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1.
Food Chem ; 459: 140438, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39024878

RESUMO

To investigate the structural characteristics of cell wall pectic polysaccharides from wampee, water soluble pectin (WSP), chelator-soluble pectin (CSP) and sodium carbonate-soluble pectin (SSP) were purified. And the inhibitory effects of wampee polyphenol (WPP) on pectinase when these cell wall pectic polysaccharides were used as substrates were also explored. Purified WSP (namely PWSP) had the lowest molecular weight (8.47 × 105 Da) and the highest GalA content (33.43%). While purified CSP (called PCSP) and SSP contained more abundant rhamnogalacturonan I side chains. All of them were low-methoxy pectin (DE < 50%). Enzyme activity and kinetics analysis showed that the inhibition of pectinase by wampee polyphenol was reversible and mixed type. When SSP was used as the substrate, WPP had the strongest inhibition (IC50 = 1.96 ± 0.06 mg/mL) on pectinase. Fluorescence quenching results indicated that WPP inhibited enzyme activity by interacting with substrates and enzymes. Therefore, WPP has the application potential in controlling softening of fruits and vegetables.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39013587

RESUMO

BACKGROUND AND AIM: Helicobacter pylori infection is linked to various gastrointestinal conditions, such as chronic active gastritis, peptic ulcers, and gastric cancer. Traditional treatment options encounter difficulties due to antibiotic resistance and adverse effects. Therefore, the aim of this study was to explore the effectiveness of a new treatment plan that combines vonoprazan (VPZ), amoxicillin, and bismuth for the eradication of H. pylori. METHODS: A total of 600 patients infected with H. pylori were recruited for this multicenter randomized controlled trial. Patients treated for H. pylori elimination were randomly assigned at a 1:1 ratio to receive 14 days of vonoprazan-based triple therapy (vonoprazan + amoxicillin + bismuth, group A) or standard quadruple therapy (esomeprazole + clarithromycin + amoxicillin + bismuth, group B). Compliance and adverse effects were tracked through daily medication and side effect records. All patients underwent a 13C/14C-urea breath test 4 weeks after treatment completion. RESULTS: Intention-to-treat (ITT) and per-protocol (PP) analyses revealed no substantial differences in H. pylori eradication rates between groups A and B (ITT: 83.7% vs 83.2%; PP: 90.9% vs 89.7%). However, significant differences were observed in the assessment of side effects (13.7% vs 28.6%, P < 0.001). Specifically, group A had significantly fewer "bitter mouths" than group B did (3.7% vs 16.2%, P < 0.001). CONCLUSION: Triple therapy comprising vonoprazan (20 mg), amoxicillin (750 mg), and bismuth potassium citrate (220 mg) achieved a PP eradication rate ≥90%, paralleling standard quadruple therapy, and had fewer adverse events and lower costs (¥306.8 vs ¥645.8) for treatment-naive patients.

3.
J Formos Med Assoc ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39013749

RESUMO

BACKGROUND: Secondary pneumonia has a significant clinical impact on critically ill patients with COVID-19. AIM: Considering potential geographic variations, this study explores the clinical implications of secondary pneumonia within East Asian populations. METHODS: This multicenter, retrospective cohort study enrolled critical COVID-19 patients requiring intensive care units (ICUs) admission in Taiwan from December 31, 2020, to June 1, 2022. FINDINGS: Among the 187 critical COVID-19 patients, 80 (42.8%) developed secondary pneumonia. The primary causative pathogens were gram-negative bacilli (GNB) (76.8%). Gram-positive cocci and fungi were mainly observed during the initial two weeks of ICU stay. Notably, the incidence of pulmonary aspergillosis was 9.2% during the first week of ICU stay and all Staphylococcus aureus were susceptible to methicillin. Multi-drug resistant organisms (MDROs) were responsible for 28.3% of the cases, exhibiting significantly longer ICU stays compared to the non-MDRO group (median, 27 vs. 14 days, P < 0.001). In the multivariate analysis, Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores were associated with a significantly increased risk of secondary pneumonia. In-hospital mortality was significantly higher in patients with secondary pneumonia than in those without (37.7% vs. 16.7%, P = 0.02) and survival analysis demonstrated gram-negative bacilli-related secondary pneumonia contributed to a worse prognosis. CONCLUSIONS: Secondary pneumonia in critical COVID-19 patients significantly raised in-hospital mortality and extended hospital and ICU stays. Moreover, the presence of GNB notably predicted an unfavorable prognosis.

