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1.
Materials (Basel) ; 17(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38998216

RESUMO

Recent advances in the leisure boat industry have spurred demand for improved materials for propeller manufacturing, particularly high-strength aluminum alloys. While traditional Al-Si alloys like A356 are commonly used due to their excellent castability, they have limited mechanical properties. In contrast, 7xxx series alloys (Al-Zn-Mg-Cu based) offer superior mechanical characteristics but present significant casting challenges, including hot-tearing susceptibility (HTS). This study investigates the optimization of 7xxx series aluminum alloys for low-pressure die-casting (LPDC) processes to enhance propeller performance and durability. Using a constrained rod-casting (CRC) method and finite element simulations, we evaluated the HTS of various alloy compositions. The results indicate that increasing Zn and Cu contents generally increase HTS, while a sufficient Mg content of 2 wt.% mitigates this effect. Two optimized quaternary Al-Zn-Mg-Cu alloys with relatively low HTS were selected for LPDC propeller production. Simulation and experimental results demonstrated the effectiveness of the proposed alloy compositions, highlighting the need for further process optimization to prevent hot tearing in high Mg and Cu content alloys.

2.
Angew Chem Int Ed Engl ; : e202409655, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967990

RESUMO

5,18-Dimesitylorangarin and its BF2 complex were synthesized by double SNAr reaction of 3,5-dibromo-BODIPY with a-(pyro-2-ly)dipyrrin as the first examples of meso-aryl-substituted orangarin. These orangarins, delineated as [20]pentaphyrin(1.0.1.0.0), are strongly antiaromatic but rather stable. The free base orangarin was coupled by oxidation with MnO2 to give a 11,11'-linked dimer, a cyclooctatetraene(COT)-centered trimer, and a spiro-trimer. Fused COT-centered 3H-orangarin dimer was oxidized to the corresponding 2H-orangarin dimer, which was further coupled to give a triply COT centered 2H-orangarin tetramer. 3H-Orangarin oligomers are all antiaromatic as evinced by extremely low-field-shifted 1H NMR signals of the inner NH and ill-defined absorption spectra with broad tails. In contrast, COT-centered 2H-orangarin dimer and tetramer show moderately low-field-shifted NH signals and intense NIR absorbance over 900 nm, suggesting the effective p-conjugation through the COT bridge and almost non-antiaromatic character. These orangarin oligomers exhibit many reversible redox potentials owing to the intramolecular electronic interactions. Regardless of the different aromatic characters, all the orangarin monomers and oligomers exhibit very rapid excited-state decays.

3.
Circ Heart Fail ; : e011123, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38979607

RESUMO

BACKGROUND: Systemic hemodynamics and specific ventilator settings have been shown to predict survival during venoarterial extracorporeal membrane oxygenation (ECMO). How the right heart (the right ventricle and pulmonary artery) affect survival during venoarterial ECMO is unknown. We aimed to identify the relationship between right heart function with mortality and the duration of ECMO support. METHODS: Cardiac ECMO runs in adults from the Extracorporeal Life Support Organization Registry between 2010 and 2022 were queried. Right heart function was quantified via pulmonary artery pulse pressure (PAPP) for pre-ECMO and on-ECMO periods. A multivariable model was adjusted for modified Society for Cardiovascular Angiography and Interventions stage, age, sex, and concurrent clinical data (ie, pulmonary vasodilators and systemic pulse pressure). The primary outcome was in-hospital mortality. RESULTS: A total of 4442 ECMO runs met inclusion criteria and had documentation of hemodynamic and illness severity variables. The mortality rate was 55%; nonsurvivors were more likely to be older, have a worse Society for Cardiovascular Angiography and Interventions stage, and have longer pre-ECMO endotracheal intubation times (P<0.05 for all) than survivors. Increasing PAPP from pre-ECMO to on-ECMO time (ΔPAPP) was associated with reduced mortality per 2 mm Hg increase (odds ratio, 0.98 [95% CI, 0.97-0.99]; P=0.002). Higher on-ECMO PAPP was associated with mortality reduction across quartiles with the greatest reduction in the third PAPP quartile (odds ratio, 0.75 [95% CI, 0.63-0.90]; P=0.002) and longer time on ECMO per 10 mm Hg (beta, 15 [95% CI, 7.7-21]; P<0.001). CONCLUSIONS: Early on-ECMO right heart function and interval improvement from pre-ECMO values were associated with mortality reduction during cardiac ECMO. Incorporation of right heart metrics into risk prediction models should be considered.

