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1.
Heliyon ; 10(15): e35117, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39170279

RESUMO

Nurses in intensive care units are subjected to high levels of work-related stress and must cope with psychological distress. This preliminary study explored the effects of an online supportive music and imagery intervention on these nurses' perceived stress, psychological distress, and sleep quality. A prospective pre-post design was employed to investigate the effectiveness of online supportive music and imagery interventions. The intervention comprised five weekly sessions, each lasting 50-60 min, which included verbal interactions and listening to music, and were facilitated by trained music therapists. Perceived stress and psychological distress were measured before and after the five-week program to investigate its effectiveness, and the current stress level and emotional state were measured before and after each session to explore changes over the intervention period. Sleep quality was measured weekly. In total, 29 participants completed the program. The results showed a significant decrease in perceived stress (d = 0.45, p = .045) and psychological distress (d = 0.53, p = .045) after the intervention. Regarding changes over the intervention period, the findings demonstrated a significant main effect of the number of sessions on perceived stress (p = 0.001), energy (p = 0.001), and tension (p = 0.023), whereas the effects on perceived valence and scores on the Korean version of the Insomnia Severity Index were not significant. Moreover, a significant post-session main effect was observed for all perceived stress and emotion ratings (p < 0.001). Online supportive music and imagery interventions may help reduce stress levels and enhance positive emotional states among nurses in intensive care units. Integrating self-work into supportive music imagery interventions may increase adherence to the intervention and extend its effect.

2.
Cancer Med ; 13(16): e70104, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39171503

RESUMO

OBJECTIVES: We aimed to identify predictive markers for metachronous gastric cancer (MGC) in early gastric cancer (EGC) patients curatively treated with endoscopic submucosal dissection (ESD). MATERIALS AND METHODS: From EGC patients who underwent ESD, bulk RNA sequencing was performed on non-cancerous gastric mucosa samples at the time of initial EGC diagnosis. This included 23 patients who developed MGC, and 23 control patients without additional gastric neoplasms for over 3 years (1:1 matched by age, sex, and Helicobacter pylori infection state). Candidate differentially-expressed genes were identified, from which biomarkers were selected using real-time quantitative polymerase chain reaction and cell viability assays using gastric cell lines. An independent validation cohort of 55 MGC patients and 125 controls was used for marker validation. We also examined the severity of gastric intestinal metaplasia, a known premalignant condition, at initial diagnosis. RESULTS: From the discovery cohort, 86 candidate genes were identified of which KDF1 and CDK1 were selected as markers for MGC, which were confirmed in the validation cohort. CERB5 and AKT2 isoform were identified as markers related to intestinal metaplasia and were also highly expressed in MGC patients compared to controls (p < 0.01). Combining these markers with clinical data (age, sex, H. pylori and severity of intestinal metaplasia) yielded an area under the curve (AUC) of 0.91 (95% CI, 0.85-0.97) for MGC prediction. CONCLUSION: Assessing biomarkers in non-cancerous gastric mucosa may be a useful method for predicting MGC in EGC patients and identifying patients with a higher risk of developing MGC, who can benefit from rigorous surveillance.


Assuntos
Biomarcadores Tumorais , Segunda Neoplasia Primária , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Masculino , Feminino , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade , Idoso , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/patologia , Ressecção Endoscópica de Mucosa , Proteína Quinase CDC2/genética , Proteína Quinase CDC2/metabolismo , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/metabolismo , Infecções por Helicobacter/complicações , Infecções por Helicobacter/genética , Gastroscopia , Regulação Neoplásica da Expressão Gênica , Metaplasia/genética , Metaplasia/patologia , Helicobacter pylori/isolamento & purificação , Estudos de Casos e Controles
3.
Biochem Biophys Res Commun ; 738: 150536, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39146619

RESUMO

S100 calcium-binding protein P (S100P) is a secretory protein that is expressed in various healthy tissues and tumors. Megakaryocyte-secreted S100P promotes osteoclast differentiation and function; however, its receptor and cellular signaling in osteoclasts remain unclear. Receptor for advanced glycation end products (RAGE), which is the receptor for S100P on cancer cells, was expressed in osteoclast precursors, and S100P-RAGE binding was confirmed through co-immunoprecipitation. Additionally, the phosphorylation of ERK and NF-κB was increased in S100P-stimulated osteoclast precursors but was inhibited by addition of the RAGE antagonistic peptide (RAP). S100P-induced osteoclast differentiation and excessive bone resorption activity were also reduced by the addition of RAP. This study demonstrates that S100P, upon binding with RAGE, activates the ERK and NF-κB signaling pathways in osteoclasts, leading to increased cell differentiation and bone resorption activity.

