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1.
Front Cardiovasc Med ; 11: 1306055, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38689859

RESUMO

Introduction: Signal-averaged electrocardiography (SAECG) provides diagnostic and prognostic information regarding cardiac diseases. However, its value in other nonischemic cardiomyopathies (NICMs) remains unclear. This study aimed to investigate the role of SAECG in patients with NICM. Methods and results: This retrospective study included consecutive patients with NICM who underwent SAECG, biventricular substrate mapping, and ablation for ventricular arrhythmia (VA). Patients with baseline ventricular conduction disturbances were excluded. Patients who fulfilled at least one SAECG criterion were categorized into Group 1, and the other patients were categorized into Group 2. Baseline and ventricular substrate characteristics were compared between the two groups. The study included 58 patients (39 men, mean age 50.4 ± 15.5 years), with 34 and 24 patients in Groups 1 and 2, respectively. Epicardial mapping was performed in eight (23.5%) and six patients (25.0%) in Groups 1 and 2 (p = 0.897), respectively. Patients in Group 1 had a more extensive right ventricular (RV) low-voltage zone (LVZ) and scar area than those in Group 2. Group 1 had a larger epicardial LVZ than Group 2. Epicardial late potentials were more frequent in Group 1 than in Group 2. There were more arrhythmogenic foci within the RV outflow tract in Group 1 than in Group 2. There was no significant difference in long-term VA recurrence. Conclusion: In our NICM population, a positive SAECG was associated with a larger RV endocardial scar, epicardial scar/late potentials, and a higher incidence of arrhythmogenic foci in the RV outflow tract.

2.
Methods Appl Fluoresc ; 12(3)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702877

RESUMO

In this research, we synthesized and constructed a novel gelator (namedQN) combining quinoline and naphthalene that self-assembled in N, N-dimethylformamide (DMF) to form a stable supramolecular gel (namedOQN). Under UV light, gelOQNexhibited extremely bright yellow fluorescence. The gelOQNshowed excellent sensing performance for both Fe3+and Cu2+, with a fluorescence 'turn-off' detection mechanism and the lowest detection limit of 7.58 × 10-8M and 1.51 × 10-8M, respectively. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectra, x-ray powder diffraction (XRD), rheological measurements, x-ray photoelectron spectroscopy (XPS), and fluorescence spectroscopy were used to characterize the gelOQN. TheOQNion-responsive membrane created is an excellent fluorescent writing material.

3.
J Agric Food Chem ; 72(20): 11331-11340, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38721769

RESUMO

Research on mesoionic structures in pesticide design has gained significant attention in recent years. However, the 1-position of pyridino[1,2-a]pyrimidine is usually designed with 2-chlorothiazole, 2-chloropyridine, or cyano moieties commonly found in neonicotinoid insecticides. In order to enrich the available pharmacophore library, here, we disclose a series of new pyridino[1,2-a]pyrimidine mesoionics bearing indole-containing substituents at the 1-position. Most of these target compounds are confirmed to have good insecticidal activity against aphids through bioevaluation. In addition, a three-dimensional structure-activity relationship model is established to allow access to optimal compound F45 with an LC50 value of 2.97 mg/L. This value is comparable to the property achieved by the positive control triflumezopyrim (LC50 = 2.94 mg/L). Proteomics and molecular docking analysis suggest that compound F45 has the potential to modulate the functioning of the aphid nervous system through its interaction with neuronal nicotinic acetylcholine receptors. This study expands the existing pharmacophore library for the future development of new mesoionic insecticides based on 1-position modifications of the pyridino[1,2-a]pyrimidine scaffold.