4.
Front Immunol ; 15: 1369385, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915417

RESUMO

Introduction: This study aimed to demonstrate the potential of activated leukocyte cell adhesion molecule (ALCAM), hemopexin (HPX), and peroxiredoxin 6 (PRDX6) as urine biomarkers for systemic lupus erythematosus (SLE). Methods: Urine samples were collected from 138 Korean patients with SLE from the Ajou Lupus Cohort and 39 healthy controls (HC). The concentrations of urine biomarkers were analyzed using enzyme-linked immunosorbent assay kits specific for ALCAM, HPX, and PRDX6, respectively. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic utility, and Pearson's correlation analysis was conducted to assess the relationships between the disease activity and urine biomarkers. Results: Patients with SLE and patients with lupus nephritis (LN) showed significantly elevated ALCAM, HPX, and PRDX6 levels compared with HCs. ALCAM, HPX, and PRDX6 showed significant diagnostic values, especially for lupus nephritis (LN), with areas under the receiver operating characteristic curve for LN was 0.850 for ALCAM (95% CI, 0.778-0.921), 0.781 for HPX (95% CI, 0.695-0.867), and 0.714 for PRDX6 (95% CI, 0.617-0.812). Correlation analysis revealed that all proteins were significantly associated with anti-double stranded DNA antibody (ALCAM, r = 0.350, p < 0.001; HPX, r = 0.346, p < 0.001; PRDX6, r = 0.191, p = 0.026) and SLEDAI (ALCAM, r = 0.526, p < 0.001; HPX, r = 0.479, p < 0.001; PRDX6, r = 0.262, p = 0.002). Results from the follow-up of the three biomarker levels in these patients revealed a significant decrease, showing a positive correlation with changes in SLEDAI-2k scores (ALCAM, r = 0.502, p < 0.001; HPX, r = 0.475, p < 0.001; PRDX6, r = 0.245, p = 0.026), indicating their potential as indicators for tracking disease activity. Discussions: Urinary ALCAM, HPX, and PRDX6 levels have diagnostic value and reflect disease activity in Korean patients with SLE, emphasizing their potential for non-invasive monitoring and treatment response evaluation.


Assuntos
Biomarcadores , Lúpus Eritematoso Sistêmico , Peroxirredoxina VI , Humanos , Feminino , Masculino , Biomarcadores/urina , Adulto , Lúpus Eritematoso Sistêmico/urina , Lúpus Eritematoso Sistêmico/diagnóstico , República da Coreia , Peroxirredoxina VI/urina , Pessoa de Meia-Idade , Proteínas Fetais/urina , Estudos Longitudinais , Índice de Gravidade de Doença , Adulto Jovem , Antígenos CD/urina , Curva ROC , Moléculas de Adesão Celular Neuronais/urina , Estudos de Casos e Controles , Nefrite Lúpica/urina , Nefrite Lúpica/diagnóstico , Molécula de Adesão de Leucócito Ativado
5.
J Korean Med Sci ; 39(22): e175, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38859738

RESUMO

BACKGROUND: Multiple myeloma (MM) patients are at risk of skeletal-related events (SREs) like spinal cord compression, pathologic fractures, bone surgery, and radiation to bone. Real-world data regarding SREs in MM are limited. METHODS: We conducted a large, retrospective, nationwide cohort study using the Korean Health Insurance Review and Assessment Service (HIRA) database from 2007 to 2018. RESULTS: Over a 12-year study period, we identified 6,717 patients who developed symptomatic MM. After a median follow-up of 35.1 months (interquartile range [IQR], 20.8-58.2 months), 43.6% of these patients experienced SREs, and 39.6% had four or more SREs. One in five patients (20.0%) experienced pathologic fractures within the first year of follow-up. The median time to first SRE was 9.6 months (IQR, 1.2-25.8 months), with 3.0 months in the group with prior SREs and 19.8 months in the group without prior SREs. During follow-up, 78.5% of patients received bisphosphonates. Multiple logistic regression analysis revealed several factors associated with an increased risk of SREs, including being female (odds ratio [OR], 1.44), aged 50 or older (OR, 1.87), having cerebrovascular disease (OR, 1.34), undergoing first-line chemotherapy regimens not containing bortezomib or lenalidomide (OR, 1.49), and being in the group with prior SREs and bisphosphonate use (OR, 5.63), compared to the group without prior SREs and without bisphosphonate use. CONCLUSION: This population-based study is the first to report the incidence and risk factors of SREs in Korean MM patients, which can be used to assess their bone health.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/patologia , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/complicações , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Difosfonatos/uso terapêutico , Fatores de Risco , Bases de Dados Factuais , República da Coreia/epidemiologia , Conservadores da Densidade Óssea/uso terapêutico , Razão de Chances , Fraturas Espontâneas/etiologia , Fraturas Espontâneas/epidemiologia , Compressão da Medula Espinal/etiologia , Adulto , Modelos Logísticos
6.
Int J Mol Sci ; 25(12)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38928513

