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OBJECTIVE: Identifying the Seizure Occurrence Period (SOP) in extended EEG recordings is crucial for neurologists to diagnose seizures effectively. However, many existing computer-aided diagnosis systems (CADs) for Epileptic Seizure Detection (ESD) primarily focus on distinguishing between ictal and interictal states in EEG recordings. This focus has limited their application in clinical settings, as these systems typically rely on super vised learning approaches that require labeled data. APPROACH: To address this, our study introduces an unsupervised learning framework for ESD using a 1D-Cascaded Convolutional Autoencoder (1D-CasCAE). In this approach, EEG recordings from selected patients in the CHB-MIT datasets are first segmented into 5-second epochs. Eight informative channels are chosen based on the correlation coefficient and Shannon entropy. The 1D-CasCAE is designed to autonomously learn the characteristic patterns of interictal (non-seizure) segments through downsampling and upsampling processes. The integration of adaptive thresholding and a moving window significantly enhances the model's robustness, enabling it to accurately identify ictal segments in long EEG recordings. MAIN RESULTS: Experimental results demonstrate that the proposed 1D-CasCAE effectively learns normal EEG signal patterns and efficiently detects anomalies (ictal segments) using reconstruction error. When compared with other leading methods in anomaly detection, our model exhibits superior performance, as evidenced by its average Gmean, sensitivity, specificity, preci sion, and false positive rate scores of 98.00±3.51%, 94.94±6.92%, 99.60±0.30%, 79.92±13.56% and 0.0044±0.0030/h of a typical patient in CHB-MIT datasets. SIGNIFICANCE: Finally, the developed model framework can be employed in clinical settings, replacing the manual inspection process of EEG signals by neurologists. This automated system can adapt to each patient's SOP through the use of variable time windows for seizure detection.
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OBJECTIVE: Young migraine patients often present with white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI). This study aimed to analyze whether synthetic (Syn) T2-FLAIR and Syn double inversion recovery (DIR) can reveal WMHs more clearly and sensitively than conventional T2-FLAIR. MATERIALS AND METHODS: Conventional MRI and Syn MRI data from 50 young migraine patients were analyzed prospectively. WMHs in each anatomical region (periventricular, deep white matter, and juxtacortical) were recorded separately. The differences in the clarity of lesion boundaries and the number of lesions displayed in the three sequences in the same anatomical region were analyzed. RESULTS: A total of 80 (periventricular area, 15; deep white matter, 31; juxtacortical area, 34), 163 (17, 50, 96), and 134 (18, 42, 74) lesions were observed with conventional T2-FLAIR, Syn T2-FLAIR, and Syn DIR, respectively. Syn T2-FLAIR and Syn DIR can show lesions more clearly than conventional T2-FLAIR (all P < 0.001). There was no significant difference in the number of lesions observed in the periventricular white matter among the three sequences (P = 0.159, 0.083, 0.322). Syn T2-FLAIR and Syn DIR can detect more lesions in the deep white matter than conventional T2-FLAIR (P < 0.001, P = 0.006). Syn T2-FLAIR revealed more lesions in the juxtacortical white matter than Syn DIR and conventional T2-FLAIR imaging (all P < 0.001), and conventional T2-FLAIR revealed the fewest lesions (P < 0.001). CONCLUSION: Syn T2-FLAIR and Syn DIR sequences can clearly and sensitively detect WMHs, especially in deep and juxtacortical white matter areas.
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Apple replant disease (ARD) is a worldwide problem that threatens the industry. However, the genetic mechanism underlying plant disease resistance against ARD remains unclear. In this study, a negative regulatory microRNA in Malus domestica, mdm-miR397b \, and its direct target MdLAC7b (Laccase) was selected for examination based on our previous small RNA and degradome sequencing results. Overexpressing the mdm-miR397b-MdLAC7b module altered the lignin deposition and JA contents in apple roots, which also led to increased resistance to Fusarium solani. Additionally, Y1H library screening using mdm-miR397b promoter recombinants identified a transcription factor, MdERF61, that represses mdm-miR397b transcriptional activity by directly binding to two GCC-boxes in the mdm-miR397b promoter. In summary, our results suggest that the MdERF61-mdm-miR397b-MdLAC7b module plays a crucial role in apple resistance to F. solani and offers insights for enhancing plant resistance to soilborne diseases in apple.