Assuntos
Afídeos , Desenho de Fármacos , Indóis , Inseticidas , Simulação de Acoplamento Molecular , Pirimidinas , Inseticidas/química , Inseticidas/síntese química , Inseticidas/farmacologia , Animais , Pirimidinas/química , Pirimidinas/farmacologia , Pirimidinas/síntese química , Afídeos/efeitos dos fármacos , Indóis/química , Indóis/farmacologia , Indóis/síntese química , Relação Estrutura-Atividade , Estrutura Molecular , Receptores Nicotínicos/metabolismo , Receptores Nicotínicos/química , Receptores Nicotínicos/efeitos dos fármacos
4.
Artigo em Inglês | MEDLINE | ID: mdl-38632022

RESUMO

BACKGROUND: The prognosis for people living with HIV (PLWH) who develop lymphomas has been greatly improved by combination antiretroviral therapy (cART) and anti-CD20 monoclonal antibodies. However, real-world clinical data on this patient group in Asia are limited. METHODS: Treatment outcomes were retrospectively examined for 104 PLWH with lymphomas between 2000 and 2019. The cohort comprised five PLWH with Hodgkin lymphoma (HL) and 99 with non-Hodgkin lymphomas, including 61 with diffuse large B-cell lymphoma (DLBCL), 19 with Burkitt lymphoma (BL), nine with primary central nervous system lymphoma (PCNSL) and ten with other subtypes. RESULTS: The 5-year overall survival (OS) rates were as follows: HL (100%), PCNSL (76.2%), other subtypes (60.0%), BL (57.4%), and DLBCL (55.6%). Individuals who achieved complete response (CR) to front-line therapies had a significantly better 5-year OS rate than those without (96.2% vs. 17.8%, p < 0.001). PLWH who received cART for ≤6 months had significantly lower CD4+ T-cell counts at lymphoma diagnosis than those who received cART for longer periods (p = 0.048). Additionally, the 5-year OS rate was better for PLWH who received cART for ≤6 months before lymphomas diagnosis than those who received cART for longer periods (64.5% vs. 51.9%, p = 0.114). CONCLUSIONS: PLWH with DLBCL or BL had OS rates compatible to patients without HIV infection. Better outcomes for patients achieving CR to front-line therapy and those with shorter cART duration before lymphoma diagnosis suggest an underlying biological distinction in the lymphomas and the involvement of immunity, which warrants further studies.

5.
Nurse Educ Today ; 138: 106155, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38603829

RESUMO

BACKGROUND: Good nursing leadership management positively correlates with patient care quality and an organization's performance. Plans to nurture top-notch talents and strengthen management functions are essential to retain key talents and achieve sustainability. The leadership training for nursing staff should begin early to cope with complex clinical situations. OBJECTIVES: To compare the impact of leadership training on high-performing young nurses' (young nursing elite) management functions and team behavior. SETTING: A public teaching hospital in Taipei, Taiwan. METHODS: This research implemented a longitudinal quasi-experimental study with a fixed time series design; the target subjects were youth nursing elites who received training, along with their direct managers and peers, for a total of 102 participants. The training course intervention included the classroom teaching of leadership management functions, arranging internships in the hospital's internal administrative units and professional nursing institutions, and the direct managers sharing their experiences during teaching. We measured the outcome indicators before the course intervention, at the end of the course intervention, and three months after using the management function and team behavior scales. RESULTS: The mean score of the direct managers' assessments regarding the youth nursing elite's pre-test team behavior was 4.18. This improved by 0.68 points (p < .001) after the program intervention and improved by 0.65 points (p < .001) three months after the program compared to the pre-test. There was no statistically significant difference between the two groups as analyzed using GEE. The mean score of the pre-test self-assessment management function of the young nursing elite was 3.27. This improved by 1.06 points (p < .001) after the program intervention and by 1.14 points (p < .001) three months after the program compared to the pre-test. There was no statistically significant difference between the three groups using GEE analysis. CONCLUSIONS: Leadership training enhances young nursing professionals' leadership function and team behavior.