RESUMO

Arterial macrophage cholesterol accumulation and impaired cholesterol efflux lead to foam cell formation and the development of atherosclerosis. Modified lipoproteins interact with toll-like receptors (TLR), causing an increased inflammatory response and altered cholesterol homeostasis. We aimed to determine the effects of TLR antagonists on cholesterol efflux and foam cell formation in human macrophages. Stimulated monocytes were treated with TLR antagonists (MIP2), and the cholesterol efflux transporter expression and foam cell formation were analyzed. The administration of MIP2 attenuated the foam cell formation induced by lipopolysaccharides (LPS) and oxidized low-density lipoproteins (ox-LDL) in stimulated THP-1 cells (p < 0.001). The expression of ATP-binding cassette transporters A (ABCA)-1, ABCG-1, scavenger receptor (SR)-B1, liver X receptor (LXR)-α, and peroxisome proliferator-activated receptor (PPAR)-γ mRNA and proteins were increased (p < 0.001) following MIP2 administration. A concentration-dependent decrease in the phosphorylation of p65, p38, and JNK was also observed following MIP2 administration. Moreover, an inhibition of p65 phosphorylation enhanced the expression of ABCA1, ABCG1, SR-B1, and LXR-α. TLR inhibition promoted the cholesterol efflux pathway by increasing the expression of ABCA-1, ABCG-1, and SR-B1, thereby reducing foam cell formation. Our results suggest a potential role of the p65/NF-kB/LXR-α/ABCA1 axis in TLR-mediated cholesterol homeostasis.


Assuntos
Transportador 1 de Cassete de Ligação de ATP , Colesterol , Células Espumosas , Lipoproteínas LDL , Receptores X do Fígado , Receptores Toll-Like , Humanos , Células Espumosas/metabolismo , Células Espumosas/efeitos dos fármacos , Colesterol/metabolismo , Receptores X do Fígado/metabolismo , Receptores Toll-Like/metabolismo , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Transportador 1 de Cassete de Ligação de ATP/genética , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/farmacologia , PPAR gama/metabolismo , Células THP-1 , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Lipopolissacarídeos/farmacologia , Receptores Depuradores Classe B/metabolismo , Receptores Depuradores Classe B/genética
7.
Clin Exp Med ; 24(1): 133, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900301

RESUMO

This study aimed to investigate the serum and expression levels of C-X-C motif chemokine ligand 9 (CXCL9), CXCL10, CXCL11, and CXC receptor 3 (CXCR3) in minor salivary glands (MSGs) of patients with primary Sjögren's syndrome (pSS), and to explore their correlations with clinical parameters. Serum samples from 49 patients diagnosed with pSS, 33 patients with rheumatoid arthritis (RA), and 30 healthy controls (HCs) were collected for measurements of CXCL9, CXCL10, CXCL11, and CXCR3. Additionally, CXCL levels in the MSG tissues were measured in 41 patients who underwent MSG biopsy. Correlations between CXCL and CXCL/CXCR levels in serum/MSG tissues and clinical factors/salivary scintigraphy parameters were analyzed. Serum CXCL11 and CXCR3 showed statistically significant differences among patients with pSS and RA and HCs (serum CXCL11, pSS:RA:HC = 235.6 ± 500.1 pg/mL:90.0 ± 200.3 pg/mL:45.9 ± 53.6 pg/mL; p = 0.041, serum CXCR3, pSS:RA:HC = 3.27 ± 1.32 ng/mL:3.29 ± 1.17 ng/mL:2.00 ± 1.12 ng/mL; p < 0.001). Serum CXCL10 showed a statistically significant difference between pSS (64.5 ± 54.2 pg/mL) and HCs (18.6 ± 18.1 pg/mL, p < 0.001), while serum CXCL9 did not exhibit a significant difference among the groups. Correlation analysis of clinical factors revealed that serum CXCL10 and CXCL11 levels positively correlated with erythrocyte sedimentation rate (r = 0.524, p < 0.001 and r = 0.707, p < 0.001, respectively), total protein (r = 0.375, p = 0.008 and r = 0.535, p < 0.001, respectively), globulin (r = 0.539, p < 0.001 and r = 0.639, p < 0.001, respectively), and European Alliance of Associations for Rheumatology SS Disease Activity Index (r = 0.305, p = 0.033 and r = 0.321, p = 0.025). Additionally, serum CXCL10 negatively correlated with the Schirmer test score (r = - 0.354, p = 0.05), while serum CXCL11 positively correlated with the biopsy focus score (r = 0.612, p = 0.02). In the MSG tissue, the percentage of infiltrating CXCL9-positive cells was highest (75.5%), followed by CXCL10 (29.1%) and CXCL11 (27.9%). In the correlation analysis, CXCL11-expressing cells were inversely related to the mean washout percentage on salivary gland scintigraphy (r = - 0.448, p = 0.007). Our study highlights distinct serum and tissue chemokine patterns in pSS, emphasizing CXCL9's potential for early diagnosis. This suggests that CXCL10 and CXCL11 are indicators of disease progression, warranting further investigation into their roles in autoimmune disorders beyond pSS.