4.
Lung ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38884647

RESUMO

PURPOSE: Bronchiectasis is predominantly marked by neutrophilic inflammation. The relevance of type 2 biomarkers in disease severity and exacerbation risk is poorly understood. This study explores the clinical significance of these biomarkers in bronchiectasis patients. METHODS: In a cross-sectional cohort study, bronchiectasis patients, excluding those with asthma or allergic bronchopulmonary aspergillosis, underwent clinical and radiological evaluations. Bronchoalveolar lavage samples were analyzed for cytokines and microbiology. Blood eosinophil count (BEC), serum total immunoglobulin E (IgE), and fractional exhaled nitric oxide (FeNO) were measured during stable disease states. Positive type 2 biomarkers were defined by established thresholds for BEC, total IgE, and FeNO. RESULTS: Among 130 patients, 15.3% demonstrated BEC ≥ 300 cells/µL, 26.1% showed elevated FeNO ≥ 25 ppb, and 36.9% had high serum total IgE ≥ 75 kU/L. Approximately 60% had at least one positive type 2 biomarker. The impact on clinical characteristics and disease severity was variable, highlighting BEC and FeNO as reflective of different facets of disease severity and exacerbation risk. The combination of low BEC with high FeNO appeared to indicate a lower risk of exacerbation. However, Pseudomonas aeruginosa colonization and a high neutrophil-to-lymphocyte ratio (NLR ≥ 3.0) were identified as more significant predictors of exacerbation frequency, independent of type 2 biomarker presence. CONCLUSIONS: Our study underscores the distinct roles of type 2 biomarkers, highlighting BEC and FeNO, in bronchiectasis for assessing disease severity and predicting exacerbation risk. It advocates for a multi-biomarker strategy, incorporating these with microbiological and clinical assessments, for comprehensive patient management.

5.
BMC Cancer ; 24(1): 691, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844880

RESUMO

PURPOSE: The potential efficacy of metformin in breast cancer (BC) has been hotly discussed but never conclusive. This genetics-based study aimed to evaluate the relationships between metformin targets and BC risk. METHODS: Metformin targets from DrugBank and genome-wide association study (GWAS) data from IEU OpenGWAS and FinnGen were used to investigate the breast cancer (BC)-metformin causal link with various Mendelian Randomization (MR) methods (e.g., inverse-variance-weighting). The genetic association between type 2 diabetes (T2D) and the drug target of metformin was also analyzed as a positive control. Sensitivity and pleiotropic tests ensured reliability. RESULTS: The primary targets of metformin are PRKAB1, ETFDH and GPD1L. We found a causal association between PRKAB1 and T2D (odds ratio [OR] 0.959, P = 0.002), but no causal relationship was observed between metformin targets and overall BC risk (PRKAB1: OR 0.990, P = 0.530; ETFDH: OR 0.986, P = 0.592; GPD1L: OR 1.002, P = 0.806). A noteworthy causal relationship was observed between ETFDH and estrogen receptor (ER)-positive BC (OR 0.867, P = 0.018), and between GPD1L and human epidermal growth factor receptor 2 (HER2)-negative BC (OR 0.966, P = 0.040). Other group analyses did not yield positive results. CONCLUSION: The star target of metformin, PRKAB1, does not exhibit a substantial causal association with the risk of BC. Conversely, metformin, acting as an inhibitor of ETFDH and GPD1L, may potentially elevate the likelihood of developing ER-positive BC and HER2-negative BC. Consequently, it is not advisable to employ metformin as a standard supplementary therapy for BC patients without T2D.