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BACKGROUND: The effectiveness of sentinel lymph node biopsy (SLNB) versus axillary lymph node dissection (ALND) in managing early-stage male breast cancer (MBC) patients with T1-2 tumors and limited lymph node metastasis, all receiving radiotherapy, remains uncertain. This study examines trends and survival outcomes for SLNB and ALND in the United States. METHODS: We conducted a retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) data from 2010 to 2020 for MBC patients with T1-2 tumors and 1-2 positive lymph nodes undergoing radiotherapy. Patients were classified by nodes removed (SLNB ≤5, ALND ≥10), comparing overall survival (OS) and breast cancer-specific survival (BCSS) between the groups before and after propensity score matching. RESULTS: Of 299 MBC patients analyzed, SLNB usage increased from 18.8% in 2010 to 61.0% in 2020. Multivariable logistic regression highlighted significant associations of SLNB use with diagnosis year, race, surgery type, positive lymph node count, and metastasis size. No significant differences in 5-year OS (77.98% SLNB vs. 85.85% ALND, p = 0.337) or BCSS (91.54% SLNB vs. 94.97% ALND, p = 0.214) were observed. Propensity score matching (96 patients per group) confirmed similar 5-year OS (83.9% for SLNB vs. 82.0% for ALND, p = 0.925) and BCSS (90.1% for SLNB vs. 96.9% for ALND, p = 0.167). CONCLUSION: SLNB and ALND provide comparable survival outcomes in early-stage MBC patients with limited lymph node metastasis undergoing radiotherapy. The increased utilization of SLNB supports its consideration to reduce surgical morbidity in selected MBC patients despite limited direct evidence.
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Axila , Neoplasias da Mama Masculina , Excisão de Linfonodo , Metástase Linfática , Estadiamento de Neoplasias , Programa de SEER , Biópsia de Linfonodo Sentinela , Humanos , Masculino , Neoplasias da Mama Masculina/patologia , Neoplasias da Mama Masculina/cirurgia , Neoplasias da Mama Masculina/mortalidade , Excisão de Linfonodo/estatística & dados numéricos , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Linfonodos/patologia , Linfonodos/cirurgia , Estados Unidos/epidemiologia , Pontuação de Propensão , AdultoRESUMO
Background: The phase 2 PERMEATE study has shown the antitumor activity and safety of pyrotinib plus capecitabine in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer and brain metastases. In this report, survival results were updated with extended follow-up. Methods: Between January 29, 2019 and July 10, 2020, adult patients with HER2-positive metastatic breast cancer who had radiotherapy-naïve brain metastases (cohort A, n = 59) or progressive disease after radiotherapy (cohort B, n = 19) were enrolled and received pyrotinib (400 mg once daily) and capecitabine (1000 mg/m2 twice daily on days 1-14 of each 21-day cycle) until disease progression or unacceptable toxicity. Secondary endpoints progression-free survival (PFS) and overall survival (OS) were updated, and post-hoc central nervous system (CNS)-PFS was analyzed. This study is registered with ClinicalTrials.gov (NCT03691051). Findings: As of February 2, 2023, the median follow-up duration was 30.9 months (interquartile range, 16.1-39.8). Median PFS was 10.9 months (95% confidence interval [CI], 7.6-14.6) in cohort A and 5.7 months (95% CI, 3.4-11.5) in cohort B. Median OS was 35.9 months (95% CI, 24.4-not reached) in cohort A and 30.6 months (95% CI, 12.6-33.3) in cohort B. Median CNS-PFS was 13.6 months (95% CI, 9.0-15.8) in cohort A and 5.7 months (95% CI, 3.4-11.5) in cohort B. Median OS was 34.1 months (95% CI, 21.7-not reached) for 14 patients with intracranial progression only in cohort A who restarted pyrotinib plus capecitabine after local radiotherapy. Interpretation: These data support further validation in a randomized controlled trial for the assessment of pyrotinib in combination with capecitabine as systemic therapy for patients with HER2-positive breast cancer and brain metastases. Funding: National Cancer Center Climbing Foundation Key Project of China, Jiangsu Hengrui Pharmaceuticals.