Assuntos
Quimiocina CXCL10 , Quimiocina CXCL11 , Receptores CXCR3 , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/patologia , Síndrome de Sjogren/sangue , Síndrome de Sjogren/metabolismo , Feminino , Pessoa de Meia-Idade , Masculino , Receptores CXCR3/metabolismo , Adulto , Quimiocina CXCL11/sangue , Quimiocina CXCL10/sangue , Idoso , Glândulas Salivares Menores/patologia , Glândulas Salivares Menores/metabolismo , Quimiocina CXCL9/sangue , Soro/química , Soro/metabolismo
8.
Radiol Cardiothorac Imaging ; 6(3): e230177, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38722232

RESUMO

Purpose To develop a deep learning model for increasing cardiac cine frame rate while maintaining spatial resolution and scan time. Materials and Methods A transformer-based model was trained and tested on a retrospective sample of cine images from 5840 patients (mean age, 55 years ± 19 [SD]; 3527 male patients) referred for clinical cardiac MRI from 2003 to 2021 at nine centers; images were acquired using 1.5- and 3-T scanners from three vendors. Data from three centers were used for training and testing (4:1 ratio). The remaining data were used for external testing. Cines with downsampled frame rates were restored using linear, bicubic, and model-based interpolation. The root mean square error between interpolated and original cine images was modeled using ordinary least squares regression. In a prospective study of 49 participants referred for clinical cardiac MRI (mean age, 56 years ± 13; 25 male participants) and 12 healthy participants (mean age, 51 years ± 16; eight male participants), the model was applied to cines acquired at 25 frames per second (fps), thereby doubling the frame rate, and these interpolated cines were compared with actual 50-fps cines. The preference of two readers based on perceived temporal smoothness and image quality was evaluated using a noninferiority margin of 10%. Results The model generated artifact-free interpolated images. Ordinary least squares regression analysis accounting for vendor and field strength showed lower error (P < .001) with model-based interpolation compared with linear and bicubic interpolation in internal and external test sets. The highest proportion of reader choices was "no preference" (84 of 122) between actual and interpolated 50-fps cines. The 90% CI for the difference between reader proportions favoring collected (15 of 122) and interpolated (23 of 122) high-frame-rate cines was -0.01 to 0.14, indicating noninferiority. Conclusion A transformer-based deep learning model increased cardiac cine frame rates while preserving both spatial resolution and scan time, resulting in images with quality comparable to that of images obtained at actual high frame rates. Keywords: Functional MRI, Heart, Cardiac, Deep Learning, High Frame Rate Supplemental material is available for this article. © RSNA, 2024.


Assuntos
Aprendizado Profundo , Imagem Cinética por Ressonância Magnética , Humanos , Masculino , Imagem Cinética por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Feminino , Estudos Prospectivos , Estudos Retrospectivos , Coração/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos
9.
Technol Health Care ; 32(S1): 361-369, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38759061

RESUMO

BACKGROUND: Studies investigating postural balance during various infant care postures have not been reported yet. OBJECTIVE: The aim of this study was to measure static postural balance when holding an infant dummy in-arms and carrying an infant dummy on back according to different infant dummy weights. METHODS: Sixteen healthy young subjects participated in a balance test. Infant dummies with weights of 4.6 kg (1-month) and 9.8 kg (12-month) were used in this study. All subjects were asked to naturally stand on a force platform in two infant care postures (holding an infant in-arms and carrying an infant on one's back). Center of pressure (COP) was measured from the force platform. Quantitative variables were derived from the COP. Two-way repeated measure analysis of variance (ANOVA) was performed to determine main effects of infant care postures, infant weight, and their interactions on COP variables. RESULTS: Back carrying a 12-month infant dummy had the greatest amplitude in all COP variables. Back carrying posture showed significantly greater mean distance and peak power, faster mean velocity, and wider COP area compared to holding posture (P< 0.05). There were significant weight effects of most COP variables mainly in AP direction (P< 0.01). CONCLUSIONS: Our results could contribute to the prevention of musculoskeletal diseases or prevention of fall due to various infant care activities by developing an assisting device to improve postural balance.


