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1.
Nat Commun ; 15(1): 4672, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824151

RESUMO

The oxygen evolution reaction, which involves high overpotential and slow charge-transport kinetics, plays a critical role in determining the efficiency of solar-driven water splitting. The chiral-induced spin selectivity phenomenon has been utilized to reduce by-product production and hinder charge recombination. To fully exploit the spin polarization effect, we herein propose a dual spin-controlled perovskite photoelectrode. The three-dimensional (3D) perovskite serves as a light absorber while the two-dimensional (2D) chiral perovskite functions as a spin polarizer to align the spin states of charge carriers. Compared to other investigated chiral organic cations, R-/S-naphthyl ethylamine enable strong spin-orbital coupling due to strengthened π-π stacking interactions. The resulting naphthyl ethylamine-based chiral 2D/3D perovskite photoelectrodes achieved a high spin polarizability of 75%. Moreover, spin relaxation was prevented by employing a chiral spin-selective L-NiFeOOH catalyst, which enables the secondary spin alignment to promote the generation of triplet oxygen. This dual spin-controlled 2D/3D perovskite photoanode achieves a 13.17% of applied-bias photon-to-current efficiency. Here, after connecting the perovskite photocathode with L-NiFeOOH/S-naphthyl ethylamine 2D/3D photoanode in series, the resulting co-planar water-splitting device exhibited a solar-to-hydrogen efficiency of 12.55%.

3.
J Neurol ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38839639

RESUMO

Video head impulse tests (video-HITs) are commonly used for vestibular evaluation; however, the results can be contaminated by various artifacts, including technical errors, recording problems, and participant factors. Although video-HITs can be used in patients with Parkinson's disease (PD), the effect of neck rigidity has not been systematically investigated. This study aimed to investigate the effect of neck rigidity on video-HIT results in patients with PD. We prospectively recruited 140 consecutive patients with PD (mean age ± standard deviation = 68 ± 10 years, 69 men) between September 2021 and April 2024 at Korea University Medical Center. The video-HIT results were compared with those of 19 age- and sex-matched healthy participants. Neck rigidity was stratified as a subdomain of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor part (MDS-UPDRS-III). In 59 patients, the vestibulo-ocular reflex (VOR) gain was overestimated in at least one canal plane (58/140, 41%), mostly in the anterior canal (AC, n = 44), followed by the horizontal (HC, n = 15) and posterior canals (PC, n = 7). VOR gain overestimation was also observed in patients with no (18/58, 35%), subtle (20/58, 34%), or mild (17/58, 29%) neck rigidity. Multivariable logistic regression analysis showed that VOR overestimation was positively associated with neck rigidity (odds ratio [OR] [95% confidence interval] = 1.51 [1.01-2.25], p = 0.043). The head velocities of patients decreased during head impulses for the AC (p = 0.033 for the right AC; p = 0.014 for the left AC), whereas eye velocities were similar to those of healthy participants. Our findings suggest that neck rigidity may be a confounder that can contaminate video-HIT results. Thus, the results of video-HITs, especially for the AC, should be interpreted with the context of head velocity during head impulses in patients with neck rigidity.

4.
Hip Pelvis ; 36(2): 120-128, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38825821

RESUMO

Purpose: The purpose of this study was to compare the clinical and radiographic outcomes with use of short-curved stems versus standard-length single wedged stems over a minimum follow-up period of five years. Materials and Methods: A retrospective study of primary total hip arthroplasties performed using the Fitmore® stem (127 hips, 122 patients) and the M/L taper® stem (195 hips, 187 patients) between October 2012 and June 2014 was conducted. The clinical and radiographic outcomes were obtained for evaluation over a minimum follow-up period of five years. Results: In both the Fitmore® and M/L taper® groups, the mean Harris hip score improved from 52.4 and 48.9 preoperatively to 93.3 and 94.5 at the final follow-up, respectively (P=0.980). The mean Western Ontario and McMaster Universities Osteoarthritis Index scores also improved from 73.3 and 76.8 preoperatively to 22.9 and 25.6 at the final follow-up, respectively (P=0.465). Fifteen hips (Fitmore®: 14 hips; M/L taper®: one hip, P<0.001) developed intraoperative cracks and were treated simultaneously with cerclage wiring. Radiography showed a radiolucent line in 24 hips in the Fitmore® group and 12 hips in the M/L taper® group (P=0.125). Cortical hypertrophy was detected in 29 hips (Fitmore® group: 28 hips; M/L taper® group: one hip, P<0.001). Conclusion: Similarly favorable clinical and radiographic outcomes were achieved with use of both short-curved stems and standard-length single wedged stems. However, higher cortical hypertrophy and a higher rate of femoral crack were observed with use of Fitmore® stems.