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Introduction: Limosilactobacillus reuteri effectively colonizing the gut, secretes antimicrobial compounds and strengthens immune system function. Considering these health benefits, increasing its stress assessments efficiency could improve its commercial viability. Methods: In this work, the resistance of L. reuteri FP41 to acid, bile salts, and freeze-drying was examined. Results: The findings showed that strain FP41 demonstrated a strong resistance to acid/bile salt stresses. The transcriptome revealed a significant up-regulation of various stress response genes, including those related to membrane integrity, glutamine metabolism, OsmC family protein, ABC transporters, and chaperonin. Subsequent research demonstrated that overexpression of three stress response-specific proteins, including glutamate decarboxylase GatD, osmotically induced bacterial protein OsmC, and membrane protein component CsbD, significantly increased the survival rate of L. reuteri Z204 under acid/bile salts stress. Notably, overexpression of the OsmC, CsbD, and GatD proteins also enhanced the survival of L. reuteri after freeze-drying. Discussion: The development of a unique cross-protection method is highlighted in this study, that might significantly increase cellular resistance to acid, bile salts, and cold stresses. This finding could significantly impact the way that L. reuteri is employed in industrial manufacturing processes.
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Background: Abemaciclib was the first cyclin-dependent kinase 4/6 (CDK4/6) inhibitor approved globally in the adjuvant setting for high-risk hormone-receptor positive (HR+)/human epidermal growth factor 2 negative (HER2-) early breast cancer (EBC), based on the phase III monarchE trial. Objective: To report an exploratory Chinese population analysis based on the preplanned overall survival (OS) interim analysis with 5-year efficacy results of monarchE. Design and methods: Patients with HR+/HER2-, high-risk (⩾4 positive lymph nodes, or 1-3 nodes and either tumor size ⩾5 cm, histologic grade 3, or Ki-67 ⩾20%) EBC were randomized (1:1) to abemaciclib (150 mg twice daily for 2 years) plus endocrine therapy (ET), or ET alone. This analysis included Chinese patients enrolled in mainland China, Hong Kong, and Taiwan. The primary endpoint was invasive disease-free survival (IDFS); key secondary endpoints included distant relapse-free survival (DRFS), safety, and patient-reported outcomes (PROs). Results: Overall, 501 Chinese patients were included (abemaciclib + ET, n = 259; ET, n = 242). With a median follow-up of 53 months, the addition of abemaciclib to ET resulted in improvements in IDFS (estimated 5-year IDFS rate: 85.9% vs 79.1%; hazard ratio (HR), 0.65 (95% confidence interval (CI) 0.41-1.03)) and DRFS (estimated 5-year DRFS rate: 88.4% vs 82.3%; HR, 0.65 (95% CI, 0.39-1.07)). The most common grade ⩾3 treatment-emergent adverse events in the abemaciclib + ET versus ET groups were neutropenia (24.7% vs 0.8%) and leukopenia (22.4% vs 0.4%). Generally, no clinically meaningful difference in PROs (endocrine symptoms and fatigue) was observed between groups, except for diarrhea. Conclusion: At this prespecified OS interim analysis, which provides 5-year data, the addition of abemaciclib to ET in Chinese patients with high-risk HR+, HER2- EBC was associated with sustained and clinically meaningful improvements in IDFS and DRFS, with acceptable safety and tolerability profiles and minimal impact on PROs. These results represent the first full report of a CDK4/6 inhibitor in Chinese patients with EBC and support the positive benefit-risk profile of adjuvant abemaciclib + ET in Chinese patients. Trial registration: ClinicalTrials.gov identifier: NCT03155997 (first posted: May 16, 2017).