4.
Radiat Oncol ; 19(1): 110, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39152502

RESUMO

BACKGROUND: Adaptive therapy has been enormously improved based on the art of generating adaptive computed tomography (ACT) from planning CT (PCT) and the on-board image used for the patient setup. Exploiting the ACT, this study evaluated the dose delivered to patients with non-small-cell lung cancer (NSCLC) patients treated with stereotactic ablative radiotherapy (SABR) and derived relationship between the delivered dose and the parameters obtained through the evaluation procedure. METHODS: SABR treatment records of 72 patients with NSCLC who were prescribed a dose of 60 Gy (Dprescribed) to the 95% volume of the planning target volume (PTV) in four fractions were analysed in this retrospective study; 288 ACTs were generated by rigid and deformable registration of a PCT to a cone-beam computed tomography (CBCT) per fraction. Each ACT was sent to the treatment planning system (TPS) and treated as an individual PCT to calculate the dose. Delivered dose to a patient was estimated by averaging four doses calculated from four ACTs per treatment. Through the process, each ACT provided the geometric parameters, such as mean displacement of the deformed PTV voxels (Warpmean) and Dice similarity coefficient (DSC) from deformation vector field, and dosimetric parameters, e.g. difference of homogeneity index (ΔHI, HI defined as (D2%-D98%)/Dprescribed*100) and mean delivered dose to the PTV (Dmean), obtained from the dose statistics in the TPS. Those parameters were analyzed using multiple linear regression and one-way-ANOVA of SPSS® (version 27). RESULTS: The prescribed dose was confirmed to be fully delivered to internal target volume (ITV) within maximum difference of 1%, and the difference between the planned and delivered doses to the PTV was agreed within 6% for more than 95% of the ACT cases. Volume changes of the ITV during the treatment course were observed to be minor in comparison of their standard deviations. Multiple linear regression analysis between the obtained parameters and the dose delivered to 95% volume of the PTV (D95%) revealed four PTV parameters [Warpmean, DSC, ΔHI between the PCT and ACT, Dmean] and the PTV D95% to be significantly related with P-values < 0.05. The ACT cases of high ΔHI were caused by higher values of the Warpmean and DSC from the deformable image registration, resulting in lower PTV D95% delivered. The mean values of PTV D95% and Warpmean showed significant differences depending on the lung lobe where the tumour was located. CONCLUSIONS: Evaluation of the dose delivered to patients with NSCLC treated with SABR using ACTs confirmed that the prescribed dose was accurately delivered to the ITV. However, for the PTV, certain ACT cases characterised by high HI deviations from the original plan demonstrated variations in the delivered dose. These variations may potentially arise from factors such as patient setup during treatment, as suggested by the statistical analyses of the parameters obtained from the dose evaluation process.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Tomografia Computadorizada de Feixe Cônico , Neoplasias Pulmonares , Radiocirurgia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos Retrospectivos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Radioterapia de Intensidade Modulada/métodos
5.
Front Bioeng Biotechnol ; 12: 1433087, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39157445

RESUMO

Introduction: This study aimed to identify differences in voice characteristics and changes between patients with dysphagia-aspiration and healthy individuals using a deep learning model, with a focus on under-researched areas of pre- and post-swallowing voice changes in patients with dysphagia. We hypothesized that these variations may be due to weakened muscles and blocked airways in patients with dysphagia. Methods: A prospective cohort study was conducted on 198 participants aged >40 years at the Seoul National University Bundang Hospital from October 2021 to February 2023. Pre- and post-swallowing voice data of the participants were converted to a 64-kbps mp3 format, and all voice data were trimmed to a length of 2 s. The data were divided for 10-fold cross-validation and stored in HDF5 format with anonymized IDs and labels for the normal and aspiration groups. During preprocessing, the data were converted to Mel spectrograms, and the EfficientAT model was modified using the final layer of MobileNetV3 to effectively detect voice changes and analyze pre- and post-swallowing voices. This enabled the model to probabilistically categorize new patient voices as normal or aspirated. Results: In a study of the machine-learning model for aspiration detection, area under the receiver operating characteristic curve (AUC) values were analyzed across sexes under different configurations. The average AUC values for males ranged from 0.8117 to 0.8319, with the best performance achieved at a learning rate of 3.00e-5 and a batch size of 16. The average AUC values for females improved from 0.6975 to 0.7331, with the best performance observed at a learning rate of 5.00e-5 and a batch size of 32. As there were fewer female participants, a combined model was developed to maintain the sex balance. In the combined model, the average AUC values ranged from 0.7746 to 0.7997, and optimal performance was achieved at a learning rate of 3.00e-5 and a batch size of 16. Conclusion: This study evaluated a voice analysis-based program to detect pre- and post-swallowing changes in patients with dysphagia, potentially aiding in real-time monitoring. Such a system can provide healthcare professionals with daily insights into the conditions of patients, allowing for personalized interventions. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05149976.

