos , Estudos de Amostragem , Resultado do Tratamento , Cicatrização/fisiologiaRESUMO
BACKGROUND: Accurate response parameters are important for patients with brain metastasis (BM) undergoing clinical trials using immunotherapy, considering poorly defined enhancement and variable responses. This study investigated MRI-based surrogate endpoints for patients with BM receiving immunotherapy. METHODS: Sixty-three non-small cell lung cancer patients with BM who received immune checkpoint inhibitors and underwent MRI were included. Tumor diameters were measured using a modification of the RECIST 1.1 (mRECIST), RANO-BM, and iRANO adjusted for BM (iRANO-BM). Tumor volumes were segmented on 3D contrast-enhanced T1-weighted imaging. Differences between the sum of the longest diameter (SLD) or total tumor volume at baseline and the corresponding measurement at time of the best overall response were calculated as "changes in SLDs" (for each set of criteria) and "change in volumetry," respectively. Overall response rate (ORR), progressive disease (PD) assignment, and progression-free survival (PFS) were compared among the criteria. The prediction of overall survival (OS) was compared between diameter-based and volumetric change using Cox proportional hazards regression analysis. RESULTS: The mRECIST showed higher ORR (30.1% vs. both 17.5%) and PD assignment (34.9% vs. 25.4% [RANO-BM] and 19% [iRANO-BM]). The iRANO-BM had a longer median PFS (13.7 months) than RANO-BM (9.53 months) and mRECIST (7.73 months, P = 0.003). The change in volumetry was a significant predictor of OS (HR = 5.87, 95% CI: 1.46-23.64, P = 0.013). None of the changes in SLDs, as determined by RANO-BM or iRANO-BM, were significant predictors of OS, except for the mRECIST, which exhibited a weak association with OS. CONCLUSION: Quantitative volume measurement may be an accurate surrogate endpoint for OS in patients with BM undergoing immunotherapy, especially considering the challenges of multiplicity and the heterogeneity of sub-centimeter size responses.
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Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Prognóstico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Imageamento por Ressonância Magnética , Estudos RetrospectivosRESUMO
Compared with conventional liquid electrolytes, solid electrolytes can better improve the safety properties and achieve high-energy-density Li-ion batteries. Sulfide-based solid electrolytes have attracted significant attention owing to their high ionic conductivities, which are comparable to those of their liquid counterparts. Among them, Li thiophosphates, including Li-argyrodites, are widely studied. In this study, Li thiophosphate solid electrolytes containing BH4 - anions are prepared via a simple and fast milling method even without heat treatment. The synthesized materials exhibit a high ionic conductivity of up to 11 mS cm-1 at 25 °C, which is much higher than reported values. To elucidate the mechanism behind, the thiophosphate local structure, whose effect on the ionic conductivity remains unclear to date, is investigated. Raman and solid-state NMR spectroscopies are performed to identify the thiophosphate local structure in the sulfide samples. Based on the analysis results, the ratios of the different thiophosphate units in the prepared electrolyte samples are determined. It is found that the thiophosphate local structure can be varied by changing the amount of LiBH4 and the milling conditions, which significantly impact the ionic conductivity. The all-solid-state cell with the prepared solid electrolyte exhibits superior cycle and rate performances.
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Background: Acquired von Willebrand syndrome (AVWS) has not been investigated in Korean patients with Philadelphia chromosome-negative myeloproliferative neoplasm. Methods: This study analyzed the prevalence at diagnosis and clinical features of AVWS in patients with essential thrombocythemia (ET), polycythemia vera (PV), prefibrotic/early primary myelofibrosis (pre-PMF), or overt PMF (PMF) diagnosed between January 2019 and December 2021 at Chungam National University Hospital, Daejeon, Korea. AVWS was defined as below the lower reference limit (56%) of ristocetin cofactor activity (VWF:RCo). Results: Sixty-four consecutive patients (36 with ET, 17 with PV, 6 with pre-PMF, and 5 with PMF; 30 men and 34 women) with a median age of 67 years (range, 18â87 yr) were followed for a median of 25.1 months (range, 2.6â46.4 mo). AVWS was detected in 20 (31.3%) patients at diagnosis and was most frequent in ET patients (41.4%), followed by patients with pre-PMF (33.3%) and PV (17.6%) patients. VWF:RCo was negatively correlated with the platelet count (r=0.937; P=0.002). Only one episode of minor bleeding occurred in a patient with ET and AVWS. Younger age (<50 yr) [odds ratio (OR), 7.08; 95% confidence interval (CI), 1.27â39.48; P=0.026] and thrombocytosis (>600×109/L) (OR, 13.70; 95% CI, 1.35â138.17; P=0.026) were independent risk factors for developing AVWS. Conclusion: AVWS based on VWF:RCo was common in patients with ET and pre-PMF, but less common in patients with PV in the Korean population. Clinically significant bleeding is rare in these patients.