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The high water solubility and flammability of polyvinyl alcohol (PVA) limits its further widespread use in areas such as bioplastic and green packaging. In this study, double-crosslinked polyvinyl alcohol/starch bioplastics (named PDA) were fabricated using PVA, dialdehyde starch (DAS), and phytic acid (PA), resulting in a material with superior water resistance, flame retardancy, and excellent degradability. PA not only plays the role of catalyst for the chemical crosslinking but also as the physical crosslinker to form the intermolecular hydrogen bonds with PVA and DAS. This chemically and physically double cross-linked network structure results in PDA bioplastics with excellent toughness and water resistance. Specifically, the optimal formulation with 15 % PA content, designated as PDA15, exhibited a high toughness of 35.5 MJ/m3 and demonstrated prolonged shape retention in the boiling water. Additionally, PA also serves as a flame-retardant and antibacterial agent; the PDA15 achieved a high limit oxygen index (LOI) value of 40.0 % and passed the UL-94 V-0 rating without melt dripping, along with better degradability compared to pure PVA film. These outstanding performances make the PDA bioplastics highly promising for various applications, particularly in disposable plastics and laminated flexible packaging materials.
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BACKGROUND: Frailty is prevalent among older patients in intensive care units (ICUs) and poses significant challenges to recovery. Despite its importance, there is limited research on effective nurse-led frailty management strategies in this context. OBJECTIVE: The purpose of this qualitative study was to explore nurses' perceptions of frailty management in cardiac ICUs through the lens of the Wuli-Shili-Renli (WSR) system approach. METHODS: Sixteen nurses from two tertiary hospitals in Shandong province, China, participated in semi-structured interviews. Participants were selected based on their involvement in frailty training, educational background, and cardiac ICU work experience. Thematic analysis was conducted to identify key themes and sub-themes. RESULTS: Analysis in three categories revealed the need for foundational support, including the need for appropriate screening tools, updated evidence-based practices, and institutional support. Closed-loop management involved frailty screening, personalized program implementation, information management, and follow-up assessment. Personnel training and coordination emphasized enhancing nurses' professionalism, multidisciplinary teamwork, and cooperation from patients and their caregivers. CONCLUSION: The insights gained can inform evidence-based practices and improve the quality of care provided to frail patients in cardiac ICUs. There is a need for future research to empirically investigate these strategies.
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Enfermagem de Cuidados Críticos , Fragilidade , Pesquisa Qualitativa , Humanos , Feminino , Fragilidade/enfermagem , Masculino , Enfermagem de Cuidados Críticos/métodos , China/epidemiologia , Idoso , Unidades de Terapia Intensiva/organização & administração , Adulto , Pessoa de Meia-Idade , Unidades de Cuidados Coronarianos/organização & administração , Idoso FragilizadoRESUMO
6PPD-quinone (6PPD-Q) is frequently detected in various environmental media, and the environmentally relevant concentrations can be fatal to Oncorhynchus mykiss. Notably, 6PPD-Q has two enantiomers (S-6PPD-Q and R-6PPD-Q). In this study, O. mykiss was separately exposed to each enantiomer and racemate of 6PPD-Q for 96 h at environmentally relevant concentrations, and livers were collected. Effects on the biochemical, pathological, and ultrastructural changes were assessed, and metabolomics was conducted to elucidate the potential hepatotoxicity mechanism. Compared with the control treatment, the levels of catalase (CAT, all treatments except for 0.1 µg/L rac-6PPD-Q), and glutathione-S-transferase (GST, all treatments) significantly declined. Hepatocyte space became smaller, nuclear morphology changed, and nucleolysis occurred. Mitochondrial malformation and vesicle-like structure dilation of the endoplasmic reticulum (ER) were observed in the hepatocytes, which was most serious after S-6PPD-Q exposure. Some amino acid metabolism, folate biosynthesis, taurine and hypotaurine metabolism and purine metabolism were disturbed, consistent with mitochondrial dysfunction and ER stress. The differential metabolites were in the order of S-6PPD-Q (216) > rac-6PPD-Q (88) > R-6PPD-Q (56). Thus, 6PPD-Q-induced hepatic mitochondrial dysfunction and ER stress, causing metabolic disturbance and oxidative stress might be the toxic mechanism of 6PPD-Q in O. mykiss liver, and S-6PPD-Q effects were the most serious.