Assuntos
Neoplasias da Mama , Diabetes Mellitus Tipo 2 , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Metformina , Humanos , Metformina/uso terapêutico , Metformina/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/tratamento farmacológico , Feminino , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicações , Quimioterapia Adjuvante/métodos , Hipoglicemiantes/uso terapêutico , Polimorfismo de Nucleotídeo Único
6.
Artigo em Inglês | MEDLINE | ID: mdl-38929040

RESUMO

Despite the lack of evidence, opioids are still routinely used as a solution to long-term management for chronic noncancer pain (CNCP). Given the significant risks associated with long-term opioid use, including the increased number of unregulated opioid pills at large in the opioid ecosystem, opioid cessation or reduction may be the desired goal of the patient and clinician. Viable nonpharmacological interventions (NPIs) to complement and/or replace opioids for CNCP are needed. Comprehensive reviews that address the impact of NPIs to help adults with CNCP reduce opioid use safely are lacking. We conducted a literature search in PubMed, CINAHL, Embase, PsycINFO, and Scopus for studies published in English. The initial search was conducted in April 2021, and updated in January 2024. The literature search yielded 19,190 relevant articles. Thirty-nine studies met the eligibility criteria and underwent data extraction. Of these, nineteen (49%) were randomized controlled trials, eighteen (46%) were observational studies, and two (5%) were secondary analyses. Among adults with CNCP who use opioids for pain management, studies on mindfulness, yoga, educational programs, certain devices or digital technology, chiropractic, and combination NPIs suggest that they might be an effective approach for reducing both pain intensity and opioid use, but other NPIs did not show a significant effect (e.g., hypnosis, virtual reality). This review revealed there is a small to moderate body of literature demonstrating that some NPIs might be an effective and safe approach for reducing pain and opioid use, concurrently.


Assuntos
Analgésicos Opioides , Dor Crônica , Humanos , Dor Crônica/tratamento farmacológico , Dor Crônica/terapia , Analgésicos Opioides/uso terapêutico , Transtornos Relacionados ao Uso de Opioides , Manejo da Dor/métodos
7.
Gut Microbes ; 16(1): 2361490, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38860456

RESUMO

The role of gut microbiota in host defense against nontuberculous mycobacterial lung disease (NTM-LD) was poorly understood. Here, we showed significant gut microbiota dysbiosis in patients with NTM-LD. Reduced abundance of Prevotella copri was significantly associated with NTM-LD and its disease severity. Compromised TLR2 activation activity in feces and plasma in the NTM-LD patients was highlighted. In the antibiotics-treated mice as a study model, gut microbiota dysbiosis with reduction of TLR2 activation activity in feces, sera, and lung tissue occurred. Transcriptomic analysis demonstrated immunocompromised in lung which were closely associated with increased NTM-LD susceptibility. Oral administration of P. copri or its capsular polysaccharides enhanced TLR2 signaling, restored immune response, and ameliorated NTM-LD susceptibility. Our data highlighted the association of gut microbiota dysbiosis, systematically compromised immunity and NTM-LD development. TLR2 activation by P. copri or its capsular polysaccharides might help prevent NTM-LD.


Assuntos
Disbiose , Microbioma Gastrointestinal , Infecções por Mycobacterium não Tuberculosas , Receptor 2 Toll-Like , Disbiose/microbiologia , Animais , Receptor 2 Toll-Like/metabolismo , Receptor 2 Toll-Like/genética , Humanos , Camundongos , Masculino , Feminino , Infecções por Mycobacterium não Tuberculosas/microbiologia , Pessoa de Meia-Idade , Fezes/microbiologia , Idoso , Prevotella , Pneumopatias/microbiologia , Micobactérias não Tuberculosas , Suscetibilidade a Doenças , Camundongos Endogâmicos C57BL , Pulmão/microbiologia
8.
Nat Med ; 30(7): 1923-1932, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38898120