6.
Adv Sci (Weinh) ; : e2405154, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39159072

RESUMO

Electrochemical CO2 reduction reaction (CO2RR) to produce value-added multi-carbon chemicals has been an appealing approach to achieving environmentally friendly carbon neutrality in recent years. Despite extensive research focusing on the use of CO2 to produce high-value chemicals like high-energy-density hydrocarbons, there have been few reports on the production of propane (C3H8), which requires carbon chain elongation and protonation. A rationally designed 0D/2D hybrid Cu2O anchored-Ti3C2Tx MXene catalyst (Cu2O/MXene) is demonstrated with efficient CO2RR activity in an aqueous electrolyte to produce C3H8. As a result, a significantly high Faradaic efficiency (FE) of 3.3% is achieved for the synthesis of C3H8 via the CO2RR with Cu2O/MXene, which is ≈26 times higher than that of Cu/MXene prepared by the same hydrothermal process without NH4OH solution. Based on in-situ attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and density functional theory (DFT) calculations, it is proposed that the significant electrocatalytic conversion originated from the synergistic behavior of the Cu2O nanoparticles, which bound the *C2 intermediates, and the MXene that bound the *CO coupling to the C3 intermediate. The results disclose that the rationally designed MXene-based hybrid catalyst facilitates multi-carbon coupling as well as protonation, thereby manipulating the CO2RR pathway.

7.
J Korean Med Sci ; 39(32): e229, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39164054

RESUMO

BACKGROUND: We aimed to evaluate long-term outcomes of gamma knife radiosurgery (GKS) for cerebral cavernous malformations (CCMs). METHODS: Among the 233 CCM patients who underwent GKS, 79 adult patients (96 lesions) followed for over 10 years were included and analyzed retrospectively. Annual hemorrhage rate (AHR) was analyzed the entire cohort of 233 patients and the subset of 79 enrolled patients by dividing lesions into overall CCM lesions and brainstem lesions. AHR, neurologic outcome, adverse radiation effect (ARE), and changes of lesions in magnetic resonance imaging (MRI) were compared before and after GKS. Cox-regression analysis was performed to identify risk factors for hemorrhage following GKS. RESULTS: Mean follow-up duration of 79 enrolled patients was 14 years (range, 10-23 years). The AHR of all CCMs for entire cohort at each time point was 17.8% (pre-GKS), 5.9% (≤ 2 years post-GKS), 1.8% (≤ 10 years post-GKS). The AHR of all CCM for 79 enrolled patients was 21.4% (pre-GKS), 3.8% (2 years post-GKS), 1.4% (10 years post-GKS), and 2.3% (> 10 years post-GKS). The AHR of brainstem cavernous malformation (CM) for entire cohort at each time point was 22.4% (pre-GKS), 10.1% (≤ 2 years post-GKS), 3.2% (≤ 10 years post-GKS). The AHR of brainstem CM for 79 enrolled patients was 27.2% (pre-GKS), 5.8% (2 years post-GKS), 3.4% (10 years post-GKS), and 3.5% (> 10 years post-GKS). Out of the 79 enrolled patients, 35 presented with focal neurologic deficits at the initial clinical visit. Among these patients, 74.3% showed recovery at the last follow-up. Symptomatic ARE occurred in five (6.4%) patients. No mortality occurred. Most lesions were decreased in size at the last follow-up MRI. Previous hemorrhage history (hazard ratio [HR], 8.38; 95% confidence interval [CI], 1.07-65.88; P = 0.043), and brainstem location (HR, 3.10; 95% CI, 1.26-7.64; P = 0.014) were significant risk factors for hemorrhage event. CONCLUSION: GKS for CCM showed favorable long-term outcomes. GKS should be considered for CCM, especially when it has a previous hemorrhage history and brainstem location.