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Fígado , Oncorhynchus mykiss , Animais , Fígado/efeitos dos fármacos , Fígado/metabolismo , Quinonas/toxicidade , Glutationa Transferase/metabolismoRESUMO
Isopyrazam (IPZ) is a new chiral fungicide. For bioactivity, there was a 3.37-1578 times difference among the four stereoisomers. For Alternaria alternata and Phoma multirostrata, cis-(1S,4R,9S)-IPZ had the greatest activity. Using cis-IPZ might improve the efficacy and reduce the dosage of the racemate by 54.7-72.2% for A. alternata and P. multirostrata. To zebrafish, trans-IPZ showed the highest acute toxicity (LC50, 0.096 mg/L). The degradation half-lives of IPZ stereoisomers in the five crops ranged from 3.50 to 15.2 days. Cis-IPZ was preferentially degraded in grape, pear, and celery. The residual concentrations of IPZ in grape and celery were still higher than the maximum residue limit, and the acute and chronic dietary intake risks of IPZ in celery were unacceptable (RQa: 146-250%, HQ: 117-200%), which were worthy of further researching. Based on the research results, it is safer and more reasonable to use IPZ in the form of a racemate with a high ratio of cis-IPZ.
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Frutas , Fungicidas Industriais , Verduras , Peixe-Zebra , Fungicidas Industriais/química , Fungicidas Industriais/toxicidade , Frutas/química , Verduras/química , Animais , Estereoisomerismo , Contaminação de Alimentos/análise , Medição de Risco , Vitis/química , Piridinas/química , Piridinas/toxicidade , Alternaria/metabolismo , Alternaria/química , Alternaria/efeitos dos fármacos , Humanos , Norbornanos , PirazóisRESUMO
Purpose: The purpose of this study was to investigate the association between retinal nerve fiber layer (RNFL) thickness and high-density lipoprotein cholesterol (HDL-C) in a healthy population. Methods: This cross-sectional study included 31,738 UK Biobank participants with high quality optical coherence tomography (OCT) images, excluding those with neurological or ocular diseases. The locally estimated scatterplot smoothing (LOESS) curve and multivariable piecewise linear regression models were applied to assess the association between HDL-C and RNFL thickness, and HDL-C subclasses were further analyzed using nuclear magnetic resonance (NMR) spectroscopy. Results: Multivariate piecewise linear regression revealed that high HDL-C levels (>1.7 mmol/L in women or > 1.5 mmol/L in men) were associated with thinner RNFL thickness (women: ß = -0.13, 95% confidence interval [CI] = -0.23 to -0.02, P = 0.017; male: ß = -0.23, 95% CI = -0.37 to -0.10, P = 0.001). Conversely, a significant positive association between HDL-C and RNFL thickness was observed when HDL-C was between 1.4 and 1.7 mmol/L for female participants (ß = 0.13, 95% CI = 0.02 to 0.24, P = 0.025). NMR analysis showed that these associations are potentially driven by distinct HDL-C subclasses. Conclusions: This study revealed an association between HDL-C levels and retinal markers of neurodegenerative diseases, suggesting that elevated HDL-C may serve as a new risk factor for neurodegenerative conditions. These findings may contribute to the implementation of preventive interventions and improved patient outcomes.
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HDL-Colesterol , Fibras Nervosas , Células Ganglionares da Retina , Tomografia de Coerência Óptica , Humanos , Feminino , Masculino , Estudos Transversais , Tomografia de Coerência Óptica/métodos , Fibras Nervosas/patologia , Pessoa de Meia-Idade , Células Ganglionares da Retina/patologia , Reino Unido/epidemiologia , HDL-Colesterol/sangue , Idoso , Bancos de Espécimes Biológicos , Adulto , Biobanco do Reino UnidoRESUMO
This paper summarizes the recent progress of diverse high-performance fibers in their properties, applications and the challenges.