5.
Hip Pelvis ; 36(2): 155-160, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38825825

RESUMO

We report two cases of postoperative total hip arthroplasty periprostehtic fracture of the acetabulum which treated by open reduction with internal fixation without acetabular cup revision. From these cases, we should consider open reduction with internal fixation as the first treatment option in cases where spot welding of the cup to the host bone is observed.

6.
Discov Nano ; 19(1): 83, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714640

RESUMO

We present the first work of the synthesis mechanism from graphene quantum dots (GQDs) to carbon nanotubes (CNTs) by an ion-sputtering assisted chemical vapor deposition. During the annealing process, a Pt thin film deposited by the ion-sputtering was dewetted and agglomerated to form many nanometer-sized particles, leading to Pt nanoparticles (PtNPs) that can act as catalysts for creating carbon allotropes. The shape of the allotropes can be effectively tailored from GQDs to CNTs by controlling three key parameters such as the dose of catalytic ions (D), amounts of carbon source (S), and thermal energy (T). In our work, it was clearly proved that the growth control from GQDs to CNTs has a comparably proportional relationship with D and S, but has a reverse proportional relationship with T. Furthermore, high-purity GQDs without any other by-products and the CNTs with the cap of PtNPs were generated. Their shapes were appropriately controlled, respectively, based on the established synthesis mechanism.

7.
BMC Vet Res ; 20(1): 233, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38807154

RESUMO

Canine mammary gland tumors (MGT) have a poor prognosis in intact female canines, posing a clinical challenge. This study aimed to establish novel canine mammary cancer cell lines from primary tumors and characterize their cellular and molecular features to find potential therapeutic drugs. The MGT cell lines demonstrated rapid cell proliferation and colony formation in an anchorage-independent manner. Vimentin and α-SMA levels were significantly elevated in MGT cell lines compared to normal canine kidney (MDCK) cells, while CDH1 expression was either significantly lower or not detected at all, based on quantitative real-time PCR (qRT-PCR) analysis. Functional annotation and enrichment analysis revealed that epithelial-mesenchymal transition (EMT) phenotypes and tumor-associated pathways, particularly the PI3K/Akt signaling pathway, were upregulated in MGT cells. BYL719 (Alpelisib), a PI3K inhibitor, was also examined for cytotoxicity on the MGT cell lines. The results show that BYL719 can significantly inhibit the proliferation of MGT cell lines in vitro. Overall, our findings suggest that the MGT cell lines may be valuable for future studies on the development, progression, metastasis, and management of tumors.


Assuntos
Doenças do Cão , Neoplasias Mamárias Animais , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Animais , Cães , Feminino , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Doenças do Cão/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transdução de Sinais , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia
8.
Eye Vis (Lond) ; 11(1): 17, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711111

RESUMO

BACKGROUND: Artificial intelligence (AI) that utilizes deep learning (DL) has potential for systemic disease prediction using retinal imaging. The retina's unique features enable non-invasive visualization of the central nervous system and microvascular circulation, aiding early detection and personalized treatment plans for personalized care. This review explores the value of retinal assessment, AI-based retinal biomarkers, and the importance of longitudinal prediction models in personalized care. MAIN TEXT: This narrative review extensively surveys the literature for relevant studies in PubMed and Google Scholar, investigating the application of AI-based retina biomarkers in predicting systemic diseases using retinal fundus photography. The study settings, sample sizes, utilized AI models and corresponding results were extracted and analysed. This review highlights the substantial potential of AI-based retinal biomarkers in predicting neurodegenerative, cardiovascular, and chronic kidney diseases. Notably, DL algorithms have demonstrated effectiveness in identifying retinal image features associated with cognitive decline, dementia, Parkinson's disease, and cardiovascular risk factors. Furthermore, longitudinal prediction models leveraging retinal images have shown potential in continuous disease risk assessment and early detection. AI-based retinal biomarkers are non-invasive, accurate, and efficient for disease forecasting and personalized care. CONCLUSION: AI-based retinal imaging hold promise in transforming primary care and systemic disease management. Together, the retina's unique features and the power of AI enable early detection, risk stratification, and help revolutionizing disease management plans. However, to fully realize the potential of AI in this domain, further research and validation in real-world settings are essential.