Assuntos
Hemangioma Cavernoso do Sistema Nervoso Central , Imageamento por Ressonância Magnética , Radiocirurgia , Humanos , Adulto , Masculino , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Estudos Retrospectivos , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem , Adolescente , Seguimentos , Modelos de Riscos Proporcionais , Idoso , Fatores de Risco , Tronco Encefálico/patologia , Tronco Encefálico/diagnóstico por imagem
8.
J Crit Care ; 84: 154898, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39163654

RESUMO

PURPOSE: To investigate the relationship between contrast medium administration and long-term mortality and renal function in patients with septic acute kidney injury (AKI). MATERIALS AND METHODS: We performed a retrospective, propensity-matched cohort study involving 1521 adult patients admitted with septic shock. Patients with septic AKI who underwent contrast or non-contrast CT scans were enrolled. The primary outcomes were the rates of 90-day mortality and dialysis within 90 days. The secondary outcomes included worsening of AKI, in-hospital mortality, and maintenance of dialysis after 90 days. RESULTS: During the study period, 609 patients with septic AKI were identified; 220 (36.1%) underwent contrast CT and 389 (63.9%) underwent non-contrast CT. After propensity score matching, 133 pairs were obtained. There were no significant differences between the contrast and non-contrast CT groups in 90-day mortality (54.9% vs. 58.6%, P = 0.579), dialysis within 90 days (6.8% vs. 8.3%, P = 0.655), worsening AKI (2.3% vs. 3.0%, P = 0.706), in-hospital mortality (10.6% vs. 14.4%, P = 0.369), or maintenance of dialysis after 90 days (0.0% vs. 0.8%, P > 0.99). CONCLUSIONS: The administration of intravenous contrast medium was not associated with long-term mortality, deterioration of renal function, or dialysis in patients with septic AKI.

9.
Cancer Res Treat ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39164082

RESUMO

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform - FiRST Cancer Panel (FCP) - over seven years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. 97.6% of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53(56.2%), PIK3CA(31.2%), GATA3(13.8%), BRCA2(10.2%), and amplifications of CCND1(10.8%), FGF19(10.0%), and ERBB2(9.5%). NGS analysis of ERBB2 amplification correlated well with HER2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. 10.3% of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. . Conclusion: Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

10.
iScience ; 27(8): 110380, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39165843

RESUMO

Histone H3K9 methylated heterochromatin silences repetitive non-coding sequences and lineage-specific genes during development, but how tissue-specific genes escape from heterochromatin in differentiated cells is unclear. Here, we examine age-dependent transcriptomic profiling of terminally differentiated mouse retina to identify epigenetic regulators involved in heterochromatin reorganization. The single-cell RNA sequencing analysis reveals a gradual downregulation of Kdm3b in cone photoreceptors during aging. Disruption of Kdm3b (Kdm3b +/- ) of 12-month-old mouse retina leads to the decreasing number of cones via apoptosis, and it changes the morphology of cone ribbon synapses. Integration of the transcriptome with epigenomic analysis in Kdm3b +/- retinas demonstrates gains of heterochromatin features in synapse assembly and vesicle transport genes that are downregulated via the accumulation of H3K9me1/2. Contrarily, losses of heterochromatin in apoptotic genes exacerbated retinal neurodegeneration. We propose that the KDM3B-centered epigenomic network is crucial for balancing of cone photoreceptor homeostasis via the modulation of gene set-specific heterochromatin features during aging.

11.
J Korean Med Sci ; 39(31): e223, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39137810

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory cutaneous disorder, that emerges from intricate interplays among genetic predisposition, immune dysregulation, environmental factors, and compromised skin barrier. Understanding the inflammatory pathway in AD is important due to its fundamental role in the pathogenesis of AD. This study aimed to explore the diverse spectrum of proteins linked to the inflammation of AD and the relationship between systemic biomarkers and clinical severity in AD. METHODS: We examined the blood samples from 48 patients with AD and 48 healthy controls (HCs) using the Proximity Extension Assay (Olink). Differentially expressed proteins (DEPs) were identified and Pearson correlation analysis was conducted to determine systemic proteomic biomarkers associated with severity of AD. RESULTS: A total of 29 DEPs were significantly up-regulated and 2 DEPs were significantly down-regulated in AD compared with the HC. The MCP-4, IL-18, MCP-3, TNFRSF9, and IL-17C were the top 5 highest DEPs associated with the severity of AD. CONCLUSION: Our study sheds light on the intricate network of inflammatory proteins in AD and their potential implications for disease severity. Our results indicate that these systemic inflammatory proteins could be valuable for assessing AD severity and enhancing our understanding of the disease's complexity and its potential management strategies.