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CONTEXT: Dietary factors are crucial in the onset and development of autoimmune thyroid disease (AITD), but the relationship between specific fatty acids and AITD remains unexplored. METHODS: We analyzed the US National Health and Nutrition Examination Survey (NHANES) 2007-2012 data on 3949 men and 3964 women aged 20 years and over with valid data on TPOAb, TgAb and details of fat intake, using multivariable regression models to examine the relationship of fat intake and specific fatty acid intake with thyroid autoimmunity. RESULTS: Of the 7913 participants, 7.5% had TgAb seropositivity and 11.9% had TPOAb seropositivity. The seropositivity of TgAb and TPOAb was more common in low-fat intake participants. In the overall population and men, fats were associated with thyroid autoimmunity before and after full adjustment for age, ethnicity, body mass index, smoking status and urine iodine concentration (total fat: OR=0.64, 95% CI 0.49 to 0.83; SFA: OR=0.65, 95% CI 0.51 to 0.84; MUFA: OR=0.65, 95% CI 0.50 to 0.85; PUFA: OR=0.76, 95% CI 0.57 to 0.995, after full adjustment in men). Some specific fatty acids followed a similar pattern. The association between fats and TgAb seropositivity was significant in the overall population and men. The association between fats and TPOAb seropositivity was only found in the overall population. CONCLUSION: We found a strong association between fat consumption and thyroid autoimmunity in the overall population and men from the nationally representative population-based survey. Fat and fatty acid consumption may be of benefit to individuals with thyroid autoimmunity.
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PURPOSE: To assess the myopic shift in unilateral cataract children undergoing primary intraocular lens implantation and its association with preoperative ocular parameters. SETTING: Single center. DESIGN: Retrospective study. METHOD: Children who underwent unilateral primary IOL implantation and followed up for 3 years were included. Myopic shift and preoperative ocular parameters were compared between the treated and the fellow eyes. The correlation between myopic shift and ocular parameters was assessed using partial correlation analysis. Potential factors influencing myopic shift were determined using linear regression analysis. RESULTS: A total of 126 patients (252 eyes) were included. Longer preoperative axial length (AL) and steeper average keratometry (AK) in the treated eyes were noted in the whole cohort and patients aged 2 to <4 years (all p < .05). At 3 years postoperatively, mean myopic shift ranged from 3.53 diopters for children aged 1 to <2 years to 1.99 diopters for the ≥6 years. A greater myopic shift in the treated eyes was found in all except children aged ≥6 years (p > .05). Preoperative interocular AL difference (IALD) was negatively correlated with myopic shift (r = 0.32, p < .001). Regression analysis revealed that younger age and smaller IALD were associated with greater myopic shift (p < .001 and p = .001, respectively). CONCLUSION: A greater myopic shift was observed in children with younger age at surgery and smaller IALD. To mitigate long-term anisometropia, selecting target refraction for unilateral pediatric cataracts should consider children's age, refractions of the fellow eyes, and preoperative IALD.
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BACKGROUND: In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks of high-level clinical evidence. This study aimed to compare the safety and long-term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy (NAC) followed by MIE. METHODS: A prospective, single-center, open-label, randomized phase III clinical trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned to receive either neoadjuvant toripalimab (240 mg) plus paclitaxel (175 mg/m2) + cisplatin (75 mg/m2) (toripalimab group) or paclitaxel + cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After surgery, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The primary endpoint was event-free survival (EFS). The pathological complete response (pCR) and overall survival (OS) were key secondary endpoints. Adverse events (AEs) and quality of life were also assessed. RESULTS: Between May 15, 2020 and August 13, 2021, 252 ESCC patients ranging from T1N1-3M0 to T2-3N0-3M0 were enrolled for interim analysis, with 127 in the toripalimab group and 125 in the chemotherapy group. The 1-year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; P = 0.05). The 1-year OS rates were 94.1% and 83.0% in the toripalimab and chemotherapy groups, respectively (HR = 0.48; 95% CI = 0.24 to 0.97; P = 0.037). The patients in the toripalimab group had a higher pCR rate (18.6% vs. 4.6%; P = 0.001). The rates of postoperative Clavien-Dindo grade IIIb or higher morbidity were 9.8% in the toripalimab group and 6.8% in the chemotherapy group, with no significant difference observed (P = 0.460). The rates of grade 3 or 4 treatment-related AEs did not differ between the two groups (12.5% versus 12.4%). CONCLUSIONS: The interim results of this ongoing trial showed that in resectable ESCC, the addition of perioperative toripalimab to NAC is safe, may improve OS and might change the standard treatment in the future.