RESUMO

Although comprehensive biomarker testing is recommended for all patients with advanced/metastatic non-small cell lung cancer (NSCLC) before initiation of first-line treatment, tissue availability can limit testing. Genomic testing in liquid biopsies can be utilized to overcome the inherent limitations of tissue sampling and identify the most appropriate biomarker-informed treatment option for patients. The Blood First Assay Screening Trial is a global, open-label, multicohort trial that evaluates the efficacy and safety of multiple therapies in patients with advanced/metastatic NSCLC and targetable alterations identified by liquid biopsy. We present data from Cohort D (ROS1-positive). Patients ≥18 years of age with stage IIIB/IV, ROS1-positive NSCLC detected by liquid biopsies received entrectinib 600 mg daily. At data cutoff (November 2021), 55 patients were enrolled and 54 had measurable disease. Cohort D met its primary endpoint: the confirmed objective response rate (ORR) by investigator was 81.5%, which was consistent with the ORR from the integrated analysis of entrectinib (investigator-assessed ORR, 73.4%; data cutoff May 2019, ≥12 months of follow-up). The safety profile of entrectinib was consistent with previous reports. These results demonstrate consistency with those from the integrated analysis of entrectinib in patients with ROS1-positive NSCLC identified by tissue-based testing, and support the clinical value of liquid biopsies to inform clinical decision-making. The integration of liquid biopsies into clinical practice provides patients with a less invasive diagnostic method than tissue-based testing and has faster turnaround times that may expedite the reaching of clinical decisions in the advanced/metastatic NSCLC setting. ClinicalTrials.gov registration: NCT03178552 .


Assuntos
Benzamidas , Carcinoma Pulmonar de Células não Pequenas , Indazóis , Neoplasias Pulmonares , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Indazóis/uso terapêutico , Indazóis/efeitos adversos , Benzamidas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/genética , Adulto , Idoso de 80 Anos ou mais , Biópsia Líquida , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos
9.
Neurochem Res ; 49(8): 2197-2214, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38834846

RESUMO

Neuroinflammation and endothelial cell apoptosis are prominent features of blood-brain barrier (BBB) disruption, which have been described in Alzheimer's disease (AD) and can predict cognitive decline. Recent reports revealed vascular ß-amyloid (Aß) deposits, Muller cell degeneration and microglial dysfunction in the retina of AD patients. However, there has been no in-depth research on the roles of inflammation, retinal endothelial cell apoptosis, and blood-retinal barrier (BRB) damage in AD retinopathy. We found that Raddeanin A (RDA) could improve pathological and cognitive deficits in a mouse model of Alzheimer's disease by targeting ß-amyloidosis, However, the effects of RDA on AD retinal function require further study. To clarify whether RDA inhibits inflammation and apoptosis and thus improves BRB function in AD-related retinopathy. In vitro we used Aß-treated HRECs and MIO-M1 cells, and in vivo we used 3×Tg-AD mice to investigate the effect of RDA on BRB in AD-related retinopathy. We found that RDA could improve BRB function in AD-related retinopathy by inhibiting NLRP3-mediated inflammation and suppressing Wnt/ß-catenin pathway-mediated apoptosis, which is expected to improve the pathological changes in AD-related retinopathy and the quality of life of AD patients.


Assuntos
Doença de Alzheimer , Apoptose , Barreira Hematorretiniana , Camundongos Transgênicos , Retina , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Apoptose/efeitos dos fármacos , Barreira Hematorretiniana/efeitos dos fármacos , Barreira Hematorretiniana/metabolismo , Retina/efeitos dos fármacos , Retina/metabolismo , Retina/patologia , Camundongos , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Camundongos Endogâmicos C57BL , Humanos , Peptídeos beta-Amiloides/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/fisiologia , Masculino
10.
Artigo em Inglês | MEDLINE | ID: mdl-38874461

RESUMO

BACKGROUND: Among Asian Americans, Filipino Americans (FAs)-who constitute the fourth largest US immigrant group and who fill in health care workforce shortages-experience high prevalence but low control rates of high blood pressure (HBP). Research reveals that patients' illness perceptions, their common-sense model (CSM) of the illness, influence treatment behaviors, and management outcomes. However, scarce information exists about FAs' perceptions about HBP. PURPOSE: To address this gap, we conducted a cross-sectional study to (a) identify the illness perceptions of hypertensive FAs, (b) classify these perceptions into clusters, and (c) determine the association between illness perceptions and BP control. METHODOLOGY: The responses of 248 FAs with HBP to the Brief Illness Perception Questionnaire were analyzed using JMP Pro version 17 to discover their CSMs or illness perceptions. We used iterative K means cluster analysis to classify variations in CSMs and analysis of means chart to determine the association of illness perceptions and BP control. RESULTS: Hypertensive FAs expressed threatening (negative) views of HBP through their emotional perceptions of the illness and its chronic time line, whereas their positive views centered on their cognitive beliefs about understanding HBP and its controllability. Based on the biomedical model of HBP, the overall illness perceptions or CSMs encompassed three clusters. Generally, threatening illness perceptions were associated with stage 2 HBP. CONCLUSIONS/IMPLICATIONS: The findings underscore the need for nurse practitioners to elicit, listen, discern, and understand the illness perceptions or CSMs of hypertensive FAs to improve BP treatment and control with scientifically and culturally tailored interventions.