Assuntos
Biomarcadores , Dermatite Atópica , Proteômica , Índice de Gravidade de Doença , Humanos , Dermatite Atópica/sangue , Dermatite Atópica/patologia , Dermatite Atópica/diagnóstico , Biomarcadores/sangue , Biomarcadores/metabolismo , Feminino , Masculino , Adulto , Estudos de Casos e Controles , Adulto Jovem , Inflamação/metabolismo , Adolescente , Pessoa de Meia-Idade
12.
Nat Commun ; 15(1): 7008, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39143141

RESUMO

Proton-activated chloride (PAC) channels, ubiquitously expressed in tissues, regulate intracellular Cl- levels and cell death following acidosis. However, molecular mechanisms and signaling pathways involved in PAC channel modulation are largely unknown. Herein, we determine that phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] of the plasma membrane inner leaflet is essential for the proton activation of PAC channels. PI(4,5)P2 depletion by activating phosphatidylinositol 5-phosphatases or Gq protein-coupled muscarinic receptors substantially inhibits human PAC currents. In excised inside-out patches, PI(4,5)P2 application to the cytoplasmic side increases the currents. Structural simulation reveals that the putative PI(4,5)P2-binding site is localized within the cytosol in resting state but shifts to the cell membrane's inner surface in an activated state and interacts with inner leaflet PI(4,5)P2. Alanine neutralization of basic residues near the membrane-cytosol interface of the transmembrane helice 2 significantly attenuates PAC currents. Overall, our study uncovers a modulatory mechanism of PAC channel through inner membrane PI(4,5)P2.


Assuntos
Membrana Celular , Fosfatidilinositol 4,5-Difosfato , Fosfatidilinositol 4,5-Difosfato/metabolismo , Humanos , Membrana Celular/metabolismo , Células HEK293 , Canais de Cloreto/metabolismo , Canais de Cloreto/genética , Prótons , Sítios de Ligação , Animais , Técnicas de Patch-Clamp , Anoctaminas/metabolismo , Anoctaminas/genética , Anoctaminas/química , Proteínas de Transferência de Fosfolipídeos
13.
J Hazard Mater ; 477: 135237, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39094305

RESUMO

This study presents a thorough investigation of the novel application of graphene oxide (GO) modified with melamine formaldehyde to fabricate granular three-dimensional GO (3D-GO), followed by the introduction of UiO-66 doping (3D-GO/U) for high uranium (U) adsorption. The U(VI) adsorption isotherms revealed that 3D-GO/U-10 with 10 % UiO-66 incorporation exhibited an impressive adsorption capacity of 375.5 mg g-1 and remained high U(VI) sorption performance in wide pH range. The introduction of UiO-66 to 3D-GO (3D-GO/U-10) led to the deagglomeration of the UiO-66 particles. The in situ surface-enhanced-Raman-spectroscopy-analysis and density-functional-theory simulations showed the symmetric metal center site Zr-O2 on UiO-66 was discovered to exhibit the highest adsorption energy (-3.21 eV) for U(VI) species due to the electrons transfer from the oxygen atom to U(VI) drives the covalent bonding between the symmetric metal center sites Zr-O2 and U(VI) on 3D-GO/U-10. The 3D-GO/U-10 was regenerated using a 0.1 M Na2CO3/0.01 M H2O2 solution and achieved up to 89.7 % U(VI) removal in the 5th cycle. The continuous flow column experiments results revealed 3D-GO/U-10 can regenerate and maintain a U(VI) removal capacity of ∼76 % for up to 4 cycles column experiments. Therefore, 3D-GO/U-10 exhibits great potential for removing U(VI) from water bodies.