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This study validates the beneficial role of residual Li compounds on the surface of Ni-rich cathode materials (LiNixCoyMnzO2, NCM). Residual Li compounds on Ni-rich NCM are naturally formed during the synthesis procedure, which degrades the initial Coulombic efficiency and generates slurry gelation during electrode fabrication in Li-ion batteries (LIBs) using liquid electrolytes. To solve this problem, washing pretreatment is usually introduced to remove residual Li compounds on the NCM surface. In contrast to LIBs, we found that residual Li compounds can serve as a functional layer that suppresses the interfacial side reactions of the NCM in all-solid-state batteries (ASSBs). The formation of resistive phosphate-based compounds from the undesirable side reaction during the initial charging step is suppressed by the residual Li compounds on the surface of the NCM, thereby reducing polarization growth in ASSBs and enhancing rate performances. The advantageous effects of the intrinsic residual Li compounds on the NCM surface suggest that the essential washing process of the NCM for the liquid-based LIB system should be reconsidered for ASSB systems.
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Carcinoembryonic antigen (CEA) is the most widely used tumor marker in metastatic colorectal cancer (mCRC). However, its potential as a predictive marker of progression in mCRC during systemic chemotherapy, particularly in patients receiving monoclonal antibodies as a combination therapy, has remained of interest. Herein, we investigated whether CEA changes could predict disease progression and clinical outcomes in patients with mCRC cotreated with systemic chemotherapy and/or biologic agents. A total of 1261 patients with mCRC undergoing a first-line systemic treatment were included in this retrospective study. We analyzed the optimal cut-off value for CEA changes to predict progression at the first response evaluation by the treatment arm (chemotherapy alone, chemotherapy plus anti-vascular endothelial growth factor (VEGF) monoclonal antibody [mAb], and chemotherapy plus anti-epidermal growth factor receptor [EGFR] mAb). These cut-off values were then used to predict overall survival (OS) and progression-free survival (PFS). When stratified by their treatment arm, 891 (70.6%), 266 (21.0%), and 104 (8.2%) of the study patients were included in the chemotherapy alone-, anti-VEGF mAb, and anti-EGFR mAb groups, respectively. The optimal CEA cut-off values were 16.5% and 38.9% increase in the whole cohort and anti-EGFR mAb group, respectively, and these values showed high sensitivity and specificity for predicting disease progression. The patients in the entire population and anti-EGFR mAb group with CEA changes below these cut-off values showed significantly better OS and PFS outcomes compared those whose changes were above cut-off values. Among the patients with mCRC treated with anti-VEGF mAb, no associations were found between OS or PFS outcomes and CEA changes. CEA is potentially a good surrogate marker for predicting disease progression and survival outcomes in patients with mCRC receiving first-line systemic chemotherapy alone or chemotherapy with anti-EGFR mAb, whereas it is less effective in those treated with anti-VEGF mAb.
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Antineoplásicos , Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Antígeno Carcinoembrionário , Neoplasias Colorretais/patologia , Estudos Retrospectivos , Receptores ErbB/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Progressão da Doença , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
BACKGROUND: The transition of human epidermal growth factor receptor 2 (HER2) status after neoadjuvant chemotherapy (NAC) in HER2-low breast cancer has not been thoroughly evaluated. Here, we evaluated the HER2 transition among HER2-zero and HER2-low breast cancer cases post-NAC and its impact on clinical outcomes. METHODS: We included 1288 patients with HER2-low or zero breast cancer who underwent NAC and surgery between 2014 and 2018 and had paired pre- and post-therapeutic HER2 status results. RESULTS: Among patients who were HER2-zero pre-NAC (n = 650), 68% and 29% were HER2-zero and HER2-low, respectively, post-NAC. Among patients who were HER2-low pre-NAC (n = 638), 32% of patients showed HER2 changes (low to zero), and 59% of patients had a constant HER2-low status post-NAC. Patients with constant HER2-low or transitions from HER2-low to zero had a higher proportion of hormone receptor positivity (84% and 79%) than those with changes from HER2-zero to low (77%) or with constant HER2-zero (56%), respectively. Multivariable logistic regression analysis revealed that patients with oestrogen receptor positivity had a higher probability of gaining HER2-low expression than those with oestrogen receptor negativity (odds ratio 2.48). No significant differences were observed in terms of overall survival or disease-free survival between patients with and without HER2-changes according to their hormone receptor status, except in the post-therapeutic HER2-low, hormone receptor-negativity subset. CONCLUSION: Temporal heterogeneity of HER2-low expression is observed in substantial numbers of post-NAC breast cancer patients. Clinical outcomes show no significant associations, except in the post-therapeutic HER2-low, hormone receptor negativity subset. The prognostic implications of HER2 transition in HER2-low breast cancer require further investigation.