Assuntos
Peso Corporal , Equilíbrio Postural , Postura , Humanos , Equilíbrio Postural/fisiologia , Masculino , Postura/fisiologia , Lactente , Feminino , Peso Corporal/fisiologia , Cuidado do Lactente/métodos , Adulto Jovem
10.
Int J Biol Macromol ; 270(Pt 1): 132178, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38735614

RESUMO

In response to escalating environmental concerns and the urgent need for sustainable drug delivery systems, this study introduces biodegradable pH-responsive microcapsules synthesized from a blend of gelatin, alginate, and hyaluronic acid. Employing the coacervation process, capsules were created with a spherical shape, multicore structure, and small sizes ranging from 10 to 20 µm, which exhibit outstanding vitamin E encapsulation efficiency. With substantial incorporation of hyaluronic acid, a pH-responsive component, the resulting microcapsules displayed noteworthy swelling behavior, facilitating proficient core ingredient release at pH 5.5 and 7.4. Notably, these capsules can effectively deliver active substances to the dermal layer under specific skin conditions, revealing promising applications in topical medications and cosmetics. Furthermore, the readily biodegradable nature of the designed capsules was demonstrated through Biochemical Oxygen Demand (BOD) testing, with over 80 % of microcapsules being degraded by microorganisms after one week of incubation. This research contributes to the development of responsive microcapsules and aligns with broader environmental initiatives, offering a promising pathway to mitigate the impact of microplastics while advancing various applications.


Assuntos
Alginatos , Cápsulas , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Gelatina , Ácido Hialurônico , Ácido Hialurônico/química , Alginatos/química , Gelatina/química , Concentração de Íons de Hidrogênio , Preparações de Ação Retardada/química , Portadores de Fármacos/química , Vitamina E/química
11.
Vaccine ; 42(18): 3756-3767, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38724417

RESUMO

A Newcastle disease virus (NDV)-vectored vaccine expressing clade 2.3.4.4b H5 Hemagglutinin was developed and assessed for efficacy against H5N1 highly pathogenic avian influenza (HPAI) in specific pathogen-free (SPF) chickens, broilers, and domestic ducks. In SPF chickens, the live recombinant NDV-vectored vaccine, rK148/22-H5, achieved complete survival against HPAI and NDV challenges and significantly reduced viral shedding. Notably, the live rK148/22-H5 vaccine conferred good clinical protection in broilers despite the presence of maternally derived antibodies. Good clinical protection was observed in domestic ducks, with decreased viral shedding. It demonstrated complete survival and reduced cloacal viral shedding when used as an inactivated vaccine from SPF chickens. The rK148/22-H5 vaccine is potentially a viable and supportive option for biosecurity measure, effectively protecting in chickens against the deadly clade 2.3.4.4b H5 HPAI and NDV infections. Furthermore, it aligns with the strategy of Differentiating Infected from Vaccinated Animals (DIVA).


Assuntos
Anticorpos Antivirais , Galinhas , Patos , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Virus da Influenza A Subtipo H5N1 , Influenza Aviária , Vírus da Doença de Newcastle , Vacinas de Produtos Inativados , Vacinas Sintéticas , Eliminação de Partículas Virais , Animais , Galinhas/imunologia , Influenza Aviária/prevenção & controle , Influenza Aviária/imunologia , Vírus da Doença de Newcastle/imunologia , Vírus da Doença de Newcastle/genética , Virus da Influenza A Subtipo H5N1/imunologia , Virus da Influenza A Subtipo H5N1/genética , Virus da Influenza A Subtipo H5N1/patogenicidade , Patos/virologia , Patos/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/genética , Organismos Livres de Patógenos Específicos , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/genética , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/imunologia , Doença de Newcastle/prevenção & controle , Doença de Newcastle/imunologia , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/genética
12.
Cancer Res Treat ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38697850