Assuntos
Hospitais de Ensino , Liderança , Humanos , Taiwan , Estudos Longitudinais , Feminino , Masculino , Adulto , Recursos Humanos de Enfermagem Hospitalar/educação
6.
Chem Biol Interact ; 395: 111013, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38663798

RESUMO

Ulcerative colitis is a chronic disease with colonic mucosa injury. Nitazoxanide is an antiprotozoal drug in clinic. Nitazoxanide and its metabolite tizoxanide have been demonstrated to activate AMPK and inhibit inflammation, therefore, the aim of the present study is to investigate the effect of nitazoxanide on dextran sulfate sodium (DSS)-induced colitis and the underlying mechanism. Oral administration of nitazoxanide ameliorated the symptoms of mice with DSS-induced colitis, as evidenced by improving the increased disease activity index (DAI), the decreased body weight, and the shortened colon length. Oral administration of nitazoxanide ameliorated DSS-induced intestinal barrier dysfunction and reduced IL-6 and IL-17 expression in colon tissues. Mechanistically, nitazoxanide and its metabolite tizoxanide treatment activated AMPK and inhibited JAK2/STAT3 signals. Nitazoxanide and tizoxanide treatment increased caudal type homeobox 2 (CDX2) expression, increased alkaline phosphatase (ALP) activity and promoted tight junctions in Caco-2 cells. Nitazoxanide and tizoxanide treatment restored the decreased zonula occludens-1(ZO-1) and occludin protein levels induced by LPS or IL-6 in Caco-2 cells. On the other hand, nitazoxanide and tizoxanide regulated macrophage bias toward M2 polarization, as evidenced by the increased arginase-1expression in bone marrow-derived macrophages (BMDM). Nitazoxanide and tizoxanide reduced the increased IL-6, iNOS and CCL2 pro-inflammatory gene expressions and inhibited JAK2/STAT3 activation in BMDM induced by LPS. In conclusion, nitazoxanide protects against DSS-induced ulcerative colitis in mice through improving intestinal barrier and inhibiting inflammation and the underlying mechanism involves AMPK activation and JAK2/STAT3 inhibition.


Assuntos
Colite Ulcerativa , Sulfato de Dextrana , Mucosa Intestinal , Nitrocompostos , Fator de Transcrição STAT3 , Tiazóis , Animais , Tiazóis/farmacologia , Tiazóis/uso terapêutico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colite Ulcerativa/metabolismo , Nitrocompostos/farmacologia , Camundongos , Humanos , Células CACO-2 , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Sulfato de Dextrana/toxicidade , Fator de Transcrição STAT3/metabolismo , Masculino , Janus Quinase 2/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Inflamação/tratamento farmacológico , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Interleucina-6/metabolismo , Modelos Animais de Doenças
7.
BMC Cardiovasc Disord ; 24(1): 150, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475731

RESUMO

BACKGROUND AND AIMS: The present study aimed to investigate the predictive ability of selected adiposity indices, such as body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC), and waist-to-height ratio (WHtR), for new-onset hypertension in metabolically healthy Taiwanese adults. The study also sought to establish sex-specific cutoff points for these indices and to analyze the risk of new-onset hypertension, taking into account sex and age. METHODS: This prospective cohort study utilized the Taiwan Biobank database to examine metabolically healthy participants aged between 20 and 65 at baseline. Four adiposity indices, namely BMI, WHR, WC, and WHtR, were calculated and used to predict new-onset hypertension over 4 years. Receiver operating characteristics (ROCs) and areas under the curve (AUCs) were used to evaluate the effectiveness of the parameters in predicting new-onset hypertension over 4 years. Sex-specific cutoff points were identified and used to assess the risk of new-onset hypertension. RESULTS: This study analyzed 13,375 participants over 4.28 years. The incidence of new-onset hypertension was 17.65%. The new-onset rate of hypertension was 34.39% in men and 65.61% in women. Adiposity indices effectively predict new-onset hypertension, with WHtR having the highest predictive value (i.e., AUC) for both sexes. The classification of participants into low and high categories for each adiposity index was based on sex-specific cutoff points, and the risk of new-onset hypertension was assessed according to sex and age. This study found that high adiposity indices predicted a significantly higher risk of new-onset hypertension in metabolically healthy adults. The risk was equal for both sexes. Young women had a higher risk of new-onset hypertension than middle-aged women when they were further categorized. All risk ratios of the indices in young women were over two-fold and significant. CONCLUSION: According to the sex-specific cutoff point, high adiposity indices had a higher predictive value for new-onset hypertension in metabolically healthy Taiwanese young women.