11.
Sci Total Environ ; 939: 173643, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38821282

RESUMO

Mariculture effluent polishing with microalgal biofilm could realize effective nutrients removal and resolve the microalgae-water separation issue via biofilm scraping or in-situ aquatic animal grazing. Ubiquitous existence of antibiotics in mariculture effluents may affect the remediation performances and arouse ecological risks. The influence of combined antibiotics exposure at environment-relevant concentrations towards attached microalgae suitable for mariculture effluent polishing is currently lack of research. Results from suspended cultures could offer limited guidance since biofilms are richer in extracellular polymeric substances that may protect the cells from antibiotics and alter their transformation pathways. This study, therefore, explored the effects of combined antibiotics exposure at environmental concentrations towards seawater Chlorella sp. biofilm in terms of microalgal growth characteristics, nutrients removal, anti-oxidative responses, and antibiotics removal and transformations. Sulfamethoxazole (SMX), tetracycline (TL), and clarithromycin (CLA) in single, binary, and triple combinations were investigated. SMX + TL displayed toxicity synergism while TL + CLA revealed toxicity antagonism. Phosphorus removal was comparable under all conditions, while nitrogen removal was significantly higher under SMX and TL + CLA exposure. Anti-oxidative responses suggested microalgal acclimation towards SMX, while toxicity antagonism between TL and CLA generated least cellular oxidative damage. Parent antibiotics removal was in the order of TL (74.5-85.2 %) > CLA (60.8-69.5 %) > SMX (13.5-44.1 %), with higher removal efficiencies observed under combined than single antibiotic exposure. Considering the impact of residual parent antibiotics, CLA involved cultures were identified of high ecological risks, while medium risks were indicated in other cultures. Transformation products (TPs) of SMX and CLA displayed negligible aquatic toxicity, the parent antibiotics themselves deserve advanced removal. Four out of eight TPs of TL could generate chronic toxicity, and the elimination of these TPs should be prioritized for TL involved cultures. This study expands the knowledge of combined antibiotics exposure upon microalgal biofilm based mariculture effluent polishing.


Assuntos
Antibacterianos , Biofilmes , Chlorella , Água do Mar , Poluentes Químicos da Água , Chlorella/fisiologia , Chlorella/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Antibacterianos/toxicidade , Poluentes Químicos da Água/toxicidade , Água do Mar/química , Medição de Risco , Eliminação de Resíduos Líquidos/métodos , Aquicultura , Microalgas/efeitos dos fármacos , Microalgas/fisiologia
12.
Cell Transplant ; 33: 9636897241249556, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38742734

RESUMO

Pancreatic islet transplantation is one of the clinical options for certain types of diabetes. However, difficulty in maintaining islets prior to transplantation limits the clinical expansion of islet transplantations. Our study introduces a dynamic culture platform developed specifically for primary human islets by mimicking the physiological microenvironment, including tissue fluidics and extracellular matrix support. We engineered the dynamic culture system by incorporating our distinctive microwell-patterned porous collagen scaffolds for loading isolated human islets, enabling vertical medium flow through the scaffolds. The dynamic culture system featured four 12 mm diameter islet culture chambers, each capable of accommodating 500 islet equivalents (IEQ) per chamber. This configuration calculates > five-fold higher seeding density than the conventional islet culture in flasks prior to the clinical transplantations (442 vs 86 IEQ/cm2). We tested our culture platform with three separate batches of human islets isolated from deceased donors for an extended period of 2 weeks, exceeding the limits of conventional culture methods for preserving islet quality. Static cultures served as controls. The computational simulation revealed that the dynamic culture reduced the islet volume exposed to the lethal hypoxia (< 10 mmHg) to ~1/3 of the static culture. Dynamic culture ameliorated the morphological islet degradation in long-term culture and maintained islet viability, with reduced expressions of hypoxia markers. Furthermore, dynamic culture maintained the islet metabolism and insulin-secreting function over static culture in a long-term culture. Collectively, the physiological microenvironment-mimetic culture platform supported the viability and quality of isolated human islets at high-seeding density. Such a platform has a high potential for broad applications in cell therapies and tissue engineering, including extended islet culture prior to clinical islet transplantations and extended culture of stem cell-derived islets for maturation.