RESUMO

Purpose: This study aimed to compare tumor tissue DNA (ttDNA) and circulating tumor DNA (ctDNA) to explore the clinical applicability of ctDNA and to better understand clonal evolution in patients with metastatic colorectal cancer undergoing palliative first-line systemic therapy. Materials and Methods: We performed targeted sequencing analysis of 88 cancer-associated genes using germline DNA, ctDNA at baseline (baseline-ctDNA), and ctDNA at progressive disease (PD-ctDNA). The results were compared with ttDNA data. Results: Among 208 consecutively enrolled patients, we selected 84 (41 males; median age 59, range 35 to 90) with all four sample types available. A total of 202 driver mutations were found in 34 genes. ttDNA exhibited the highest mutation frequency (n=232), followed by baseline-ctDNA (n=155) and PD-ctDNA (n=117). Sequencing ctDNA alongside ttDNA revealed additional mutations in 40 patients (47.6%). PD-ctDNA detected 13 novel mutations in 10 patients (11.9%) compared to ttDNA and baseline-ctDNA. Notably, 7 mutations in 5 patients (6.0%) were missense or nonsense mutations in APC, TP53, SMAD4, and CDH1 genes. In baseline-ctDNA, higher maximal variant allele frequency (VAF) values (p=0.010) and higher VAF values of APC (p=0.012), TP53 (p=0.012), and KRAS (p=0.005) mutations were significantly associated with worse overall survival. Conclusion: While ttDNA remains more sensitive than ctDNA, our ctDNA platform demonstrated validity and potential value when ttDNA was unavailable. Post-treatment analysis of PD-ctDNA unveiled new pathogenic mutations, signifying cancer's clonal evolution. Additionally, baseline-ctDNA's VAF values were prognostic after treatment.

13.
Circ Cardiovasc Imaging ; 17(5): e016420, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38716661

RESUMO

BACKGROUND: Echocardiographic (2-dimensional echocardiography) thresholds indicating disease or impaired functional status compared with normal physiological aging in individuals aged ≥65 years are not clearly defined. In the present study, we sought to establish standard values for 2-dimensional echocardiography parameters related to chamber size and function in older adults without cardiopulmonary or cardiometabolic conditions. METHODS: In this cross-sectional study of 3032 individuals who underwent 2-dimensional echocardiography at exam 6 in the MESA (Multi-Ethnic Study of Atherosclerosis), 608 participants fulfilled our inclusion criteria of healthy aging, with normative values defined as the mean ± 1.96 standard deviation and compared across sex and race and ethnicity. Functional status measures included NT-proBNP (N-terminal pro-B-type natriuretic peptide), 6-minute walk distance, and Kansas City Cardiomyopathy Questionnaire. Prognostic performance using MESA cutoffs was compared with established guideline cutoffs using time-to-event analysis. RESULTS: The normative aging cohort (69.5±7.0 years, 46.2% male, 47.5% White) had lower NT-proBNP, higher 6-minute walk distance, and higher (better) Kansas City Cardiomyopathy Questionnaire summary values. Women had significantly smaller chamber sizes and better biventricular systolic function. White participants had the largest chamber dimensions, whereas Chinese participants had the smallest, even after adjustment for body size. Current guidelines identified 81.6% of healthy older adults in MESA as having cardiac abnormalities. CONCLUSIONS: Among a large, diverse group of healthy older adults, we found significant differences in cardiac structure and function by sex and race/ethnicity, which may signal sex-specific cardiac remodeling with advancing age. It is crucial for existing guidelines to consider the observed and clinically significant differences in cardiac structure and function associated with healthy aging. Our study highlights that existing guidelines, which grade abnormalities in echocardiographic cardiac chamber size and function based on younger individuals, may not adequately address the anticipated changes associated with normal aging.


Assuntos
Fragmentos de Peptídeos , Humanos , Feminino , Masculino , Idoso , Estudos Transversais , Idoso de 80 Anos ou mais , Fragmentos de Peptídeos/sangue , Função Ventricular Esquerda/fisiologia , Peptídeo Natriurético Encefálico/sangue , Valores de Referência , Estados Unidos/epidemiologia , Aterosclerose/etnologia , Aterosclerose/fisiopatologia , Aterosclerose/diagnóstico por imagem , Fatores Etários , Ecocardiografia/métodos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Função Ventricular Direita/fisiologia , Teste de Caminhada , Valor Preditivo dos Testes , Envelhecimento Saudável/etnologia , Pessoa de Meia-Idade
14.
Front Microbiol ; 15: 1383779, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741747

RESUMO

Introduction: The effects of fructo-oligosaccharides (FOS) on atopic dermatitis (AD) have not been determined. Methods: In a randomized, double-blind, placebo-controlled trial, children with AD aged 24 months to 17 years received either advanced FOS containing 4.25 g of 1-kestose or a placebo (maltose) for 12 weeks. Results: The SCORAD and itching scores were reduced in patients treated with both FOS (all p < 0.01) and maltose (p < 0.05 and p < 0.01). Sleep disturbance was improved only in the FOS group (p < 0.01). The FOS group revealed a decreased proportion of linoleic acid (18:2) esterified omega-hydroxy-ceramides (EOS-CERs) with amide-linked shorter chain fatty acids (C28 and C30, all p < 0.05), along with an increased proportion of EOS-CERs with longer chain fatty acids (C32, p < 0.01). Discussion: FOS may be beneficial in alleviating itching and sleep disturbance, as well as improving skin barrier function in children with AD.