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Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Esofágicas , Terapia Neoadjuvante , Humanos , Masculino , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Feminino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Idoso , Estudos Prospectivos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Esofagectomia/métodos , Esofagectomia/efeitos adversos , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Cisplatino/efeitos adversos , Adulto , Resultado do TratamentoRESUMO
BACKGROUND: In this study, exhaled breath testing has been considered a promising method for the detection and monitoring of breast cancer (BC). METHODS: A high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS) platform was used to detect volatile organic compounds (VOCs) in breath samples. Then, machine learning (ML) models were constructed on VOCs for the diagnosis of BC and its progression monitoring. Ultimately, 1981 women with useable breath samples were included in the study, of whom 937 (47.3 %) had been diagnosed with BC. VOC panels were used for ML model construction for BC detection and progression monitoring. RESULTS: On the blinded testing cohort, this VOC-based model successfully differentiated patients with and without BC with sensitivity, specificity, and area under receiver operator characteristic curve (AUC) values of 85.9 %, 90.4 %, and 0.946. The corresponding AUC values when differentiating between patients with and without lymph node metastasis (LNM) or between patients with tumor-node-metastasis (TNM) stage 0/I/II or III/IV disease were 0.840 and 0.708, respectively. While developed VOC-based models exhibited poor performance when attempting to differentiate between patients based on pathological patterns (Ductal carcinoma in situ (DCIS) vs Invasive BC (IBC)) or molecular subtypes (Luminal vs Human epidermal growth factor receptor 2 (HER2+) vs Triple-negative BC (TNBC)) of BC. CONCLUSION: Collectively, the HPPI-TOFMS-based breathomics approaches may offer value for the detection and progression monitoring of BC. Additional research is necessary to explore the fundamental mechanisms of the identified VOCs.
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Biomarcadores Tumorais , Neoplasias da Mama , Testes Respiratórios , Compostos Orgânicos Voláteis , Humanos , Neoplasias da Mama/diagnóstico , Feminino , Compostos Orgânicos Voláteis/análise , Biomarcadores Tumorais/análise , Testes Respiratórios/métodos , Pessoa de Meia-Idade , Adulto , Idoso , Aprendizado de Máquina , Fótons , Espectrometria de Massas , Progressão da DoençaRESUMO
Fertilization introduces parental genetic information into the zygote to guide embryogenesis. Parental contributions to postfertilization development have been discussed for decades, and the data available show that both parents contribute to the zygotic transcriptome, suggesting a paternal role in early embryogenesis1-6. However, because the specific paternal effects on postfertilization development and the molecular pathways underpinning these effects remain poorly understood, paternal contribution to early embryogenesis and plant development has not yet been adequately demonstrated7. Here our research shows that TREE1 and its homologue DAZ3 are expressed exclusively in Arabidopsis sperm. Despite presenting no evident defects in sperm development and fertilization, tree1 daz3 unexpectedly led to aberrant differentiation of the embryo root stem cell niche. This defect persisted in seedlings and disrupted root tip regeneration, comparable to congenital defects in animals. TREE1 and DAZ3 function by suppression of maternal RKD2 transcription, thus mitigating the detrimental maternal effects from RKD2 on root stem cell niche. Therefore, our findings illuminate how genetic deficiencies in sperm can exert enduring paternal effects on specific plant organ differentiation and how parental-of-origin genes interact to ensure normal embryogenesis. This work also provides a new concept of how gamete quality or genetic deficiency can affect specific plant organ formation.