Assuntos
Adiposidade , Hipertensão , Adulto , Pessoa de Meia-Idade , Masculino , Humanos , Feminino , Adulto Jovem , Idoso , Estudos Prospectivos , Fatores de Risco , Obesidade/epidemiologia , Índice de Massa Corporal , Relação Cintura-Quadril , Circunferência da Cintura , Razão Cintura-Estatura
8.
Artigo em Inglês | MEDLINE | ID: mdl-38480093

RESUMO

BACKGROUND: Patients with hematological malignancies (HM) were at a high risk of developing severe disease from coronavirus disease 2019 (COVID-19). We aimed to assess the clinical outcome of COVID-19 in hospitalized patients with HM. METHODS: Adult patients with HM who were hospitalized with a laboratory-confirmed COVID-19 between May, 2021 and November, 2022 were retrospectively identified. Primary outcome was respiratory failure requiring mechanical ventilation or mortality within 60 days after hospitalization. We also analyzed associated factors for de-isolation (defined as defervescence with a consecutive serial cycle threshold value > 30) within 28 days. RESULTS: Of 152 eligible patients, 22 (14.5%) developed respiratory failure or mortality in 60 days. Factors associated with developing respiratory failure that required mechanical ventilation or mortality included receipt of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) (adjusted hazards ratio [aHR], 5.10; 95% confidence interval [CI], 1.64-15.85), type 2 diabetes mellitus (aHR, 2.47; 95% CI, 1.04-5.90), lymphopenia at admission (aHR, 6.85; 95% CI, 2.45-19.15), and receiving <2 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines (aHR, 3.00; 95% CI, 1.19-7.60). Ninety-nine (65.1%) patients were de-isolated in 28 days, against which two hazardous factors were identified: receipt of B-cell depletion therapies within one year prior to COVID-19 (aHR, 0.55, 95% CI, 0.35-0.87) and lymphopenia upon admission (aHR, 0.65; 95% CI, 0.43-1.00). CONCLUSION: We found a high rate of respiratory failure and mortality among patients with HM who contracted the SARS-CoV-2. Factors associated with developing respiratory failure or mortality in 60 days included receipt of allo-HSCT, type 2 diabetes mellitus and lymphopenia upon admission. Having received ≥2 doses of vaccination conferred protection against clinical progression.

9.
bioRxiv ; 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38496667

RESUMO

Nutrient sensing and the subsequent metabolic responses are fundamental functions of animals, closely linked to diseases such as type 2 diabetes and various obesity-related diseases. Drosophila melanogaster has emerged as an excellent model for investigating metabolism and its associated disorders. In this study, we used live-cell imaging to demonstrate that the fly functional homolog of mammalian glucagon, Adipokinetic hormone (AKH), secreted from AKH hormone-producing cells (APCs) in the corpora cardiaca, stimulates intracellular Ca 2+ waves in the larval fat body/adipose tissue to promote lipid metabolism. Further, we show that specific dietary amino acids activate the APCs, leading to increased intracellular Ca 2+ and subsequent AKH secretion. Finally, a comparison of Ca 2+ dynamics in larval and adult fat bodies revealed different mechanisms of regulation, highlighting the interplay of pulses of AKH secretion, extracellular diffusion of the hormone, and intercellular communication through gap junctions. Our study underscores the suitability of Drosophila as a powerful model for exploring real-time nutrient sensing and inter-organ communication dynamics.