15.
Sci Rep ; 14(1): 10201, 2024 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702399

RESUMO

The importance of neuroinflammation during the ischemic stroke has been extensively studied. The role of CD4+CD25+ regulatory T (Treg) cells during the recovery phase have shown infarct size reduction and functional improvement, possibly through the mitigation of inflammatory immune responses. We aimed to investigate the molecular factors involved in microglia-Treg cell communication that result in Treg trafficking. First, we observed the migration patterns of CD8+ (cytotoxic) T cells and Treg cells and then searched for chemokines released by activated microglia in an oxygen-glucose deprivation (OGD) model. The transwell migration assay showed increased migration into OGD media for both cell types, in agreement with the increase in chemokines involved in immune cell trafficking from the mouse chemokine profiling array. MSCV retrovirus was transduced to overexpress CCR4 in Treg cells. CCR4-overexpressed Treg cells were injected into the mouse transient middle cerebral artery occlusion (tMCAO) model to evaluate the therapeutic potential via the tetrazolium chloride (TTC) assay and behavioral tests. A general improvement in the prognosis of animals after tMCAO was observed. Our results suggest the increased mobility of CCR4-overexpressed Treg cells in response to microglia-derived chemokines in vitro and the therapeutic potential of Treg cells with increased mobility in cellular therapy.


Assuntos
Movimento Celular , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média , AVC Isquêmico , Receptores CCR4 , Linfócitos T Reguladores , Animais , Receptores CCR4/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Camundongos , AVC Isquêmico/imunologia , AVC Isquêmico/metabolismo , AVC Isquêmico/patologia , Infarto da Artéria Cerebral Média/imunologia , Infarto da Artéria Cerebral Média/metabolismo , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Microglia/metabolismo , Microglia/imunologia , Masculino , Camundongos Endogâmicos C57BL , Quimiocinas/metabolismo
16.
Ann Rheum Dis ; 83(8): 1028-1033, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38594057

RESUMO

OBJECTIVE: To investigate the risk of cardiovascular disease (CVD) associated with increasing dose of a non-steroidal anti-inflammatory drug (NSAID) in patients with ankylosing spondylitis (AS). METHODS: Using the Korean National Health Insurance database, patients newly diagnosed with AS without prior CVD between 2010 and 2018 were included in this nationwide cohort study. The primary outcome was CVD, a composite outcome of ischaemic heart disease, stroke or congestive heart failure. Exposure to NSAIDs was evaluated using a time-varying approach. The dose of NSAIDs was considered in each exposure period. Cox proportional hazard regression was used to investigate the risk of CVD associated with NSAID use. RESULTS: Of the 19 775 patients (mean age, 36 years; 75% were male), 19 706 received NSAID treatment. During follow-up period of 98 290 person-years, 1663 cases of CVD occurred including 1157 cases of ischaemic heart disease, 301 cases of stroke and 613 cases of congestive heart failure. Increasing dose of NSAIDs was associated with incident CVD after adjusting for confounders (adjusted HR (aHR) 1.10; 95% CI 1.08 to 1.13). Specifically, increasing dose of NSAIDs was associated with incident ischaemic heart disease (aHR 1.08; 95% CI 1.05 to 1.11), stroke (aHR 1.09; 95% CI 1.04 to 1.15) and congestive heart failure (aHR 1.12; 95% CI 1.08 to 1.16). The association between NSAID dose and higher CVD risk was consistent in different subgroups. CONCLUSION: In a real-world AS cohort, higher dose of NSAID treatment was associated with a higher risk of CVD, including ischaemic heart disease, stroke and congestive heart failure.


Assuntos
Anti-Inflamatórios não Esteroides , Doenças Cardiovasculares , Espondilite Anquilosante , Humanos , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/complicações , Espondilite Anquilosante/epidemiologia , Masculino , Feminino , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Adulto , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/induzido quimicamente , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/induzido quimicamente , Relação Dose-Resposta a Droga , Modelos de Riscos Proporcionais , Estudos de Coortes , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/induzido quimicamente , Fatores de Risco , Incidência
17.
Nat Commun ; 15(1): 2913, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575609

RESUMO

Carbaporphyrin dimers, investigated for their distinctive electronic structures and exceptional properties, have predominantly consisted of systems containing identical subunits. This study addresses the associated knowledge gap by focusing on asymmetric carbaporphyrin dimers with Janus-like characteristics. The synthesis of a Janus-type carbaporphyrin pseudo-dimer 5 is presented. It displays antiaromatic characteristics on the fused side and nonaromatic behavior on the unfused side. A newly synthesized tetraphenylene (TPE) linked bis-dibenzihomoporphyrin 8 and a previously reported dibenzo[g,p]chrysene (DBC) linked bis-dicarbacorrole 9 were prepared as controls. Comprehensive analyses, including 1H NMR spectral studies, single crystal X-ray diffraction analyses, and DFT calculations, validate the mixed character of 5. A further feature of the Janus pseudo-dimer 5 is that it may be transformed into a heterometallic complex, with one side coordinating a Cu(III) center and the other stabilizing a BODIPY complex. This disparate regiochemical reactivity underscores the potential of carbaporphyrin dimers as versatile frameworks, with electronic features and site-specific coordination chemistry controlled through asymmetry. These findings position carbaporphyrin dimers as promising candidates for advances in electronic structure studies, coordination chemistry, materials science, and beyond.