9.
Int J Heart Fail ; 6(2): 56-69, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38694933

RESUMO

Background and Objectives: The number of people with heart failure (HF) is increasing worldwide, and the social burden is increasing as HF has high mortality and morbidity. We aimed to provide updated trends on the epidemiology of HF in Korea to shape future social measures against HF. Methods: We used the National Health Information Database of the National Health Insurance Service to determine the prevalence, incidence, hospitalization rate, mortality rate, comorbidities, in-hospital mortality, and healthcare cost of patients with HF from 2002 to 2020 in Korea. Results: The prevalence of HF in the total Korean population rose from 0.77% in 2002 to 2.58% (1,326,886 people) in 2020. Although the age-standardized incidence of HF decreased over the past 18 years, the age-standardized prevalence increased. In 2020, the hospitalization rate for any cause in patients with HF was 1,166 per 100,000 persons, with a steady increase from 2002. In 2002, the HF mortality was 3.0 per 100,000 persons, which rose to 15.6 per 100,000 persons in 2020. While hospitalization rates and in-hospital mortality for patients with HF increased, the mortality rate for patients with HF did not (5.8% in 2020), and the one-year survival rate from the first diagnosis of HF improved. The total healthcare costs for patients with HF were approximately $2.4 billion in 2020, a 16-fold increase over the $0.15 billion in 2002. Conclusions: The study's results underscore the growing socioeconomic burden of HF in Korea, driven by an aging population and increasing HF prevalence.

10.
Semin Arthritis Rheum ; 66: 152440, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38579593

RESUMO

BACKGROUND/PURPOSE: Vasculitis as an immune-related adverse event (irAE) from checkpoint inhibitor therapy (ICI) to treat cancer is a rare clinical event, and little is known regarding its nosology, clinical manifestations, or response to treatment and outcomes. METHODS: To address these gaps, we used the Preferred Reporting Items for Systemic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) framework to further define this complication. Two independent PUBMED searches in September and November of 2022 revealed 127 publications with 37 excluded from title by relevance, 43 excluded by article type, and 23 excluded due to lack of biopsy results, or biopsy negative for vasculitis. Twenty-nine documented cases from 24 publications were included for final analysis. Basic demographics, ICI details, timing of onset of vasculitis symptoms, irAE treatment and outcomes were collected. The vasculitides were classified using 2022 ACR/EULAR Vasculitis Classification Criteria as well as 2012 Revised Chapel-Hill Nomenclature. Adaptations from Naidoo et al. 2023 [1] consensus definitions for irAEs were used and efforts were made to classify steroid-responsive versus unresponsive irAEs. RESULTS: Of the 29 cases reviewed, the average age of patients was 62.1 ± 11.0, composed of 58.6 % (n = 17) male and 41.3 % (n = 12) female. Prominent cancer types were lung cancer (41.4 %; n = 12), melanoma (41.4 %; n = 12), and renal cancer (10.3 %; n = 3), with majority being stage 4 (75.9 %, n = 22) and stage 3 (10.3 %, n = 3). Only 8 cases met the ACR/EULAR criteria, and by Chapel-Hill Nomenclature, approximately a third were small-vessel vasculitis (31.0 %; n = 9) with n = 4 positive for ANCA. Most biopsies were taken from the skin (37.9 %, n = 11) and kidney (24.1 %, n = 7). Patients were either treated with single (65.5 %, n = 19), dual (17.2 %; n = 5), or sequential (17.2 %; n = 5) ICI regimen which included anti-PD-1 therapy in all but one case, with mean of 8.7 ± 10.5 cycles received. Mean time to onset of symptoms from start of ICI was 7.2 ± 7.8 months, with 55.2 % occurring >3 months since the initial immunotherapy. Vasculitis treatment included glucocorticoids in 96 % of cases and immunotherapy was often discontinued (44.8 %; n = 13). Clinical improvement of irAE was documented in 86.2 % (n = 25). Data were missing in terms of fate of ICI (34.5 %; n = 10) and tumor outcomes (41.4 %; n = 12). Cancer progressed in 20.7 % (n = 6), stable in 34.5 % (n = 10) cases, and 6 patients died of all-causes. CONCLUSION: Vasculitis as an irAE appears clinically heterogeneous and rare. Among reported cases with adequate documentation, vasculitis is of delayed onset following the initiation of immunotherapy. Outcomes of ICI-vasculitis were generally favorable, responding to glucocorticoids and immunotherapy withdrawal. There is an urgent need for more standardized reporting of rare irAEs such as vasculitis to clarify clinical risks, classification, relationship to immunotherapy and outcomes.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Vasculite , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Vasculite/induzido quimicamente , Vasculite/imunologia , Idoso
11.
bioRxiv ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38585873