10.
J Xray Sci Technol ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38552134

RESUMO

Highlights: • Introduce a data augmentation strategy to expand the required different morphological data during the training and learning phase, and improve the algorithm's feature learning ability for complex and diverse tumor morphology CT images.• Design attention mechanisms for encoding and decoding paths to extract fine pixel level features, improve feature extraction capabilities, and achieve efficient spatial channel feature fusion.• The deep supervision layer is used to correct and decode the final image data to provide high accuracy of results.• The effectiveness of this method has been affirmed through validation on the LITS, 3DIRCADb, and SLIVER datasets. BACKGROUND: Accurately extracting liver and liver tumors from medical images is an important step in lesion localization and diagnosis, surgical planning, and postoperative monitoring. However, the limited number of radiation therapists and a great number of images make this work time-consuming. OBJECTIVE: This study designs a spatial attention deep supervised network (SADSNet) for simultaneous automatic segmentation of liver and tumors. METHOD: Firstly, self-designed spatial attention modules are introduced at each layer of the encoder and decoder to extract image features at different scales and resolutions, helping the model better capture liver tumors and fine structures. The designed spatial attention module is implemented through two gate signals related to liver and tumors, as well as changing the size of convolutional kernels; Secondly, deep supervision is added behind the three layers of the decoder to assist the backbone network in feature learning and improve gradient propagation, enhancing robustness. RESULTS: The method was testing on LITS, 3DIRCADb, and SLIVER datasets. For the liver, it obtained dice similarity coefficients of 97.03%, 96.11%, and 97.40%, surface dice of 81.98%, 82.53%, and 86.29%, 95% hausdorff distances of 8.96 mm, 8.26 mm, and 3.79 mm, and average surface distances of 1.54 mm, 1.19 mm, and 0.81 mm. Additionally, it also achieved precise tumor segmentation, which with dice scores of 87.81% and 87.50%, surface dice of 89.63% and 84.26%, 95% hausdorff distance of 12.96 mm and 16.55 mm, and average surface distances of 1.11 mm and 3.04 mm on LITS and 3DIRCADb, respectively. CONCLUSION: The experimental results show that the proposed method is effective and superior to some other methods. Therefore, this method can provide technical support for liver and liver tumor segmentation in clinical practice.

11.
BMJ Open ; 14(3): e078782, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38490656

RESUMO

OBJECTIVES: This study aimed to investigate the impact of adjuvant chemotherapy (ACT) on survival outcomes in older women with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (BC). DESIGN: A retrospective cohort study using data from the Surveillance, Epidemiology, and End Results database, which contains publicly available information from US cancer registries. SETTING AND PARTICIPANTS: The study included 45 762 older patients with BC aged over 65 years diagnosed between 2010 and 2015. METHODS: Patients were divided into two groups based on age: 65-79 years and ≥80 years. Propensity score matching (PSM) was employed to balance clinicopathological characteristics between patients who received ACT and those who did not. Data analysis used the χ2 test and Kaplan-Meier method, with a subgroup analysis conducted to identify potential beneficiaries of ACT. OUTCOME MEASURES: Overall survival (OS) and cancer-specific survival (CSS). RESULTS: Due to clinicopathological characteristic imbalances between patients with BC aged 65-79 years and those aged ≥80 years, PSM was used to categorise the population into two groups for analysis: the 65-79 years age group (n=38 128) and the ≥80 years age group (n=7634). Among patients aged 65-79 years, Kaplan-Meier analysis post-PSM indicated that ACT was effective in improving OS (p<0.05, HR=0.80, 95% CI 0.73 to 0.88), particularly in those with advanced disease stages, but did not show a significant benefit in CSS (p=0.09, HR=1.13, 95% CI 0.98 to 1.31). Conversely, for patients aged ≥80 years, ACT did not demonstrate any improvement in OS (p=0.79, HR=1.04, 95% CI 0.79 to 1.36) or CSS (p=0.09, HR=1.46, 95% CI 0.69 to 2.26) after matching. Subgroup analysis also revealed no positive impact on OS and CSS. CONCLUSIONS: Patients with HR+/HER2- BC ≥80 years of age may be considered exempt from ACT because no benefits were found in terms of OS and CSS.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Pontuação de Propensão , Programa de SEER , Quimioterapia Adjuvante/métodos
12.
BMC Cancer ; 24(1): 321, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454345