14.
Med ; 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39153473

RESUMO

BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) tend to be excluded or under-represented in randomized clinical trials evaluating the effects of potent P2Y12 inhibitor monotherapy after short-term dual antiplatelet therapy (DAPT). METHODS: Individual patient data were pooled from randomized clinical trials that included STEMI patients undergoing drug-eluting stent (DES) implantation and compared ticagrelor monotherapy after short-term (≤3 months) DAPT versus ticagrelor-based 12-month DAPT in terms of centrally adjudicated clinical outcomes. The co-primary outcomes were efficacy outcome (composite of all-cause death, myocardial infarction, or stroke) and safety outcome (Bleeding Academic Research Consortium type 3 or 5 bleeding) at 1 year. FINDINGS: The pooled cohort contained 2,253 patients with STEMI. The incidence of the primary efficacy outcome did not differ between the ticagrelor monotherapy group and the ticagrelor-based DAPT group (1.8% versus 2.0%; hazard ratio [HR] = 0.88; 95% confidence interval [CI] = 0.49-1.61; p = 0.684). There was no difference in cardiac death between the groups (0.6% versus 0.7%; HR = 0.89; 95% CI = 0.32-2.46; p = 0.822). The incidence of the primary safety outcome was significantly lower in the ticagrelor monotherapy group (2.3% versus 4.0%; HR = 0.56; 95% CI = 0.35-0.92; p = 0.020). No heterogeneity of treatment effects was observed for the primary outcomes across subgroups. CONCLUSIONS: In patients with STEMI treated with DES implantation, ticagrelor monotherapy after short-term DAPT was associated with lower major bleeding without an increase in the risk of ischemic events compared with ticagrelor-based 12-month DAPT. Further research is necessary to extend these findings to non-Asian patients. FUNDING: This study was funded by Biotronik (Bülach, Switzerland).

15.
Front Pharmacol ; 15: 1425550, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39148538

RESUMO

Introduction: Dupilumab is the first biological treatment for atopic dermatitis (AD). Dupilumab-associated ocular surface disease (DAOSD) is one of the most commonly reported side effects in patients with AD during dupilumab treatment. This study aimed to identify risk factors for DAOSD in a real-world setting and construct a risk-scoring system for predicting DAOSD risk. Methods: A retrospective analysis was conducted for dupilumab-treated adult patients with AD between April 2019 and September 2023 at Yeouido St. Mary's Hospital in Korea. Patients aged ≥18 years who received dupilumab to treat AD were included. Univariate and multivariable logistic regression analyses were performed to determine independent risk factors for DAOSD. A risk scoring system was constructed to predict DAOSD risk based on the adjusted odd ratios of significant variables. Results: Of the 97 dupilumab-treated patients, 28 (28.9%) developed DAOSD. Among them, three (10.7%) patients discontinued dupilumab due to ocular side effects. In the multivariable analysis, older age, history of conjunctivitis, and a baseline Eczema Area and Severity Index (EASI) score ≥28 were independent risk factors for developing DAOSD. Using these variables, a risk-scoring system was constructed. The predicted DAOSD risks for AD patients with 0, 1, 2, 3, 4, and 5 points were 5.8%, 14.2%, 30.7%, 54.3%, 76.2%, and 89.6%, respectively. Conclusion: In this study, the patient's age, history of conjunctivitis, and higher baseline EASI score were significantly associated with DAOSD. This risk-scoring system would help identify high-risk patients requiring more caution when initiating dupilumab treatment.

16.
PeerJ ; 12: e17509, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39161969

RESUMO

Background: Hip fractures are a common and debilitating condition, particularly among older adults. Loss of muscle mass and strength is a common consequence of hip fractures, which further contribute to functional decline and increased disability. Assessing changes in individual thigh muscles volume in follow-up patients can provide valuable insights into the quantitative recovery process and guide rehabilitation interventions. However, accurately measuring anatomical individual thigh muscle volume can be challenging due to various, labor intensive and time-consuming. Materials and Methods: This study aimed to evaluate differences in thigh muscle volume in followed-up hip fracture patients computed tomography (CT) scans using an AI based automatic muscle segmentation model. The study included a total of 18 patients at Gyeongsang National University, who had undergone surgical treatment for a hip fracture. We utilized the automatic segmentation algorithm which we have already developed using UNETR (U-net Transformer) architecture, performance dice score = 0.84, relative absolute volume difference 0.019 ± 0.017%. Results: The results revealed intertrochanteric fractures result in more significant muscle volume loss (females: -97.4 cm3, males: -178.2 cm3) compared to femoral neck fractures (females: -83 cm3, males: -147.2 cm3). Additionally, the study uncovered substantial disparities in the susceptibility to volume loss among specific thigh muscles, including the Vastus lateralis, Adductor longus and brevis, and Gluteus maximus, particularly in cases of intertrochanteric fractures. Conclusions: The use of an automatic muscle segmentation model based on deep learning algorithms enables efficient and accurate analysis of thigh muscle volume differences in followed up hip fracture patients. Our findings emphasize the significant muscle loss tied to sarcopenia, a critical condition among the elderly. Intertrochanteric fractures resulted in greater muscle volume deformities, especially in key muscle groups, across both genders. Notably, while most muscles exhibited volume reduction following hip fractures, the sartorius, vastus and gluteus groups demonstrated more significant disparities in individuals who sustained intertrochanteric fractures. This non-invasive approach provides valuable insights into the extent of muscle atrophy following hip fracture and can inform targeted rehabilitation interventions.