RESUMO

Lysosomal storage diseases (LSDs) comprised ~50 monogenic diseases characterized by the accumulation of cellular material in lysosomes and associated defects in lysosomal function, but systematic molecular phenotyping is lacking. Here, we develop a nanoflow-based multi-omic single-shot technology (nMOST) workflow allowing simultaneously quantify HeLa cell proteomes and lipidomes from more than two dozen LSD mutants, revealing diverse molecular phenotypes. Defects in delivery of ferritin and its autophagic receptor NCOA4 to lysosomes (ferritinophagy) were pronounced in NPC2-/- cells, which correlated with increased lyso-phosphatidylcholine species and multi-lamellar membrane structures visualized by cryo-electron-tomography. Ferritinophagy defects correlated with loss of mitochondrial cristae, MICOS-complex components, and electron transport chain complexes rich in iron-sulfur cluster proteins. Strikingly, mitochondrial defects were alleviated when iron was provided through the transferrin system. This resource reveals how defects in lysosomal function can impact mitochondrial homeostasis in trans and highlights nMOST as a discovery tool for illuminating molecular phenotypes across LSDs.

12.
Clin Auton Res ; 34(2): 269-279, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38652421

RESUMO

PURPOSE: The specific characteristics of autonomic involvement in patients with early Parkinson's disease (PD) are unclear. This study aimed to evaluate the characteristics of autonomic dysfunction in drug-naïve patients with early-stage PD without orthostatic hypotension (OH) by analyzing Valsalva maneuver (VM) parameters. METHODS: We retrospectively analyzed drug-naïve patients without orthostatic hypotension (n = 61) and controls (n = 20). The patients were subcategorized into early PD (n = 35) and mid-PD (n = 26) groups on the basis of the Hoehn and Yahr staging. VM parameters, including changes in systolic blood pressure at late phase 2 (∆SBPVM2), ∆HRVM3, Valsalva ratio (VR), pressure recovery time, adrenergic baroreflex sensitivity, and vagal baroreflex sensitivity, were assessed. RESULTS: In the early PD group, ∆SBPVM2, a marker of sympathetic function, was significantly lower compared with that in controls (risk ratio = 0.95, P = 0.027). Receiver operating characteristic (ROC) curve analysis showed an optimal cut-off value of -10 mmHg for ∆SBPVM2 [P = 0.002, area under the curve (AUC): 0.737]. VR exhibited an inverse relationship with Unified Parkinson's Disease Rating Scale Part 3 scores in the multivariable regression analysis (VR: P = 0.038, ß = -28.61), whereas age showed a positive relationship (age: P = 0.027, ß = 0.35). CONCLUSION: The ∆BPVM2 parameter of the VM may help detect autonomic nervous system involvement in early-PD without OH. Our results suggest that sympathetic dysfunction is an early manifestation of autonomic dysfunction in patients with PD.


Assuntos
Doenças do Sistema Nervoso Autônomo , Barorreflexo , Doença de Parkinson , Manobra de Valsalva , Humanos , Doença de Parkinson/fisiopatologia , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Masculino , Feminino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/etiologia , Manobra de Valsalva/fisiologia , Barorreflexo/fisiologia , Sistema Nervoso Simpático/fisiopatologia , Pressão Sanguínea/fisiologia
13.
JAMA Netw Open ; 7(4): e246878, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38630474