Assuntos
Arabidopsis , Diferenciação Celular , Herança Paterna , Raízes de Plantas , Nicho de Células-Tronco , Arabidopsis/citologia , Arabidopsis/embriologia , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Diferenciação Celular/genética , Fertilização , Regulação da Expressão Gênica de Plantas , Raízes de Plantas/citologia , Raízes de Plantas/embriologia , Raízes de Plantas/genética , Regeneração/genética , Plântula/genética , Plântula/crescimento & desenvolvimento , Animais , Sementes/citologia , Sementes/embriologia , Sementes/genética , Transcrição Gênica , Herança Paterna/genéticaRESUMO
The development of multifunctional wound adhesives is critical in clinical settings due to the scarcity of dressings with effective adhesive properties while protecting against infection by drug-resistant bacteria. Polysaccharide and gelatin-based hydrogels, known for their biocompatibility and bioactivity, assist in wound healing. This study introduces a multifunctional bioadhesive hydrogel developed through dynamic covalent bonding and light-triggered covalent bonding, comprising oxidized hyaluronic acid, methacrylated gelatin, and the bacteriocin recently discovered by our lab, named jileicin (JC). The adhesion strength of the hydrogel, measured at 180 kPa, was 4.35 times higher than that of the fibrin glue. Furthermore, the hydrogel demonstrated robust platelet adhesion, procoagulant activity, and outstanding hemostatic properties in a mouse liver injury model. Incorporating JC significantly enhanced the phagocytosis and bactericidal capabilities of the macrophages. This immunomodulatory function on host cells, coupled with its potent bacterial membrane-disrupting ability, makes JC an effective killer against methicillin-resistant Staphylococcus aureus. In wound repair experiments on diabetic mice with infected full-thickness skin defects, the hydrogel treatment group showed a notable reduction in bacterial load, accelerated M2-type macrophage polarization, diminished inflammation, and hastened wound healing. Owing to its outstanding biocompatibility, antibacterial activity, and controlled adhesion, this hydrogel presents a promising therapeutic option for treating infected skin wounds.
Assuntos
Antibacterianos , Diabetes Mellitus Experimental , Gelatina , Ácido Hialurônico , Hidrogéis , Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Gelatina/química , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Antibacterianos/química , Antibacterianos/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Adesivos Teciduais/química , Adesivos Teciduais/farmacologia , Humanos , MasculinoRESUMO
Postharvest rot caused by various fungal pathogens is a damaging disease affecting kiwifruit production and quality, resulting in significant annual economic losses. This study focused on isolating the strain P3-1W, identified as Diaporthe eres, as the causal agent of 'Hongyang' postharvest rot disease in China. The investigation highlighted cell wall degrading enzymes (CWDEs) as crucial pathogenic factors. Specially, the enzymatic activities of cellulase, ß-galactosidase, polygalacturonase, and pectin methylesterases peaked significantly on the second day after infection of D. eres P3-1W. To gain a comprehensive understanding of these CWDEs, the genome of this strain was sequenced using PacBio and Illumina sequencing technologies. The analysis revealed that the genome of D. eres P3-1W spans 58,489,835 bp, with an N50 of 5,939,879 bp and a GC content of 50.7%. A total of 15,407 total protein-coding genes (PCGs) were predicted and functionally annotated. Notably, 857 carbohydrate-active enzymes (CAZymes) were identified in D. eres P3-1W, with 521 CWDEs consisting of 374 glycoside hydrolases (GHs), 108 carbohydrate esterase (CEs) and 91 polysaccharide lyases (PLs). Additionally, 221 auxiliary activities (AAs), 91 glycosyltransferases (GTs), and 108 carbohydrate binding modules (CBMs) were detected. These findings offer valuable insights into the CAZymes of D. eres P3-1W.