Assuntos
Colágeno , Ilhotas Pancreáticas , Alicerces Teciduais , Humanos , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Alicerces Teciduais/química , Porosidade , Técnicas de Cultura de Células/métodos , Técnicas de Cultura de Células/instrumentação , Transplante das Ilhotas Pancreáticas/métodos
13.
Respir Res ; 25(1): 203, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730430

RESUMO

BACKGROUND: Although electronic nose (eNose) has been intensively investigated for diagnosing lung cancer, cross-site validation remains a major obstacle to be overcome and no studies have yet been performed. METHODS: Patients with lung cancer, as well as healthy control and diseased control groups, were prospectively recruited from two referral centers between 2019 and 2022. Deep learning models for detecting lung cancer with eNose breathprint were developed using training cohort from one site and then tested on cohort from the other site. Semi-Supervised Domain-Generalized (Semi-DG) Augmentation (SDA) and Noise-Shift Augmentation (NSA) methods with or without fine-tuning was applied to improve performance. RESULTS: In this study, 231 participants were enrolled, comprising a training/validation cohort of 168 individuals (90 with lung cancer, 16 healthy controls, and 62 diseased controls) and a test cohort of 63 individuals (28 with lung cancer, 10 healthy controls, and 25 diseased controls). The model has satisfactory results in the validation cohort from the same hospital while directly applying the trained model to the test cohort yielded suboptimal results (AUC, 0.61, 95% CI: 0.47─0.76). The performance improved after applying data augmentation methods in the training cohort (SDA, AUC: 0.89 [0.81─0.97]; NSA, AUC:0.90 [0.89─1.00]). Additionally, after applying fine-tuning methods, the performance further improved (SDA plus fine-tuning, AUC:0.95 [0.89─1.00]; NSA plus fine-tuning, AUC:0.95 [0.90─1.00]). CONCLUSION: Our study revealed that deep learning models developed for eNose breathprint can achieve cross-site validation with data augmentation and fine-tuning. Accordingly, eNose breathprints emerge as a convenient, non-invasive, and potentially generalizable solution for lung cancer detection. CLINICAL TRIAL REGISTRATION: This study is not a clinical trial and was therefore not registered.


Assuntos
Aprendizado Profundo , Nariz Eletrônico , Neoplasias Pulmonares , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Respiratórios/métodos , Neoplasias Pulmonares/diagnóstico , Estudos Prospectivos , Reprodutibilidade dos Testes
14.
PLoS One ; 19(5): e0303046, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38753697

RESUMO

Osimertinib has demonstrated efficacy in patients with epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer (NSCLC) in clinical trials. However, real-world data on its effectiveness remain scarce. Taiwanese patients with T790M-positive locally advanced or metastatic NSCLC and progressive disease following treatment with at least one EGFR tyrosine kinase inhibitor (TKI) were enrolled from the osimertinib early access program. Of the 419 patients (mean age, 63 years; female, 67%), 53% were heavily pretreated (≥ third-line [3L]), making osimertinib a fourth-line (4L) intervention. The median progression-free survival (PFS) was 10.5 months (95% confidence interval [CI]: 8.95-11.41); the 18-month PFS rate was 26.5%. The median overall survival (OS) was 19.0 months (95% CI: 16.30-20.95); the 24-month OS rate was 40.9%. The objective response rate was 32.46%, and the disease control rate was 86.38%. The median time to treatment discontinuation of osimertinib monotherapy was 11.9 months (95% CI: 10.49-13.11). Subgroup analyses of median PFS and OS in the chemotherapy combination group vs. the osimertinib monotherapy group yielded no difference. Central nervous system (CNS) metastasis, number of prior lines of therapy, and types of initial EGFR-TKIs did not significantly impact outcomes. The median PFS values were 9.0 (95% CI: 5.18-11.34) and 10.9 (95% CI: 9.18-11.90) months with and without CNS metastasis, respectively, and 10.8 (95% CI: 8.59-12.69), 13.6 (95% CI: 10.89-16.3), and 9.2 (95% CI: 7.8-10.62) months for second-line (2L), 3L, and ≥4L therapy, respectively. In patients who received osimertinib as 2L therapy, the median PFS values in response to prior afatinib, erlotinib and gefitinib treatment were 11.2 (95% CI: 4.85-4.79), 10.5 (95% CI: 8.59-20.26) and 8.7 (95% CI: 7.21-16.79) months, respectively. Overall, real-world data from Taiwan support the clinical benefits of osimertinib in EGFR T790M -positive NSCLC.