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Neoplasias da Mama , Humanos , Feminino , Prognóstico , Receptores de Estrogênio/metabolismo , Terapia Neoadjuvante , Receptor ErbB-2/metabolismo , Intervalo Livre de Doença , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia AdjuvanteRESUMO
BACKGROUND: Peripartum cardiomyopathy, one of the most fatal conditions during delivery, results in heart failure secondary to left ventricular systolic dysfunction. Left ventricular dysfunction can result in abnormalities in electrocardiography. However, the usefulness of electrocardiography in the identification of peripartum cardiomyopathy in pregnant women remains unclear. OBJECTIVE: This study aimed to evaluate the effectiveness of a 12-lead electrocardiography-based artificial intelligence/machine learning-based software as a medical device for screening peripartum cardiomyopathy. STUDY DESIGN: This retrospective cohort study included pregnant women who underwent transthoracic echocardiography between a month before and 5 months after delivery and underwent 12-lead electrocardiography within 30 days of echocardiography between December 2011 and May 2022 at Seoul National University Hospital. The performance of 12-lead electrocardiography-based artificial intelligence/machine learning analysis (AiTiALVSD software; version 1.00.00, which was developed to screen for left ventricular systolic dysfunction in the general population) was evaluated for the identification of peripartum cardiomyopathy. In addition, the performance of another artificial intelligence/machine learning algorithm using only 1-lead electrocardiography to detect left ventricular systolic dysfunction was evaluated in identifying peripartum cardiomyopathy. The results were obtained under a 95% confidence interval and considered significant when P<.05. RESULTS: Among the 14,557 women who delivered during the study period, 204 (1.4%) underwent transthoracic echocardiography a month before and 5 months after delivery. Among them, 12 (5.8%) were diagnosed with peripartum cardiomyopathy. The results showed that AiTiALVSD for 12-lead electrocardiography was highly effective in detecting peripartum cardiomyopathy, with an area under the receiver operating characteristic of 0.979 (95% confidence interval, 0.953-1.000), an area under the precision-recall curve of 0.715 (95% confidence interval, 0.499-0.951), a sensitivity of 0.917 (95% confidence interval, 0.760-1.000), a specificity of 0.927 (95% confidence interval, 0.890-0.964), a positive predictive value of 0.440 (95% confidence interval, 0.245-0.635), and a negative predictive value of 0.994 (95% confidence interval, 0.983-1.000). In addition, a 1-lead (lead I) artificial intelligence/machine learning algorithm showed excellent performance; the area under the receiver operating characteristic, area under the precision-recall curve, sensitivity, specificity, positive predictive value, and negative predictive value were 0.944 (95% confidence interval, 0.895-0.993), 0.520 (95% confidence interval, 0.319-0.801), 0.833 (95% confidence interval, 0.622-1.000), 0.880 (95% confidence interval, 0.834-0.926), 0.303 (95% confidence interval, 0.146-0.460), and 0.988 (95% confidence interval, 0.972-1.000), respectively. CONCLUSION: The 12-lead electrocardiography-based artificial intelligence/machine learning-based software as a medical device (AiTiALVSD) and 1-lead algorithm are noninvasive and effective ways of identifying cardiomyopathies occurring during the peripartum period, and they could potentially be used as highly sensitive screening tools for peripartum cardiomyopathy.
Assuntos
Cardiomiopatias , Aprendizado Profundo , Disfunção Ventricular Esquerda , Humanos , Feminino , Gravidez , Função Ventricular Esquerda , Volume Sistólico , Estudos Retrospectivos , Inteligência Artificial , Período Periparto , Eletrocardiografia , Cardiomiopatias/diagnóstico , Cardiomiopatias/etiologia , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/epidemiologiaRESUMO
Background: Although atherosclerosis is likely to be involved in the development of arterial thrombotic events in patients with essential thrombocythemia (ET), abdominal aortic calcification (AAC) has rarely been investigated. We evaluated the prevalence and clinical relevance of AAC at the time of ET diagnosis. Methods: This retrospective study included patients newly diagnosed with ET who underwent abdominal computed tomography (CT) at the time of diagnosis between January 2002 and December 2021 at Chungnam National University Hospital, Daejeon, Korea. CT images were reviewed and an aortic calcification score was assigned. Results: Of the 94 patients (median age, 62 yr; range, 18â90 yr), AAC was detected in 62 (66.0%). AAC was most commonly mild (33.0%), followed by moderate (22.7%) and severe (5.3%). Old age [odds ratio (OR), 34.37; 95% confidence interval (CI), 12.32â95.91; Pï¼0.001] was an independent risk factor for AAC. The patients with AAC had a higher WBC count (11.8±4.7 vs. 9.7±2.9×109/L, P=0.017), higher neutrophil-to-lymphocyte ratio (4.3±2.7 vs. 3.1±1.5, P=0.039), and higher JAK2V617F positivity (81.5% vs. 58.8%, P=0.020) compared to those without AAC. AAC was an independent risk factor for arterial thrombotic vascular events that occurred before or at diagnosis of ET (OR, 4.12; 95% CI, 1.11â15.85; P=0.034). Conclusion: AAC is common in patients with ET and is associated with arterial thrombotic events.