RESUMO

BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. METHODS: This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. DISCUSSION: This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. TRIAL REGISTRATION: ChiCTR1800017646.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia , Quimioterapia de Consolidação , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase III como Assunto , Estudos de Equivalência como Asunto
13.
Clin Nucl Med ; 49(5): 462-463, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38466017

RESUMO

ABSTRACT: A 57-year-old man presented with odynophagia for 1 week was referred for FDG PET/CT scan to rule out recurrent hypopharyngeal cancer. The FDG PET/CT showed hypermetabolic lesions in hypopharyngeal area and adjacent cervical spine with pneumorrhachis, the presence of intraspinal air, on attenuation CT images, which might indicate a life-threatening infection. An emergency MRI confirmed the presence of cervical spondylodiscitis with an epidural abscess. The patient rapidly progressed to quadriplegia and difficulty voiding on the same day as the PET/CT scan, leading to emergent operation. The patient received antibiotics treatment and discharged 4 months later without evidence of cancer recurrence.


Assuntos
Neoplasias Hipofaríngeas , Pneumorraque , Masculino , Humanos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Tomografia Computadorizada por Raios X/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos
15.
Mol Cell Proteomics ; 23(5): 100747, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38490531

RESUMO

Although immune tolerance evolved to reduce reactivity with self, it creates a gap in the adaptive immune response against microbes that decorate themselves in self-like antigens. This is particularly apparent with carbohydrate-based blood group antigens, wherein microbes can envelope themselves in blood group structures similar to human cells. In this study, we demonstrate that the innate immune lectin, galectin-4 (Gal-4), exhibits strain-specific binding and killing behavior towards microbes that display blood group-like antigens. Examination of binding preferences using a combination of microarrays populated with ABO(H) glycans and a variety of microbial strains, including those that express blood group-like antigens, demonstrated that Gal-4 binds mammalian and microbial antigens that have features of blood group and mammalian-like structures. Although Gal-4 was thought to exist as a monomer that achieves functional bivalency through its two linked carbohydrate recognition domains, our data demonstrate that Gal-4 forms dimers and that differences in the intrinsic ability of each domain to dimerize likely influences binding affinity. While each Gal-4 domain exhibited blood group-binding activity, the C-terminal domain (Gal-4C) exhibited dimeric properties, while the N-terminal domain (Gal-4N) failed to similarly display dimeric activity. Gal-4C not only exhibited the ability to dimerize but also possessed higher affinity toward ABO(H) blood group antigens and microbes expressing glycans with blood group-like features. Furthermore, when compared to Gal-4N, Gal-4C exhibited more potent antimicrobial activity. Even in the context of the full-length protein, where Gal-4N is functionally bivalent by virtue of Gal-4C dimerization, Gal-4C continued to display higher antimicrobial activity. These results demonstrate that Gal-4 exists as a dimer and exhibits its antimicrobial activity primarily through its C-terminal domain. In doing so, these data provide important insight into key features of Gal-4 responsible for its innate immune activity against molecular mimicry.