Assuntos
Acrilamidas , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Mutação , Inibidores de Proteínas Quinases , Humanos , Acrilamidas/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Compostos de Anilina/uso terapêutico , Feminino , Receptores ErbB/genética , Receptores ErbB/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Idoso , Adulto , Inibidores de Proteínas Quinases/uso terapêutico , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Metástase Neoplásica , Intervalo Livre de Progressão , Indóis , Pirimidinas
16.
Artigo em Inglês | MEDLINE | ID: mdl-38598400

RESUMO

Electronic healthcare (e-health) allows smart devices and medical institutions to collaboratively collect patients' data, which is trained by artificial intelligence (AI) technologies to help doctors make diagnosis. By allowing multiple devices to train models collaboratively, federated learning is a promising solution to address the communication and privacy issues in e-health. However, applying federated learning in e-health faces many challenges. First, medical data are both horizontally and vertically partitioned. Since single horizontal federated learning (HFL) or vertical federated learning (VFL) techniques cannot deal with both types of data partitioning, directly applying them may consume excessive communication cost due to transmitting a part of raw data when requiring high modeling accuracy. Second, a naive combination of HFL and VFL has limitations including low training efficiency, unsound convergence analysis, and lack of parameter tuning strategies. In this article, we provide a thorough study on an effective integration of HFL and VFL, to achieve communication efficiency and overcome the above limitations when data are both horizontally and vertically partitioned. Specifically, we propose a hybrid federated learning framework with one intermediate result exchange and two aggregation phases. Based on this framework, we develop a hybrid stochastic gradient descent (HSGD) algorithm to train models. Then, we theoretically analyze the convergence upper bound of the proposed algorithm. Using the convergence results, we design adaptive strategies to adjust the training parameters and shrink the size of transmitted data. The experimental results validate that the proposed HSGD algorithm can achieve the desired accuracy while reducing communication cost, and they also verify the effectiveness of the adaptive strategies.

17.
BMC Microbiol ; 24(1): 119, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580930

RESUMO

Obesity is a metabolic disorder closely associated with profound alterations in gut microbial composition. However, the dynamics of species composition and functional changes in the gut microbiome in obesity remain to be comprehensively investigated. In this study, we conducted a meta-analysis of metagenomic sequencing data from both obese and non-obese individuals across multiple cohorts, totaling 1351 fecal metagenomes. Our results demonstrate a significant decrease in both the richness and diversity of the gut bacteriome and virome in obese patients. We identified 38 bacterial species including Eubacterium sp. CAG:274, Ruminococcus gnavus, Eubacterium eligens and Akkermansia muciniphila, and 1 archaeal species, Methanobrevibacter smithii, that were significantly altered in obesity. Additionally, we observed altered abundance of five viral families: Mesyanzhinovviridae, Chaseviridae, Salasmaviridae, Drexlerviridae, and Casjensviridae. Functional analysis of the gut microbiome indicated distinct signatures associated to obesity and identified Ruminococcus gnavus as the primary driver for function enrichment in obesity, and Methanobrevibacter smithii, Akkermansia muciniphila, Ruminococcus bicirculans, and Eubacterium siraeum as functional drivers in the healthy control group. Additionally, our results suggest that antibiotic resistance genes and bacterial virulence factors may influence the development of obesity. Finally, we demonstrated that gut vOTUs achieved a diagnostic accuracy with an optimal area under the curve of 0.766 for distinguishing obesity from healthy controls. Our findings offer comprehensive and generalizable insights into the gut bacteriome and virome features associated with obesity, with the potential to guide the development of microbiome-based diagnostics.