Assuntos
Fraturas do Quadril , Músculo Esquelético , Coxa da Perna , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Fraturas do Quadril/cirurgia , Fraturas do Quadril/diagnóstico por imagem , Idoso , Estudos Retrospectivos , Coxa da Perna/diagnóstico por imagem , Coxa da Perna/lesões , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/lesões , Idoso de 80 Anos ou mais , Algoritmos , Inteligência Artificial , Seguimentos , Tamanho do Órgão
17.
Artigo em Inglês | MEDLINE | ID: mdl-39109557

RESUMO

AIM: This study aimed to explore the relationships between serum cortisol levels, personality traits, and the development of Post-Traumatic Stress Disorder (PTSD) over 2 years among individuals with physical injuries. METHODS: Participants were consecutively recruited from a trauma center and followed prospectively for 2 years. At baseline, serum cortisol levels were measured, and personality traits were categorized into five dimensions (Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness), using the Big Five Inventory-10. The diagnosis of PTSD during follow-up (at 3, 6, 12, and 24 months post-injury) was determined using the Clinician-Administered PTSD Scale for DSM-5. Binary and multinomial logistic regression analyses were conducted to examine the interactions between cortisol levels, personality traits, and PTSD development. RESULTS: Among 923 patients analyzed, 112 (12.1%) were diagnosed with PTSD at some point during the study period, with prevalence rates decreasing from 8.8% at 3 months to 3.7% at 24 months post-injury. Direct associations between cortisol levels or personality traits and PTSD were not observed. However, a significant interaction between lower cortisol levels and higher Neuroticism in relation to PTSD risk was identified, especially during the early follow-up periods (3 to 6 months), but this association waned from the 12-month follow-up onward. CONCLUSION: Our findings reveal Neuroticism-dependent associations between serum cortisol levels and PTSD development, exhibiting temporal variations. These results suggest that PTSD development may be influenced by a complex, time-sensitive interplay of biological and psychosocial factors, underscoring the importance of considering individual differences in stress reactivity and personality in PTSD research and treatment.

18.
Sci Rep ; 14(1): 17994, 2024 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-39097625

RESUMO

CD73 is a cell-surface ectoenzyme that hydrolyzes the conversion of extracellular adenosine monophosphate to adenosine, which in turn can promote resistance to immune checkpoint blockade therapy. Immune response may therefore be improved by targeting tumor CD73, and this possibility underlines the need to non-invasively assess tumor CD73 level. In this study, we developed a cysteine site-specific 89Zr-labeled anti-CD73 (89Zr-CD73) IgG immuno-PET technique that can image tumor CD73 expression in living bodies. Anti-CD73 IgG was reduced with tris(2-carboxyethyl)phosphine, underwent sulfohydryl moiety-specific conjugation with deferoxamine-maleimide, and was radiolabeled with 89Zr. CT26 mouse colon cancer cells, CT26/CD73 cells engineered to constitutively overexpress CD73, and 4T1.2 mouse breast cancer cells underwent cell binding assays and western blotting. Balb/c nude mice bearing tumors underwent 89Zr-CD73 IgG PET imaging and biodistribution studies. 89Zr-CD73 IgG showed 20-fold higher binding to overexpressing CT26/CD73 cells compared to low-expressing CT26 cells, and moderate expressing 4T1.2 cells showed uptake that was 38.9 ± 1.51% of CT26/CD73 cells. Uptake was dramatically suppressed by excess unlabeled antibody. CD73 content proportionately increased in CT26 and CT26/CD73 cell mixtures was associated with linear increases in 89Zr-CD73 IgG uptake. 89Zr-CD73 IgG PET/CT displayed clear accumulation in CT26/CD73 tumors with greater uptake compared to CT26 tumors (3.13 ± 1.70%ID/g vs. 1.27 ± 0.31%ID/g at 8 days; P = 0.04). Specificity was further supported by low CT26/CD73 tumor-to-blood ratio of 89Zr-isotype-IgG compared to 89Zr-CD73 IgG (0.48 ± 0.08 vs. 2.68 ± 0.52 at 4 days and 0.53 ± 0.07 vs. 4.81 ± 1.02 at 8 days; both P < 0.001). Immunoblotting and immunohistochemistry confirmed strong CD73 expression in CT26/CD73 tumors and low expression in CT26 tumors. 4T1.2 tumor mice also showed clear 89Zr-CD73 IgG accumulation at 8 days (3.75 ± 0.70%ID/g) with high tumor-to-blood ratio compared to 89Zr-isotype-IgG (4.91 ± 1.74 vs. 1.20 ± 0.28; P < 0.005). 89Zr-CD73 IgG specifically targeted CD73 on high expressing cancer cells in vitro and tumors in vivo. Thus, 89Zr-CD73 IgG immuno-PET may be useful for the non-invasive monitoring of CD73 expression in tumors of living subjects.