16.
PLoS One ; 19(3): e0300173, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38547184

RESUMO

Large primary tumor volume has been identified as a poor prognostic factor of esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT). However, when neoadjuvant CCRT and surgery are adopted, the prognostic impact of primary tumor and lymph node (LN) volume on clinical outcomes in ESCC remains to be elucidated. This study included 107 patients who received neoadjuvant CCRT and surgery for ESCC. The volume of the primary tumor and LN was measured using radiotherapy planning computed tomography scans, and was correlated with overall survival (OS), disease-free survival (DFS), and cancer failure pattern. The median OS was 24.2 months (IQR, 11.1-93.9) after a median follow-up of 18.4 months (IQR, 8.1-40.7). The patients with a baseline LN volume > 7.7 ml had a significantly worse median OS compared to those with smaller LN volume (18.8 vs. 46.9 months, p = 0.049), as did those with tumor regression grade (TRG) 3-5 after CCRT (13.9 vs. 86.7 months, p < 0.001). However, there was no association between OS and esophageal tumor volume (p = 0.363). Multivariate analysis indicated that large LN volume (HR 1.753, 95% CI 1.015-3.029, p = 0.044) and high TRG (HR 3.276, 95% CI 1.556-6.898, p = 0.002) were negative prognostic factors for OS. Furthermore, large LN volume was linked to increased locoregional failure (p = 0.033) and decreased DFS (p = 0.041). In conclusion, this study demonstrated that large LN volume is correlated with poor OS, DFS, and locoregional control in ESCC treated with neoadjuvant CCRT and esophagectomy.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , Terapia Neoadjuvante/métodos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/tratamento farmacológico , Estadiamento de Neoplasias , Prognóstico , Linfonodos/patologia , Quimiorradioterapia/métodos , Estudos Retrospectivos , Esofagectomia/métodos
17.
J Formos Med Assoc ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360489

RESUMO

BACKGROUND: Endovascular thrombectomy (EVT) is a time-sensitive treatment for acute ischemic stroke with large vessel occlusion. To optimize transfer efficiency, a web-based platform was introduced in the Tainan Stroke Network (TSN). We assessed its application and effectiveness in regional stroke care. METHOD: This new web-based platform containing a questionnaire-style interface was introduced on October 1, 2021. To assess the transfer efficiency and patient outcomes, acute stroke patients transferred from PSCs to CSC for EVT from April 01, 2020, to December 30, 2022, were enrolled. The patients were classified into the traditional transferal pathway (TTP) group and the new transferal pathway (NTP) group depending on mode of transfer. Patient characteristics, time segments after stroke onset and outcome were compared between groups. RESULT: A total of 104 patients were enrolled, with 77 in the TTP group and 27 in the NTP group. Compared to the TTP group, the NTP group had a significantly shorter onset-to-CSC door time (TTP vs. NTP: 267 vs. 198 min; p = 0.041) and a higher EVT rate (TTP vs. NTP: 18.2% vs. 48.1%, p = 0.002). Among EVT patients, those in the NTP group had a significantly shorter CSC door-to-puncture time (TTP vs. NTP: 131.5 vs. 110 min; p = 0.029). The NTP group had a higher rate of good functional outcomes at 3 months (TTP vs. NTP: 21% vs. 61.5%; p = 0.034). CONCLUSION: This new web-based EVT transfer system provides notable improvements in clinical outcomes, transfer efficiency, and EVT execution for potential EVT candidates without markedly changing the regional stroke care paradigm.

18.
Head Neck ; 46(5): 1063-1073, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38385970

RESUMO

BACKGROUND: For R/M HNSCC, the differences in prognosis and treatment options between distant metastasis (DM) and locoregional recurrence, especially in the DM group, remain unclear. METHODS: From the Taiwan Head Neck Society registry database, patients who were diagnosed with R/M HNSCC and received cetuximab-based frontline therapy were collected for analysis. RESULTS: Among the enrolled patients, 59.3% (491/827) belonged to the DM group. The DM group had less primary site of oral cavity, less betel nut chewing, higher lactate dehydrogenase (LDH) levels, and higher LDH/albumin ratio compared with the non-DM group. For the patients with primary site of oral cavity and current smokers, DM coexisted with poorer outcomes. In the DM group, EXTREME-like regimen was more suitable for older patients, those with elevated LDH, and those with higher LDH/albumin ratio than TPExtreme-like regimen. CONCLUSION: DM coexisted with poorer prognosis in certain groups. LDH-associated biomarkers may aid treatment options for DM patients.