Assuntos
Clostridiales , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/genética , Metagenoma , Obesidade/microbiologia , Bactérias/genética , Fezes/microbiologia , Akkermansia
18.
Sensors (Basel) ; 24(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38543990

RESUMO

The evaluation of blasting vibrations primarily hinges on two physical quantities: velocity and acceleration. A significant challenge arises when attempting to reference the two types of vibration data in relation to one another, such as different types of seismometers, noise, etc., necessitating a method for their equivalent transformation. To address this, a transformation method is discussed in detail with a case study, and equations for the ratio (Ra) of the particle peak velocity (PPV) to the particle peak acceleration (PPA) are proposed. The findings are twofold: (1) The conventional data conversion processes often suffer from low accuracy due to the presence of trend terms and noise in the signal. To mitigate this, the built-in MATLAB function is used for trend term elimination, complemented by a combined approach that integrates CEEMDAN with WD/WDP for noise reduction. These significantly enhance the accuracy of the transformation. (2) This analysis reveals a positive power function correlation between Ra and the propagation distance of the blast vibrations, contrasted by a negative correlation with the maximum charge per delay. Intriguingly, the Ra values observed in pre-splitting blasting operations are consistently lower than those in bench blasting. The established Ra equations offer a rapid, direct method for assessing the transformation between the PPV and PPA, providing valuable insights for the optimization of blasting design.

19.
Phytomedicine ; 127: 155463, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38452694

RESUMO

BACKGROUND: Ferroptosis, a unique type of cell death triggered by iron-dependent lipid peroxidation, plays a critical role in the pathogenesis of Alzheimer's disease (AD), a debilitating condition marked by memory loss and cognitive impairment due to the accumulation of beta-amyloid (Aß) and hyperphosphorylated Tau protein. Increasing evidence suggests that inhibitors of ferroptosis could be groundbreaking in the treatment of AD. METHOD: In this study, we established in vitro ferroptosis using erastin-, RSL-3-, hemin-, and iFSP1-induced PC-12 cells. Using MTT along with Hoechst/PI staining, we assessed cell viability and death. To determine various aspects of ferroptosis, we employed fluorescence probes, including DCFDA, JC-1, C11 BODIPY, Mito-Tracker, and PGSK, to measure ROS production, mitochondrial membrane potential, lipid peroxidation, mitochondrial morphology, and intracellular iron levels. Additionally, Western blotting, biolayer interferometry technology, and shRNA were utilized to investigate the underlying molecular mechanisms. Furthermore, p-CAX APP Swe/Ind- and pRK5-EGFP-Tau P301L overexpressing PC-12 cells, along with Caenorhabditis elegans (C. elegans) strains CL4176, CL2331, and BR5270, were employed to examine ferroptosis in AD models. RESULTS: Here, we conducted a screening of our natural medicine libraries and identified the ethanol extract of Penthorum chinense Pursh (PEE), particularly its ethyl acetate fraction (PEF), displayed inhibitory effects on ferroptosis in cells. Specifically, PEF inhibited the generation of ROS, lipid peroxidation, and intracellular iron levels. Furthermore, PEF demonstrated protective effects against H2O2-induced cell death, ROS production, and mitochondrial damage. Mechanistic investigations unveiled PEF's modulation of intracellular iron accumulation, GPX4 expression and activity, and FSP1 expression. In p-CAX APP Swe/Ind and pRK5-EGFP-Tau P301L overexpressing PC-12 cells, PEF significantly reduced cell death, as well as ROS and lipid peroxidase production. Moreover, PEF ameliorated paralysis and slowing rate in Aß and Tau transgenic C. elegans models, while inhibiting ferroptosis, as evidenced by decreased DHE intensity, lipid peroxidation levels, iron accumulation, and expression of SOD-3 and gst-4. CONCLUSION: Our findings highlight the suppressive effects of PEF on ferroptosis in AD cellular and C. elegans models. This study helps us better understand how ferroptosis affects AD and emphasizes the potential of PCP as a candidate for AD intervention.


Assuntos
Doença de Alzheimer , Ferroptose , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Caenorhabditis elegans , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Ferro/metabolismo
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