18.
ACS Appl Mater Interfaces ; 16(15): 19121-19136, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38588341

RESUMO

Plate-type hollow black TiO2 (HL/BT) with a high NIR reflectance was fabricated for the first time as a LiDAR-detectable black material. A TiO2 layer was formed on commercial-grade glass by using the sol-gel method to obtain a plate-type structure. The glass template was then etched with hydrofluoric acid to form a hollow structure, and blackness was further achieved through NaBH4 reduction, which altered the oxidation state of TiO2 to black TixO2x-1 or Ti4+ to Ti3+ and Ti2+. The blackness of the HL/BT material was maintained by a novel approach that involved etching prior to reduction. The thickness of the TiO2 layer was controlled to maximize the NIR reflectance when applied as paint. The HL/BT material with a thickness of 140 nm (HL/BT140) showed a blackness (L*) of 13.3 and high NIR reflectance of 23.6% at a wavelength of 905 nm. This is attributed to the effective light reflection at the interface created by the TiO2 layer and the hollow structure. Plate-type HL/BT140 provides excellent spreadability, durability, and thermal stability in practical paint applications compared with sphere-type materials due to the higher contacting area to the applied surface, making it suitable for use as a LiDAR-detectable inorganic black pigment in autonomous environments.

19.
Clin Exp Rheumatol ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38634363

RESUMO

OBJECTIVES: This study aimed to identify the risk factors associated with overall adverse events (AEs) and infections in patients with rheumatoid arthritis (RA) and comorbid interstitial lung disease (ILD), receiving biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs), using data from the Korean College of Rheumatology Biologics registry. METHODS: We analysed data from a cohort of 2,266 adult patients with RA who received b/tsDMARDs, including 169 patients with comorbid ILD. We identified the risk factors for overall AEs and infections in both the all RA group and the subgroup of patients with RA-ILD and investigated the impact of infections on mortality in patients with RA-ILD. RESULTS: Among all patients with RA, 45.7% withdrew b/tsDMARDs, whereas among those with RA-ILD, a higher proportion of 57.4% withdrew their treatment regimen. The main reason for withdrawing b/tsDMARDs in the RA-ILD group was AEs, with infections accounting for the largest proportion of reported AEs. In multivariable analysis of the risk factors for overall AEs and infections in the RA-ILD group, older age was identified as a risk factor for overall AEs (odds ratio [OR], 3.01; p=0.014), and only a current smoking status was identified as a risk factor for infections (OR, 2.11; p=0.035). CONCLUSIONS: Patients with RA-ILD exhibited a higher rate of b/tsDMARDs withdrawal due to overall AEs and infections than those with RA without ILD. In the RA-ILD group, older age was identified as a risk factor for overall AEs, whereas a current smoking status was identified as a risk factor for infections.

20.
J Colloid Interface Sci ; 667: 663-678, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38670010

RESUMO

HYPOTHESIS: The development of highly NIR reflective black single-shell hollow nanoparticles (BSS-HNPs) can overcome the Light Detection and Ranging (LiDAR) sensor limitations of dark-tone materials. The crystalline phase of TiO2 and the refractive index can be controlled by calcination temperature. The formation of hollow structure and the refractive index is expected to simultaneously increase the light reflection and LiDAR detectability. EXPERIMENTS: The BSS-HNPs are synthesized using the sol-gel method, calcination, NaBH4 reduction, and etching to form a hollow structure with true blackness. The computational bandgap calculation is conducted to determine the bandgap energy (Eg) of the white and black TiO2 with different crystalline structures. The blackness of the as-synthesized materials is determined by the Commission on Illumination (CIE) L*a*b* color system. FINDINGS: The hydrophilic nature of BSS-HNPs enables the formulation of hydrophilic paints, allowing the mono-layer coating. With the synergistic effects of hollow structure and the refractive index, BSS-HNPs manifested superb NIR reflectance at LiDAR detection wavelengths. The high detectability, blackness, and hollow structure of BSS-HNPs can expand the variety of LiDAR-detectable dark-tone materials.

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