RESUMO

Importance: The associations between blood pressure (BP) decreases induced by medication and functional outcomes in patients with successful endovascular thrombectomy remain uncertain. Objective: To evaluate whether BP reductions induced by intravenous BP medications are associated with poor functional outcomes at 3 months. Design, Setting, and Participants: This cohort study was a post hoc analysis of the Outcome in Patients Treated With Intra-Arterial Thrombectomy-Optimal Blood Pressure Control trial, a comparison of intensive and conventional BP management during the 24 hours after successful recanalization from June 18, 2020, to November 28, 2022. This study included 302 patients who underwent endovascular thrombectomy, achieved successful recanalization, and exhibited elevated BP within 2 hours of successful recanalization at 19 stroke centers in South Korea. Exposure: A BP decrease was defined as at least 1 event of systolic BP less than 100 mm Hg. Patients were divided into medication-induced BP decrease (MIBD), spontaneous BP decrease (SpBD), and no BP decrease (NoBD) groups. Main Outcomes and Measures: The primary outcome was a modified Rankin scale score of 0 to 2 at 3 months, indicating functional independence. Primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and mortality due to index stroke within 3 months. Results: Of the 302 patients (median [IQR] age, 75 [66-82] years; 180 [59.6%] men), 47 (15.6%)were in the MIBD group, 39 (12.9%) were in the SpBD group, and 216 (71.5%) were in the NoBD group. After adjustment for confounders, the MIBD group exhibited a significantly smaller proportion of patients with functional independence at 3 months compared with the NoBD group (adjusted odds ratio [AOR], 0.45; 95% CI, 0.20-0.98). There was no significant difference in functional independence between the SpBD and NoBD groups (AOR, 1.41; 95% CI, 0.58-3.49). Compared with the NoBD group, the MIBD group demonstrated higher odds of mortality within 3 months (AOR, 5.15; 95% CI, 1.42-19.4). The incidence of symptomatic intracerebral hemorrhage was not significantly different among the groups (MIBD vs NoBD: AOR, 1.89; 95% CI, 0.54-5.88; SpBD vs NoBD: AOR, 2.75; 95% CI, 0.76-9.46). Conclusions and Relevance: In this cohort study of patients with successful endovascular thrombectomy after stroke, MIBD within 24 hours after successful recanalization was associated with poor outcomes at 3 months. These findings suggested lowering systolic BP to below 100 mm Hg using BP medication might be harmful.


Assuntos
Hipertensão , Acidente Vascular Cerebral , Idoso , Feminino , Humanos , Masculino , Pressão Sanguínea , Hemorragia Cerebral , Estudos de Coortes , Hipertensão/epidemiologia , Pressão , Acidente Vascular Cerebral/cirurgia , Idoso de 80 Anos ou mais
14.
Eye (Lond) ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38653749

RESUMO

BACKGROUND/OBJECTIVES: To determine long-term outcomes of patients referred with proliferative diabetic retinopathy (PDR) from diabetic eye screening programmes (DESP) to tertiary care centres in the United Kingdom (UK). METHODS: Retrospective multicentre study of patients referred from two DESPs in the UK over a 36-month period (2007-9) and followed-up for 10 years. Critical outcomes included severe vision loss (SVL) and the need for vitrectomy. Other outcomes assessed included moderate vision loss (MVL), and patient survival time. Univariate and multiple variable Cox proportional hazards regressions were used to analyse survival outcomes. RESULTS: 212 eyes of 150 patients were referred with a diagnosis of PDR. 109 eyes of 72 patients were confirmed to have active PDR and included in the study. 61% of patients had low-risk PDR, while 39% exhibited high-risk features in at least one eye. Eight (7.3%) eyes developed SVL and 16 (14.7%) MVL during follow up. Vitrectomy was required in 24% (95% CI: 15 to 31%) of all PDR eyes and was most commonly performed for vitreous haemorrhage (65%). The 10-year survival in all PDR patients was 76% (95% CI: 63 to 85%) with the mean time to death for all deceased patients being 5.4 ± 3.6 years. On multivariable analysis, only age was found to have a significant association with the survival of patients with PDR. CONCLUSIONS: During the 10 year follow up SVL was uncommon, but MVL occurred in almost one-fifth of the eyes. Approximately 1 in 4 eyes required vitrectomy, highlighting its significance in patient management.

15.
Jpn J Infect Dis ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38684427

RESUMO

The accurate identification of individuals without prior infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pivotal for seroepidemiological research and vaccine trials. Because of widespread COVID-19 vaccination, the anti-nucleocapsid antibody continues to serve as a valuable marker for individuals without a history of COVID-19. This study aimed to comprehensively assess anti-nucleocapsid antibody positivity using diverse commercial and in-house immunoassays among individuals who contracted COVID-19 more than 3 years ago. We enrolled 44 participants with laboratory-confirmed COVID-19 between January and May 2020 from Seoul National University Hospital and its community treatment centers. The results showed anti-nucleocapsid antibody positivities ranged from 45.5% to 87.9% depending upon the immunoassay used. The study highlights the importance of considering the limited anti-nucleocapsid antibody positivity in participants with a distant COVID-19 history in seroepidemiological or vaccine research.

16.
Biomater Sci ; 12(9): 2445, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38598178

RESUMO

Correction for 'Hybrid protein microspheres and their responsive release behaviors and inhibitory effects on melanin synthesis' by Ee Taek Hwang et al., Biomater. Sci., 2024, https://doi.org/10.1039/d4bm00106k.