Assuntos
5'-Nucleotidase , Neoplasias do Colo , Cisteína , Tomografia por Emissão de Pósitrons , Zircônio , Animais , 5'-Nucleotidase/metabolismo , Zircônio/química , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/metabolismo , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Camundongos , Linhagem Celular Tumoral , Tomografia por Emissão de Pósitrons/métodos , Cisteína/metabolismo , Humanos , Radioisótopos , Feminino , Camundongos Endogâmicos BALB C , Distribuição Tecidual , Camundongos Nus , Proteínas Ligadas por GPI/metabolismo , Proteínas Ligadas por GPI/imunologia , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo
19.
Hepatol Commun ; 8(8)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39101773

RESUMO

BACKGROUND: Intermediate cell carcinoma (Int-CA) is a rare and enigmatic primary liver cancer characterized by uniform tumor cells exhibiting mixed features of both HCC and intrahepatic cholangiocarcinoma. Despite the unique pathological features of int-CA, its molecular characteristics remain unclear yet. METHODS: RNA sequencing and whole genome sequencing profiling were performed on int-CA tumors and compared with those of HCC and intrahepatic cholangiocarcinoma. RESULTS: Int-CAs unveiled a distinct and intermediate transcriptomic feature that is strikingly different from both HCC and intrahepatic cholangiocarcinoma. The marked abundance of splicing events leading to intron retention emerged as a signature feature of int-CA, along with a prominent expression of Notch signaling. Further exploration revealed that METTL16 was suppressed within int-CA, showing a DNA copy number-dependent transcriptional deregulation. Notably, experimental investigations confirmed that METTL16 suppression facilitated invasive tumor characteristics through the activation of the Notch signaling cascade. CONCLUSIONS: Our results provide a molecular landscape of int-CA featured by METTL16 suppression and frequent intron retention events, which may play pivotal roles in the acquisition of the aggressive phenotype of Int-CA.


Assuntos
Carcinoma Hepatocelular , Colangiocarcinoma , Perfilação da Expressão Gênica , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Transcriptoma , Masculino , Metiltransferases/genética , Metiltransferases/metabolismo , Transdução de Sinais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Feminino , Pessoa de Meia-Idade
20.
Heliyon ; 10(14): e34551, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39130459

RESUMO

In this study, the corrosion behavior and degradation mechanism of Ti-Pt-coated stainless steel bipolar plates were investigated through electrochemical tests and surface analysis in a polymer electrolyte membrane water electrolysis (PEMWE) operating environment. The coated bipolar plate has a corrosion current density of only 1.68 × 10-8 A/cm2, which is an order of magnitude lower than that of the bare SS316L substrate (1.94 × 10-7 A/cm2), indicating that its corrosion resistance is superior to that of bare SS316L substrate. However, in the PEMWE operating environment, the protection efficiency of the coating and the corrosion resistance of the coated bipolar plate decreased. The degradation of the coated bipolar plate can be attributed to electrolyte penetration into the blistering areas of the coating layer with micro voids. Defects in the coating layer occur because of the pressure of oxygen gas generated within the coating layer under high-potential conditions, thereby exposing the substrate to the electrolyte and corrosion.

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