Assuntos
Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Cetuximab/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Taiwan , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/patologia , Albuminas
19.
Bioconjug Chem ; 35(2): 154-163, 2024 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-38320084

RESUMO

Conventional techniques for purifying macromolecular conjugates often require complex and costly installments that are inaccessible to most laboratories. In this work, we develop a one-step micropreparative method based on a trilayered polyacrylamide gel electrophoresis (MP-PAGE) setup to purify biological samples, synthetic nanoparticles, as well as biohybrid complexes. We apply this method to recover DNA from a ladder mixture with yields of up to 90%, compared to the 58% yield obtained using the conventional crush-and-soak method. MP-PAGE was also able to isolate enhanced yellow fluorescence protein (EYFP) from crude cell extract with 90% purity, which is comparable to purities achieved through a more complex two-step purification procedure involving size exclusion and immobilized metal-ion affinity chromatography. This technique was further extended to demonstrate size-dependent separation of a commercial mixture of graphene quantum dots (GQDs) into three different fractions with distinct optical properties. Finally, MP-PAGE was used to isolate DNA-EYFP and DNA-GQD bioconjugates from their reaction mixture of DNA and EYFP and GQD precursors, samples that otherwise could not be effectively purified by conventional chromatography. MP-PAGE thus offers a rapid and versatile means of purifying biological and synthetic nanomaterials without the need for specialized equipment.


Assuntos
Proteínas , Pontos Quânticos , Eletroforese em Gel de Poliacrilamida , Pontos Quânticos/química , Cromatografia de Afinidade , DNA
20.
Cancer ; 130(11): 1972-1981, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38306242

RESUMO

BACKGROUND: Glofitamab is a bispecific antibody with promise for treating relapsed/refractory B-cell lymphoma according to a phase 1/2 clinical trial. This study examined its real-world effectiveness. METHODS: This was an investigator-initiated, multicenter retrospective study including 34 patients who had relapsed/refractory B-cell lymphomas after at least three prior lines of therapy and received glofitamab monotherapy in a compassionate use program in Taiwan between January 2021 and October 2022. RESULTS: At a median follow-up of 15.9 months, 56% of patients responded to glofitamab and 23% achieved complete remission. Response to the previous line of therapy significantly correlated with response to glofitamab (p = .020). Most responses were durable; only five out of the 19 responders had documented disease recurrence at the data cutoff date. The estimated progression-free survival (PFS) was 3.2 months, and the estimated 1-year PFS was 33% for the entire cohort. PFS was better for responders than nonresponders (median PFS, 16.9 vs. 1.8 months; 1-year PFS, 60% vs. 0%). Forty-three cytokine release syndrome (CRS) events were observed, three of which were grade 3; all were manageable without glofitamab discontinuation. No immune effector cell-associated neurotoxicity was reported. Among seven hepatitis B virus (HBV) carriers (six had antiviral prophylaxis) and 14 patients with remote HBV (four had antiviral prophylaxis), no HBV reactivation was observed. CONCLUSIONS: In this real-world cohort, glofitamab exhibited effectiveness comparable to trial results without excessive CRS or new safety issues. With appropriate prophylaxis, glofitamab-treated patients with chronic or remote HBV infection are unlikely to experience virus reactivation.


Assuntos
Anticorpos Biespecíficos , Linfoma de Células B , Terapia de Salvação , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Linfoma de Células B/tratamento farmacológico , Terapia de Salvação/métodos , Estudos Retrospectivos , Adulto , Taiwan , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Biespecíficos/efeitos adversos , Idoso de 80 Anos ou mais , Intervalo Livre de Progressão , Recidiva Local de Neoplasia/tratamento farmacológico , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos
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