17.
Clin Cancer Res ; 30(9): 1788-1800, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38587547

RESUMO

PURPOSE: Prostate-specific membrane antigen (PSMA)-based images, which visually quantify PSMA expression, are used to determine prostate cancer micrometastases. This study evaluated whether a circulating tumor cell (CTC)-based transcript platform, including PSMA mRNA, could help identify potential prognostic markers in prostate cancer. EXPERIMENTAL DESIGN: We prospectively enrolled 21 healthy individuals and 247 patients with prostate cancer [localized prostate cancer (LPCa), n = 94; metastatic hormone-sensitive prostate cancer (mHSPC), n = 44; and metastatic castration-resistant prostate cancer (mCRPC), n = 109]. The mRNA expression of six transcripts [PSMA, prostate-specific antigen (PSA), AR, AR-V7, EpCAM, and KRT 19] from CTCs was measured, and their relationship with biochemical recurrence (BCR) in LPCa and mCRPC progression-free survival (PFS) rate in mHSPC was assessed. PSA-PFS and radiological-PFS were also calculated to identify potential biomarkers for predicting androgen receptor signaling inhibitor (ARSI) and taxane-based chemotherapy resistance in mCRPC. RESULTS: CTC detection rates were 75.5%, 95.3%, and 98.0% for LPCa, mHSPC, and mCRPC, respectively. In LPCa, PSMA [hazard ratio (HR), 3.35; P = 0.028) and PSA mRNA (HR, 1.42; P = 0.047] expressions were associated with BCR. Patients with mHSPC with high PSMA (HR, 4.26; P = 0.020) and PSA mRNA (HR, 3.52; P = 0.042) expressions showed significantly worse mCRPC-PFS rates than those with low expression. Increased PSA and PSMA mRNA expressions were significantly associated with shorter PSA-PFS and radiological PFS in mCPRC, indicating an association with drug resistance. CONCLUSIONS: PSMA and PSA mRNA expressions are associated with BCR in LPCa. In advanced prostate cancer, PSMA and PSA mRNA can also predict rapid progression from mHSPC to mCRPC and ARSI or taxane-based chemotherapy resistance.


Assuntos
Antígenos de Superfície , Biomarcadores Tumorais , Glutamato Carboxipeptidase II , Estadiamento de Neoplasias , Células Neoplásicas Circulantes , Antígeno Prostático Específico , Humanos , Masculino , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Antígeno Prostático Específico/sangue , Idoso , Glutamato Carboxipeptidase II/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Antígenos de Superfície/genética , Antígenos de Superfície/metabolismo , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso de 80 Anos ou mais , Estudos Prospectivos , Calicreínas/sangue , Calicreínas/genética , Regulação Neoplásica da Expressão Gênica
19.
Materials (Basel) ; 17(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38473587

RESUMO

The spring-in phenomenon of the composite parts can affect the assembly process. This study aims to predict the spring-in phenomenon of a carbon fiber reinforced plastic (CFRP) part. Here, we predict the spring-in of the CFRP part using a coupled analysis of the forming and cooling processes during the stamping process. First, a simulation of the entire forming process, such as the transfer of the composite laminate, gravity analysis, and forming was performed to obtain the temperature distribution of the CFRP part. Subsequently, a finite-element (FE) simulation of the cooling process was conducted to predict the spring-in phenomenon of the shaped CFRP part using the temperature data obtained in the forming simulation. Finally, a CFRP part was manufactured and compared with the results of the FE simulation.

20.
iScience ; 27(3): 109256, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38455976

RESUMO

To address the challenge of solid tumor targeting in CAR-T therapy, we utilized the A56 antigen, which is uniquely expressed on a diverse range of cancer cells following the systemic administration of an oncolytic vaccinia virus (OVV). Immunohistochemical assays precisely confirmed exclusive localization of A56 to tumor tissues. In vitro studies demonstrated a distinct superiority of A56-dependent CAR-T cytotoxicity across multiple cancer cell lines. Building on these in vitro observations, we strategically administered A56 CAR-T cells, OVV, and hydroxyurea (HU) combination in HCT-116 tumor-bearing non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, leading to a significant reduction in tumor size and an extended time to progression. Consequently, A56-targeting combinatorial immunotherapy provides the benefit of reducing inadvertent CAR-T effects on normal cells while preserving its effectiveness against cancer cells. Furthermore, our approach of implanting A56 via OVV on tumors facilitates a wide therapeutic application of CAR-T cells across various solid tumors.

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